Tumors of the testis

1. Overview

• Most important cause of firm, painless enlargement of testis.
• Two main categories:
  • Germ cell tumors (95 %) — mostly malignant.
  • Sex cord–stromal tumors — Sertoli or Leydig; uncommon + usually benign.

Predisposing factors

• Cryptorchidism (3–5× ↑ risk), orchitis, testicular dysgenesis.
• Genetics: whites 5× risk vs blacks.
• Isochromosome 12p (i(12p)) in nearly all germ cell tumors; extra 12p → progression + treatment failure.
• p53 mutations common.
• GCNIS (germ cell neoplasia in situ) — precursor of seminomas + non-seminomas.

2. Germ Cell Tumors

A) Tumors of ONE histological type (60 %)

Seminoma

• Most common testicular germ cell tumor.
• Young men 30–49 yr; unilateral palpable mass.
• Arises from GCNIS.
• Gross: soft, well-demarcated, gray-white tumor bulging from cut surface; no necrosis, no hemorrhage.
• Histology:
  • Sheets / lobular configuration with fibrous septa.
  • Pale cells (glycogen-rich); prominent central nucleoli.
  • Lymphocytic infiltrate (T cells) + plasma cells.
  • Syncytiotrophoblasts may produce hCG (~15 %).
• Mets: retroperitoneal, mediastinal, cervical LN; distant mets late.
• Tx: radical orchiectomy + radiation (very radiosensitive).

Spermatocytic tumor (spermatocytic seminoma)

• Rare (1–4 % of seminomas); only in descended testes.
• Older men (mean 55 yr); painless testicular swelling.
• In contrast to seminomas:
  • NOT from intratubular GCNIS.
  • No lymphocytic infiltrate, no syncytiotrophoblasts.
  • Not admixed with other germ cell tumor types.
  • Do NOT metastasize.

Embryonal carcinoma

• Malignant germ cell tumor of primitive epithelial cells recapitulating early embryonic development.
• Peak age 30 yr (10 yr younger than seminoma).
• Gross: poorly demarcated, soft, tan-white with hemorrhage + necrosis.
• Histology:
  • Solid sheets, glandular, or papillary patterns.
  • Large cells, basophilic cytoplasm, prominent nucleoli.
  • Often contains yolk sac + choriocarcinoma cells.
  • Infiltrates tunica albuginea + epididymis → disrupts testis shape.
• Aggressive; early metastasis.

Yolk-sac tumor

• #1 primary testicular neoplasm in children < 3 yr.
• Germ cell neoplasm reminiscent of embryonic / fetal yolk sac + extra-embryonic mesenchyme.
• Multiple patterns: glandular, reticular, papillary.
• Schiller-Duval bodies (glomeruloid structures) + hyaline globules.
• ↑ Serum AFP (tumor marker).

Choriocarcinoma

• Malignant tumor of syncytiotrophoblasts + cytotrophoblasts + intermediate trophoblasts.
• Young men 25–35 yr.
• Hemorrhagic tumor with necrosis.
• Histology:
  • Syncytiotrophoblasts — large multinucleated cells with irregular nuclei.
  • Cytotrophoblasts — pale cytoplasm with large nucleus + prominent nucleolus.
• Early hematogenous spread to lungs, liver, brain.
• ↑↑ hCG (syncytiotrophoblasts) → gynecomastia.

Teratoma

• Tumor from germ cells with more than one embryonic layer.
• All age groups; most malignant in adults.
• Associated with GCNIS + 12p amplification (post-pubertal type):
  • Malignant; mature + immature elements.
  • Secondary somatic malignancy possible (sarcoma, adenocarcinoma, SCC).
• NOT associated (pre-pubertal type):
  • No atypia, GCNIS, or necrosis; dermoid cysts are specialized variants.

B) Tumors of MORE THAN ONE histological type (40 %)

Mixed germ cell tumors

• More than one component.
• Average age 30 yr.
• Clinically treated as non-seminoma regardless of seminoma component.
• Often solid, cystic, necrotic, hemorrhagic.
• Most common combination: embryonal carcinoma + teratoma, seminoma, or yolk sac.
• Tumor markers: ↑ AFP + ↑ hCG.
• High-risk metastasis: embryonal carcinoma, choriocarcinoma (vascular invasion).

3. Sex Cord–Stromal Tumors (5 %)

• Leydig cell tumor: androgens → precocious puberty in children, gynecomastia in adults.
• Sertoli cell tumor: usually benign; may produce androgens or estrogens.

4. Clinical Features + Diagnosis

• Slowly enlarging painless testicular mass.
• Mets to iliac, para-aortic, mediastinal, supraclavicular LN; NOT inguinal LN.
• Non-seminomas metastasize earlier by both lymphatic + hematogenous routes.
• Hematogenous mets to liver, lungs, brain, bones.

Diagnosis

• Physical exam, testicular ultrasound, chest X-ray / CT for staging.
• Radical orchiectomy — no biopsy (risk of seeding).
• Tumor markers: LDH, AFP, hCG.

5. Treatment + Staging

Treatment

• Seminoma — very radiosensitive + chemotherapy.
• Non-seminoma — platinum-based chemotherapy.

Staging

• Stage I: confined to testis.
• Stage II: regional LN mets only.
• Stage III: non-regional LN / distant mets.

6. Tumor Marker Quick Reference

Tumor	AFP	hCG	LDH
Seminoma	−	+/− (~15 %)	+
Yolk sac	+++	−	+
Choriocarcinoma	−	+++	+
Embryonal	+/−	+/−	+
Teratoma (mature)	−	−	−

💡 High-yield: 95 % germ cell + malignant; firm painless mass. Isochromosome 12p marker. Cryptorchidism = 3–5× ↑ risk. Seminoma = #1, young men, GCNIS, pale glycogen cells + lymphocytic infiltrate, very radiosensitive. Embryonal carcinoma = aggressive, hemorrhagic, ~30 yr. Yolk sac = #1 in kids <3 yr, Schiller-Duval bodies, ↑ AFP. Choriocarcinoma = syncytio/cytotrophoblasts, ↑↑ hCG + gynecomastia, early hematogenous mets. Teratoma = post-pubertal malignant. Mixed = most common non-seminoma; ↑ AFP + hCG. Mets: iliac/para-aortic/mediastinal LN (NOT inguinal). Tx: orchiectomy + seminoma → radiation, non-seminoma → platinum chemo. Markers: AFP = yolk sac, hCG = choriocarcinoma, LDH.