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PA28.1 | Testicular Tumors — SDL Guide (Part 2)

Non-Seminomatous GCTs — Embryonal Carcinoma and Yolk Sac Tumor

Embryonal Carcinoma

Embryonal carcinoma is the most aggressive and undifferentiated NSGCT, histologically resembling cells of the early embryo (inner cell mass).

Gross: Small, poorly circumscribed, variegated cut surface with prominent hemorrhage and necrosis — contrasting with the homogeneous seminoma.

Microscopic: Large pleomorphic cells arranged in solid sheets, acini (gland-like spaces), or papillae. Cells have amphophilic (dark) cytoplasm, indistinct borders, large irregular nuclei with prominent nucleoli, and numerous mitoses. The "messy" architecture distinguishes it from the orderly seminoma.

Markers: AFP ± elevated; β-hCG ± elevated (STGCs may be present); OCT3/4 positive.

Medical histology diagram of embryonal carcinoma showing pleomorphic tumor cells in solid sheets and pseudoglandular spaces with mitotic figures and adjacent fibrous stroma. — **Panel A:** Medium-power H&E field showing tumor cells, pseudoglandular pattern, mitotic figure, prominent nucleolus, and fibrous stroma.. **Panel B:** Magnified cellular detail showing pleomorphic nucleus, prominent nucleolus, amphophilic cytoplasm, and mitotic figure.. **Panel C:** Architectural schematic showing solid sheets, pseudoglandular spaces, and adjacent fibrous stroma..

Yolk Sac Tumor (Endodermal Sinus Tumor)

Yolk sac tumor (YST) recapitulates the yolk sac (extraembryonic endoderm) and is the most common testicular GCT in children under 3 years (pure form). In adults, it almost always occurs as a component of a mixed GCT.

Gross: Mucoid, gelatinous cut surface; yellow-white; may show cysts.

Microscopic: Multiple patterns possible, but the Schiller-Duval body is pathognomonic — a central fibrovascular core lined by tumor cells within a cystic space, mimicking the glomeruloid structure of the primitive yolk sac. Cells are cuboidal with vacuolated cytoplasm. Intracellular and extracellular hyaline globules that are AFP-positive on immunohistochemistry are characteristic.

A three-panel medical diagram shows the Schiller-Duval body of yolk sac tumor with its fibrovascular core, cuboidal tumor cells, cystic space, and AFP marker correlation. — **Panel A:** High-power histology of yolk sac tumor showing Schiller-Duval body, fibrovascular core, cuboidal tumor cells, cystic space, flat lining cells, and glomeruloid pattern.. **Panel B:** Simplified diagnostic schematic showing central fibrovascular core surrounded by tumor cells projecting into a cystic space, resembling a renal glomerulus.. **Panel C:** Clinical marker correlation showing AFP markedly elevated, beta-hCG negative in pure yolk sac tumor, and occurrence in young children..

Markers: AFP — markedly elevated (the most specific marker for YST); β-hCG — negative in pure YST.

Behaviour (children): Highly curable with surgery ± chemotherapy, even if AFP initially elevated.

SELF-CHECK

A 2-year-old boy is brought with a painless right testicular mass. Orchiectomy shows a tumor with Schiller-Duval bodies and intracytoplasmic hyaline globules. Which serum tumor marker is MOST likely to be markedly elevated?

A. A. β-hCG

B. B. AFP (α-fetoprotein)

C. C. LDH

D. D. Testosterone

Reveal Answer

Answer: B. B. AFP (α-fetoprotein)

Yolk sac tumor (endodermal sinus tumor) — the most common testicular tumor in young children — produces AFP as it recapitulates yolk sac (hepatoid) differentiation. Schiller-Duval bodies are the pathognomonic histological feature. AFP is markedly elevated; β-hCG is not a feature of pure YST. LDH is non-specific and reflects bulk, not a specific marker for YST. Testosterone elevation is a feature of Leydig cell tumors.

Choriocarcinoma and Teratoma

Choriocarcinoma

Choriocarcinoma recapitulates placental trophoblast and is the most aggressive testicular GCT. Pure choriocarcinoma is rare (~0.3% of GCTs) but choriocarcinoma elements are common in mixed GCTs.

Gross: Characteristically small primary tumor with massive systemic metastases — the retroperitoneal nodes may be unaffected while pulmonary, hepatic, and brain metastases are already present. The cut surface shows hemorrhage and necrosis (trophoblast invades vessels).

Microscopic: Biphasic pattern — the defining requirement:
- Cytotrophoblasts: Mononuclear cells with clear cytoplasm and distinct cell membranes
- Syncytiotrophoblasts (STGCs): Large multinucleated cells with abundant eosinophilic vacuolated cytoplasm — these produce β-hCG

Both components must be present for the diagnosis; STGCs alone do not make choriocarcinoma.

Markers: β-hCG — markedly elevated (very high levels correlate with prognosis); AFP negative in pure choriocarcinoma.

Behaviour: Hematogenous spread occurs very early (even with microscopic primary) — to lungs, liver, brain. This is why choriocarcinoma presents with distant metastases despite a small primary. Prognosis is worse than other GCT subtypes.

Three-panel histology diagram of testicular choriocarcinoma showing cytotrophoblasts, syncytiotrophoblast giant cells, hemorrhage, and beta-hCG hormone mimicry. — **Panel A:** Medium-power H&E field showing cytotrophoblasts, syncytiotrophoblasts (STGCs), and prominent hemorrhage.. **Panel B:** Magnified cellular detail showing mononuclear cytotrophoblasts beside multinucleated syncytiotrophoblast giant cells with vacuolated eosinophilic cytoplasm.. **Panel C:** Clinical-pathology schematic showing beta-hCG release from choriocarcinoma and hormone mimicry effect on Leydig cells..

Teratoma

Teratoma contains mature or immature tissues from two or three germ layers (ectoderm, mesoderm, endoderm).

Gross: Heterogeneous — cysts containing mucus, hair, keratin; solid areas of cartilage, bone, neural tissue.

Microscopic: Tissues of varying differentiation — squamous epithelium (ectoderm), smooth muscle, cartilage, bone (mesoderm), intestinal-type mucous glands (endoderm). Mature teratoma in adults is NOT benign (unlike ovarian mature teratoma in females) — it can metastasise. The retained i(12p) alteration distinguishes adult testicular teratoma from the truly benign prepubertal form.

Markers: In a pure teratoma, AFP and β-hCG may be slightly elevated if there are minor components of other lineages; generally not a marker-secreting tumor.

Histology diagram of mature testicular teratoma showing squamous epithelium, smooth muscle, and mucinous columnar epithelium labeled as ectoderm, mesoderm, and endoderm derivatives. — **Panel A:** Low-power mature testicular teratoma showing keratinizing stratified squamous epithelium — ectoderm; smooth muscle bundles — mesoderm; mucus-secreting columnar epithelium — endoderm; color legend for germ layers.. **Panel B:** High-power ectoderm derivative: keratinizing stratified squamous epithelium with basal layer and keratin debris.. **Panel C:** High-power mesoderm derivative: interlacing smooth muscle bundles with spindle cells and cigar-shaped nuclei.. **Panel D:** High-power endoderm derivative: mucinous columnar epithelium forming glands with pale mucin vacuoles and basal nuclei..

CLINICAL PEARL

Choriocarcinoma and 'hormone mimicry': Because choriocarcinoma produces very high β-hCG, it can stimulate Leydig cells via cross-reactivity with LH receptors, causing gynecomastia (breast enlargement in males). A young man with a testicular mass + gynecomastia should raise the suspicion for choriocarcinoma or a β-hCG-secreting mixed GCT. Similarly, hyperthyroidism can occur (β-hCG cross-reacts with TSH receptors at very high levels). Don't mistake gynecomastia for a Leydig cell tumor without checking β-hCG first.

Mixed GCTs, Sex Cord-Stromal Tumors, and Lymphoma

Mixed Germ Cell Tumors

Mixed GCTs contain two or more histological components and constitute approximately 50% of all NSGCTs. The most common combination is embryonal carcinoma + teratoma (teratocarcinoma). The clinical behavior is governed by the most aggressive component present.

Key rule: The final tumor marker profile and staging reflect ALL components — a mixed GCT with any choriocarcinoma element will have markedly elevated β-hCG; one with yolk sac tumor will have elevated AFP.

Low-power mixed germ cell tumor histology shows embryonal carcinoma on the left and mature teratomatous cartilage and glands on the right, with magnified labeled insets. — **Panel A:** Low-power mixed GCT with left embryonal carcinoma zone, right mature teratoma zone, dashed interface, solid malignant sheets, cartilage island, and glandular structures.. **Panel B:** Embryonal carcinoma component showing solid sheets of primitive malignant cells, amphophilic cytoplasm, pleomorphic nuclei, prominent nucleoli, mitotic figures, and necrosis.. **Panel C:** Mature teratoma component showing hyaline cartilage, chondrocytes in lacunae, mature glandular epithelium, and glandular lumina..

Sex Cord-Stromal Tumors (~5% of testicular tumors)

Leydig cell tumor: Most common sex cord-stromal tumor. The Leydig cell is the testosterone-producing interstitial cell.
- Clinical: Precocious puberty in boys (excess testosterone); gynecomastia in adults (peripheral conversion of excess androgen to estrogen, or direct estrogen production).
- Gross: Well-circumscribed, golden-brown (lipid-rich) nodule.
- Microscopic: Large polygonal cells with abundant eosinophilic granular cytoplasm and round nuclei. Pathognomonic feature: Reinke crystalloids — rectangular eosinophilic rod-shaped cytoplasmic inclusions (seen in ~25–40%).
- Behaviour: ~90% benign. Malignant in ~10% — diagnosed by metastasis, not histology alone.

Sertoli cell tumor: Rare; tubular architecture; may produce estrogen → gynecomastia.

Lymphoma (~5% of testicular tumors)

Testicular lymphoma is the most common testicular tumor in men >60 years. Most are diffuse large B-cell lymphomas (DLBCL). Bilateral involvement occurs in 20–38% of cases (unlike GCTs which are very rarely bilateral). Associated with systemic dissemination; prognosis is poorer than primary nodal DLBCL.