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Testis and Ovary Tumours - Robbins & Kumar Basic Pathology

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TESTICULAR TUMOURS

Classification

1. Seminomas (~50% of all GCTs)
2. Nonseminomatous tumours (embryonal carcinoma, yolk sac tumour, choriocarcinoma, teratoma, mixed)

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Pathogenesis

• Incidence lowest in Africa and Asia; rising worldwide
• Family history: fathers and sons - 4x risk; brothers of affected males - 8-10x risk
• Cryptorchidism - associated with cancer in undescended testis AND contralateral descended testis; found in ~10% of testicular cancer cases
• Intersex syndromes (androgen insensitivity, gonadal dysgenesis) increase risk
• Chromosome 12p: extra copies (usually isochromosome i[12p]) found in virtually ALL germ cell tumours
• KIT oncogene mutations: found in up to 25% of tumours
• Most tumours in postpubertal males arise from a precursor - germ cell neoplasia in situ (GCNIS)

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Individual Tumour Types

1. SEMINOMA (~50% of GCTs)

• Gross: soft, well-demarcated, gray-white homogeneous mass; foci of coagulative necrosis (no hemorrhage)
• Histo: large uniform cells with:
  • Distinct cell borders
  • Clear glycogen-rich cytoplasm
  • Round nuclei with conspicuous nucleoli
  • Small lobules with fibrous septa
  • Lymphocytic infiltrate (characteristic)
  • May have granulomatous reaction
• ~15% contain syncytiotrophoblasts → mildly elevated serum hCG (10-15% stage I; 30-50% disseminated)
• Histologically identical to dysgerminoma (ovary) and germinoma (CNS/extragonadal)

2. SPERMATOCYTIC TUMOUR (formerly Spermatocytic Seminoma)

• Rare (~1-2% of GCTs); affects older males (usually >65 years)
• Slow-growing; does NOT metastasize
• NOT associated with GCNIS; lacks i(12p); gains chromosome 9q
• Excellent prognosis with surgical resection

3. EMBRYONAL CARCINOMA (~2-3% pure; often mixed)

• Gross: ill-defined invasive mass with hemorrhage and necrosis; primary may be small even with systemic metastases
• Histo: large cells with basophilic cytoplasm, indistinct borders, large hyperchromatic nuclei, prominent nucleoli; solid sheets, primitive glands, or papillae

4. YOLK SAC TUMOUR (Endodermal Sinus Tumour)

• Most common testicular tumour in children < 3 years (excellent prognosis in this age group)
• In adults: rarely pure; usually mixed with embryonal carcinoma
• Histo: microcysts, lacelike/reticular patterns, glands, papillae
• Pathognomonic: Schiller-Duval bodies (primitive glomerulus-like structures)
• AFP (alpha-fetoprotein) positive (eosinophilic hyaline globules containing AFP and α1-antitrypsin)

5. CHORIOCARCINOMA

• Highly malignant; primary often small and nonpalpable despite extensive metastases
• Histo: cytotrophoblast-like cells capped by eosinophilic syncytiotrophoblasts
• Markedly elevated serum hCG
• Spreads haematogenously early (lungs, liver, brain)

6. TERATOMA

• Germ cells differentiate along multiple somatic lineages
• Gross: heterogeneous - solid, cartilaginous, cystic areas
• Histo: neural tissue, muscle, cartilage, squamous epithelium, thyroid-like tissue, bronchial epithelium, intestinal wall elements
• Prepubertal type: NOT associated with GCNIS or i(12p) → benign
• Postpubertal/adult type: considered malignant regardless of maturity of elements
• Teratoma with somatic-type malignancy: rare transformation into squamous cell carcinoma, adenocarcinoma, or sarcoma; resistant to standard GCT chemotherapy

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Clinical Features of Testicular GCTs

• Presentation: painless testicular mass (nontranslucent - unlike hydrocele)
• Standard management: radical orchiectomy (biopsy avoided due to tumor spillage risk)
• Tumour markers:
  • AFP: yolk sac tumour; elevated in nonseminomatous GCTs
  • hCG: choriocarcinoma, seminoma (low elevation)
  • LDH: correlates with tumour bulk

• Seminomas: radiosensitive; excellent prognosis even with metastases
• Nonseminomatous GCTs: treated with BEP chemotherapy; cure rates >90% even with metastatic disease
• Key staging: limited to testis → retroperitoneal lymph nodes → hematogenous spread (lung, liver, brain)

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OVARIAN TUMOURS

Overview

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A. SURFACE EPITHELIAL TUMOURS

• Type I carcinoma: low-grade, arises from borderline tumours or endometriosis; includes low-grade serous, endometrioid, mucinous; has KRAS/BRAF/ERBB2 mutations; wild-type TP53
• Type II carcinoma: high-grade serous; arises from serous tubal intraepithelial carcinoma (STIC); TP53 mutations in >95%

• Increasing age
• Early menarche/late menopause
• Nulliparity
• Family history
• BRCA1 or BRCA2 mutations (found in 5-10% familial cases; 20-60% lifetime risk of ovarian cancer)
• Oral contraceptive use is protective (suppresses ovulation)

1. SEROUS TUMOURS (most common)

• Gross: large spherical/ovoid cystic structures (up to 30-40 cm); multiloculated with septa; filled with clear serous fluid; papillary projections into cystic cavities (more prominent in malignant)
• Histo benign: single layer columnar epithelium lining cysts
• Histo malignant (high-grade): complex papillary and solid architecture; psammoma bodies (laminated calcifications) characteristic
• 25% of benign tumours bilateral; 65% of malignant bilateral

2. MUCINOUS TUMOURS

• Gross: multiloculated cysts filled with gelatinous/mucinous material
• Histo: glands and cysts lined by mucin-secreting columnar cells resembling endocervical or intestinal epithelium
• Usually unilateral; less commonly malignant than serous
• Rupture → pseudomyxoma peritonei (gelatinous implants on peritoneum)

3. ENDOMETRIOID CARCINOMA

• Accounts for ~20% of ovarian carcinomas
• Resemble uterine endometrial glands histologically
• 20% bilateral; 15-30% coexist with endometrial carcinoma (synchronous primary)
• Associated with endometriosis

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B. GERM CELL TUMOURS OF OVARY

1. MATURE CYSTIC TERATOMA (Dermoid Cyst)

• Most common ovarian germ cell tumour; 96% benign
• Tissues from all three germ layers: skin, hair, teeth, sebaceous material
• Bilateral in 15%
• Malignant transformation rare (<2%): most commonly squamous cell carcinoma

2. DYSGERMINOMA

• Ovarian counterpart of testicular seminoma
• Most common malignant germ cell tumour of ovary
• Occurs in young women/girls
• Radiosensitive; good prognosis
• Bilateral in ~15%

3. ENDODERMAL SINUS TUMOUR (Yolk Sac Tumour)

• Elevated AFP
• Schiller-Duval bodies
• Highly malignant; seen in young females

4. CHORIOCARCINOMA (ovarian)

• Extremely rare primary; very malignant
• Elevated hCG

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C. SEX CORD-STROMAL TUMOURS (Ovary)

1. GRANULOSA CELL TUMOUR

• Most important clinically (~5% of malignant ovarian tumours)
• Functionally active: secretes estrogen → endometrial hyperplasia/carcinoma (in adults); precocious puberty (in children)
• Call-Exner bodies (characteristic): small follicles filled with eosinophilic secretion
• Low malignant potential but late recurrences possible
• Inhibin is a useful tumour marker

2. THECOMA-FIBROMA GROUP

• Thecoma: estrogen-secreting; post-menopausal women
• Fibroma: associated with Meigs syndrome (ovarian fibroma + ascites + right-sided pleural effusion)

3. SERTOLI-LEYDIG CELL TUMOUR (Androblastoma)

• Secretes androgens → virilization
• Rare; most are benign or low-grade malignant

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Key Tumour Markers Summary

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Testicular vs. Ovarian Germ Cell Tumour Counterparts

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