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INDIAN JOURNAL OF PATHOLOGY: RESEARCH AND PRACTICE

Editor-in-Chief

R.K. Bhatnagar
Professor (Pathology) Rtd.
Maulana Azad Medical College, Delhi

National Editorial Board


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Banushree CS, Puducherry
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Indian Journal of Pathology: Research and Practice (IJPRP) (pISSN: 2278-148X, eISSN: 2455-5320) is
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Indian Journal of Pathology: Research and Practice / Volume 7 Number 6 / June 2018
719

Indian Journal of Pathology: Research and Practice

VOLUME 7 NUMBER 6,
JUNE 2018
Contents

Original Research Articles

Analysis of Cervico- Vaginal Lesions in Women using Pap Smear: A


Histopathological Study 723
Anand Nagalikar, Rashmi Chandragouda Meti

Histopathology and Clinical Correlation of Tortion of Ovary 727


Dost Mohamed Khan, Naseem Norunnisa, Abilash S.C.,
Revathishree R., N. Thamarai Selvi, Pushkar Chaudhary

Histopathological Patterns of Gall Bladder Diseases in Routine


Cholecystectomy Specimens: A Hospital-Based Study from
a Rural Medical College, Uttar Pradesh 731
Praneeta J. Singh, Sheetal G. Gole

Spectrum of Ovarian Lesions: An Institutional Study 737


Bhangale Harshada R., Pathade Smita C., Mendhe Runali D.,
Borole Bharat S., Sangole Vilas M.

A Study on Histopathological Patterns of Thyroid Lesions and its


Cytological Correlation: An Experience of A Rural
Tertiary Care Center 741
S. Kalyani, J. Kolsamma Nasrin, O.A. Meharaj Banu, S.R. Murali Prasath,
R. Uma, S.R. Jayakarthiga

Evaluation of Hematological Scoring System in the Diagnosis


of Neonatal Sepsis 746
Kumarguru B.N., Chandrakala R. Lyer, Ramaswamy A.S.,
Naveen G., Suma H.R., Amita Ray

Histopathological Patterns in Abnormal Uterine Bleeding at a


Tertiary Hospital 754
Pradeep Jadhav, Dipti Patel, S.N. Chawla

Histopathological Study of the Architectural Patterns of in Situ Carcinoma


in Cases of Invasive Breast Cancer 758
Apoorva A.N., Shilpa L., Prakash C.J., Shivarudrappa A.S.

Hematological Indices in Thyroid Disorders 764


K.R. Shouree, M. Bharathi

Screening of Blood Donors for Transfusion Transmitted Infections: Is


Zero Risk Blood Supply Possible? 768
Smita C. Pathade, Anagha P. Amale, Harshada R. Bhangale,
Runali D. Mendhe, Vilas M. Sangole
Indian Journal of Pathology: Research and Practice / Volume 7 Number 6 / June 2018
720

Image Analysis and Image Classifier Using Neural Network with


Machine Learning to Perform Differential Leucocyte Count 772
Swaroop Raj B.V., Divya C., Smitha B.V.

A Study of High Risk Operational Link for Gastritis Assessment (OLGA)


Stages in South Indian Subjects 776
Thara Keloth, Marie Moses Ambroise, Thomas Alexander, Susy S. Kurian

Histopathological Spectrum of Breast Lumps: A One Year


Retrospective Study 782
Hawaldar Ranjana, Patidar Ekta, Sodani Sadhna

Is Cervical Cancer Incidence Decreasing in the Urban Population of


India with Developing Healthcare, Socio Demographic Progress
and Awareness Programmes? 786
Sujata Mallick, Mahasweta Mallik

Clinicopathological Study of Primary Epithelial Malignant Tumours of


Thyroid Gland in a Tertiary Care Centre, Kolar 792
Pradeep Mitra V., Manjula K., CSBR Prasad

Histopathological Evaluation of Non-Neoplastic and Neoplastic


Lesions of Cervix 797
Arpita Singh, Shilpa L., Shivarudrappa A.S.

Case Report

Reactive Angioendotheliomatosis in the Setting of Leprosy: A


Previously Un-Described Association 805
Poorvi Kapoor, Vishwanath B.K., Vardendra Kulkarni, Prakash Kumar, Rajashekar K.S.

Guidelines for Authors 809

Indian Journal of Pathology: Research and Practice / Volume 7 Number 6 / June 2018
721
Indian Journal of Pathology: Research and Practice

IJPRP Volume 7 Number 6, June 2018

Editorial

I
n the previous issue of May we had nice articles on Cytology, Histopathology and Hematology. We had articles
from tertiary hospitals, biochemical parameters especially hormonal dysfunctions of ovary and pituitary
adenoma. We had original articles on cytomorphology of thyroid and different pattern of cystic lesion of
ovary, clinicopathological studies on breast smears. We had studies on oncocytic cells in diagnosis, sarcoma  of
uterus, PAP’s smear in cervical infections, pleomorphic adenoma of salivary gland, rural blood bank donors
differences etc. etc. We had different types of anemia’s in school going children, manual liquid based cytology in
FNAC’s and sigma matics eosinophilic enteropathic lesions in intestinal biopsies, clinicopathological study of
biopsy from post transplant of liver cases in south India, CD4 count in PLHIV cases in India and primary tubal
cystadenocarcinoma: A rare case. Other articles are also interesting and good.
In India we had heavy downpour in last few weeks especially in Bombay (Maharashtra), Gujarat and subsequently
landslides and big gaping holes on roads and societies and house collapses with few human deaths. We also had
heavy downpour in North East, West Bengal and Bihar subsequently flooding of fields and houses. In Delhi though
we had minor rain falls, but few houses collapses in eastern NCR and we also had road collapses of 30x20 feet.
Causing worry of the local residents and rescue workers had to vacate some houses. So we need extra care by the
builders, contractors and Civil Engineers in planning the sky rise buildings for safety of future residents of them.
Now-a-days we are getting’s lots of ads in different programs of TV and especially news. In the observation made
by the authors mainly constipation among delhites and its remedies are advertised- may be because of food habits
and life style.

R.K. Bhatnagar
Editor-in-Chief,
Professor of Pathology (Rtd.),
Maulana Azad Medical College, Delhi

Indian Journal of Pathology: Research and Practice / Volume 7 Number 6 / June 2018
722

Indian Journal of Pathology: Research and Practice / Volume 7 Number 6 / June 2018
723
Indian Journal of Pathology: Research and Practice

IJPRP Volume 7 Number 6, June 2018


DOI: http://dx.doi.org/10.21088/ijprp.2278.148X.7618.1

Original Research Article

Analysis of Cervico- Vaginal Lesions in Women using Pap Smear: A


Histopathological Study

Anand Nagalikar1, Rashmi Chandragouda Meti2

1
Associate Professor, Department of Pathology, ESIC Medical College, Gulburga, Karnataka 585106, India. 2Associate Professor,
Department of Microbiology, Kamineni Institute of Medical Sciences, Narketpalli, Nalgonda, Telangana 508254, India.

Abstract

Background: Cervical cancer is one of the leading cancers in women. The confirmation
of the disorder can be possible by Pap smear. The present study was conducted to assess the
cases of cervical cancer in women using cervical Pap smear.
Corresponding Author: Materials & Methods: This study was conducted in the Department of Pathology, ESIC
Medical College, Gulburga, Karnataka (India) on 1080 cervico-vaginal smears which were
Rashmi Chandragouda Meti, checked for the epithelial abnormalities such as atypical squamous cells of uncertain
Associate Professor, significance (ASCUS), low-grade squamous intraepithelial lesion (LSIL), non neoplastic
Department of Microbiology,
intraepithelial lesion (NILM), high-grade squamous intraepithelial lesion (HSIL) and
Kamineni Institute of Medical
Sciences, Narketpalli, Nalgonda, squamous cell carcinoma (SCC).
Telangana 508254, India. Results: Among 1080 Pap smears, 35 were unsatisfactory, 990 were NILM, 32 were LSIL, 10
E-mail: were HSIL, 5 were SCC and 8 were ASCUS. The difference was significant (0.01). 1 case of
anagalikar@gmail.com ASCUS, 2 cases of LSIL were seen in age group 31-40 years. 2 cases of ASCUS, 3 cases of LSIL
and 1 case of HSIL was seen in age group 41-50 years, 2 cases of ASCUS, 22 cases of LSIL, 6
(Received on 17.03.2018,
Accepted on 04.04.2018) cases of HSIL were seen in age group 51-60 years, 5 cases of LSIL, 3 cases of were seen in age
group 61-70 years. 3 cases of ASCUS were seen in age group 71-80 years. The difference was
significant (P- 0.01). The various changes were atrophy (30), non-specific inflammation
(55), trichomoniasis (10), candidiasis (25), reactive (25), no other changes (840) and bacterial
vaginosis (5). The difference was significant (P- 0.01).
Conclusion: Cervical cancer is one of the leading cause of death in women. Pap smear is
considered to be effective in detection of lesions in women. It is economical and non sophisticated
procedure. Careful Pap smear analysis can be proved beneficial in preventing lesions.
Keywords: Cervical Cancer; Smear; Trichomoniasis.

Introduction Infection with some types of HPV is the greatest risk


factor for cervical cancer, followed by smoking.HIV
Cervical cancer is a cancer arising from the cervix. infection is also a risk factor. Not all of the causes of cervical
It is leading cause of cancer in women. It constitutes cancer are known, however, and several other contributing
approximately 5 lacs new cases annually. In India it factors have been implicated. Early on, typically no
is estimated, that the number of cases are over 1.5 symptoms are seen. Later symptoms may include abnormal
lacs. It is due to the abnormal growth of cells that vaginal bleeding, pelvic pain, or pain during sexual
have the ability to invade or spread to other parts of intercourse. While bleeding after sex may not be serious,
the body [1]. it may also indicate the presence of cervical cancer [2].
Indian
© Red Journal of Pathology:Pvt.
Flower Publication Research
Ltd. and Practice / Volume 7 Number 6 / June 2018
724 Anand Nagalikar & Rashmi Chandragouda Meti / Analysis of Cervico- Vaginal Lesions in Women
using Pap Smear: A Histopathological Study

The Pap smear can be used as a screening test, but is (LSIL), non neoplastic intraepithelial lesion (NILM), high-
false negative in up to 50% of cases of cervical cancer. grade squamous intraepithelial lesion (HSIL) and
Confirmation of the diagnosis of cervical cancer or squamous cell carcinoma (SCC). Results thus obtained
precancer requires a biopsy of the cervix. This is often were subjected to statistical analysis. P value < 0.05 was
done through colposcopy, a magnified visual inspection considered significant.
of the cervix aided by using a dilute acetic acid solution
to highlight abnormal cells on the surface of the cervix.
Medical devices used for biopsy of the cervix include Results
punch forceps, Spira Brush CX, Soft Biopsy, or Soft-ECC
Graph 1 shows that among 1080 Pap smears, 35 were
[3]. The present study was conducted to analyze cervico-
unsatisfactory, 990 were NILM, 32 were LSIL, 10 were HSIL,
vaginal lesions in women using Pap smears.
5 were SCC and 8 were ASCUS. The difference was
significant (0.01).
Materials & Methods Graph 2 shows that 1 case of ASCUS, 2 cases of LSIL
were seen in age group 31-40 years. 2 cases of ASCUS, 3
This study was conducted in the Department of cases of LSIL and 1 case of HSIL was seen in age group
Pathology, ESIC Medical College, Gulburga, Karnataka, 41-50 years, 2 cases of ASCUS, 22 cases of LSIL, 6 cases of
India. It included 1080 cervico-vaginal smears. All were HSIL were seen in age group 51-60 years, 5 cases of LSIL,
informed regarding the study and written consent was 3 cases of were seen in age group 61-70 years. 3 cases of
obtained. For smear collections, the samples were ASCUS were seen in age group 71-80 years. The difference
collected using Ayer’s spatula or an endocervical brush. was significant (P- 0.01).
The smears were then fixed in alcohol and stained using
the Papanicolaou’s technique. Table 1 shows that various changes were atrophy (30),
non-specific inflammation (55), trichomoniasis (10),
All smears were reported using modified Bethesda candidiasis (25), reactive (25), no other changes (840)
System. The epithelial abnormalities were classified as and bacterial vaginosis (5). The difference was
atypical squamous cells of uncertain significance significant (P- 0.01).
(ASCUS), low-grade squamous intraepithelial lesion

Graph 1: Distribution of patients

Table 1: Non neoplastic cytological diagnosis in pap smear

Signs Number P value


Atrophy 30
Non specific inflammation 55
Trichomoniasis 10 0.01
Candidiasis 25
Bacterial Vaginosis 5
Reactive changes 25
No other changes 840

Indian Journal of Pathology: Research and Practice / Volume 7 Number 6 / June 2018
Anand Nagalikar & Rashmi Chandragouda Meti / Analysis of Cervico- Vaginal Lesions in Women 725
using Pap Smear: A Histopathological Study

Graph 2: Age related distribution of patients

Discussion vaginosis (5). Pap smear testing is a very useful, simple,


economical and safe tool to detect pre invasive cervical
Human papillomavirus (HPV) infection appears to be epithelial lesions. This is similar to Banik et al [9].
involved in the development of more than 90% of cases;
most people who have had HPV infections, however, do A study by Geetu et al. [10] found a total of 2028 cases.
not develop cervical cancer. Other risk factors include 49 (2.41%) cases revealed epithelial abnormalities. The
smoking, a weak immune system, birth control pills, most frequent epithelial cell abnormality was low grade
starting sex at a young age, and having many sexual squamous intra epithelial Lesion (32 cases, 1.58%).
partners, but these are less important. The role of the Nearly half of the patients with abnormal pap smears
Pap smear as a cancer screening tool for the cervix has been presented with a normal looking cervix. Epithelial
substantiated by several studies in the last 50 years and abnormality was more prevalent in post-menopausal
the method has resulted in falling incidence and mortality age group. Hence on a routine basis, every woman
rates of cervical cancer in the developed world [4]. above the age of 30 must be subjected to Pap smear and
Papanicolaou (Pap) smear testing is an effective this must be continued even in post-menopausal period
method of detecting, preventing and delaying the as most of patients with epithelial abnormalities in our
progress of cervical cancer. Even as liquid-based study falls in this group.
cytology is popular in the developed countries, in low
resource settings, a conventional Pap test is the main Conclusion
screening system. It is a well-known fact that the burden
of cervical cancer has been reduced dramatically after Cervical cancer is one of the leading cause of death in
the introduction of screening programmes [5]. women. Pap smear is considered to be effective in
We found that among 1080 Pap smears, 35 were detection of lesions in women. It is economical and non
unsatisfactory, 990 were NILM, 32 were LSIL, 10 were HSIL, sophisticated procedure. Careful Pap smear analysis can
5 were SCC and 8 were ASCUS. Our results are in be proved beneficial in preventing lesions.
agreement with Bal MS et al [5]. We found that maximum
lesions were seen in age group of 51-60 years. This is in
References
agreement with Patel M et al [6]. However, Gupta K [7]
reported higher prevalence in age group 31-40 years. This 1. Ali F, Kuelker R, Wassie B. Understanding cervical cancer in
is in agreement with Sarma U et al [8]. the context of developing countries. Ann Trop Med Public
We found that various changes were atrophy (30), non- Health 2012;22(5):3-15.
specific inflammation (55), trichomoniasis (10), candidiasis 2. Denny L. The prevention of cervical cancer in developing
(25), reactive (25), no other changes (840) and bacterial countries.BJOG 2005;112:1204-12.

Indian Journal of Pathology: Research and Practice / Volume 7 Number 6 / June 2018
726 Anand Nagalikar & Rashmi Chandragouda Meti / Analysis of Cervico- Vaginal Lesions in Women
using Pap Smear: A Histopathological Study

3. Solomon D, Davey D, Kurman R et al. The 2001 Bethesda 7. Sarma U, Mahanta J, Talukdar K. Pattern of Abnormal
system: Terminology for Reporting Results of Cervical Cervical Cytology in women attending a Tertiary Hospital.
Cytology. JAMA2002;287:2114-19. IJSRP2012;2.
4. Bal MS, Malik NP, Sharma VK, Verma N, Gupta A. Prevalence 8. Gupta K, Malik NP, Sharma VK, Verma N, Gupta A.
of cervical dysplasia in western Uttar Pradesh. J Cytol 2013; Prevalence of cervical dysplasia in western Uttar Pradesh.
30:257-62. J Cytol 2013; 30:257-62.
5. Patel MM, Pandya AN, Modi J. Cervical Pap smear study and 9. Banik U, Bhattacharjee P, Ahamad SU, Rahman Z. Pattern
its utility in cancer screening, to specify the strategy for of epithelial cell abnormality in Pap smear: A clinicopathological
cervical cancer control. Nat J Com Med 2011;1:49–51. and demographic correlation. Cytojournal 2011;8:8.
6. Gupta, Goyal R, Suri AK, Mohi MK. Detection of abnormal 10. Geetu, Changhua, Wen F. Clinical utility of Liqui-PREPTM
cervical cytology in Papanicolaou smears. J Cytol 2012;29: cytology system for primary cervical cancer screening in a
45-7. large urban hospital setting in China. J Cytol 2009;26:20-5.

Indian Journal of Pathology: Research and Practice / Volume 7 Number 6 / June 2018
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Indian Journal of Pathology: Research and Practice

IJPRP Volume 7 Number 6, June 2018


DOI: http://dx.doi.org/10.21088/ijprp.2278.148X.7618.2

Original Research Article

Histopathology and Clinical Correlation of Tortion of Ovary

Dost Mohamed Khan1, Naseem Norunnisa2, Abilash S.C.3, Revathishree R.4, N. Thamarai Selvi5,
Pushkar Chaudhary6

1
Associate Professor 2Professor 3Associate Professor 4Associate Professor 5Assistant Professor 6Postgraduate Student, Dept. of Pathology,
Shri Sathya Sai Medical College & Research Institute, SBV ( DEEMED-TO BE- UNIVERSITY), Nellikuppam, Tamil Nadu 603108, India.

Abstract

Ovarian cysts and tumours are the major problems in women. Vast majority of ovarian
cysts are benign in nature. Ovarian cysts are usually asymptomatic, they are found as an
incidental finding during routine ultasonogram. Torsion ovary is a infrequent complication
Corresponding Author: which may present as abdominal pain or acute abdomen.
Methodology: The present study was two year retrospective study conducted during the
Abilash S.C., period of Jan 2014 until Dec 2015. 29 cases with adnexal torsion who underwent surgery
Associate Professor,
Dept. of Pathology,
during this period were included in the study. The clinical details and gross findings were
Shri Sathya Sai Medical College recorded from hospital registry. The histopathology slides were retrieved and findings were
& Research Institute, SBV recorded.
(DEEMED-TO BE- UNIVERSITY) Results: Out of 29 cases 15 cases (51%) were seen between 20-30 years and the common
Nellikuppam, Tamil Nadu 603108,
presenting complaint was abdominal pain. The most common presentation (66%) was on
India.
E-mail: the right side and minority (1%) of these lesions were found to be bilateral. Functional cyst
abey4aris@gmail.com was the more prevalent type of lesion 14 cases(48.28) followed by benign serous cystadenoma
9 cases (31%).
(Received on 04.06.2018,
Conclusion: Acknowledging the fact that majority ovarian cysts were seen in young
Accepted on 22.06.2018)
females, early diagnosis and prompt intervention of cases with rupture or torsion should be
made in consideration of the preserving the adnexa.
Keywords: Ovarian Cysts; Torsion; Hemorrhage.

Introduction [2,3]. Some lesions arepredominantly tumors that can be


benign, borderline, and malignant, Amongst which benign
During infancy and adolescence, which are hormonally epithelial neoplasms are the most common, thatiscystic
active periods ofdevelopment, cystic lesions of the ovary in nature [2,4] .
are most common [1]. Ovarian lesions may be functional
or pathological type, in which functional onesare the most One study revealed that the commonest pathology was
common presenting cystic lesions like follicular and corpus corpus luteum (45%), and the rare one being pregnancy
luteal cysts [2]. Most of cysticlesions were simple cysts, luteum (1%). 7% of the cases presented bilaterally, 51% of
while very few consists of complex cysticarchitecture. cases in left ovary and 42% were in right ovary [5]. Another
Literature reveals that around 90% of these cysts resolvesby study showed that most common ruptured cyst wasluteal
itself [3]. These cysts are most common in young females cyst [6]. Single ovarian or bilateral torsion is seen in small
in twenties because of failure of ovulation with very few girlsalso [7]. Mostly 1 to 3 ovarian follicles can be filled
women in perimenopausal and postmenopausal age groups with fluid following ovulation and lead to formation of

Indian
© Red Journal of Pathology:Pvt.
Flower Publication Research
Ltd. and Practice / Volume 7 Number 6 / June 2018
728 Dost Mohamed Khan, Naseem Norunnisa, Abilash S.C. et al. / Histopathology and Clinical Correlation of Tortion of Ovary

luteal cysts which causes pain on the ipsilateral side or diagnosis. Pathological and clinical symptoms were
all over thepelvis and may even lead to torsion. recorded and were analyzed using statistical software
Torsion distorts flow of lymphatic drainage which SPSS, version.
cause edema, leading toenlargement of ovary causing
hemorrhage. Any delay in management, may cause Results
arterial & venousthrombosis leading to necrosis [3].
Polycystic ovaryalong with oligomenorrhoea or amenorrhea This study has shown that the adnexal torsion frequently
or infertility with anovulation may lead to adnexal torsion occurs on the right side (66%) followed by left side (33%)
[3].Ovarian cystic masses with an average size may cause (Table1). The most common age for adnexal torsion was
a pressure to the adjacent organs [8]. 20-30 years (51%)(Table 2).
From pathological point of view, 48% of adnexal
Materials and Methods torsion was due to the ovarian functional masses, 13%
due to the benign serous cystadenoma followed by
A retrospective analysis was done by reviewing the mucinosis cystadenoma (13%) and dermoid cyst(7%)
surgical gross and microscopic examination reports of (Table 2). Regarding clinical symptoms, 93% of patients
patients who underwent surgical management for referred with abdominal pain, 65% abdominal and
ovarian cystic lesions from January 2014 until December pelvic tenderness,62% nausea and vomiting, 58% cervix
2015. The presumptive diagnosis obtained from gross pain in moving, and the other cases have been
examination was compared with the final histopathological mentioned in (Table 3).

Table 1: Frequency place of adnexal torsion

Adnexal Torsion Percent

Right 66%
Left 33%
Bilateral 1%

Table 2: Age distribution of adnexal masses

S. No Adnexal Mass Quantity Age Distribution


20-30 30-40 40-50 50-60

1 Functional 14 10 3 1
2 Benign serous cystadenoma 9 4 2 1 2
3 Mucinous cystadenoma 4 - 1 2 1
4 Dermoid Cyst 2 1 1
Percentage 51% 24% 14% 10%

Fig. 2: The torsed ovary is enlarged, edematous, engorged with blood,


Fig. 1: Shows ovary enlarged, edematous and hemorrhagic cystic cavities and maybe infarcted

Indian Journal of Pathology: Research and Practice / Volume 7 Number 6 / June 2018
Dost Mohamed Khan, Naseem Norunnisa, Abilash S.C. et al. / Histopathology and Clinical Correlation of Tortion of Ovary 729

Table 3: Clinical Features of Adnexal torsion

Clinical Signs Quantity Percent

Abdominal pain 27 93%


Abdominal & Pelvic Tenderness 19 65%
Nausea & Vomiting 18 62%
Painful cervix movement 17 58%
Tachycardia 16 55%
Urinary signs 15 51%
Rebound Tenderness 14 48%
Tachypnea 11 37%
Orthostatic changes 9 31%
Fever>38. 8 27%

Fig. 3: Shows Ovarian torsion with normal uterus and cervix Fig. 5: Shows hemorrhage in the cystic areas

Fig. 6: Shows benign serous cystadenoma features with edema and


Fig. 4: Shows Hemorrhage and necrosis in the ovarian parenchyma hemorrhage

Discussion tenderness in the lower quadrants [1]. 9 out of 14 cases


Partial or complete rotation of ovary hampering of functional ovarian masses grossly showed enlarged,
vascular supply leading to ovarian torsion.Ovarian torsion edematous and hemorrhagic cystic cavities(Figure 1&2).
occurs mainly in young lady (15–30 years) and in Microscopically showed marked hemorrhage, marked
postmenopausal women [9] which depicts bimodal age acute and chronic inflammatory cell collections(Figure
population. The majority of ovarian torsion is more 4). Remaining 5 cases showed hemorrhage,acute
common in functional and benign lesions [10,11]. This study inflammatory cell collections with focal preservation of
was compared with Myers et al [12]. The major clinical follicles(Figure 5). 6 out of 9 cases of benign serous
features were abdominal pain,abdominal or pelvic cystadenoma grossly showed ovarian torsion with

Indian Journal of Pathology: Research and Practice / Volume 7 Number 6 / June 2018
730 Dost Mohamed Khan, Naseem Norunnisa, Abilash S.C. et al. / Histopathology and Clinical Correlation of Tortion of Ovary

normal uterus and cervix (Figure 3). Microscopically 4. Purcell K, Wheeler JE. Benign disorders of the ovarian and
showed hemorrhage, profound acute and chronic oviducts, in Decherney AH, Lauren N. Current obstetric and
inflammatory cell collections, and infarct (Figure 6). gynecologic diagnosis and treatment. 9th ed. USA: Mc-
Remaining 3 cases showed focal torsion with serous Graw-Hill Medical; 2003.pp.708-14.
cystadenoma features. All the cases mucinous 5. Chapron C, Dubuisson JB, Fritel X, Rambaud D. Diagnosis
cystadenoma and dermoid cyst showed fresh and old and management of organic ovarian cysts: indications and
hemorrhages, fibrous proliferation and necrosis with procedures for laparoscopy. Hum Reprod Update
1996;2(5):435-46.
signs of mucinous cystadenoma and dermoid cyst
features.This study is compared with Chen M et al [9]. 6. Mohammad Jafary R. Saadati N. A Survey on pathology
clinical sign and symptoms of ovarian cyst in Imam
The present study shows 66% of lesions on the right Hospital. Scientific medical journal 2010;8(4):503-9.
side ovary,this finding was in concurrence with the study
7. Au Rousseau V, massicot R, Darwish AA, Saadat F,
done by Myers E et al [2]. Rupture and torsion in the left
Emergency management and conservative surgery of
side is probably protected by rectosigmoid . Like studies ovarian torsion in children: a report of 40 cases so J Pediatr
Golash V et al. [12], Narducci F et al. [13], the present study Adolesc. Gynecology 2008;21(4):201-6.
showed most common torted mass was ovarian functional
8. Sagiv R, Golan A, Glezerman M. Laparoscopic management
masses and benign serous cystadenoma. Our study also of extremely large ovarian cysts. Obstet Gynecol 2005;
depicts, the rarely torted ovarian mass was dermoid cyst. 105(6):1319-22.
9. Chen M, Chen CD, Yang YS. Torsion of the previously normal
Conclusion uterine adnexa. Evaluation of the correlation between the
pathological changes and the clinical characteristics. Acta
The delay in the diagnosis of ovarian torsion mainly Obstet Gynecol Scand 2001;80:58-60.
due to the presenting non specific clinical features, 10. Rosai J. Female reproductive system In: Rosai and
thereforerequired high level attention to treat the Ackerman’s Surgical Pathology, 9th ed. Vol 2; Index: Laksme
ovarian torsion and to preventcomplications. Most of Traders; 2005:1659-74.
the ovarian masses were benign and occurred duringthe 11. Kumar V, Abbas A, Fausto N, The female genital system and
productive ages,any suspicious case of ovarian rupture Breast. In: Robbin and Cotran Pathologic Basis of Diseases
or torsion must bekept under control, and prompt 7th ed. USA: WB Saunders Company; 2004:695-700.
treatment is compulsory for them. 12. Golash V, Willson PD. Early laparoscopy as a routine
Procedure in the management of acute abdominal pain: A
review of 1, 320 patients. Urg Endosc. 2005;19(7):882- 5.
References
13. Narducci F, Orazi G, Cosson M. Ovarian Cysts: surgical
1. Brandt ML, Helmrath MA. Ovarian cysts in infants and indications and access. J Gynecol Obstet Biol 2001;30:
children. Semin Pediatr Surg. 2005;142:78-85. (Suppl): s59- 67.

2. Myers E. The ovarian cysts. Obstet Gynecol J 2005;30:357- 60.


3. Kazzi, Amin Antione; ovarian cysts. Emerg Med Clin North
Am. Aug 2004;22(3);683-96.

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Indian Journal of Pathology: Research and Practice

IJPRP Volume 7 Number 6, June 2018


DOI: http://dx.doi.org/10.21088/ijprp.2278.148X.7618.3

Original Research Article

Histopathological Patterns of Gall Bladder Diseases in Routine


Cholecystectomy Specimens: A Hospital-Based Study from a Rural Medical
College, Uttar Pradesh

Praneeta J. Singh1, Sheetal G. Gole2


1
Associate Professor, Department of Pathology, K.D. Medical College Hospital and Research Center, Akbarpur, Mathura,  Uttar Pradesh,
281406, India. 2Professor & Head, Department of Pathology, Employee’s State Insurance Corporation Medical College & Hospital, Faridabad,
Haryana, 121001, India.

Abstract

Introduction:Cholelithiasis is the most common disease affecting gallbladder.


Gallstones cause several histological changes in gallbladder mucosa like acute and chronic
inflammation, metaplasia, hyperplasia, calcification and dysplasia. Present study evaluates
the incidence of various histopathological lesions observed in routine cholecystectomy
Corresponding Author: specimen.
Sheetal G. Gole, Material and methods:This was a hospital based prospective study conducted over a
Professor & Head, Department of period of 1 year. Detailed gross examination was done in total 325 routine cholecystectomy
Pathology, Employee’s State specimens and microscopic examination was done on slides stained with hematoxylin and
Insurance Corporation Medical eosin stain.
College & Hospital, Faridabad,
Haryana, 121001, India. Results: Maximum number of patients were in the age group of 21-40 years (49.85%).
Number of female patients was 253 (77.85%) and that of male patients was 72 (22.15%). On
E-mail: gross examination, gallstones were found in 239 cases (73.54%). Maximum number of cases
drsheetalgole@rediffmail.com 216 (66.46%) and 166 (51.07%) showed normal wall thickness and normal mucosa respectively.
Most common histopathological diagnosis was chronic non-specific cholecystitis in 270
(Received on 31.03.2018, (83.07%) cases followed by 8 (2.46%) cases each of follicular cholecystitis, cholesterolosis
Accepted on 23.04.2018)
and adenomyomatosis. Epithelial changes like metaplasia seen in 28 (8.61%)cases,
hyperplasia in 17 (5.23%)cases, reactive atypia in 6 (1.85%) cases and dysplasia in 3 (0.92%).
Conclusion: Chronic cholecystitis was the most common histopathological diagnosis
and it was found to be associated with various changes in gallbladder mucosa like gastric
and intestinal metaplasia, hyperplasia and dysplasia. Variants of cholecystitis like
xanthogranulomatous cholecystitis, follicular cholecystitis and eosinophilic cholecystitis
were also reported. The present study highlights the value of submitting all routine
cholecystectomies for thorough histopathological examination.
Keywords: Chronic Cholecystitis; Gallstones; Acute Emphysematous Cholecystitis;
Porcelain Gall Bladder; Dysplasia.

Introduction and chronic cholecystitis, xanthogranulomatous


cholecystitis, cholesterolosis, adenomyomatosis, polyp,
Cholelithiasis is most common disease affecting mucocele of gallbladder and most common
gallbladder. In India prevalence of gallstone disease is histopathological lesion being non-specific cholecystitis.
reported to be higher in North India [1]. Changes in gallbladder mucosa associated with
Histopathological examination of cholecystectomy cholelithiasis like metaplasia, reactive atypia and
specimens reveals various lesions of gallbladder like acute dysplasia are postulated to be the precursors for

Indian
© Red Journal of Pathology:Pvt.
Flower Publication Research
Ltd. and Practice / Volume 7 Number 6 / June 2018
732 Praneeta J. Singh & Sheetal G. Gole / Histopathological Patterns of Gall Bladder Diseases in Routine
Cholecystectomy Specimens: A Hospital-Based Study from a Rural Medical College, Uttar Pradesh

gallbladder carcinoma. Thus, histopathological examination Results


of gallbladder specimen forms an important diagnostic
tool [2]. Total 325 routine cholecystectomy specimens were
studied over a period of 1 year. Age of the patients ranged
Present study evaluates the incidence of various
from 9 years to 78 years. Maximum number of patients
histopathological lesions observed in routine
were in the age group of 21-40 years (49.85%) as shown
cholecystectomy specimen.
in Table 1. Number of female patients was 253 (77.85%)
and that of male patients was 72 (22.15%).
Material and Methods On gross examination, gallstones were found in 239
(73.54%) cases while it was absent in 86 (26.46%) cases.
This was a hospital based prospective study conducted Cholesterol stones (yellow stones) were most common
over a period of 1 year in the Department of Pathology at occurrence seen in 130 (54.39%)cases followed by
a rural tertiary care hospital in North India. All routine pigmented stones in 93 (38.91%)cases and mixed stones in
cholecystectomy specimens sent for histopathological 16 (6.69%) cases. Out of total 325 cases, wall thickness was
examinationduring the study period were included in the normal in 216 (66.46%) cases and it was > 0.3 cm in 109
study. (33.54%) cases. Mucosa was normal in 166 (51.07%),
Cases with clinical suspicion of gall bladder carcinoma atrophied in 132 (40.61%), ulcerated in 7 cases (2.15%),
(GBC) were excluded from the study. Detailed gross strawberry like in 10 (3.07%), hyperplastic in 6 (1.85%),
examination of gallbladder was done and its size, external calcified in 2 (0.62%), necrotic in 1 (0.3%), and cystic in 1
surface appearance, appearance of mucosa, thickness (0.3%).
of the wall, presence of any suspicious lesion on cut Most common histopathological diagnosis was chronic
surface and presence of any gallstones were noted. In some non-specific cholecystitis in 270 cases (83.07%), of which
cases of cholelithiaisis, already cut opened gall bladder 200 (74.07%) cases were associated with gallstones and in
specimens were received without gall stones. In such cases 70 (25.93%) cases gallstone was absent as shown in Table
absence of gallstone was recorded in gross examination. 2. Eight cases (2.46%) each of follicular cholecystitis,
Three sections were taken from gallbladder each cholesterolosis and adenomyomatosis were reported.
representing fundus, body and neck. Additional sections Acute cholecystitis was reported in 5 cases (1.54%),of which
were taken from any suspicious areas. Histopathological gallstone was present in1 case (20%)and absent in 4 cases
sections were stained using hematoxylin and eosin (H&E) (80%). One case (0.30%) of acute emphysematous
stain. cholecystitis was reported in adult female with no prior
history of diabetes mellitus. Culture for organism

Table 1: Age wise distribution of cases


Age group Total number (%)
0-20 11 (3.38)
21-40 162 (49.85)
41-60 114 (35.07)
61-80 38 (11.70)

Table 2: Distribution of cases according to histopathological diagnoses and type of gallstone

Histopathological Diagnoses Total no. of cases Distribution of cases according to gallstones


N (%) Gallstone present Gallstone
Yellow Pigment Mixed Total absent

Chronic non-specific cholecystitis 270 (83.07) 106 80 14 200 (74.07) 70 (25.93)


Chronic cholecystitis with dysplasia 03 (0.92) 02 01 - 03 (100) -
Acute cholecystitis 05 (1.54) - 01 - 01 (20) 04 (80)
Acute on chronic cholecystitis 04 (1.23) 03 - - 03 (75) 01 (25)
Acute emphysematous cholecystitis 01 (0.30) 01 - - 01 (100) -
Follicular cholecystitis 08 (2.46)) 04 03 - 07 (87.5) 01 (12.5)
Eosinophilic cholecystitis 02 (0.62) - - - - 02 (100)
Lymphoeosinophilic cholecystitis 07 (2.15) 02 04 - 06 (85.71) 01 (14.29)
Cholesterolosis 08 (2.46) 06 - 01 07 (87.5) 01 (12.5)
Xanthogranulomatous cholecystitis 06 (1.85) 04 01 01 06 (100) -
Porcelain gallbladder 02 (0.62) - 01 - 01 (50) 01 (50)
Mucocele of gallbladder 01 (0.30) - - - - 01 (100)
Adenomyomatosis 08 (2.46) 02 02 - 04 (50) 04 (50)

Indian Journal of Pathology: Research and Practice / Volume 7 Number 6 / June 2018
Praneeta J. Singh & Sheetal G. Gole / Histopathological Patterns of Gall Bladder Diseases in Routine 733
Cholecystectomy Specimens: A Hospital-Based Study from a Rural Medical College, Uttar Pradesh

Fig. 1A: Xanthogranulomatous cholecystitis (H&E,10X) B: Xanthogranulomatous cholecystitis (H&E,40X) C: Follicular cholecystitis
(H&E,10X), D: Eosinophilic cholecystitis (H&E,40X)

Fig. 2A: Gastric metaplasia in case of chronic cholecystitis (H&E,40X), B: Segmental adenomyosis (H&E,40X), C: Porcelain gall
bladder showing calcification (H&E,40X), D: Acute emphysematous cholecystitis (H&E,40X)

Indian Journal of Pathology: Research and Practice / Volume 7 Number 6 / June 2018
734 Praneeta J. Singh & Sheetal G. Gole / Histopathological Patterns of Gall Bladder Diseases in Routine
Cholecystectomy Specimens: A Hospital-Based Study from a Rural Medical College, Uttar Pradesh

identification was not done in this case. In both cases (0.62%) in 53.4). Mathur SK et al [7] ] reported thickened
of eosinophilic cholecystitis, gallstone was absent. Out of gallbladder wall in 53.6% cases and normal thickness in
7 cases (2.15%) of lymphoeosinophilic cholecystitis, 46.4% cases.
gallstones were present in 6 cases (85.71%) and In present study, on gross examination mucosa was
absent in 1 case (14.29%). All 6 cases (1.85%) of normal in maximum number of cases 166 (51.07%).
xanthogranulomatous cholecystitis were associated with Similar finding was reported by Baidya R et al [6] while
gallstones. Porcelain gallbladder was reported in 2 cases Khanna R et al [5] reported equal number of cases with
(0.62%)out of which one was associated with gallstone normal and atrophic mucosa.
while in 1 case gallstone was absent. Mucocele of
gallbladder was reported in 1 case (0.30%). In 3 cases Metaplasia
(0.92%) dysplasia was seen in association with chronic
The review of literature shows that cholelithiasis and
cholecystitis associated with gallstones as shown in
inflammation leads to gastric or intestinal type of
Table 2.
metaplasia in gallbladder mucosa which in turn can be
On microscopic examination following epithelial associated with dysplasia and carcinoma [8,9]. Studies
changes were noted: metaplasia in 28 cases (8.61%) out have reported that gastric metaplasia was the most
of which gastric antral metaplasia seen in 16 cases common type of metaplasia in cases of chronic
(4.92%) and intestinal metaplasia in 12 cases (3.69%), cholecystitis or cholelithiasis [8].
hyperplasia in 17 cases (5.23%), reactive atypia in 6 cases
In present study metapalsia was reported in 28 cases
(1.85%) and dysplasia in 3 cases (0.92%).
(8.61%) which is higher as compared to study by Zahrani
IH et al.[10](3%) and Stancu M et al.[11] (5%) and lower as
Discussion compared to study by Arathi NA et al.[12](18.6%).On
dividing metaplasia into two categories as gastric and
In India gallstone disease affects younger age group as intestinal metaplasia, occurrence of gastric antral
compared to the western population with a female metaplasia was slightly higher than intestinal
predominance [11]. In present study also maximum metaplasia [4.92% and 3.69% respectively] in present study.
number of patients 162 (49.85%) belonged to the younger (Figure 2A) Significantly higher percentage of gastric
age group of 21-40 years with sex wise distribution showing metaplasia was reported by Zahrani IH et
female predominance (77.85%). Similar findings were al.[10](88%)Stancu M et al.[11](83.7%) and Arathi NA et
reported by Khan S et al [3]. al.[12](79.5%). While studies by Mathur SK et al.[7](pyloric
In the present study, gallstones were present in 239 cases metaplasia in 10% cases and intestinal metaplasia in 8%)
(73.54%). In retrospective study by Khan S et al [3]. it was and Khanna R et al.[5] (antral metaplasia in 16.5%,
observed that though clinical data given on histopathology intestinal metaplasia in 15.5%) reported no significant
form by surgeons showed presence of gallstones in 99.2% difference in occurrence of gastric and intestinal
patients but all of it was not received in the laboratory metaplasia.
since in many cases the stones were handed over to the
Hyperplasia
patients’ relatives after the surgery. Similar practice of
handing over gallstones to patients’ relatives was carried Studies have suggested hyperplasia of gallbladder
out at our hospital. Present study was a prospective study mucosa could be a precursor lesion of carcinoma
so cases where cholelithiasis was mentioned on gallbladder [13].
histopathology form but no stone was received in In present study epithelial hyperplasia was seen in 17
histopathology laboratory, absence of gallstone was cases. Higher percentage of epithelial hyperplasia (69%)
recorded in gross examination. This may have lead to less was reported by Khanna R et al.[5], Baidya R et al.[6] (46.2%),
number of cholelithiasis cases in present study. Kaur A et al.[14](25.02%) and Stancu M et al. [11] (7.8%).
In North India cholesterol gall stones (>80%) are In present study dysplasia associated with cholelithiasis
common while pigment gallstones are more common was seen in 3(0.92%)cases. In all 3 cases of dysplasia, whole
in South India [4]. Present study was conducted in North gallbladder was submitted for histopathological
India and most common gallstone was cholesterol examination to rule out any associated carcinoma.
gallstone 130 (54.39%) cases. Dysplasia was distinguished from reactive metaplasia on
In present study, wall thickness was normal in basis of nuclear features like chromatin pattern, presence
maximum number of cases 216 (66.46%) and increased or absence of prominent nucleoli and loss of polarity and
in 109 cases (33.54%). Similar findings were reported by presence or absence of intraepithelial neutrophils. Studies
Khanna R et al [5]. (57.5% normal thickness and 42.5% by Sharma I et al.[15](1.3%) and Baidya R et al.[6](1.3%)
thickened wall) and Baidya R et al [6]. from Nepal (normal reported similar percentage of dysplasia while higher

Indian Journal of Pathology: Research and Practice / Volume 7 Number 6 / June 2018
Praneeta J. Singh & Sheetal G. Gole / Histopathological Patterns of Gall Bladder Diseases in Routine 735
Cholecystectomy Specimens: A Hospital-Based Study from a Rural Medical College, Uttar Pradesh

percentage dysplasia was reported by Khanna R et Similarly, in present study an isolated case of acute
al.[5](8.5%) and lower percentage of dysplasia (0.4%) emphysematous cholecystitis (Figure 2D) was reported
was reported by Stancu M et al [11]. in young female with no prior history of diabetes
In present study most, common histopathological mellitus. As culture was not done in this case causative
diagnosis was chronic non-specific cholecystitis in 270 organism could not be identified.
(83.07%) which is comparable to other studies [3,15,16].
Five cases (1.72%) of acute cholecystitis were seen in Conclusion
present study. Similar finding was reported by Khan S et
al.[3] (2.7%) while Talreja V et al.[16]reported higher Cholelithiasis was common in younger age group with
incidence of acute cholecystitis (6.32%) cases. a female predominance. Chronic cholecystitis was most
In present study acute on chronic cholecystitis was common histopathological diagnosis and it was found
reported in 4 cases (1.38%)while Mathur SK et al.[7]reported to be associated with various changes in gallbladder
higher percentage of such cases (12%). mucosa like gastric and intestinal metaplasia,
hyperplasia and dysplasia. In few cases variants of
In present study 7 cases (2.41%) of Xanthogranulomatous
cholecystitis (Figure 1AB) and 2 cases (0.69%)of cholecystitis like xanthogranulomatous cholecystitis,
Eosinophilic cholecystitis (Figure 1D) were reported. follicular cholecystitis, eosinophilic cholecystitis was
Similar findings were reported that Khan S et al.[3]and also reported. The present study highlights the value of
Sharma I et al [15]. submitting all routine cholecystectomies for thorough
In present study 7 cases (2.41%) of Follicular cholecys- histopathological examination.
titis(Figure 1C) were reported. Higher percentage of cases
(5%) was reported by Mathur SK et al.[7]while Khan S et References
al.[3]reported lower percentage of cases (0.25%).
Cholesterosis was reported in 5 cases (1.72%)in present 1. Kapoor VK, McMichael AJ. Gallbladder cancer: an ‘Indian’
study, while higher percentage of cases were reported by disease. Natl Med J India2003;16(4):209-13.
Khan S et al.[3] (10%), Mathur SK et al.[7] (6%), Sharma I 2. Taha MM Hassan, Anil Mohan Rao. S. Benign Mimickers of
et al.[15] (4.4%) and Talreja V et al.[16](12.31%). Gall Bladder Carcinoma in Cholecystectomy Specimens:
Histopathological Study. International Journal of Scientific
Adenomyomatosis of gallbladder is a tumor like lesion Research. 2015;4(7).
but some studies have suggested that it may have
3. Khan S, Jetley S, Husain M. Spectrum of histopathological
malignant potential and may act as precursor for
lesions in cholecystectomy specimens: A study of 360 cases
developing carcinoma [19].
at a teaching hospital in South Delhi. Arch IntSurg 2013;
In present study adenomyomatosis (Figure 2B) was 3(2):102-5.
reported in 6 cases (2.07%), which is less as compared to 4. Choudhuri G, Agarwal DK, Negi TS. Polarizing microscopy
study done by Mathur SK et al [7] and higher as compared of partially dissolved gallstone powder: A simple technique
to study done by Khan S et al [3]. for studying gallstone composition. J Gastroenterol Hepatol
In present study one case of porcelain gallbladder 1995;10(3):241–5.
(Figure 2C) was seen in which full thickness of gallbladder 5. Khanna R, Chansuria R, Kumar M, Shukla HS. Histological
wall was involved and it was replaced by calcified fibrosis changes in gallbladder due to stone disease. Indian J Surg
and mucosa was completely denuded. 2006;68(4):201-4.
Previously many studies reported that absence of 6. Baidya R, Sigdel B, Baidya NL. Histopathological changes
mucosa in cases of porcelain gallbladder with extensive in gallbladder mucosa associated with cholelithiasis.
calcification reduces the risk of subsequent development Journal of Pathology of Nepal 2012;2(3):224-5.
of carcinoma [17]. However recent studies suggested that 7. Mathur SK, Duhan A, Singh S, Aggarwal M, Aggarwal G, Sen
pattern or the depth of calcification should not be R, et al. Correlation of gallstone characteristics with
considered while predicting the risk of developing mucosal changes in gall bladder. Trop Gastroenterol 2012;
carcinoma in the future [17]. 33(1):39-44.

Acute emphysematous cholecystitis is a form of acute 8. Mukhopadhyay S, Landas SK. Putative precursors of
gallbladder dysplasia: A review of 400 routinely resected
cholecystitis reported to be more common in older
specimens. Arch Pathol Lab Med 2005;129(3):386–90.
patients with history of diabetes mellitus and Clostridium
is the most common causative agent [18]. Khare S et al.[18] 9. Nora Katabi. Neoplasia of Gallbladder and Biliary
reported a case of acute emphysematous cholecystitis Epithelium. Archives of Pathology & Laboratory Medicine
2010;134(11):1621-7.
in young nondiabetic patient caused by Escherichia coli.

Indian Journal of Pathology: Research and Practice / Volume 7 Number 6 / June 2018
736 Praneeta J. Singh & Sheetal G. Gole / Histopathological Patterns of Gall Bladder Diseases in Routine
Cholecystectomy Specimens: A Hospital-Based Study from a Rural Medical College, Uttar Pradesh

10. Zahrani IH, Mansoor I. Gallbladder pathologies and cholelithiasis. 15. Sharma I, Choudhary D. Histopathological patterns of gall
Saudi Med J 2001;22(10):885-9. bladder diseases with special reference to incidental
11. Caruntu ID, Giu ca S, Dobrescu G. Hyperplasia, metaplasia, cases: a hospital-based study. International Journal of
dysplasia and neoplasia lesions in chronic cholecystitis – Research in Medical Sciences. 2015;3(12):3553-7.
a morphologic study. Romanian J of Morphol Embryol 16. Talreja V, Ali A, Khawaja R, Rani K, Samnani SS, Farid FN.
2007;48(4):335–42. Surgically resected gall bladder: Is histopathology needed
12. Arathi NA, Awasthi S, Kumar A. Pathological profile of for all? Surg Res Pract. 2016;Article ID 9319147.
cholecystectomies in a tertiary centre. National Journal of 17. Machado NO. Porcelain Gallbladder Decoding the malignant
Medical and Dental Research 2013;2(1):28-38. truth. Sultan Qaboos University Med J 2016;16(4):416–21.
13. Albores-Saavedra J, Molberg K, Henson DE. Unusual 18. Khare S and Pujahari AK. A Rare Case of Emphysematous
malignant epithelial tumors of the gallbladder. Semin Diagn Cholecystitis. J Clin Diagn Res 2015;9(9):13-14.
Pathol 1996;13(4):326-38. 19. Ozgonul A, Bitiren M, Guldur ME, Sogut O, Yilmaz LE. Fundal
14. Kaur A, Dubey VK, Mehta KS. Gallbladder mucosal changes Variant Adenomyomatosis of the Gallbladder: Report of
associated with chronic cholecystitis and their relationship Three Cases and Review of the Literature. J Clin Med Res
with carcinoma gallbladder. Surgery ASCOMS, JK Science. 2010;2(3):150–3.
2011;14(2):89-92.

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Indian Journal of Pathology: Research and Practice

IJPRP Volume 7 Number 6, June 2018


DOI: http://dx.doi.org/10.21088/ijprp.2278.148X.7618.4

Original Research Article

Spectrum of Ovarian Lesions: An Institutional Study

Bhangale Harshada R.1, Pathade Smita C.2, Mendhe Runali D.3, Borole Bharat S.4, Sangole Vilas M.5

1
Post Graduate Student (JR III) 2Associate Professor 3PG Student (JR II) 4Professor 5Professor and Head, Department of Pathology, Dr.
Ulhas Patil Medical College & Hospital, Jalgaon, Maharashtra 425309, India.

Abstract

Introduction: Ovary is the commonest site for developing non-neoplastic and neoplastic
lesions. These lesions can occur in any age group from childhood to postmenopausal women.
Aims and Objectives: This study was conducted to analyse the histopathological features
Corresponding Author: of all ovarian lesions and classify them.
Smita Charandas Pathade Materials and Methods: Present study is a prospective study of 52 cases carried out over
Associate Professor, a period of one year from July 2016 to July 2017 . All patients admitted in gynaecologyward
Department of Pathology, posted for oophorectomywith or without hysterectomywere included in the study. Salient
Dr. Ulhas Patil Medical College & findings related to individual case alongwith final histopathogical diagnosis were noted.
Hospital, Jalgaon, Maharashtra
425309, India. Results: There were total 58 lesions; out of which 37 were non-neoplastic; 13 were benign;
E-mail: and 8 lesions were of malignant variety. The most common age group involved was 40-59
drsmitajadhav2005@yahoo.com years. The commonest symptom was abdominal pain and the right sided ovary was commonly
involved. Follicular cyst was the commonest non-neoplastic lesion; whereas most common
(Received on 07.05.2018, benign lesion was mucinous cystadenoma . Serous cystadenocarcinoma was the commonest
Accepted on 22.05.2018) malignant lesion.
Conclusion: Ovaries can be affected by variety of non-neoplastic and neoplastic lesions.
Good clinical history and physical examination together with USG findings helps in probable
diagnosis. Specific diagnosis is based mainly on routine gross and histopathological
examination of the specimen. The study of macroscopic and microscopic features of
different ovarian tumors enables categorization into morphological type which helps the
gynecologists for proper management.
Keywords: Histopathology; Neoplastic Lesions; Non-Neoplastic Lesions; Ovarian Lesions.

Introduction The most common types of lesions encountered in


the ovary include functional or benign cysts and
The ovaries are paired intra-pelvic organs of the female tumours. Both ovarian neoplastic and non-neoplastic
reproductive system. Each ovary consists of variety of cells lesions possess a great challenge to gynecological
that describes itsstructural complexity. This variety of cells oncologist. Some non-neoplastic lesions of the ovary
can give rise to benign, malignant or borderline tumours. usually present as a pelvic mass and mimic an ovarian
This is due to the complex structure of the ovary [1] as well neoplasm. Therefore, their proper recognition and
as its typical functions. These occur with the cyclical classification is important to allow appropriate
changes that take place every month constantly [2]. therapy [3].

Indian
© Red Journal of Pathology:Pvt.
Flower Publication Research
Ltd. and Practice / Volume 7 Number 6 / June 2018
738 Bhangale Harshada R., Pathade Smita C., Mendhe Runali D. et al. / Spectrum of Ovarian Lesions – An Institutional Study

The non-neoplastic lesions forming pelvic masses and The tissues were processed by routine paraffin
mimicking ovarian tumours can be categorized into technique and sections were stained with haematoxylin
follicular cyst, simple cysts, corpus luteal cysts, and eosin. Microscopic slides were studied thoroughly
endometriotic cysts and hemorrhagic cysts. WHO and final histopathological diagnosis was given after
classification of ovarian neoplasms is based on the most discussing the case in our department. Neoplastic
probable tissue of origin, accordingly they are lesions were categorized as per WHO classification.
categorized as surface epithelial tumours, sex cord
stromal tumours, germ cell tumours, metastatic
tumours and tumours from ovarian soft tissue. Each Results
category is further divided into subtypes.Ovarian
Total 58 ovaries of 52 patients were analyzed in this
carcinoma accounts for the greatest number of deaths
study; out of which 36 lesions (62.1%) were non-neoplastic
from malignancies of female genital tract and is the fifth
and 22 lesions (37.9%) were neo-plastic (Table 1).
leading cause of cancer fatalities [4]. Distinction between
non-neoplastic lesions and neoplastic lesions of ovary on The most common age group involved by non-
histopathological basis is necessary since proper neoplastic lesions of ovary was 20-39 years accounting
treatment depends upon the histological abnormality [5]. for 48.6% incidence; whereas that of neoplastic lesions
was 40-59 years (47.6%).

Materials and Methods Out of all 52 cases, 46 specimens (88.5%) were


unilateral and only 6 specimens (11.5%) were bilateral.
Present study is a prospective study of 52 cases carried Out of all 58 ovarian specimens, 39 ovaries (67.2%) were
out over a period of one year from July 2016 to July 2017 cystic, 13 ovaries (22.4%) were solid and cystic and 6
. All patients admitted in gynecology ward posted for
ovaries (10.3%) were solid on gross examination (Table 2).
oophorectomy with or without hysterectomy were included
in the study. Detail clinical history was taken. Thorough The most common non-neoplastic lesion was follicular
physical examination was carried out. Findings of USG cyst accounting for 20 lesions (55.6%) followed by
abdomen and pelvis were noted. Oophorectomy specimens hemorrhagic cyst which was observed in 15 ovaries (41.7%)
(with or without hysterectomy) received in histopathology (Table 3). There was a single case of corpus luteal cyst.
section of Central clinical laboratory were studied in detail. As shown in table IV, out of total 22 neoplastic lesions,
The ovarian specimens were analyzed macroscopically 14 lesions were benign and 8 lesions were malignant.
for various parameters like size, external surface,
Amongst 14 benign lesions, the most common was serous
consistency, cut section appearance - Solid or cystic. If
cystadenoma with 28.6% incidence followed by mature
solid, its color, presence or absence of necrotic and
cystic teratoma accounting for 21.4% incidence; 2
hemorrhagic areas, if cystic - contents of cyst, number of
lesions of fibrothecoma and mucinous cystadenomaa
locules, thickness of cyst wall, smooth or rough internal
surface, presence of papillary excrescences, mention of each and single case of fibroma, serous cystadenofibroma
solid areas etc. Grossing was done according to standard and Brenner’s tumour were also encountered.
operating procedure and appropriate sections were There were total 8 malignant lesions; out of which,
submitted for tissue processing. the most common was serous cystadenocarcinoma

Table 1: Distribution ofall ovarian lesions

Distribution of lesions No. of cases %


Non-neoplastic lesions 36 62.1
Benign neoplastic lesions 14 24.1
Malignant neoplastic lesions 8 13.8

Table 2: Distribution ofcases according to gross features

Gross features No. of lesions %

Cystic 39 67.2
Solid and cystic 13 22.4
Solid 6 10.3
Total 58 100.0

Indian Journal of Pathology: Research and Practice / Volume 7 Number 6 / June 2018
Bhangale Harshada R., Pathade Smita C., Mendhe Runali D. et al. / Spectrum of Ovarian Lesions – An Institutional Study 739

Table 3: Distribution of non-neoplastic lesions

Non-neoplastic lesions No. of cases %


Follicular cyst 20 55.6
Luteal cyst 1 2.8
Hemorrhagic cyst 15 41.7
Total 36 100.0

Table 4: Distribution of Neoplastic lesions

All neoplastic lesions No. of cases %

Fibroma 1 4.8
Fibrothecoma 2 9.5
Mucinous cystadenoma 3 14.3
Serous cystadenoma 2 9.5
Mature cystic teratoma 2 9.5
Recurrent fibromatosis 1 4.8
Brenner's tumour 1 4.8
Serous adenofibroma with atypia 1 4.8
Serous cystadenocarcinoma 4 19.0
Mucinous cystadenocarcinoma 1 4.8
Mixed germ cell tumour 2 9.5
Krukenberg'stumour 1 4.8
Total 21 100

with 50% incidence followed by mixed germ cell tumour concordance with studies reported by Kanthikar et al.
accounting for 25% incidence. Mucinous cystadenocarcinoma [12] and Prakash et al [13]. However, both of the above
and Krukenberg’stumour eachhad 12.5% incidence. mentioned authors reported their second most common
lesions as corpus luteal cyst which has only 2.7%
incidence in our study.
Discussion
We reported more benign lesions than malignant
Ovarian cancer is the second leading cause of lesions which correlates well with studies reported by Gupta
mortality among all gynecological cancers [6]. et al. [14] and Prakash et al [13].
Due to similar clinical presentation, there is confusion Most common benign lesion was serous cystadenoma
in the diagnosis of non-neoplastic and neoplastic lesions in our study as well as studies reported by Thakkar et al.
of ovary, although it is diagnosed as a mass or cystic lesion [1] and Prakash et al [13]. However, our second most
on ultrasonography and hence removed prophylactically common lesion was mature cystic teratoma which
in routine oophorectomies and hysterectomies [7]. correlates well with study by Thakkar et al [1] but is in
contrast with the study by Prakash et al [13]. Also none of
In present study, maximum number of non-neoplastic
the above authors reported any case of benign Brenner’s
lesions were found in 2nd and 3rd decade of life; whereas
tumour which has 4.8% incidence in our study.
that of neoplastic lesions were found in 4th and 5th decade
of life. Similar findings were observed by Kar et al[8] and The incidence of fibroma, fibrothecoma and serous
Pathade et al.[9] However, Ramachandran et al [10] cystadenofibroma are well in concordance with the study
reported maximum number of neoplastic lesions in 2nd reported by Prakash et al [13].
and 3rd decade of life. Amongst all 8 malignant ovarian lesions, serous
In present study, the incidence of non- neoplastic cystadenocarcinoma was the commonest, which
lesiosn (62.1%) was more common than neoplastic lesions correlates well with almost all studies mentioned above.
(37.9%). Similarly, Zaman et al. [11] and Kanthikar et al
[12] reported more non-neoplastic lesions than neoplastic
Conclusion
lesions which is in contrast with the study reported by
Prakash et al. [13] who reported more incidence of To conclude, number of various clinical parameters
neoplastic lesions. such as age of the patient, location/laterality of the
Follicular cyst was the commonest finding in non- lesion, on one hand and histological type of ovarian
neoplastic lesions with 55.6% incidence which is in lesion on the other hand are all interrelated.

Indian Journal of Pathology: Research and Practice / Volume 7 Number 6 / June 2018
740 Bhangale Harshada R., Pathade Smita C., Mendhe Runali D. et al. / Spectrum of Ovarian Lesions – An Institutional Study

All these clinical and histomorphological parameters 7. Kurman RJ, Norris HJ. Malignant germ cell tumours of the
and advanced newer diagnostic modalities like ovary. Hum Pathol. 1977;8(5):551–64.
immunohistochemistry and morphometric analysisif 8. KTushar, Asanranthi K, Mohapatra PC. Intraoperative
required can help in early diagnosis so as to plan the line cytology of ovarian tumours. J ObstetGynecol India. 2005;
of treatment which in turn have prognostic significance. 55(4):345-49.

Also passive surveillance and community screening 9. Pathade SC, Amale AP, Sangole VM, Mendhe RD.
Clinicopathological study of ovarian lesions. Indian
facility along with spreading awareness among public
Journal of Pathology Research and Practice. April-June
and doctors and educating people will be helpful in early 2017;6(2):237-41.
detection of the ovarian lesions.
10. Ramachandran G, Harilal KR, Chinnamma K, Thangavelu
H. Ovarian neoplasms -A study of 903 cases. J
References ObstetGynecol India. 1972;22:309 -15.
11. Zaman S, Majid S, Hussain M, Chugtai O, Mahboob J,
1. Thakkar NN, Shah SN. Histopathologicalstudy of ovarian Chugtai S. A retrospective study of ovariantumours and
lesions. IJSR. Oct 2015;4(10):1745-49. tumour - like lesions. J Ayub Med Coll Abbottabad. 2010;
2. Prabhakar BR, MangiK.Ovarian tumors-Prevalence in 22(1):104-8.
Punjab. Indian J PatholMicrobiol. 1989;32(4):276-81. 12. Kanthikar SN, Dravid NV,Deore PN, Nikumbh DB,
3. Srikanth S, Anandam G. Bilateral dermoid cyst of ovary. Suryawanshi KH. Clinico-Pathological Study of Neoplastic
Med J DY Patil Univ. 2014;7:4923. and Non-Neoplastic Ovarian Lesion. Journal of Clinical and
Diagnostic Research. 2014 Aug;8(8):FC04-FC07.
4. Rosai J,Rosai and Ackerman’s Surgical pathology. 9th
Edition. New Delhi: Elsevier; 2004.1674p. 13. Prakash A, Chinthakndi S, Duraiswami R, Indira V.
Histopathological study of ovarian lesions in a tertiary care
5. Gurung P, Hirachand S, Pradhanang S. Histopathological center in Hyderabad, India - a retrospective five-year study.
study of ovarian cystic lesions in Tertiary Care Hospital of Int J Adv Med. June2017;4(3):745-49.
Kathmandu, Nepal. Journal of Institute of Medicine.
December 2013;35(3):44-47. 14. Gupta SC, Singh PA, Mehrotra TN, AgarwalR.Indian J Pathol.
Microbiol. 1986;29:354-62.
6. Modugno F. Ovarian cancer and polymorphisms in the
androgen and progesterone receptor genes. Am J
Ep­idemol. 2004;159(4):319–35.

Indian Journal of Pathology: Research and Practice / Volume 7 Number 6 / June 2018
741
Indian Journal of Pathology: Research and Practice

IJPRP Volume 7 Number 6, June 2018


DOI: http://dx.doi.org/10.21088/ijprp.2278.148X.7618.5

Original Research Article

A Study on Histopathological Patterns of Thyroid Lesions and its


Cytological Correlation: An Experience of A Rural Tertiary Care Center

S. Kalyani1, J. Kolsamma Nasrin2, O.A. Meharaj Banu3, S.R. Murali Prasath4, R. Uma5, S.R.
Jayakarthiga6
1
Associate Professor 2,6Tutor, 3,5Senior Assistant Professor, 4Assistant Professor, Department of Pathology, Govt. Thiruvarur Medical
College, Thiruvarur, Tamil Nadu 610004, India.

Abstract

Objective: Thyroid lesions are the most common endocrine problem encountered in
routine clinical practice. This study describes the various spectrums of thyroid lesions in
surgically resected specimen and its correlation with age, gender and cytological findings.
Corresponding Author:
Materials and methods: A retrospective study of thyroid lesions were conducted in the
J. Kolsamma Nasrin Department of pathology, Government Thriuvarur medical college, Thiruvarur over a
Tutor, period of 1 year from Jan 2016 to Dec 2016. Totally 145 cases were studied which include 109
Department of Pathology, non neoplastic, 7 benign and 29 malignant cases. Pre operative FNAC evaluation was
Govt. Thiruvarur Medical College, performed in patients with nodular thyroid enlargement. Out of 145 cases pre operative
Thiruvarur, Tamil Nadu 610004, cytological correlation was available for 52 cases.
India.
E-mail: Results: Totally 145 surgically resected thyroid specimens were received during the study
nasrin.jkols@yahoo.com period of one year with a female: male ratio of 10.7: 1. The age group ranges from 14 years
to 67 years and peak incidence was noted in 31-40 years group. Most common lesion noted
(Received on 14.05.2018, was nodular goiter (54%) followed by thyroid malignancies (20%). Other lesions observed
Accepted on 09.06.2018) were thyroiditis (14%), follicular adenoma (5%), nodular hyperplasia with thyroiditis ( 6%)
and toxic goiter (1%). Among the malignant tumours, the predominant lesion was papillary
carcinoma (90%) followed by follicular (7%) and medullary carcinoma (3%).
Conclusion: Non neoplastic lesions are more common than neoplastic lesions with a
striking female predominance. This study shows increased prevalence of thyroid lesions
with a rising incidence of papillary carcinoma thyroid among the middle aged individuals.
Keywords: Thyroid lesions; FNAC; Papillary Carcinoma; Goitre

Introduction [4]. Thyroid malignancies represent 1.5% of all cancer


but it is the commonest endocrine cancer accounting for
Thyroid lesions are one of the most common endocrine 92% of all endocrine malignancies [5].
problem second to diabetes [1] with greater part of them
are benign in nature [2] . They are endemic in mountainous
regions of the world having little iodine supply in soil and Materials and Method
water. The prevalence and pattern of thyroid disorders A retrospective descriptive study of thyroid lesions was
depend on various factors including sex, age, ethnic and conducted in the Department of pathology, Government
geographical patterns [3]. Most of the thyroid lesions are Thiruvarur medical college, Thiruvarur over a period of 1
benign nodule and only 5% are considered to be malignant year from Jan 2016 to Dec 2016. All the biopsy reports

Indian
© Red Journal of Pathology:Pvt.
Flower Publication Research
Ltd. and Practice / Volume 7 Number 6 / June 2018
742 S. Kalyani, J. Kolsamma Nasrin, O.A. Meharaj Banu et al. / A Study on Histopathological Patterns of Thyroid Lesions
and its Cytological Correlation: An Experience of A Rural Tertiary Care Center

were retrieved and various clinical parameters include 17% respectively [Table 2]. Among the 29 malignant
age, gender, thyroid profiles and relevant investigations tumours, the predominant lesion was papillary
like FNAC & radiological reports were evaluated. All the carcinoma (90%) (Figure 2) followed by follicular (7%)
biopsies were fixed in 10% buffered formalin and routinely (Figure 3) and medullary carcinoma (3%).
processed for paraffin embedding and sections were Most common histopathological type papillary
stained with Haematoxylin and Eosin. carcinoma observed was conventional type (55%) (Figure
4) followed by its variants (19%). Among the variants
Results follicular type constitutes (14%) followed by
microcarcinoma, macrofollicular variant [Table 3] and
A total of 145 surgically resected thyroid specimens were oncocytic variant (4% each) (Figure 5). About 5 cases
received during the one year study period. Resected were associated with Hashimotos thyroiditis (19%).
specimens ranged from hemithyoidectomy to total Preoperative cytological evaluation was available for
thyroidectomy. The common presenting symptom is 52 (37%) cases. Cytological diagnosis includes Benign
thyroid enlargement includes multinodular goiter (61%) (81%), Suspicious follicular neoplasm (4%) and
followed by solitary nodule (28%) and diffuse malignancy (15%). (Table 4)
symmetrical enlargement (11%). Age incidence ranged
from 14-67 years with a mean age of 38 years and peak
age incidence noted in the age group 31-40 years (34%)
followed by 41-50 years (25%) [Chart 1]. Sex predilection
was seen for females (91%) with a female: male ratio
was 10.1:1 [chart 2]. Only 6% of cases were observed in
age group below 20 years.
Of the total 145 cases non neoplastic lesion
constitutes 75% followed by malignant lesion (20%) and
benign 5%. [Chart 3] Most common non neoplastic lesion
was nodular goiter (54%) followed by thyroiditis (14%)
Figure 1). Carcinoma accounts for 29 cases (20%) with
highest incidence seen in the age group 31-40 years
followed closely by 41-50 years. The frequency of
carcinomas among male and females were 38% and
Fig. 1: Gross appearance of Hashimoto thyroiditis
Table 1: Histopathological types of thyroid lesions
Diagnosis No of cases Percentage

Nodular goiter (MNG + Adenomatous goiter) 78 54%


Nodular hyperplasia with thyroiditis 8 6%
Toxic goiter 2 1%
Hashimotos thyroiditis 21 14%
Follicular adenoma 7 5%
Papillary carcinoma – conventional type 14 10%
Papillary carcinoma associated with Hashimotos thyroiditis 5 3%
Papillary carcinoma variants 7 5%
Follicular carcinoma 2 1%
Medullary carcinoma 1 1%

Table 2: Sex wise distribution of Thyroid Carcinomas


N %

Male 5/13 38%


Female 24/132 18%

Table 3: Histopathological types of Papillary carcinoma


Conventional type 14 55%
Conventional associated with hashimoto thyroiditis 5 19%
Follicular variant 4 14%
Macrofollicular variant 1 4%
Oncocytic ariant 1 4%
Microcarcinoma variant 1 4%

Indian Journal of Pathology: Research and Practice / Volume 7 Number 6 / June 2018
S. Kalyani, J. Kolsamma Nasrin, O.A. Meharaj Banu et al. / A Study on Histopathological Patterns of Thyroid Lesions 743
and its Cytological Correlation: An Experience of A Rural Tertiary Care Center

Fig. 4: Papillary carcinoma thyroid


Fig. 2: FNAC of Papillary carcinoma of Thyroid

Fig. 3: Gross- Follicular Carcinoma of Thyroid Fig. 5: Oncocytic variant of Papillary carcinoma Thyroid

Table 4: Preoperative Cytological distribution of thyroid lesions

FNAC diagnosis N %
Benign 42 81%
Suspicious follicular lesion 2 4%
Malignancy 8 15%

Chart 1: Age wise distribution of thyroid


lesions

Indian Journal of Pathology: Research and Practice / Volume 7 Number 6 / June 2018
744 S. Kalyani, J. Kolsamma Nasrin, O.A. Meharaj Banu et al. / A Study on Histopathological Patterns of Thyroid Lesions
and its Cytological Correlation: An Experience of A Rural Tertiary Care Center

neoplastic, 5% benign and 20% malignant similar to


studies conducted by Hussain et al [8], Joseph et al [7 ]
and Rahman et al [9]. Compared to other studies, the
present study showed higher female predilection with
female: male ratio noted was10.1:1. Female: male ratio
noted in previous studies were 3.4:1 ( Chukudebelu et
al)[10], 4.5:1 (Tsegaye et al) [11]. Various reports from
the United States of America, Saudi Arabia and Pakistan,
which recorded female to male ratios of 7:1, 6.2:1 and
4.5:1, respectively [12,13,14]. The commonest non
neoplastic lesion observed in this study was simple
nodular goiter (54%) similar to studies by Tsegaye et al
Chart 2: Sex wise distribution of thyroid lesions [11] Ijomone et al in Nigeria reported 59.4% [15], Misiakos
et al in Greece (54.9%) [16] Joseph et al (71.5%) [7].
Among the non neoplastic lesions, the second
commonest pathology observed was thyroiditis (14%)
in concordance with studies by Joseph et al (22.97%) [7]
and Sherine I Salama et al (7.6%) [18]. Other studies
reported low incidence of thyroiditis were Rahman et al
in Bangaladesh (2.7%) [9], Raphael solomon et al in
Nigeria (0.4%) [17], Misiakos et al in Greece (3.8%) [16].
Thyroiditis was noted as an associated finding in 6% of
nodular goiter compared to a study by Joseph et al [7]
showed 17.6% of multinodular goiters.
In this study neoplastic lesions constituted 25%,
within the neoplastic lesions malignancy (20%)
predominates over benign adenomas (5%) concordant
with studies by Abdulkader Albasri et al. [19] and Joseph
Chart 3: Histopathological categorization et al [7]. This study showed low incidence of benign
follicular adenoma (5%) similar to studies Abdulkader
Albasri et al(8.6%) [19] and Joseph et al (3.3%) [7] and
About 41 (78.8%) cases were correlated and 11 (21.2%)
cases were not correlated with histopathological discordant to studies by Ijomone EA et al (52.4%) [15],
diagnosis. About 6 cases of papillary carcinoma, 2 cases Raphael solomon et al in Nigeria (52.2%) [17]. Thyroid
of follicular adenoma were reported in cytology as adenoma (5%) was the only benign lesion observed in
nodular goiter. 1 case of follicular carcinoma reported this study. Papillary carcinoma was the most common
as granulomatous thyroiditis in cytology, and 2 cases of malignant lesion accounting 90% of malignant lesions
nodular colloid goiter were reported as papillary and 17.9% of all thyroid lesions which is similar to
carcinoma in cytology. Overall malignancy rate after findings by Abdulkader Albasri et al [19], Chukudebelu et
thyroidectomy was 15/52 cases (28%). al [10], Ariyibi et al [20] and Ashwini K et al [24]. In contrast
to most other studies, Olurin et al [21], Omran et al [22]
found that follicular carcinoma was the commonest
Discussion malignant neoplasm. The probable explanation was
wide prevalence of iodine deficiency or partly by the miss
Thyroid lesions are the most common endocrine interpretation of the follicular variant of papillary
disease encountered worldwide. Majority of the patients carcinoma as follicular carcinoma in earlier
are from developing countries due to the increased classification of thyroid neoplasms. The peak age
prevalence of iodine deficiency. Clinical presentation of incidence of papillary carcinoma was 3rd and 4th decade
thyroid disease may be in the form of multinodular, similar to studies by Ariyibi et al [20], Joseph et al [7] and
solitary or diffuse enlargement [6]. in contrast to study by Abdullah H. Darwish et al [23], he
In this study, the peak incidence of thyroid lesions are observed most of the papillary carcinoma were
seen in the age group 31-40 years (34%) with mean age diagnosed more than 60 years. Most recent studies have
of presentation was 38 years in concordance with reported incidence of thyroid malignancy in Hashimoto
studies conducted by Joseph et al (7). The overall thyroiditis was 29.4% [25]. We observed coexistent
distribution thyroid lesions in this study were 75% non papillary carcinoma and Hashimoto thyroiditis in 5

Indian Journal of Pathology: Research and Practice / Volume 7 Number 6 / June 2018
S. Kalyani, J. Kolsamma Nasrin, O.A. Meharaj Banu et al. / A Study on Histopathological Patterns of Thyroid Lesions 745
and its Cytological Correlation: An Experience of A Rural Tertiary Care Center

cases (19%). Follicular variant (14%) was the most 9. Rahman M A, Gogoi M, Goswami A; Thyroid nodule, int j
common variant observed among the papillary contemporary Med research, 2017 June;4(6).
carcinoma and one case in each variant includes 10. Chukudebelu O,Dias A,Timon C; Changing trends in
microcarcinoma, macrofollicular and oncocytic variant thyroidectomy, ir med j 2012 jun;105(6);167-9.
consistent with study by Sherine I Salama et al [18]. 11. Tsegaya B, Ergete W. Histopathological pattern of thyroid
Incidence of other malignancies observed were 2 cases diseaas.East AfrMed J 2003;80:525-8.
of follicular carcinoma and 1 case of medullary 12. Galofr JC, Lomvardias S, Davies TF. Evalauation and
carcinoma. In this study cytological correlation was treatment of thyroid nodulesa clinical guide. MT. SinaiJ
performed in 52 cases. About 78.8% of cases correlated Med 2008;75:299-311.
and 21.1% not correlated with histopathology. In our
13. Bouq YA, Fazilli FM, Gaffar HA. A current pattern of
study, 9 patients with false negative and 2 cases with surgically treated thyroid diseases in the medinah region
false positive diagnoses were reported among malignant of Saudi Arabia.JK-practioner 2006;13;9-14.
cases. The overall incidence of malignancy was
14. Bukhari U,Saqid S.Histopathological audit of goiter; Astudy
increased from 15% to 25% after thyroidectomy.
of 998 thyroid lesion. Pak J Med Sci 2008;24;442-6.
15. Ijomone EA, Duduyemi BM, Udoye E, Nwosu SO;
Conclusion Histopathological review of thyroid diseases in southern
Nigeria-a ten year retrospective study, journal of medicine
In our study nodular goiter was the most common & medical sciences 2014 June;5(6):127-32.
histopathological lesion followed by thyroiditi. 16. Misiakos E, Margari N, Meristoudis C, Machairas N, Schizas
Malignant neoplasms were more common than benign D, Petropoulos K, Spathis A, Karakitsos P, Machairas A;
neoplasms. Papillary carcinoma was the most common World JCLin cases. 2016;4(2);38-48.
malignant neoplasm. This study show increased 17. Raphael S, Yawale L, Mohammed AZ, Histopathological
prevalence of thyroid lesions with a rising incidence of pattern of thyroid lesion in Kano, Nigeria: A 10 year
papillary carcinoma thyroid among the middle aged retrospective review (2002-2011).NigerJ Basic clinSci
individuals. Improved imaging techniques and correct 2015;12:55-60.
FNA diagnoses may facilitate early diagnosis of 18. Sherine I, Layala s, Mohamed H, Jaudah A; Histopathological
malignant thyroid lesions. pattern of thyroid lesions in western region of Saudi
Arabia; The new Egyptian journal of med; 2009
June;40(6):580-85.
Refrences 19. Abdulkader A, Zeinab S, Akbar SH, Ahmed A;
Histopathological patterns of thyroid disease in AlMadinah
1. Kochupillai N.Clinical endocrinology in India.CurrSci,
region of saudia Arabia, asian pacific journal of cancer
2000;79:1061-7.
prevention, 2015;15:3133-37.
2. Burguera B,Gharib H. Thyroid incidentalomas. prevalance,
20. Ariyibi O, Duduyemi BM, Akang E, Oluwasola O;
diagnosis,significance and management.Endocrinol metab
Histopathological patterns of throid Neoplasms in Ibadan
clin north am, 2000;29;187-203.
Nigeria: atwenty year retrospective study;int journal
3. Mackenzie EJ, Mortimer RH. Thyroid nodule and thyroid Tropical disease &health, 2013;3(2);148-56.
cancer.MedJAust. 2004;180;242-7.
21. Olurin EO, Itrayemi SO, Oluwasanii JO, Ajayi OO. The
4. Darwish AH,AlSindiKA, El Kafsi J, Bacantab M.Pttern of pattern of throid gland diseases in Ibadan, Nigeria. Niger
thyroid disease-A histopathological study.Bahrain Medical MedJ 1973;3;58-65.
Bulletin. 2006;28;1-6.
22. Omran M, Ahmed ME. Carcinomaof thyroid in Khartoum.
5. SushelC, Khanzada TW, Zulfikar I,SamadA. Histopathological east Afr Med J, 1993;70(3);159-62.
pattern of diagnoses in patients undergoing thyroid
23. Abulla H, Khalid A, Jihene El; Pattern of thyroid diseases-A
operations.Rawal Med j; 2009;34;14-6.
histopathological study; Bahrain medical bulletin, 2006
6. Elahi S, Manzoor-ul-Hassan A, Syed Z, Nazeer L, Nagara Dec;28(4):1-6.
SA, Hder SW. Astudy of goiter among female adolescents
24. Ashwini K, Anitha B, Letha P. Pttern of thyroid disorder in
refrred to centre for nuclear medicine, Lahore. PakJ MedSci
thyroidectomy specimen.int J Med scie Pub Health.
2005;21;56-61.
2014:3;1446-8.
7. Joseph E, Varghese A, Celine TM, Anna M, Usha P; Int journal
25. Anand A, Ranjan S, Jitendra K, NUzhat H, Abhinav arun.
of research in medical science; Astudy on histopathological
Papillary Thyroid Cancer and Hashimoto’s Thyroiditis: An
pattern of thyroid lesions in a tertiary care hospital, Int j
Association Less Understood. Indian J SurgOncol. 2014
Res in Med sci, 2016 Dec;4(12);5252-5255.
sep;5(3);199-204.
8. Hussain N, Anwar. M, Naia N, Ali Z. Pttern of surgically treated
thyroid diseases in Karachi. Biomedicall; 2005;21:18-20.

Indian Journal of Pathology: Research and Practice / Volume 7 Number 6 / June 2018
746
Indian Journal of Pathology: Research and Practice

IJPRP Volume 7 Number 6, June 2018


DOI: http://dx.doi.org/10.21088/ijprp.2278.148X.7618.6

Original Research Article

Evaluation of Hematological Scoring System in the Diagnosis of Neonatal


Sepsis

B.N. Kumarguru1, Chandrakala R. Iyer2, A.S. Ramaswamy3, G. Naveen4, H.R. Suma5, Amita
Ray6

1
Associate Professor 3Professor and Head, Department of Pathology 2Associate Professor, Department of Paediatrics 5Former Associate Professor,
Department of Biochemistry, P.E.S. Institute of Medical Sciences and Research, Kuppam, Andhra Pradesh 517425, India. 4Associate Professor,
Department of Microbiology, Karwar Institute of Medical Sciences, Karwar, Karnataka 581301, India. 6Professor and Head, Department of
Obstetrics and Gynecology, IQ City Medical College, Durgapur, West Bengal 713206, India.

Abstract

Corresponding Author: Introduction: Neonatal septicemia constitutes one of the major public health problems
throughout the world. Early diagnosis of neonatal sepsis poses a great challenge.
Chandrakala R. Iyer Hematological scoring system [HSS] formulated by Rodwell et al. can be used to establish
Associate Professor, early diagnosis of sepsis in neonates.
Department of Paediatrics,
P.E.S. Institute of Medical Sciences Objectives: To evaluate the utility of conventional HSS and modified HSS as a diagnostic
and Research, Kuppam, Andhra tool in the setting of neonatal sepsis and to evaluate the role of additional parameters like
Pradesh 517425, India. nucleated RBC count, Neutrophil Lymphocyte Ratio [NLR] and Platelet Lymphocyte Ratio
E-mail: [PLR] in the diagnosis of neonatal sepsis.
drchandrakalar@gmail.com
Materials and Methods: The study was conducted in hematology section of the
(Received on 13.04.2018, department of pathology at a rural tertiary care referral institute. It was a prospective study
Accepted on 05.05.2018) done over a period of six months from January 2015 to June 2015. Fifty-one cases were
analyzed. All high risk neonates admitted to NICU [Neonatal Intensive Care Unit] were
included in the study. Clinically, neonates were grouped into three categories. Conventional
hematological scoring system [HSS] and Modified hematological scoring system were
applied to all the cases. Additional hematological parameters like nucleated RBC count,
NLR and PLR were also evaluated.
Results: Both conventional hematological scoring system and modified hematological
scoring system were found to be statistically significant by Chi-square test (P < 0.05) for
clinical correlation. NLR ratio was statistically significant (P < 0.05) for clinical correlation.
Nucleated RBC count and PLR were found to be statistically not significant (P > 0.05) for
clinical correlation. Sensitivity of conventional HSS and modified HSS were similar (100%)
with respect to total WBC count, immature polymorphonuclear neutrophils (PMN) count,
immature: total PMN ratio, immature: mature PMN ratio and degenerative changes in PMN.
Specificity of total WBC count was better in conventional HSS. Specificity of platelet count
was better in modified HSS.
Conclusion: Hemalotogical scoring system is a useful, simple and reliable tool for
evaluating neonatal sepsis. But, modified HSS appears to be more meaningful scoring system
than conventional HSS.
Keywords: Diagnostic; Parameter; Neutrophils.

© Red Flower Publication Pvt. Ltd. Indian Journal of Pathology: Research and Practice / Volume 7 Number 6 / June 2018
Kumarguru B.N., Chandrakala R. Lyer, Ramaswamy A.S. et al. / Evaluation of Hematological Scoring System in the 747
Diagnosis of Neonatal Sepsis

Introduction Sepsis” included neonates presenting with clinical signs of


sepsis and any of the microbiological cultures [Blood or
Sepsis is a systemic inflammatory response syndrome CSF or urine] were positive. Ancillary laboratory
associated with infection diagnosed on either investigations included investigations like C-Reactive
microbiological culture or strong clinical evidence of protein [CRP] and serum bilirubin levels.
infection [1]. Neonatal sepsis is a clinical syndrome
Complete blood count parameters were obtained from
resulting from effects of local and system infection during
Autoanalyser Sysmex K21. Autoanalyser values were
first month of life [2]. Neonatal septicemia constitutes one
verified by peripheral smear examination. Peripheral
of the major public health problems throughout the world
smears were interpreted and reported according to the
[3]. According to National Neonatal Perinatal Database
standard reference range values in neonates. Convention
[NNPD], the incidence of neonatal sepsis has been reported
hematological scoring system [HSS] and modified
to be 30/1000 live births [2]. Neonatal infections are causing
hematological scoring system were applied to all the cases.
1.6 million deaths annually in developing countries [1].
The criteria and parameters used in conventional HSS
Early diagnosis of neonatal sepsis is a vexing problem and modified HSS are depicted in Table 1. Additional
and a great challenge [3]. Blood culture is considered to hematological parameters like nucleated RBC count, NLR
be gold standard for the diagnosis of septicaemia [2]. But, and PLR were also evaluated
it is a time consuming investigation which requires a
minimum of 48 -72 hours. Timely diagnosis of neonatal Statistical Analysis
septicemia is critical because the illness can progress more Socio-demographic variables were represented using
rapidly in neonates than in adults [3,4]. Newer inflammatory frequencies and percentages. Chi-square test exact test
markers like interleukin-6, interleukin-8 and plasma was used for categorical variables. Sensitivity,
elastase are highly sensitive and specific for diagnosing specificity, positive predictive value (PPV), negative
neonatal sepsis and septic shock. But they require predictive value (NPV) and efficacy of individual
sophisticated and expensive kits [1]. Early diagnosis of parameters were evaluated. All statistical analysis was
sepsis helps the clinician to administer early treatment performed by STATA version 13.
with appropriate antibiotics [2]. Hematological scoring
system [HSS] formulated by Rodwell et al can be used to
establish early diagnosis of sepsis in neonates [5]. The Results
present study was undertaken to evaluate the utility of
Fifty-one cases of high risk neonates admitted to NICU
conventional HSS and modified HSS as a diagnostic tool
[Neonatal Intensive Care Unit] were analyzed. The age
in the setting of neonatal sepsis and to evaluate the role of
of high risk neonates admitted to NICU ranged from new
additional parameters like nucleated RBC count, Neutrophil
born baby to 26 days with a mean of 2.29 days. Most of
Lymphocyte Ratio [NLR] and Platelet Lymphocyte Ratio
the neonates were new born [31 cases (60.78%)]. Male
[PLR] in the diagnosis of neonatal sepsis.
neonates [33 cases (64.71%)] constituted predominant
population with a male to female ratio of 1.8:1. Term
Materials and Methods neonates [29 cases (56.86%)] constituted predominant
population in comparison with preterm neonates [22
The study was conducted in hematology section of the cases (43.14%)].
department of pathology at a rural tertiary care referral Clinically high risk neonates were categorized as no
institute. It was a prospective study done over a period of sepsis [19 cases (37.25%)], probable sepsis [28 cases
six months from January 2015 to June 2015. Fifty-one cases (54.9%) and definite sepsis [4 cases (7.84%)]. Neonates
were analyzed. All high risk neonates admitted to NICU affected by sepsis [including both probable sepsis and
[Neonatal Intensive Care Unit] were included in the study. definite sepsis] constituted 32 cases (62.75%). Early onset
Those cases, in which complete hematological profile could sepsis [21 cases (65.63%) was predominantly seen in
not be performed, were excluded from the study. comparison with late onset sepsis [11 cases (34.38%)].
Clinically, neonates were grouped into three categories. Male neonates [25 cases (78.13%) were predominantly
Category of “No Sepsis” included neonates presenting affected by sepsis with a male to female ratio of 3.6:1.
with clinical signs of sepsis and any of the microbiological Term neonates [24 cases (75%)] were predominantly
cultures [Blood or CSF or urine] were negative and ancillary affected by sepsis in comparison with preterm neonates
laboratory investigations were not significant. Category [8 cases (25%)]. Culture was positive in four cases
of “Probable sepsis” included neonates presenting with (12.5%). Blood culture was positive in three cases (9.68%).
clinical signs of sepsis, microbiogical cultures [Blood or The organisms isolated from blood sample included
CSF or urine] were negative, but and ancillary laboratory Streptococci, Klebsiella and Non-fermenting gram
investigations were significant. Category of “Definite negative bacilli. Urine culture was positive in one case
Indian Journal of Pathology: Research and Practice / Volume 7 Number 6 / June 2018
748 Kumarguru B.N., Chandrakala R. Lyer, Ramaswamy A.S. et al. / Evaluation of Hematological Scoring System in the
Diagnosis of Neonatal Sepsis

(3.13%)]. Fungi (candida) was isolated from urine sample is suspected” and constituted 25 cases (49.02%). Group 3
constituting one case (3.13%)]. [score  5] represented the category with interpretation of
Conventional HSS proposed by Rodwell et al. was “sepsis is very likely” and constituted 17 cases (33.33%).
applied to evaluate all the cases. Based on the scoring Modified HSS was found to be statistically significant by
system, cases were categorized into three groups. Group Chi-square test (P < 0.05) for clinical correlation [Table 3].
1 [score 0-2] represented the category with interpretation NLR was in normal range in 12 cases (23.53%), increased
of “sepsis is very unlikely” and constituted 5 cases (9.8%). in 29 cases (56.86%) and decreased in 10 cases (19.61%).
Group 2[score 3-4] represented the category with The values were statistically significant (P < 0.05) for clinical
interpretation of “sepsis is suspected” and constituted correlation. PLR was in normal range in 28 cases (54.9%),
39 cases (76.47%). Group 3 [score  5] represented the increased in 7 cases (13.73%) and decreased in 16 cases
category with interpretation of “sepsis is very likely” and (31.37%). The values were statistically not significant
constituted 7 cases (13.73%). Conventional HSS was (P > 0.05) for clinical correlation. Nucleated RBC count
found to be statistically significant by Chi-square test (P was increased in 32 cases (62.74%) and was statistically
< 0.05) for clinical correlation [Table 2]. The scoring not significant (P > 0.05) for clinical correlation. It had
system was statistically significant for detecting early sensitivity of 50%, specificity of 36.17%, PPV of 6.9% and
onset sepsis and late onset sepsis (P < 0.05). NPV of 89.47%.
Similarly, modified HSS was applied to all the cases.
Sensitivity
Based on the scoring system, cases were categorized
into three groups. Group 1 [score 0-2] represented the Sensitivity of conventional HSS and Modified HSS were
category with interpretation of “sepsis is very unlikely” similar with respect to total WBC count, immature PMN
and constituted 9 cases (17.65%). Group 2 [score 3-4] count, immature: total PMN ratio, immature: mature PMN
represented the category with interpretation of “sepsis ratio and degenerative changes in PMN. [Figure 1 and

Table 1: Comparison of Conventional HSS and Modified HSS

Conventional HSS
HSS Modified
Modified HSSHSS
Parameters Criteria
Abnormality Score Parameters Criteria
Abnormality Score

Total WBC Count ≤ 5000/µl 1 Total WBC Count Increased or decreased for the given 1
age
≥ 25000//µl 1 Normal for the given age 0
≥ 30000/µl for 12 to 24 hrs 1
≥ 21000//µl for Day 2 onwards 1

Total PMN count No Mature PMN seen 2 Total PMN count No Mature PMN seen 2
Increased or Decreased 1 Increased or decreased for the given 1
age
1800- 5400 /µl 0 Normal for the given age 0

Immature PMN count > 600 1 Immature PMN count > 600 1
<600 0 < 600 0
Immature: Total PMN ≥ 0.12 1 Immature: Total PMN ≥ 0.2 1
ratio ratio
< 0.12 0 < 0.2 0
Immature: Mature ≥ 0.3 1 Immature: Mature ≥ 0.3 1
PMN ratio PMN ratio
< 0.3 0 < 0.3 0
Degenerative Changes Toxic granules or cytoplasmic 1 Degenerative Changes Toxic granules or cytoplasmic 1
in PMN vacuoles in PMN vacuoles
No Toxic granules or 0 No Toxic granules or cytoplasmic 0
cytoplasmic vacuoles vacuoles
Platelet Count ≤ 150000/µl 1 Platelet Count Decreased for the given age 1
> 150000/µl 0 Normal for the given age 0
Interpretation of scores Interpretation of scores
≤2 Sepsis is very unlikely ≤2 Sepsis is very unlikely
3 or 4 Sepsis is suspected 3 or 4 Sepsis is suspected
≥5 Sepsis is very likely ≥5 Sepsis is very likely
Minimum score 0 Minimum score 0
Maximum score 8 Maximum score 8

Indian Journal of Pathology: Research and Practice / Volume 7 Number 6 / June 2018
Kumarguru B.N., Chandrakala R. Lyer, Ramaswamy A.S. et al. / Evaluation of Hematological Scoring System in the 749
Diagnosis of Neonatal Sepsis

Figure 2] Modified HSS showed better sensitivity with Positive Predictive Value [PPV]
respect to total PMN count and platelet count. According PPV of conventional HSS and modified HSS were similar
to both conventional HSS and modified HSS, sensitivity with respect to immature PMN count, immature: mature
was highest for immature PMN count, immature: total PMN ratio and degenerative changes in PMN. Modified
PMN ratio, immature: mature PMN ratio and degenerative HSS showed lower PPV with respect to total WBC count.
changes in PMN [Table 3]. However, modified HSS showed better PPV with respect to
total PMN count, immature: total PMN ratio and platelet
Specificity
count. According to conventional HSS, PPV was highest
Specificity of conventional HSS and modified HSS were for degenerative changes in PMN and least for total PMN
similar with respect to immature PMN count, immature: count. According to modified HSS, PPV was highest for
mature PMN ratio and degenerative changes in PMN. platelet count and least for total WBC count [Table 3].
Modified HSS showed lower sensitivity with respect to
total WBC count. However, modified HSS showed better Negative Predictive Value [NPV]
sensitivity with respect to total PMN count, immature: NPV of conventional HSS and modified HSS were
total PMN ratio and platelet count. According to similar with respect to immature PMN count, immature:
conventional HSS, specificity was highest for total WBC total PMN ratio, immature: mature PMN ratio and
count and least for immature: total PMN ratio. According degenerative changes in PMN. Modified HSS showed lower
to modified HSS, specificity was highest for platelet count NPV with respect to total WBC count. However, modified
and least for immature PMN count [Table 3]. HSS showed better NPV with respect to total PMN count

Table 2: Comparison of distribution of cases according to Conventional HSS and Modified HSS in relation to clinical categories

Conventional Hematological Scoring system


Clinical category Group 1 Group 2 Group 3 Total P Value

No sepsis 4 14 1 19
Probable sepsis 1 25 2 28 P<0.05
Definite sepsis 0 0 4 4
Total 5 39 7 51

Modified Hematological Scoring system


Clinical category Group 1 Group 2 Group 3 Total P Value
No sepsis 8 8 3 19
Probable sepsis 1 17 10 28 P<0.05
Definite sepsis 0 0 4 4
Total 9 25 17 51

Table 3: Comparison of performance of individual hematological parameters of Conventional HSS and Modified HSS

Conventional Hematological Scoring system


Parameters Sensitivity [%] Specificity [%] PPV [%] NPV [%] Efficacy [%]
Total WBC Count 50 91.49 33.33 95.56 88.24
Total PMN count 50 21.28 5.13 83.33 23.53
Immature PMN count 100 12.77 8.89 100 19.61
Immature: Total PMN ratio 100 4.26 8.16 100 11.76
Immature: Mature PMN ratio 100 42.55 12.9 100 47.06
Degenerative Changes in PMN 100 85.11 36.36 100 86.21
Platelet Count 50 80.85 18.18 95 78.43

Modified Hematological Scoring system


Parameters Sensitivity [%] Specificity [%] PPV [%] NPV [%] Efficacy [%]

Total WBC Count 50 44.68 7.14 91.30 45.10


Total PMN count 75 40.43 9.68 95 43,14
Immature PMN count 100 12.77 8.89 100 19.61
Immature: Total PMN ratio 100 56.67 11.76 100 41.17
Immature: Mature PMN ratio 100 42.55 12.9 100 47.06
Degenerative Changes in PMN 100 85.11 36.36 100 86.21
Platelet Count 75 89.36 37.5 97.67 88.24

Indian Journal of Pathology: Research and Practice / Volume 7 Number 6 / June 2018
750 Kumarguru B.N., Chandrakala R. Lyer, Ramaswamy A.S. et al. / Evaluation of Hematological Scoring System in the
Diagnosis of Neonatal Sepsis

Fig. 1: Microphotograph of peripheral smear showing toxic granules Fig. 2: Microphotograph of peripheral smear showing cytoplasmic
(Arrow) in neutrophil. [Leishman stain, X1000] vacuolation (Arrow) in neutrophil. [Leishman stain, X1000]
Table 4: Comparison of performance of hematological parameters in various studies
Sensitivity Specificity PPV NPV
Authors Cases Highest Lowest Highest Lowest Highest Lowest Highest Lowest

Khair BK 12/100 I:T ratio Total WBC Total WBC I:T ratio Total WBC I:M ratio I:T ratio Immature
et al[3] (>0.2), I:M count count (>0.2) [4%] count [11%] (>0.2), I:M PMN count
[2010] ratio [50%] [91%] [43%] ratio [80%]
[100%] [100%]
Narasimh 12/50 Total PMN Total WBC Total WBC Immature I:T ratio Degenerati Degenerati Immature
a A et al[4] count count count PMN count (≥ 0.12) ve changes ve changes PMN count
[2011] [89.87%] [10.52%] [91.66%] [8.3%] [88.88%] [66.66%] [40%] [11.11%]
Makkar M 42/110 Immature I:M ratio I:M ratio Total PMN I:M ratio Total PMN Immature I:M ratio
et al[6] PMN count [53.12%] [97.22%] count [94.44%] count PMN count [70%]
[2013] [96.87%] [72.22%] [74.35%] [97.05%]
Majumdh 20/60 I:T ratio Total WBC Total WBC I:T ratio Degenerati I:M ratio I:T ratio Degenerati
ar A et al[7] (>0.2), I:M count count (>0.2) [5%] ve changes [12%] (>0.2), I:M ve changes
[2013] ratio [45%] [85%] [55%] ratio [50%]
[100%] [100%]
Meirina F 10/40 I:T ratio (≥ Degenerati Degenerati Total PMN I:M ratio Degenerati I:T ratio (≥ Degenerati
et al[5] 0.12), Total ve changes ve changes count [63%] ve changes 0.12), Total ve changes
[2015] PMN count [0%] [100%] [20%] [0%] PMN count [75%]
[100%] [100%]
Debroy A 10/40 I:T ratio (≥ Total PMN I:T ratio (≥ Degenerati I:T ratio (≥ Degenerati I:T ratio (≥ Total PMN
et al[9] 0.12) [90%] count 0.12) ve changes 0.12) ve changes 0.12) count
[2016] [40%] [96.6%] [53%] [100%] [26.13%] [96.6%] [76%]
Bhalodia 48/150 I:M ratio Total PMN I:M ratio Platelet I:M ratio Total PMN I:M ratio Platelet
MJ et al[2] [93.7%] count [94.44%] count [93%] count [94%] count
[2017] [45.8%] [55.9%] [46%] [58%]
Present
study
Conventio 4/51 Immature Total WBC Total WBC I:T ratio Degenerati Total PMN Immature Total PMN
nal HSS PMN count, count, count (>0.2) ve changes count PMN count, count
I:T ratio (≥ Total PMN [91.49%] [4.26%] [36.36%] [5.13%] IT ratio, IM [83.33%]
0.12), IM count, ratio,
ratio, Platelet Degenerati
Degenerati count ve changes
ve changes [50%] [100%]
[100%]
Modified 4/51 Immature Total WBC Platelet Immature Platelet Total WBC Immature Total WBC
HSS PMN count, count count PMN count count count PMN count, count
IT ratio (≥ [50%] [89.36%] [12.77%] [37.5%] [7.14%] IT ratio, IM [91.30%]
0.2), IM ratio,
ratio, Degenerati
Degenerati ve changes
ve changes [100%]
[100%]

Indian Journal of Pathology: Research and Practice / Volume 7 Number 6 / June 2018
Kumarguru B.N., Chandrakala R. Lyer, Ramaswamy A.S. et al. / Evaluation of Hematological Scoring System in the 751
Diagnosis of Neonatal Sepsis

and platelet count. According to both conventional HSS [3], Makkar M et al.[6] and Saleem M et al.[8] found that
and modified HSS, NPV was highest for immature PMN preterm neonates were predominantly affected.
count, immature: total PMN ratio, immature: mature PMN The present study was compared with other studies
ratio and degenerative changes in PMN [Table 3]. with respect to the performance of seven parameters of
HSS. [Table 4] In contrast to other studies, the number
Efficacy
of cases of proven sepsis was very less [only four cases].
Efficacy of conventional HSS and modified HSS were The reason may be mainly due to contamination
similar with respect to immature PMN count, immature: interfering with growth of the organisms. Most of the
mature PMN ratio and degenerative changes in PMN. studies considered only positive blood culture as the
Modified HSS showed lower efficacy with respect to total criteria to clinically categorize a case as definite sepsis.
WBC count. However, modified HSS showed better In contrast, Kar SS et al. [10] included positive blood culture
efficacy with respect to total PMN count, immature: total and positive Cerebrospinal fluid [CSF] culture as criteria
PMN ratio and platelet count. According to conventional to clinically categorize a case as definite sepsis in their
HSS, efficacy was highest for total WBC count and least study. Similarly, even in the present study, any positive
for immature: total PMN ratio. According to Modified microbiogical cultures [Blood or CSF or urine] was
HSS, efficacy was highest for platelet count and least considered as a criteria to clinically categorize a case as
for immature PMN count [Table 3]. definite sepsis. This is because, the neonatal sepsis is
considered as a clinical syndrome resulting from effects
of local and system infection during first month of life [2].
Discussion
In the present study, Immature PMN count showed very
Neonatal sepsis is a serious public health problem with high sensitivity and NPV in both conventional and modified
significant morbidity and mortality [2]. The neonates are HSS. Similarly, Makkar M et al.[6] observed highest
more prone to bacterial invasion than the older children senstivity and NPV with respect to Immature PMN count.
and adults because of their weaker immune system [6]. Sensitivity and NPV for I:T ratio was very high in both
Even though it is a life threatening condition; it is treatable conventional and modified HSS, in the present study. Khair
by timely administration of antibiotics. The limitations in KB et al.[3], Merina F et al.[5], Majumdhar A et al.[7] and
the diagnosis of neonatal sepsis are quiet frustrating and Debroy A et al.[9] also documented similar observation in
a vexing problem for the clinician. Although, the blood their study. I: M Ratio had very high sensitivity and NPV in
culture is considered as gold standard diagnostic test, it both conventional and modified HSS in the present study.
has low sensitivity A rapid diagnostic tool with greater Bholodia MJ et al. [2] also recorded similar observation. In
sensitivity are desirable [2]. The hematological scoring the present study, degenerative changes also had very
system is a simple, quick, reliable and cost effective tool high sensitivity and NPV in both conventional and modified
which can be used as screening test for the early diagnosis HSS. In contrast, Meirina F et al. [5] documented lowest
of neonatal sepsis [1,2]. The current study deals with sensitivity and NPV.
evaluation of the utility of conventional HSS and modified
HSS as a diagnostic tool in the setting of neonatal sepsis In the present study, total WBC count showed highest
and evaluation of the role of additional parameters like specificity and a low sensitivity by Conventional HSS.
nucleated RBC count, NLR and PLR in the diagnosis of Khair KB et al.[3], Narasimha A et al.[4] and Majumdhar A
neonatal sepsis. et al.[7] also made similar observations. I: T ratio had
lowest specificity by convention HSS in the present study.
In the present study, most of the neonates presented Khair KB et al.[3] and Majumdhar A et al.[7] documented
on day 1 of their life. Makkar M et al. [6] also documented similar findings. In contrast, Debroy A et al.[9] observed
similar observation. Khair KB et al. [3] observed that most highest specificity for I:T ratio. In the present study, platelet
of the neonates presented in first week of their life. Males count had highest specificity in modified HSS. In
were predominantly affected in the present study. Similarly, contrast, Bholodia MJ et al.[2] observed lowest specificity
Bhalodia MJ et al. [2], Khair KB et al. [3], Merina F et al.[5], for platelet count. Immature PMN count showed lowest
Majumdhar A et al.[7] and Saleem M et al.[8] observed specificity by modified HSS in the present study. Narasimha
that males were predominantly affected in their study. In A et al.[4] also documented similar finding in their study.
contrast, females were predominantly affected in a study
conducted by Makkar M et al [6]. Narasimha A et al.[4] In the present study, degenerative changes in PMN
documented equal distribution among both sexes in their showed highest PPV by conventional HSS. Similarly,
study. In the present study, term neonates were Majumdhar A et al. [7] observed highest PPV for
predominantly affected. Bhalodia MJ et al [2]. also degenerative changes in PMN. In contrast, Narasimha A et
documented similar finding. Merina F et al [5]. recorded al.[4], Merina F et al.[5] and Debroy A et al.[9] documented
equal distribution in their study. In contrast, Khair KB et al lowest PPV for degenerative changes in PMN. Total PMN

Indian Journal of Pathology: Research and Practice / Volume 7 Number 6 / June 2018
752 Kumarguru B.N., Chandrakala R. Lyer, Ramaswamy A.S. et al. / Evaluation of Hematological Scoring System in the
Diagnosis of Neonatal Sepsis

count showed lowest PPV by conventional HSS in the females. Saleem M et al. [8] had considered CRP as one
present study. Bholodia MJ et al. [2] and Makkar M et al. [6] of the criterion for assessing neonatal sepsis in their study.
also recorded similar observation in their study. In the The basis for using modified HSS in the present study
present study, platelet count showed highest PPV and is that, the peripheral smear report should correspond
total WBC count showed lowest PPV by modified HSS. In with reference range used in the hematology laboratory.
contrast, Khair KB et al. [3] documented highest PPV for In the present study, hematological reference range
total WBC count in their study. given by AACC (American Association for clinical
Additional parameters like NLR, PLR and nucleated RBC chemistry) press [Fifth edition] was used. By using
count, were also evaluated in the present study. Neutrophil modified HSS, the scoring system, the reference range
lymphocyte ratio was increased in 29 cases (56.86%) and used in a laboratory and the peripheral smear report, all
the values were found to be statistically significant (P < the three would correspond and correlate. In the
0.05) for clinical correlation. But the PLR was increased in conventional HSS, the scoring system may not
only 7 cases (13.73%) and the values were statistically not correspond to the reference range used in the laboratory
significant (P > 0.05) for clinical correlation. Omran A et al. or the peripheral smear report. For instance, the neonate
[11] also made similar observations in their study in their may not have thrombocytopenia according to the
study. NLR showed significant difference between sepsis reference range, but it may correspond to a score of 1, if
group and control group. But, the difference in PLR conventional HSS is used.
between both the groups were not significant [11]. In the Each laboratory may have their own reference range.
present study, nucleated RBC count was increased in 32 It may not be possible to have fixed value for platelet count
cases (62.74%) and was statistically not significant (P > and fixed range for total WBC count. By considering this,
0.05) for clinical correlation. In contrast, Abhishek MG et in the present study, when both the scoring systems were
al. [12] documented lower sensitivity, lower NPV, higher compared, modified HSS appeared to be more
specificity and higher PPV. It was concluded that nucleated meaningful than conventional HSS. Additional
RBC was a reliable marker than other hematological parameters like NLR may also be incorporated into
markers like total WBC count, ESR and toxic granulation scoring system, if proved to be useful by future studies.
in neutrophils [12]. But nucleated RBC count may also be
increased in conditions like birth asphyxia, which needs to
be considered. Limitations of the Study
The table 4 reveals considerable variations in the The number of cases of proven sepsis was very less
findings in different studies. This is because, the criteria and constituted only four cases. The cause for such less
used for analyzing seven parameters was not uniform. culture positivity can be attributed to technical
Narasimha A et al.[4], Merina F et al.[5], Makkar M et al.[6] difficulties encountered in isolating the organisms and
and Debroy A et al.[9] considered I:T ratio of  0.12 in contamination. Though the blood culture is considered
their study. While Khair KB et al.[3], Bholodia MJ et al. [2] a gold standard for the diagnosis of neonatal
and Majumdhar A et al.[7] considered I:T ratio of  0.2 in septicaemia, it is time consuming, has low yield (8-73%)
their study. In the present study, when both the values and low sensitivity [1,2].
were compared, it was found that I:T ratio of   0.12 Furthermore, the suspected sepsis group is a difficult
(Conventional HSS) has more false positives than I:T ratio diagnostic group and could not be ignore, because fatal
of  0.2 (Modified HSS). Hence I:T ratio of  0.2 appears to infection has been reported even in the absence of positive
be a better parameter. blood culture [3].
Majority of the study applied a platelet count of
 150000/µl as a criterion for considering sepsis. In contrast,
Majumdhar A et al. [7] applied a platelet count of  100000/ Conclusion
mm3 as a criterion for considering sepsis. In the present
Hematological scoring system is a useful, simple and
study, a platelet count of  150000/mm3 was used as a
reliable tool for evaluating neonatal sepsis. HSS helps the
criterion for considering sepsis in conventional HSS.
clinician to stratify high risk neonates efficiently and
Platelet count “decreased for the given age of the neonate”
institute appropriate treatment. Both conventional HSS
was applied as a criterion in modified HSS. This is because;
and modified HSS were found to be statistically
the platelet count reference range may vary in neonates
significant. But, modified HSS appears to be more
of different age groups and also among males and
meaningful scoring system than conventional HSS.
females.
Additional parameters like NLR needs to be explored and
Similarly, even Total WBC count may vary in neonates may be incorporated into the scoring system, if proved to
of different age groups and also among males and be useful by future studies.

Indian Journal of Pathology: Research and Practice / Volume 7 Number 6 / June 2018
Kumarguru B.N., Chandrakala R. Lyer, Ramaswamy A.S. et al. / Evaluation of Hematological Scoring System in the 753
Diagnosis of Neonatal Sepsis

References judicious use of antibiotics in neonatal septicaemia in


developing countries. Journal of Applied Hematology
1. Chaware SA, Birare SD, Ghatale RD. Evaluation of 2013;4:110-3.
hematological scoring system in early diagnosis of neonatal
8. Saleem M, Shah KI, Cheema SM, Azam M. Hematological
sepsis. International Journal of Medical Pediatrics and
Scoring System for Early Diagnosis of Neonatal Sepsis.
Oncology 2016;2:149-51.
JRMC;2014:18:68-72.
2. Bhalodia MJ, Hippargi SB, Patil MM. Role of Hematological
9. Debroy A, Joshi D, Sinha T. Reappraisal of the
Scoring System in Diagnosis of Neonatal Sepsis. J of Clin
Hematological Scoring System (HSS) for early diagnosis of
Neonatol 2017;6:144-7.
neonatal sepsis in a remote geographical location of North
3. Khair KB, Rahman MA, Sultana T, Roy CK, Rahman MQ, East India. Indian Journal of Pathology and Oncology
Shahidullah M, et al. Role of Hematological Scoring System 2016;3:366-71.
in Early Diagnosis of Neonatal Septicaemia. BSMMU J
10. Kar SS, Dube R, Mahapatro S, Kar SS. The Role of Clinical
2010;3:62-7.
Signs in the Diagnosis of Late-onset Neonatal Sepsis and
4. Narasimha A, Kumar MLH. Significance of Hematological Formulation of Clinical Score. Indian Journal of Clinical
Scoring System (HSS) in Early Diagnosis of Neonatal Sepsis. Practice 2013;23:654-60.
Indian J Hematol Blood Transfus 2011;27:14-7.
11. Omran A, Maaroof A, Saleh MH, Abdelwahab A.Salivary C-
5. Meirina F, Lubis B, Sembiring T, Rosdiana N, Siregar OR. Reactive protein, mean platelet volume and neutrophil
Hematological scoring system as an early diagnostic tool lymphocyte ratio as diagnostic markers for neonatal sepsis.
for neonatal sepsis. Paediatr Indones 2015;55:315-21. J Pediatr (Rio J) 2018;94:82-7.
6. Makkar M, Gupta C, Pathak R, Garg S, Mahajan NC. 12. Abhishek MG, Sanjay M. Diagnostic efficacy of Nucleated
Performance Evaluation of Hematological Scoring System Red blood cell count in the early diagnosis of neonatal
in Early Diagnosis of Neonatal Sepsis. J of Clin Neonatol sepsis. Indian Journal of Pathology and Oncology
2013;2:25-9. 2015;2:182-5.
7. Majumdar A, Jana A, Jana A, Biswas S, Bhattacharyya S.
Hematological Scoring System (HSS): A guide to decide

Indian Journal of Pathology: Research and Practice / Volume 7 Number 6 / June 2018
754
Indian Journal of Pathology: Research and Practice

IJPRP Volume 7 Number 6, June 2018


DOI: http://dx.doi.org/10.21088/ijprp.2278.148X.7618.7

Original Research Article

Histopathological Patterns in Abnormal Uterine Bleeding at a Tertiary


Hospital

Pradeep Jadhav1, Dipti Patel2, S.N. Chawla3


1
Associate Professor 2Assistant Professor 3Professor, Dept. of Pathology, American International Institute of Medical Sciences, Udaipur,
Rajasthan 313001, India.

Abstract

Background: Abnormal uterine bleeding (AUB) is related with patient’s social,familial


and personal life because of the considerable morbidity it causes. The aim of the study was
to examine the histopathological patterns of endometrium in patients presenting with
AUB as well as to find out its incidence in different age groups.

Corresponding Author: Materials and Methods: This is a retrospective study, conducted in the Department of
Pathology, in a tertiary care teaching hospital, Udaipur from Jan. 2016 to Jan. 2018. The
Pradeep Jadhav, study includes cases of AUB with a probable endometrial cause.The study was done in the
Associate Professor, form of measures and percentages and showen as tables where found necessary.
Dept. of Pathology,
American International Institute of Results: A total of 215 cases were studied.The age of the patients were from 18-72 years.
Medical Sciences, Udaipur, Incidence of AUB was most common in the perimenopausal age group. Menorrhagia was
Rajasthan 313001, India. the most common presenting complaint. Proliferative endometrium was the most common
E-mail: histopathological finding and was seen in 35.34% patients, followedby secretory
psjadhav9656@gmail.com endometrium in 18.60% patients, and disordered proliferative endometrium in 17.67%
patients.Hyperplasia was seen in 16.73% cases. Malignancy was detected in 2.36% of cases
(Received on 12.05.2018, and all were endometrial carcinoma.
Accepted on 09.06.2018)
Conclusions: Themain indication of endometrial biopsies is to rule out malignancy and
endometrial hyperplasia in women over 35 years of age group. When no organic pathology
was found,different physiological patterns like secretory phase,proliferative phase and other
endometrial changes were observed. The most common endometrial pathology observed
was proliferative phase endometrium.
Keywords: Abnormal Uterine Bleeding; Dilatation and Curettage; Endometrium.

Introduction Abnormal uterine bleeding is the most common cause


for performing an endometrial biopsy. AUB is the term
Most common tissue specimens received inthe that refers to any nonphysiologic uterine bleeding.
pathology laboratory are endometrial biopsies and Causes of abnormal uterine bleeding differ according
curretings. The surgical pathologist faces a unique
to the age and menstrual status of the patient so these
challenge due to different aspects of these specimens.As
two parameters are very important data for analysis of
the cyclical hormonal influences and pregnancy affects
the causes of bleeding [1].
uterine growth, the endometrium undergoes different
types of morphologic changes especially during the Anovulation, adenomyosis, polyps and fibroid are the
reproductive years. These morphologic changes are important causes of AUB. Endometritis, hyperplasia,
complicated by the biopsy induced artifacts. disordered proliferative endometrium, cyclic endometrium,

© Red Flower Publication Pvt. Ltd. Indian Journal of Pathology: Research and Practice / Volume 7 Number 6 / June 2018
Pradeep Jadhav, Dipti Patel, S.N. Chawla / Histopathological Patterns in Abnormal Uterine Bleeding at a Tertiary Hospital 755

polyps and carcinoma are the endometrial causes of AUB (41-50 years) and postmenopausal (> 50 years). 10%
[1]. Also important are endocrine disorders and formalin was used as fixative for fixation of endometrial
pregnancy. specimens obtained by endometrial biopsy or curettage.
Menorrhagia, polymenorrhoea, metrorrhagia, and The specimens were processed routinely and stained
intermenstrual bleeding are the most common with Haematoxylin and Eosin (H&E) stain.
presentations. Dilatation and Curettage is important.
safe and effectivediagnostic procedure in assessment Results
of abnormal uterine bleeding [2].
For diagnosis of the etiology of AUB, histopathological A total of 215 endometrial biopsies and curettings from
examination of the endometrial biopsies and curettings patients with abnormal uterine bleeding (AUB) were
is consideredthe genuine diagnostic test [1]. studied. The cause of AUB could be determined in only
203 out of 215 endometrial biopsies as 12 biopsy
specimens were inadequate for evaluation.
Materials and Methods
Of the 203 cases, 158 (77.83%) were due to functional
This is a retrospective study carried out in department causes as no organic pathology was found, while the
of pathology of a tertiary hospital of American remaining 45 cases (28.47%) showed definite endometrial
pathology (Table 1).
International Institute of Medical Sciences ,Udaipur. A
total 215 patients operated for D&C for abnormal Perimenopausal age group was the most commonly
uterine bleeding from Jan 2016 to Jan 2018 ,were included affected age group (55.34%) followed by reproductive
in this study. The patients presenting with AUB were from age group 34.88%(Table 2).
18 to 72 years. The histopathological findings of AUB were Out of 215 cases of abnormal uterine bleeding,
categorized into functional and organic causes. The proliferative endometrium was the most common
functional causes of AUB included in this study were normal (35.34%cases) followed by secretory endometrium
proliferative phase and secretory phase endometrium (18.60%). Disordered proliferative endometrium (17.67%)
and other abnormal physiological changes in the and endometrial hyperplasia (17.73%) were the next
endometrium (atrophic endometrium, weakly proliferative common lesions. Endometrial carcinoma was present
endometrium, disordered proliferative endometrium and in 2.36% of cases (Table 3).
pill endometrium). Hyperplasia, polyp and endometrial Out of the 158 functional cases of AUB, proliferative
carcinoma, the intrauterine lesions included in this study endometrium and secretory endometrium werethe most
were the organic causes. Patients with bleeding disorders, common patterns and were seen in 76 cases (48.10%) and
cervical or vaginal pathology, leiomyoma and 40(25.31%) cases, respectively. This was followed by
pregnancywere excluded. 38(24.05%) cases of disordered proliferative endometrium.
Medical Records Department provided clinical data Amongst the 45 organic lesions causing AUB,
related to age, abnormal bleeding patterns, menstrual endometrial hyperplasia was the most common
history and gynaecological examination findings.The andseen in 36 (73.46%) cases.Hyperplasia without atypia
histopathology slides were collected from histopathology was the most common type of hyperplasia and was
section of pathology department and were reviewed. observed in 28 (62.22%) patients. The other organic
Patients were also categorized into the following causes of AUB observed in this study include 5 (11.11%)
agegroups: reproductive (18-40 years), perimenopausal cases of malignancy.

Table 1: Distribution of cases of AUB according to cause

Cause of AUB Total Percentage


Functional causes 158 77.83%
Organic causes 45 22.17%
Total 203 100%

Table 2: Age group of patients presenting with AUB

Age group (in years) Total Percentage

18 - 40 years (reproductive) 75 34.88


41- 50 years (perimenopausal) 119 55.34
> 50 years (postmenopausal) 21 9.78
Total 215 100

Indian Journal of Pathology: Research and Practice / Volume 7 Number 6 / June 2018
756 Pradeep Jadhav, Dipti Patel, S.N. Chawla / Histopathological Patterns in Abnormal Uterine Bleeding at a Tertiary Hospital

Table 3: Histopathological patterns according to age group

Histopathological pattern Age group (yrs) Total %


18-40 41-50 >50

Proliferative phase 40 36 0 76 35.34


Secretory phase 25 15 0 40 18.60
Atrophic 0 0 4 4 1.86
Disordered proliferative 8 30 0 38 17.67
Endometrial polyp 0 2 2 4 1.86
Hyperplasia without atypia 0 26 9 35 16.27
Hyperplasia with atypia 0 0 1 1 0.46
Endometrial carcinoma 0 0 5 5 2.36
Inadequate for evaluation 2 10 0 12 5.58
Total 75 119 21 215 100

Discussion The incidence of endometrial carcinoma in the present


study was 2.36%. Gerald et al.[9] and Khan et al.[10]
In our study we received 215 curettage samples. All observed similar findings accounting for 1.7% and 0.4%
samples were processed but 12 samples showed only respectively (Table 6).
blood clots,so they were labelled inadequate.
Khan et al. [10] found incidence of endometrial polyp
In our study menorrhagia was the most common 0.4%. With respect to this our findings were almost same
complaint (50.25%). Similar to this, Archana et al. [3] found (1.86%).
menorrhagia in (43.85%) cases.
In conclusion, particularly in patients of premenopausal
In our study, proliferative phase of endometrium was and postmenopausal bleeding histopathological
found in (35.34%) cases. Similar to this Jairajpuri et al. [4], examination of endometrium obtained by dilatation and
Khare et al.[5], Abdullah et al.[6], found proliferative phase curettage remains a a very important approach to an
endometrial in (24.92%), (26.8%), (21.7%) cases respectively etiological diagnosis. As the patient’s age increases ,the
(Table 4). frequency of intrauterine diseases revealed by curettage
The distribution of types of endometrial hyperplasia in increases. Generally the diagnostic yield is low in patients
our study is compared with other studies as shown in Table younger than 30 years.
5. Simple hyperplasia without atypia of endometrium was However, endometrial dilation and curettage can be
the most common type according to Pilli et al.[7] and avery good approach in cases of abnormal uterine
Vakiani et al.[8].Our study also closely correlates with their bleeding in women over 35 years, particularly if the
study. presentation is with irregular vaginal bleeding.

Table 4: Comparision of incidence of proliferative phase endometrium with different studies

Name of the study Incidence of proliferative phase

Jirajpuri et al.[4] 24.92%


Khare et al.[5] 26.8%
Abdullah et al.[6] 21.7%
Present study 35.34%

Table 5: Comparision of types of hyperplasia with different studies

Name of the study Hyperplasia without atypia Hyperplasia with atypia

Pilli et al.[7] 100% 0%


Vakiani et al.[8] 97.60% 2.40%
Present study 97.22% 2.78%

Table 6: Comparision of incidence of endometrial carcinoma with different studies

Name of the study Incidence of endometrial carcinoma


Gerald et al.[9] 1.7%
Khan et al.[10] 0.4%
Present study 2.36%

Indian Journal of Pathology: Research and Practice / Volume 7 Number 6 / June 2018
Pradeep Jadhav, Dipti Patel, S.N. Chawla / Histopathological Patterns in Abnormal Uterine Bleeding at a Tertiary Hospital 757

References 6. Layla Abdullah, Nabeel S. Bondayji. Histopathological


pattern of endometrial sampling performed for abnormal
1. Diagnosis of endometrial biopsies and curettings. A uterine bleeding. Bahrain Med Bull. 2011;33(4):1-6.
practical approach second edition. Michael T. Mazur,
7. Pilli GS, Sthi B, Dhaded AV. Dysfunctional uterine bleeding.
Robert J. Kurman. December 15, 2004.
Study of 100 cases. J Obstet Gynecol India. 2002;52(3):87-9.
2. Sajitha, et al. Endometrial pathology in AUB. CHRISMED
8. Vakiani M, Vavilis D, Agorastos T, Stamatopoulos P, Assimaki
Journal of Health and Research /Vol 1/Issue 2/Apr-Jun 2014.
A, Bontis J. Histopathological findings of the endometrium
3. Archana Bhosle, Michelle Fonseca. Evaluation and in patients with dysfunctional uterine bleeding. Clin Exp
histopathological correlation of abnormal uterine Bleeding Obstet Gynecol. 1996;23(4):236-9.
in perimenopausal women. Bombay Hosp J. 2010;52(1):
9. Gerald Dafe Furae, Jonathan Umezuluike Aligbe.
69-72.
Histopathological patterns of endometrial lesions in
4. Zeeba S. Jairajpuri, S. Rama and S. Jetky. Atypical uterine patients with abnormal uterine bleeding in a cosmopolitan
bleeding: histopathological audit of endometrium. A study population. J Basic Clin Reprod Sci. 2013;2(2):101-4.
of 638 cases. Al Ameen J Med Sci. 2013;6(1):21-8.
10. Sadia Khan, Sadia Hameed, Aneela Umber. Histopathlogic
5. A. Khare, R. Bansal, S. Sharma, P. Elhence, N. Makkar, Y. pattern of endometrium on diagnostic D & C in patients
Tyagi. Morphological spectrum of endometrium in patients with abnormal uterine bleeding. 2011;17(2):166-70.
presenting with dysfunctional uterine bleeding. People’s J
Sci Res. 2012;5(2):13-6.

Indian Journal of Pathology: Research and Practice / Volume 7 Number 6 / June 2018
758
Indian Journal of Pathology: Research and Practice

IJPRP Volume 7 Number 6, June 2018


DOI: http://dx.doi.org/10.21088/ijprp.2278.148X.7618.8

Original Research Article

Histopathological Study of the Architectural Patterns of in Situ Carcinoma


in Cases of Invasive Breast Cancer

Apoorva A.N.1, Shilpa L.2, Prakash C.J.3, Shivarudrappa A.S.4

1
Post Graduate 2Asssistant Professor 3,4
Professor, Department of Pathology, Vydehi Institute of Medical Sciences and Research Centre,
Bengaluru, Karnataka 560066, India.

Abstract

Context: In situ carcinoma in breast can be studied at two levels:


1. different morphologic patterns
2. by utilizing a prognostic grading system like the Van Nuys system. This study would
provide information regarding the patterns, classification, prognostic grading, also predict
the risk of recurrence after excision and assist in selecting treatment options.
Aims:
Corresponding Author:
• To estimate the cases displaying different architectural patterns of in situ carcinoma in
Shilpa L., invasive breast cancers.
Asssistant Professor,
• Determination of prognostic index (Van Nuys) of in situ carcinoma based on these
Department of Pathology,
Vydehi Institute of Medical patterns.
Sciences and Research Centre, Methods and Material: A Cross sectional study of 40 Modified Radical Mastectomy
Bengaluru, Karnataka 560066, specimens collected for a period of 18 months in our Tertiary care hospital. For histopathology
India.
study, specimens were fixed in 10% formalin, processed, paraffin embedded, sections (3-5 ì
E-mail:
dr.shilpahpt@gmail.com thickness) taken, stained with Haematoxylin and Eosin and studied under light microscope.
Statistical analysis used: Continuous variables are expressed as mean ±SD whereas
(Received on 27.04.2018, categorical variables are expressed as percentages. Data was analysed using SPSS version
Accepted on 24.05.2018)
20. P value < 0.0 was considered as statistically significant.
Results: All architectural patterns of DCIS either single or mixed were present in the
cases of invasive breast carcinoma, with solid [9 (36%) cases]: most common single
architectural pattern and Solid and comedo [7 (47%) cases]: the most common mixed
architectural pattern. High grade ductal carcinoma in situ was seen in 18 patients (45% of
cases), intermediate grade in 17 patients (43%) and low grade was seen in 5 patients (12%).
Conclusions: The current study provides evidence of the frequency of significant
histologic heterogeneity of in situ carcinoma, with at least 2 different architectural patterns
of ductal carcinoma in situ commonly present in individual lesions.
Keywords: Ductal Carcinoma; In Situ Component; Histological Grading.

Introduction common cause for cancer-related mortality [1]. The


number of women with breast cancer is expected to
Carcinoma of the breast is the most common increase by a third in the next 20 years [1,2].
carcinoma in women (31%) and is the second most

© Red Flower Publication Pvt. Ltd. Indian Journal of Pathology: Research and Practice / Volume 7 Number 6 / June 2018
Apoorva A.N., Shilpa L., Prakash C.J. et al. / Histopathological Study of the Architectural Patterns 759
of in Situ Carcinoma in Cases of Invasive Breast Cancer

Breast carcinoma is a group of genetically distinct sections were taken of 4- 6 microns thickness and stained
diseases with different behaviors. Outcomes are with routine haematoxylin and eosin stain.
maximized when therapy is tailored to individual patient The in situ carcinoma cases are divided into pure and
and disease characters.[3] Breast carcinoma emerges mixed patterns depending on the type of architectural
by a multistep process which can be broadly equated to pattern studied. If only a single pattern was present then
transformation of normal cells via the steps of hyperplasia, it is termed ‘pure’ and if more than one pattern was
premalignant change and in situ carcinoma [4,5]. noted then it is termed ‘mixed’. Nuclear grading is based
In situ carcinoma can be studied at two levels either by on the size of malignant cells nuclei in comparison to
using the different morphological patterns or by using a normal ductal epithelial cells. Grade 1, 2 and 3 were
prognostic grading system like the Van Nuys system. diagnosed when the nuclei of the malignant cells were
between 1.5 and 2 times, 2 and 2.5 times and greater
Few studies have demonstrated that coexisting DCIS
than 2.5 times that of normal ductal epithelial cells,
may be associated with less aggressiveness but not in others
respectively. The Van Nuys Prognostic Index (VNPI)
[6,7]. This study was conducted to describe the different
combines three significant predictors of local
architectural patterns of DCIS in invasive breast cancer
recurrence: tumor size, margin width, and pathologic
patients and to assess whether associated with
classification. Scores of 1 (best) to 3 (worst) were
aggressiveness of the coexisting invasive ductal carcinoma.
assigned for each of the 3 predictors and then totalled
to give an overall VNPI score ranging from 3 to 9. [8]
Materials and Methods Using the modified Bloom Richardson grading
system, the resection specimens were classified into 3
The study included consecutive cases of invasive breast grades based on the percentage of tubule formation,
cancers with an in situ component over the period of three degree of nuclear pleomorphism and number of mitosis.
years from January 2011 to July 2014. For the retrospective Those with score 3-5, 6-7 and 8-9 were assigned a grade
study cases archived in the Department of Pathology, 1, 2 and 3 respectively. The digital images of the selected
Vydehi Institute of Medical Sciences and Research Centre, tissue preparations were photographed from the
Bengaluru between January 2011 and July 2012 were Olympus light microscope using a Sony Cybershot DSC-
selected. For the prospective study, specimens and slides WX200/NCE32 digital camera.
received by the Department of Pathology, Vydehi Institute
of Medical Sciences and Research Centre, Bengaluru, from
August 2012 to July 2014 were included. Those patients Results
who had underwent trucut biopsies or lumpectomy
without axillary clearance, cases of exclusive carcinoma Forty patients who fulfilled the inclusion criteria were
in situ without an invasive component and improperly recruited for the study. The age of the study population
fixed tissues were excluded from the study. was 46.4±11.7 years. Twenty patients (50%) were in the
premenopausal and perimenopausal age group (< 47
The medical records of the patients were examined and
years), ten patients (25%) were in the menopausal and
data regarding age, menopausal state, location of the
postmenopausal age group each. In twenty five cases
tumor with respect to site (right or left) and quadrant
tumours were located in outer quadrants whereas in
(inner, outer or centre), size of tumor assessed clinically
nine cases tumours were located in inner quadrants. In
by palpation and mammography reports were noted. five cases tumour were located centrally whereas one
The modified radical mastectomy specimens received case involved all the quadrants. Tumour size was smaller
were examined grossly for size, shape, colour and than 2 cm in seven (17.5%) patients, between 2 and 5 cm
consistency. Changes in the nipple and skin were also in 24 (60%) patients and larger than 5 cm in 9 (22.5%)
noted wherever relevant. The mastectomy specimens patients. Twenty one tumours were classified as grade I, 13
were cut serially at a distance of 2- 3 cm. Cut surfaces tumours as grade II and 6 tumours as grade III on histology.
were noted for tumor, colour, size, extension, Various architectural patterns of ductal carcinoma
involvement of skin and secondary changes such in situ associated with 40 cases of invasive carcinoma
necrosis, cystic degeneration, haemorrhage and are summarised in table 1 and representative
fibrosis. The axillary tail was dissected and as many photographs are depicted in figure 1. Pure patterns were
nodes as possible were isolated in fresh state and their observed in 24 patients whereas mixed forms were 16
number and size were noted. patients. Solid pattern was the most common pure form
The specimen is then fixed in 10% formalin for 24- 48 whereas solid and comedo was the most common mixed
hours. Several bits were taken from the tumor proper, pattern. None of the variables differed significantly
its margins, nipple and lymph nodes. They were processed between patients with pure form of DCIS and mixed forms
by the routine paraffin embedding technique and multiple (Table 2).
Indian Journal of Pathology: Research and Practice / Volume 7 Number 6 / June 2018
760 Apoorva A.N., Shilpa L., Prakash C.J. et al. / Histopathological Study of the Architectural Patterns
of in Situ Carcinoma in Cases of Invasive Breast Cancer

Necrosis was more commonly associated with with solid pattern than those with other patterns (p= 0.015).
comedo pattern (p=0.00021) and cribriform (p= 0.029) Solid pattern was associated with lower histological
than solid patterns whereas it was more commonly grades than others. There were no significant differences
associated with comedo pattern than micro papillary with respect to any other variables (Table 3).
pattern (0.0047). Vascular invasion was more common Necrosis was more commonly associated with solid
in patients with solid pattern than those with comedo and comedo pattern than micro papillary and cribriform
pattern (p=0.04) and cribriform pattern (p=0.017). Lymph pattern (p = 0.0233) and solid and cribriform pattern (p =
node involvement stage 1 was more common in patients 0.0112) whereas it was more commonly associated with
Table 1: Distribution of growth pattern in patients with invasive carcinoma

DCIS with a single growth pattern 24 (60%)


Micropapillary 1 (2.5%)
Cribriform 5 (12.5%)
Solid 11 (27.5%)
Comedo 7 (17.5%)

DCIS with a mixed growth pattern 16 (40%)


Solid and comedo 7 (17.5%)
Solid and cribriform 3 (7.5%)
Cribriform and micropapillary 2 (5%)
Solid, comedo and cribriform 3 (7.5%)
Solid, comedo and micropapillary 1 (2.5%)

Table 2: Comparison of variables between patients with single and mixed ductal carcinoma in situ patterns
Single (24) Mixed (16) P value

Age (years) 47.46±11.38 46.56±11.46 0.809


Tumour size (cm3) 56.30±98.11 31.22±38.07 0.337
Maximum tumor dimension (cm) 3.79±2.30 4.66±2.50 0.267
Quadrants - Outer: inner: central: all 15: 4: 4:1 13: 1: 2: 0 0.285
VNIP score 6.04±1.46 6.12±1.14 0.849
Tubule formation (%) 15.08±10.09 15.00±10.32 0.980
Mitotic figure/hpf 7.67±6.15 6.25±7.61 0.520
Nuclear grade 2: 10: 12 2: 7: 7 0.89
Paget’s disease of the nipple – Yes/No 1:23 0:16 0.6
Skin discolouration – Yes/No 12:12 9:7 0.475
Necrosis – Yes/No 11:13 10:6 0.239
Calcification – Yes/No 11:13 5:11 0.278
Lymphatic invasion – Yes/No 9:15 3:13 0.181
Perineural invasion – Yes/No 1:23 1:15 0.646
Vascular invasion – Yes/No 8:16 4:12 0.420
Lymphnode involvement – 0: 1: 2: 3 2: 11: 9: 2 0: 7: 7: 2 0.659
Histological grade – 1:2:3 15: 5: 4 7: 7: 2 0.300

Table 3: Comparison of variables among patients with different forms of single ductal carcinoma in situ
Comedo Cribriform Micro Papillary Solid (n=11) P value
(n=7) (n=5) (n=1)
Age (years) 48.00±7.72 37.00±4.00 45 52.09±13.29 0.097
Tumour size (cm3) 82.49±134.32 59.30±120.61 1.5 43.26±67.25 0.821
Maximum tumor dimension (cm) 4.52±2.850 4.26±3.26 2.0 3.28±1.40 0.588
Quadrants - Outer: inner: central: all 3: 1: 2: 1 2: 2: 1: 0 1: 0: 0: 0 7: 3: 1: 0 0.782
VNIP score 6.85±1.06 5.40±1.51 4 6.00±1.48 0.161
Tubule formation (%) 12.85±9.06 10.40±7.30 20 18.18±11.67 0.467
Mitotic figure/hpf 10.71±7.95 3.80±2.77 3 7.90±5.46 0.239
Nuclear grade- low: intermediate: high 1: 2: 4 1: 3: 1 0: 0: 1 2: 5: 6 0. 349
Paget’s disease of the nipple – Yes/No 1: 6 0: 5 0: 1 0:11 0.469
Skin discolouration – Yes/No 3: 4 3: 2 1: 0 6: 5 0.698
Necrosis – Yes/No 7: 0 3: 2 0: 1 1: 10 0.001
Calcification – Yes/No 2: 5 1: 4 0: 1 8: 3 0.101
Lymphatic invasion – Yes/No 5: 2 0: 5 0: 1 4: 7 0.071
Perineural invasion – Yes/No 1: 6 0: 5 0: 1 0: 11 0.469
Vascular invasion – Yes/No 1: 6 0: 5 0: 1 7: 4 0.034
Lymphnode involvement – 0: 1: 2: 3 1: 3: 2: 1 0: 1: 3: 1 1: 0: 0: 0 0: 7: 4: 0 0.049
Histological grade – 1:2:3 3: 0: 4 3: 2: 0 1: 0: 0 8: 3: 0 0.038

Indian Journal of Pathology: Research and Practice / Volume 7 Number 6 / June 2018
Apoorva A.N., Shilpa L., Prakash C.J. et al. / Histopathological Study of the Architectural Patterns 761
of in Situ Carcinoma in Cases of Invasive Breast Cancer

solid, comedo and cribriform pattern than solid, comedo Discussion


and micro papillary (p = 0.0143) and micro papillary and
cribriform (p = 0.0253). There were no significant In this study invasive carcinomas along with an in situ
differences with respect to any other variables (table 4). component were studied and the architectural pattern of
in situ component was compared with the macroscopic
Necrosis was more common with any comedo group
and histopathologic features of coexisting invasive
than cribriform (p = 0.0024), micro papillary (p = 0.0011)
carcinoma. This is one of the very few studies that have
and solid patterns (p = 0.0006).
Table 4: Comparison of variables among patients with different forms of mixed ductal carcinoma in situ

Micropapillary Solid + Solid + Solid + comedo + Solid + comedo +


+ cribriform comedo cribriform cribriform micropapillary
(n=2) (n=7) (n=3) (n=3) (n=1)

Age (years) 54.00±26.87 47.57±10.82 51.33±3.05 37.66±2.51 37 0.461


Tumour size (cm3) 54.75±41.36 23.43±35.79 13.05±15.26 61.33±54.01 2.88 0.422
Maximum tumor 7.25±1.76 3.60±2.23 4.16±0.76 6.66±3.21 2.4 0.170
dimension (cm)
Quadrants - Outer: inner: 2: 0: 0: 0 7: 0: 0: 0 1: 1: 1: 0 2: 0: 1: 0 1: 0: 0: 0 0.340
central: all
VNIP score 6.00±1.41 6.71±1.11 5.00±1.00 6.33±0.57 5 0.211
Tubule formation (%) 27.50±17.67 15.00±7.63 20.00±8.66 5.00±0.00 5 0.089
Mitotic figure/hpf 3.50±0.71 8.42±10.99 2.66±1.52 5.33±4.16 10 0.824
Paget’s disease of the 0: 2 0:7 0: 3 0: 3 0: 1 ------
nipple – Yes/No
Skin discolouration – 1: 1 5: 2 0: 3 1: 2 0: 1 0.244
Yes/No
Necrosis – Yes/No 0: 2 6: 1 0: 3 3: 0 1: 0 0.015
Calcification – Yes/No 1: 1 3: 4 1: 2 0: 3 0: 1 0.629
Lymphatic invasion – 1: 1 1: 6 0: 3 1: 2 0: 1 0.607
Yes/No
Perineural invasion – 0: 2 1: 6 0: 3 0: 3 0: 1 0.849
Yes/No
Vascular invasion – 1: 1 2: 5 0: 3 0: 3 1: 0 0.222
Yes/No
Lymphnode involvement 0: 2: 0: 0 0: 2: 4: 1 0: 0: 2: 1 0: 2: 1: 0 0: 1: 0: 0 0.428
– 0: 1: 2: 3
Histological grade – 1:2:3 2: 0: 0 2: 4: 1 2: 1: 0 1: 1: 1 0: 1: 0 0.588

Table 5: Comparison of variables among ductal carcinoma in situ patients with a pattern in any combination

Any comedo Any cribriform Any micropapillary Any solid P value


(n=18) (n=13) (n=4) (n=25)
Age (years) 45.50±9.08 43.07±11.30 47.50±17.54 48.40±11.47 0.557
Tumour size (cm3) 51.57±89.66 48.39±76.98 28.47±38.62 34.63±52.22 0.835
Maximum tumor dimension (cm) 4.40±2.69 5.25±2.739 4.72±3.09 3.84±2.057 0.423
Quadrants - Outer: inner: central: all 13: 1: 3: 1 7: 3: 3: 0 4: 0: 0: 0 18: 4: 3: 0 0.625
VNIP score 6.61±1.03 5.61±1.19 5.25±1.25 6.08±1.28 0.070
Tubule formation (%) 11.94±8.06 14.00±11.01 20.00±14.71 15.40±10.09 0.467
Mitotic figure/hpf 8.88±8.41 3.84±2.60 5.00±3.36 7.20±6.95 0.206
Nuclear grade 0: 2: 2
Paget’s disease of the nipple – Yes/No 1: 17 0: 13 0: 4 0: 25 0.499
Skin discolouration – Yes/No 9: 9 4: 9 2: 2 12: 13 0.711
Necrosis – Yes/No 17: 1 6: 7 1: 3 11: 14 0.002
Calcification – Yes/No 5: 13 3: 10 1: 3 12: 13 0.354
Lymphatic invasion – Yes/No 7: 11 2: 11 1: 3 6: 19 0.509
Perineural invasion – Yes/No 2: 16 0: 13 0: 4 1: 24 0.501
Vascular invasion – Yes/No 4: 14 1: 12 2: 2 10: 15 0.129
Lymphnode involvement – 0: 1: 2: 3 1: 8: 7: 2 0: 5: 6: 2 1: 3: 0: 0 0: 12: 11: 2 0.290
Histological grade – 1:2:3 6: 6: 6 8: 4: 1 3: 1: 0 13: 10: 2 0.227

Indian Journal of Pathology: Research and Practice / Volume 7 Number 6 / June 2018
762 Apoorva A.N., Shilpa L., Prakash C.J. et al. / Histopathological Study of the Architectural Patterns
of in Situ Carcinoma in Cases of Invasive Breast Cancer

studied the effect of various patterns of DCIS on The study had few limitations. Firstly, the study was
histological aggressiveness of the coexisting invasive characterised by a small sample size. Secondly, the study
ductal carcinoma. included only the architectural patterns of DCIS
Only a small proportion of DCIS exist as pure whereas andthere were no cases of lobular carcinoma or an
the remaining coexist with invasive cancer. In a study by associated lobular in situ component. Thirdly, the
Scripcaru et al.,[5],265 of the 289 DCIS cases coexisted histological features of invasive ductal carcinoma with
with invasive cancer. The single pattern (79/133) was or without DCIS were not compared. Lastly, the effect of
most common whereas mixed form accounted for the DCIS pattern on the long term outcome was not studied.
rest (54/133) of the DCIS associated with invasive
carcinoma. Similar findings were also found in our study Conclusion
with slight predominance of single pattern (24/40). In
the Scripcaru et al, study solid pattern (54/97) was the All architectural patterns of DCIS can coexist either in
most common whereas micro papillary (4/97) was the single or mixed variety with invasive breast carcinomas.
least common [5]. Similarly, in our study solid pattern (11/ The comedo DCIS pattern either in pure or mixed form is
24) was the most common whereas the micro papillary associated with necrosis whereas pure solid pattern is
was the least common (1/24). associated with histologically less aggressive tumours.
The significance of nuclear grade as a criterion for The study suggests that patterns of DCIS coexisting with
classifying DCIS into high and low nuclear grade of invasive carcinoma may have a prognostic role in the
malignancy has been well-emphasized [9]. In the series by assessment of prognosis in breast carcinoma patients.
Lennington et al., the mixed DCIS were more frequently of However, larger follow-up studies are required to confirm
intermediate grade whereas in Scripcaru et al., 12%, 45% this issue.
and 43% had low, intermediate and high nuclear grades
respectively. Similarly in our study 12.5%, 43.7% and 43.7%
Acknowledgement
cases had low, intermediate and high nuclear grades
respectively [5,10]. Although, few studies have reported NIL
lower nuclear grades with solid pattern, there were no
significant differences in nuclear grades of various single
patterns. Similar results are also reported by Scripcaruet Conflict of Interest
al [5]. Even, the VNPI which has been considered as an
important prognostic marker of DCIS was also not NIL
significantly different among various patterns.
Presence of necrosis has been demonstrated as an References
independent poor prognostic factor in patients with
carcinoma breast [11]. In our study necrosis was more 1. Leonard GD, Swain SM. Ductal carcinoma in situ,
commonly associated with comedo and cribriform complexities and challenges. J Natl Cancer Inst. 2004;
patterns than solid pattern whereas comedo pattern 96(12):906–20.
more frequently had necrosis than micro papillary 2. Pinder SE, O’Malley FP, Breast Pathology, Chapter 17.
pattern. Among the mixed patterns, combinations of Morphology of Ductal Carcinoma in situ, Churchill-
solid and comedo patterns, and solid, comedo and Livingstone, New York, NY, USA, 1st edition, 2006.pp.191-
cribriform patterns had more frequent necrosis than 200.
other combinations. 3. Lester SC. The Breast. In: Kumar V, Abbas AK, Fausto N, Aster
JC, Editors. Pathologic Basis of Disease. 8th Edition.
Presence of lympho-vascular invasion is also an
Philadelphia. Saunders. An imprint of Elsevier.
independent predictor of prognosis in breast carcinoma 2010.pp.1065-1095.
patients [12]. Different patterns of DCIS did not differ with
4. Tumors of the breast. I. O Ellis, S. E, Pinder, A. H. S. Lee, C. W.
respect to lymphatic and perineural invasion. Vascular
Elaston, Editors. Diagnostic Histopathology of Tumors 4th
invasion was more commonly associated with solid
edition, Churchill, Livingstone. An imprint of Elsevier.
pattern suggesting solid pattern may be more aggressive. 2013.pp.865-930.
However, lymph node involvement was less aggressive
5. Scripcaru G, Zardawi IM, “Mammary Ductal Carcinoma In
with solid pattern suggesting the contrary. In line with this
situ: A Fresh Look at Architectural Patterns,” International
solid pattern was associated with lower histological grades Journal of Surgical Oncology, vol. 2012, Article ID 979521, 5
of coexisting invasive cancer. However, the data on pages, 2012. doi:10.1155/2012/979521
association of DCIS pattern with grade of coexisting
6. Wong H, Lau S, Leung R, Chiu J, Cheung P, Wong TT, Liang
invasive cancer is extremely limited.
R, Epstein RJ, Yau T. Coexisting ductal carcinoma in situ

Indian Journal of Pathology: Research and Practice / Volume 7 Number 6 / June 2018
Apoorva A.N., Shilpa L., Prakash C.J. et al. / Histopathological Study of the Architectural Patterns 763
of in Situ Carcinoma in Cases of Invasive Breast Cancer

independently predicts lower tumor aggressiveness in 10. Lennington WJ, Jensen RA, Dalton LW, Page DL. Ductal
node-positive luminal breast cancer. Med Oncol. 2012 carcinoma in situ of the breast. Heterogeneity of individual
Sep;29(3):1536-42. lesions. Cancer 1994;73:118-124.
7. Wong H, Lau S, Yau T, Cheung P, Epstein RJ. Presence of an 11. Maiorano E, Regan MM, Viale G, et al. Prognostic and
in situ component is associated with reduced biological predictive impact of central necrosis and fibrosis in early
aggressiveness of size-matched invasive breast cancer. Br breast cancer. Results from two International Breast Cancer
J Cancer. 2010 Apr 27;102(9):1391-6. Study Group randomized trials of chemoendocrine
8. Gilleard O, Goodman A, Cooper M, Davies M, Dunn J. The adjuvant therapy. Breast cancer research and treatment.
significance of the Van Nuys prognostic index in the 2010;121(1):211-218.
management of ductal carcinoma in situ. World Journal of 12. Liu YL, Saraf A, Lee SM, et al. Lymphovascular invasion is
Surgical Oncology. 2008;6:61. an independent predictor of survival in sreast cancer after
9. Silverstein M, Lagios MD, Craig PH, Waisman JR, Lewinsky neoadjuvant chemotherapy. Breast cancer research and
BS, Colburn WJ, Poller DN. A prognostic index for ductal treatment. 2016;157(3):555-564.
carcinoma in situ of the breast. Cancer. 1996 Jun
1;77(11):2267-74.

Indian Journal of Pathology: Research and Practice / Volume 7 Number 6 / June 2018
764
Indian Journal of Pathology: Research and Practice

IJPRP Volume 7 Number 6, June 2018


DOI: http://dx.doi.org/10.21088/ijprp.2278.148X.7618.9

Original Research Article

Hematological Indices in Thyroid Disorders

K.R. Shouree1, M. Bharathi2


1
Post Graduate 2Professor and Head, Department of Pathology, Mysore Medical College and Research Institute, Mysore, Karnataka
570001, India.

Abstract

Context: Thyroid hormones are the important hormone helping in body metabolism.
Every cell in the body depends on thyroid hormones for regulation of their metabolism. They
are also known to play an important role in hematopoiesis. This study was done to know the
impact of thyroid disorders like hypothyroidism and hyperthyroidism on various
haematological indices which we see in routine complete blood count done using automated
Corresponding Author: cell counter.
K.R. Shouree, Aims: To study the effect of hypothyroidism and hyperthyroidism on various
Post Graduate, hematological indices
Department of Pathology,
Mysore Medical College and Settings and Design: Prospective study
Research Institute, Mysore, Methods and Material: A total of 150 including 50 hypothyroid, 50 hyperthyroid and 50
Karnataka 570001, India. control subjects were evaluated. A comparison was done on different parameters.
E-mail:
shoukr.139@gmail.com Statistical analysis used: Results were reported as mean SD for variables. ANOVA and
POST HOC test were used to calculate the significance of difference between two groups. P
(Received on 13.04.2018, value <0.05 was considered as a significant change.
Accepted on 05.05.2018)
Results:A statistical difference was observed for MCV and MCH but other parameters did
not show any statistically significant difference.
Conclusions: All the patients with thyroid disorders should be periodically evaluated for
hematological changes.
Keywords: Thyroid Hormones; Hypothyroid; Hyperthyroid.

Inroduction produced by hypothalamus [1-3]. The association of


thyroid disorders and abnormalities in hematological
The thyroid gland being the largest endocrine gland of parameters is well known. In 1979, Fein showed that Graves’
human body is vital for body metabolism. It secretes disease is associated with anemia[4]. Horton observed a
hormones like triiodothyronine (T3) and thyroxine (T4) decreased number of red blood cells (RBCs) in the
which primarily influence the metabolic rate and protein peripheral blood (PB) of patients after thyroidectomy [5].
synthesis. Also play an important role in early brain Hypothyroidism can cause certain forms of anemia on
development, somatic growth, bone maturation and the one hand or hyperproliferation of immature erythroid
production of red blood cells. Hormone output from the progenitors on the other hand. The anemia is usually
thyroid is regulated by Thyroid stimulating hormone macrocytic hypochromic anemia of moderate severity
(TSH) secreted from the anterior pituitary gland which [5]. In contrast, anemia is not frequently observed in
is regulated by Thyrotropin releasing hormone (TRH) patients with hyperthyroidism, whereas erythrocytosis is

© Red Flower Publication Pvt. Ltd. Indian Journal of Pathology: Research and Practice / Volume 7 Number 6 / June 2018
K.R. Shouree & M. Bharathi / Hematological Indices in Thyroid Disorders 765

fairly common [4,6]. It has been found that all TSH value and without any thyroid and hematological
haematological parameters return to normal when a disorder) = 50 Initially, two separate blood samples were
euthyroid state is achieved [7]. As far as white blood cells taken from each patient, 2 mL of uncoagulated sample
and thrombocytes are concerned, a slightly depressed from each patient for thyroid hormone assay and EDTA
total leucocyte count, neutropenia, and thrombocytopenia whole blood sample for whole blood count. Serum
have been observed in hypothyroid patients [8]. samples were used to determine level of T3, T4 and TSH.
Furthermore, elevated, normal, or slightly depressed total Complete blood cell count was measured with EDTA
leucocyte counts have been found in hyperthyroid patients, anticoagulated sample . The study was approved by the
with only a relative decrease in the number of neutrophils institutional ethics committee.
and a relative increase in the number of eosinophils and
mononuclear cells (MNCs). Nevertheless, hyperplasia of
all myeloid cell lines in hyperthyroidism and their Results
hypoplasia in hypothyroidism were reported by
In 50 patients with hypothyroidism, mean age 28 years
Axelrod [9].
and in 50 patients with hyperthyroidism, mean age was
In the present study, we attempted to evaluate the 30years and in control group, the mean age was 25years
effect of thyroid dysfunction on various hematological (Table 1). Comparison of different parameters revealed
parameters. that red cell indices including MCV and MCH have
significant statistical difference (P value <0.05) but no
difference was observed for Hb, RBC, Hct, RDW, PC, PDW,
Materials and Methods
Pct, and MCHC. Comparison between control group and
This was a prospective study comprising of a total of two study groups revealed statistically significant
166. Based on TSH value (normal range 0.3500–4.9400 difference in MCV, MCH and Pct but no significant
IU/mL), the study group was divided into three subgroups: difference was observed for Hb, RBC, Hct, RDW, PC, PDW,
Hypothyroid (TSH>4.94I U/dL) = 50 Hyperthyroid and MCHC (Table 2).
(TSH<0.35I U/dL) = 50 Euthyroid or control group (normal
Table 1: Descriptive Analysis of Patients with Hypothyroidism and Hyperthyroidism

Number Age Max Min Male Female TSH T3 T4


(Mean) (years) (years) % % (mIU/ml) (mg/ml) (mg/ml)

Hypothyroidism 50 28 55 12 5 45 5.34 1.19 1.53


Hyperthyroidism 50 30 52 15 10 40 0.20 1.57 1.52
Control 50 25 58 16 12 38 2.8 0.9 7.2

Table 2: Comparison between Blood Cell Count, RBC and Platelet Indices in Patients with Hypothyroidism and Hyperthyroidism

Index No. of Patients Mean Std. Deviation P-value


MCV (fl) Hypothyroidism 50 86.0 12.04 0.22
Control 50 83.1 11.63
Hyperthyroidism 50 80.0 11.2 0.047
MCH (pg) Hypothyroidism 50 27.4 3.84 0.42
Control 50 28.0 3.92
Hyperthyroidism 50 25.0 3.16 0.02
MCHC (g/dL) Hypothyroidism 50 31.0 4.34 0.58
Control 50 31.2 4.37
Hyperthyroidism 50 31.5 4.41 0.56
Hb (g/dL) Hypothyroidism 50 11.2 1.57 0.63
Control 50 11.1 1.55
Hyperthyroidism 50 11.0 1.54 0.90
RBC (million/mm3) Hypothyroidism 50 4.13 0.58 0.77
Control 50 4.08 0.57
Hyperthyroidism 50 4.46 0.63 0.12
Hct (%) Hypothyroidism 50 34.2 4.79 0.60
Control 50 35.6 4.98
Hyperthyroidism 50 34.0 4.76 0.99

Indian Journal of Pathology: Research and Practice / Volume 7 Number 6 / June 2018
766 K.R. Shouree & M. Bharathi / Hematological Indices in Thyroid Disorders

Index No. of Patients Mean Std. Deviation P-value

RDW (%) Hypothyroidism 50 16.8 2.35 0.98


Control 50 15.0 2.1
Hyperthyroidism 50 15.4 2.16 0.48
Platelet count Hypothyroidism 50 2.00 0.28 0.88
(lacs/dL) Control 50 2.50 0.35
Hyperthyroidism 50 2.20 0.31 0.94
PDW (%) Hypothyroidism 50 0.18 0.031 0.60
Control 50 0.19 0.031
Hyperthyroidism 50 0.23 0.031 0.80
Pct (%) Hypothyroidism 50 15.00 2.1 0.045
Control 50 16.00 2.24
Hyperthyroidism 50 15.50 2.17 0.46

Abbreviations:
MCV- Mean Corpuscular volume
MCH- Mean Corpuscular Hemoglobin
MCHC- Mean Corpuscular Hemoglobin concentration
Hb- Hemoglobin
Hct-Hematocrit
RDW-Red cell distribution width
PDW- Platelet distribution width
Pct- plateletcrit

Discussion References

Thyroid hormones play an important physiological role 1. Ahmed OM, El Gareib AW, El Bakry AM et al. Thyroid
in metabolic activity of human body. They also have role hormones status and brain development interactions. Int
in erythropoiesis by induction of erythropoietin secretion J Dev Neurosci 2008;26(2):147- 209.
and proliferation of erythroid progenitors [10,11]. 2. Saranac L, Zivanoic S, Bjelkovic B et al. Why is the thyroid
Thyroid dysfunctions including hypothyroidism and so prone to autoimmune disease? Horm Res Pediatr 2011;
hyperthyroidism affect blood cells and cause anemia. 75(3):157-65.
They may also cause pancytopenia. Other blood cell 3. Koibuchi N, Chin WW. Thyroid hormone action and brain
indices including MCV, MCH, and MCHC also could development. Trends EndocrinolMetab2000;11(4):
change during thyroid dysfunction. According to our 123-28.
study, MCV, MCH and Pct show significant difference 4. H.G. Fein and R.S. Rivlin. Anemia in thyroid diseases,
between two groups of patients but no statistically Medical Clinics of North America 1975;59(5):1133–45.
significant difference was found in Hb, MCHC, RDW, Pct,
5. L Horton, RJ Coburn, JM England R.L. Himsworth. The
Hct and RBC. Comparison of two groups with control
haematology of hypothyroidism. Quarterly Journal of
group revealed statistically significant difference in MCV, Medicine 1976;45(177):101–23.
MCH, but no difference was observed for Hb, MCHC, RDW,
platelet count, Hct, RBC, PDW and Pct. 6. R Corrocher, MQuerena, AM Stanzial, G de Sandre.
Microcytosis in hyperthyroidism: haematological profile
Kawa et al. reported that RBC, Hb and Hct in patients
in thyroid disorders. Haematologica 1981;66( 6):779–86.
with hyperthyroidism were significantly higher than in
control group while RBC and Hb were decreased in 7. JA Perlman, PM Sternthal . Effect of 131I on the anemia of
hypothyroidism and Hct was increased. They also hyperthyroidism. Journal of Chronic Diseases 1983;36(5):
showed that MCH and MCHC were lower in both groups 405–12.
in comparison with control group and MCV was 8. CSP Lima, D E ZantutWittmann, V Castro et al.
increased in two study groups [12]. Pancytopenia in untreated patients with Graves’ disease
Thyroid 2006; vol16(4):403–09.
9. AR Axelrod, L. Berman. The bone marrow in hyperthyroidism
Conclusion and hypothyroidism. Blood 1951; vol 6(5):436–53.
According to obtained data, it is important to monitor 10. Das KC, Mukherjee M, Sarkar TK et al. Erythropoiesis and
the patients with hypothyroidism and hyperthyroidism erythropoietin in hypo and hyperthyroidism. J
for probable hematological changes. ClinEndocrinolMetab 1975;40(2):211-20.

Indian Journal of Pathology: Research and Practice / Volume 7 Number 6 / June 2018
K.R. Shouree & M. Bharathi / Hematological Indices in Thyroid Disorders 767

11. Golde DW, Bersch N, Chopra IJ et al. Thyroid hormone 12. Kawa MP, Grymula K, Paczkow E et al. Clinical relevance of
stimulates erythropoiesis in vitro. Br JHaematol 1977; thyroid dysfunction in human erythropoiesis, biochemical
37(2):173-77. and molecular studies. Eur J Endocrinol 2010;162(2):295-305.

Indian Journal of Pathology: Research and Practice / Volume 7 Number 6 / June 2018
768
Indian Journal of Pathology: Research and Practice

IJPRP Volume 7 Number 6, June 2018


DOI: http://dx.doi.org/10.21088/ijprp.2278.148X.7618.10

Original Research Article

Screening of Blood Donors for Transfusion Transmitted Infections: Is Zero


Risk Blood Supply Possible?

Smita C. Pathade1, Anagha P. Amale2, Harshada R. Bhangale3, Runali D. Mendhe4, Vilas M.


Sangole5
1
Associate Professor 2Associate Professor 3,4Post Graduate Student 5Professor and HOD, Department of Pathology, Dr. Ulhas Patil Medical
College and Hospital, Jalgaon, Maharashtra 425001, India.

Abstract

Context: Blood transfusion service is a vital part of the National health service and there
is no substitute for human blood and its components. Main objective of National blood
policy is to provide safe, adequate quantity of blood, blood components and products.
However window period blood donation may not be picked up by the routinely employed
screening methods and may carry the risk of transfusing transfusion transmitted infections
Corresponding Author:
(TTI).
Smita C. Pathade, Aims: Aim of the present study is to find the seroprevalence of transfusion transmitted
Associate Professor, diseases (viz. HIV, HBV, HCV infection, syphilis and malaria) in blood donors.
Department of Pathology,
Dr. Ulhas Patil Medical College and Methods and Material: Present study is a retrospective study carried out in hospital
Hospital, Jalgaon, Maharashtra attached blood bankof Medical college in rural area of Maharashtra. All blood donations
425309, India. received during a period of seven years i.e from January 2010 to December 2016 were included
E-mail: in the study. Results of screening tests performed for HIV, HBV, HCV infection, syphilis and
smitacpathade@gmail.com malaria were noted. Data obtained was tabulated and seroprevalence of individual infecton
derived.
(Received on 25.04.2018,
Accepted on 14.05.2018) Results: The seroprevalence of transfusion transmitted infections in blood donors in
present study is 1.46% with seroprevalence of 0.20% for HIV, 1.11% for HBV, 0.12% for HCV
infection and 0.02% for syphilis.
Conclusions: Seroprevalence of TTIs among blood donors has a decreasing trend.
However the risk of transmitting infection through blood transfusion even though negligible
still persists.
Keywords: Blood Donors; Seroprevalence; Transfusion Transmitted Infections.

Introduction development of policies, infrastructures and training of


personnel, WHO is working along with National
Blood is vital and is the most essential lifesaving authorities to promote safe blood and to reduce the
substance. It cannot be produced artificially. Thus the spread of HIV and other TTI in all countries [1]. Even after
only source to obtain blood for the purpose of blood all the ongoing efforts and technological advances zero
transfusion is from human beings. The major aim of risk blood supply appears to be a dream.
blood transfusion is to make transfusion safe and
beneficial. With continuous research and development How far we are away from completely safe blood
in the field of blood banking the risk of transmission of supply? As an attempt to answer this question, we
transfusion transmitted infections (TTI) is decreasing conducted a retrospective study which involved
day by day. By advocating and assisting in the collecting data from our hospital attached blood bank.

© Red Flower Publication Pvt. Ltd. Indian Journal of Pathology: Research and Practice / Volume 7 Number 6 / June 2018
Smita C. Pathade, Anagha P. Amale, Harshada R. Bhangale et al. / Screening of Blood Donors for Transfusion 769
Transmitted Infections: Is Zero Risk Blood Supply Possible?

Material and Methods Observation / Results

Total number of blood donations received and Total number of donors screened during the period of
the number of sero-reactive blood bags were noted 7 years from January 2010 to December 2016 was 14,227.
from January 2010 to December 2016. This included Total 209 donors tested seropositive for one of the TTI
unpaid voluntary donors as well as replacement viz. HIV, HBV, HCV and syphilis. All PBS samples screened
donors. Demographic details about the donors were were negative for malarial parasite. We came across 3
not included in the study as main aim of the study co- infections, of which 2 case were seroreactive for HBV
was to know the seroprevalence of TTI in donor and HCV and one case was seroreactive for HCV and syphilis.
group. Out of total 209 seroreactive donor blood bags, 159
Our blood bank follows the rules and regulations laid tested positive for HBV, 29 for HIV, 18 for HCV and 3 were
down by National blood policy. Strict donor selection found positive for syphilis giving seroprevalence of
criteria’sare adhered to by highly competent medical 1.11%, 0.20%, 0.12% and 0.02 % respectively (Table 1).
officers. Screening of donated blood is done for Overall seropositivity is highest for HBV infection,
common TTIs like HIV, HBV, HCV, syphilis and malaria followed by that for HIV infection. Maximum numbers of
by experienced and highly competent technicians and HBV seropositive cases were detected in year 2012.
pathologists. Similarly for HCV infection as well maximum
Screening for HIV infection is done using QualisaTM seropostivity was detected in the same year i.e. 2012.
microwell enzyme immunoassay HIV4.0 kit. This kit is Reason for which cannot be explained. A fluctuating
intended to be used for the detection of antibodies to trend is seen for HIV seropositivity over the years.
HIV 1/2 and “O” subtype virus and HIV-1 p24 antigen in
human serum or plasma.
Discussion
Screening for HBV infection is done using QualisaTM
microwell enzyme immunoassay HBsAg kit. This kit is NACO in 2016 preliminaryreport mentioned the
intended to be used for the detection of hepatitis B National seropositivity of TTIs among blood donors as
surface antigen (HBsAg) in human serum or plasma. 0.13%, 0.93%, 0.3%, 0.18% and 0.03% for HIV, HBV, HCV,
Similarly for HCV infection, Qualisa TM microwell syphilis and malaria respectively [2]. In present study, the
enzyme immunoassay HCV kit was employed. This is a seroprevalence of HIV, HBV, HCV, syphilis and malaria is found
third generation enzyme immunoassay and is intended to be 0.20%, 1.11%, 0.12%, 0.02% and 0.00% respectively.
to be used for the detection of antibodies to hepatitis C Our data correlates well with National statistics.
virus in human serum or plasma. Multiple studies related to seroprevalence of TTIs
Screening of syphilis was done using rapid plasma among blood donors are reported from various parts of
reagin test. For detection of malaria, peripheral blood India [3-13]. Similar studies are reported from other parts
smears (PBS) were prepared and reported by pathologist. of the world as well [14- 16]. Table 2 shows the results of
studies carried out in India, Pakistan, New Ethiopia and
Statistical Analysis Tanzania.
The data obtained was tabulated. Seropositive cases Table 3 shows the seroprevalence studies carried out in
were distributed year wise and overall percentage of India between year 1990 and 2000. During this time period
seropositivity was derived. Seroprevalence of HIV, HBV, mean seroprevalence of HIV, HBV, HCV infection and syphilis
HCVinfection and syphiliswas derived. is 0.36%, 6.2%, 0.9% and 0.67% respectively.

Table 1: Year wise distribution of seropositivity for TTIs in blood donors

Sr. No. year Number of donors Test results


HIV HBsAg HCV Syphilis Malaria

1 2010 784 5 9 1 0 0
2 2011 2000 7 28 4 1 0
3 2012 3077 5 46 6 0 0
4 2013 2650 4 27 0 1 0
5 2014 2076 2 23 4 0 0
6 2015 2002 1 11 2 1 0
7 2016 1638 5 15 1 0 0
Total 14,227 29 (0.20%) 159 (1.11%) 18 (0.12%) 3 (0.02%) 0

Indian Journal of Pathology: Research and Practice / Volume 7 Number 6 / June 2018
770 Smita C. Pathade, Anagha P. Amale, Harshada R. Bhangale et al. / Screening of Blood Donors for Transfusion
Transmitted Infections: Is Zero Risk Blood Supply Possible?

Table 4 shows the seroprevalence studies carried out that measures to control the incidence of HBV should be
in India between year 2001 and 2016. During this time intensified.
period mean seroprevalence of HIV, HBV, HCV infection One of the limitations of our study is that we could
and syphilis is 0.23%, 1.20%, 0.40% and 0.23% not recheck the results of screening test by confirmatory
respectively. Thus we can infer that the seroprevalence test due to lack of facilities in our blood bank.Individual
of TTIs among blood donors has a decreasing trend in Donor Nucleic Acid Testing (ID-NAT) is the latest
different parts of India technological advance in ensuring the safety of the
In present study, seroprevalence of HBV is high as nation’s blood supply. ID-NAT is a direct test which
compared to that of other TTIs. Similar finding is targets the viral DNA/RNA. Multiple studies conducted
reflected in all other studies listed in table 2 [3-16]. As blood in India to evaluate the benefits of NAT in blood banks
donors are part of general population, we can suggest have concluded with favorable results [7, 17].

Table 2: Results of studies carried out in India and abroad

Sr. No. Study group / State Year of study Seroprevalence


HIV HBV HCV Syphilis Malaria

Indian studies
1 Patil et al 3, Karnataka 2011- 2012 0.42% 1.88% 0.28%
2 Srikrishna et al 4 Bangalore 1997- 1998 0.44% 1.86% 1.02% 1.6%
3 Fernandes et al 5 Karnataka 2008- 2009 0.06% 0.34% 0.06% 0.11% 0.01%
4 Mathaiet al 6Kerala 1994- 1999 0.2% 13.3% 1.4% 0.2%
5 Prasad et al 7 Bangalore 2006- 2011 0.23% 0.53% 0.05% 0.05%
6 Garg et al 8Jodhpur Rajasthan 1994- 1999 0.44% 3.44% 0.28% 0.22%
7 Jain et al 9 Jaipur 2009-2010 0.33% 1.5% 0.63% 0.16%
8 Arora et al 10 South Haryana 2002- 2006 0.3% 1.7% 1.0% 0.9%
9 Chaurasiaet al 11New Delhi 2011- 2013 0.27% 1.38% 0.54% 0.32%
10 Giri et al 12,Pravara 2009- 2010 0.07% 1.09% 0.74% 0.07%
11 Chandekar et al13, Mumbai 2007- 2011 0.26% 1.30% 0.25% 0.28%
12 Present study 2010- 2016 0.20% 1.11% 0.12% 0.02% 0.00%

Studies carried out of India


13 Arshad et al 14, Pakistan Before 2016 0.04% 1.84% 1.7% 2.1% 0.07%
14 Tessema et al 15, New Ethiopia 2003- 2007 3.8% 4.7% 0.7% 1.3%
15 Matee et al 16, Tanzania 2004- 2005 3.8% 8.8% 1.5% 4.7%

Table 3: Results of seroprevalence studies carried out in India between year 1990 and 2000

Sr. No. Study group/ State Year Seroprevalence


HIV HBV HCV Syphilis
1 Srikrishna et al 4,Bangalore 1997-1998 0.44% 1.86% 1.02% 1.6%
2 Mathaiet al 6,Kerala 1994-1999 0.2% 13.3% 1.4% 0.2%
3 Garg et al 8,Jodhpur Rajasthan 1994- 1999 0.44% 3.44% 0.28% 0.22%
Mean Seroprevalence 0.36% 6.2% 0.9% 0.67%

Table 4: Results of seroprevalence studies carried out in India between year 2001 and 2016

Sr. No Study group/ State Year Seroprevalence


HIV HBV HCV Syphilis
3
1 Patil et al , Karnataka 2011- 2012 0.42% 1.88% 0.28% -
2 Fernandes et al 5 Karnataka 2008- 2009 0.06% 0.34% 0.06% 0.11%
3 Prasad et al 7 Bangalore 2006- 2011 0.23% 0.53% 0.05% 0.05%
4 Jain et al 9 Jaipur 2009-2010 0.33% 1.5% 0.63% 0.16%
5 Arora et al 10 South Haryana 2002- 2006 0.3% 1.7% 1.0% 0.9%
6 Chaurasiaet al 11New Delhi 2011- 2013 0.27% 1.38% 0.54% 0.32%
7 Giri et al 12,Pravara 2009- 2010 0.07% 1.09% 0.74% 0.07%
8 Chandekar et al13, Mumbai 2007- 2011 0.26% 1.30% 0.25% 0.28%
9 Present study 2010- 2016 0.20% 1.11% 0.12% 0.02%
Mean Seroprevalence 0.23% 1.20% 0.40% 0.23%

Indian Journal of Pathology: Research and Practice / Volume 7 Number 6 / June 2018
Smita C. Pathade, Anagha P. Amale, Harshada R. Bhangale et al. / Screening of Blood Donors for Transfusion 771
Transmitted Infections: Is Zero Risk Blood Supply Possible?

Conclusion 7. Prasad S, Uma Bai KR. Seropositivity of HIV, Hepatitis B


and C, and syphilis among blood donors: A retrospective
The seroprevalence of TTIs in blood donors in present study. Asian journal of transfusion science. 2014
study is 1.46%, with 0.20% for HIV, 1.11% for HBV, 0.12% June;8(1):66–67.doi:10.4103/0973-6247.126705.
for HCV and 0.02% for syphilis. Measures to reduce the 8. Garg S, Mathur DR, Garg DK. Comparison of seropositivity
incidence of HBV infection in general population should of HIV, HBV, HCV and syphilis in replacement and voluntary
be intensified so as to reduce the incidence of HBV blood donors in western India. Indian J PatholMicrobiol.
infection in blood donors. If individual donor Nucleic acid 2001 Oct;44(4):409–12.
testing (ID – NAT) is performed for TTIs, on blood donor 9. Jain R, Aggarwal P, Gupta GN. Need for nucleic acid testing
samples, we can come more close to zero risk blood in countries with high prevalence of transfusion transmitted
transfusion. infections. ISRN Hematology. 2012 August. DOI:10.5402/
2012/718671.https://www.researchgate.net/publication/
231176761.
Acknowledgement 10. Arora D, Arora B, KhetarpalA.Seroprevalence of HIV, HBV,
HCV and syphilis in blood donors in southern Haryana.
We would like to express our gratitude towards the Indian J PatholMicrobiol. 2010 June;53(2):308-9.
expert technical assistance provided by Mr. Amol
11. Chaurasia R, Aman S, Das B, Chatterjee K. Screenng
Chaudhari (Techncal Supevisor), Mr. Sayyed Shaikh Sir donated blood for transfusion transmitted infections by
(Senior Technician) and Mr. Ritesh Warke (Technician) serology along with NAT and response rate to notification
working at hospital attached blood bank of DUPMC, of reactive results: An Indian experience. Journal of blood
Jalgaon. transfusion. 2014 Nov; http://dx.doi.org/10.1155/2014/
412105.
12. Giri PA, Deshpande JD, Phalke DB, Karle LB. Seroprevalence
References
of transfusion transmissible infections among voluntary
blood donors at a tertiary care teaching hospital in rural
1. Choudhry M, Choudhry VP. Prevention and control of HIV
area of India. J Family Med Prim Care. 2012 June;1(1):48-51.
among blood products and IV drug users. In: Choudhry VP,
Saxena R, Pati HP, editors. Recent advances in 13. Chandekar SA, Amonkar GP, Desai HM, Valvi N, Puranik GV.
haematology. 1sted. New Delhi: Jaypee Brothers Medical Seroprevalence of transfusion transmitted infections in
Publishers(P) Ltd; 2004.pp.165–82. healthy blood donors: A 5 year tertiary care hospital
experience. J Lab Physicians. 2017 Dec;9(4):283-287.
2. National AIDS Control Organization (NACO) and National
Blood Transfusion Council (NBTC), Ministry of health and 14. Arshad A, Borhany M, Anwar N, Naseer I, Ansari R, Boota S
family welfare, Government of India in collaboration with et al. Prevalence of transfusion transmissible infectionsin
U.S centers for disease control and prevention (HHS/ CDC) blood donors of Pakistan. BMC Hematol. 2016;16:27.
division of global HIV and TB (DGHT), India, Christian doi:10.1186/s12878-016-0068-2.
medical college, Vellore & Christian medical association of 15. Tessema B, Yismaw G, Kassu A, Amsalu A, Mulu A, Emmrich
India (CMAI), New Delhi. Assessment of NACO supported F et al. Seroprevalence of HIV, HBV, HCV and syphilis
blood banks.A preliminary report 2016. infections among blood donors at Gondar University
3. Patil VS, Patil PM. Seroprevalence of transfusion teaching hospital, Northwest Ethiopia: declining trends
transmissible infections among blood donors, A over a period of five years. BMC infect Dis. 2010;10:111.
retrospective study. Indian journal of pathology research 16. Matee MI, Magesa PM, Lyamuya EF. Seroprevalence of
and practice.2017;6(2):303-6. human immunodeficiency virus, hepatitis B and C viruses
4. Srikrishna A, Sitalakshmi S, Damodar P. How safe are our and syphilis among blood donors at the Muhimbil National
safe donors? Indian J pathol microbial.1999;42(4):411-16. hospital in Dar Es Salaam, Tanzania.BMC public health.
2006;6:21.
5. Fernandes H, D’souza PF, D’souza PM. Prevalence of
transfusion transmitted infections in voluntary and 17. Shrivastava M, Mishra S. Nucleic acid amplification testing
replacement donors. Indian J Hematol Blood Transfus. (NAT): An innovative diagnostic approach for enhancing
2010Sept;26(3):89-91.doi:10.1007/s12288-010-0044-0. blood safety. National journal of laboratory medicine. 2017
Apr;6(2): IRO1 – IRO6. DOI: 10.7860/NJLM/2017/26201:2205.
6. Mathai J, Sulochana PV, Satyabhama S, Nair PK, Sivakumar
S. Profile of transfusion transmissible infections and
associated risk factors among blood donors of Kerala.
Indian J PatholMicrobiol. 2002 July;45(3):319-22.

Indian Journal of Pathology: Research and Practice / Volume 7 Number 6 / June 2018
772
Indian Journal of Pathology: Research and Practice

IJPRP Volume 7 Number 6, June 2018


DOI: http://dx.doi.org/10.21088/ijprp.2278.148X.7618.11

Original Research Article

Image Analysis and Image Classifier Using Neural Network with Machine
Learning to Perform Differential Leucocyte Count

Swaroop Raj B.V.1, Divya C.2, Smitha B.V.3

1
Assistant Professor, Department of Pathology, 2Assistant Professor, Department of Anatomy, Sri Devaraj Urs Medical College, Tamaka,
Kolar, Karnataka 563101, India. 3Software Engineer

Abstract

Introduction: A five part differential leucocyte count is provided by a hematology analyser


with abnormalities being detected as flags which are then later on reviewed and confirmed
Corresponding Author: by a pathology trainee or pathologist based on the difficulty level of that individual case or
Swaroop Raj B.V.,
knowledge of the particular trainee. Peripheral smear examination is considered the gold
Assistant Professor, standard and is time consuming and subjective.
Department of Pathology, Methods: Using a self prepared 1500 leishman stained leucocyte image dataset the
Sri Devaraj Urs Medical College, machine learning programme tensor flow from google using image intensity, histogram
Tamaka, Kolar, Karnataka 563101,
and convolutional neural network was trained and this was put to test on 80 random leucocyte
India.
E-mail: images.
dr.swaroop.raj@gmail.com Results: Only 65% concordance was obtained on 5 tier leucocyte differential count.
However 95% concordance was achieved by using a two tier leucocyte differential
(Received on 10.04.2018,
classification of polynuclear and mononuclear cells.
Accepted on 05.05.2018)
Conclusion: Larger dataset of images are needed before image analysis using this model
can be used routinely to substitute or as addon to routine peripheral smear examination.
Keywords: Image Classifier; Differential Leucocyte Count; TensorFlow; Peripheral Smear.

Introduction in leucocyte classification on leishman stained


peripheral smears and have revealed high accuracy and
A five part differential count is routinely provided by a sensitivity of this method [1-6]. Convolutional neural
hematology analyser with abnormalities being detected network is a software algorithm which uses deep learning
as flags which are then later on reviewed and confirmed and minimal image processing for image classification
by a pathology trainee or pathologist based on the and recognition.
difficulty level of that individual case or knowledge of
the particular trainee / pathologist. Differential count Many newer analysers have peripheral smear staining
by hematology analyser is accurate in most instances, and image analysis of slides for morphological
however has its own limitations and hence peripheral differential count analysis. However these features are
smear examination is considered the gold standard for only seen in high end and costly analysers and not
differential counts. Peripheral smear differential count routinely not available in most hematology analysers.
accuracy is largely dependent on the observer and hence This study was done to see if image analysis by
its main limitations being subjectivity and level of machine learning using convolutional neural network
knowledge of the observer. Studies have been done using can provide accurate differential count and remove the
neural network based approach using machine learning subjectivity and inter-observer variability that is usually
© Red Flower Publication Pvt. Ltd. Indian Journal of Pathology: Research and Practice / Volume 7 Number 6 / June 2018
Swaroop Raj B.V., Divya C., Smitha B.V. / Image Analysis and Image Classifier Using Neural Network with Machine 773
Learning to Perform Differential Leucocyte Count

associated with manual peripheral smear examination machine learning framework considering manual
and can this be an alternate cheap solution for leucocyte differential count as a gold standard.
laboratories in developing countries where high end Concordance percentage was calculated as the
analysers with image analysis may not be a viable accuracy for the test.
option.

Objectives Results
To perform manual leucocytedifferential count and Training set images for tensorflow software were taken
leucocytedifferential count usingtensorflow an open from routinely processed peripheral smears with dataset
source machine learning framework using image composed of 300 images of leucocytes classified manually
analysis on leishman stained peripheral smears by a pathologist as monocyte, lymphocyte, neutrophil,
To correlate the differential leucocyte count between eosinophil and basophil. The images were rotated and
manual and tensorflow machine learning framework. flipped to increase the size of training set to 1500 images.
Tensor flow an open source software uses inception
architecture formachine learning and runs on python
Materials and Methods script in command prompt in windows 10 operating
system. After training the software using the 1500 image
Sample Size Calculation was done using sensitivity of dataset, we ran the 80 images test set and obtained
test derived from the study done by Mu Chun Su et al [4]. concordant results in 65% images and discordant results
with sensitivity of the new test as 97%, Precision of 5% in 35% of the test set images. Detailed analysis of the
and desired confidence level being 99%. A sample size of resultsare tabulated below in Table 1.
80 test images was calculated. The average sensitivity, specificity, positive predictive
Methodology - EDTA samples received at Department value and negative predictive value for leucocyte
of Pathology, Central Diagnostic Laboratory Services, R differential count using tensor flow was 44.4%, 87.3%,
L Jalappa Hospital and Research Centre, Tamaka 37.8% and 86.8% respectively. As only 65% concordance
attached to Sri Devaraj Urs Medical College between percentage and low sensitivity and specificity was
December 15th – January 15th were included in the study. obtaing for the five stage classification of leucocytes we
Peripheral smears were prepared by following standard modified our leucocyte differential classification to a
operating procedures for the same and stained with simpler classification.
Leishman stain. Differential leucocyte count was done Hence we reran the dataset classifying the images as
manually by two pathologists and done simultaneously only polynuclear and mononuclear leucocytes
on same fields by neural network based machine learning considering all leucocytes except lymphocytes and
algorithm by processing images taken by Axiocam ERc monocytes as polynuclear and lymphocytes and
5s CMOS sensor mounted on Primostar Zeiss microscope monocytes as mononuclear. Using this classification
using Zen Blue software at 400x magnification. when we ran the test set thepercentage of concordance
Proforma was filled and corresponding differential results increased to 95% from the previously obtained
leucocyte count by manual and image analysis method 65%. Detailed analysis of the results are tabulated below
was documented. in Table 2.
Statistical Analysis The average sensitivity, specificity, positive predictive
value and negative predictive value for leucocyte
Sensitivity, Specificity, Positive predictive value and
differential count using tensor flow classifying images
Negative predictive value was calculated forleucocyte
as only polynuclear and mononuclear cells was 93.3%.
differential count using tensor flow an open source

Table 1: Sensitivity, Specificity, Positive predictive value and Negative predictive value for 5 type leucocyte
differential count using tensor flow

Sensitivity (%) Specificity Positive predictive Negative Predictive


(%) value (%) value (%)
Neutrophil 70.5 62 76.6 54.5
Eosinophil 20 96 25 94.7
Basophil 66.6 93.5 28.5 98.6
Monocyte 0 100 0 98.7
Lymphocyte 65 85 59 87.9
Average 44.4 87.3 37.8 86.8

Indian Journal of Pathology: Research and Practice / Volume 7 Number 6 / June 2018
774 Swaroop Raj B.V., Divya C., Smitha B.V. / Image Analysis and Image Classifier Using Neural Network with Machine
Learning to Perform Differential Leucocyte Count

Limitations of this was to obtain similar staining Discussion


properties of all dataset and test set images, small size
of the data set and preprocessing in the data set such as Sensitivity and specificity of our study was similar
nuclear segmentation and cell discrimination. other studies being > 90% when simplified two type
leucocyte classification was used. However the 5 type
The figure 1 below shows the percentage of confidence
leucocyte differential count had a low sensitivity of 44%.
score for the particular category.
Our study with a limited dataset of 1500 images
Figure 1 Tensor Flow image classifier classifying the
obtained an accuracy of 95% with the two step
various images and its confidence level with a score of
classification of leucocytes when compared to other
more than 50% considered as significant.
studies which have all attained an accuracy of more

Table 2: Sensitivity, Specificity, Positive predictive value and Negative predictive value for simplified 2 type leucocyte
differential count using tensor flow

Sensitivity Specificity Positive predictive value (%) Negative Predictive value (%)
(%) (%)

Polynuclear 96.6 90 96.6 90


Mononuclear 90 96.6 90 96.6
Average 93.3 93.3 93.3 93.3

Fig. 1:

Table 3: Comparison of sensitivity and specificity of leucocyte differential count using machine learning in other studies

Sensitivity Specificity
(%) (%)
Mu-Chun Su et al4 94.9 99.2
Present Study using 5 type leucocyte differential count 44.4 87.3
Present Study using simplified 2 type leucocyte differential count 93.3 93.3

Table 4: Comparison of accuracy of leucocyte differential count using machine learning in other studies

Present Study Choi JW et al7 Mathur A et al8

Accuracy 95 % 97.6 % 92.7 %


Dataset - images 1500 6000 267

Indian Journal of Pathology: Research and Practice / Volume 7 Number 6 / June 2018
Swaroop Raj B.V., Divya C., Smitha B.V. / Image Analysis and Image Classifier Using Neural Network with Machine 775
Learning to Perform Differential Leucocyte Count

than 90%. Studies by Ramesh N et al, Shahih I et al and five types of white blood cells. In Proceedings of the 32nd
Rawat et al have all obtained accuracy of more than Annual International Conference of the IEEE Engineering
90% using more complex machine learning algorithms.9- in Medicine and Biology Society (EMBC ’10), 2010
11
We can see that lower the images in the dataset, lower Sep.pp.5593–96.
the accuracy and the only way to obtain higher 3. M. Ghosh, D. Das, S. Mandal et al. Statistical pattern analysis
accuracy was to increase the number of dataset images of white blood cell nuclei morphometry. In Proceedings
which trains the computer in assessing difficult images of the IEEE Students’ Technology Symposium (TechSym’
10), 2010.pp.59–66.
and even classifying at higher level classification such
as the classical five level classification which was 4. Mu-Chun Su, Chun-Yen Cheng, and Pa-Chun Wang. A
achieved in other studies [6]. Further studies need to be Neural-Network-Based Approach to White Blood Cell
using more complex image processing and machine Classification. The Scientific World Journal, vol. 2014,
Article ID 796371, 9 pages, 2014. 
learning algorithm using stain normalization, leucocyte
segmentation, nuclear / cytoplasmic segmentation and 5. Z., Mazin, et al. Neural Network Classification of White
feature extraction to achieve higher accuracy. Blood Cell Using Microscopic Images. International
Journal of Advanced Computer Science and Applications,
2017;8(5).
6. Mohammed EA, Mohamed MM, Far BH, Naugler C.
Conclusion
Peripheral blood smear image analysis: A compre- hensive
The present study yielded satisfactory results with the review. J Pathol Inform. 2014;5(1):9.
limited dataset achieving more than 90% sensitivity, 7. Choi JW, Ku Y, Yoo BW, Kim J-A, Lee DS, Chai YJ, et al. White
specificity and concordance on the two tier leucocyte blood cell differential count of maturation stages in bone
differential count. However large dataset of training marrow smear using dual-stage convolutional neural
networks.  2017.
images along with complex image processing will be
needed to achieve similar results on the standard 5 type 8. Mathur A, Tripathi AS, Kuse M. Scalable system for
leucocyte differential count and to use real time classification of white blood cells from Leishman stained
classification to be used in a more practical situation. blood stain images. J Pathol Inform 2013;4:15.
9. Ramesh N, Dangott B, Salama ME, Tasdizen T. Isolation
and two-step classification of normal white blood cells in
Reference peripheral blood smears. J Pathol Inform 2012;3:13.
10. Shahin AI, Guo Y, Amin KM, Sharawi AA. White blood cells
1. S. H. Rezatofighi, K. Khaksari, and H. Soltanian-Zadeh,
identification system based on convolutional deep neural
“Automatic recognition of five types of white blood cells in
learning networks. Computer methods and programs in
peripheral blood,” in Proceedings of the International
biomedicine. 2017 Nov 16.
Conference of Image Analysis and Recognition, 2010;6112:
161–172. 11. Rawat, J., Singh, A., Bhadauria, H.S. et al. Leukocyte
Classification using Adaptive Neuro-Fuzzy Inference
2. P.R. Tabrizi, S.H. Rezatofighi, and M.J. Yazdanpanah, “Using
System in Microscopic Blood Images. Arab J Sci Eng
PCA and LVQ neural network for automatic recognition of
2017.pp.1-18. https://doi.org/10.1007/s13369-017-2959-3.

Indian Journal of Pathology: Research and Practice / Volume 7 Number 6 / June 2018
776
Indian Journal of Pathology: Research and Practice

IJPRP Volume 7 Number 6, June 2018


DOI: http://dx.doi.org/10.21088/ijprp.2278.148X.7618.12

Original Research Article

A Study of High Risk Operational Link for Gastritis Assessment (OLGA)


Stages in South Indian Subjects

Thara Keloth1, Marie Moses Ambroise2, Thomas Alexander3, Susy S. Kurian4


1
Senior Resident, Department of Pathology, Jawaharlal Institute of Postgraduate Medical Education and Research, Puducherry-
605006,India. 2Associate Professor, Department of Pathology, Pondicherry Institute of Medical Sciences, Puducherry-605014, India. 3 Professor,
Department of Gastroenterology, Pondicherry Institute of Medical Sciences, Puducherry-605014, India. 4 Professor, Department of Pathology,
Pondicherry Institute of Medical Sciences, Puducherry-605014,India.

Abstract

Background: The OLGA staging system which was developed in 2005 assesses the stage
of gastric atrophy and also predicts the risk of gastric carcinoma development. High risk
Corresponding Author: OLGA stages carry a significant risk for developing gastric carcinoma. A worldwide study of
OLGA gastritis staging showed no cases of high risk OLGA stages in a centre from North
Marie Moses Ambroise, India. The present study was undertaken to estimate the prevalence of high risk OLGA stages
Associate Professor,
among dyspeptic patients in a South Indian population and also study the correlation
Department of Pathology,
Pondicherry Institute of Medical with relevant clinico-pathological parameters.
Sciences, Puducherry 605014, Materials and Methods:Ninety-six patients attending the Gastroenterology OPD with
India dyspepsia were studied . Gastric biopsies were collected according to the Sydney-Houston
biopsy protocol and were assessed using the OLGA system.
E-mail:
drmosesambroise1978@gmail.com Results:The prevalence rate of high risk OLGA stages (III& IV) in this study was 6.25% and
that of low risk OLGA stages (0, I & II) was 93.75%. The prevalence rate of H.pylori in this
(Received on 15.05.2018, study was 62%.
Accepted on 09.06.2018)
Conclusion: The prevalence rate of high risk OLGA stages was 6.25% in subjects with
dyspepsia among this South Indian population.
Keywords: Atrophic Gastritis; Gastric Carcinoma; Helicobacter Pylori.

Introduction The OLGA system was developed in 2005 and was


derived from the modified Sydney system. The
Gastric carcinoma is the second most common cancer histological OLGA staging is based on the location and
in Chennai as recorded in the Chennai registry. It extent of atrophy as present in the antrum, the incisura
accounts for 9.3% of all cancers among men, being and the corpus. High risk OLGA stages (Stages III and
second only to lung carcinoma which has a IV) are generally associated with greater risk of
prevalence of 9.8%. On an all Indian basis, the states developing gastric carcinoma [5-9]. This study was
with the highest prevalence are Arunachal Pradesh undertaken in order to estimate the prevalence of high
(20.7% among men) and Mizoram (15.5% among risk OLGA stages among dyspeptic patients, since there
men) [1,2]. is a high prevalence of gastric carcinoma in this region
It is generally known that gastric carcinoma is of the country. The study also aimed to assess the
preceded by H.pylori associated chronic atrophic correlation of OLGA stages with relevant clinico-
gastritis with or without intestinal metaplasia [3,4]. pathological parameters.

© Red Flower Publication Pvt. Ltd. Indian Journal of Pathology: Research and Practice / Volume 7 Number 6 / June 2018
Thara Keloth, Marie Moses Ambroise, Thomas Alexander et al. / A Study of High Risk Operational Link for Gastritis 777
Assessment (OLGA) Stages in South Indian Subjects

Materials and Methods scale according to the Visual Analog Scale of the
modified Sydney system [11]. OLGA stage was
Patient selection determined in each case according to the recommendations
of the OLGA staging tutorial (Table 1) [5,6].
This cross-sectional study was carried out over a
period of 22 months, from October 2014 to July 2016. Statistical Analysis
Patients who attended the outpatient department of the
The Pearson’s Chi-square test and Fisher’s Exact test
Gastroenterology services of PIMS with dyspeptic
were used for categorical variables. The One-Way ANOVA
symptoms (abdominal pain, discomfort, vomiting, nausea,
was used to compare the mean age. A two sided p value
burping, belching and bloating) were evaluated with a
less than 0.05 was considered statistically significant for
questionnaire. The questionnaire included details about
all tests. The data was entered in Microsoft Excel (Microsoft
duration and nature of symptoms, family history of gastric
Corp., USA) and analyzed using IBM SPSS Statistics for
cancer, history of smoking, and alcohol consumption
Windows (version 20. 0. Armonk, New York: IBM
(frequency , amount in volume and duration). The amount
Corporation).
of alcohol consumed in grams/week was calculated, using
the above details and patients were categorized into four The study was approved by the Institutional Ethics
groups in accordance with a previous study: no Committee (IEC) and written informed consent was
alcohol,<60g/week (Mild), 60-140g/week (Moderate), >140g/ obtained from all the participants.
week (Heavy) [10].
Only those who had dyspeptic symptoms for a minimum Results
period of three months were included in the study.
Exclusion criteria were as follows: i)bleeding disorders ii) A total of 96 cases of dyspepsia were included in the
end stage liver disease iii) history of prior gastric surgeries study after applying exclusion criteria. The baseline
iv)newly diagnosed or past history of gastric cancer v) characteristics and OLGA staging are shown in Table 2. In
inadequate biopsy this study, 93.75% of the 96 cases showed low risk OLGA
stages (stages 0, I &II) and 6.25% of cases showed high risk
Endocscopy OLGA stages (stages III & IV). There was no significant
Patients were subjected to upper gastrointestinal (GI) association of OLGA staging with age , sex and smoking
endoscopy after obtaining written consent. Biopsies history. The majority of OLGA stage III/IV cases (84%) were
from atleast five sites were obtained according to the above 30 years of age. OLGA staging was significantly
Sydney-Houston protocol [11]. associated with alcohol intake.Only two cases had a family
history of gastric carcinoma.
Histology
About a third of the cases (35.4%) had normal
All specimens were routinely processed and sections endoscopic study. Another third of cases (29.2%) were
were stained with Haematoxylin and Eosin (H&E), Alcian diagnosed endoscopically as having gastritis while the
blue (for acidic mucin) and modified Giemsa (for H.pylori) remaining third (35.4%) were diagnosed with different
stains. The biopsy specimens were assessed by an lesions including oesophageal and duodenal lesions.
experienced expert GI Pathologist who was blinded to Sixty two percent of the total cases were positive for
both the clinical details and endoscopic findings. H.pylori. There was significant association of H.pylori load
The histological slides were assessed for five parameters on the surface epithelium with OLGA stages with a ‘p’ value
(H.pylori, activity, chronicity, atrophy and intestinal of 0.022. The H.pylori load showed an increasing trend
metaplasia) in the antrum, corpus and incisura angularis from stage 0 to stage III and then a decreasing trend
separately. Load of H. pylori, grade of atrophy and towards stage IV (Figure 1).
intestinal metaplasia (IM) were assessed using a four-tier

Table 1: OLGA staging system

Corpus
Atrophy score No atrophy Mild atrophy Moderate atrophy Severe atrophy

No atrophy Stage 0 Stage I Stage II Stage II


(including
incisura)

Mild atrophy Stage I Stage I Stage II Stage III


Antrum

Moderate atrophy Stage II Stage II Stage III Stage IV


Severe atrophy Stage III Stage III Stage IV Stage IV

Indian Journal of Pathology: Research and Practice / Volume 7 Number 6 / June 2018
778 Thara Keloth, Marie Moses Ambroise, Thomas Alexander et al. / A Study of High Risk Operational Link for Gastritis
Assessment (OLGA) Stages in South Indian Subjects

Table 2: OLGA staging and baseline characteristics

Total OLGA staging P value


Stage 0 Stage I Stage II Stage III Stage IV

Number 96 3 (3.1%) 44(45.8%) 43(44.8%) 4 (4.2%) 2 (2.1%)

Age mean (SD) 43.5(12.0) 42.7(17.2) 42.3(12.4) 45.4(11.6) 33.8 (6.2) 50 (0) 0.316

Sex
Female 32(33.3%) 0 19(43.2%) 11 (25.6%) 2 (50%) 0 0.205
Male 64(66.7%) 3 (100%) 25(56.8%) 32 (74.4%) 2 (50%) 2 (100%)

Smoking

Smoker 11*(11.5%) 0 5 (11.4 %) 5 (11.6%) 1 (25 %) 0


Non-smoker 85(88.5%) 3(100 %) 39(88.6%) 38(88.4%) 3 (75 %) 2 (100 %) 0.946
Alcohol

No alcohol 61(63.5%) 1 (33.3%) 33(75%) 25 (58.1%) 2 (50 %) 0


Mild alcohol 11(11.5%) 0 6 (13.6%) 5 (11.6%) 0 0 0.003
Moderate alcohol 10(10.4%) 2 (66.7%) 4 (9.1%) 3 (7.0 %) 1 (25 %) 0
Heavy alcohol 14(14.6%) 0 1 (2.3%) 10 (23.3%) 1 (25 %) 2(100 %)

* includes 10 current smokers and 1 ex-smoker

n=96

Fig. 1: Association of H. pylori load with OLGA stages


Shows significant association between the severity of H. pylori load and OLGA stages (2911x1600 pixels)

Intestinal metaplasia was present in 45% of the total Severe atrophy was found most frequently in the
cases and majority was of mild or moderate severity. incisura (5.2 % of all cases) compared to the antrum
There was a significant association between severity of (1 %) and corpus (1%). Moderate atrophy was also found
IM and high risk OLGA stages (p=0.001) (Figure 2). most frequently in the incisura (42.7% of all cases)
Atrophy and Intestinal Metaplasia according to compared to the antrum (41.7% of all cases) and the
Location: corpus (4.2%).

Indian Journal of Pathology: Research and Practice / Volume 7 Number 6 / June 2018
Thara Keloth, Marie Moses Ambroise, Thomas Alexander et al. / A Study of High Risk Operational Link for Gastritis 779
Assessment (OLGA) Stages in South Indian Subjects

n=96

Fig. 2: Association of Intestinal Metaplasia with OLGA stages


Shows significant association between the severity of IM and OLGA stages(2911x1600 pixels)

Moderate to severe intestinal metaplasia was found in that region. The centre included in the study from
more frequently in the antrum (10.4 % of all cases) as North India showed no cases of high risk OLGA stages
compared to the incisura (6.3 %) and corpus (3.1%). [8]. Notably the H. pylori prevalence was highest in India
(75%)in this multicentre study. Our study did reveal high-
risk OLGA in young adults also. Perhaps this reflects the
Discussion lower incidence of gastric carcinoma in North India
compared to the South [16].
The percentage of high -risk OLGA cases varies across
regions. In a long term follow-up study from Italy, Rugge High-risk OLGA stages increased significantly with age
et al found that high-risk OLGA stages constituted 11% in both H. pylori positive and negative cases [13]. It is
of their 93 cases at enrolment and 14 % after a follow-up interesting to note that the mean age of high–risk OLGA
period of atleast 12 years [7]. After the follow-up period cases was lower in our study compared to other countries.
,only cases with high-risk OLGA at enrolment developed The mean age of cases in OLGA stage II/III/IV in two Western
invasive carcinoma and high-grade intra-epitheial studies were 64.4/67.1/67.5 and 63.7/60.6/66.4 [17,18]. The
neoplasia. In a Chinese study, Zhou et al assessed OLGA in Tunisian study revealed them to be 54.6/44.2/58. In our
cases of functional dyspepsia and suspected early gastric study the mean age was 45.4/ 33.8/50 and majority of
cancer(EGC) and found the proportion of high–risk OLGA stage III cases were found in the 20-40 age group. This
to be 52.1% and 22.4% in the EGC and non-EGC groups could be due to poor sanitary conditions, higher
[12]. A study from South Korea found 16.6% of cases to be prevalence of H. pylori infection and genetic predisposition.
high-risk OLGA [13] whereas a study from Tunisia revealed All our high-risk OLGA cases were positive for H.pylori. The
the proportion to be only 6 % [14]. Our study found 6.25 % Korean study found smoking to be a riskfactor for high-
cases to be having high-risk OLGA.The age standardised risk OLGA. We however did not find a significant association
rates for gastric cancer in South Korea, China, Italy, Tunisia between smoking and high-risk OLGA probably due to the
and India are 41.8, 22.7, 8.2, 4.2 and 6.1 [15]. lower number of smokers in our study. In the Korean study,
A worldwide study of OLGA gastritis staging in young 41.8 % of the participants were smokers whereas only 11.5
adults (18-40 years)which included a centre from North % were smokers in our study [13]. Globally smoking is
India (Delhi) [8] and East Asian countries showed acknowledged to be a risk factor for gastric cancer.
prevalence of high risk OLGA stages of 6 % in South Korea However tobacco chewing and cigarette smoking did not
in keeping with the high prevalence of gastric carcinoma emerge as high risk factors for gastric cancer in a study

Indian Journal of Pathology: Research and Practice / Volume 7 Number 6 / June 2018
780 Thara Keloth, Marie Moses Ambroise, Thomas Alexander et al. / A Study of High Risk Operational Link for Gastritis
Assessment (OLGA) Stages in South Indian Subjects

from Chennai region [19]. An earlier study from Mumbai Conclusion


also showed that bidi or cigarette smoking were not high
risk factors for gastric cancer [20].
In conclusion, the prevalence rate of high risk OLGA
H.pylori is high in prevalence in South India (57.7%) , stages was 6.25% in subjects with dyspepsia among this
as has been reported in various studies [21-25]. H.pylori South Indian population. The biopsy sampling protocol
prevalence in this study (62%)correlates with the must routinely include incisura angularis for accurate
reported prevalence in this region. The H.pylori load on OLGA staging .
the gastric surface showed an increasing trend from
OLGA stages 0 to III, and a decreasing trend towards Strengths and Limitations of the Study
stage IV (Figure 2). This is probably explained by less
The strengths of this study include its prospective nature,
availability of mucus-bicarbonate for this acid sensitive
adequate sample size and a rigorous biopsy sampling
organism in severe gastric atrophy.
protocol. Non-consecutive selection of cases is a
The degree of IM generally reflects the severity of limitation.
atrophic gastritis. The significant association of severe
IM with high risk OLGA in this study probably correlates
with severe IM being a premalignant lesion. References
A previous study showed that the sensitivity and 1. Leading sites of cancer. In: Three Year Report of the PBCRs
specificity of endoscopy for the histological diagnosis of (2012-2014). Three year Report of Population Based Cancer
atrophy was found to be 61.5 and 57.7%, respectively, Registries 2012-2014. [Last accessed on 2018 March 30].
in the antrum, and 46.8 and 76.4%, respectively, in the Available from: http://www.pbcrindia.org.
body of the stomach [26]. Mucosal inflammation 2. Comparison of Cancer Incidence and Patterns of all
reduces the sensitivity of endoscopy ,especially in Population Based Cancer Registry.In: Three Year Report of
individuals below 50 years of age [26]. The absence of the PBCRs (2012-2014). [Last accessed on 2018 March 30].
rugae and the presence of visible vessels in the gastric Available from: http://www.pbcrindia.org.
mucosa can predict severe atrophy but with a relatively 3. Correa P. The biological model of gastric carcinogenesis.
low sensitivity [27,28]. A high index of suspicion of IARC SciPubl 2004;(157):301–10.
gastric atrophy is important in the young age group, 4. Ghoshal UC, Chaturvedi R, Correa P. The enigma of
and histological confirmation of the diagnosis is Helicobacter pylori infection and gastric cancer. Indian J
necessary [26]. Narrow-band imaging and magnifying Gastroenterol 2011;29(3):95–100.
endoscopy corresponds better with histology scores 5. Rugge M, Genta RM; OLGA Group.Staging gastritis: an
[29]. Endoscopic atrophy was not evident in all cases international proposal. Gastroenterology 2005;129(5):
of high-grade OLGA in our study. However we did not 1806–7.
attempt a detailed analysis since endoscopic-histology 6. Rugge M, Correa P, Di Mario F, El-Omar E, Fiocca R, Genta
correlation was not our objective. RM, et al. OLGA staging for gastritis: A tutorial. Dig Liver Dis
2008;40(8):650–8.
Biopsy protocols are also important to categorise
OLGA because of topographical differences in the 7. Rugge M, Boni MDE, Lli GP, Bona MDE, Giacomelli L, Fassan
atrophy and intestinal metaplasia. The management M. Gastritis OLGA-staging and gastric cancer risk/ : a twelve-
year clinico-pathological follow-up study. Aliment
of precancerous conditions and lesions in the stomach
Pharmacol Ther 2010;31:1104–11.
(MAPS) guideline recommends at least four
nontargeted biopsies of two topographic sites (at the 8. Rugge M, Kim JG, Mahachai V, Miehlke S, Pennelli G, Russo
VM, et al. OLGA gastritis staging in young adults and
lesser and greater curvature, from both the antrum and
country-specific gastric cancer risk. Int J Surg Pathol
the corpus), in contrast to the modified Sydney 2008;16(2):150–4.
Protocol which mandates a biopsy from the incisura
9. Rugge M, Meggio A, Pennelli G, Piscioli F, Giacomelli L, De
angularis also [28]. It is important to include the incisura
Pretis G ,et al. Gastritis staging in clinical practice: the OLGA
angularis in the biopsy sampling protocol because staging system. Gut 2007;56(5):631–6.
atrophy is more prevalent in this location as compared
10. Gao L, Weck MN, Stegmaier C, Rothenbacher D, Brenner H.
to the corpus and antrum. A recent study by Isajevs et
Alcohol consumption and chronic atrophic gastritis:
al showed that the proportions of patients in the OLGA Population-based study among 9,444 older adults from
high-risk groups was underestimated by 35% when the Germany. Int J Cancer 2009;125(12):2918–22.
biopsy protocol did not incorporate an incisura
11. Dixon MF, Genta RM, Yardley JH, Correa P. Classification
angularis site [30]. Our study also reveals that 50% of and Grading of Gastritis. The Updated Sydney System.
the high-risk OLGA cases would be underestimated if International workshop on the histopathology of gastritis,
the incisura angularis is not included. Houston 1994. Am J Surg Pathol 1996;20(10):1161–81.

Indian Journal of Pathology: Research and Practice / Volume 7 Number 6 / June 2018
Thara Keloth, Marie Moses Ambroise, Thomas Alexander et al. / A Study of High Risk Operational Link for Gastritis 781
Assessment (OLGA) Stages in South Indian Subjects

12. Zhou Y, Li HY, Zhang JJ, Chen XY, Ge ZZ, Li XB. Operative 22. Thirumurthi S, Graham DY. Helicobacter pylori infection in
link on gastritis assessment stage is an appropriate predictor India from a western perspective. Indian J Med Res
of early gastric cancer. World J Gastroenterol. 2016;22 2012;136(4):549–62.
(13):3670–8. 23. Shah H, Shah P, Jarag M, Shah R, Shah P, Naik K. Prevalence
13. Nam JH, Choi IJ, Kook MC, Lee JY, Cho SJ, Nam SY, et al. of Helicobacter pylori infection in gastric and duodenal
OLGA and OLGIM stage distribution according to age and lesions as diagnosed by endoscopic biopsy. Int J Med Sci
Helicobacter pylori status in the Korean population. Public Health 2016;5(1):93–6.
Helicobacter 2014;19(2):81-9. 24. Hemalata M, Sahadev R, Nanda N, Preethan KN, Suguna B
14. Ben Slama S, Ben Ghachem D, Dhaoui A, Jomni MT, Dougui V. Prevalence of Helicobacter pylori infection and
MH, Bellil K. Helicobacter pylori gastritis: assessment of histomorphologic spectrum in endoscopic biopsies.Int J
OLGA and OLGIM staging systems. Pan Afr Med J 2016 Biomed Res 2013;4(11):608–14.
(4);23:28. 25. Adlekha S, Chadha T, Krishnan P, Sumangala B. Prevalence
15. Globocan 2012: Esimated cancer incidence, mortality and of Helicobacter Pylori Infection Among Patients Undergoing
Prevalence worldwide in 2012. International agency for Upper Gastrointestinal Endoscopy in a Medical College
research on cancer.Downloaded from http://globocan.iarc. Hospital in Kerala, India. Ann Med Health Sci Res 2014;3(4):
fr/Pages/summary_table_site_sel.aspx. 559–63.
16. Asthana S, Labani P, Labani S. A review on cancer incidence 26. Eshmuratov A, Nah JC, Kim N, Lee HS, Lee HE, Lee BH, et al.
in India from 25 population-based cancer registries.J Dr The correlation of endoscopic and histological diagnosis
NTR Univ Heal Sci 2015;4(3):150. of gastric atrophy. Dig Dis Sci 2010;55(5):1364-75.
17. Rugge M, Fassan M, Pizzi M, Farinati F, Sturniolo GC, Plebani 27. RedeenS, Petersson F, JonssonKA ,Borch K. Relationship of
M, et al. Operative link for gastritis assessment vs operative gastroscopic features to histological findings in gastritis
link on intestinal metaplasia assessment. World J and Helicobacter pylori infection in a general population
Gastroenterol. 2011;17(41):4596–601. sample. Endoscopy 2003;35(11):946–50.
18. Capelle LG, de Vries AC, Haringsma J, Ter Borg F, de Vries 28. Dinis-Ribeiro M, Areia M, de Vries AC, Marcos-Pinto R,
RA, Bruno MJ, et al. The staging of gastritis with the OLGA Monteiro-Soares M, O’Connor A, et al. Management of
system by using intestinal metaplasia as an accurate precancerous conditions and lesions in the stomach
alternative for atrophic gastritis. Gastrointest Endosc (MAPS): guideline from the European Society of
2010;71(7):1150–8. Gastrointestinal Endoscopy (ESGE), European Helicobacter
19. Sumathi B, Ramalingam S, Navaneethan U, Jayanthi V. Risk Study Group (EHSG), European Society of Pathology (ESP),
factors for gastric cancer in South India. Singapore Med J and the Sociedade Portuguesa de EndoscopiaDigestiva
2009;50(2):147-51. (SPED). Endoscopy 2012;44(1):74–94.

20. Rao DN, Ganesh B, Dinshaw KA, Mohandas KM.A case- 29. Saka A, Yagi K, Nimura S. OLGA- and OLGIM-based staging
control study of stomach cancer in Mumbai, India.Int J of gastritis using narrow-band imaging magnifying
Cancer 2002 10;99(5):727-31. endoscopy.Dig Endosc 2015;27(7):734-41.

21. Misra V, Pandey R, Misra SP, Dwivedi M. Helicobacter pylori 30. Isajevs S , Liepniece-Karele I, Janciauskas D, Moisejevs G,
and gastric cancer/ : Indian enigma. World J Gastroenterol Funka K, Kikuste I, et al. The effect of incisuraangularis
2014;20(6):1503–9. biopsy sampling on theassessment of gastritis stage.Eur J
Gastroenterol Hepatol 2014;26(5):510-3.

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IJPRP Volume 7 Number 6, June 2018


DOI: http://dx.doi.org/10.21088/ijprp.2278.148X.7618.13

Original Research Article

Histopathological Spectrum of Breast Lumps: A One Year Retrospective


Study

Hawaldar Ranjana1, Patidar Ekta2, Sodani Sadhna3

1
Consultant Pathologist 2Pathologist, Sampurna Sodani Diagnostic Clinic, Indore, Madhya Pradesh 452001, India. 3Associate Professor,
Department of Microbiology, MGM Medical college, Indore, Madhya Pradesh 452001, India.

Abstract

Introduction: In India, breast carcinoma is the second most common cause of death in
women next only to cervical cancer and the incidence is as high as 20 per 1,00,000 women.
The benign lesions are most common in the first few decades of life while incidence of
malignant lesions peaks after menopause. The world wide incidence of breast cancer is
Corresponding Author:
estimated to be 1.38 million cases which is approximately 10.9% of the total malignancies
Ranjana Hawaldar, detected every year.
Consultant Pathologist, Materials and Methods: The present retrospective study was undertaken to know the
Sampurna Sodani diagnostic
histopathological spectrum of the breast lumps received in the histopathology department
clinic, Indore, Madhya Pradesh
452001, India. of Sampurna Sodani Diagnostic Clinic, a stand alone diagnostic centre of Central Madhya
E-mail: Pradesh. A total of 91 breast specimens, including biopsy, lumpectomy and mastectomy
drranjana@sampurnadiagnostics.com specimens were included in the study.
Results: Out of these 91 cases, 80 cases (87.9%) were benign in nature and 11 cases
(Received on 28.05.2018,
(12.08%) were of malignant nature. Fibroadenoma was the most common benign neoplasm
Accepted on 09.06.2018)
constituting 79.12% of all cases followed by chronic mastitis (4.39%), fibrocystic disease
(2.1%) and benign phylloides tumor and lactating adenoma (1.09%) each. Of the malignant
neoplasms, ductal carcinoma was the most common (8.79%) of all lesions followed by
papillary carcinoma (2.1%) and one case of medullary carcinoma with an incidence of
1.09% of all malignancies.
Conclusion: Palpable and non - palpable lumps in breasts are common in females and
require histopathological diagnosis for proper and timely management. Benign diseases of
breasts are far more common than malignancies and fibroadenoma is the most common
benign neoplasm.
Keywords: Breast Lump; Fibroadenoma; Ductal Carcinoma; Benign; Malignant.

Introduction breast lumps may be of developmental origin or due to


inflammatory causes or may be due to proliferation of
the stromal or epithelial components and may be of
The human breast is composed of special epithelium malignant nature too [2]. While benign lumps constitute
and stromal tissue. Lumps are common finding in breast majority of the lesions found in the breast, some of the
tissue and comprise of both benign and malignant benign lesions are precursor to malignant change [3].
lesions. It is one of the commonest cause of cancer According to certain reports, the incidence of breast
related morbidity and mortality in females [1]. Benign cancer in young patients is about 25% in Asia as

© Red Flower Publication Pvt. Ltd. Indian Journal of Pathology: Research and Practice / Volume 7 Number 6 / June 2018
Hawaldar Ranjana, Patidar Ekta, Sodani Sadhna / Histopathological Spectrum of Breast Lumps: 783
A One Year Retrospective Study

compared Western world.4 Histopathological examination A total of 91 cases of breast lumps in females were
of these breast lesions plays a pivotal role in diagnosis, included in the study. The females were divided into 10-
treatment and prognosis of patients with these disorders [5]. 20, 21-30, 31-40, 41-50, 51-60, 61-70 years of age group.
In India, breast carcinoma is the second most They were further divided into benign and malignant
common cause of death in women next only to cervical categories and also on the basis of site of the lesion.
cancer and the incidence is as high as 20 per 1,00,000
women [6]. The benign lesions are most common in the Results
first few decades of life while incidence of malignant
lesions peaks after menopause [8]. The world wide A total of 91 cases of breast lesions were included in the
incidence of breast cancer is estimated to be 1.38 million study. Out of these 91 cases, 80 cases (87.9%) were benign
cases which is approximately 10.9% of the total in nature and 11 cases (12.08%) were of malignant nature.
malignancies detected every year [9]. Fibroadenoma was the most common benign neoplasm
Now-a-days, due to increasing awareness among the constituting 79.12% of all cases followed by chronic
general population, along with campaigns carried out mastitis (4.39%), fibrocystic disease (2.1%) and benign
by healthcare professionals, the lumps are being phylloides tumor and lactating adenoma (1.09%) each.
detected at an early stage by radiological and Of the malignant neoplasms, ductal carcinoma was the
cytological methods and treatment, either surgical or most common (8.79%) of all lesions followed by papillary
palliative, is initiated at an early stage, thereby carcinoma (2.1%) and one case of medullary carcinoma
increasing the chances of a positive outcome. with an incidence of 1.09% of all malignancies.

The present retrospective study was undertaken to Of the benign neoplasms, fibroadenoma was the most
know the histopathological spectrum of the breast common (90%), followed by chronic mastitis(5%),
lumps received in the histopathology department of fibrocystic disease (2.5%) and benign phylloides tumour
Sampurna Sodani Diagnostic Clinic, a stand alone and lactating adenoma (1.25%) each.
diagnostic centre of Central Madhya Pradesh. In the malignant category, ductal carcinoma was
found in 72.72% cases, papillary carcinoma in 18.18%
and medullary carcinoma in 9.09% cases (Table 1).
Materials and Methods
In 10-20 years age group , fibroadenoma was seen in
This one year retrospective study was undertaken in 21 cases out of 22 cases (95.45%) and 1 case of lactating
the Department of Histopathology of Sampurna Sodani adenoma (4.54%).
Diagnostic for a period of one year from January 2017 to In 21-30 years age group too, fibroadenoma was most
December 2017 to study the frequency and common (94.8%) with one case of mastitis (2.56%) and
histopathological spectrum of breast lesions. A total of one case of papillary carcinoma (2.56%).
91 breast specimens, including biopsy, lumpectomy and
As age increased the incidence of malignant lesions
mastectomy specimens were included in the study.
increased with 3 cases (50%) of ductal carcinoma in 41-
The tissue was fixed in 10% Formalin and after proper 50 years of age, 40% in 51-60 years of age and 66.66% in
fixation, paraffin blocks were prepared from the tissue. 61-70 years of age (Table 2).
5 micron sections were made from these blocks and
According to site of involvement right breast was
stained with H & E stain. The relevant clinical and surgical
most commonly involved in 51 cases (56.04%), left breast
information was retrieved from the records.

Table 1: Showing incidence of benign and malignant lumps

Sr. No. Name of the Lesion Total Cases Overall Percentage


In Numbers In Percentage

1 Fibroadenoma 72 90% 79.12%


2 Benign Phylloide Tumor 1 1.25% 1.09%
3 Fibrocystic Disease 2 2.5% 2.19%
4 Chronic Mastitis 4 5% 4.39%
5 Lactating Adenoma 1 1.25% 1.09%
6 Ductal Carcinoma 8 72.72% 8.79%
7 Papillary Carcinoma 2 18.18% 2.19%
8 Medullary Carcinoma 1 9.09% 1.09%

Indian Journal of Pathology: Research and Practice / Volume 7 Number 6 / June 2018
784 Hawaldar Ranjana, Patidar Ekta, Sodani Sadhna / Histopathological Spectrum of Breast Lumps:
A One Year Retrospective Study

Table 2: Showing agewise incidence of benign and malignant lumps

Sr. Age Benign Malignant Total


No (yrs) Total Percentage Total Percentage Cases
Cases Cases

1 10 - 20 Fibroadenoma 21 95.45% 0 0 22
Lactating 1 4.54%
Adenoma
2 21 - 30 Fibroadenoma 37 94.8% Papillary Carcinoma 1 2.56% 39
Chronic Mastitis 1 2.56%
3 31 - 40 Fibroadenoma 10 62.5% Ductal Carcinoma 1 6.25% 16
Fibrocystic 2 12.5%
Chronic Mastitis 3 18.75%
4 41 - 50 Fibroadenoma 3 50% Ductal Carcinoma 3 50% 06

5 51 - 60 Fibroadenoma 1 20% Ductal Carcinoma 2 40% 05


Medullary 1 20%
Carcinoma
Papillary Carcinoma 1 20%

6 61 - 70 Phylloides Tumor 1 33.3% Ductal Carcinoma 2 66.66% 03


80 87.91% 11 12.08% 91

Table 3: Showing incidence of breast lumps according to site of involvement

Sr. No. Age (yrs) Left Right Bilateral Total Cases

1 10 - 20 9 13 0 22
2 21 - 30 14 23 2 39
3 31 - 40 7 9 0 16
4 41 - 50 3 3 0 6
5 51 - 60 2 3 0 5
6 61 - 70 3 0 0 3
38 (41.75%) 51(56.04%) 2 (2.19%) 91

in 38 (41.75%) cases and both breasts were involved in 2 also reported 74.75% benign lesions and 25.25% malignancies
(2.19%) cases (Table 3). [14]. Commonest malignancy was fibroadenoma and
Fibroadenoma was most frequently found in 2nd commonest malignancy was infiltrating duct cancer in
decade followed by 1st decade. Malignant tumors were their study which correlates with ourstudy where fibroadenoma
most common beyond 4th decade of life. was commonest benign neoplasm (79.12%).
U.R. Singh et al. in their study had 80-70% benign
lesions and 19.3% malignant lesions [15]. Rasheed et al.,
Discussion Malik et al. and Kulkarni s et al. in their studies had similar
observations with benign breast lesions outnumbering
Breast lesions are a common cause of morbidity and malignant lesions [16,17,18].
mortality in females and also have cosmetic
implications. The most common presenting symptoms Similar observations were made by Abu Khalid et al in
of breast lesions are pain, lumpy feeling, nipple discharge their study [19]. In their study, the maximum cases of
and palpable lumps. Mastalgia is the most common breast lump were in 3rd and 4th decades while in our study
presenting symptom and can be treated medically [10]. we found maximum cases in 21-30 year of age group.
Benign breast lumps are most common as compared to The peak incidence of malignancy was observed 4th
malignancies and inflammations [11]. Several factors like decades of life. In our study, the youngest case of
nullipathy, age at first birth, menopausal age etc play an malignancy was observed in 21-30 years of age which
important role in the aetiogensis of these was diagnosed as papillary carcinoma.
neoplasms[12,13].
Benign neoplasms are more common than the Conclusion
malignant neoplasms all over the world. In our study
also, benign conditions were more common (87.9%) as Palpable and non - palpable lumps in breasts are
compared to cancer (12.08%). Gogoi et al in their study common in females and require histopathological

Indian Journal of Pathology: Research and Practice / Volume 7 Number 6 / June 2018
Hawaldar Ranjana, Patidar Ekta, Sodani Sadhna / Histopathological Spectrum of Breast Lumps: 785
A One Year Retrospective Study

diagnosis for proper and timely management. Benign 9. Ferlay J, Shin HR, Bray F, Forman D, Mathers C, Parkin DM.
diseases of breasts are far more common than Estimates of world wide burden of cancer in 2008 Int J
malignancies and fibroadenoma is the most common Cancer. 2010 Dec 15;127(12):2893-917.
benign neoplasm. Increasing awareness and screening 10. Hafiz Muhammad Aslam, Shafaq Saleem, Hiba Arshad
programmes have been effective in detecting these Shaikh, Nazish Shahid, Anum Mughal, and Ribak
lumps at an early stage thereby enhancing the quality UmaClinico- pathological profile of patients with breast
of life. As more and more women are undergoing diseases Diagn Pathol. 2013;8:77.
mammographic screening, the diagnosis of benign and 11. Mansoo I Profile of female breast lesions in Saudi Arabia.
malignant breast lesions is increasing . Histopathology J Pak Med Assoc. 2001 Jul;51(7):243-7.
is an important diagnostic tool and upon correlating it 12. Hislop TG, Elwood JM Risk factors for benign breast
with clinical and radiological findings as well as with disease: A 30-year cohort study. Can Med Assoc J. 1981 Feb
FNAC findings, occult malignancies are being detected 1;124(3):283-91.
at an earlier stage. 13. Parazzini F, La Vecchia C, Franceschi S, Decarli A, Gallus G,
Regallo M, Liberati A, Tognoni GRisk factors for pathologically
confirmed benign breast disease. Am J Epidemiol. 1984
Conflict of Interest Jul;120(1):115-22.
None 14. Gogoi G, Diganta B. Histopathological spectrum of breast
lesions- a hospital based study. IJHRMLP 2016 Jan;2(1):73-78.
15. Singh U.R., Thakur A.N, Shah S.P. Mishra. Histomorphological
References Spectrum Of Breast Diseases. J NepMed Assoc 2000;39:
338-341.
1. Anyikam A, Nzegwu MA, Ozumba BC, Okoye I, Olusina DB.
Benign breast lesions in Eastern Nigeria.Saudi Med J 16. Abdul A. Rasheed, Shaveta Sharma, Mohsin-ul-Rasool,
2008;29:241-44. Shazia Bashir, Ather Hafiz, N. Bashir A. Three Year Study of
Breast Lesions in Women aged 15-70 years in a Tertiary Care
2. Tavassoli FA, Devilee P. Pathology and Genetics of Tumours
Hospital Scholars Journal of Applied Medical Sciences
of the Breast and Female Genital Organs.France: IARC 2003.
2014;2(1B):166-168.
3. Santen RJ, Mansel R. Benign breast disorders. N Engl J Med
17. Malik R, Bharadwaj VK. Breast lesions in young females—a
2005;353:275-85.
20-year study for significance of early recognition. Indian J
4. Chaudhuri M, Sen S, Sengupta J. Breast lumps: a study of Pathol Microbiol. 2003 Oct;46(4):559-62.
10 years. J Indian Med Assoc 1995;93:455-57.
18. Kulkarni Sangeeta, Vora Ila MGhorpade Kanchanmala G
5. Abdolrasoul Talei, Majid Akrami, Maral Mokhtari and Srivastava Shanu. Histopathological spectrum of breast
Sedigheh TahmasebiSurgical and Clinical Pathology of lesions with reference touncommon casesJ Obstet
Breast Diseases Chapter 3 ,2015. Gynecol India. 2009;59(5):444-52.
6. Desai M. Role of obstetrician and gynecologist in management 19. Abu Khalid Muhammad Maruf Raza, Zaman Ahmed,
of breast lump. J Obstet Gynaecol India 2003;53:389-91. Muhammad Rafiqul Islam Study of Breast Lump - A
7.   Sharkey FE, Craig Allred DC, Valente PT. Breast. In: Histopathological Audit of Five Years Specimen in a Medical
Damjanov I, Linder J, (eds.) Anderson’s Pathology. 10th ed. College of Bangladesh Arch Microbiol Immunology 2017;1
St. Louis: Mosby, 1996;2354-85. (1):27-32.

8. Merih Guray , Aysegul A. SahinBenign Breast Diseases:


Classification, Diagnosis, and Management; The Oncologist;
2006;11:435-49.

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Indian Journal of Pathology: Research and Practice

IJPRP Volume 7 Number 6, June 2018


DOI: http://dx.doi.org/10.21088/ijprp.2278.148X.7618.14

Original Research Article

Is Cervical Cancer Incidence Decreasing in the Urban Population of India


with Developing Healthcare, Socio Demographic Progress and Awareness
Programmes?

Sujata Mallick1, Mahasweta Mallik2

1
Associate Professor, Department of Pathology, KPC Medical College, Jadavpur, Kolkata, West Bengal 700032, India. 2Associate Professor,
Department of Pathology, Government Medical College Ambikapur, Surguja, Chhattisgarh 497001, India.

Abstract

Context: Last few decades saw rapid decline of cervical cancer worldwide. However,
75% of the new cases are reported to occur in developing countries due lack of awareness
Corresponding Author: among the female population.
Aims: This study was conducted to determine the prevalence of cervical carcinoma in
Mahasweta Mallik,
the urban female population and to evaluate the clinical findings, assess the socio-
Associate Professor,
Department of Pathology,
demographic and risk factors associated with unhealthy cervix in the study group.
Government Medical College Settings and Design: This was a descriptive study carried out in KPC medical college
Ambikapur, Surguja, Kolkata from December 2014 to December 2017
Chhattisgarh 497001, India.
E-mail: Methods and Material: Pap smear screening was done on 328 patients presenting with
mahasweta3112@yahoo.com unhealthy cervix, out of which biopsy was obtained from 172 patients. Risk factors, clinical
findings and knowledge about awareness programs were taken into consideration. The
(Received on 13.04.2018, cytological results were correlated with the clinical findings and compared with the biopsy
Accepted on 05.05.2018) results.
Results: A total of 19.2% patients presented with epithelial cell abnormality in unhealthy
cervical smears. Early age at marriage, multiparity , use of contraceptives and age at first
sexual intercourse were 76.4%, 32.2%, 28.3% and 69.9%. Awareness about cause, symptoms,
pap test was 5.6%, 6.7% and 6.3%. Risk factors and clinical findings like unhealthy cervix with
discharge, erosion and congestion showed significant association (p=0.05%) with cancer.
Pap smear of unhealthy cervix showed 73.4% sensitivity and 84.3% accuracy with biopsy.
Conclusions: Thus in developing countries implementation of more rigorous screening
programs and spread of awareness about unhealthy cervix should help bring down the rate
of cervical cancer.
Keywords: Pap Smear; Risk Factors Cervix; Cervical Smears; Papanicolaou Test; Uterine
Cervical Neoplasms.

Introduction women above 15years of age is 365.71 million who are


at a risk of developing cervical cancer. Approximately
The worldwide rate of cancer cervix has come down. 132,000 new cases are diagnosed and 74,000 deaths
However, it is ranked as the most frequent cause of occur annually in India, accounting to one third of the
cancer among women in India. The population of Indian global cervical cancer deaths [1]. Mortality due to

© Red Flower Publication Pvt. Ltd. Indian Journal of Pathology: Research and Practice / Volume 7 Number 6 / June 2018
Sujata Mallick & Mahasweta Mallik / Is Cervical Cancer Incidence Decreasing in the Urban Population of India with 787
Developing Healthcare, Socio Demographic Progress and Awareness Programmes?

cervical cancer can be reduced with a sensitive and a The results of cytology were analyzed according to
very simple test i.e. pap test. In India, utilisation of this the Bethesda system of classification 2014 and results
test is only 2.6% to 6.9% as it depends upon the were correlated clinically and with biopsy. Patients with
knowledge about cervical cancer risk factors, healthy cervix and known cases of cervical cancer or
symptoms, its screening methods [2]. This extensive whose previous pap smear report had shown dysplastic
study on all parameters associated with unhealthy changes were excluded from the study. Inadequate
cervix was carried out to highlight the gaping need for smears and normal smears were excluded from the study.
educating the community, even the urban population
about the socio-demographic, risk factors and
screening methods available for carcinoma cervix. Results

Cervical cytology interpretation according to


Subjects and Methods Bethesda classification revealed 80.7% of cases were
negative for intraepithelial lesion or malignant cell
This was a descriptive study carried out in the (NILM). 19.2% of cases showed epithelial cell abnormality.
Department of Pathology, KPC Medical College during Atypical Squamous cells of Undetermined Significance
the period from December 2014 to December 2017. No (or ASCUS) was the most common epithelial cell
ethical issues were there as the results were observed abnormality(7% of cases) followed by Low Grade
from routine history and cytological and histopathological Intraepithelial Lesion (or LSIL)(4.8% of cases), High Grade
examination. After taking history and clinical Squamous Intraepithelial Lesion (or HSIL) (4.5%),
examination, Pap smear was obtained from women Squamous Cell Carcinoma (1.2%), Atypical Glandular
attending the outpatient department of Gynecology Cells of Undetermined Significance (or AGUS) (0.9%), and
with unhealthy cervix. Patients with unhealthy looking Adenocarcinoma (0.6%).
cervix with discharge or bleeding or whose naked eye The maximum numbers of patients were in the age
observation of cervix showed congestion, erosion and group 61-70 years comprising 23.4% of the total cases.
polyp were included in the unhealthy category and were
duly recorded. The total number of cases observed and Under the NILM category, 52.3% of cases showed non-
recorded was 328 over a period of three years. Biopsy specific inflammation, 5.3% of cases showed shift in
was taken in cases with Pap smear showing positive for vaginal flora. Among the organisms seen in smear, most
dysplasia or cancer. History of the associated risk factors common was Candida in 22.4% smears, Trichomonas
were recorded like parity (Nulliparous, para 1-2, para 3-4, vaginalis in 9.8% smears, bacterial vaginosis in 7.2%
para >5), age at marriage (<20 years, 20-25 years, >25 smears and 1.4% showed granulomatous lesion. Mixed
years), age at first intercourse, use of contraceptives like infection, Candida with bacterial vaginosis or TVwere
condoms or OCP, socioeconomic status (Modified seen in 0.9% of cases each and HPV induced changes
Prasad’s classification, per capita income-Low income were seen in 0.7% of cases.
group-<Rs.1529, Middle income group-Rs. 1530- Rs. 5109, Forty-nine percent women were not aware of Pap
High income group- >Rs. 5110.). The women were smear screening programs, 6.3% were aware of such
enquired whether they were aware about cause, programs but had not availed them and only 4.5% had
symptoms about cervical cancer, had undergone Pap undergone Pap smear screening previously. 5.6% was
smear screening before or were aware of such screening aware about the cause of cervical cancer, 6.7% were
programs. aware of the symptoms of cervical cancer like discharge,

Table 1: Distribution of Pap smear findings according to different age groups

Age NILM ASCUS AGUS LSIL HSIL SCC Adeno

21-30 49 (92.4%) 3 (5.6%) 1 (1.8%)


31-40 54 (88.5%) 2 (3.2%) 1 (1.6%) 3 (4.9%) 1 (1.6%)
41-50 28 (66.6%) 2 (4.7%) 1 (2.3%) 4 (9.5%) 4 (9.5%) 2(4.7%) 1 (2.3%)
51-60 42 (70%) 7 (11.6%) 2 (3.3%) 6(10%) 3 (5%)
61-70 67(84.8%) 5 (6.3%) 1 (1.2%) 2 (2.5%) 2 (2.5%) 1 (1.2%) 1 (1.2%)
>71 25 (73.5%) 4 (11.7%) 3 (8.8%) 2 (5.8%)

NILM-Negative for Intraepithelial Lesion or malignant cells, ASCUS-Atypical Squamous cells of Undetermined Significance,
AGUS-Atypical Glandular cells of Undetermined Significance,
LSIL-Low Grade Squamous Intraepithelial Lesion, HSIL-High Grade Squamous Intraepithelial Lesion,
SCC-Squamous Cell Carcinoma, Adeno-Adenocarcinoma

Indian Journal of Pathology: Research and Practice / Volume 7 Number 6 / June 2018
788 Sujata Mallick & Mahasweta Mallik / Is Cervical Cancer Incidence Decreasing in the Urban Population of India with
Developing Healthcare, Socio Demographic Progress and Awareness Programmes?

bleeding. 49.6% of women gave history of marrying at up to few classes and 21.7% had higher education. 88.5%
age below 20 years and 76.4% of them showed abnormal of women with higher education were aware of pap
cells in Pap smear. smear test and 21.5% with school education knew about
these tests through camps, master health checkups. No
Women with 3-4 children formed the majority of cases
one among the illiterates was aware of such tests or had
(57%), among whom epithelial cell abnormality was
undergone any routine pap test before.
present in 82.2%. 61.4% were less than 18years at first
sexual intercourse, 38.6% were more than 18years with The most common clinical finding was discharge per
83.3% of positive for abnormal cells from age less than vagina constituting 43.2% of cases. Other findings were
18 years. 28.3% were using contraceptives with only bleeding PV 29.5%, congestion 16.7%, cervical polyp 6.4%
8.3% using condoms and 91.7% using OCP and erosion 3.9%. Epithelial cell abnormality was found
maximum in patients presenting with congestion (29%),
(oral contraceptive pills). 56.4% f our study group were
discharge (17.6%) followed by bleeding (12.3%).
smokers. Awareness about cause, symptoms, pap test
Significant association was found in women having
was 5.6%, 6.7% and 6.3%. 36.2% were in the low income
discharge (p-value=0.003), congestion (p-value=0.001)
group <1529, 58.7% were in the middle income group with the risk of developing carcinoma cervix.
1530-5109 and 5.1% were in the high income group >5110.
62.5% from the low income group showed positive for Out of 328 cases, a total of 172 patients underwent
epithelial cell abnormality. biopsy and 71.5% of cases among them were found to
have chronic cervicitis. Among dysplasia, CIN I was found
95.8% of the women were married. Others were in 9.8% cases followed by CINIII in 8.7% of cases and CINII
widowed, separated or left by husband, divorced. 23.6% in 4.6% of cases. 5.2% of cases showed invasive
of the women were illiterate, 54.7% had done schooling carcinoma in biopsy (3.4% SCC, 1.7% Adenocarcinoma).
Table 2: Proportion of Pap smear findings with Clinical Findings
Clinical Findings NILM ASCUS AGUS LSIL HSIL SCC Adeno

Discharge 117(82.3%) 8 (5%) 2 (1%) 7 (4%) 5(3.5%) 2(2%) 1 (0.7%)


Bleeding 85 (87.6%) 6 (6%) 2 (2%) 3 (3%) 1(1%)

Erosion 9 (69.2%) 1 (7.6%) 1 (7.6%) 2 (15.3%)


Congestion 39 (70.9%) 5 (9%) 1 (1.8%) 4 (7.2%) 4 (7.2%) 1(1.8%) 1(1.8%)
Polyp 15 (71.4%) 3(14.2%) 2 (9.5%) 1(4.7%)
NILM-Negative for Intraepithelial Lesion or malignant cells,
ASCUS-Atypical Squamous cells of Undetermined Significance, AGUS-Atypical Glandular cells of Undetermined Significance,
LSIL-Low Grade Squamous Intraepithelial Lesion, HSIL-High Grade Squamous Intraepithelial Lesion,
SCC-Squamous Cell Carcinoma, Adeno-Adenocarcinoma
Table 3: Proportion of Biopsy Positive Cases with Individual Pap smear lesions
Pap smear Chronic cervicitis CINI CINII CINIII SCC Adeno+AIS

Inflammation 109 (100%) - - - - -


ASCUS 12 (52.1%) 8 (34.7%) 2 (8%) 1(4%) - -
AGUS 2(66%) - - - - 1(33%)
LSIL - 9(56.2%) 25 (4%) 3 (18.7%) - -
HSIL - - - 2 (13.3%) 11 (73.3%) 2(13.3%)
SCC - - - - 4(100%) -
Adeno - - - - - 2(100%)
ASCUS-Atypical Squamous cells of Undetermined Significance, AGUS-Atypical Glandular cells of Undetermined Significance,
LSIL-Low Grade Squamous Intraepithelial Lesion, HSIL-High Grade Squamous Intraepithelial Lesion, SCC-Squamous
Cell Carcinoma, Adeno-Adenocarcinoma, CIN-Cervical Intraepithelial Neoplasia,AIS-Adenocarcinoma in Situ
Table 4: Comparision of our study with other significant studies
Pap Findings NILM ASCUS AGUS LSIL HSIL SCC Adeno

Pradhan N et al52007 83% 3% 7% 1% 0% 0%


Patel et al26 2011 59.68% 4.1% 0.5% 0.1% 0.1% 0.7% 0%
Nikumbh et al10 2011 94.2% 0.96% 0.4% 0.96% 1.98% 0.4% 0%
Bal et al 13 2012 74.3% 0.3% 0% 2.7% 0.3% 1% 0.3%
Jha et al 272012 38.29% 3.92% 0.75% 2.7% 1.47% 0% 0%
NILM-Negative for Intraepithelial Lesion or malignant cells,
ASCUS-Atypical Squamous cells of Undetermined Significance, AGUS-Atypical Glandular cells of Undetermined Significance,
LSIL-Low Grade Squamous Intraepithelial Lesion, HSIL-High Grade Squamous Intraepithelial Lesion, SCC-Squamous
Cell Carcinoma, Adeno-Adenocarcinoma , CIN-Cervical Intraepithelial Neoplasia,

Indian Journal of Pathology: Research and Practice / Volume 7 Number 6 / June 2018
Sujata Mallick & Mahasweta Mallik / Is Cervical Cancer Incidence Decreasing in the Urban Population of India with 789
Developing Healthcare, Socio Demographic Progress and Awareness Programmes?

Validity tests of Pap smear showed 73.4% sensitivity, Our study found 61.4% to be less than 18years age at
high specificity of 88.6%, high positive predictive value first sexual intercourse while Raychaudhary S et al. [9]
of 72% and a negative predictive value of 89.3%. found 79.2% to be less than 18 years at first intercourse.
Accuracy of the test was 84.3%. Wahi et al. [13] surveyed 26,110 women in Agra district in
Statistical analysis used: SPSS version 16 was used for India and found the importance of early marriage and
data analysis. P<0.05 was accepted as significant. A multiple pregnancies as risk factors for cervical cancers.
multivariate model using binary logistic regression was Repeated pregnancy causes laceration of the cervix
built to determine the prognostic risk factors for cervical which allows organisms to ascend from the vagina and
carcinoma. infect the cervical canal. So, women with high parity are
more prone to develop carcinoma cervix which was
elaborated in the studies by Nikumbh et al. [14] (48%),
Discussion Jha et al. [15] (32.65%) and Kharbanda [12] (51.9%).
Kharbanda et al. [12] found 54% to use contraception
Cancer cervix is a major cause for cancer mortality and 47.7%of the study population to be illiterate.
globally but especially in the developing countries like Shankar et al. [16] found 33.1% to be smokers while
India. In today’s era, the age –adjusted incidence rate of 55.84%were unaware of the symptoms of cervical cancer
cancer cervix reported by many of the Indian cancer while our study found 56.4% to be smokers. Siddharthar
registries are much higher than the world age adjusted et al. [17] found 45% of the study population lacking
incidence rate of 7.9/100,000 population [3]. Since cervix is awareness of cervical cancer.
a relatively accessible organ, the logistics for screening
Discharge was the most common symptom
cervical cancer is simple [4]. However there are no
associated with unhealthy cervix as reported by Bal et
government sponsored screening programmes. Cancer
al. [18] (59%), Nikumbh et al. [14] (69.3%) and Jha et al.
cervix is common in women with early initial sexual
activity, early age at marriage, multiple pregnancies, use [15] (44.56%). The most common sign was erosion
of oral contraceptives, high parity and multiple sexual highlighted in the studies by Jha et al. [15] and Bal et al.
partners and lack of awareness [5]. Unhealthy cervix is [18] with 13.52% and 35.7% of cases respectively.
present due to low income, illiteracy, poor personal Siddharthar et al. [17] found 15.3% bleeding during or
hygiene, and multiparity [6]. after sex, 10.3% to have vaginal bleeding after
menopause. Our study found 43.2% cases to be
The data found in our study was compared to the data associated with discharge and 29.5% cases to be
from other studies from different parts of our country. associated with bleeding.
The mean age of the patients in the present study was
48.8 years. N.R. Varughese [7] et al found the mean age to NILM was the commonest lesion in different studies.
be 35+ or – 12.90 years with the age range from 15-50 LSIL was more common than HSIL. Pradhan N et al. [8]
years, S. Awasthy [5] found the mean age to be (LSIL-7%), Bal et al. [18] and Jha et al. [15] (LSIL-2.7% each)
34.5+9.23years. Pradhan et al. [8] found mean age to be found similar results. Squamous cell carcinoma was
38.1years. N.R. Varughese [7] found 92.8% women to be present in 1.2% of the total cases which was comparable
married , Raychaudhary S [9] found 88.7% to be married. to the other studies.
28.9% had heard of cervical cancer while our study found Among the organisms present, the most common
95.8% married women and only those in the literate group organism in our study was Candida . Other studies by
had heard of cervical cancer programmes. According to Nikumbh et al. [14], Bal et al.[18], Jha et al. [15] found
Awasthy S et al. [5] , three fourth of their study population Trichomonas vaginalis to be the most common organism
(74.2%) knew that cervical cancer could be detected by a present. Candida and TV were most commonly associated
simple screening test. Studies by Vallikad [10] and with discharge.
Bhattacharya et al. [11] found the majority of patients
It was found that the sensitivity of the present study was
with unhealthy cervix to be in the low socioeconomic group.
73.4% which was comparable to the other studies (Verma
Lack of awareness and poor hygiene are some of its major
et al. [19] 76.9% for LSIL, 66.6% for HSIL, Vidya Rani SM
reasons. Raychaudhary S [9] found monthly income <1000-
[20], 52.94%, Gravitt PE [21] 78.2%, Goel et al. [22] (50%)
6.8%, 1000-2000-23.5%, 2001-3000-38.9%, 3001-4000-12.7%,
and Rao SJ [23] (55.4%) while Chaudhary RD [24] had a
4001-5000-10.4%, >5000-7.7% corroborating with our
low sensitivity 25.4%. The specificity (88.6%) was
studies.
comparable with studies Verma et al 96.2% LSIL, 97.6%
Kharbanda et al. [12], Raychaudhary S [9], Pradhan N HSIL, Vidya Rani SM 96.38%, Gravitt PE 86%, Chaudhary
[8] et al. [7] found women whose age at marriage was less RD 99.27%, Goel et al. [18] (97%),and Rao SJ [19] (96.8%).
than 20 years to be 30%, 82%,69% respectively while our Positive predictive value (72.2%) was comparable to
study found 49.6% of women below 20 years at marriage. studies by Vidya Rani SM 71.42%, Chaudhary RD 94.12%,

Indian Journal of Pathology: Research and Practice / Volume 7 Number 6 / June 2018
790 Sujata Mallick & Mahasweta Mallik / Is Cervical Cancer Incidence Decreasing in the Urban Population of India with
Developing Healthcare, Socio Demographic Progress and Awareness Programmes?

Jain et al (91.1%) and Bhatla et al. [17] (100%). Negative for cervical pap smear examination. 2.Creating
predictive value of 89.3% was comparable to Vidya Rani awareness among Indian women about the risk factors
SM 98.7%, Chaudhary RD 74.32%. Accuracy of 84.3% was of cervical cancer. 3. Increasing patient compliance by
comparable to Vidya Rani SM 91%, Chaudhary RD 76%. convincing all positive or suspicious of positive cases to
The goal of cervical screening is to identify and go for histopathological examination.
remove precancerous lesions of the cervix in order to
reduce prevalence of cervical cancer. Pap smear has a Acknowledgement
good sensitivity and high specificity for detecting pre-
cancerous lesions of cervix. However, the education of Technical staff of Pathology Department, KPC medical
the masses, community participation, and compliance college, Jadavpur.
for routine pap test is the need of the hour. From our
results we find literacy has a major role in creating Key Messages
awareness about the importance of the cervical Incidence of carcinoma cervix can be brought down
screening programme. So we need to reach out to the if risk factors are identified at an early stage and mass
illiterate population more by organising health camps screening programs using simple measures like pap
[25]. The low socioeconomic group has more prevalence smear examination are implemented, where awareness
of risk factors. So, the provision for free health checkups of cervical cancer and associated risk factors is still very
among the poor will go a long way to bring down the less even in the urban population..
morbidity and mortality due to this disease. High parity
is again a risk factor for cervical carcinoma, so
counselling in the hospitals during child birth will create References
more awareness among the female population. Use of
condoms, OCP’s can help bring down the rate of cervical 1. Kaarthigeyan K. Cervical cancer in India and HPV vaccination.
Indian J of Med and Paediatr Oncol. 2012; 33(1):7-12.
cancer. This can be highlighted in the awareness
programmes. Early age at marriage prevalent in the low 2. Nigar A. Awareness of cervical cancer risk factors and
socioeconomic class can lead to cervical cancer which screening methods among women attending a tertiary
should be propagated through mass education [26]. hospital in lucknow, India. Int J of Repd, Contracept, Obstet
and Gynecol. 2017Dec;6(12):5592-95.
Females, especially married ones, should go through
3. Bobdey S, Sathwara J, Jain A,Balasubramaniam. Burden
cervical cancer screening programmes after 30 years of ofcervical cancer and role of screening in India. Indian J
age or if symptomatic. Community needs to be Med Paediatr Oncol. 2016 Oct-Dec;37(4):278-85.
enlightened about symptoms of cervical cancer like
4. Pradhan B, Pradhan SB, Mital VP. Correlation of PAP smear
discharge, bleeding, erosion etc. through diffuse findings with clinical findings and cervical biopsy.
educational activities [27]. Research is needed to determine Kathmandu Univ. Med. J. 2007;5(4):461-67.
how to communicate the benefits of the screening
5. Awasthy S, Reshma J, Avani D. Epidemiology of cervical
programs to women and their husbands and to explore
cancer with special focus on India. Int J of Women’s Health.
the role of cultural beliefs, stigma, gender inequities and 2015;7:405-14.
other factors in order to ensure that investments in cervical
cancer prevention result in the greatest impact [28]. The 6. Parazzini F,Vecchia C L, Negri E, Fedele L, Franceschi S,
Gallotta L. Risk Factors for Cervical Intraepithelial
high prevalence of cervical cancer even in the urban
Neoplasia. Cancer 1992;69:2276-82.
population of our country highlights the ineffectiveness of
our screening measures and awareness programs. 7. Varughese NR, Samuel CJ, Dabas P. Knowledge and
practices of cervical cancer screening among married
Limitations women in a semi urban population of Ludiana, Chrismed J
of Health and Res. Punjab. 2016;3(1):51-54.
Biopsy from all positive and suspicious cases could not
8. Pradhan N,Giri K,Rana A. Cervical cytology study in
be obtained due to failure of patient’s compliance.
unhealthy and healthy looking cervix. N. J. Obstet. Gynecol.
Follow up was not possible in many cases. 2007 Nov-Dec; 2(2):42-47.
9. Raychaudhuri S, Mandal S. Socio-Demographic and
behavioural risk factors for cervical cancer and knowledge,
Conclusion attitude and practice in rural and urban areas of North
Bengal, India.Asian Pacific J CancerPrev. 2012;13:1093-96.
Our study highlights the following points -1. In order to
decrease the prevalence of carcinoma cervix in our 10. Vallikad E. Cervical cancer: the Indian perspective. FIGO
26th Annual Report on the Results of Treatment in
country, we shoud introduce more screening programs
Gynecological Cancer. Int J Gynaecol Obstet. 2006 Nov;95
and make it mandatory for women above 30 years to go Suppl 1:S215-33.

Indian Journal of Pathology: Research and Practice / Volume 7 Number 6 / June 2018
Sujata Mallick & Mahasweta Mallik / Is Cervical Cancer Incidence Decreasing in the Urban Population of India with 791
Developing Healthcare, Socio Demographic Progress and Awareness Programmes?

11. Bhattacharyya SK, Basu S, Banerjee S, Dastidar AG, Bagchi 20. Vidya Rani SM, Rao PS, Prajwal S, Mitra S. correlation of pap
SR. An epidemiological survey of carcinoma cervix in north smear and colposcopic finding of unhealthy cervix with
Bengal zone. J Indian Med Assoc. 2000 Feb;98(2):60-1,66. histopathology report. J of Dent and Med Sci. 2017
12. Kharbanda P, Singh DK, Anand R, Singh A. Study of Mar;1693):25-31.
awareness amongst women in rural and urban areas about 21. Gravitt PE, Paul P, KatkiHA, Vendantham H, Ramakrishna
early detection of cervicalcancer by pap smear. Indian J G, Sudula M. Effectiveness of VIA, PAP and HPV DNA testing
path and Oncol. 2015Dec;2(4):219-29. in a cervical cancer screening program in a peri-urban
13. Wahi, P. N., Mali, S., and Luthra, U. K. Factors influencing community in Andhra Pradesh, India. PLOS ONE. 2010;
cancer of the uterine cervix in north India. Cancer 1969; 5(10):e13711.
23:1221-26. 22. Goel A, Gandhi G, Batra S, Bhambhani S, Zutshi V, Sachdeva
14. Nikumbh D B, Nikumbh R D, Dombale V D, Jagtap S V, Desai P, Visual inspection of the the cervix with acetic acid for
S R. Cervicovaginal Cytology: Clinicopathological and cervical intraepithelial lesion. Int J. Gynecol. Obstet.
Social Aspect of Cervical Cancer Screening in Rural 2005;88:25-30.
(Maharashtra) India. Int. J. of Health Sci. & Research 2012; 23. Rao SJ. Trends in cervical cancer screening in developing
192:125-32. countries. World J. Obstet. Gynecol. 2012;1(4):46-54.
15. Jha BM, Patel M, Patel K, Patel J. A study on cervical pap 24. Chaudhary RD, Inamdar SA, Hariharan C.Correlation of
smear examination in patient living with HIV. Nat. J. of diagnostic efficacy of unhealthy cervix by cytology,
med. research 2012 Mar;2(1):81-84. colposcopy and histopathology in women of rural area. Int
16. Shankar A, Roy S, Rath GK, Chakraborty A, Kamal VK, Biswas Jour of Repd, Contracept, Obstet, and Gynaecol.
AS. Impact of cancer awareness drive on generating 2014;3(1):2320-70.
awareness of and improving screening for cervical cancer: 25. Patel M M, Pandya A N, Modi J. Cervical pap smear study
Astudyamong schoolteachers in India. J of Glo Oncology. and its utility in cancer screening, to specify the strategy
2018;4:1-7. for cervical cancer control. Nat. J. of comm. med. 2011;
17. Siddharthar J, RajkumarB, Deivasigamani K, Knowledge, 2(1):49- 51.
Awareness andPrevention of Cervical Cancer among 26. Mishra GA, PimpleSA, Shastri SS. An overview of prevention
women attending a tertiary care hospital in Puducherry, and early detection of cervical cancers. Indian J Med
India. J Clin Diagn Res. 2014Jun;8(6):OC01-OC03. Paediatr Oncol. 2011Jul-Sep;32(3);125-132.
18. Bal M S, Goyal R, Suri A K, M K. Detection of abnormal 27. Awasthy S, Quereshi MA, Kurian B, Leelamoni K. Cervical
cervical cytology in Papanicolaou smears. J Cytol. 2012 cancer screening: Current knowledge and practice among
Jan-Mar;29(1):45–47. women in a rural population of Kerela, India. Indian Jour
19. Verma A, Singhal A. A Study on Cervical Cancer Screeningin MedRes. 2012Aug;136(2):205-210.
symptomatic women using pap smear in a tertiary care 28. Krishnan S, Madsen E, Porterfield D, Varghese B. Advancing
hospital in rural area of Himanchal Pradesh,India. Middle cervical cancer prevention in India: Implementation
East Fertility Society Jour. 2017;22(1);39-42. Science Priorities. Oncologist. 2013Dec;18(12):1285-1297.

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Indian Journal of Pathology: Research and Practice

IJPRP Volume 7 Number 6, June 2018


DOI: http://dx.doi.org/10.21088/ijprp.2278.148X.7618.15

Original Research Article

Clinicopathological Study of Primary Epithelial Malignant Tumours of


Thyroid Gland in a Tertiary Care Centre, Kolar

Pradeep Mitra V.1, Manjula K.2, CSBR Prasad3

1
Final year PG 2Associate Professor 3Professor and HOD, Department of Pathology Sri Devaraj Urs Medical College, Tamaka, Kolar,
Karnataka 563101, India.

Abstract

Clinicopathological study of primary epithelial malignant tumours of thyroid gland: in


a tertiary care centre, Kolar. Introduction Thyroid malignancy is the most common
malignancy in endocrine system accounting for 87% of all endocrine gland tumors [1]. The
Corresponding Author: incidence of thyroid cancers has been in the rising in the past two decades. The increase in
incidence may be due to early detection of asymptomatic cases through screening tests
Dr Manjula K.,
Associate Professor,
[2,3]. These epithelial tumors are characterized by unique clinical, molecular and biological
Dept. of Pathology, features [2,4]. Hence it is important to know the different histomorphology of these tumors
Sri Devaraj Urs Medical College, to foresee prognosis and guide the treatment for better outcome. Materials and methods
Tamaka, Kolar, Karnataka 563101, The study was conducted in the department of Pathology, Sri Devaraj Urs Medical College,
India. Kolar constituent college Sri Devaraj Urs Academy of higher education and Research. All
E-mail: the primary malignant epithelial thyroid carcinoma cases were retrieved from the archives
Gkpmanju966@rediffmail.com of Pathology from January 2010 to December 2016 for the duration of 7 years. Results Total
numbers of primary epithelial malignancies were 62 cases (2.5% of all malignant cases).
(Received on 15.05.2018,
Accepted on 09.06.2018)
The most common thyroid malignancy was the papillary carcinoma (54 cases, 87%)
Conclusions Primary epithelial tumors of thyroid accounted to 100% of thyroid malignancy.
Most patients presented with neck mass. Papillary carcinoma accounted to 87% of epithelial
carcinoma, more common in females. Anaplastic and follicular carcinoma was seen in
older age, were associated with distant metastasis
Keywords: Malignant Epithelial Tumors; Papillary Carcinoma; Medullary Carcinoma;
Vascular Invasion.

Introduction molecular and biological features [2,4]. Most patients


may present to the clinician as a solitary nodule,
Thyroid malignancy is the most common Multinodular goiter or with an enlarged cervical
malignancyin endocrine system accounting for 87% of lymphnode[5]. Hence, it is important to know the different
all endocrine gland tumors [1]. The incidence of thyroid histomorphology of these tumors to foresee prognosis
cancers has been in the rising in the past two decades. and guide the treatment for better outcome.
The increase in incidence may be due to early detection
of asymptomatic cases through screening tests [2,3]. Aims and Objectives
Most primary thyroid tumors are epithelial tumors To study clinical presentation and various
that originate from thyroid follicular cells. These pathological parameters of primary epithelial tumors
epithelial tumors are characterized by unique clinical, of thyroid gland.

© Red Flower Publication Pvt. Ltd. Indian Journal of Pathology: Research and Practice / Volume 7 Number 6 / June 2018
Pradeep Mitra V., Manjula K., CSBR Prasad / Clinicopathological Study of Primary Epithelial Malignant Tumours 793
of Thyroid Gland in a Tertiary Care Centre, Kolar

Materials and Methods Histopathological Parameters


The most common primary epithelial malignancy
The study was conducted in the department of
was papillary thyroid carcinoma (54 cases, 87%)
Pathology, Sri Devaraj Urs Medical College, Kolar
followed by medullary carcinoma (2 cases, 3.3%),
constituent college Sri Devaraj Urs Academy of higher
follicular carcinoma (3 cases, 5 %) anaplastic carcinoma
education and Research. All the primary malignant
(2 case, 3.2%), and hurthle cell carcinoma (1 case, 1.6%)
epithelial thyroid carcinoma cases were retrieved from
(Table 1.)
the archives of Pathology from January 2010 to
December 2016 for the duration of 7 years. Available Microscopic variants of papillary carcinoma were
clinical data such as Age, Sex, clinical presentation and Classical (61.1%), Follicular (22.2%), Micropapillary
other investigation were collected and reviewed. (11.1%), Tall cell variant (1.85%), Well differentiated
Histopathological Details regarding the size of the tumor, carcinoma NOS (1.85%) and Encapasulated warthin like
microscopic type, microscopic variant, extra thyroidal variant (1.85%). (Table 2).
extension, tumor margin, extra capsularspread, Average size of the tumor was 3.8 cms. Tumor stage
multicentricity, lymphnode status, grade of the tumor was available for 59 cases of which T1–10 cases, T2-18
and tumor stage were recorded in the data sheet and cases, T3 - 25 cases, T4- 5 cases. Extra thyroidal extension
analyzed was seen in 12cases (13.7%). 9 cases are of papillary thyroid
carcinoma, 2 anaplastic carcinoma and one case of
follicular carcinoma.Vascular invasion was seen in 4 cases
Results (6.89%), 2 cases are anaplastic carcinoma and 2 are
follicular carcinoma. Surgical resected margin was positive
Total numbers of primary epithelial malignancies
in onecase of anaplastic carcinoma (1.72%). Cervical
were 62cases (2.5% of all malignant cases). The most
Lymphnode resection was available in 45cases of which
common thyroid malignancy was the papillarycarcinoma
33cases showed papillary carcinomatumor deposits, 3
(54 cases, 87%).
were medullary carcinoma and 1 was anaplastic
Clinical Presentation carcinoma. 2 cases of papillary carcinoma showed distant
metastasis to scalp.
The most common age of presentation was in the 3 rd
decade (44.8%) followed by 4th decade (18.9%). The
median age was 36 years with a range of 12 to 80 years. Discussion
The Male: Female ratio was 1:3.8. The most common
clinical presentation was neck mass (52.2%) followed In the present study, primary epithelial malignant
by solitary nodule (28.8%), difficulty in swallowing tumors of thyroid accounted to 100% of all thyroid
(13.3%) cervical lymphadenopathy (3.3%) and scalp cancers. The median age of presentation was 36years;
swelling (2.2%). maximum cases were seen in 3rd decade. Studies done
by Niazi S [5] et al. and ALAmri AM [1] also reported

Table 1: Primary epithelial malignant tumors of thyroid gland

Tumor type No of cases %

Papillarythyroid carcinoma 54 87
Medullary carcinoma 2 3.2
Follicular carcinoma 3 4.8
Hurthle cell carcinoma 1 1.6
Anaplastic carcinoma 2 3.2
Total 62 100%

Table 2: Variants of papillary thyroid carcinoma

Variant of Papillarythyroid carcinoma No of cases %

Classical 33 61.1
Follicular 12 22.2
Micropapillary 6 11.6
Tall cell variant 1 1.85
Well differentiated carcinoma NOS 1 1.85
Encapsulated warthin like 1 1.85
Total 54 100%

Indian Journal of Pathology: Research and Practice / Volume 7 Number 6 / June 2018
794 Pradeep Mitra V., Manjula K., CSBR Prasad / Clinicopathological Study of Primary Epithelial Malignant Tumours
of Thyroid Gland in a Tertiary Care Centre, Kolar

malignancy of thyroid more common in 3rd decade. The enlargement [11,12,13]. One case was an incidental
male: female ratio was 1:3.8 and it has been well finding presented to us with scalp swelling. Most of the
documented in the literature that thyroid disorders are cases were in T2 and T3 stage and vascular invasion was
more common in females than in males. Hence, thyroid seen in 2 cases.
disorder or enlargement in males should be considered We had two medullary carcinomas (3.2%) in our
with higher degree of suspicion [6]. study, incidence was comparatively low. In other studies
In other studies male to female ratio shows variation incidence varies from 3.5% to 9.7% [5,8,12]. Medullary
(Table 3) and are different, with male predominance in carcinoma arises from the C cells of ultimobranchial
Saudi Arabia [7]. The most common clinical presentation body of neural crest and secretes calcitonin. There are
was of swelling in front theneck (neck mass) similar to most commonly sporadic than familial. Histological
other studies. Rare presentation in our study was two features (Figure 2) include Round, plasmacytoid, polygonal
patients presenting with scalp swelling, later or spindle cells with coarsely clumped chromatin and
histopathological examination showed metastatic indistinct nucleoli. Amyloid deposits from calcitonin are
follicular carcinoma and papillary carcinoma. frequently present in the stroma.
Papillary carcinoma of thyroid was the most common There were 3 cases of follicular carcinoma ( 4.8%) with
malignant primary epithelial tumor of thyroid follicles of varying sizes (microfollicular, normofollicular
accounting to 87%. The classical histomorphological or macrofollicular), showed capsular or vascular
features (Figure 1) are the presence of papillae with central invasion. One case presented with distant metastasis to
fibrovascular core, ground glass nuclei, nuclear grooves, scalp and femur.
nuclear molding and overlapping and pseudo inclusions. Anaplastic carcinoma in our study comprised of 2 cases
Different variants of Papillary Carcinoma thyroid (3.2%). Incidence and age of presentation is similar to
includes Classic, follicular, cribriform, micropapillary, tall other studies [5,8]. Both patients were more than 50years,
cell like, encapsulated warthin like, diffuse Sclerosing, females, presented with difficulty in swallowing. Tumor
oncoytic and clear cell type. In the present study, showed extrathyroidal extension. Microscopically( Figure
classical variant of papillary carcinoma thyroid was the 3) composed of highly pleomorphic cells arranged in
most common histological variant. Table 4 compares clusters and sheets with squamous foci. Vascular invasion
variants of papillary carcinoma with other studies. was seen.
Lymph node metastasis was seen in 33cases (53%). We had one case of hurthle cell carcinoma (1.2%)
Studies have shown that more than 50% of patients of presented as neck mass in 40 years female. This tumor
papillary carcinoma may show nodal metastasis. (Figure 4) was composed of cells with abundant granular
Patients may come with only cervical lymph node cytoplasm. Cells were arranged in sheets, trabeculae,
Table 3: Comparison of present study with other studies

Al-amriAM.1 NiaziS Et al5 GillandFD et Present study


(SaudiArabia) (Lahore) al8(USA)

total number of cases 143 170 15698 62


male : female ratio 1:7.2 1:3.25 1:2.9 1:3.8
age group 3rddecade 3rddecade 4thdecade 3rddecade
papillary carcinoma thyroid 51.7% 68.23% 75.5% 87%
Follicular carcinoma 9.7% 14.11% 16.9% 4.8%
anaplastic carcinoma 3.49% 5.88% 1.5% 3.2%
medullary carcinoma 0 6.47% 3.2% 3.2%
lymphnode metastasis 20% 27.5% - 25.3%

Table 4: Variants of papillary carcinoma thyroid

MuzaffirM et al9 Girardi et al10 NiaziS et al5 Present study


(Rawalpindi) (Brazil) (Lahore)

Classical 58(70.7%) 164(62.3%) 83(71.5%) 33(61.1%)


Follicular 13(15.9%) 83(31.5%) 17(14.6%) 12(22.2%)
columnar cell variant 6(7.3%) 1(0.3%) 0 0
tall cell 3(3.7%) 1(0.3%) 0 1(1.85%)
encapsulated 1(1.2%) 0 8(6.8%) 1(1.85%)
Occult 1(1.2%) 0 0
Oncocytic 0 10(3.8%) 0 0
warthin like 0 4(1.5%) 1(1..85%)

Indian Journal of Pathology: Research and Practice / Volume 7 Number 6 / June 2018
Pradeep Mitra V., Manjula K., CSBR Prasad / Clinicopathological Study of Primary Epithelial Malignant Tumours 795
of Thyroid Gland in a Tertiary Care Centre, Kolar

Fig. 4: Hurthle cell carcinoma (Hand E, X400)

Fig. 1: Papillary carcinoma (Hand E, X400) small follicles. Showed areas of infarction, which may
be due to fine needle aspiration. Some authers consider
hurthle cell neoplasm as a variant of follicular neoplasm
instead of a separate entity [14,15]. Criteria of malignancy
are same as follicular tumors, but they differ in prognosis
and treatment modalities [14].

Conclusions

Primary epithelial tumors of thyroid accounted to 100%


of thyroid malignancy. Most patients presented with neck
mass. Papillary carcinoma accounted to 87% of epithelial
carcinoma, more common in females. Anaplastic and
follicular carcinoma was seen in older age, were associated
with distant metastasis

References
Fig. 2: Medullary carcinoma (Hand E, X400)
1. Al-amri AM. Pattern of thyroid cancer in the eastern
province of Saudi Arabia: University hospital experience.
Journal Cancer Therapy 2012;3:187-91.
2. Katoh H, Yamashita K, Enomoto T, Watanabe M.
classification and general consideration of thyroid cancer.
SciMedCentral. 2015;3(1):1045-52.
3. Rendl G et al. clinicopathological characteristics of thyroid
cancer in the federal state of Salzburg.WienKlin Wochenchr
2017;129:540-44.
4. Scopa CD. Histopathology of thyroid tumors. An overview.
Hormones 2004;3(2)100-10.
5. Niazi S, Arshad M, Bukhari MH. A clinicopathological study
of thyroid cancers at King Edward medical university/ Mayo
Hospital, Lahore. Annals 2011;11:268-274.
6. Li Volsi VA. Follicular lesions of the thyroid.In: Surg Path of
the thyroid. Philadelphia WB Saunders; 1990:173-212.
7. Al – Balawri IA, Meir HM, Yousaf MK, Nayel HA, Al-Mobarek
MF. Differentiated thyroid carcinoma refered for radioiodine
Fig. 3: Anaplastic carcinoma (Hand E, X400) therapy. Saudi Med J 2001;22;497-503.

Indian Journal of Pathology: Research and Practice / Volume 7 Number 6 / June 2018
796 Pradeep Mitra V., Manjula K., CSBR Prasad / Clinicopathological Study of Primary Epithelial Malignant Tumours
of Thyroid Gland in a Tertiary Care Centre, Kolar

8. Gilland FD, Hunt WC, Morris DM, Key CR. Prognostic factors 12. Shibata Y, Yamashita S, Masyakin VB, Panasyuk GD, Nagataki
for thyroid carcinoma. A population based study and results S. 15 years after Chernobyl: new evidence of thyroid cancer.
(SEER) Program 1973-1991. Cancer1997;79(3):1973-1991. Lancet 2001;358:1965-6.
9. Muzaffar M, Nigar E, Mushtaq S, Mamoon N. the 13. Livolsi VA. Papillary neoplasms of the thyroid: pathologic
morphological variants of papillary carcinoma of the and prognostic features. Ajcp 1992;97:426-34.
thyroid: a clinic pathological study- AFIP experience. Journl 14. chanJKC.The thyroid gland. Diagnostic histopathology of
of Pak med assn 2000;9:133-37. tumors, Elsevier saunders 2013.1177-1251.
10. Girardi MF, Barra MB, ZettlerCG.Variants of papillary thyroid 15. Evans HL.Sellin VR. Follicular and hurthle cell carcinoma of
carcinoma: association with histopathological prognostic the thyroid: a comparative study. Am J Surg Pathol
factors. Braz J Otorhinolaryngol. 2013;79:738-44. 1998;22:1512-20.
11. Schlumberger MJ. Papillary and follicular thyroid
carcinoma. New Eng J of Medinine 1998;338:297-306.

Indian Journal of Pathology: Research and Practice / Volume 7 Number 6 / June 2018
797
Indian Journal of Pathology: Research and Practice

IJPRP Volume 7 Number 6, June 2018


DOI: http://dx.doi.org/10.21088/ijprp.2278.148X.7618.16

Original Research Article

Histopathological Evaluation of Non-Neoplastic and Neoplastic Lesions of


Cervix

Arpita Singh1, Shilpa L.2, Shivarudrappa A.S.3


1
Post Graduate 2Asssistant Professor 3Professor, Department of Pathology, Vydehi Institute of Medical Sciences and Research Centre,
Bengaluru, Karnataka 560066, India.

Abstract

Background: Cervix is one of the most common target organs for both non neoplastic
and neoplastic diseases of the female genital tract. Cervical cancer is the second most
common cancer worldwide having poor prognosis. Carcinoma cervix is the commonest
Corresponding Author: malignancy in Indian women. (Human papilloma virus) HPV infection plays major role in
cervical lesions; in which high risk types particularly HPV 16 causes dysplasia and Carcinoma
Shilpa L.,
Asssistant Professor,
of cervix.
Department of Pathology, Materials and Methods: This prospective study was undertaken in the Department of
Vydehi Institute of Medical Pathology, Vydehi Institute of Medical Sciences and Research Centre for a period of 1.5 year
Sciences and Research Centre, from January 2015 to May 2016.
Bengaluru, Karnataka 560066,
India. Results: 100 cases were included in the study. Out of 100 cases majority were inflammatory
E-mail: i.e. 54% followed by 21% of Cervical Intraepithelial Neoplasia (CIN), 17% invasive carcinoma,
dr.shilpahpt@gmail.com 6% benign and 2% of non-neoplastic cervical glandular lesions. Immunohistochemistry
was done in (Chronic non-specific cervicitis) CNSC associated with squamous metaplasia
(Received on 05.05.2018,
and koilocytosis, all non-neoplastic cervical glandular lesions, precancerous lesions and
Accepted on 22.05.2018)
invasive carcinomas.
Conclusion: However, there are many lesions that are mistakenly over diagnosed to be
neoplastic. Therefore, it is recommended to further studies to evaluate these non-neoplastic
lesions of the uterine cervix on a community basis. Overexpression of the protein p16INK4A
encoded by tumor suppressor gene INK4A is a characteristic of dysplastic & neoplastic
alterations of cervical epithelium. The proportion of p16INK4A positive samples increases in
the following row: CIN I- CIN II- CIN III- Invasive carcinomas. However p16INK4A negative
cervical neoplasms & carcinomas do exists.
Keywords: Neoplastic Lesions; Cervix; Carcinomas.

Introduction and mortality. Sexually active women are more prone


for cervical disease [2, 3].

The infections of female genital tract are the gateway Incidence of cervical lesions varies according to age.
predisposing the women not only to tubal infertility but Early recognition of infections &amp; inflammatory
also increase risk of ectopic pregnancy [1]. Cervical lesions can prevent considerable damage to the cervix.
lesions are more frequent and commonly It also helps to decrease morbidity and mortality.
encountered day today problem of gynaecological Cervical cancer is the second most common cancer
lesions in women. Cervical lesions, both neoplastic worldwide. Carcinoma cervix is the commonest
&amp; non-neoplastic, are prime reason for morbidity malignancy in India. Early sexual activity, sexually

Indian
© Red Journal of Pathology:Pvt.
Flower Publication Research
Ltd. and Practice / Volume 7 Number 6 / June 2018
798 Arpita Singh, Shilpa L. & Shivarudrappa A.S. / Histopathological Evaluation of Non-Neoplastic and
Neoplastic Lesions of Cervix

transmitted diseases, viral infections, low socio economic P16INK4A Immunohistochemistry staining
status, injury related to multiple births are the various • Cut the tissue section on a microtome with a thickness
factors contributing for the carcinoma cervix [4]. of 3 microns.
According to World Health Organisation (WHO 2012)
cervical cancer is said to be the world’s second deadly • Bake sections for 1 hour at 60o prior to test
cancer with an estimate of about 493,243 women • De- paraffinize& re hydrate the tissue slides and wash
diagnosed with it &amp; 273,505 dying from it per year. in running tap water for 5 minutes.
Cervical cancer is most commonly seen in women of
• Allow sections to soak in PBS (wash buffer) for 2
reproductive age group. Human Papillomavirus
minutes in staining jar.
infection (HPV) is the central cause of cervical cancer
along with several host and environmental factors. HPV • Antigen retrieval by using EZ AR1 or EZ AR2 in
16 &amp; 18 is known to cause majority of cervical microwave oven or EZ RETRIVER at -
cancers [5, 6]. Though HPV is a necessary cause of cervical
Cycle 1: 850 for 5min or 500 watts for 5 min
cancer, other cofactors are also necessary for progression
of HPV infection to cancer. Screening for precancerous Cycle 2: 980 for 15 min or 750 watts for 15 min
lesions can help in early detection and treatment. PAP • Allow the slides to cool at room temperature for 15
smear is the most commonly used screening test for mins
cervical cancer. Other methods are visual inspection of
the cervix with acetic acid (VIA), magnified visual inspection • Wash with PBS (WASH BUFFER) for 2 times with a time
with acetic acid (VIAM), &amp; visual inspection with lugols gap of 30 secs for each wash.
iodine [7]. • Mark around the sections with HYDROPHOBIC (PAP)
Cervical screening with PAP smear has dramatically pen (if available).
reduce the number of mortality from cervical cancer. • Apply Peroxidase block (3% H2O2) and incubate for 10
With the introduction of HPV vaccination there is mins at room temperature (200-250C).
significance decrease in the number of cervical cancer • Wash with PBS (WASH BUFFER) for 3 times with a time
cases. Prophylactic vaccines for cervical cancer target gap of 30 secs for each wash.
HPV 16 & 18. Two commonly available vaccines in India
are Ceravarix &amp; Gardasil. • Apply Power Block & incubate for 5 mins at room
temperature (200-250C).
The aim of the present histopathological study is to
evaluate the neoplastic & non neoplastic lesions of the • Drain the excess power block. DO NOT WASH SLIDES
cervix along with various types of cervical lesions showing with PBS (WASH BUFFER) after Power Block.
incidence and age wise distribution and to study the • Apply Primer antibody & incubate for 1 hour in a
histopathological features of all the lesions of cervix. closed chamber at room temperature.
• Wash with PBS (WASH BUFFER) for 3 times with a gap
Materials and Methods of 30 sec for each wash.
• Apply Super Enhancer & incubate for 20 min in a closed
The present study was undertaken in the Department
chamber at room temperature (200-250).
of Pathology, Vydehi Institute of Medical Sciences and
Research Centre, Bangalore, India. One and a half year • Wash with PBS (WASH BUFFER) for 4 mins with a time
prospective study was done for a period of 1 ½ years gap of 30secs for each wash.
from January 2015 to May 2016, and consists of 100 • Apply Polymer HRP and incubate for 30 mins in a
patients. The specimens included in the study will be closed chamber at room temperature (200-250).
received in different forms such as, punch biopsy,
hysterectomy, endocervical curettage and polypectomy • Wash with PBS (WASH BUFFER) for 4 times with a time
specimens. The entire specimen were fixed in 10% neutral gap of 30 sec for each wash.
buffered formalin; tissues processed; paraffin embedded • Apply DAB Substrate and incubate for 7-10 mins.
tissue blocks will be prepared which will be cut at 4-5 • Wash with PBS (WASH BUFFER) for 4 times with a time
microns thickness. They will be subsequently stained gap of 30 sec for each wash.
with Haematoxylin and Eosin. Immunohistochemistry
was done in all precancerous and non neoplastic cervical • Wash with DI water for 4 times with a time gap of 30
glandular lesions. The histopathological classification secs for each wash.
of tumors was done according to recommendation by • Counter stain with Hematoxylin.
WHO. • Dehydrate, Clear & Mount.

Indian Journal of Pathology: Research and Practice / Volume 7 Number 6 / June 2018
Arpita Singh, Shilpa L. & Shivarudrappa A.S. / Histopathological Evaluation of Non-Neoplastic and 799
Neoplastic Lesions of Cervix

Interpretation of p16INK4a staining Punch biopsy was the most common type of specimen
The distribution of p16INK4a positivity was done, as received for histopathological evaluation followed by
follows hysterectomy, endocervical curettage & Polypectomy
(Table 1).
Negative (&lt; 1% of the cells were positive),
The most common age group of the study was 41-50
Sporadic (isolated cells were positive, but &lt; 5%), years, with the mean age of 43.46 years (Table 2).
Focal (small cell clusters, but &lt; 25% of the cells were Among 54 inflammatory lesions, chronic nonspecific
positive) and, cervicitis was the commonest inflammatory lesion found
Diffuse (&gt; 25% of the cells were stained). in 94.5 % of the cases followed by 5.5% cases of
polypoidal endocervicitis. Chronic non-specific cervicitis
was associated with other histological changes like
Results nabothian cyst, squamous metaplasia, epidermidisation
& koilocytic change (Table 3).
The present study was done to analyse the Non
neoplastic & neoplastic lesions of cervix encountered in Only 2 categories of benign cervical lesions were
our institution. The study was done for a period of observed: endocervical polyp and leiomyoma (Table 4).
January 2015 to May 2016 (11/2years), and consists of CIN III was the most common precursor lesion
100 patients. accounting for 57.14% of the cases (Table 5, 6).

Table 1: Distribution of types of specimen in the study

Type of specimen No of cases (n) %

Punch biopsy 47 47%


Hysterectomy 40 40%
Endocervical curettage 08 8%
Polypectomy 05 5%

Table 2: Age distribution of cervical lesions

Age group Type of lesion Total


Inflammatory Non neoplastic glandular lesions Benign CIN Malignant
21-30 13 - 1 - 1 15
31-40 15 - 2 8 4 29
41-50 20 2 3 5 4 34
51-60 5 - - 2 7 14
61-70 1 - - 6 1 8
Total 54 2 6 21 17 100

Table 3: Histopathological distribution of cervical lesions

Cervical lesions n %

Non- neoplastic
Inflammatory 54 54 %
Non-neoplastic cervical glandular lesion 2 2%

Neoplastic
Benign 6 6%
CIN 21 21%
Malignant 17 17%
Total 100 100%

Table 4: Distribution of benign cervical lesions

Type of lesion No of cases Percentage


Leiomyoma 2 33.33%
Endocervical polyp 4 66.66%
Total 6 100%

Indian Journal of Pathology: Research and Practice / Volume 7 Number 6 / June 2018
800 Arpita Singh, Shilpa L. & Shivarudrappa A.S. / Histopathological Evaluation of Non-Neoplastic and
Neoplastic Lesions of Cervix

Squamous cell carcinoma was the most common Immunohistochemistry (p16 expression)
invasive carcinoma, followed by neuroendocrine Following histopathological reporting all the cases
carcinoma and adenocarcinoma (Table 7). of CNSC associated with squamous metaplasia and
Invasive carcinomas were common in the females koilocytosis, cases of non-neoplastic glandular lesions,
with age more than 31 years. Only 1 case of all precancerous lesions & invasive carcinoma were
malignancy was seen in the age group of 21-30 years taken up for p16 marker study/ staining. In this research
[Table 8]. study, all the cases of CNSC and non- neoplastic
Squamous cell carcinoma was further graded as well glandular lesions were negative for p16.
differentiated SCC comprising of 50% cases, moderately In the present study CIN accounted for 21 cases; p16
differentiated SCC 35.71% cases and poorly was positive in 15(71.42%) cases and negative in
differentiated SCC 14.28% cases [Table 9]. 6(28.57%) cases.

Table 5: Age distribution of benign cervical lesions

Age group( years) Lesion Ttal


Leiomyoma Endocervical polyp
21-30 1 - 1
31-40 1 1 2
41-50 - 3 3
51-60 - - -
61-70 - - -
Total 2 4 6

Table 6: Age wise distribution of Cervical Intraepithelial Neoplasia

Age in years CIN I CIN II CIN III Total

21-30 0 0 0 0
31-40 3 1 4 8
41-50 2 0 3 5
51-60 0 0 2 2
61-70 1 2 3 6
Total 6 3 12 21
Percentage 28.57 14.28 57.14 100

Table 7: Histologic types of Invasive carcinoma

Cervical malignancy Number Percentage


Squamous cell carcinoma 14 82.35%
Adenocarcinoma 1 5.88%
Neuroendocrine carcinoma 2 11.76%
Total 17 100%

Table 8: Histologic types & age wise distribution of Invasive cancers

Cervical malignancies 21-30 years 31-40 years 41-50 years 51-60 years 61-70 years Total

Squamous cell carcinoma 1 2 3 4 4 14


Adenocarcinoma - 1 - - - 1
Neuroendocrine carcinoma - 1 1 - - 2
Total 1 4 4 4 4 17

Table 9: Distribution of Squamous cell carcinoma according to grades

Grades No of cases Percentage

Well differentiated 7 50%


Moderately differentiated 5 35.71%
Poorly differentiated 2 14.28%
Total 14 100%

Indian Journal of Pathology: Research and Practice / Volume 7 Number 6 / June 2018
Arpita Singh, Shilpa L. & Shivarudrappa A.S. / Histopathological Evaluation of Non-Neoplastic and 801
Neoplastic Lesions of Cervix

Out of 12 cases ofCIN III,11 cases were positive & only diffuse positivity, while 10 cases of Squamous cell
one case was negative. Most cases of CIN III showed carcinomashowed diffuse positivity (Table 10).
diffuse positivity. 17 cases of carcinoma cervix were
observed which included 14 cases of SCC, 2 cases of
Small cell carcinoma & 1 case of Adenocarcinoma. Discussion
All of the cases of carcinoma were positive for p16 i.e. Cervix is one of the most common target organs for
100%. Adenocarcinoma & Small cell carcinoma showed both non-neoplastic and neoplastic diseases of female
Table 10: p16 expression in cervical lesions

Lesions Staining Total


Negative Sporadic Focal Diffuse

CNSC with koilocytic change and squamous metaplasia 5 - - - 5


Non neoplastic glandular lesions 2 - - - 2
CIN I 4 - 1 1 6
CIN II 1 1 1 - 3
CIN III 1 1 3 7 12
SCC - 1 3 10 14
Adenocarcinoma - - - 1 1
Neuroendocrine carcinoma - - - 2 2
Total 13 3 8 21 45

A B
A B
Fig. 4: Poorly Differentiated Squamous cell Carcinoma - Cervix
Fig. 1: Chronic non specific Cervicitis with squamous metaplasia A: Hematoxylin& Eosin stain (40x). B: p16 showing diffuse positivity(40x).
A: Hematoxylin& Eosin stain (40x). B: Negative for p16 stain (40x)

A B A B
Fig . 2: Cervical Intraepithelial Neoplasia-I Fig. 5: Clear cell Adenocarcinoma- Cervix
A: Hematoxylin& Eosin stain (40x). B: p16 stain showing diffuse positivity A: Hematoxylin& Eosin stain (40x). B: p16 stain showing diffuse positivity
(40x) ( 40x)

A B A B
Fig. 3: Cervical Intraepithelial Neoplasia- II Fig. 6: Neuroendocrine tumor - Cervix
A: Hematoxylin& Eosin stain (40x). B: p16 showing focal positivity (40x) A: Hematoxylin& Eosin stain (40x). B: Diffuse positivity for p16 (40x).

Indian Journal of Pathology: Research and Practice / Volume 7 Number 6 / June 2018
802 Arpita Singh, Shilpa L. & Shivarudrappa A.S. / Histopathological Evaluation of Non-Neoplastic and
Neoplastic Lesions of Cervix

genital tract. If untreated reproductive tract infections Age distribution of cervical lesions
can lead to adverse health outcomes such as infertility, The age of presentation of various cervical lesions was
ectopic pregnancy. Sexually transmitted causes include between 21 to 70 years. The mean age of the study was
viruses such as HPV and HSV. 43.46 years. Nwachokor FN et al (2013) in their study found
HPV cervicitis is a causal risk factor for maximum no. of non-neoplastic lesions in the age group
condylomataacuminatum, pre invasive CIN I, II, III and 40-49 years [10].
eventually cervical cancer. These lesions constitute a
source of morbidity and mortality in women worldwide Histopathological distribution of cervical lesions
hence the need to analyze them to provide a baseline In the present study, non-neoplastic lesions were more
data of the pattern of these lesions in our local common than neoplastic lesions. Non neoplastic lesions
environment. comprised 56% of cases, 6% lesions were benign, 21%
CIN and 17% lesions were malignant. Non neoplastic
In the present study 100 cases of cervical specimens
lesions included non- specific cervicitis, granulomatous
were sent to department of pathology, in our tertiary
cervicitis and non-neoplastic cervical glandular lesions.
institute from January 2015 to May 2016. The specimens
were processed routinely and sections were stained by This study showed more cases of CNSC were associated
H&E and pre-cancerous and cancerous lesions were with nabothian cyst as compared to study done by
stained with p16. Grewal et al [8]. Number of cases of CIN was more as
compared to the other studies by Jyothi et al and Grewal
Distribution of types of specimens et al [1, 8]. (Table 11).
In the present study majority were punch biopsy
Non-neoplastic cervical glandular lesions
specimens (47%), followed by 40% specimens of
hysterectomy. Grewal et al (2016) in their study on 311 In the present study 2 non neoplastic cervical glandular
cases found 70% specimens were hysterectomy lesions were encountered. 1 case of microglandular
specimens followed by 23.7% cervical punch biopsy hyperplasia was observed in the present study.
specimens [8]. Pallipady et al (2011)in their study encountered 2.6%
Mainali N et al (2014) in their study on 100 cases also cases of microglandular hyperplasia and 2.46% tunnel
found 71% hysterectomy specimens and 29% cervical clusters [11].Hatwal et al (2016) in their study found
biopsies [9]. 1.26% cases of microglandular hyperplasia [12].

Table 11: Comparative analysis of cervical lesions


Cervical lesions Jyothi et al (2016)1 Grewal et al (2016)8 Present study

Non-specific cervicitis 45.11% 70.92% 53%


Granulomatous cervicitis 0.66% - 1%
Non- neoplastic cervical glandular lesions - 6% 2%
Benign lesions 5.5% 2.82% 6%
CIN 5.6% 11.58 21%
Malignant lesions 43.2% 8.68 17%

Benign cervical lesions

Table 12: Comparative analysis of benign cervical lesions


Lesions Usha et al13 Jyothi et al (2015)1 Present study

Endocervical polyp 84.48% 73.5% 66.66%


Leiomyoma 6.03% 26.47% 33.33%

Results were concordant with the results of Usha et al and Jyothi et al [13,1]. (Table 12).

Cervical Intraepithelial lesions

Table 13: Comparative analysis of CIN

Lesions Hall et al14 Zhao et al (2015)15 Present study

CIN I 47.8% 95.9% 28.57%


CIN II 41.1% 2% 14.28%
CIN III 11.1% 2.1% 57.14%

Indian Journal of Pathology: Research and Practice / Volume 7 Number 6 / June 2018
Arpita Singh, Shilpa L. & Shivarudrappa A.S. / Histopathological Evaluation of Non-Neoplastic and 803
Neoplastic Lesions of Cervix

In the studies done by Hall et al and Zhao et al maximum These observations support that p16 is a specific
no. of cases were CIN I which is not comparable with this marker for cells that express the viral E6-E7 oncogenes
study as in the present study we encountered maximum and retain the capacity to replicate thus displaying a
no of cases of CIN III [14, 15]. (Table 13). high degree of genetic instability
In conclusion, the results of the present study indicate
Invasive Carcinomas
that p16 INK 4a expression in tissues can be used to
17 cases of invasive carcinomas were encountered. identify progressive cervical neoplasia and hypothesized
Maximum no. of the carcinomas was squamous cell to be HPV-transformed cells. (Table 15).
carcinoma followed by neuroendocrine tumour and
adenocarcinoma. Malignancy was more commonly
observed above the age of 31 years. Conclusion
Adenocarcinoma shows columnar cells with elongated, Cervical lesions are more frequent and commonly
hyperchromatic nuclei that may show marked atypia with encountered day today problem of gynaecological
nuclear pleomorphism and coarse chromatin. Microscopic lesions in women. Cervical lesions, both neoplastic and
features of neuroendocrine tumours include cells arranged non-neoplastic, are prime reason for morbidity and
in sheets and cords with inconspicuous cytoplasm. The mortality in women. Inflammatory lesions are the most
cells have hyperchromatic nuclei with ûnely stippled frequent non- neoplastic cervical lesions. These lesions
chromatin, inconspicuous nucleoli, and high nuclear to therefore account for significant amount of gynecological
cytoplasmic ratio. problems in our environment. Adequate cervical screening
Table 14 showed maximum number of squamous cell with follow up histological biopsies is a relevant tool in
carcinomas. The results are concordant with the studies diagnosing them to enhance early detection of
done by Sapurkar et al, Menczer and Jyothi et al premalignant and malignant cervical lesions.
[16,17,and 1]. In the present study 11.76% of
neuroendocrine tumours were seen which were not Financial Disclosure Statement: No
observed in the studies done by the above authors.
Conflict of Interest: Nil
p16INK4a expression in cervical lesions
Immunochemical detection of p16INK4a shows that References
majority of the cases of CIN, invasive cervical carcinoma
differ from normal cervical epithelium of healthy women. 1. Jyothi V, Manoja V, Sridha Reddy K. A Clinicopathological
In the present study we found that all cases of CNSC Study on cervix. Journal of Evolution of medical &amp;
which were associated with squamous metaplasia, dental Sciences 2015;13:2120-26.
koilocytic change & non neoplastic cervical glandular 2. Sebanti G, Rekah D, Sibani S. A profile of adolescent girls
lesion were negative for p16. Volgareva et al in their study with gynaecological problems. Obstes Gynaecol India
also observe that that no cases of non-specific cervicitis 2005;55:353-55.
& cervical ectopia showed focal, diffuse, sporadic 3. Workowski KA, Bolan GA. Sexually transmitted diseases
positivity, so the results of the present are in concordant treatment guidelines. Centers for disease control &amp;
with the study done by Volgareva et al [18,19]. prevention. MMWR Recomm Rep 2015;64:1-137.

Table 14: Comparative analysis of invasive carcinomas

Lesions Solapurkar et al16 Menczer 201117 Jyothi et al1 Present study

Squamous cell carcinoma 95.70 80.6 98.89 82.35


Adenocarcinoma 1.28 11.8 0.70 5.88
Adenosquamous carcinoma 0.64 3.9 0.36 --
Neuroendocrine carcinoma - - - 11.76

Table 15: Comparative analysis of p16INK4a in dysplasia and neoplastic lesions

Lesions Volgareva at el18 Klaes et al19 Present Study


Positive Negative Positive Negative Positive Negative

CIN I 14% 63% 63.82% 36.17% 33.33% 66.66%


CIN II 32% 68% 56.25% 43.75% 66.66% 33.33%
CIN III 54% 46% 85% 15% 91.6% 8.33%
Invasive carcinomas 96.2% 3.8% 91.67% 8.33% 100% -

Indian Journal of Pathology: Research and Practice / Volume 7 Number 6 / June 2018
804 Arpita Singh, Shilpa L. & Shivarudrappa A.S. / Histopathological Evaluation of Non-Neoplastic and
Neoplastic Lesions of Cervix

4. Dubey K, Garewal J, Kumar NN, Sharma R. 12. Hatwal D, Batra N, Kumar A, Chaudhary S, Bhatt S.
Histopathological study of Non Neoplastic lesion in cervix Spectrum of neoplastic Lesions of Uterine cervix in
at tertiary care center;International Journal O Medical Uttarakhand:National Journal of Laboratory Medicine
Research &amp; health Sciences 2016;5:42-19. 2016;5:39-43.
5. Schlecht NF, Kulaga S, Robitaille J, Ferreira S, Santos M, 13. Usha, Narang BR, Tiwari P, Asthana AK, Jaiswal V. A
Miyamura RA et al. Persistent Human Papillomavirus clinicomorphological study of benign tmors of cervix. J
Infection as a Predictor of Cervical Intraepithelial Obstet Gynecol 1992;42-228.
Neoplasia: JAMA 2001;286:3106-14. 14. Hall DA. Dysplasia of the cervix. Am J Obstel Gynecol
6. Boshart M, Gissmann L, Ikenberg H, Kleinheinz A, Scheurlen 1968;100:662.
W, Zur H. A new type of papilloma virus DNA, its presence in 15. Zhao Y, Chang IJ, et al. Distribution of Cervical
genital cancer biopsies and in cell lines derived from intraepithelial neoplasia on the cervix in Chinese women:
cervical cancer. The EMBO journal 1984;3:1151-57. pooled analysis of 19 population based screening studies.
7. Burd EM. Human papilloma virus and cervical cancer. Clin BMC cancer 2015;15:485.
Microbiol Rev 2003;6:1-17. 16. Solakpurkar ML. Histological study of uterine cervix in
8. Garewal A, Khatri SL, Saxena V, Gupta S, Singh S, Dubey S. malignant and benign lesions J Obstet Gynecol India
Clinicopathological Evaluation of Non Neoplastic and 1985;35:933.
Neoplastic Lesions of Uterine cervix. IJIR 2016;2:426-30. 17. Menczer J. cervical neoplasia in Israeli Jewish women:
9. Mainali N, Sinha AK, Upadhaya P, Uprety D. A study on mast characteristics in a low risk Population. IMAJ 2011;13:700-
cell variation in neoplastic and non neoplastic disease of 704.
uterine cervix. Journal of Pathology of Nepal 2014;4: 658- 18. Volgareva G, Zavalishina L, Andreeva Y, Frank G, Krutikova
62. E, Golovina D et al. Protein p16 as a marker of dysplastic
10. Nwachokor FN, Forae GC. Morphological spectrum of non- &amp; neoplastic alterations in cervical epithelial cells.
neoplastic lesions of the uterine cervix in Warri, South- BMC Cancer 2004;4:58.
South, Nigeria. Niger J Clin Pract 2013;16:429-32. 19. Klaes R, Friedrich T, Spitkovsky D, Ridder R, Rudy W, Petry
11. Pallipady A, Illanthody S, Vaidya R, Ahmed Z, Suvarna R, U, et al. Overexpression of p16 INK4a as a specific marker
Metkar G. A Clinico- Morphological Spectrum of the Non for dysplastic and neoplastic epithelial cells of the cervix
Neoplastic Lesions of the Uterine Cervix at AJ Hospital, uteri. Int J. Cancer 2001;92:276-84.
Mangalore. Journal of Clinical and Diagnostic Research
2011;5:546-50.

Indian Journal of Pathology: Research and Practice / Volume 7 Number 6 / June 2018
805
Indian Journal of Pathology: Research and Practice

IJPRP Volume 7 Number 6, June 2018


DOI: http://dx.doi.org/10.21088/ijprp.2278.148X.7618.17

Case Report

Reactive Angioendotheliomatosis in the Setting of Leprosy: A Previously


Un-Described Association

Poorvi Kapoor1, Vishwanath B.K.2, Vardendra Kulkarni3, Prakash Kumar4, Rajashekar K.S.5

1
PG Student 3Associate 4Professor 5Professor and Head, Dept. of Pathology, 2Professor, Dept. of Dermatology, JJM Medical College,
Davangere, Karnataka 577004, India.

Abstract
Corresponding Author: Cutaneous reactive angioendotheliomatosis (CRA) is a group of benign skin disorders
which comprise 3 main entities: reactive angioendotheliomatosis (RAE), intralymphatichistiocytosis
Poorvi Kapoor,
and diffuse dermal angiomatosis (DDA). These disorders are characterized by vascular
PG Student, Dept. of Pathology,
JJM Medical College, Davangere,
proliferations which are either intraluminal or periluminal. Of these, RAE is well known to
Karnataka 577004, India. arise in association with chronic systemic disorders. We report a case of a 37 year old female,
E-mail: who presented with multiple, painless skin coloured nodules over the extensor aspect of her
swift.cynic@gmail.com upper limb and foot. She also had multiple painful, erythematous nodules over the upper as
well as lower limb. Light microscopy of the painless nodules, showed features suggestive of
(Received on 17.04.2018, RAE. The painful,erythematous papules of the upper limb, showed features consistent with
Accepted on 05.05.2018) Borderline Lepromatous Leprosy. Immunohistochemistry with CD31 and CD34 showed
positivity of the spindle cells lining the capillaries, proving its vascular origin. To our
knowledge, this is the first case to be reported of RAE occurring in the setting of leprosy.
Keywords: Reactive Angioendotheliomatosis; Leprosy; Skin.

Introduction Case Report

Reactive angioendotheliomatosis is a benign vascular A 37 year old female, came to the dermatology
proliferation known to arise in the setting of chronic outpatient department, with complaints of painless
systemic illnesses. It is a part of cutaneous reactive swellings over her upper and lower limbs. She also gave
angiomatosis (CRA) along with intralymphatichistiocytosis, a history of evanescent, painful skin lesions, over her
as well as diffuse dermal angiomatosis. Six entities have upper and lower limb, along with complaints of fever
been described under the broad heading of CRA by and malaise. The duration of these symptoms was
Rongioletti F et al [1]. RAE is seen as erythematous patches around 3 months. On examination, there were multiple
and plaques, usually in the extremities [2], but can occur erythematous papules over the flexors of her upper and
anywhere in the body. lower limbs, as well as firm, well defined, skin coloured
It has known to be associated with a wide variety of nodules over the lower limbs and foot. Her right ulnar
disorders, of which chronic systemic disorders, infections and left common peroneal nerves were palpable and
and paraproteins are common. It is characterized by enlarged.
endoluminal proliferation of capillaries, which may Light microscopy of the erythematous papules
obliterate the lumen, along with the presence of showed peri-adnexal histocytic aggregates admixed
histiocytes within thesevascular lumina [3]. These lesions with a few lymphocytes, with a normal overlying
disappear on resolution of the underlying cause which epidermis, suggestive of Borderline Lepromatous
precipitated it. leprosy. The nodules from the lower limb showed a

Indian
© Red Journal of Pathology:Pvt.
Flower Publication Research
Ltd. and Practice / Volume 7 Number 6 / June 2018
806 Poorvi Kapoor, Vishwanath B.K., Vardendra Kulkarni et al. / Reactive Angioendotheliomatosis in the Setting
of Leprosy: A Previously Un-Described Association

dermal lesion composed of numerous capillary sized blood


vessels lined by plump endothelium, some containing
erythrocytes, which were surrounded by a sparse
lymphocytic infiltrate. This lesion appeared to be within a
pre-existing thrombosed, large vessel in the dermis. There
were no features of atypia in the lesion.
Immunohistochemistry for CD34 and CD31 showed
positivity for the cells lining these vessels, confirming
their vascular origin.

Fig. 4: Borderline lepromatous leprosy showing aggregates of histiocytes


in peri-adnexal location with few admixed lymphocytes.

Fig. 1: Shows erythematous papules of leprosy

Fig. 5: Reactive angioendotheliomatosis with proliferating capillaries


seen within a thrombosed vessel containing few erythrocytes.
CD34
CD31

Fig. 2: Shows a firm nodule of RAE

Fig. 6: Reactive angioendotheliomatosis with proliferating capillaries


Fig. 3: Borderline lepromatous leprosy showing aggregates of histiocytes seen within a thrombosed vessel containing few erythrocytes.
in peri-adnexal location with few admixed lymphocytes. CD34
CD31

Indian Journal of Pathology: Research and Practice / Volume 7 Number 6 / June 2018
Poorvi Kapoor, Vishwanath B.K., Vardendra Kulkarni et al. / Reactive Angioendotheliomatosis in the Setting 807
of Leprosy: A Previously Un-Described Association

involvement and has been extensively studied. Chronic


inflammation, caused by leprosy leads to release of
cytokines and chemokines, which in turn causes
endothelial cell activation. This causes vasodilation,
proliferation and angiogenesis [13]. Certain recent studies
have proven angiogenesis by demonstrating positivity
for CD31 and CD105 [14]. Increased Vascular endothelial
growth factor (VEGF) and tissue factor was observed in
non-reactional leprosy by Noguiera MRS et al in their
study [15].
It has been surmised that the proliferation of
vasculature in RAE is in response to hypoxia induced by
occlusive or sub-occlusive processes, especially those
Fig. 7: Endothelial cells show positivity for CD34 induced by chronic inflammatory processes. The theory
that all the various types of CRA are a continuum of this
evolving response to microthrombi has been proposed,
with the early stages showing proliferation of histiocytes
within the vascular luminaand later showing a
proliferation of endothelial cells and pericytes [16].
Depending on the time of biopsy and severity of
underlying condition, the variations in histological
presentation have been proposed. Studies have shown
that separate treatment is not needed for RAE, instead,
treatment of underlying disorder will cause resolution
of these lesions as well.
Leprosy shows an increase in endothelial expression
and markers of angiogenesis, indicates that the same
process which induces angiogenesis, may as well induce
Fig. 8: Endothelial cells show positivity for CD31
vascular proliferation seen in RAE.
Treatment of leprosy with certain anti-angiogenic
Discussion factors has been speculated to reduce damage by
Reactive angioendotheliomatosis has been leprosy reactions and treatment with these factors may
considered a benign vascular disorder, whose exact help in the further management of leprosy [15]. RAE lesions
aetiopathogenesis is not yet completely understood. It may well respond to this line of therapy due to the same
was first reported by Gottron and Nikolowsky [4]. It is pathogenesis.
considered to be a marker of an underlying systemic illness Due to strong suspicion of leprosy, but different
[5]. It has been associated with deposition of cryoproteins appearing skin lesions, both the painless and painful
within the lumen, with anti-phospholipid syndrome,as well lesions were sampled, albeit at a time gap of nearly three
as chronic disseminated intravascular coagulation and weeks. Further systemic illnesses were not looked for, as
chronic lymphocytic leukaemia [6-9]. In a study of 15 cases there was clear-cut clinical and histological evidence of
by McMenamin ME et al, it was found that 11 cases had leprosy in this case.
associated systemic diseases like renal disease, alcoholic
cirrhosis, glioblastomamultiforme and rheumatoid
arthritis [10]. Most of the reported cases have included Conclusion
conditions such as sub-acute bacterial endocarditis [4],
Leprosy, being a chronic inflammatory condition with
tuberculosis [11], liver failure [12] and renal failure [10].
significant angiogenesis, helps support the pathogenesis
Hitherto, none of the reported cases so far show an
of RAE and helps explain the occurrence of two different
association with leprosy.
types of lesions in the same patient. It is imperative to
RAE presents variably, and macules, papules, nodules sample different looking lesions, to ensure that a co-
and plaque formation have been reported. They may existing lesion not be mistaken as being a part of the
occasionally ulcerate and undergo necrosis [10]. same disease. Treatment with anti-angiogenic factors
Leprosy is a chronic granulomatous disease caused may not only take care of the damage caused in leprosy
byMycobacterium leprae. It manifests as neural and skin by host-response, but may also aid in resolution of RAE.

Indian Journal of Pathology: Research and Practice / Volume 7 Number 6 / June 2018
808 Poorvi Kapoor, Vishwanath B.K., Vardendra Kulkarni et al. / Reactive Angioendotheliomatosis in the Setting
of Leprosy: A Previously Un-Described Association

Acknowledgements Dermatol 2003;44:151–55.


8. Bolton-Maggs PH, Rustin MH. Diffuse angioma-like
We would like to thank Dr.Sneha S Gandhi for her changes associated with chronic DIC. ClinExpDermatol
valuable insight,acumen and accurate inputs. 1988;13:180-2.
9. Mariñas EA, Vidaurrazaga N, Burgos-Bretones JJ, et al.
Conflicts of Interest Cutaneous reactive angiomatosis associated with chronic
lymphoid leukemia. Am J Dermatopathol 2008;30:604-7.
There are no conflicts of interest.
10. McMenamin ME, Fletcher CDM. Reactive Angioendotheliomatosis.
A Study of 15 Cases Demonstrating a Wide Clinicopathologic
Spectrum. Am J SurgPathol 2002;26:685-97.
References
11. Wick MR, Rocamora A. Reactive and malignant
1. Rongioletti F, Rebora A: Cutaneous reactive ‘angioendotheliomatosis’: a discriminant clinicopathologic
angiomatoses: patterns and classification of reactive study. J CutanPathol 1988;15:260–71.
vascular proliferation. J Am AcadDermatol 2003;49:887-96. 12. Quinn TR, Alora MB, Momtaz KT, et al. Reactive
2. Requena L, El-Shabrawi-Caelen L, Walsh SN, Segura S, angioendotheliomatosis with underlying hepatopathy and
Ziemer M, Hurt MA, Sangüeza OP, Kutzner H: hypertensive portal gastropathy. Int J Dermatol 1998;
Intralymphatichistiocytosis. A clinicopathologic study of 37:382–5.
16 cases. Am J Dermatopathol 2009;31:140-51. 13. Huggenberger R, Detmar M. The cutaneous vascular system
3. Patterson JW editor.Vascular tumors. In: Weedon’s skin in chronic skin inflammation. J InvestigDermatolSympProc
pathology. 4th Ed. Churchill Livingstone: China 2016 2011;15:24-32. doi:https://doi.org/10.1038/jidsymp.2011.5.
pp.888-925. 14. Soares CT, Rosa PS, Trombone APF, Fachin LRV, Ghidella
4. Gottron HA, Nikolowski W. ExtrarenaleLohlei- CC, Ura S, et al. Angiogenesis and Lymphangiogenesis in
Herdnephrtis der Haut bei Endocarditis. Arch the Spectrum of Leprosy and Its Reactional Forms. PLoS
KlinExpDermatol 1958;207:156–76. ONE 2013;8(9):e74651. https://doi.org/10.1371/journal.
5. LeBoit PE et al. Vascular tumours. In: Pathology and pone.0074651.
genetics of skin tumours. 3rd Ed. Lyon: IARC, 2006.pp.233- 15. Nogueira MRS, Latini ACP, Nogueira MES. The involvement
46. of endothelial mediators in leprosy.Memórias do
6. LeBoit PE, Solomon AR, Santa Cruz DJ, et al. Angiomatosis InstitutoOswaldo Cruz. 2016;111(10):635-41.
with luminal cryoprotein deposition. J Am AcadDermatol 16. Corti MA, Rongioletti F, Borradori L, Beltraminelli H.
1992;27:969–73. Cutaneous reactive angiomatosis with combined
histological pattern mimicking a cellulitis. Dermatology
7. Thai K-E, Barrett W, Kossard S. Reactive angioendotheliomatosis
2013;227:226-30.
in the setting of antiphospholipid syndrome. Australas J

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References Organization; 1997.
List references in alphabetical order. Each listed
reference should be cited in text (not in alphabetic Reference from electronic media
order), and each text citation should be listed in the [9] National Statistics Online—Trends in suicide by
References section. Identify references in text, tables, method in England and Wales, 1979-2001. www.statistics.
and legends by Arabic numerals in square bracket (e.g.
Indian Journal of Pathology: Research and Practice / Volume 7 Number 6 / June 2018
Guidelines for Authors 811

downloads/theme_health/HSQ 20.pdf (accessed Jan form and copyright transfer form has to be submitted
24, 2005): 7-18. Only verified references against the in original with the signatures of all the contributors
original documents should be cited. Authors are within two weeks of submission. Hard copies of images
responsible for the accuracy and completeness of their should be sent to the office of the journal. There is no
references and for correct text citation. The number of need to send printed manuscript for articles submitted
reference should be kept limited to 20 in case of major online.
communications and 10 for short communications.
More information about other reference types is Reprints
available at www.nlm.nih.gov/bsd/uniform_requirements.
html, but observes some minor deviations (no full stop Journal provides no free printed reprints, however a
after journal title, no issue or date after volume, etc). author copy is sent to the main author and additional
copies are available on payment (ask to the journal
office).
Tables
Tables should be self-explanatory and should not Copyrights
duplicate textual material.
The whole of the literary matter in the journal is
Tables with more than 10 columns and 25 rows are copyright and cannot be reproduced without the
not acceptable. written permission.
Table numbers should be in Arabic numerals,
consecutively in the order of their first citation in the
text and supply a brief title for each. Declaration
Explain in footnotes all non-standard abbreviations A declaration should be submitted stating that the
that are used in each table. manuscript represents valid work and that neither this
manuscript nor one with substantially similar content
For footnotes use the following symbols, in this
under the present authorship has been published or is
sequence: *, ¶, †, ‡‡,
being considered for publication elsewhere and the
authorship of this article will not be contested by any
Illustrations (Figures) one whose name (s) is/are not listed here, and that the
Graphics files are welcome if supplied as Tiff, EPS, or order of authorship as placed in the manuscript is final
PowerPoint files of minimum 1200x1600 pixel size. The and accepted by the co-authors. Declarations should be
minimum line weight for line art is 0.5 point for optimal signed by all the authors in the order in which they are
printing. mentioned in the original manuscript. Matters appearing
in the Journal are covered by copyright but no objection
When possible, please place symbol legends below
will be made to their reproduction provided permission
the figure instead of to the side.
is obtained from the Editor prior to publication and due
Original color figures can be printed in color at the acknowledgment of the source is made.
editor’s and publisher’s discretion provided the author
agrees to pay.
Approval of Ethics Committee
Type or print out legends (maximum 40 words, We need the Ethics committee approval letter from
excluding the credit line) for illustrations using double an Institutional ethical committee (IEC) or an
spacing, with Arabic numerals corresponding to the institutional review board (IRB) to publish your Research
illustrations. article or author should submit a statement that the
study does not require ethics approval along with
Sending a revised manuscript evidence. The evidence could either be consent from
patients is available and there are no ethics issues in the
While submitting a revised manuscript, contributors
paper or a letter from an IRB stating that the study in
are requested to include, along with single copy of the
question does not require ethics approval.
final revised manuscript, a photocopy of the revised
manuscript with the changes underlined in red and
copy of the comments with the point to point Abbreviations
clarification to each comment. The manuscript Standard abbreviations should be used and be spelt
number should be written on each of these documents. out when first used in the text. Abbreviations should not
If the manuscript is submitted online, the contributors’ be used in the title or abstract.

Indian Journal of Pathology: Research and Practice / Volume 7 Number 6 / June 2018
812 Guidelines for Authors

Checklist Numerals from 1 to l0 spelt out


• Manuscript Title • Numerals at the beginning of the sentence spelt
out
• Covering letter: Signed by all contributors
• Previous publication/ presentations mentioned,
Source of funding mentioned Tables and figures
• Conflicts of interest disclosed • No repetition of data in tables and graphs and in
text.
• Actual numbers from which graphs drawn,
Authors
provided.
• Middle name initials provided.
• Figures necessary and of good quality (color)
• Author for correspondence, with e-mail address
• Table and figure numbers in Arabic letters (not
provided.
Roman).
• Number of contributors restricted as per the
• Labels pasted on back of the photographs (no
instructions.
names written)
• Identity not revealed in paper except title page (e.g.
• Figure legends provided (not more than 40 words)
name of the institute in Methods, citing previous
study as ‘our study’) • Patients’ privacy maintained, (if not permission
taken)
• Credit note for borrowed figures/tables provided
Presentation and Format
• Manuscript provided on a CDROM (with double
• Double spacing
spacing)
• Margins 2.5 cm from all four sides
• Title page contains all the desired information. Submitting the Manuscript
Running title provided (not more than 50
characters) • Is the journal editor’s contact information current?

• Abstract page contains the full title of the • Is the cover letter included with the manuscript?
manuscript Does the letter:

• Abstract provided: Structured abstract provided 1. Include the author’s postal address, e-mail address,
for an original article. telephone number, and fax number for future
correspondence?
• Key words provided (three or more)
2. State that the manuscript is original, not previously
• Introduction of 75-100 words published, and not under concurrent consideration
• Headings in title case (not ALL CAPITALS). elsewhere?
References cited in square brackets 3. Inform the journal editor of the existence of any
• References according to the journal’s instructions similar published manuscripts written by the
author?
Language and grammar 4. Mention any supplemental material you are
• Uniformly American English submitting for the online version of your article.
Contributors’ Form (to be modified as applicable
• Abbreviations spelt out in full for the first time. and one signed copy attached with the manuscript)

Indian Journal of Pathology: Research and Practice / Volume 7 Number 6 / June 2018

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