Ovarian Cancer

CHAP. 33 Ovarian Cancer

December 9 1997

1st year resident OB & GY

Sung Hee Oh. M.D

EPITHELIAL OVARIAN CANCER

90 % of ovarian cancer

from the coelomic epithelium or mesothelium

1. PATHOLOGY

*borderline tumors

"tumor of low malignant potential"

tend to remain confined to the ovary for long periods, occur predominantly in premenopausal
women and are associated with a very good prognosis

uncommon, metastatic implants may occur

The criteria for the diagnosis of borderline tumors

Epithelial proliferation with papillary formation and pseudostratification

Nuclear atypia and increased mitotic activity

Absence of true stromal invasion (without tissue destruction)

20-25% of borderline malignant tumors spread beyond the ovary

based on the histologic features of the primary tumors

1) Serous tumors

invagination of the surface ovarian epithelium

secrete serous fluid

Psammoma body

papillary ingrowths

a . borderline serous tumors

10% of all avarian serous tumors

50% occur before the age of 40 years

40% of women with ovarian serous bordeline tumors have extraovarian implants

40% of theses women eventually die of disease

non-invasive group (only three of 50)/invasive group (four of six), Bell et all

b . malignant serous carcinomas

well differentiated

: papillary and glandular structures

nuclei are uniformly round to oval with 0-2 mitoses per high powered field
poorly differentiated

: solid sheets of cells

nuclear pleomorphism, high mitotic activity usually 2-3 mitoses per HPF

2) mucinous tumors

8-10%

they may reach an enormous size, filling the entire abdominal cavity

a . bordeline mucinous tumors

enigma

b . malignant mucinous carcinomas

papillary proliferations -less common

bilateral tumors occur in 8-10% of cases

intraovarian in 95-98% of cases

malignant develops in 5-10% of benign mucinous cysts

c . pseudomyxoma peritonei

neoplastic epithelium secretes large amouts of gelatinous mucinous material

3) Endometrioid tumors

6-8%

malignant potential of endometriosis is very low, although a transition from benign to malignant epithelium may be demonstrated (hemorrhagic foci)

a . borderline endometrioid tumors

wide morphologic spectrum

endometrial polyp or complex endometrial hyperplasia with crowding of glands

some bordeline malignant tumors have a prominent fibromatous component (adenofibroma)

b . malignant endometrioid carcinomas

adenomatous pattern with all the potential variations of epithelia fond in the uterus

adenocarcinoma with benign- appearing squamous metaplasia gas an excellent prognosis

patients with mixed adenosquamous carcinomas have a very low survival rate

c . multifocal disease

Endometrioid tumors of the ovary are often saaociated with similar lesions
in the endometrium

metastatic from uterus to ovaries have a 30-40% 5-year survival

synchronous multifocal disease have a 75-80% 5-year survival

4) Clear cell (mesonephroid) tumors

3%

hypercalcemia or hyperpyrexia and most such cases are associated with metastatic disease

* malignant clear cell carcinomas

clear cells and hobnails cells

: the tall clear cells have abundant clear or vacuolated cytoplasm, hyperchromatic,
irregular nuclei, and nucleoli of various sizes

hobnails cells project their nuclei to the atypical cytoplasm

focal areas of endometriosis and endometrioid carcinoma sometimes occur

histologically identical to that seen in the uterus or vagina of the young patient who has
been who has exposed to DES in uterus

5) Brenner tumors

a. borderline Brenner tumors

the epithelium dose not invade the stroma

low-grade papillary transitional cell carcinoma of the urinary bladder

complete surgical removal usually results in cure

b . malignant Brenner tumors

rare

benign Brenner tumors coexisting with invasive transitional cells or another type of
carcinoma

c . transitional cell tumors

a primary ovarian carcinoma resembling transitional cell carcinoma of the urinary
bladder without a recognizable Brenner tumor

more than 50% of TCC are more sensitive to chemotherapy and have a more favorable
prognosis than other pool differentiated ovarian carcinomas of comparable stage
more frequently diagnosed in an advanced stage---- poorer survival rate

6) Undifferentiated carcinomas

a . large cell types

large round to oval nuclei, prominent nucleoli , a moderate amount of cytoplasm and
high mitotic activity are arranged in solid without glandular or squamous differentation

b . small cell types

small, hyperchromatic nuclei, scanty cytoplasm and high mitotic activity
in young women (hypercalcemia)

immunohistochemical stains - lymphoma, leukemia or sarcoma

7) Mesotheliomas

fibrosarcomatous/tubopapillary/carcinomatous/mixed

multiple intraperitoneal masses

develop after hysterectomy and bilateral salpingo-oophorectomy for benign disease

8) peritoneal carcinomas

primary malignant transformation of the peritoneum

simulates ovarian cancer clinically

the overall prognosis for borderline serous peritoneal tumors is excellent

appearance of a moderately to poorly differentiated serous ovarian carcinoma

primary peritoneal endometrioid carcinoma less common

2. Clinical features

more than 80% of epithelial ovarian cancers are fond in postmenopausal women

62 years

about 30% of ovarian neoplasms in postmenopausal women are malignant whereas only about
7% of ovarian epithelial tumors in premenopausal patients are frankly malignant

1) screening

transvaginal ultrasonography

: a very high (>95%) sensitivity for the detection of early-stage ovarian cancer, although
this test alone might require as many as 10-15 laparotomy procedures for each case of per
ovarian cancer detected

CA 125

: Sweden and the U.K.

with elevated CA 125 levels (>30u/ml) have undergone abdominal ultrasonography and
14 ovarian cancers have been discovered among 27,000 women screened

about four laparotomies were performed for each case of cancer detected

considering the false-positive results for both CA 125 and transvaginal ultrasonography,
particularly for premenopausal women, these tests are not cost-effective and should not be
used routinely to screen for ovarian cancer

2) genetic risk for epithelial ovarian cancer

familial or hereditary patterns account for fewer than 5% of all malignancies

a . site- specific familial ovarian cancer

the risk of developing epithelial ovarian cancer is higher in the presence of a positive
family history

hereditary ovarian cancers generally occur in women about 10 years younger than those with
nonhereditary tumors (before 50 years)

b . Breast/ovarian familial cancer syndrome

combination of epithelial ocarina and breast cancers, affecting a mixture of first and
second degree relatives

a young age, and the breast cancers may be bilateral

autosomal dominant mode of inheritance

two-to four fold greater than the general population

17q chromosome, the BRCA1 gene

prospect of screening of women at risk

individuals who have a mutation in the BRCA1 have a cumulative lifetime risk of
85-90% of developing breast cancer and 50% risk of ovarian cancer

c . Lynch II syndrome

the Lynch II syndrome (hereditary nonpolyposis colon cancer) which includes multiple
adenocarcinomas involves a combination of familial colon cancer and a high rate of
ovarian , endometrial, and breast cancers and other malignancies of the gastrointestinal
and genitourinary systems

The current recommendations of the Committee on Gynecologic Practice of the
American College of Obstetricians and Gynecologists are summarized below

Women who wish to preserve their reproductive capacity should undergo periodic
screening by transvaginal ultrasonography every 6 months and should consider
prophylatic oophorctomy when childbearing has been completed.

Oral contraceptives may be given to a young woman before she has children,
although the protective effect for women at high risk has not been evaluated.
Women with familial ovarian or hereditary breast/ovarian cancer syndrome who do
not wish to maintain their fertility should be offered prophylactic bilateral
saopingo-oophorectomy. The risk should be clearly documented, preferably
satablished by pedigree analysis, before oophorectomy. These women should be
counseled that this operation does not offer absolute protection because
perotomenal carcinomas oc asionally can occur after bilateral oophorectomy.

The role of BRCA1 testing in these women in being evaluated
Women with a documented Lynch II syndrome should be treated in the same
manner as women with familial breast/ovarian cancer syndrome , but in addition,
they should undergo periodic screening mammography, colonoscopy, and
endometrial biopsy

3) Symptoms

no symptoms for long periods of time

urinary frequency or constipation

lower abdominal distention, pressure, or pain (dyspareunia)

acute symptoms, such as pain secondary to rupture or torsion are unsual

in advanced stage disease : symptoms related to the presence of ascites omental metastsis, or
bowel metastasis

--- abdominal distention, bloating , constipation, nausea, anorexia ,early satiety

4) Signs

solid, irregular, fixed pelvic mass is highly suggestive of an ovarian malignancy
upper abdominal mass or ascites is present

ovaries-not palpable (at least 1 year)

: postmenopausal ovary syndrome ? only about 3 % of palpable masses measuring <5cm
in postmenopausal women are malignant

5) Diagnosis

serum CA125

useful in distinguishing malignant from benign pelvic masses

postmenopausal patients- >95U/ml : malignancy

premenopausal patient- observation : mobile, mostly cystic, unilateral and of regular contour

no more than 2 months , hormonal suppression

with the oral contraceptive ----> regress

not regress or increases in size---> must be removed surgically

>8cm in diameter , solid, relatively fixed , or irregularly shaped---> laparotomy

Exploratory laparotomy

routine hematologic and biochemical assessments

x-ray of the chest , IVP, barium enema or colonoscopy (over the 45years),
bilateral mammography

Cervical cytologic study

Endometrial biopy and an endocervical curretage ? irregular menses or
postmenopausal vaginal bleeding

6) Patterns of spread

a . transcoelomic

by exfoliation of cells that implant along the surfaces of the peritoneal cavity
tend to follow the circulatory path of the peritoneal fluid

up the paracolic gutters, especially on the right , along the intestinal mesenteries,
to the right hemidiaphragm

posterior cul-de-sac, paracolic gutters, right hemidiaphragm, liver capsule, the peritoneal
surfaces of the intestine and their mesenteries

seldom invades the intestinal lumen (carcinomatous ileus)

b . lymphatic

advanced stage disease : supraclavicular lymph node

78% of patients with stage III disease have metastases to the pelvic lymph node

para-aortic lymph nodes was 18% in stage I, 20% in stage II, 42% in stage III, and
67% in stage IV

c . hematogenous

uncommon

3 . Prognostic factors

1) Pathologic factors

: histologic grade --- significant heterogeneity of tumors and observational bias, the value of histologic grade as an independent prognostic factor has not been clearly established

2) biological factors

: low-stage cancers tend to be diploid and high-stage tumors tend to be aneuploid
flow cytometric analysis also provides data on the cell cycle, and the proliferation fraction (S phase) determined by this technique has correlated with prognosis in some studies

30%- HER-s/neu oncogene, poorer prognosis

3) clinical factors

the extent of residual disease after primary surgey, the volume of ascites, patient age, and performance status----- all independent prognosis variables

4 . Staging

: FIGO system --- based on findings at surgical exploration

1) technique for surgical staging

any free fluid, pelvic cul-de-sac
peritonea washing (no free fluid), recovering 50-100ml of saline from the pelvic
cul-de-sac , each paracolic gutter, and beneath each hemidiaphragm, with the
use of a rubber cathethe attached to the end of a bulb syringe
a systematic exploration of all the intra- abdominal surfaces and viscera is performed
: clockwise fashion from the cecum cephalad along the paracolic gutter and the ascending
colon to the right kidney, the liver and gall bladder, the right hemidiaphragm the
entrance to the lessser sac at the paraaortic area across the transverse colon to the left
hemidiaphragm down the left gutter and the descending colon to the rectosigmoid
colon
any suspicious areas or adhesions on the peritoneal surfaces should be biopsied
No ---- peritoneum of the pelvic cul-de-sac, both paracolic gutters, the peritoneum
over the bladder, and the intestinal mesenteries
diaphragm --- by biopsy or by scraping with a tongue depressor and obtaining a sample
for cytologic assessment
the omentum should be resected from the transverse colon "infracolic omentectomy
if the gastrocolic ligament is palpably normal, it does not need to be resected
to evaluate the pelvic and paraaortic lymph node