Carcinoma Ovary

Ovarian cancer is the most lethal gynaecological malignancy because it presents late ("silent killer") and spreads transcoelomically across the peritoneum. NEET PG loves the histological classification, the tumour marker matched to each type, FIGO staging principles, and platinum–taxane chemotherapy. Master those four pillars and most questions fall.

Epidemiology & risk factors

Ovarian cancer is the third most common gynaecological cancer in India (after cervix and breast-uterus depending on region) but carries the highest case-fatality of any female genital tract cancer. Lifetime risk in the general population is ~1.3%; with a BRCA1 mutation it rises to 35–46%, and with BRCA2 to 13–23%.

The unifying theme of risk is "incessant ovulation" — anything that increases the number of lifetime ovulatory cycles increases risk; anything that suppresses ovulation protects.

Increase risk	Decrease risk (protective)
Early menarche, late menopause	Multiparity
Nulliparity / infertility	Combined oral contraceptive pills (strongest modifiable protection; ~50% reduction with 5 yr use)
BRCA1/BRCA2, Lynch (HNPCC)	Breast-feeding
Family history of ovarian/breast/colon ca	Tubal ligation, hysterectomy
Increasing age (epithelial: postmenopausal)	Salpingo-oophorectomy
Talc, asbestos (weak)	—

High-yield: Combined OCPs are the single most important protective factor and reduce risk by ~50% after 5 years of use — protection persists for decades after stopping.

High-yield: BRCA1 confers the highest hereditary risk; Lynch syndrome (HNPCC, MMR gene mutation) links ovarian (usually endometrioid) + endometrial + colorectal cancers.

Classification (the master table)

Ovarian tumours arise from three cell origins. ~90% of malignancies are epithelial; germ-cell tumours dominate in young women.

Origin	Benign / common types	Malignant types	Marker / hallmark
Surface epithelium (~65–70% of all; 90% of cancers)	Serous cystadenoma, mucinous cystadenoma, Brenner	Serous (most common ca), mucinous, endometrioid, clear cell, undifferentiated	CA-125
Germ cell (~15–20%; mostly benign)	Mature cystic teratoma (dermoid)	Dysgerminoma, yolk sac (endodermal sinus), immature teratoma, choriocarcinoma, embryonal	AFP, β-hCG, LDH (see below)
Sex-cord stromal (~5–10%)	Fibroma, thecoma	Granulosa cell, Sertoli–Leydig	Inhibin, oestrogen / androgen
Metastatic	—	Krukenberg (from stomach/breast)	Signet-ring cells

High-yield: Overall the most common ovarian tumour (benign + malignant) is the serous tumour; the most common ovarian malignancy is serous cystadenocarcinoma; the most common benign ovarian tumour in young women is the mature cystic teratoma (dermoid); the most common ovarian tumour in pregnancy is the dermoid cyst.

Epithelial ovarian cancer — pathology

The modern dualistic model divides epithelial cancer into two pathways:

• Type I (low grade): slow-growing, often from endometriosis or borderline tumours — low-grade serous, mucinous, endometrioid, clear cell. Mutations: KRAS, BRAF, PTEN, ARID1A. Relatively chemo-resistant.
• Type II (high grade): aggressive, presents at advanced stage — high-grade serous carcinoma (HGSC). Mutation: TP53 (~96%) and BRCA. Origin is now believed to be the fimbrial end of the fallopian tube (serous tubal intraepithelial carcinoma, STIC) rather than the ovarian surface itself — a frequently tested concept.

Histological pearls:

• Serous: Psammoma bodies (concentric laminated calcifications); commonest, often bilateral.
• Mucinous: large, multiloculated; rupture → pseudomyxoma peritonei (gelatinous ascites — though many are now attributed to appendiceal primaries).
• Endometrioid: ~15–20% coexist with endometrial carcinoma; arises in endometriosis.
• Clear cell: worst prognosis, chemo-resistant, hobnail cells, associated with endometriosis and hypercalcaemia/thromboembolism.
• Brenner: transitional (urothelial-like) epithelium with "coffee-bean" nuclear grooves; usually benign.

Germ cell tumours — markers are everything

These occur in young women/adolescents, are often unilateral, grow rapidly, and are highly chemosensitive (BEP regimen).

Tumour	Marker	Classic feature
Dysgerminoma	LDH (± β-hCG)	Most common malignant germ cell tumour; counterpart of seminoma; most radiosensitive ovarian tumour; "fried-egg" cells
Yolk sac (endodermal sinus)	AFP	Schiller–Duval bodies (glomerulus-like); rapid growth
Choriocarcinoma	β-hCG	—
Embryonal carcinoma	AFP + β-hCG	—
Immature teratoma	AFP (variable)	Graded by neuroepithelium
Mature teratoma (dermoid)	None	Benign; struma ovarii (thyroid tissue) → thyrotoxicosis; risk of torsion

High-yield mnemonic — markers: "LDH for Dys, AFP for Yolk, hCG for Chorio." Dysgerminoma = LDH; Yolk sac = AFP; Choriocarcinoma = β-hCG.

High-yield: Dysgerminoma is the most common malignant germ-cell tumour and the only one that is radiosensitive; the most common germ-cell malignancy in pregnancy is also dysgerminoma.

Sex-cord stromal tumours — functioning hormones

Tumour	Hormone	Clinical effect / hallmark
Granulosa cell	Oestrogen + inhibin	Postmenopausal bleeding, endometrial hyperplasia/cancer, precocious puberty in girls; Call–Exner bodies (rosettes); late recurrence
Sertoli–Leydig (androblastoma)	Androgens	Virilisation, hirsutism, defeminisation; Reinke crystals
Fibroma	None	Meigs syndrome = fibroma + ascites + right pleural effusion (resolves after removal)
Thecoma	Oestrogen	Postmenopausal bleeding

High-yield: Granulosa cell tumour → inhibin marker + oestrogen excess → think endometrial hyperplasia/carcinoma. Call–Exner bodies are the histology buzzword.

Clinical features

Early disease is asymptomatic — hence late presentation. Symptoms when present are vague:

• Abdominal bloating, distension, early satiety, dyspepsia, pelvic/abdominal pain.
• Increasing abdominal girth from ascites; a fixed, hard, irregular, nodular pelvic-abdominal mass.
• Sister Mary Joseph nodule (umbilical metastasis), omental cake, pleural effusion (malignant — stage IV).
• Functioning tumours → hormonal symptoms (bleeding, virilisation, precocious puberty).

High-yield: Spread is predominantly transcoelomic (transperitoneal) — exfoliated cells follow peritoneal fluid circulation up the right paracolic gutter to the right hemidiaphragm and omentum. This is the classic "peritoneal spread pattern" NEET PG asks about. Lymphatic spread is to para-aortic nodes.

Diagnosis & investigation of choice

Stepwise approach:

Pelvic mass on exam → Transvaginal ultrasound (initial/best imaging) → CA-125 (and germ-cell markers if young) → CT abdomen/pelvis for staging/spread → Definitive diagnosis = histopathology at surgery (staging laparotomy).

• Investigation of choice for evaluating an adnexal mass = transvaginal ultrasound. Sinister sonographic features: solid areas, thick septa (>3 mm), papillary projections, bilaterality, ascites, increased vascularity on Doppler (low resistance).
• CA-125: elevated in ~80% of epithelial cancers (especially serous) but non-specific — also raised in endometriosis, PID, fibroids, pregnancy, menstruation, cirrhosis, peritonitis. More reliable in postmenopausal women. Used mainly for monitoring treatment response and recurrence, not screening.
• HE4 + CA-125 → ROMA (Risk of Ovarian Malignancy Algorithm); RMI (Risk of Malignancy Index = ultrasound score × menopausal status × CA-125) triages referral.
• Do NOT aspirate / biopsy a suspicious cyst — risk of upstaging by spillage. Diagnosis is surgical.
• Screening is NOT recommended in average-risk women (no mortality benefit; UKCTOCS/PLCO trials negative).

High-yield: CA-125 is for monitoring, not screening. In a postmenopausal woman a solid/complex adnexal mass with raised CA-125 is cancer until proven otherwise.

FIGO staging (surgicopathological)

Staging is surgical, based on findings at laparotomy with peritoneal washings, omentectomy, and node sampling.

Stage	Extent
I	Limited to ovaries (IA one ovary; IB both; IC capsule rupture / surface involvement / malignant washings)
II	Pelvic extension (uterus, tubes — IIA; other pelvic tissue — IIB)
III	Peritoneal spread outside pelvis and/or retroperitoneal nodes (IIIA microscopic; IIIB ≤2 cm; IIIC >2 cm or capsular liver/spleen)
IV	Distant metastasis — IVA = malignant pleural effusion (positive cytology); IVB = parenchymal liver/spleen, extra-abdominal organs, inguinal nodes

High-yield: Most epithelial cancers present at stage III (advanced). Malignant pleural effusion = stage IVA. Capsular rupture or positive peritoneal cytology upgrades stage I to IC.

Management & drug of choice

Treatment hinges on staging surgery + platinum–taxane chemotherapy.

General flow: Suspicious mass → exploratory laparotomy with comprehensive surgical staging / cytoreduction (debulking) → if advanced, achieve optimal debulking (residual <1 cm; ideally R0/no visible disease) → adjuvant carboplatin + paclitaxel (6 cycles) → maintenance (bevacizumab and/or PARP inhibitor) → surveillance with CA-125.

• Surgery: total abdominal hysterectomy + bilateral salpingo-oophorectomy + omentectomy + peritoneal washings + para-aortic & pelvic node sampling + appendicectomy (mucinous). The single most important prognostic factor that surgery controls is the amount of residual disease — optimal cytoreduction improves survival.
• Chemotherapy: carboplatin + paclitaxel is the standard first-line regimen (drug of choice for epithelial cancer). Neoadjuvant chemotherapy is used for bulky stage III/IV unsuitable for primary optimal debulking, followed by interval debulking.
• Targeted maintenance: PARP inhibitors (olaparib, niraparib) especially in BRCA-mutated/HRD tumours; bevacizumab (anti-VEGF).
• Germ cell tumours: fertility-sparing unilateral salpingo-oophorectomy in young women + BEP chemotherapy (Bleomycin, Etoposide, cisPlatin). Dysgerminoma is also radiosensitive but chemo preferred to preserve fertility.
• Sex-cord stromal: surgery; chemo (BEP/platinum) for advanced.
• Borderline (low malignant potential) tumours: surgery alone, excellent prognosis, no routine chemo.

High-yield: First-line chemo for epithelial ovarian cancer = carboplatin + paclitaxel. Germ-cell tumours = BEP. "Platinum-sensitive" recurrence = relapse ≥6 months after platinum → re-challenge with platinum.

Complications

• Malignant ascites and bowel obstruction (omental/peritoneal disease) — the usual mode of death.
• Torsion (especially dermoid, benign cysts) → acute abdomen, surgical emergency.
• Rupture → chemical/pseudomyxoma peritonei (mucinous), upstaging.
• Pleural effusion (Meigs in benign fibroma; malignant in stage IV).
• Paraneoplastic: hypercalcaemia (clear cell, small-cell), cerebellar degeneration.
• Chemotherapy toxicity: carboplatin → myelosuppression; paclitaxel → peripheral neuropathy, hypersensitivity; bleomycin → pulmonary fibrosis; cisplatin → nephro/ototoxicity.

Key differentials

• Benign ovarian cyst / functional cyst — simple, thin-walled, anechoic, resolves on follow-up.
• Endometrioma ("chocolate cyst") — homogeneous ground-glass echoes; raises CA-125 (a common trap).
• Tubo-ovarian abscess / PID — fever, tenderness, raised inflammatory markers; CA-125 may be raised.
• Pedunculated/degenerating fibroid — uterine origin.
• Krukenberg tumour — bilateral metastatic ovarian masses with signet-ring cells from a GI (usually gastric) or breast primary; always look for a primary.
• Ectopic pregnancy, hydrosalpinx — in reproductive age with positive β-hCG.

High-yield: Bilateral solid ovarian masses with signet-ring cells = Krukenberg tumour; hunt for a stomach primary. Pseudomyxoma peritonei is classically linked to mucinous tumours but often originates from the appendix.

Recently asked / exam angle

• Tumour marker matched to histology: AFP → yolk sac, hCG → choriocarcinoma, LDH → dysgerminoma, inhibin → granulosa, CA-125 → epithelial. (Single most repeated theme.)
• Most common ovarian malignancy = serous cystadenocarcinoma; most common germ-cell malignancy = dysgerminoma.
• Mode of spread = transcoelomic / transperitoneal (right paracolic gutter to diaphragm).
• Origin of high-grade serous carcinoma = fallopian tube fimbria (STIC) — newer favourite.
• Histology buzzwords: psammoma bodies (serous), Schiller–Duval bodies (yolk sac), Call–Exner bodies (granulosa), Reinke crystals (Sertoli–Leydig), coffee-bean nuclei (Brenner), hobnail cells (clear cell), signet-ring (Krukenberg).
• Meigs syndrome triad and struma ovarii causing thyrotoxicosis.
• Best initial imaging = TVS; CA-125 for monitoring not screening; staging is surgical; first-line chemo = carboplatin + paclitaxel; germ cell = BEP.
• Most important prognostic factor after stage = residual disease after debulking.
• OCP is protective; BRCA1 highest hereditary risk; clear cell = worst histology prognosis.

Rapid revision

1. Most lethal gynae cancer; "silent killer" — most present at stage III.
2. Serous cystadenocarcinoma = commonest ovarian malignancy; bilateral, psammoma bodies.
3. Spread is transcoelomic → right paracolic gutter → diaphragm/omentum (omental cake).
4. Markers: CA-125 (epithelial), AFP (yolk sac), β-hCG (choriocarcinoma), LDH (dysgerminoma), inhibin (granulosa).
5. Dysgerminoma = commonest germ-cell malignancy, only radiosensitive one, marker LDH.
6. Yolk sac → Schiller–Duval bodies; granulosa → Call–Exner bodies + oestrogen; Sertoli–Leydig → Reinke crystals + virilisation.
7. Meigs syndrome = fibroma + ascites + right pleural effusion (resolves post-op).
8. High-grade serous carcinoma arises from fallopian tube fimbria (STIC); driver mutation TP53; clear cell = worst prognosis.
9. TVS = best initial imaging; CA-125 for monitoring, NOT screening; diagnosis is surgical.
10. Standard chemo = carboplatin + paclitaxel; germ cell = BEP; BRCA/HRD → PARP inhibitors.
11. OCPs reduce risk ~50%; BRCA1 = highest hereditary risk; Lynch links ovarian + endometrial + colon.
12. Krukenberg = bilateral metastatic ovary, signet-ring cells, gastric primary; optimal debulking (residual disease) is the key modifiable prognostic factor.