GYNECOLOGY PLENARY 4

Canlas I, Canseco K, Caoile MC, Carino UV, Catibog IB, Charmino C, Chu B, Chua NV, Cinco NK

HISTORY, SALIENT FEATURES, APPROACH TO DIAGNOSIS

The Case
18 year old Nulligravid CC: foul-smelling vaginal discharge not associated with any other signs and symptoms PSHx: works as a GRO in a karaoke club, and admits to having sexual activity with her clients

Physical Examination
Pelvic Examination: Within normal limits. Speculum Exam:
2x2 cm shallow erosion on the anterior lip of the cervix moderate amounts of yellow-brown foul smelling discharge

Diagnostic Workup
cervical discharge was collected for Pap smear Acetic acid was applied lesion turned acetowhite Pap and Colposcopy: punctuations, presence of koilocytes and dysplastic cells Biopsy: CIN II

Salient Features
18 year old nulligravid foul-smelling vaginal discharge GRO (+) sexual activity Pelvic Examination: Within normal limits. Speculum Exam: 2x2 cm shallow erosion on the anterior lip of the cervix, moderate amounts of yellow-brown foul smelling discharge Pap and Colposcopy: acetowhite epithelium, punctuations, presence of koilocytes and dysplastic cells Biopsy: CIN II

Approach to Diagnosis

Bacterial Vaginosis, Trichomonal Vaginosis, Gonorrhea, Chlamydia

DIFFERENTIAL DIAGNOSIS

Trichomonal Vaginosis
Rule IN Yellow-brown foul smelling vaginal discharge (+) sexual activity Rule OUT absence of accompanying symptoms, such as dyspareunia and vulvar irritation failure of pap smear to reveal T. Vaginalis

Bacterial Vaginosis
Rule IN Foul smelling vaginal discharge (+) sexual activity Rule OUT Absence of the characteristic discharge of BV: thin, gray, and homogenous failure of pap smear to reveal clue cells

Gonorrhea
Rule IN Foul smelling vaginal discharge (+) sexual activity Rule OUT Discharge was yellow brown in contrast to gonorrhea which has creamy or green, pus like or bloody vaginal discharge

Chlamydia
Rule IN Foul smelling vaginal discharge (+) sexual activity Rule OUT Discharge was yellow brown in contrast to Chlamydia which has milky or mucuslike vaginal discharge

WORKING DIAGNOSIS

Working Diagnosis
Cervical Intraepithelial Neoplasia II

CERVICAL INTRAEPITHELIAL NEOPLASIA (CIN)

Dysplasia
cervical epithelial atypia that is intermediate between the normal epithelium and CIS mild, moderate and severe depending on the degree of involvement of the epithelial thickness by the atypical cells

Cervical Intraepithelial Neoplasia (CIN)

denote the whole range of cellular atypia confined to the epithelium CIN 1 = mild dysplasia CIN 2 = moderate dysplasia CIN 3 = severe dysplasia and CIS

Koilocytic or Condylomatous Atypia

human papillomavirus (HPV) infection atypical cells with a perinuclear cavitation or halo in the cytoplasm indicating the cytopathic changes due to HPV infection

Etiopathogenesis of CIN
certain oncogenic types of human papillomaviruses (HPV) sexual intercourse at an early age multiple sexual partners Multiparity long-term oral contraceptive use tobacco smoking low socioeconomic status infection with Chlamydia trachomatis micronutrient deficiency diet deficient in vegetables and fruits HPV types 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59 and 68 are strongly associated with CIN and invasive cancer

Clinical Features of CIN

no specific symptoms and no characteristic clinical features turn white on application of 3-5% acetic acid iodine-negative on application of Lugols iodine solution

Diagnosis and Grading of CIN by cytology

Nuclear enlargement with variation in size and shape, and Irregular chromatin distribution with clumping Hyperchromasia Low grade CIN: Abnormal nuclei in superficial or intermediate cells High grade CIN: abnormality in nuclei of parabasal and basal cells nuclear-cytoplasmic ratio: one of the most important basis for assessing the grade of CIN Increased ratios:more severe degrees of CIN

Diagnosis and grading of CIN by histopathology

CIN 1
minimal nuclear abnormalities few mitotic figures Undifferentiated cells are confined to the deeper layers (lower third) of the epithelium

Diagnosis and grading of CIN by histopathology

CIN 2
dysplastic cellular changes mostly restricted to the lower half or the lower twothirds of the epithelium more marked nuclear abnormalities

Diagnosis and grading of CIN by histopathology

CIN 3
differentiation and stratification may be totally absent or present only in the superficial quarter of the epithelium with numerous mitotic figures Nuclear abnormalities extend throughout the thickness of the epithelium

Natural History of Cervical Cancer Precursor

CIN Category Regression Persistence Progression to CIN3 11% 22% Progression to Invasive Cancer 1% 1.5% 12%

CIN 1 CIN 2 CIN 3

57% 43% 32%

32% 35% 56%

DIAGNOSTIC WORK-UPS

Acetic Acid Test

attractive alternative to PAP smears
ease of use, low-cost and fewer physician visits any trained nurse or physician able to use a speculum can do the test.

Tools needed: speculum, lamp, cotton swab, and acetic acid (vinegar); there is no pathologist or physician needed. (-) test: patient can be told immediately without having to return to the doctor for results.

Acetic Acid Test

5% acetic acid is applied to the cervix with a large cotton swab and left for 30-60 seconds, after which the cervix is visually examined with the naked eye and a lamp. Pre-cancerous lesions with a higher ratio of intracellular proteins turn white when combined with acetic acid. Normal cervices without any precancerous lesion do not change color.

Acetic Acid Test

The result of the acetic acid wash test of the patient is an acetowhite epithelium, an indication that it is a pre-cancerous lesion.

Papanicolaou Test
checks for changes in the cervix that may become cancerous abnormal early precancer changes called dysplasia or cervical intraepithelial neoplasia (CIN). Dysplasia and CIN are graded as mild, moderate, or severe. Mild dysplasia (CIN 1) usually goes away on its own. Moderate (CIN 2) and severe (CIN 3) dysplasia indicate more serious changes.

Colposcopy
most commonly used in the diagnosis of cervical intraepithelial neoplasia (CIN) and lower genital tract carcinoma (Dresang, 2005). A colposcope, a specialized camera, is utilized to examine an illuminated, magnified view of the cervix, the tissue of the vagina, and vulva.

Colposcopy
Low power (2x to 6x): to obtain a general impression of the surface architecture. Medium (8x to 15x) and high (15x to 25x): utilized to evaluate the vagina and cervix. higher powers: necessary to identify certain vascular patterns which may indicate the presence of more advanced precancerous or cancerous lesions

Colposcopy
Using cotton swabs, an acetic acid solution and iodine solution (Lugol's or Schiller's) are applied to the surface to improve visualization of abnormal areas. The transformation zone is a critical area on the cervix where many precancerous and cancerous lesions most often arise.

Colposcopy
The observation of a well demarcated, dense, opaque, acetowhite area closer to or abutting the squamocolumnar junction in the transformation zone after application of 5% acetic acid is critical.
the most important of all colposcopic signs, and is the hallmark of colposcopic diagnosis of cervical neoplasia.

Colposcopy
Other abnormal colposcopic findings most frequently observed include: punctated blood vessels mosaics white rings around the gland openings

Colposcopy
The colposcopy examination, as well as the Pap smear, revealed presence of dysplastic cells as well as koilocytes which are atypical cells with a perinuclear cavitation or halo in the cytoplasm indicating the cytopathic changes due to HPV infection.

Biopsy
Patients with malignant findings on colposcopy or cytology are frequently subjected to cervical biopsy. The technique of cervical biopsy includes: 1. Punch biopsy: involves the removal of a small piece of tissue from the cervix and one or more punch biopsies may be performed on different areas of the cervix. 2. cone biopsy or conization: utilizes a laser or scalpel to remove a large cone-shaped piece of tissue from the cervix.

Biopsy
CIN is the preinvasive stage of cervical cancer. It denotes atypical changes in the transformation zone, the part of the cervix in which exposed normal columnar epithelium is gradually replaced by normal squamous epithelium through metaplasia (Boskey, 2010).

Biopsy
The biopsy results of the patient revealed a histologic diagnosis of CIN Grade 2, that is, dysplastic cellular changes are mostly restricted to the lower half or the lower twothirds of the epithelium, with more marked nuclear abnormalities than in CIN 1.

Adjunctive Studies for further investigation of Probable STIs

Bacterial Vaginosis and Trichomonal Vaginitis Gonorrhea Chlamydia

Bacterial Vaginosis and Trichomonal Vaginitis

Wet mount.
vaginal discharge mixed with saline solution on a microscopic slide presence of white blood cells and clue cells

Whiff test
Potassium Hydroxide (KOH) added to vaginal discharge strong fishy odor

Gram stain
presence of increased number of leukocytes along with the motile trichomonads, large gram positive rods (Lactobacillus), small gram variable rods (Gardnerella), small gram negative rods (Bacteroides), and curved gram variable rods (Mobiluncus) 0 is negative, 4-6 is intermediate, and 7-10

Gonorrhea
Thayer-Martin Medium Culture
sample specimen like body fluids combined with substances that promote only the growth of gonorrhea bacteria.

Nucleic Acid Amplification Test (NAAT)

designed to amplify nucleic acid sequences that are specific for the organism being detected ability of NAATs to detect N. gonorrhoeae without a pelvic examination or intraurethral swab specimen is a key advantage of NAATs

Chlamydia
Polymerase Chain Reaction (PCR)
detects or finds the genetic material (DNA) of Chlamydia bacteria most sensitive test available

Direct Florescent Antibody (DFA) Test

detects antigen the Major Outer Membrane Protein (MOMP) or lipopolysaccharide by the antigen-antibody reaction Specimen is obtained with a swab or endocervical brush rolled over a slide to be fixed and stained Only Chlamydia trachomatis will stain with the anti-MOMP antibodies

Chlamydia
Enzyme Immunoassay (EIA)
detect chlamydial lipopolysaccharide with a monoclonal or polyclonal antibody that has been labeled with an enzyme colorless substrate colored product detected by a spectrophotometer

Observation and Immediate Treatment, Future Management Plans, On whether vaccines will benefit the patient

MANAGEMENT

MANAGEMENT

OBSERVATION

IMMEDIATE TREATMENT

patient is an adolescent
CIN 2 lesions in adolescents regress spontaneously at higher rates

MANAGEMENT

OBSERVATION
Counselling

IMMEDIATE TREATMENT

Follow-up after 4-6 months for 24 months

Pap smear

Colposcopy

NORMAL (2x)
ANNUAL PAP SMEAR

PERSISTENT Lesions for PERSISTENT Lesions 24 months

MANAGEMENT

OBSERVATION

IMMEDIATE TREATMENT

patient may fail to followup

MANAGEMENT

OBSERVATION

IMMEDIATE TREATMENT
Ablative Method Excision Method LEEP
Cryotherapy

Cryotherapy
most practical and cost-effective method of treatment an ablative method: physically destructive therapeutic procedure for lesions involving the ectocervix; endocervical canal lesions not included

Cryotherapy
done by placing a probe against the cervix which cools the cervix to sub-zero temperatures effective destruction temperature:
-20 to -30C

commonly used gases:

CO2 and NO2 (cool below -20 to -30C)

Cryotherapy
If living tissue is frozen to a temperature of 20C or lower for at least 1 minute cryonecrosis ensues rapid freeze followed by a slow thaw is the most damaging to cells, especially neoplastic cells sequence of two freeze-thaw cycles may produce more tissue destruction than a single cycle

Cryotherapy
Healing period

takes place throughout the first 6 weeks after cryotherapy patient may experience some mild cramps and a clear or lightly bloodstained watery discharge for up to 4-6 weeks after treatment Donts

use a vaginal douche or tampons have sexual intercourse for one month after treatment

Cryotherapy
Cervical stenosis: 1% reduced mucus production: 5-10% Treatment failure: 5-10%

Cryotherapy
Advantages Limitations

Can be done in out-patient setting Less cost Less intensive labor No known adverse effect in fertility and pregnancy

Not adequate to treat lesions involving the endocervical canal No pathology specimen available for reassessment of grade of lesion present and the adequacy of removal margin Relatively long recovery time

Loop Electrosurgical Excision Procedure (LEEP)

an excision method: less destructive in tissue removal both therapeutic and diagnostic for lesions involving the endocervical canal other than the ectocervix removal of the whole lesion and the transformation zone by means of excision allows sending of the affected tissue to the histopathological laboratory for examination aim of this method is to rule out any microinvasive or occult invasive disease prior to treatment

Loop Electrosurgical Excision Procedure (LEEP)

involves the application of radiofrequency electric current on tissues should only be initiated in the patient if theres no evidence of infection present (e.g., pelvic inflammatory disease, cervicitis, vaginal trichomoniasis, and bacterial vaginosis)
If the mentioned diseases are present
delay LEEP treat infection/s first then proceed to LEEP

Loop Electrosurgical Excision Procedure (LEEP)

The least amount of power that will effectively perform the electrosurgery should be used
to minimize the risk to the patients normal tissues to ensure that the excised specimen is in an acceptable condition for pathological assessment

Loop Electrosurgical Excision Procedure (LEEP)

Healing period
The patient may be able to return to normal activities within 1 to 3 days after the procedure patient may have brown or black discharge until two weeks post-operation

Loop Electrosurgical Excision Procedure (LEEP)

Donts
use a vaginal douche, tampon have sexual intercourse for one month

Consult immediately if
discharge persists for more than two weeks discharge has become malodorous, w/ or w/o abdominal pain Profuse bleeding

Loop Electrosurgical Excision Procedure (LEEP)

surgical complications, such as intraoperative hemorrhage, postoperative hemorrhage, and cervical stenosis occur at acceptably low rates Treatment failure: 10%

Loop Electrosurgical Excision Procedure (LEEP)

Advantages Limitations

able to adequately excise the majority of cervical lesions including those in the endocervical canal Provides tissue for examination Less pain/painless Minimal bleeding

May be associated w/ increased obstetrical risks, like premature delivery and low birth weight (not applicable to the patient)

Future Plans for the Patient

Patient must never fail to follow-up after treatment so that regression, persistence, or progression of the disease, as well as treatment complications may be determined, and appropriate retreatment can be administered.

Post-Treatment Management Option No. 1

Follow-up after 9-12 months

Pap smear

Colposcopy

Cervical biopsy

ECC

NORMAL Follow-up after 3-5 years Pap smear & Colposcopy

PERSISTENT LESIONS Retreat (Cryotherapy or LEEP)

Post-Treatment Management Option No. 2 (if treated w/ LEEP)

Inadequate Margin Excision Follow-up after 3,9,& 15 months

Adequate Margin Excision Follow-up after 9-12 months

Pap smear

Colposcopy

Cervical biopsy

ECC

NORMAL Follow-up after 3-5 years Pap smear & Colposcopy

PERSISTENT LESIONS Retreat (Cryotherapy or LEEP)

Post-Treatment Management Option No. 3

Follow-up after 4-6 months Pap smear 3x

Results Negative 3x Annual Pap Smear

ASCUS PRESENT in any Pap Smear Colposcopy Retreat as indicated (Cryotherapy or LEEP)

Post-Treatment Management Option No. 4

Follow-up after 6 months HPV DNA Testing

HPV negative Annual Pap Smear

HPV positive
Colposcopy Retreat as indicated (Cryotherapy or LEEP)

Will Vaccination Benefit the Patient?

These vaccines may not benefit the patient, as these only have prophylactic effects and dont have proven therapeutic effects:
Cervarix (bivalent vaccine against HPV 16 & 18) Gardasil (quadrivalent vaccine against HPV 6, 11, 16, &18)

Will Vaccination Benefit the Patient?

However, recent studies have revealed the promising therapeutic effects of some vaccines in the reduction of pre-cancerous cervical lesions
vaccinia virus recombinant MVA E2 HPV16 L1E7 chimeric virus-like particles (CVLP)