OS 215: Reproduction and Hormonal Regulation EXAM 1

Lecture 2: Ovarian and Fallopian Tube Pathology

Dr. Agustina Abelardo November 6, 2014

TOPIC OUTLINE  symptoms mimic acute abdomen/ectopic

I. Ovarian Disorders pregnancy
A. Follicular Cyst
B. Corpus Luteum Cyst
C. PCOS
D. Pregnancy Luteoma
II. Ovarian Tumors
A. Clinical Findings in Ovarian Tumors
B. Classification
C. General Features of Surface Epithelial-
Stromal Tumors
D. Hereditary Ovarian Cancer
E. Clinical and Molecular Features of 5 Most
Common Types
III. Fallopian Tube Disorders Figure 2. Gross specimen showing a Corpus Luteum
A. Hydatid Cyst of Morgagni cyst. Has bright yellow peripheral lining when it is cut
B. PID open with a hemorrhagic center
C. Usual Bacterial Salpingitis
D. Salpingitis Isthmica Nodosa (SIN)
E. Ectopic Pregnancy
IV. Tumors of the Fallopian Tube
A. Benign
B. Malignant
C. Secondary tumors

I. OVARIAN DISORDERS
A. Follicular Cyst
 Most common ovarian mass
 Non-neoplastic cyst, accumulation of fluid in a follicle
 Should be >2.5 cm
 Originate from an unruptured Graafian follicle or a
ruptured one but immediately resealed; so lined by:
o Inner Granulosa Cells – flattened out by serous
fluid
o Outer Theca Cells – pale appearance (luteinized)
w/ included cytoplasm
 Accumulation of fluid within follicle so it may rupture
o rupture may lead to sterile peritonitis with pain
Figure 1. Follicular cyst histology with theca,
granulosa cells.
 Tumors arising from granulosa cell layer are called
Granulosa Cell Tumor
o Granulosa cells are described as coffee bean
shaped/ovoid having a central cleavage
 Tumors arising from thecal layer are called thecoma
 Tumors arising from the stroma is known as fibroma
Figure 3. Histologic section of a hemorrhagic corpus
luteum cyst. Luteinized granulosa cells lining the
hemorrhagic area to the right. These contain abundant
eosinophilic and granular cytoplasm. The luteinized theca
cells in outer border
C. Polycystic Ovarian Syndrome
 Complex endocrine disorder characterized by
hyperandrogenism, menstrual abnormalities,
polycystic ovaries, chronic anovulation, and
decreased fertility
 Also associated with obesity, type 2 diabetes, and
premature atherosclerosis
 In young women with irregular bleeding due to chronic
anovulation, hirsutism, and/or infertility
 Abnormal gonadotropin release (low FSH, high LH),
hyperandrogenemia, elevated serum estrone level
 Endometrium varies from inactive to hyperplastic
D. Pregnancy Luteoma
 Well circumscribed nodule which contains spaces
filled with pale fluid or colloid-like material, consists of
luteinized cells
 Physiologic response to elevated gonadotropins
 Degenerate within days to weeks postpartum to
shrunken nests of degenerating lipid-filled luteoma
cells

B. Corpus Luteum Cyst II. OVARIAN TUMOR

 Most common ovarian mass in pregnancy
 Non-neoplastic cyst
 Also >2.5cm
 Corpus means body and Luteum means yellow so
”yellow body”
 Most common ovarian mass in pregnancy
 May also be seen in H mole
 Remnant of follicle after ovulation
o Has bright yellow outer (luteinized theca) lining
 May accumulate fluid and blood inside the cyst
o Due to delayed resolution of central cavity of
corpus luteum
 Rupture of this accumulation leads to
hemoperitoneum
 Primary ovarian tumors are classified based on the
tissue of origin. The three ovarian components are:
o Surface epithelium
o Germ cells
o Stroma
 Secondary or metastatic ovarian tumors come from
non-ovarian origins (ex. colon, appendix, breast)
A. Clinical Findings of Ovarian Tumors
 Signs of seeding from malignant surface
o Derived cancers: malignant ascites and
increased abdominal girth
o Induration of rectal pouch on digital rectal exam
o Increased obstruction with colicky pain
 Palpable ovarian mass in a postmenopausal woman
o ovaries should not be palpable if postmenopause
 Malignant pleural effusion
o Common site for ovarian cancer metastasis

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 Ovarian and Fallopian Tube Pathology OS 215

 Cystic teratomas undergo torsion leading to infarction o Endometrioid

o Radiographs show calcifications from bone and  Malignant tumors associated with
teeth endometrial CA (15-30% of cases)
 Signs of hyperestronism from estrogen-secreting  Resemble endometrial CA
tumors  Commonly bilateral
o Bleeding from endometrial hyperplasia/ cancer
o 100% superficial squamous cells in cervical pap
smear
 Hirsutism or virilization from androgen-secreting
tumors
 Tumor markers
o Increased serum cancer antigen 125 (CA 125
and HE4: only increased in surface-derived
malignant tumors)
o For assessment of ovarian neoplasms before and
after treatment

B. Classification of Ovarian Tumors Figure 6. Endometrioid adenofibroma: High

SURFACE EPITHELIUM TUMORS power view showing glands and squamous
 Accounts for 65% -70% of ovarian tumors morules. Squamous morules may be associated
 Derived from coelomic epithelium with loose stromal reaction which should not be
o malignant tumors commonly seed the omentum mistaken for desmoplasia of cancer.
 Three major histologic types based on the
differentiation of the neoplastic epithelium o Clear cell
o Serous  Multiple complex papillae lined by clear or
o Mucinous hobnail cells with eccentric bulbous nuclei
o Endometrioid  Rarely bilateral
 Can also be classified based on the proliferation of
epithelium leading to > benign (-oma), borderline
(LMP), malignant (-carcinoma)
o Serous
 most common group of primary benign &
malignant tumors
 cysts lined by ciliated cells (similar to
fallopian tube)
 most tumors that are bilateral
 psammoma bodies

Figure 7. Clear-cell carcinoma. Note the eccentric nuclei

and abundant clear cytoplasm as well as a chronic
inflammatory infiltrate

a o Brenner
 Usually benign
 Contain Walthard’s nests (transitional-like
epithelium)

b
Figure 4. Microphotographs of a serous cystadenoma
in (a) scanning view and (b) showing the columnar
epithelium
o Mucinous
 Cysts lined by mucus-secreting cells (similar
to endocervix)
 Large multiloculated tumors
 Seeding produces pseudomyxoma peritonei
 mucinous material in abdominal cavity;
causes distension
Figure 5. Microphotograph of a mucinous
cystadenoma.
Figure 8. Micrograph of a Brenner tumour (H&E stain).
Observe the histologic detail of characteristic epithelial
nests within the ovarian stroma
GERM CELL TUMORS
 Account for 15% to 20% of ovarian tumors, relatively
small number of tumors
o Teratoma/ Cystic teratoma: Usually benign;
less than 21% become malignant (usually
squamous cancer; ectodermal differentiation
(hair, sebaceous glands, teeth) most prominent;
most of these derivatives are found in nipple-like
structure in the cyst wall called Rokistansky
tubercle
 Immature malignant types: contain mature
and immature elements (e.g. muscle,
neuroepithelium)
 Struma ovarii type: has functioning thyroid
role

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Figure 9. Teratoma. The benign teratoma shown here
contains cartilage, adipose tissue, and intestinal glands on
the right; on the left, there are a lot of thyroid follicles. This
is aspecialized form of teratoma termed struma ovarii.
o Dysgerminoma: same histologic picture as
seminoma of testis; characteristic increase in
serum LDH; associated with streak gonads of
Turner’s syndrome
Figure 10. Dysgerminoma. This neoplasm is composed
of sheets and cords of large polyhedral cells with large
nuclei and pale pink to watery cytoplasm. There is a scant
lymphoid infiltrate and virtually no fibrous stroma.
o Yolk sac tumor: malignant tumor being most
common in girls <4yo; contain Schiller-Duval
bodies (glomerulus-like structure composed of a
central blood vessel enveloped by tumor cells
within a space that is also lined by tumor cells);
increased AFP
Figure 11. Yolk sac carcinoma showing a Schiller-
Duval body
SEX CORD STROMAL TUMORS
 Account for 3-5% of ovarian tumors, derived from
stromal cells; may be hormone producing
 All cell types from undifferentiated gonadal
mesenchyme (Sertoli, Leydig, theca and granulosa
cells) can be identified in the ovary
 Can be feminizing or masculinizing depending on the
cell type of the tumor
o Thecoma-fibroma: benign tumor associated with
Meig’s syndrome (ascites, R-sided pleural
effusion); regression of the effusions follows
removal of tumor
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Ovarian and Fallopian Tube Pathology OS 215
Figure 12. Thecoma-fibroma
o Granulosa cell tumor: low grade malignant
tumor; feminizing tumor (produces estrogen) that
contains Call-exner bodies (small, distinctive,
gland-like structures filled with an acidophilic
material recall immature follicles)
Figure 13. Granulosa cell tumor
o Sertoli-Leydig cell: benign masculinizing tumor
(produces androgen); pure Leydig cell tumors
contain cells with crystals of Reinke
Figure 14. Sertoli-Leydig Cell Tumor
o Gonadoblastoma: malignant tumor with mixture
of germ cell tumor (dysgerminoma) and sex-cord
stromal tumor; associated with abnormal sexual
development in 80% of cases; commonly calcify
METASTATIC TUMORS
 From FGT: tubal, cervical, endometrial CA, uterine
sarcomas, trophoblastic tumors, vulvar & vaginal
tumors
 Breast CA
 CA of stomach including Krunkenberg tumor
characterized by mucin filled signet ring cells within a
cellular stroma
 Intestinal CA, lung CA, kidney urinary bladder, and
ureteral CA
 Tumors of appendix (appendix: origin of mucinous
neoplasms)
 Tumors of pancreas, liver, biliary tract
o Krukenberg tumor: contains signet-ring cells from
hematogenous spread usually of a gastric cancer
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 Ovarian and Fallopian Tube Pathology OS 215
o serous tumors: poor prognosis
 Clinical: adnexal mass, ascites, elevated serum level
of CA 125; CA19-9 in mucinous tumors
 Stromal component: may secrete estrogenic or
androgenic hormones (functioning stroma)

D. Hereditary Ovarian Cancer

Figure 16. Krukenberg tumor with encircled signet ring
cell
C. General Features of Surface Epithelial-Stromal
Tumors
 Subclassified by epithelial cell type/s, relative
amounts off epithelial & stromal components, location
of epithelial elements (exophytic/endophytic/both),
growth patterns, nuclear features
 Benign tumors
o absent or minimal cellular stratification or atypia
o no invasion
 Borderline tumors (tumors of LMP)
o Epithelial stratification
o Atypia
o No invasion
 Carcinomas
o Exhibit invasion
 Grading
o As proposed by FIGO, WHO, GOG
o based on architectural and nuclear features
 two-tier grading system is used in serous carcinoma
 Family history
o Strongest risk factor in at least 10%
o Occur in younger age than sporadic counterparts
 3 syndromes
o Site-specific ovarian cancer (linked to BRCA
abnormality)
o breast-ovarian cancer syndrome (linked to BRCA
abnormality)
o hereditary nonpolyposis colorectal cancer
(HNPCC Lynch II) Syndrome (related to
mutations ins DNA mismatch repair genes, esp
MLN1, MSH2, MSH6)
 if BRCA abnormality is detected,
prophylactic mastectomy can be done (i.e.
Angelina Jolie’s case)
 BRCA-related ovarian carcinomas
o Usually HGSC (high grade serous carcinoma)
o At risk to tubal carcinoma
 HNPCC-related ovarian carcinomas
o Affected females have 40-60% lifetime risk of
developing endometrial carcinoma and 9-12%
risk of ovarian cancer (may be synchronous)
o Usual types are endometrioid and clear cell CA

E. Ovarian Carcinoma: Clinical and Molecular Features of 5 Most Common Types

HGSCA LGSCA MCA ECA CCCA
Risk Factors BRCA1/2 ? ? HNPCC ?
Precursor Lesions Tubal Serous BL tumor Cystadenoma? Atypical Atypical
intraepithelial CA BL tumor? endometriosis endometriosis
Pattern of Spread Very early Transcoelomic Usually confined to Usually confined to Usually confined to
transcoelomic spread ovary pelvis pelvis
spread
Molecular BRCA, p53 BRAF, KRAS KRAS, HER2 PTEN. ARID1A
HNF1. ARID1A
Abnormalities
Chemosensitivity High Intermediate Low High Low
Prognosis poor intermediate favorable favorable Intermediate
HGSCA= high grade serous carcinoma, LGSCA=low grade serous carcinoma, MCA=mucinous CA, ECA=endometrioid CA, CC=clear
cell, BL=borderline

III. FALLOPIAN TUBE DISORDERS C. Usual Bacterial Salpingitis

A. Hydatid Cyst of Morgagni  Acute
 Cystic mullerian remnant; often around fimbriated end
of tube

Figure 18. Histopathology of acute salpingitis. Tubal

mucosa becomes hyperemic, edematous and infiltrated
with neutrophils and the lumen becomes infiltrated with
Figure 17. Torted Hydatids of Morgagni purulent exudate. Note that neutrophils are present in the
walls and also in the lumen.
B. Pelvic Inflammatory Disease o Important cause of infertility in these areas
 Often due to N. gonorrheae or C. trachomatis o Very dull serosa with adhesion
 most often cause of hydrosalpinx o If it is cut open, a necrotic material or dilated
 other pathogens: lumen is seen which is filled with pus
o Bacteroides  Chronic
o Streptococci o The state wherein the combination of adhesions
o Clostridium and suppuration rarely permits the resolution of
acute salpingitis
o Without the intervention of antibiotics during the
acute stage, chronic inflammation ensues

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 Ovarian and Fallopian Tube Pathology OS 215
o It may persist for years resulting in fibrosis and
obstruction and is an important cause of female
infertility
o Sometimes inflammation dies down but the
obstructed tube becomes massively distended.
o There are abundant lymphoplasmacytic infiltrates
in tubal wall
o Occasionally, lymphoid follicles are formed

Figure 21. Tubal Ectopic Pregnancy

Figure 19. Comparison between a normal ampulla and
ampulla with chronic salpingitis. Note that the image on
the left shows the normal arrangement of folds in the
ampulla of fallopian tube. However, in chronic salpingitis,
tubal folds are already fused as shown in the right image.
 Tuberculous
o Dilated lumen filled with caseous or cheese-like
to cord-like material
o Granulomatous inflammation with Langhans type
multi-nucleated giant cells and caseation
necrosis
o Epithelioid cells constitute a granuloma
o Secondary to Mycobacteria
Figure 20. Granulomatous salpingitis. The figure on the
upper left is a multinucleated giant cell of the Langhans
type. The surrounding cells are the epitheloid cells
constituting a granuloma. The structure at the bottom is a
tubal gland.
IV. TUMORS OF THE FALLOPIAN TUBE
 Benign
1. Adenomatoid tumor
2. Adenomatous polyp
3. Papilloma
4. Adenofibroma
 Malignant
o Tubal carcinomas: <1% of gyne cancers
o Carriers of BRCA1 or BRCA2 germ-line
mutations are at risk more than ovarian
carcinomas
o Manifestations: seen in 2nd to 9th decades of life,
abnormal vaginal bleeding , elevated CA 125
o If BRCA-related, usually fimbrial in risk-reducing
salpingo-oophorectomy (RRSO); if not, may be
ampularry or isthmic
o Tumor is either localized or diffuse soft, gray to
pink, rarely multifocal
o 70% serous, 10%endometrioid, rest are other
types
o STIC: found in BRCA patients
o SEE-FIM (sectioning and extensive examination
of fimbira): applied for RRSO specimens to
increase frequency of detection
 Secondary Tumors
o From other female genital tract sites: direct
spread of ovarian tumor, esp. serous carcinoma
o From extragenital sites: breast, GIT, urinary
bladder
One Eight, Dominate!
End of Transcription

 Actinomycotic Eka: Happy birthday, Jay! :D

Hi Roxy, Ria, Johna, Ances, Abby! So happy
D. Salpingitis Isthmica Nodosa (SIN) we’re together ulit in BSLR-W! :*
 Invagination of mucosa to muscle
Mario: <3 This trans was made with love and affection.
 Complications:
Charoooot. Hello OTN cysts, seatmates,
o Infertility
anatomates and all the mates!
o Ectopic pregnancy
Jan: 
E. Ectopic Pregnancy
 Implantation of fetus outside the normal uterine
location, often in ampulla of tubes, also in ovaries,
abdominal cavity
 Causes: scarring from previous PID, endometriosis,
altered tubal motility
o With a background of PID, there is a
predisposition to have an ectopic pregnancy
secondary to chronic salpingitis (most common
predisposition)
 Clinical features include pain and hemoperitoneum
 Complications: rupture, abortion/death, hematosalpinx
 Diagnosis:
o B-hCG: best screening test
o Vaginal ultrasound: confirm and check for an
amniotic sac
o Laparoscopy: for equivocal cases

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