Ovarian Tumours

Ovarian tumours are a hugely heterogeneous group because the ovary contains three distinct cell lineages — surface (coelomic) epithelium, germ cells and sex cord-stromal cells — each capable of giving rise to benign, borderline and malignant neoplasms. For NEET PG, the favourite hooks are histological recall items: psammoma bodies, Call-Exner bodies, Schiller-Duval bodies, Reinke crystals and the marker panels (LDH, AFP, hCG, inhibin, CA-125).

Classification — the master framework

The single most important step is to slot a tumour into one of three (plus metastatic) categories. This decides age, markers, behaviour and treatment.

Category	Approx. frequency	Typical age	Most common subtype
Surface epithelial-stromal	65-70% of all; ~90% of malignant	Adults, >40 yr	Serous tumours
Germ cell	15-20%	Children & young women (<20 yr)	Mature cystic teratoma (dermoid)
Sex cord-stromal	5-10%	Any age (varies)	Fibroma / granulosa cell tumour
Metastatic (secondary)	~5%	Variable	Krukenberg (from stomach)

High-yield: Surface epithelial tumours are the most common ovarian tumours overall and account for the great majority of ovarian cancers. Germ cell tumours dominate in the young; sex cord-stromal tumours are the hormonally active group.

Diagnostic flow: Age + ultrasound morphology → tumour markers → categorise lineage → histology (the gold standard) → stage surgically.

Surface epithelial-stromal tumours

These arise from the coelomic epithelium covering the ovary (and possibly the fallopian tube fimbria for high-grade serous cancer). Each subtype recapitulates a Müllerian-derived epithelium.

Serous tumours

• Lined by ciliated, fallopian-tube-like epithelium; filled with thin serous fluid.
• Serous cystadenoma (benign): thin-walled, often unilocular cyst lined by a single layer of bland cells. Frequently bilateral.
• Borderline serous tumour: epithelial stratification, tufting and atypia without stromal invasion.
• Serous cystadenocarcinoma: the most common malignant ovarian tumour; commonly bilateral; complex papillary, solid-cystic mass.

High-yield: Psammoma bodies — laminated, concentric calcified spherules — are characteristic of serous tumours (especially papillary serous carcinoma). Also seen in papillary thyroid carcinoma, meningioma and mesothelioma.

High-grade serous carcinoma shows TP53 mutation and is now thought to often originate from serous tubal intraepithelial carcinoma (STIC) at the fimbrial end of the tube. Low-grade serous carcinoma carries KRAS/BRAF mutations.

Mucinous tumours

• Lined by tall, mucin-secreting columnar (intestinal/endocervical-type) epithelium; tend to form large, multiloculated cysts.
• Usually unilateral (a useful contrast to serous, which is often bilateral).
• Associated with KRAS mutations.
• Pseudomyxoma peritonei — gelatinous mucinous ascites filling the peritoneum — is classically linked to mucinous ovarian tumours, but most cases actually originate from a ruptured appendiceal mucinous neoplasm with secondary ovarian involvement.

Feature	Serous	Mucinous
Lining epithelium	Ciliated, tubal-type	Mucin-secreting columnar
Laterality	Often bilateral	Usually unilateral
Size	Moderate	Often very large
Loculation	Often unilocular	Multilocular
Marker hint	CA-125, psammoma bodies	CEA, CA 19-9, pseudomyxoma

Endometrioid & clear cell tumours

• Endometrioid carcinoma: tubular glands resembling the endometrium; ~15-20% co-exist with endometrial carcinoma of the uterus; arises from endometriosis/endometriotic cysts.
• Clear cell carcinoma: "hobnail" cells with clear (glycogen-rich) cytoplasm; strongly associated with endometriosis; relatively chemoresistant; raised risk of paraneoplastic hypercalcaemia and venous thrombosis.

Brenner tumour

• Usually benign, solid; nests of transitional (urothelium-like) epithelium with "coffee-bean" nuclei (longitudinal grooves) set in dense fibrous stroma.

High-yield: CA-125 is the serum marker for epithelial ovarian cancer — best for monitoring treatment response and recurrence, not for screening (it rises in endometriosis, PID, pregnancy, cirrhosis, menstruation).

Germ cell tumours

Derived from primordial germ cells; predominate in children and women under 30. Mnemonic for the classic types — "DETECT": Dysgerminoma, Embryonal carcinoma, Teratoma, Endodermal sinus (yolk sac), Choriocarcinoma, mixed Types.

Teratoma

• Mature cystic teratoma (dermoid cyst): the most common germ cell tumour and most common benign ovarian tumour overall in young women. Contains tissue from all three germ layers — skin, hair, sebaceous material, teeth, cartilage. Usually benign; risk of torsion. Malignant transformation (most often squamous cell carcinoma) is rare (~1-2%).
• Struma ovarii: teratoma composed predominantly of mature thyroid tissue; may cause hyperthyroidism.
• Immature teratoma: malignant; contains immature/embryonal tissue, most importantly immature neuroepithelium (neural rosettes) — graded by the amount of neural tissue. Occurs in younger patients than mature teratoma.

High-yield: Grading of immature teratoma depends on the quantity of immature neuroepithelial tissue — this is a classic single-best-answer recall.

Dysgerminoma

• Ovarian counterpart of the seminoma of the testis; the most common malignant germ cell tumour.
• Sheets of large clear (glycogen-rich) cells with central nuclei separated by fibrous septa infiltrated by lymphocytes.
• Markers: LDH (raised) and PLAP (placental alkaline phosphatase), OCT4, c-KIT.
• Most radiosensitive and chemosensitive ovarian tumour; excellent prognosis.
• Associated with dysgenetic gonads (e.g., Turner mosaic, Swyer syndrome).

Yolk sac tumour (endodermal sinus tumour)

• Second most common malignant germ cell tumour; rapidly growing, in children/young women.
• Histology: Schiller-Duval bodies (glomeruloid perivascular structures) and intracellular/extracellular hyaline (PAS-positive) globules.
• Marker: AFP (alpha-fetoprotein).

Choriocarcinoma & embryonal carcinoma

• Choriocarcinoma: syncytio- and cytotrophoblast; marker β-hCG (very high); haemorrhagic; ovarian (non-gestational) form is chemoresistant compared with gestational.
• Embryonal carcinoma: primitive, highly malignant; may secrete both AFP and hCG.

Germ cell tumour	Hallmark histology	Tumour marker
Dysgerminoma	Clear cells + lymphocytic septa	LDH, PLAP
Yolk sac tumour	Schiller-Duval bodies	AFP
Choriocarcinoma	Syncytio/cytotrophoblast	β-hCG
Embryonal carcinoma	Primitive epithelial sheets	AFP + hCG
Immature teratoma	Immature neuroepithelium	(AFP may be mildly ↑)

Sex cord-stromal tumours

These arise from granulosa, theca, Sertoli, Leydig or fibroblast precursors. They are the hormonally functional group — present with oestrogen or androgen excess.

Granulosa cell tumour

• Low-grade malignant; produces oestrogen → inhibin.
• Histology: Call-Exner bodies — small follicle-like rosettes of granulosa cells surrounding eosinophilic material; nuclei show longitudinal "coffee-bean" grooves.
• Adult type (most common) → postmenopausal bleeding, endometrial hyperplasia/carcinoma, precocious puberty if in a child.
• Juvenile type → isosexual precocious puberty in girls.
• Marker: inhibin; can recur late (years later).

High-yield: Call-Exner bodies = granulosa cell tumour — a perennial NEET PG histology one-liner. The clinical clue is oestrogen excess (postmenopausal bleeding or precocious puberty) with raised inhibin and risk of concurrent endometrial carcinoma.

Thecoma-fibroma group

• Fibroma: benign, solid, composed of spindle fibroblasts; hormonally inactive.
• Meigs syndrome: ovarian fibroma + ascites + right-sided pleural effusion, all of which resolve after tumour removal.
• Thecoma: oestrogen-producing → may cause endometrial hyperplasia.

Sertoli-Leydig cell tumour (androblastoma / arrhenoblastoma)

• Produces androgens → virilisation / defeminisation (hirsutism, deepening voice, clitoromegaly, breast atrophy).
• Reinke crystals may be seen in the Leydig component.

Sex cord-stromal tumour	Hormone	Histology marker	Clinical effect
Granulosa cell	Oestrogen	Call-Exner bodies	Precocious puberty / PM bleeding
Thecoma	Oestrogen	Lipid-laden theca cells	Endometrial hyperplasia
Fibroma	None	Spindle fibroblasts	Meigs syndrome
Sertoli-Leydig	Androgen	Reinke crystals	Virilisation

Metastatic (secondary) ovarian tumours

• Krukenberg tumour: bilateral metastases of signet-ring (mucin-secreting) cells, classically from a gastric (or colorectal/breast) primary, spreading transcoelomically/lymphatically.

High-yield: Krukenberg = bilateral ovarian + signet-ring cells + stomach primary. Bilaterality should always raise suspicion of either serous carcinoma or metastasis.

Clinical features

Most ovarian tumours are clinically silent until large, hence the term "silent killer" for epithelial cancer. Presentations include:

• Vague abdominal distension, bloating, early satiety, pelvic pressure.
• Adnexal mass, ascites (advanced epithelial cancer).
• Acute torsion (dermoid cyst) → sudden severe pain.
• Hormonal syndromes: oestrogenic (granulosa/theca) → bleeding/precocity; androgenic (Sertoli-Leydig) → virilisation; thyrotoxicosis (struma ovarii).
• Meigs syndrome with a fibroma.

Diagnosis & investigation of choice

1. Transvaginal ultrasound → first-line imaging; assesses size, solid/cystic nature, septations, papillary projections, vascularity.
2. Tumour markers by suspected lineage: CA-125 (epithelial), AFP/LDH/β-hCG (germ cell), inhibin (granulosa).
3. CT/MRI for staging and operative planning.
4. Histopathology after surgery is the definitive (gold-standard) diagnosis; ovarian cancer is staged surgically (FIGO).
5. RMI (Risk of Malignancy Index) = ultrasound score × menopausal status × CA-125, used to triage adnexal masses.

High-yield: Ovarian carcinoma staging is surgical (FIGO), not radiological. Spread is predominantly transcoelomic (peritoneal seeding), explaining omental cake and ascites.

Management / treatment of choice

• Benign tumours / young women: cystectomy or fertility-sparing salpingo-oophorectomy.
• Epithelial ovarian carcinoma: cytoreductive (debulking) surgery — TAH + BSO + omentectomy + lymph node sampling — followed by platinum-based chemotherapy (carboplatin + paclitaxel). PARP inhibitors (olaparib) are used in BRCA-mutated/HRD tumours; bevacizumab as anti-angiogenic.
• Dysgerminoma: highly radiosensitive and chemosensitive (BEP — bleomycin, etoposide, cisplatin); fertility preservation often possible.
• Other malignant germ cell tumours: surgery + BEP chemotherapy; AFP/hCG/LDH monitored.
• Granulosa cell tumour: surgery; long follow-up with inhibin owing to late recurrence.

Complications

• Torsion, rupture, haemorrhage, infection.
• Pseudomyxoma peritonei (mucinous).
• Ascites and pleural effusion (Meigs; or malignant).
• Paraneoplastic effects: hypercalcaemia (clear cell, small cell), hormone excess.
• Malignant transformation in mature teratoma (squamous cell carcinoma).
• Concurrent endometrial carcinoma with oestrogen-secreting tumours.

Key differentials

• Functional/physiological cysts (follicular, corpus luteum) versus neoplastic cysts.
• Endometrioma ("chocolate cyst") versus haemorrhagic cyst — link to clear cell/endometrioid carcinoma.
• Tubo-ovarian abscess versus solid neoplasm (raised CA-125 can mislead).
• Ectopic pregnancy / hydrosalpinx for adnexal mass in reproductive age.
• For a bilateral solid mass — distinguish serous carcinoma from Krukenberg metastasis.

Hereditary associations

• BRCA1/BRCA2 mutations → high-grade serous carcinoma; consider risk-reducing salpingo-oophorectomy.
• Lynch syndrome (HNPCC) → endometrioid and clear cell types.
• Peutz-Jeghers syndrome → sex cord tumour with annular tubules (SCTAT).
• Gorlin syndrome → bilateral ovarian fibromas.

Recently asked / exam angle

• "Call-Exner bodies are seen in?" → Granulosa cell tumour (and the oestrogen/inhibin link).
• "Most common malignant ovarian tumour?" → Serous cystadenocarcinoma.
• "Schiller-Duval bodies / AFP marker?" → Yolk sac (endodermal sinus) tumour.
• "Marker for dysgerminoma?" → LDH (and PLAP).
• "Psammoma bodies in ovary?" → Serous tumours (papillary serous carcinoma).
• "Meigs syndrome triad?" → Fibroma + ascites + right pleural effusion, resolving after removal.
• "Bilateral signet-ring metastasis from stomach?" → Krukenberg tumour.
• "Most common benign ovarian/germ cell tumour in young women?" → Mature cystic teratoma (dermoid).
• "Struma ovarii contains?" → Thyroid tissue.
• "Reinke crystals?" → Sertoli-Leydig (Leydig) cell tumour.
• Image-based: dermoid with hair/teeth, clear cells with lymphocytes (dysgerminoma), coffee-bean nuclei (Brenner / granulosa).

Rapid revision

1. Three lineages: surface epithelial (most common, most malignant), germ cell (young), sex cord-stromal (hormonal).
2. Serous cystadenocarcinoma = most common ovarian malignancy; often bilateral; psammoma bodies.
3. Mucinous tumours = large, multilocular, usually unilateral; pseudomyxoma peritonei (usually appendiceal).
4. Mature cystic teratoma (dermoid) = most common benign germ cell tumour; risk of torsion.
5. Immature teratoma graded by immature neuroepithelium.
6. Dysgerminoma = ovarian seminoma; markers LDH + PLAP; very radiosensitive.
7. Yolk sac tumour = Schiller-Duval bodies + AFP.
8. Choriocarcinoma = β-hCG; Granulosa cell = Call-Exner bodies + inhibin + oestrogen.
9. Sertoli-Leydig = androgens + virilisation + Reinke crystals.
10. Meigs syndrome = fibroma + ascites + right pleural effusion, all reversible.
11. Krukenberg = bilateral, signet-ring cells, gastric primary.
12. Epithelial cancer: marker CA-125 (monitoring), surgical FIGO staging, treat with debulking + carboplatin/paclitaxel ± PARP inhibitor.