Sex cord stromal tumors: general, fibroma, gonadoblastoma, granulosa cell-adult, juvenile, gynandroblastoma, Leydig cell, lipid cell, myxoma, sclerosing stromal, Sertoli cell, Sertoli-Leydig, sex cord tumor with annular tubules, signet ring stromal tumor, steroid cell tumor NOS, thecoma, tumor of adrenogenital syndrome, unclassified
Other ovarian specific tumors: female adnexal tumor of wolffian origin, microcystic stromal tumor, small cell carcinoma-hypercalcemic type, pulmonary type
Other tumors not specific to ovary: adenoid cystic/basaloid carcinoma, angiomyolipoma, angiosarcoma, benign papillary mesothelioma, endometrial stromal sarcoma, fibromatosis, fibrosarcoma, granulocytic sarcoma, hemangioma, infantile hemangioendothelioma, leiomyoma, leiomyosarcoma, lymphoepithelioma-like carcinoma, lymphoma, malignant mixed mullerian tumor (MMMT), mesothelioma, metastases to ovary, mullerian adenosarcoma, myofibroblastoma, nephroblastoma, neuroendocrine carcinoma, osteoclast-like giant cell tumor, osteosarcoma, paraganglioma, PNET, rhabdomyosarcoma, squamous cell carcinoma, undifferentiated carcinoma
Other: staging, features to report
See also Ovary non tumor chapter
Germ cell tumors
Germ cell tumors - general- Ovary chapter
20% of ovarian tumors; resemble germ cell tumors in testis
Usually children and young adults
Usually benign cystic teratomas
8% are mixed
Survival: 95% disease free survival due to chemotherapy with bleomycin, etoposide and cisplatin
Case reports: systemic mast cell disease 3 months after chemotherapy for mixed malignant germ cell tumor (Hum Pathol 1998;29:1546)
Carcinoid tumors - Ovary chapter
May be a form of monodermal teratoma; 15% have cystic teratoma or mucinous neoplasm in contralateral ovary
Good prognosis if ovarian primary
1/3 are associated with carcinoid syndrome; may cause constipation due to secretion of peptide YY
Case reports: primary ovarian carcinoid with metastases and simultaneous borderline mucinous tumor and colonic adenocarcinoma (Arch Pathol Lab Med 1996;120:393)
Treatment: excision, although mucinous types are more aggressive
Gross: mean 10 cm, yellow, solid cut surface; usually unilateral
Micro: resembles carcinoid tumors elsewhere; patterns are insular (resembles appendix or small bowel tumors), trabecular (resembles stomach or rectal tumors); strumal (below), mucinous; may have abundant fibrous stroma; rarely has prominent pleomorphism, mucinous features (below) or signet ring pattern
Positive stains: chromogranin, synaptophysin, neuron specific enolase (NSE)
Negative stains: inhibin
EM: neurosecretory granules
DD: fibroma-thecoma, Brenner tumor; GI metastasis (bilateral, associated with peritoneal implants, no other teratomatous elements)
References: Arch Pathol Lab Med 1987;111:440
Mucinous (goblet cell) carcinoid - Ovary chapter
Rare; usually stage 1
Presence of frank carcinoma may be poor prognostic factor
Gross: solid nodules/areas of thickening in wall of mature cystic teratoma or solid tumors associated with other cystic tumors
Micro: often well-differentiated with small glands, many floating in mucin pools; glands lined by goblet cells and columnar cells, some neuroendocrine
References: Am J Surg Pathol 2001;25:557
Atypical mucinous carcinoid - Ovary chapter
Micro: crowded glands, some confluent with cribriform pattern and scattered microcystic glands; glands are lined by cuboidal and columnar cells, some neuroendocrine and goblet cells
Carcinoma arising in mucinous carcinoid - Ovary chapter
Micro: islands, larger nodules, closely packed glands or single cells of mainly signet ring cell type; most cells lack mucin and are severely atypical, with marked mitotic activity and necrosis
DD: metastatic mucinous carcinoid from appendix or elsewhere (ovarian origin suggested if ovarian teratoma or surface epithelial tumor present, no angiolymphatic invasion, involves only one ovary), strumal carcinoid, insular carcinoid
References: Am J Surg Pathol 2001;25:557
Strumal carcinoid - Ovary chapter
Has features of carcinoid tumor and struma ovarii
Associated with MEN IIA/III
Case reports: associated with MEN IIA (Arch Pathol Lab Med 1992;116:200)
Micro: often other teratomatous elements
Positive stains: neuron specific enolase, chromogranin, synaptophysin, thyroglobulin, PAP (similar to rectal carcinoids)
Negative stains: calcitonin
EM: numerous electron-dense neurosecretory granules, Am J Clin Pathol 1978;69:356
Choriocarcinoma - Ovary chapter
Most ovarian choriocarcinomas are metastases from uterine tumors
Pure ovarian choriocarcinomas are rare, develop from ovarian pregnancy or as a germ cell tumor (pure or mixed)
Rarely arise from surface ovarian carcinomas with choriocarcinomatous differentiation
After puberty, origin from an ovarian ectopic pregnancy cannot be excluded
Have high levels of serum hCG; monitoring serum levels is helpful in predicting recurrence
In contrast to placental tumors, nongestational tumors are usually fatal and unresponsive to chemotherapy; metastases to lungs, liver, bone and viscera are common at diagnosis
Micro: mixture of syncytial and cytotrophoblastic elements in a hemorrhagic and necrotic background
Positive stains: hCG, CD10
Less than 1% of ovarian malignancies
Counterpart of testicular seminoma
Usually young patients (81% under age 30)
5% associated with gonadal dysgenesis/Swyer syndrome (World J Surg Oncol 2007 Jun 23;5:71), androgen insensitivity or pseudohermaphroditism; rarely associated with hypercalcemia
Metastasize to opposite ovary, retroperitoneal nodes, peritoneal cavity
Rarely transforms to yolk sac tumor (Mod Path 1995;8:881)
Survival: 95%
Mixture with choriocarcinoma, yolk sac or embryonal carcinoma worsens prognosis
Treatment: surgery and chemotherapy (NOT radiotherapy, although it is effective for seminoma)
Gross: 15% bilateral; solid, nodular, small to huge, gray-pink (resembles cerebral cortex); hemorrhage and necrosis common but less prominent than other malignant tumors
Gross images: dysgerminoma #1; #2; #3 (25 cm); #4; #5; #6; #7 with focal necrosis
Micro: nests of tumor cells separated by fibrous stroma with T lymphocytes; large vesicular cells with well defined cell borders, cleared cytoplasm containing glycogen, central nuclei; 1+ prominent nucleoli; occasional granulomas; may have hCG+ syncytiotrophoblastic cells close to blood vessels or hemorrhagic foci with increased serum hCG; may have abortive yolk sac elements with increased serum AFP; may be present in wall of mature teratoma; may have pseudotubular or cord-like architecture
Early carcinomatous differentiation: 30+ mitoses per 10 high power fields, may worsen prognosis
Micro images: H&E
and FISH; H&E
and c-kit
Contributed by Dr. Semir Vranic, University of Sarajevo:
#1;
#2;
#3;
PLAP;
CD117
Virtual slides: dysgerminoma
Videos: #1
Positive stains: OCT4 (strong nuclear staining in 90%+ cells, Am J Surg Pathol 2004;28:1341), c-kit (87%, Mod Pathol 2005;18:1411), CAM5.2 (20%), AE1-AE3 (8%, Hum Pathol 2006;37:1015)
Negative stains: CK7, CK20, EMA, HMW keratin, CD30, vimentin
Molecular: 12p abnormalities in 81% (Mod Pathol 2006;19:611)
Embryonal carcinoma - Ovary chapter
Similar to testicular embryonal carcinoma
Median age 15 years, patients often present with precocious puberty, also vaginal bleeding, amenorrhea, hirsutism
Serum hCG always high (positive pregnancy test), AFP sometimes high
Gross: median 17 cm, smooth and glistening, variegated cut surface with extensive hemorrhage and necrosis
Micro: sheets and nests of large primitive cells, occasional papillae and abortive glands; syncytiotrophoblast-like tumor cells seen (hCG+)
Mixed Germ Cell tumor of Ovary - Ovary chapter
Micro images: teratomatous component of respiratory epithelium (left) with yolk sac tumor
Molecular: often isochromosome 12p in teratomatous and non-teratomatous components (Mod Pathol 2006;19:766)
Embryonal carcinoma composed primarily of embryoid bodies
Embryoid body has amniotic cavity-like structure and is continuous with intestinal duct, and rarely has squamous cell nests, while "yolk sac" is continuous with hepatic tissue
Embryoid body is not considered to be a real or teratomatous embryo, but a product of divergent differentiation into intestine and liver from the plastic epithelium, which seems to be derived from embryonic gut (Hum Pathol 1988;19:1144)
Rare monodermal teratoma composed predominantly of mature thyroid tissue
May show pathologic changes of thyroid gland including hyperfunctioning; malignancies are usually papillary thyroid carcinoma
Associated with mucinous cystadenoma, Brenner tumor, carcinoid tumor, dermoid cyst
Case reports: struma salpingis (Am J Surg Pathol 1993;17:1187), follicular variant of papillary carcinoma with intraluminal crystalloids (Arch Pathol Lab Med 1991;115:145)
Gross: resembles red-brown thyroid tissue but usually multilocular cystic; usually unilateral
Gross images: partially cystic tumor resembling thyroid #1; #2
Micro: thyroid follicles with colloid; other teratomatous elements may be present; rarely has solid or pseudotubular patterns, microfollicles, abundant eosinophilic cytoplasm, abundant clear cytoplasm or minimal thyroid follicles
Micro images: thyroid-like follicles
Virtual slides: clear cell struma ovarii
Positive stains: thyroglobulin
Molecular: BRAF mutations frequent in malignant but not benign tumors (Am J Surg Pathol 2007;31:1337)
DD: metastatic thyroid carcinoma to ovary
References: Am J Surg Pathol 1995;19:21, Am J Surg Pathol 1994;18:785, Arch Pathol Lab Med 1978;102:180
Teratoma-mature - Ovary chapter
Mature if only contains adult tissues
Usually teenage women (solid) or children (cystic)
Excellent prognosis, even if peritoneal implants are present
Rarely associated with hemolytic anemia
May rupture into peritoneal cavity causing foreign body reaction that simulates metastatic carcinoma or miliary tuberculosis
Tumors arise from a single germ cell after first meiotic division
Cystic tumors may contain squamous cell carcinoma, carcinoid tumor or adenocarcinoma
Dermoid cyst: usually means teratoma resembles skin; some use dermoid cyst and mature teratoma interchangeably
Gliomatosis peritonei: peritoneal implants exclusively composed of mature glial tissue; benign if all tissue is mature and other teratomatous elements are absent
Case reports: corticotroph pituitary adenoma (Am J Surg Pathol 1987;11:218), glomus tumor (Arch Pathol Lab Med 2000;124:1373), homunculus (fetiform) coexisting with intrauterine pregnancy (Arch Pathol Lab Med 1986;110:1192), mature teratoma with anti-Ri antibodies and memory impairment (Int Semin Surg Oncol 2004 Nov 10;1(1):11), mucinous tumor (Am J Surg Pathol 2003;27:650), nodal gliomatosis (Arch Pathol Lab Med 1986;110:975), peptic ulcer with spindle cell nodule, (Arch Pathol Lab Med 1990;114:529), pituitary tissue (Arch Pathol Lab Med 1978;102:122), prostate tissue (Am J Surg Pathol 1992;16:780, Arch Pathol Lab Med 1985;109:675), skin adnexal tumor (Arch Pathol Lab Med 1993;117:846)
Gross: solid or cystic; cystic content may contain greasy material composed of keratin, hair, teeth; rarely is “fetiform” (partial human body-like structure) or contains partial mandible; teeth may be found in Rokitansky’s protuberance-a well defined nipple-like structure covered with hair
Gross images: dermoid cyst-like #1; #3; with sebum, hair and teeth #1; #2; #3; #4; with hair, fat and teeth
Micro: ectodermal structures in 100%, mesodermal in 93%, endodermal in 71%; skin and glial tissue common; prostate tissue in 10%; still considered mature if microscopic foci of immature tissue
Micro images: mature teratoma with sebaceous glands and cartilage; thyroid, cartilage, fat & GI; glomus tumor; carcinosarcoma arising from dermoid cyst
Virtual slides: dermoid cyst; mature teratoma #1; #2
Videos: dermoid cyst; benign teratoma
DD: immature teratoma grade 1 (sample extensively to distinguish); epidermoid cyst (no skin adnexae or other tissues)
References: Am J Surg Pathol 2003;27:650
Malignant change in cystic teratoma - Ovary chapter
Tumor is apparently derived from germ cell elements of teratoma, but behavior is based on phenotype
Squamous cell carcinoma: most common malignant change in cystic teratoma; 5 year survival is 52%, dependant on histologic grade and vascular invasion; appears to arise from columnar epithelium (Am J Surg Pathol 1989;13:397)
Case reports: apocrine adenocarcinoma, (Arch Pathol Lab Med 1993;117:647), carcinosarcoma arising from dermoid cyst (BMC Cancer 2006 Mar 1;6:47), Paget’s disease in squamous epithelium (Am J Surg Pathol 1991;15:1002), small cell epidermoid carcinoma (Arch Pathol Lab Med 1995;119:551), squamous cell carcinoma in situ (Arch Pathol Lab Med 1991;115:172)
Teratoma-immature - Ovary chapter
Malignant tumor, whose tissue resembles embryonal or fetal tissue
Usually prepubertal or young women (mean 18 years)
Most recurrences within 2 years; presence of yolk sac component is best predictor of recurrence in pediatric tumors (Am J Surg Pathol 1998;22:1115)
Common errors are classifying differentiating tissue as immature and not recognizing hepatoid and well-differentiated glandular patterns of yolk sac tumor
Case reports: 17 year old woman with predominant malignant retinal anlage component, tumor parthenogenically derived, GFAP+, neuroglia by EM (Am J Surg Pathol 1985;9:221)
Treatment: surgery, multiagent chemotherapy; better prognosis if only mature teratoma found after chemotherapy, although abnormal karyotype is maintained in mature teratoma
Gross: bulky, solid or cystic with necrosis, hemorrhage
Gross images: hepatic teratoma with yolk sac component #1; #2; #3
Micro: usually neurogenic elements (GFAP+); mesodermal elements common; some tumors derived primarily of esophageal, liver and intestinal structures (endodermal)
Grading: histologic grade is based on proportion of tissue containing immature neuroepithelium
Norris grading system (correlates best with extraovarian spread, survival)
1 - abundant mature tissue, loose mesenchymal tissue with occasional mitoses, immature cartilage, tooth anlage
2 - less mature tissue than grade 1, rare foci of neuroepithelium with mitoses, < 4 low power fields in any one slide
3 - little/no mature tissue; numerous neuroepithelial elements merging with cellular stroma occupying 4+ low power fields
Micro images: immature elements #1; #2; bone; neural tissue
yolk sac tumors - #1; #2; Schiller Duval bodies #1; #2; AFP stain
Immature teratoma variants
Endodermal teratoma - Ovary chapter
High serum AFP, low serum hCG, no neuroectodermal component
Micro: early endoderm - liver, esophagus, intestine
Positive stains: AFP, alpha-1-antitrypsin
References: Hum Pathol 1993;24:364
Ependymoma - Ovary chapter
May derive from teratoma
Neuroectodermal component composed entirely of primitive ependymal structures
Appears to derive from distinct precursors or to differentiate along distinct pathways from CNS ependymoma based on different immunostaining patterns (Am J Surg Pathol 2008;32:710)
Case reports: PR+ bilateral tumors in pregnant woman (Hum Pathol 1992;23:962), 68 year old woman (Am J Surg Pathol 1993;17:623), tumor of broad ligament (Am J Surg Pathol 1984;8:203)
Micro: resembles CNS ependymoma; cells have fibrillary cytoplasmic processes, often arranged around blood vessels forming perivascular pseudorosettes
Virtual slides: ependymoma
Positive stains: CK18 (100%), ER (100%), CK7 (80%), PR (80%), 34betaE12 (60%), CAM5.2 (60%); GFAP, vimentin, neuron-specific enolase, S100, EMA
EM: cilia on surface of cysts and within intracellular lumina, abundant intermediate filaments in cytoplasmic processes, intercellular junctions
References: Hum Pathol 1984;15:632
Growing teratoma syndrome - Ovary chapter
Treatment: long term follow up since recurrent masses can appear many years after primary tumor, although most nodules appear within 2 years of initial primary
Case reports: carcinoid teratoma arising in mature teratoma of liver (Am J Surg Pathol 2007;31:1913)
Yolk sac tumor - Ovary chapter
Also called endodermal sinus tumor
May be derived from embryonal carcinoma
Usually children or young adults (median age 19 years) with abdominal pain and rapidly growing mass, increasing alpha fetoprotein (AFP) and alpha-1-antitrypsin serum levels; negative hCG
Fatal without chemotherapy since most have subclinical metastases at presentation
Case reports: with associated virilization (Am J Surg Pathol 1981;5:385)
Gross: mean 15 cm, smooth and glistening external surface, cystic cut surface with hemorrhage and necrosis; often has benign teratoma component; rarely is found in pelvis unattached to ovary
Micro: numerous patterns; Schiller-Duval body is pathognomonic - central blood vessel enveloped by germ cells within a space similarly lined by germ cells, resembles glomerulus; hyaline droplets present in all tumors (positive for AFP, PAS and alpha-1-antitrypsin)
Patterns: reticular or microcystic patterns formed by a loose network of flat/cuboidal cells;
polyvesicular vitelline pattern: in 25%; vesicular structures with eccentric constrictions surrounded by a dense spindle cell stroma; may have better prognosis in pure form
Other patterns - hepatoid (large polyhedral cells with hyaline bodies but no bile, resembles metastatic hepatocellular carcinoma), intestinal differentiation, glandular (may be cribriform or resemble endometrioid carcinoma), solid, parietal yolk sac (thick layers of basement membrane) and undifferentiated
Micro images: contributed by Dr. Debra Zynger, Northwestern University, Chicago, IL:
#1; #3; #5; #7; #8; #9; #10; #11; #12; #13; #14; #15; #17; #18; #19; #20; #21; #22; #23; #25; #26; #27; #28; #29
Micro images from liver yolk sac tumor (similar histology): yolk sac #1; #2; Schiller Duval #1; #2; AFP stain
Virtual slides: retiform tumor
Positive stains: keratin, AFP (yolk sac elements, hepatic or intestinal epithelium in teratomas), CD10
Molecular: usually aneuploid or tetraploid
References: Am J Surg Pathol 1987;11:767 (endometrioid pattern)
Sex cord-stromal tumors
Sex cord-stromal tumors-general - Ovary chapter
5% of ovarian neoplasms, 7% of malignant ovarian neoplasms
Derived from ovarian stroma, itself derived from sex cords of embryonic gonad (predecessor of Sertoli, Leydig, granulosa and theca cells)
Theca cells produce estrogens; Leydig cells produce androgens
Morphology and clinically evident hormonal activity may go together, but classify based on morphology
Positive stains: alpha-inhibin, mullerian inhibiting substance, alpha-inhibin (>95%), calretinin (more sensitive, less specific than inhibin (Am J Surg Pathol 2002;26:1477), CD99 (Arch Pathol Lab Med 2000;124:563), MART1/MelanA, WT-1
Negative stains: EMA, PLAP, CEA
Notes: anti-Mullerian hormone staining is present in only a small percentage of granulosa or Sertoli tumor cells, but is specific for these tumors (Hum Pathol 2000;31:1202), particularly compared to endometrioid tumors (Hum Pathol 1998;29:840)
Strong alpha-inhibin staining is relatively specific for ovarian sex-cord stromal proliferations, although luteinized cells from other tumors are also immunoreactiveb (Hum Pathol 1997;28:1387, Am J Surg Pathol 1997;21:583)
Common; benign; arise after puberty
40% of tumors > 6 cm are associated with ascites
Also associated with right sided hydrothorax, Meigs syndrome, basal cell nevus syndrome
Meigs syndrome: ovarian fibromas, right sided hydrothorax, ascites; after tumor excision, hydrothorax and ascites disappear
Basal cell nevus syndrome (Gorlin syndrome): autosomal dominant disease of multiple basal cell carcinomas, odontogenic keratocysts, palmoplantar pits, congenital skeletal abnormalities and ectopic calcifications, caused by mutational inactivation of the PTCH gene; also have calcified, bilateral, often multinodular ovarian fibromas
Fibrothecoma: combined fibroma and thecoma; also a generalized term for these two closely related tumors
Case reports: fibrothecoma with ascites and elevated CA125 (Arch Pathol Lab Med 2005;129:701), 69 year old woman with fibrothecoma containing minor sex cord elements and fibrosarcoma (Arch Pathol Lab Med 2003;127:81)
Treatment: excision, does not recur
Gross: mean 6 cm, usually unilateral, solid, lobulated, firm, white, may have myxoid change; not associated with adhesions
Gross images: fibroma #1; #2; fibrothecoma #1; #2
Micro: closely packed spindle cells in “feather-stitched” or storiform pattern; may have hyaline bands and edema; no atypia
Micro images: fibroma; fibrothecoma with focal fibrosarcomatous area; fig 1: bright yellow, firm, glistening soft tissue, fig 2: moderate cellularity with calcification, fig 3: cells have moderate pale vacuolated cytoplasm and oval nuclei, fig 4: focal hypercellular foci with spindle cells in fascicles, but no mitotic figures
Positive stains: CD56 (not specific), WT1, ER-beta, PR, variable smooth muscle actin, occasional S100 and CD34 (Am J Surg Pathol 2008;32:884)
Molecular: trisomy 12
DD: cellular fibroma (up to 3 mitoses/10 high power fields), fibrosarcoma (4+ mitoses/10 HPF), massive edema, fibromatosis, thecoma, Brenner tumor, Krukenberg tumor
References: Am J Surg Pathol 2002;26:1477
Cellular fibroma of ovary - Ovary chapter
Recommended to call mitotically active cellular fibroma (Am J Surg Pathol 2006;30:929)
Treatment: excision and long term follow up; occasionally recurs locally, particularly with rupture or adherence
Gross: mean 9 cm, usually solid, may have cystic component, occasionally ovarian surface adhesions or extraovarian involvement
Gross images: cellular fibroma with hemorrhagic necrosis
Micro: cellular intersecting fundles of spindle cells with bland nuclei, 4+ MF/10 HPF
DD: fibrosarcoma (severe nuclear atypia, 4+ MF/10 HPF, aggressive clinical course)
Fibroma with minor sex cord elements - Ovary chapter
Case reports: 45 year old woman (Diagn Pathol 2007 Dec 4;2:46)
Micro images: various images
Gonadoblastoma - Ovary chapter
Also called dysgenetic gonadoma
Mixture of germ cell tumor and sex-cord stromal tumor
Usually occurs in individuals with abnormal sexual development and indeterminate gonads; usually gonadal dysgenesis with Y chromosome (i.e. XY gonadal dysgenesis, XO-XY mosaicism, not XX gonadal dysgenesis); 25% risk of neoplasia in these gonads
Also present in phenotypically normal women, even during pregnancy, although ovary is never normal
Y chromosome material appears to participate in gonadoblastoma tumorigenesis (Am J Clin Pathol 1997;108:197)
Associated with ataxia-telangiectasia
80% are phenotypic women, 20% are phenotypic men with undescended testicles and female internal secondary organs
50% have coexisting dysgerminoma
Excellent prognosis if completely excised; almost never malignant
Gross: 36% bilateral, tumors usually small, may be microscopic
Micro: primitive germ cells and sex cord stromal cells surrounded by ovarian-type stroma; nests of dysgerminoma-like germ cells and sex cord derivatives resemble immature Sertoli and granulosa cells; arranged in nests surrounded by ovarian stroma containing Leydig or lutein-type cells; hyalinization and calcification are common; may be dysgerminoma if overgrowth of this component (Am J Clin Pathol 1997;108:197)
Positive staining: anti-Mullerian hormone focally (Hum Pathol 2000;31:1202)
DD: incidental finding in ovaries of normal infants/children (associated with follicular cysts, microscopic foci resembling gonadoblastoma or sex cord tumor with annular tubules)
Granulosa cell tumor-adult - Ovary chapter
Differentiation towards follicular granulosa cells
Usually women age 15+ years; 75% associated with hyperestrogenism, causes precocious puberty in children, metrorrhagia (bleeding between periods), endometrial hyperplasia / carcinoma (usually well differentiated and superficial), breast fibrocystic changes in adults
Endometrial hyperplasia regresses after tumor excision
10 year survival >90%; tends to recur locally, up to 20 years later
5-25% risk of malignancy, cannot predict from histology
Prognostic factors: stage, size, tumor rupture, nuclear atypia
Case reports: Case of the Week #96, tumor to tumor metastasis from breast cancer (Hum Pathol 2002;33:445), collision tumor with colonic adenocarcinoma (World J Surg Oncol 2007 Oct 20;5:118), recurrence after 30 years (Int Semin Surg Oncol 2004 May 11;1(1):4), associated with unusual germline p53 mutation (Mod Pathol 2004;17:868)
Gross: >95% unilateral and confined to ovary; encapsulated with smooth lobulated surface, gray or yellow, solid or cystic with straw colored or mucoid fluid; may resemble cystadenoma; androgenic tumors tend to be large
Gross images: granulosa cell tumor #1; #2; solid and cystic tumor
Micro: small, bland, cuboidal to polygonal cells in various patterns, including Call-Exner bodies (small follicle-like structures filled with acidophilic material), macrofollicular, trabecular, solid, insular patterns; cells may be luteinized (plump with ample cytoplasm), particularly during pregnancy; may have theca cell component
Cells have coffee bean nuclei with folds/grooves; may see floret giant cells, indicative of degeneration
Rarely focal hepatic cell differentiation (large cells with abundant eosinophilic, slightly granular cytoplasm; central round nuclei with single prominent nucleoli; often bile pigment in canaliculi between large cells (Am J Surg Pathol 1999;23:1089, Am J Surg Pathol 1993;17:85), pseudopapillary pattern (Am J Surg Pathol 2008;32:581)
Micro images: low/medium power - image #1; #2; #3; #4; #5
inhibin #1; #2-inhibin alpha (fig 1), CD99 (fig 4)
contributed by Dr. Sharon Bihlmeyer - low power; high power; inhibin; calretinin; CK7
Granulosa cell tumor-adult - Ovary chapter (continued)
Virtual slides: granulosa cell tumor #1; #2
Videos: #1
Positive stains: inhibin alpha, vimentin, calretinin (Am J Surg Pathol 2002;26:1477), CD99 (Mod Path 1998; 11:769), smooth muscle actin, desmoplakin, S100 (50%), keratin (dot like in 30-50%, primarily low molecular weight, Am J Surg Pathol 1992;16:962), anti-Mullerian hormone focally (Hum Pathol 2000;31:1202), desmin (35%), silver stains demonstrate reticulin surrounding cluster of cells
Negative stains: EMA
Cytology: little cytoplasm, intense indentation of nuclear membrane; resembles mesothelial cells (Am J Clin Pathol 1986;85:402)
Molecular: monosomy 22 (~40%), trisomy 12 (~30%), +14 (~30%), monosomy X (~10%), monosomy 17 (5%), although most tumors (80%) are diploid or near-diploid (Mod Path 2002;15:951)
Molecular images: FISH-trisomy 12, monosomy 17
EM: abundant intermediate filaments, desmosomes
DD: poorly differentiated ovarian surface epithelial carcinoma (diffuse cytoplasmic keratin staining, Virchows Arch A Pathol Anat Histopathol 1989;414:439), carcinoid tumor, endometrial stromal sarcoma, endometrioid carcinoma, small cell carcinoma of hypercalcemic type, pregnancy related granulosa cell proliferation (microscopic, multiple, associated with atretic follicles, Hum Pathol 1988;19:657)
Granulosa cell tumor-juvenile - Ovary chapter
5% of ovarian tumors in children
Mean age 13 years, range 0-67 years, 80% occur before age 20, 97% before age 30
Most prepubertal patients present with sexual precocity due to excessive estrogen production; rarely produce androgens (J Endocrinol Invest 2006;29:653); older patients have nonspecific abdominal swelling and pain
Rarely associated with enchondromatosis (Ollier’s disease), Mafucci syndrome, abnormal karyotype / ambiguous genitalia (Am J Surg Pathol 1985;9:737)
Case reports: Case of the Week #59, cystic tumor in 43 year old woman (Arch Pathol Lab Med 2002;126:1123), bilateral tumor in newborn with dysmorphic features (Am J Surg Pathol 1981;5:789)
Treatment: excision is usually adequate for limited disease, although late recurrence may occur (Am J Obstet Gynecol 2004;191:366)
Gross: usually unilateral, up to 12 cm; multiloculated, cystic and solid tumor with yellow-white solid areas; may have hemorrhage and necrosis
Gross images contributed by Dr. Hanni Gulwani, New Delhi (India): 3 year old girl with breast enlargement - mostly solid tumor with focal cystic change
Micro: diffuse or macrofollicular patterns with microcysts containing eosinophilic secretions, tumor cells either have scant cytoplasm or are luteinized; round/oval hyperchromatic nuclei with small nucleoli, irregular nuclear contours; no/rare nuclear grooves; high mitotic rate (mean 7/10 HPF); may have hobnail-type cells, pseudopapillary pattern (Am J Surg Pathol 2008;32:581)
Granulosa cell tumor-juvenile - Ovary chapter (continued)
Micro images: gross, H&E and inhibin; image #1; #2; #3
Micro images contributed by Dr. Hanni Gulwani, New Delhi (India): 3 year old girl with breast enlargement - well demarcated tumor with pseudolobular pattern and compressed normal ovary at periphery; primordial follicles in normal ovary; poorly formed follicles with mucoid secretions; compact spindle cell areas with hemangiopericytoma like pattern #1; #2; loose edematous areas with abortive follicles #1; #2; spindle cells are SMA+; vimentin+; high MIB-1 expression; ER+ and PR+
Virtual slides: 39 cm tumor
Positive stains: inhibin, calretinin
Negative stains: HER2
Molecular: consistent trisomy 12 (as with adult granulosa cell tumors); more aneuploidy in juvenile than adult granulosa cell tumors
DD: adult granulosa cell tumors (more regularly shaped follicles with basement membrane material, prominent nuclear grooves, no hyperchromasia), thecoma (older patients, no follicles, no atypia, no mitotic figures), clear cell carcinoma (older patients, diffuse hobnail cells, no follicles, no juvenile granulosa type cells)
References: Am J Surg Pathol 1984;8:575, Arch Pathol Lab Med 1989;113:40
Gynandroblastoma - Ovary chapter
Sex cord stromal tumor with equal numbers of granulosa-theca cells and Sertoli-Leydig cells
Very rare; variable hormones
Case reports: 24 year old woman with polycystic ovarian syndrome (Arch Pathol Lab Med 2006;130:225)
Leydig cell tumor (hilus cell tumor) - Ovary chapter
Rare, derived from hilar cells
Almost always benign
Call a nonhilar Leydig cell tumor if it occurs in ovarian cortical stroma
Symptoms: virilization, elevated 17-ketosteroid excretion, unresponsive to cortisol suppression
Treatment: excision
Gross: unilateral
Micro: large lipid laden cells with distinct borders; Reinke crystals common
Lipid (steroid, lipoid) cell tumor - Ovary chapter
Any age, usually associated with virilizing syndrome (defeminization and amenorrhea)
Cells either lutein (theca/stroma), hilar (Leydig, with Reinke crystals) or adrenal cortical type
If Cushing syndrome present, tumor often called “adrenal cortical type”
Exact origin of tumor is unknown
May be biologically active or inactive
Malignant: 25%, usually large (7 cm or more), necrosis, hemorrhage, nuclear atypia, mitoses, may have peritoneal implants
Gross: usually unilateral, yellow/brown nodules separated by fibrous trabeculae
Micro: large rounded or polyhedral cells with abundant eosinophilic or vacuolated cytoplasm
Positive stains: fat stains on fresh/frozen tissue, vimentin (75%), keratin (50%), actin (30%)
EM: increased smooth endoplasmic reticulum, mitochondria have tubulovesicular cristae
DD: tumors with secondary proliferation of steroid hormone-producing cells (stromal luteoma, luteinized granulosa cell tumor [usually juvenile], fibroma-thecoma, stromal Leydig cell tumor, proliferations at periphery of other tumors)
Some consider it a variant of fibroma-thecoma (Arch Pathol Lab Med 1993;117:802)
Gross: solid and cystic, with blood filled cysts
Micro: scattered fibroblastic cells in well-vascularized myxoid background
Sclerosing stromal tumor - Ovary chapter
Rare, benign, resembles fibroma-thecoma but in younger patients
Prominent vasculature is associated with vascular endothelial growth factor expression (Am J Surg Pathol 1998;22:83)
Micro: lobular growth pattern of cellular and hypocellular areas composed of dual cell population (collagen producing spindle cells and lipid-containing round/oval cells); interlobular fibrosis, marked vascularity
Positive stains: desmin, smooth muscle actin
Molecular: trisomy 12 by FISH
EM: luteinized theca like cells, spindle-shaped fibroblastic cells, primitive mesenchymal cells
DD: Krukenberg tumor
References: Arch Pathol Lab Med 1989;113:372
Sertoli cell tumor - Ovary chapter
Rare; excellent prognosis
Mean 30 years old, range 2-76 years
Tends to secrete estrogen/progesterone, but diagnose based on morphology, not hormones
Similar to a well differentiated Sertoli-Leydig tumor without a Leydig component; may have abundant cytoplasmic lipid
Associated with Peutz-Jeghers syndrome
Usually stage I and clinically benign (Am J Surg Pathol 2005;29:143)
Case reports: 67 year old whose tumor has various histologic patterns (Arch Pathol Lab Med 2006;130:e70)
Gross: lobulated, solid, yellow-brown, unilateral, mean 9 cm, up to 30 cm
Micro: closely packed solid or hollow tubules lined by well differentiated cuboidal to columnar epithelial cells; few or no Leydig cells, often fibromatous or sclerotic; may have amyloid-like material; other patterns include cord-like and diffuse; variable stroma; occasional cells with bizarre nuclei; minimal mitoses, minimal atypia
malignant: moderate to severe cytologic atypia and 5+ MF/10 HPF
Positive
stains:
inhibin, vimentin, CD99, CD10, AE1-3 or CAM5.2 (usually), calretinin (50%),
variable smooth muscle actin and S100
Negative stains: EMA, chromogranin
EM: tight junctions, desmosomes, abundant rough endoplasmic reticulum and lipid
DD: endometrioid carcinoma (EMA+, inhibin-), carcinoid (chromogranin+, EMA+, inhibin-)
Lipid rich variant of Sertoli cell tumor - Ovary chapter
Large Sertoli cells with abundant cytoplasmic lipid
May be associated with isosexual pseudoprecocity, Peutz-Jeghers syndrome
“Adenomas” are common in testes of those with testicular feminization (most common tumor after seminomas), but are actually hamartomas, usually bilateral
Sertoli-Leydig tumor - Ovary chapter
Also called Sertoli-stromal cell tumor; formerly called androblastoma, arrhenoblastoma
Rare, < 0.1% of ovarian neoplasms
Morphologically resembles cells of testis at various stages of development, but ultrastructurally resembles ovarian granulosa cell tumors and contains female sex chromatin
Usually young women (mean age 25 years, 75%<age 30), but 10%>age 50; some with edema are diagnosed during pregnancy
Virilization in 30-50% with oligo/amenorrhea, loss of secondary sex characteristics, breast atrophy, masculinization [clitoral hypertrophy, hirsutism, deepening of voice]; also increased RBC count, increased serum testosterone and androstenedione, variable increases in serum alpha-fetoprotein, usually normal serum 17-ketosteroids
Feminine characteristics return after surgery, but manifestations of masculinization disappear more slowly
50% have no endocrine abnormalities
2% bilateral, 97% stage I, 2% spread beyond ovary
5% recur/metastasize
Well differentiated: older age, usually not associated with masculinization; usually clinically benign
Intermediate differentiated: associated with virilization; 11% clinically malignant
Poorly differentiated: 59% clinically malignant; case report of AFP production (Arch Pathol Lab Med 1986;110:65)
Tumors with heterologous elements: 19% clinically malignant
Retiform pattern: often young girls; tumors are stage I
Some cells show differentiation into both Sertoli cells and cells of rete testis, but lack presence of sex-determining region Y (Hum Pathol 2001;32:796, Hum Pathol 1997;28:1206)
Treatment: conservative surgery if tumor confined to ovary
Case reports: 4 year old girl with retiform pattern (Arch Pathol Lab Med 2002;126:377), 13 year old girl with elevated serum AFP, heterologous elements (hepatocytes) and retiform pattern (Am J Surg Pathol 1984;8:709), 17 year old girl with elevated AFP and clusters of hepatocytes (Arch Pathol Lab Med 1995;119:1075), 22 year old woman with retiform pattern and mucinous component (Arch Pathol Lab Med 2004;128:e93)
Gross: similar to granulosa cell tumors - golden-yellow but fewer blood filled cysts, almost never have unilocular cyst
Gross images: tan multinodular tumor; solid yellow-poorly differentiated tumor
Sertoli-Leydig tumor - Ovary chapter (continued)
Micro: hemorrhage/necrosis suggests poorly differentiated tumors or heterologous elements; edematous papillae suggests retiform subtype
Degenerative changes (bizarre and multiple nuclei) have no prognostic significance
Multiple subtypes may exist in same tumor (so % add up to > 100%)
Well differentiated (Meyer type I): 11%, may be nodular; tubular (hollow > solid), easily identifiable Leydig cells and Sertoli cells in a tubular pattern; may resemble endometrioid carcinoma or atrophic seminiferous tubules; crystals of Reinke in 20%
Intermediate differentiated (Meyer type II): 54%, outlines of immature tubules with immature Sertoli cells and large Leydig cells; may have mucus filled epithelial cells, cartilage, skeletal muscle
Poorly differentiated (Meyer type III): 13%, resemble indifferent gonad; may have sarcomatous appearance, Leydig cells in 2/3; may have mucus filled epithelial cells, cartilage, skeletal muscle
Pure Sertoli cell tumors (tubular androblastoma): similar to well differentiated Sertoli-Leydig cells but no Leydig cells and no primitive stromal elements; cytoplasm may have abundant lipid; tubular or follicle-like patterns; variable amyloid
With heterologous elements (teratoid androblastoma): 22%, associated with mucinous epithelium of GI type, liver, skeletal muscle, cartilage
Retiform (“netlike”): 15%, irregular branching, elongated and narrow tubules and cysts, which often have papillary structures; also ribbons of immature Sertoli cells; degenerative cells (large, bizarre cells without mitotic activity); usually associated with intermediate or poorly differentiated tumors; often have homologous or heterologous tissues including hepatocyte differentiation (positive for AE1-AE3, CAM5.2, AFP, ferritin, Hum Pathol 1999;30:611); resemble yolk sac tumors (Schiller-Duval bodies, AFP+), serous borderline tumors (older patients, no ribbons of immature cells)
Micro images: retiform pattern; inhibin alpha (fig 2); fig 1: CT scan; fig 2A/C: network of irregularly branching, elongated and narrow tubules, fig 2B: papillary area, fig 3A: moderate to well differentiated intestinal type mucinous epithelium with goblet cells, fig 3B: focal stratification and nuclear atypia, fig 4A/B: inhibin+
Positive stains: testosterone, estradiol, cytokeratin, AFP (in hepatoid areas), CD99 (Mod Path 1998; 11:769), inhibin alpha, low molecular weight cytokeratin, anti-Mullerian hormone focally (Hum Pathol 2000;31:1202), progesterone receptor, androgen receptor, vimentin (Hum Pathol 1997;28:1206)
Negative stains: EMA, PLAP, CEA, CA19-9, CA125, S100 (use to distinguish from carcinosarcoma)
Molecular: Trisomy 8 in case report (Hum Pathol 2001;32:559)
EM: elongated nuclei with deep indentations and annulate lamellae (resemble Sertoli cells), apical microvilli and frequent desmosomes (resemble rete testis)
DD: endometrioid carcinoma with sex cord-like elements, carcinoid tumor
References: Am J Surg Pathol 1985;9:543, Am J Surg Pathol 1984;8:405, Am J Surg Pathol 1983;7:755 (retiform pattern)
Sex cord tumor with annular tubules - Ovary chapter
Distinctive ovarian tumor associated with hyperestrinism (50%)
1/3 with tumor have Peutz-Jegher’s syndrome
Peutz-Jegher’s syndrome: autosomal dominant with variable penetrance; patients have ovarian sex cord stromal tumors or tumorlets with annular tubules (almost all patients, usually bilateral, often with calcifications, tumorlets are benign); mucocutaneous melanin pigmentation (lips, oral mucosa, digits, palms, soles, genitalia); GI hamartomatous polyposis (florid epithelium supported by broad bands of smooth muscle in stalk, causes intussusception and GI bleeding); occasional adenocarcinomas of GI tract, pancreas, breast, lung; occasional cervical adenoma malignum, ovarian mucinous carcinomas; Peutz was Dutch physician 1886-1957; Jeghers was American physician born 1904
Patients without Peutz-Jegher’s syndrome have large, unilateral tumors, with transitions to granulosa cell tumors, 40% secrete estrogen, 20% are malignant
Arise in ovarian cortex from follicular granulosa cells
Micro: mixture of simple and complex annular tubules with eosinophilic hyaline bodies, often calcified; resembles granulosa cell tumor with Sertoli growth pattern; simple annular tubules are ring shaped, with peripheral oriented nuclei around a central hyalinized body composed of basement membrane material; most of ring is anuclear cytoplasmic zone
Complex annular tubules are made of intercommunicating rings revolving around multiple hyaline bodies, often calcified
Contributed images: by anonymous - 10 year old girl with precocious puberty: image#1; #2; #3; alpha-inhibin
EM: granulosa cell and Sertoli cell features (granulosa cell-deeply indented nuclei, interdigitating plasma membranes joined by abundant desmosomes; Sertoli cell-variable Charcot-Bottcher filaments as cytoplasmic inclusions), Am J Clin Pathol 1981;75:11
DD: Sertoli cell tumors, granulosa cell tumors, gonadoblastoma (different clinical background, has germ cell component)
Case reports: 37 year old woman with ovarian mass (Case of Week #184)
Steroid cell tumor, NOS - Ovary chapter
< 0.1% of all ovarian tumors
Mean age 42 years, range 2 to 80 years
Usually associated with androgenic changes (56-77%); estrogen secretion in 6-23%, Cushing syndrome in 6-10%
Usually benign in prepubertal children
Clinically malignant in 25-43%, associated with 2+ mitosis per high-power field (92% malignant); necrosis (86% malignant); 7 cm or larger (78% malignant); hemorrhage (77% malignant); and grade 2 or 3 nuclear atypia (64% malignant); some clinically malignant cases are histologically benign
Case reports: 8 year old girl with virilization (Arch Pathol Lab Med 1991;115:150), 22 year old woman with virilization (J Med Case Reports 2007 Dec 18;1:182), 24 year old woman with hirsutism and multiple sclerosis (Arch Pathol Lab Med 2003;127:890), 29 year old woman with virilization and tumor in accessory ovary in broad ligament (Arch Pathol Lab Med 1996;120:405), 35 year old woman with virilization (Arch Pathol Lab Med 2006;130:113)
Gross: up to 45 cm, solid, well-circumscribed, yellow-orange to red-brown to brown-black cut surface (depending on amount of lipid and lipochrome pigment); 6% bilateral; occasional hemorrhage and cystic degeneration
Gross images: tan brown, well circumscribed tumor with hemorrhage
Micro: usually diffusely arranged cells, also nests, clusters, cords, columns; scant stroma may be fibromatous, edematous or myxoid; tumor cells are round/polygonal with spongy to granular, eosinophilic cytoplasm with clear intracytoplasmic vacuoles; distinct cell borders; central nuclei, prominent nucleoli; no Reinke crystals, no significant nuclear atypia or mitotic activity
Gross/micro images: H&E, Oil Red O (figure 4); diffuse sheets of large polygonal cells with vacuolated cytoplasm, vesicular nuclei and nuclear pleomorphism; fig 1: bright yellow lobulated mass, fig 2: medium-large polygonal cells with eosinophilic granular cytoplasm in delicate vascularized connective tissue network, fig 3: vimentin+, fig 4: inhibin+
Positive stains: inhibin, fat stains (75%), vimentin (75%), CAM 5.2 (46%), AE1/AE3 (37%), EMA (8%), S100 (7%)
Negative stains: chromogranin A, CD15 (Leu-M1), myoglobin, neurofilament, AFP, CEA, HMB-45
DD: stromal luteoma, clear cell carcinoma, metastatic renal cell carcinoma, luteoma of pregnancy
References: Am J Surg Pathol 1987;11:835
Usually > 40 years old, 65% after menopause
May be hormonally active, associated with estrogenic and occasionally (if steroid cells present) androgenic symptoms
Usually benign
Luteinized thecomas: thecoma plus features of steroid hormone secreting cells including edema, focal mitotic activity; may be associated with sclerosing peritonitis and ascites (Am J Surg Pathol 1994;18:1, Arch Pathol Lab Med 1996;120:303
Leydig cell containing thecoma: if Reinke’s crystalloids are present in cytoplasm
Gross: unilateral (90%), well defined, firm, solid, covered by intact ovarian serosa; variable size; usually yellow; often a mixture with fibroma (white)
Gross images: thecoma #1; #2; fibrothecoma
Micro: spindle cells with moderate pale cytoplasm containing lipid droplets and central nuclei; intervening stroma has collagen deposition and focal hyaline plaque formation; some tumors are heavily calcified; may have prominent stromal hyperplasia (hyperthecosis)
Micro images: thecoma #1; #2; fibrothecoma
Virtual slides: thecoma
Videos: #1
Positive stains: Oil red O or Sudan black (fat stains) on fresh/frozen tissue; silver stains demonstrate reticulin fibers surrounding individual cells (note: reticulin surrounds clusters of cells in granulosa cell tumors)
Molecular: trisomy 12
Tumor of adrenogenital syndrome - Ovary chapter
Case reports: 36 year old woman with congenital adrenal hyperplasia with sudden aggravation of virilizing symptoms (Am J Surg Pathol 2001;25:1443)
Gross: soft brown masses in ovarian or paraovarian tissue
Micro: identical to the testicular tumor of the adrenogenital syndrome
Unclassified sex cord stromal tumors - Ovary chapter
Differential diagnosis is usually between granulosa cell tumor and Sertoli-Leydig tumor
Predominance of primitive spindle-cell stroma or cords, trabeculae or tubules with features of both tumors in different areas
5 year survival is 92% (behavior resembles Sertoli-Leydig tumors of intermediate differentiation)
References: Am J Surg Pathol 1996;20:699, Arch Pathol Lab Med 1998;122:52
Other ovarian tumors
Female adnexal tumor of wolffian origin - Ovary chapter
Originally described as arising from broad ligament, also ovary, fallopian tube and retroperitoneum
Not a sex-cord stromal tumor since wolffian/mesonephric origin, but resembles them
No stromal cells of steroid hormone secreting type, no hormonal manifestations
Wide age range (15-81 years)
Usually benign, rarely malignant with metastases to omentum, liver, lung
Case reports: 60 year old with benign appearing primary but hepatic metastases (Arch Pathol Lab Med 2000;124:431)
Gross: solid or solid/cystic, smooth surface, yellow-tan, usually unilateral, 1-20 cm, focal hemorrhage and necrosis
Gross images: tumor of broad ligament and mesosalpinx
Micro: epithelial cells form cystic structures, hollow or solid tubules, diffuse sheets; sieve-like on low power; tubules outlined by well-defined basement membrane; cells are low cuboidal with minimal eosinophilic cytoplasm, oval hyperchromatic nuclei, finely granular chromatin, no atypia, no/rare mitotic activity; hemorrhage and necrosis may be present
PAS+ basement membranes are prominent around epithelial aggregates
Micro images: H&E, CAM 5.2, vimentin
Positive stains: CD10, CAM5.2, vimentin, variable EMA
Negative stains: mucin, B72.3, CEA, S100, inhibin alpha (may be weak / focal positive)
EM: thick layer of basal lamina surrounding tubules; prominent desmosomes, distinct junctional complexes; irregular nuclei, prominent nucleoli; cilia present
EM images: thick basement membrane, desmosomes
DD: Sertoli-Leydig cell tumor (has Leydig cells, clinical hormonal effects, not in broad ligament, inhibin alpha+), endometrioid adenocarcinoma of ovary (marked atypia and mitotic activity) or fallopian tube (intraluminal mass)
References: Am J Surg Pathol 2003;27:178
Microcystic stromal tumor - Ovary chapter
First described in 2008 (Am J Surg Pathol 2008 Oct 28. [Epub ahead of print])
Mean age 45 years, range 26-63 years
Usually unilateral
Appear to have benign behavior and stromal derivation
Gross: mean 9 cm (range 2-27 cm), usually solid-cystic; solid component is firm, tan or white-tan
Micro: conspicuous microcystic change with small round/oval cystic spaces that may coalesce to larger irregular channels; often intracytoplasmic vacuoles; also solid cellular areas with fibrous bands and hyaline plaques, similar to thecoma; cells have moderate, finely granular, lightly eosinophilic cytoplasm, bland round/oval or spindled nuclei with fine chromatin and indistinct nucleoli; may have foci of bizarre nuclei; up to 2 MF/10 HPF; no morphologic features diagnostic of other sex cord stromal tumors, no epithelial elements, no germ cell elements
Positive stains: CD10, vimentin; variable keratin (25%)
Negative stains: inhibin, calretinin, EMA
Small cell carcinoma of ovary, hypercalcemic type - Ovary chapter
Mean age 23, range 9-43 years), associated with hypercalcemia in 2/3 which disappears after excision
More common than pulmonary type
Poor prognosis due to extra-ovarian spread (50% in stage IA die of disease); better prognosis if 30 years or older, normal preoperative serum calcium, < 10 cm size, no large cells (Am J Surg Pathol 1994;18:1102)
Often associated with surface epithelial tumor
Not associated with hyperestrogenic effects
May be of germ cell origin (Hum Pathol 1987;18:175)
Case reports: 26 year old woman (Arch Pathol Lab Med 2006;130:e56), 32 year old woman with bilateral pleural effusions and ovarian mass (Arch Pathol Lab Med 2003;127:e271), ectopic parathyroid hormone production (Arch Pathol Lab Med 2005;129:531)
Gross: mean 15 cm (range 6-26 cm), solid, fleshy mass with hemorrhage and necrosis
Micro: diffuse sheets of small, closely packed round cells with scant cytoplasm, small hyperchromatic nuclei with irregular chromatin clumps, small but identifiable nucleoli; cytoplasmic hyaline globules, follicle-like structures with eosinophilic fluid, frequent mitotic figures; tumor necrosis with perivascular sparing; 50% have large cells with abundant eosinophilic cytoplasm and large nuclei with prominent nucleoli; 10% have mucinous epithelial cells with intracytoplasmic mucin; no crush artifact or Azzopardi effect
Cytology: highly cellular with poorly cohesive uniform small cells with scant cytoplasm, round/oval hyperchromatic nuclei, inconspicuous nucleoli, occasional mitotic figures
Micro images: various images; fig 1: solid areas are soft, pale-tan to gray, fig 2/3: sheets of small-medium cells with scant cytoplasm, round/oval hyperchromatic nuclei, frequent mitotic figures, ectatic vessels, fig 4: vimentin+
Virtual slides: #1
Positive stains: CAM 5.2, vimentin (50%), variable chromogranin, laminin, PTH-related protein, EMA (30%)
Negative stains: B72.3, S100 (Am J Clin Pathol 1989;92:140), inhibin
Molecular: diploid
EM: poorly differentiated; abundant dilated rough endoplasmic reticulum; no neurosecretory granules (Am J Clin Pathol 1988;90:523)
DD: lymphoma (Burkitt’s), dysgerminoma, ovarian small cell carcinoma of pulmonary type, granulosa cell tumor (different morphology, not associated with hypercalcemia)
Small cell carcinoma of ovary, pulmonary type - Ovary chapter
Mean age 59 years (range 28-85 years)
Resembles conventional pulmonary small cell carcinoma
Poor prognosis
Case reports: small cell and large cell tumor in 40 year old mother and 21 year old daughter (Arch Pathol Lab Med 1995;119:523)
Gross: 50% bilateral, most have extraovarian spread at diagnosis, mean 13 cm (4-26 cm), solid with variable cysts
Micro: sheets and nests of small/medium size round/spindle cells with hyperchromatic nuclei, fine regular chromatin (not clumped), inconspicuous nucleoli, minimal cytoplasm; also crush artifact, Azzopardi effect; occasionally associated with endometrioid carcinoma; may have squamous, mucinous, Brenner differentiation
Positive stains: keratin, EMA, neuron specific enolase; occasional chromogranin
Negative stains: vimentin
Molecular: aneuploid
EM: neurosecretory granules
References: Am J Surg Pathol 1992;16:926
Other tumors (not specific to ovary)
Adenoid cystic and basaloid carcinoma - Ovary chapter
Rare; resembles salivary gland or cutaneous carcinomas, pure or mixed with conventional patterns
Adenoid cystic carcinomas are more aggressive than basaloid carcinomas; present at older age
Case reports: with myoepithelial differentiation (Arch Pathol Lab Med 2000;124:1529 and Mod Path 1996;9:413)
Micro: small uniform and basaloid cells in tubular pattern with cribriform and focal solid areas; minimal pleomorphism or mitotic activity, no necrosis
Micro images: adenoid cystic carcinoma #1; #2; #3; S100; GFAP
Positive stains: CAM 5.2, AE1-AE3, CEA, muscle-specific actin, S100
EM: convoluted nuclei and filamentous structures associated with dense bodies; PAS+ basement membrane material appears as reduplicated basal lamina
References: Mod Path 1995;8:731
Angiomyolipoma - Ovary chapter
Angiosarcoma - Ovary chapter
Rare in ovary
Median age 31 years (range 25-42 years)
Gross: unilateral, hemorrhagic, median 13 cm
Micro: variable; vascular nature often not immediately apparent, but at least focal vasoformative channels or discrete cytoplasmic vacuoles; fascicular growth pattern composed of spindle cells with ovoid nuclei and ample eosinophilic cytoplasm mimicking leiomyosarcoma; also reticular growth pattern resembling yolk sac tumor; may also resemble clear cell carcinoma of ovary
Positive stains: vascular markers for vasoformative channels
References: Am J Surg Pathol 1998;22:620
Benign papillary mesothelioma - Ovary chapter
Typically an incidental finding
Has hyalouronidase-sensitive acid-mucin staining
Endometrial stromal sarcoma - Ovary chapter
Micro: high or low grade; plump oval cells arranged around spiral artery-like vessels
May be related to massive edema, probably not related to fibromatosis of soft tissue
Menstrual abnormalities common
Gross: firm, white cut surface
Micro: spindle cells separated by dense collagen, luteinized cells present
Fibrosarcoma - Ovary chapter
Aggressive
Trisomy 8 may be helpful in distinguishing from cellular fibroma (Am J Surg Pathol 1997;21:52)
Case reports: 8 year old girl with nevoid basal cell carcinoma syndrome (Am J Surg Pathol 1984;8:231)
Gross: large, solid, with adhesions
Micro: 4 or more mitotic figures per 10 high powered fields
Granulocytic sarcoma - Ovary chapter
May be initial clinical presentation of disease
Associated with AML in bone marrow
Often fatal
Case reports: with dysplastic nevus syndrome (Arch Pathol Lab Med 1991;115:830)
Gross: often green, bilateral
Micro: diffuse growth pattern with focal cords and pseudoacinar spaces; sclerosis often present; myeloid differentiation usually not prominent
Positive stains: chloroacetate esterase, lysozyme, myeloperoxidase, CD68, CD43
DD: lymphoma
Hemangioma - Ovary chapter
Case reports: large cavernous hemangioma in 68 year old woman (Arch Pathol Lab Med 1986;110:77)
Infantile hemangioendothelioma of ovary - Ovary chapter
Also called cellular hemangioma of infancy
Case reports: newborn (Am J Surg Pathol 1997;21:1231)
Micro: well-formed blood vessels and proliferating endothelial cells arranged in solid cordlike structures; tumor entraps normal ovarian follicles
Positive stains: Factor VIII, CD34, alpha smooth-muscle actin
EM: endothelial cells focally associated with pericytes
Rare, mean 50 years (range 42-76 years) in one study of 6 patients (Arch Pathol Lab Med 1992;116:1068)
Associated with synchronous leiomyomas of uterus
Do not recur locally or metastasize, even if mitotically active
Case reports: bilateral massive leiomyomas in 21 year old (Mod Path 1992;5:586)
Gross: median 3 cm (range 0.3 to 20 cm), often in hilar region
Micro: may be cellular, have prominent mitotic activity or occasionally have bizarre nuclei or myxoid stroma
Leiomyosarcoma - Ovary chapter
Rare
62% die of disease within mean 24 months (Am J Surg Pathol 2004;28:1436)
Case reports: 58 year old with primary tumor (Arch Pathol Lab Med 1991;115:941)
Micro: usually 2 of 3 - moderate/severe cytologic atypia, 10+ MF/10 HPF, tumor cell necrosis
Positive stains: desmin, vimentin, muscle specific actin
Myxoid leiomyosarcoma - Ovary chapter
Poor prognosis
Large gelatinous mass with cystic change, necrosis, hemorrhage
Micro: elongated cells surrounded by abundant basophilic material, low mitotic count
Positive stains: smooth muscle actin
References: Hum Pathol 1991;22:1268
Lymphoepithelioma-like carcinoma - Ovary chapter
Rare in female genital tract
Case reports: 51 year old woman with ovarian tumor and nodal metastases (Arch Pathol Lab Med 2007;131:1715)
Gross images: multinodular solid tumor
Micro: undifferentiated carcinoma with pleomorphic epithelioid cells and marked lymphocytic infiltrate, resembling nasopharyngeal tumor
Micro images: various images
Usually B cell
55% bilateral
Children - usually Burkitt’s lymphoma
Adults - usually diffuse large cell or follicular lymphoma
May be difficult to determine if primary or secondary
5 year survival is 80% after surgery or chemotherapy in primary disease vs. 33% in secondary disease
Case reports: diffuse large cell lymphoma in 23 year old (Arch Pathol Lab Med 2003;127:e169)
Micro: Burkitt’s lymphoma cells tend to grow in cords or nests, forming pseudoacini, accompanied by sclerosis, resembling carcinoma; diffuse large cell lymphoma cells may appear as short fascicles and form interlacing bundles of spindle cells, resembling a stromal tumor
Micro images: diffuse large cell lymphoma #1; #2 with CD20 (fig 3), CD3 (fig 4); follicular lymphoma; Burkitt’s lymphoma; precursor T-lymphoblastic lymphoma
Negative stains: ER, PR
References: Mod Path 2001;14:1093, Am J Surg Pathol 1993;17:154, Arch Pathol Lab Med 1994;118:647
Malignant mixed mullerian tumor - Ovary chapter
Also called malignant mixed mesodermal tumor, MMMT
Postmenopausal, low parity
Very poor prognosis; stage is best predictor; most patients present at advanced stage
Gross images: contributed by Dr. Mona Kandil, Menoufiya University, Egypt - ovary; uterus; omental deposit
Micro images: contributed by Dr. Mona Kandil, Menoufiya University, Egypt - 55 year old woman with ovarian mass - high grade epithelial tumor cells and necrosis; necrotic foci; high grade malignant glands #1; #2; #3; high grade tumor cells with mitotic figures #1; #2; malignant stroma
Micro: homologous (nonspecific malignant stroma) or heterologous (malignant elements of a different tissue type, particularly cartilage); often contains hyaline droplets containing alpha-1-antitrypsin in cytoplasm (Hum Pathol 1982;13:930); rare trophoblastic tissue (Hum Pathol 1988;19:1235)
Micro images: rhabdomyosarcoma component #1; #2
Positive stains: keratin; tumor cell droplets - PAS, diastase resistant; alpha-1-antitrypsin
DD: immature teratoma (children)
References: Am J Surg Pathol 1980;4:37, Arch Pathol Lab Med 1991;115:918
Mesothelioma - Ovary chapter
Rarely presents as ovarian masses
Median age 52 years old, range 16-63 years
Patients usually present with widespread peritoneal tumor, but occasionally is limited to 1-2 ovaries
Gross: 3-15 cm, often bilateral, solid with occasional small cysts
Micro: serosa and parenchyma involved by epithelial or biphasic tumor with papillary, tubular-glandular or solid patterns; tumor cells have moderate atypia and low mitotic rate; stroma is hyalinized, occasionally with striking hyalinized cores, psammoma bodies
References: Am J Surg Pathol 1996;20:1067
Metastases to ovary - Ovary chapter
Common site for metastases; 7% of ovarian tumors are metastases
Usually are bilateral, small, multinodular surface tumors with extensive extraovarian spread
Often have unusual patterns of dissemination, unusual histologic features, angiolymphatic invasion, desmoplasia
Most common metastases are appendix (adenocarcinoid or mucinous adenocarcinoma), breast, carcinoid, colon, pancreas, stomach
May have associated ovarian stromal luteinization with masculinization
Rarely chordoma (Arch Pathol Lab Med 1990;114:208)
Abdominopelvic sarcoma of perivascular epithelioid cells metastatic to ovary - Ovary chapter
Rare tumor at any site (4 cases) described in 2001 in women 19 to 41 years presenting with mass of serosa of the ileum, uterus or pelvic cavity
Resembles angiomyolipoma and clear cell “sugar” tumor of lung
Considered a sarcoma of uncommitted perivascular epithelioid cells without smooth muscle or adipose (Mod Path 2001;14:563)
Micro: sheets of large polygonal cells with glycogen-rich clear or eosinophilic cytoplasm, moderately pleomorphic nuclei, delicate vasculature, resembling clear cell carcinoma; angiolymphatic invasion common, metastases to lymph nodes and ovary; also coagulative necrosis, occasional mitotic figures, intracytoplasmic brown pigment; no spindled cells, smooth muscle or fat
Micro images: clear cells resembling renal cell carcinoma; high power; nodal metastases HMB45+
Positive stains: HMB45, MART-1
Negative stains: S-100, vimentin, muscle-specific actin, desmin and chromogranin A
Breast carcinoma metastatic to ovary - Ovary chapter
25-38% of ovarian metastases, often microscopic
Positive stains: GCDFP-15 (Hum Pathol 1991;22:368)
Negative stains: Pax8 (usually positive in ovarian carcinomas except mucinous types, Am J Surg Pathol 2008;32:1566), WT1 (positive in 2% versus 63% of ovarian tumors, usually negative in ovarian clear cell, mucinous and endometroid subtypes), CA125 (weak/negative in breast carcinomas, 90% of ovarian carcinomas are CA125+, Am J Surg Pathol 2005;29:1482)
Cervical carcinoma metastatic to ovary - Ovary chapter
Endocervical primaries are usually HPV related and p16+ (Am J Surg Pathol 2007;31:653)
Virtual slides: #1
Colon carcinoma metastatic to ovary - Ovary chapter
Associated with advanced primary lesions, but ovarian mass may be first indication of disease
Often large, unilateral or young patient (Am J Surg Pathol 2006;30:177)
Gross: 43% bilateral, cystic, mucin producing, hemorrhagic and necrotic
Micro: well differentiated, cribriform growth, intraluminal “dirty” necrosis, segmental destruction of glands, no squamous metaplasia
Micro images: various images #1; #2; CDX2, P504S and beta-catenin staining
Stains: (a) usually CK7 negative/focal, CK20+, CEA+, HAM56-, MUC5AC-, CA125- vs ovarian primary with oppositve staining; (b) diffuse expression of CDX2, beta-catenin and P504S is virtually diagnostic (Mod Pathol 2005;18:19)
DD: endometrioid or mucinous adenocarcinoma of ovary
References: Hum Pathol 1995;26:852, Mod Path 1996;9:426, Mod Path 1994;7:396, Hum Pathol 2000;31:672, Hum Pathol 1998;29:491, Am J Surg Pathol 1987;11:114
Desmoplastic small round cell tumor metastatic to ovary - Ovary chapter
May metastasize to ovary; common in teenage girls
Extensive extraovarian tumor at presentation
Gross: often bilateral
Micro: prominent nodular ovarian growth; nests of small cells with scant cytoplasm, hyperchromatic nuclei, prominent desmoplastic stroma
Positive stains: cytokeratin, EMA, desmin, vimentin, Leu-7/CD57, S100
EM: frequent intercellular junctions, basal lamina, cytoplasmic filaments, sparse, small dense granules of either neuroendocrine or lysosomal type
References: Hum Pathol 1992;23:454
Gastric carcinoma (intestinal type) metastatic to ovary - Ovary chapter
Rare; signet-ring metastases (Krukenberg tumor, see below) are much more common
Mean 55 years old
Usually identified after gastric primary is known
Very aggressive with death within 1 year (Am J Surg Pathol 2006;30:1382)
Gross: solid and cystic
Micro: pseudoendometroid with tubulo-glandular, cribriform and papillary patterns; may have mucinous appearance; prominent necrosis
Gastrointestinal stromal tumor metastatic to ovary - Ovary chapter
Rare
Mean age 59 years, range 44-81 years
Primary usually in small bowel or its mesentery (4/5 cases)
Often death due to disease, possibly due to misdiagnosis (Am J Surg Pathol 2005;29:920)
Gross: often bilateral, solid, tan, lobulated
Micro: spindle cells and epithelioid cells, low grade features
Virtual slides: small bowel tumor
Positive stains: CD117; variable h-caldesmon, smooth muscle actin and CD34
Negative stains: desmin
DD: leiomyosarcoma (tumor in uterus, high grade, desmin+, c-kit negative)
Intrahepatic cholangiocarcinoma metastatic to ovary - Ovary chapter
Mimics primary mucinous neoplasms
Often simultaneous detection of hepatic and ovarian masses or ovarian masses detected first (Am J Surg Pathol 2007;31:1788)
62% bilateral
Micro: surface implants in 80%, infiltrative stromal invasion in 86%, multinodular growth in 48%; variably sized glands with cystic dilation, also small clusters and individual cells; tumor cells vary from tall columnar mucinous cells to flat/cuboidal cells with nonspecific features
Positive stains: CK7, variable CK20
Krukenberg tumor - Ovary chapter
Metastatic signet ring cell adenocarcinoma of ovary; usually from GI tract (signet ring type), often stomach (2/3, due to retrograde lymphatic spread, Arch Pathol Lab Med 2006;130:1725), appendix, colon or breast; primary is often clinically occult and very small
1-2% of ovarian tumors, but higher in Japan (which has higher prevalence of gastric carcinoma)
Initially described by German gynecologist and pathologist Friedrich Ernst Krukenberg (1871-1946)
Mean 45 years, range 13-84 years, 43% under age 40 years (Am J Surg Pathol 2006;30:277)
In young patients, may be mistaken for granulosa cell tumor or lipid rich tumor
Most patients die within 2 years
Symptoms: abdominal pain or swelling, ascites (with positive cytology), occasionally vaginal bleeding or virilization
Case reports: bilateral ovarian tumor due to appendiceal adenocarcinoid (Arch Pathol Lab Med 1985;109:930)
Gross: multinodular enlargement of ovaries, bilateral (63-80%), mean 10 cm, intact bosselated external surfaces without adhesions; solid, firm to edematous / gelatinous cut surface, cysts in 1/3
Gross images: #1
Micro: multiple nodules separated by normal stroma in small tumors and focally in large tumors; more cellular at peripheray and edematous / gelatinous centrally; mucin-producing signet-ring cells comprise at least 10% of neoplasm, but have variable appearance and patterns; must see intracytoplasmic mucin; commonly vascular space invasion; may have marked stromal proliferation with storiform growth and variable luteinization (pregnant and nonpregnant patients); frequently focal tubules (Am J Surg Pathol 1981;5:225), glands and cysts
Micro images: signet ring cells #1; #2
Virtual slides: bilateral tumor
Lung carcinoma metastatic to ovary - Ovary chapter
Rare, may occur without lung symptoms
Mean age 47 years, range 26-76 years
Prior diagnosis of lung cancer in only 53%, usually small cell or adenocarcinoma (Am J Surg Pathol 2005;29:997)
Case reports: 42 year old woman with pulmonary papillary adenocarcinoma (Arch Pathol Lab Med 2002;126:1101)
Gross: mean 10 cm, often bilateral
Gross/micro images: H&E, CEA
Micro: multinodular growth, widespread necrosis, extensive lymphovascular invasion; involvement of ovarian surface is rare
Micro images: adenocarcinoma, papillary-acinar type
Positive stains: CEA, TTF-1
Negative stains: CA125
Melanoma metastatic to ovary - Ovary chapter
Rare; mean age 38 years (range 21-60 years)
50% had metastatic tumor outside the ovary, 60% had known cutaneous melanoma, 15% had other pigmented lesions excised
Most die within a few years of ovarian excision (Am J Surg Pathol 2004;28:771)
Gross: often bilateral, mean 10 cm, 30% brown/black, often cystic
Gross Images: black tumor
Micro: sheets or nodules of large cells with abundant eosinophilic cytoplasm, prominent nucleoli, occasional cytoplasmic pseudoinclusions in nuclei or cytoplasmic melanin pigment; necrosis common; follicle-like spaces common; occasionally tumors have small cells with scanty cytoplasm, spindle cells or nevoid appearance
Positive stains: S100, HMB45, MART-1, vimentin; usually tyrosinase and MITF, occasionally inhibin
Negative stains: keratin, calretinin
EM: melanosomes
DD: juvenile granulosa cell tumor, small cell carcinoma
References: Am J Surg Pathol 1991;15:849, Am J Surg Pathol 1987;11:959
Neuroendocrine carcinoma metastatic to ovary - Ovary chapter
Gross images: ileal tumor
Pancreatic acinar cell carcinoma metastatic to ovary - Ovary chapter
May be detected in ovary before pancreatic primary is identified (Am J Surg Pathol 2008;32:1540)
Micro: highly cellular with minimal fibrous stroma; often acinar growth pattern of cells with eosinophilic granular cytoplasm, uniform nuclei with prominent nucleoli; resembles carcnoid tumor but chymotrypsin+, trypsin+, synaptophysin-, chromogranin-; also focal alpha-inhibin+
Pancreatic ductal carcinoma metastatic to ovary - Ovary chapter
May simulate primary ovarian cancer
Gross: large, multiloculated cystic neoplasm, usually bilateral with surface desmoplastic implants and extraovarian spread
Micro: may focally resemble benign, borderline or malignant mucinous tumor
References: Am J Surg Pathol 1989;13:748
Renal cell carcinoma metastatic to ovary - Ovary chapter
Rare, <15 cases reported
Case reports: 48 year old woman with no history given of renal mass (Arch Pathol Lab Med 2003;127:e123)
Gross: hemorrhagic and multiloculated cystic mass with focal golden-yellow solid areas
Micro: solid areas with clear, polygonal tumor cells arranged in sheets or nests surrounded by delicate, thin-walled vascular septa; bland nuclei without mitoses; dilated tubules with intratubular eosinophilic fluid or blood; no desmoplasia
Positive stains: EMA, RCC, CD10
Negative stains: AE1/AE3 (may be weak), CAM5.2 (may be weak), 34betaE12, ER, CA125, inhibin, calretinin, CD34, AFP
DD: primary clear cell carcinoma of ovary (usually unilateral, clear cells with hobnail cells lining cysts and tubules, PAS+ material in papillary cords, usually CK7+, RCC-, CD10-, renal cell carcinoma is opposite, Int J Gynecol Pathol 2003;22:272), steroid cell tumor (usually androgenic or estrogenic symptoms, not bilateral, lipid rich tumor with clear intracytoplasmic vacuoles, inhibin+, EMA-), dysgerminoma (usually 20-40 years old, unilateral, clear cells have prominent nucleoli, lacks vasculature of renal cell carcinoma, fibrous stroma has mature lymphocytes, PLAP+, EMA-)
Mullerian adenosarcoma - Ovary chapter
Low grade variant of mixed mullerian tumor; more commonly seen in endometrium and cervix
Mean age 54 years, range 30-84 years
67% have tumor rupture at or before excision
Poorer prognosis than uterine adenosarcoma, perhaps due to lack of anatomic barrier to spread
Tends to recur as pure sarcoma or adenosarcoma
Poor prognostic factors: extraovarian spread (high stage), tumor rupture, high grade, high-grade sarcomatous overgrowth, < age 53 years
Survival: 5 year-64%, 10 year-46%
Gross: 97% unilateral, mean 14 cm (range 5-50 cm); usually solid with occasional small cysts
Gross images: solid mass with soft areas
Micro: (1) conspicuous non-invasive mullerian-type glands within a predominant malignant stroma, either homologous or heterologous; (2) periglandular cuffs of cellular stroma (80%), intraglandular protrusions of cellular stroma (60%) or both, (3) at least mild stromal atypia (33%); (4) variable stromal mitotic count; usually marked stromal cellularity (resembling endometrial stromal sarcoma or cellular ovarian fibroma), other features - glands widely spaced throughout stroma (90%), occasional sarcomatous overgrowth (30%), sex cord-like elements (15%), heterologous elements (12%); may have hypocellular stromal areas
Micro images: adenosarcoma
DD: benign tumor (adenofibroma, endometriosis - lack periglandular cellular cuffs of cellular stroma, no stromal atypia), immature teratomas (younger patients, usually embryonal neuroectodermal elements, no periglandular cellular cuffs of cellular stroma), endometrial stromal sarcoma (sample thoroughly to rule out glandular component), malignant mixed mullerian tumor (glandular and stromal epithelium is obviously malignant vs. at most atypical glands in stromal sarcoma)
References: Am J Surg Pathol 2002;26:1243
Myofibroblastoma - Ovary chapter
Case reports: 22 year old woman with 9 cm tumor entirely replacing ovary (Mod Path 1999;12:907)
Micro: encapsulated, composed of cytologically bland spindled cells arranged in patterns of solitary fibrous tumor and hemangiopericytoma
Positive staining: smooth muscle actin, muscle-specific actin; focal/weak for CD34
Negative staining: S100, desmin, AE1/AE3
EM: myofibroblastic differentiation
DD: solitary fibrous tumor, hemangiopericytoma
Nephroblastoma (Wilm’s tumor) - Ovary chapter
Case reports: 19 cm multilocular mass in 21 year old woman (Hum Pathol 2000;31:761)
DD: retiform Sertoli-Leydig cell, adenosarcoma
Neuroendocrine carcinoma (nonsmall cell type) - Ovary chapter
Rare and aggressive
Associated with coexisting mucinous carcinoma, endometroid carcinoma or mature cystic teratoma
Mean 47 years, range 22-63 years
Case reports: 22 year old woman with coexisting borderline mucinous tumor (Arch Pathol Lab Med 1994;118:1032)
Treatment: TAHBSO, chemotherapy; patients with stage III/IV disease often die of disease
Gross: usually unilateral, cystic or solid/cystic, mean 16 cm (5-26 cm)
Micro: solid pattern, nests or trabeculae of large to intermediate round/oval cells with brisk mitotic activity
Positive stains: keratin cocktail, CK7, CAM 5.2, usually CK20, synaptophysin; usually chromogranin A, CD58, c-kit
References: Am J Surg Pathol 2007;31:774
Osteoclast-like giant cell tumor - Ovary chapter
Case reports: 8 cm tumor in 76 year old woman (Am J Surg Pathol 2003;27:854)
Micro: diffuse, bland-appearing osteoclast-like giant cells mixed with pleomorphic mononuclear cells; hemorrhage, large areas of necrosis, frequent mitotic figures among mononuclear cells; infiltrative border, vascular invasion; no cystic tumor; no epithelial component
Positive stains: osteoclast-like giant cells - CD68, vimentin, alpha-1-antichymotrypsin, CD45; mononuclear cells - vimentin, PCNA
Negative stains: mononuclear cells - keratin, EMA, CK7, CD45, CD68, S100
Case reports: primary osteosarcoma in 47 year old Japanese woman (Am J Surg Pathol 1988;12:567)
Gross: large multilocular cysts with blood and solid tissue
Micro: anaplasia, blood filled spaces lined with tumor cells
Rare as primary or metastasis
May be associated with hypertension
Gross: 8 to 22 cm, solid, tan, brown or yellow; often extraovarian involvement
Micro: nested zellballen pattern with clusters of cells surrounded by vascular stroma; tumor cells have abundant, eosinophilic cytoplasm with occasional clear cells or bizarre giant tumor cells
Virtual slides: paraganglioma
Positive stains: neuroendocrine markers, variable S100+ sustentacular cells, variable inhibin and calretinin
Negative stains: keratin
EM: dense core neuroendocrine granules
References: Am J Surg Pathol 2006;30:600
PNET / Ewings sarcoma - Ovary chapter
Case reports: 29 year old woman (Am J Surg Pathol 1998;22:1417)
Micro: solid nests and sheets of monotonous, primitive, small round cells with occasional rosettes
Positive stains: CD99
Molecular: t(11;22)(q24;q12), EWS-FLI-1 chimeric RNA
DD: small cell carcinoma of the ovary
Rhabdomyosarcoma - Ovary chapter
Presents as disseminated tumor in neonates or young children, with difficulty determining primary tumor site (other pediatric tumors with similar presentations include infantile myofibromatosis, neuroblastoma, lymphoma, malignant rhabdoid tumor)
Subtypes in children and 5 year survival: embryonal (49% of cases, 66%), alveolar (31% of cases, 88%), botyroid (6% of cases, 95%), spindle cell (3% of cases, 88%)
Case reports: alveolar subtype in 2 year old girl with ovarian mass and pleural effusions (Arch Pathol Lab Med 2003;127:e56)
Cytology: highly cellular, with background reactive mesothelial cells and lymphocytes; tumor cells are bizarre, discohesive giant cells with pleomorphic hyperchromatic nuclei, variable eosinophilic cytoplasm with occasional vacuoles, frequent mitotic figures
Micro images: H&E, desmin (fig 3A), myogenin (fig 3B)
Positive stains: desmin, myogenin
Molecular: t(2;13)(p36;q14) found in 60% of alveolar subtypes (Pax3 and FKHR genes), associated with older age, truncal tumors, advanced stage, poorer prognosis; t(1;13)(p36;q14) involves Pax7 and FKHR genes, associated with better prognosis
Squamous cell carcinomas - Ovary chapter
May represent extreme expression of squamous metaplasia in endometrioid carcinomas, transformation of ovarian teratomas, HPV related transformation
Often associated with dermoid cyst (50%) and endometriosis (20%)
Case reports: associated with HPV DNA 16/18 in ovary, high grade VIN and high grade SIL (Am J Surg Pathol 1996;20:767), 12 years after hysterectomy for endometriosis (Arch Pathol Lab Med 1987;111:864)
Gross: 6-35 cm, often forming mural nodules with intracavitary protrusion, focal necrosis, hemorrhage
References: Am J Surg Pathol 1996;20:823
Undifferentiated carcinoma - Ovary chapter
Mean 54 years (range 39-72 years)
Usually stage III/IV
Micro: large groups or sheets with desmoplastic stroma; foci of papillary serous, urothelial, adenocarcinoma often present; necrosis common; vascular invasion in 20%
References: Arch Pathol Lab Med 1991;115:377
Staging for Ovary and Primary Peritoneal Carcinoma (AJCC 7th) - Ovary chapter
Clinical and pathologic categories are the same
Primary tumor (T) and FIGO stages in ( ) - Ovary chapter
TX: Primary tumor cannot be assessed (example-malignant cytology of peritoneal fluid)
T0: No evidence of primary tumor
T1 (I): Tumor limited to one or both ovaries
T1a (IA): Tumor limited to one ovary, capsule intact, no tumor on ovarian surface, no malignant cells in ascites fluid or peritoneal washings
T1b (IB): Tumor limited to both ovaries, capsule intact, no tumor on ovarian surface, no malignant cells in ascites fluid or peritoneal washings
T1c (IC): Tumor limited to one or both ovaries with any of the following: capsule ruptured, tumor on ovarian surface, malignant cells in ascites or peritoneal washings
T2 (II): Tumor involves one or both ovaries with pelvic extension
T2a (IIA): Extension to or implants on uterus or fallopian tube(s); no malignant cells in ascites or peritoneal washings
T2b (IIB): Extension to or implants on other pelvic tissues; no malignant cells in ascites or peritoneal washings
T2c (IIC): Pelvic extension or implants (T2a or T2b) with malignant cells in ascites fluid or peritoneal washings
T3 (III): Tumor involves one or both ovaries with microscopically confirmed peritoneal metastasis outside the pelvis
T3a (IIIA): Microscopic peritoneal metastasis beyond pelvis (no macroscopic tumor)
T3b (IIIB): Macroscopic peritoneal metastasis beyond pelvis 2 cm or less in greatest dimension
T3c (IIIC): Peritoneal metastasis beyond pelvis more than 2 cm in greatest dimension or regional lymph node metastasis
Notes:
● Liver capsule metastasis is T3 (Stage III); liver parenchymal metastasis is M1 (Stage IV)
● Pleural effusion must have positive cytology to be considered M1 (Stage IV)
● Non-malignant ascites is not classified; ascites does not affect staging unless malignant cells are present
Regional lymph nodes (N) and FIGO stages in ( ) - Ovary chapter
NX: Regional lymph nodes cannot be assessed
N0: No regional lymph node metastasis
N1 (IIIC): Regional lymph node metastasis
Distant metastasis (M) and FIGO stages in ( ) - Ovary chapter
M0: No distant metastasis
M1 (IV): Distant metastasis (excludes peritoneal metastasis)
Anatomic Stage / Prognostic groups - Ovary chapter
Stage I: T1 N0 M0
Stage IA: T1a N0 M0
Stage IB: T1b N0 M0
Stage IC: T1c N0 M0
Stage II: T2 N0 M0
Stage IIA: T2a N0 M0
Stage IIB: T2b N0 M0
Stage IIC: T2c N0 M0
Stage III: T3 N0 M0
Stage IIIA: T3a N0 M0
Stage IIIB: T3b N0 M0
Stage IIIC: T3c N0 M0 or any T N1 M0
Stage IV: Any T Any N M1
Features to report - Ovary chapter
Specimen type
Tumor site
Specimen integrity (intact, ruptured, fragmented, other)
Tumor size
Histologic type
Histologic grade (benign, borderline, malignant - poor, moderate or well differentiated)
Invasion sites within ovary
Surface involvement
Involvement of fallopian tube, opposite ovary, other tissues
Implants: noninvasive epithelial, noninvasive desmoplastic, invasive
Margins
Angiolymphatic space involvement:
Lymph nodes positive / number of nodes examined
Extranodal extension
Presence of endometriosis or other findings
