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METASTATIC CARCINOMATO THE OVARY

Steven G. Silverberg, M.D.University of Maryland

Baltimore, Maryland, U.S.A.

CLINICAL IMPORTANCE OF METASTASES TO THE OVARY

• 10-20% of all cancers in the ovary are metastatic

• higher proportion of mucinous, ? endometrioid-appearing tumors

• surgical Rx: find metastases/“implants” vs. find the primary (first or second operation)

• chemotherapy: different for ovarian vs. other 1o sites

TIME OF DIAGNOSISOF OVARIAN METASTASES

• after primary• concurrent with primary (?FS of ovarian

tumor)• before primary (most difficult for the

pathologist; 17-38% of cases in the literature

TYPES OF CANCERS METASTASIZING TO THE OVARY

• most commonly adenocarcinomas, but anything is possible (squamous, small cell neuroendocrine, transitional cell, melanoma, sarcomas, etc.

• lymphomas/leukemic infiltrates can be 1o in the ovary or (more often) part of a disseminated process)

• if no residual ovarian tissue is found, R/O a primary parovarian process

MAIN SOURCE OF CARCINOMA METASTATIC TO THE OVARY

• genital (contralateral ovary, corpus, cervix [adeno], fallopian tube)

• extragenital (esp. colorectum, breast, stomach, pancreas, appendix)

• synchronous primaries are an important consideration mostly for genital sites

METASTATIC COLORECTAL ADENOCARCINOMA:CLINICAL FEATURES

• ~ 1/3 or more of all metastatic ovarian cancers

• 2-10% of women with colorectal carcinoma develop ovarian metastases

• up to 45% of metastases are thought clinically to be ovarian 1o

• 3% of women in one series presented with ovarian mass and unsuspected intestinal disease

METASTATIC COLORECTAL ADENOCARCINOMA:

PATHOLOGIC PROBLEMS

• 30-50% may be unilateral• usually smaller than 10 cm, but may be 20-30

cm• ~ 1/3 contain benign-appearing or borderline-

appearing foci (occasionally most or all of the sampled tumor)

• may appear mucinous or endometrioid, rarely clear cell, papillary, signet cell, or adenosquamous

SMALL CELL TUMORS IN THE OVARY:DIFFERENTIAL DIAGNOSIS

Lymphoid markers

Inhibin, calretinin

CK(7)CK, EMANE, TTF-1IHC

SheetsLut., cystsPleo.,? diff.

Small/large cellsAzzopardi effect

H&E features

LN/spleenEstrogenPerit. spread

CA++Lung 1oOther clinical features

B/UUBUBLaterality

AllYoungOlderYoungOlderAge

LymphomaJuv. GCTUndiff CAHypercalcemic SCC

Metastatic SCC

METASTASES TO THE OVARY FROM GENITAL TRACT CARCINOMAS

• endometrium• endocervix• contralateral ovary• fallopian tube

METASTASES FROM CONTRALATERAL OVARY

• LOH studies have suggested mets. more common than synchronous primaries

• usual criteria for differential diagnosis (multinodularity, surface and vascular involvement, etc.)

• serous/TCC/undiff. most frequently bilateral• clinically, staging and treatment same for

mets. and synchronous primaries

METASTASES FROM ENDOMETRIAL CARCINOMA VERSUS SEPARATE PRIMARIES

Not monoclonalMonoclonalNo vascular involvementVascular involvement

Primarily deepPrimarily surface involvedUninodularMultinodular

No other metastasesOther metastasesEndometriosisNo endometriosis

Low grade endometrioidType 2/high grade CANo myoinvasionDeep myoinvasion

YoungerOlder

Favor Synchronous PrimariesFavor Metastasis

MUCINOUS TUMORSOF OVARY AND CERVIX

(IJGP 7:99, 1988)

310316(3)Young

(Ob. Gyn. 64:553, 1984)

—145(2)Kaminski

(IJGP 1:391, 1983)

—404(1)LiVolsi

# BOTH# PRIMARY# METASTATIC# OF CASESAUTHORS

(1) 4 of 22 invasive cervical AC(2) 5 of 39 cervical mucinous AC, 6 of 51 endometrioid(3) 10 of 16 were “adenoma malignum”

MUCINOUS TUMORS OF OVARY AND CERVIX: HELPFUL CRITERIA

(Young and Scully, Int J Gynecol Pathol 7: 99, 1988)

CommonLess commonCervical tumor spread

Less commonOccasionalMucinous metaplasia of tube or endometrium

CommonUncommonLVSI in either tumor

DeepSuperficialCervical tumor invasionSimilarDissimilarTumor histology

CommonLess commonOvarian surface implantsBilateralUnilateralLaterality of ovarian tumor

ShortLongDisease-free follow-upShortLongInterval between tumors

MetastaticPrimary

Note: Endometriosis, IHC, and molecular studies not mentioned

ADENOCARCINOMAS OF OVARY AND CERVIX(Elishaev et al, AJSP 29:281-294, 2005)

• 10 Cases, all originally thought to be 1o ovarian tumors• Age 28-51• Ovary first in 2, after cervix in 3, simultaneous in 5• Ovarian tumors bilateral in 2 cases, unilateral in 8, 10 cm or

more in 7• 7 Ovarian tumors looked endometrioid, 3 mucinous; only 1 frankly

invasive• Suspicious features were combined endometrioid/mucinous

phenotype, BOT with IEC• Endocervical tumors mostly small (2 considered microinvasive)• 8 of 10 had no other metastases detected• p16 expression and identical HPV types (mostly 16) present in

cervical and ovarian tumors, ER/PR usually negative or weak