Pocket ObGyn – Ovarian / Germ Cell / Sex Cord Stromal Tumors
See Abbreviations

Epithelial Ovarian Cancer (EOC)

Definitions and Epidemiology (http://seer.cancer.gov/csr/1975_2008, accessed December 1, 2012)

• EOC is derived from surface epithelium of Incid: 12.8/100000 women/y
• 5th leading cause of cancer death in 90% of all ovarian cancers.
• Lifetime risk: 5%. Risk of death: 1%.
• Presentation red flag sx: Incidental abdominal pain, abdominal distension, loss of appetite, rectal bleeding, postmenopausal bleeding, weight loss

Pathology (Human Pathology 2009;40:1213)

• Serous tumors: Low & high grade
• 40–50% of EOC; most common type of 60% bilateral. Psammoma bodies seen in low-grade tumors. Most common in BRCA carriers & in pts w/ Lynch syn
• Mucinous tumors (Int J Gynecol Cancer 2008;18:209)
• 10% of EOC. 8–10% bilateral
• Endometrioid adenoCa
• 10% of all ovarian 28% bilateral. 42% a/w endometriosis; 15–20% a/w endometrial carcinoma
• Clear cell cystadenocarcinoma
• 10% of all ovarian 40% bilateral. A/w endometriosis & HyperCa.
• Brenner/transitional cell carcinoma
• Rare, poorly differentiated similar to high-grade transitional cell carcinoma of bladder
• Carcinosarcoma
• 1–4% of all ovarian Carcinomatous & sarcomatous elements. Often stage III or stage IV at dx. Poor overall survival.
• Metastatic tumors
• Krukenberg tumor: Signet ring cell, GI Colonic adenoCa. Pancr adenoCa. Breast cancer: Accounts for 6–40% of metastatic tumors to ovary; often bilateral. Renal cell carcinoma. Burkitt’s lymphoma. Low malig potential (borderline) tumor: Mucinous or serous.

Etiology (Gynecol Oncol 2010;119:7)

• Risk factors: Nulliparity, FHx, early menarche, late menopause, white race, increasing age, residence in North America or Northern Europe, personal h/o breast cancer, European Jewish, Icelandic or Hispanic ethnicity, talc exposure
• Protective factors: Long-term OCP use, tubal ligation, hysterectomy, breastfeeding
• Hypothesis of etiology: Incessant ovulation, gonadotropin/hormone/inflammation stimulation
• Hereditary breast & ovarian cancer (& see Ch. 1, screening)
• 10% of all ovarian BRCA1, BRCA2, & Lynch syn. Autosomal dominant.
• Lifetime risk w/ mut: 28–44%; higher w/ Cancer occurs 10 y earlier.

Diagnostic Workup

• Pelvic US: Complex adnexal mass (septations &/or solid components, size, wall loculation, papillary projections)
• Abdominopelvic CT or MRI: Complex adnexal mass, omental caking, ascites, peritoneal studding, perihepatic diaphragmatic implants, CA-125 ­ esp w/ serous tumors
• Refer to gynecologic oncologist if complex adnexal mass, elevated CA-125, ascites, significantly elevated CA-125 in premenopausal (>200 U/mL) or postmenopausal (>35 U/mL) women, FHx of breast or ovarian cancer in 1st-degree relative (Obstet Gynecol 2007;110:201)

Management

• BRCA1/BRCA2 carriers: Risk reducing BSO by age 40 or completion of child bearing

•   Surgery

Stage I: TAH, BSO, omentectomy, peritoneal biopsies, pelvic & para-aortic LND, pelvic washings

Stage I w/ desired fertility: Fertility sparing Surg w/ unilateral salpingooophorectomy, peritoneal biopsies, omentectomy, pelvic & para-aortic LND, pelvic washings

Stages II–IV: TAH, BSO, omentectomy, debulking of gross dz; optimal reduction to residual dz <1 cm

• Adjuvant chemo: Grade III or stage IC or higher: Postsurgical systemic chemo w/ platinum & paclitaxel.

 

• Neoadjuvant chemo: Used for pts who are not initial surgical Adjuvant RT not recommended.
• recurrent/persistent dz (Clin Obstet Gynecol 2012;55:114)

Carboplatin + paclitaxel for platinum sensitive dz (recurrence >6 mo from rx). Single-agent rx w/ alternative chemo agent (eg, topotecan, paclitaxel, docetaxel, gemcitabine) for platinum resistant (recurrence <6 mo from rx) or platinum refrac dz (progression during rx).

• Carcinosarcoma/MMMT: Surg + platinum-based chemo + paclitaxel or ifosfamide; role of radiation

Posttreatment Surveillance (Am J Obstet Gynecol 2011;204:466)

• Exam ± CA-125 q3mo for 3 y, then q6mo for 2 y, then yearly
• CT &/or PET, CA-125 if recurrence suspected

 

FIGO staging for ovarian cancer, 2009
		5-y survival (%)
stage i	Tumor confined to ovaries	89
ia iB ic	1 ovary; capsule intact Both ovaries; capsule intact Surface of 1 or both ovaries; capsule rupture; malig ascites, or positive peritoneal washings	IA: 94 IB: 91 IC: 80
stage ii	Tumor in 1 or both ovaries w/ extension to pelvis	II: 66
iia iiB iic	Extension to uterus or fallopian tubes Extension to other pelvic tissues Stage IIA or IIB w/ capsule rupture, malig ascites, or positive pelvic washings	IIA: 76 IIB: 67 IIC: 57
stage iii	Peritoneal implants or positive pelvic LNs Tumor limited to pelvis w/ negative LNs, but microscopic seeding of the abdominal peritoneal surfaces, or extensions to small bowel or mesentery Peritoneal implants or metastasis not exceeding 2 cm in diameter; negative LNs Peritoneal metastasis outside of pelvis & >2 cm in diameter; positive LNs	III: 34
iiia		IIIA: 45
iiiB		IIIB: 39
iiic		IIIC: 35
stage iv	Distant metastasis; malig pleural effusion; parenchymal liver metastasis	IV: 18
From Int J Gynaecol Obstet 2009;105:3; National Cancer Institute-SEER survival data 1998–2001.

Germ Cell Tumors

Definitions and Epidemiology (Cancer Treat Rev 2008;34:427)

• Cancer derived from primordial germ 1–2% of all ovarian malignancies
• 58% of all ovarian tumors in women <20 Incid: 0.41/100000 women/y

Pathology (Int J Gynecol Path 2006;25:305)

•   Dysgerminomas

1–2% all of ovarian tumors; 32% of malig germ cell tumors. Adolescents/young adults.

10–15% bilateral. Monophasic proliferation of primitive germ cells w/ infiltrating T cells.

Testicular seminoma equivalent; OCT4 positive & CD30 positive staining Lymphatic spread common; humoral HyperCa common; rapid enlargement High cure rate w/ rx (88.6%)

•   Endodermal sinus tumor (yolk sac tumor)

14–20% of malig germ cell tumors.Young girls/young women; 1/3 premenarchal Schiller–Duval bodies (microscopic feature w/ central capillary surrounded by flat-

tened parietal cells). AFP, cytokeratin, & PLAP positive staining. Unilateral, aggressive tumor

•   Embryonal carcinoma

4% of malig germ cell tumors. Avg age: 15 yo.

Cohesive groups of large primitive cells w/ overlapping nuclei, indistinct borders, syncytiotrophoblastic giant cells. hCG production leads to isosexual pseudoprecocity. Staining positive for OCT3, OCT4, & CD30.

 

•   Polyembryoma

Young girls. Numerous embryoid bodies resembling presomite embryos. hCG/AFP may be elevated.

•   Nongestational choriocarcinoma

2% of malig germ cell tumors. Cytotrophoblasts & intermediate trophoblasts capped w/ syncytiotrophoblasts in plexiform pattern. hCG, hPL, inhibin, & cytokeratin positive.

Early hematogenous spread to distant sites. Relatively chemoresistant.

•   Mixed germ cell tumor

5% of all malig germ cell tumors. 2 or more malig germ cell elements w/ at least

1 primitive. Dysgerminoma most common component.

•   Immature teratoma

Embryonic tissue; predominantly neuroepithelial. Grade 1, 2, or 3 based on quantity of neuroepithelial tissue. Unilateral.

•   Mature teratoma

Solid, cystic (dermoid, 95%), or fetiform. Composed of fetal or adult structures, no embryonal components. Most common ovarian tumor. 46XX karyotype.

Only 1–2% malig; most common malignancy is squamous cell carcinoma.

•   Monodermal teratomas

Struma ovarii, carcinoid, central nervous center tumor, carcinoma group, sarcoma group, sebaceous tumor, pituitary-type tumor, retinal anlage tumor, others.

Clinical Manifestations

• Abdominal pain (55–80%), abdominal/pelvic mass, abdominal enlargement, fever (10– 25%), ascites, ovarian torsion or rupture; abdominal distension (35%), vaginal bleeding (10%)
• Short duration of sx (2–4 w)
• 60–70% present at stage I or stage II, 20–30% stage III, stage IV Metastasis by peritoneal or lymphatic spread; hematogenous spread more common than EOC.
• Dysgerminoma a/w primary amenorrhea/gonadal dysgenesis

Diagnostic Workup

• Chest radiograph: Eval for metastasis
• Pelvic US: Cystic lesion w/ densely echogenic tubercle (Rokitansky nodule for mature teratoma). CA-125 not
• Abdominal/pelvic CT: Complex mass; fat attenuation in mature teratomas; calcification; speckled calcification in dysgerminomas (Radiographics 1998;18:1525)
• Karyotype if dysgerminoma suspected & h/o primary amenorrhea
• Staging same as for EOSs,

 

Germ cell serum tumor markers
	AFP	hCG	LDH	E2	Inhibin	Testosterone	Androgen	DHEA
Dysgerminoma	–	±	+	±	–	–	–	–
Yolk sac	±	+	±	±	–	–	–	–
Immature teratoma	±	–	±	±	–	–	–	±
Choriocarcinoma	–	+	±	–	–	–	–	–
Endodermal sinus	+	–	+	–	–	–	–	–
Polyembryoma	±	+	–	–	–	–	–	–
Mixed germ cell	±	±	±	–	–	–	–	–
Inhibin + for Granulosa cell, and +/- for Sertoli-Leydig and Gonadoblastoma. Testosterone/Androgen + for SertoliLeydig and +/- for Gonadoblastoma. See sex cord stromal tumors, below. From Pectasides D, Pectasides E, Kassanos D. Germ cell tumors of the ovary. Cancer Treat Rev. 2008;34(5):427–441.

Management

• Surg: TAH, BSO, omentectomy, peritoneal biopsies, pelvic washings, pelvic & paraaortic LND, surgical debulking if not sparing

Fertility sparing Surg poss if contralateral ovary appears nml; cystectomy may be poss. Bx contralateral ovary if dysgerminoma or if appears abn.

Second-look Surg if residual mass postchemotherapy or residual teratoma

•   Adjuvant chemo:

BEP (bleomycin, etoposide, cisplatin) is gold std Recurrence treated w/ chemo again

 

• Primary surveillance: Option for stage IA or IB
• Adjuvant radiation (RT): Alternative therapy for dysgerminomas

Posttreatment Surveillance (Am J Obstet Gynecol 2011;204:466)

• Exam & tumor marker(s) q2–4mo for 2 y, then Imaging w/ surveillance if no reliable tumor marker. CT & tumor marker(s) if recurrence suspected

• Overall prog based on stage, residual dz, histologic type, preop AFP & bhCG elevation; age not a factor

Sex Cord Stromal Tumors

Epidemiology (J Clin Oncol 2007;25:294)

• 7% of all malig ovarian Indolent course w/ favorable prog.

Pathology (J Clin Oncol 2007;25:294)

•   Granulosa cell tumor (GCT):

70% of malig sex cord-stromal tumors. Incid: 0.4–1.7/100000 women. More common in nonwhite, obese women.

3–5% of all ovarian neoplasms. Adult type-estrogen production w/ abn bleeding in 66%; EH 25–50%; endometrial cancer 5%.

Juvenile type: 90% in prepubertal girls; 95% unilateral; excellent prog.

Call–Exner bodies w/ eosinophilic material & nuclear debris, coffee bean nuclei. 95% unilateral. 78–91% stage I at dx; good prog.

•   Sertoli–Leydig cell tumors:

0.2% of all ovarian neoplasms. 98% unilateral. Avg age 20–30 y. 90% stage I; 70–90% 5-y survival; may recur soon after dx/rx Tubules of epithelial cells are steroid secreting

•   Thecoma:

Benign. Postmenopausal women. Estrogen ® EH (15%).

Luteinized thecomas ® virilization. Abundant lipid cytoplasm; solid, yellowish tumors.

•   Fibroma:

Benign. Most common sex cord-stromal tumor; 4% ovarian neoplasms.

4–8% bilateral. Postmenopausal women. Whorled bundles of spindle-shaped fibroblasts & collagen. A/w Meigs syn & basal nevus syn.

• Steroid cell tumors: 1–0.2% of all ovarian tumors. Stromal luteomas, Leydig (hilus) cell tumor, & steroid cell tumor not otherwise specified.
• Others: Sclerosing stromal tumors, sex cord tumor w/ annular tubules, gynandroblastomas

Clinical Manifestations

• Presentation: Abn bleeding, abdominal distension, abdominal pain. Isosexual precocious puberty w/ juvenile Virilization from androgens in Sertoli–Leydig. Meigs syn (fibroma, ascites, pleural effusions).

Diagnostic Workup (Radiographics 1998;18:1525)

• Pelvic US/Pelvic CT: Large, unilateral, multicystic w/ solid components; rare calcifications; carcinomatosis in GCTs (rare); well-defined hypoechoic mass for Sertoli–Leydig cell tumors; lack of papillary projections
• Pelvic MRI: High signal intensity due to tumor hemorrhage; GCTs w/ sponge-like appearance; Sertoli–Leydig cell tumors as solid mass; fibrothecomas w/ low signal intensity on T2
• Staging same as for EOSs, above

 

Sex cord-stromal tumor markers
	E2	Inhibin	Testosterone	Androgen	DHEA
Thecoma— fibroma	–	–	–	–	–
Granulosa	±	+	±	–	–
Sertoli–Leydig	±	±	±	±	±
From Pectasides D, Pectasides E, Kassanos D. Germ cell tumors of the ovary. Cancer Treat Rev. 2008;34(5):427–441. doi:10.1016/j.ctrv.2008.02.002. Epub 2008 Apr 18.

Management

• Surg: TAH, BSO, omentectomy, peritoneal biopsies, pelvic & para-aortic LND, pelvic washings. Fertility sparing Surg when poss & desired. Endometrial sampling w/ granulosa cell tumors, for See tables.

 

Posttreatment Surveillance (Am J Obstet Gynecol 2011;204:466)

• Exam & tumor marker(s) q2–4mo for 2 y, then q6mo for 3 y, then yearly
• CT & tumor marker(s) if recurrence suspected

 

Treatment of germ cell tumors
stage 1a	TAH, BSO, & staging (omentectomy, peritoneal biopsies, pelvic & para-aortic LND, pelvic washings). Fertility sparing Surg & staging if future fertility desired. Adjuvant chemo not indicated.
stage ic, malig ascites, high mitotic activity, or stage >1	TAH, BSO, staging, debulking Fertility sparing Surg & staging if future fertility desired Adjuvant chemo (BEP or platinum/taxane)
recurrent dz or pelvic/intra-abdominal dz	Secondary debulking Surg when feasible Postoperative therapy based upon prev treatments: Platinum based chemo, radiation for localized dz, or hormone therapy
distant recurrence	Platinum-based chemo, or hormonal rx in selected pts

See Abbreviations