Background & Epidemiology
Testicular tumours divide into germ cell tumours (GCTs) and non-GCTs:
- 95% are GCTs; 5% are non-germ cell (sex-cord stromal tumours, adenocarcinoma of the rete testis, lymphoma).
- 95% of GCTs originate in the testicle; 5% are primary extra-gonadal GCTs.
GCT is relatively rare overall but is the most common malignancy in males aged 20–39, accounting for 1–2% of male cancers in the US. Estimated incidence: ~74,458 worldwide and ~9,470 in the US (2020–2021). Mortality is low — ~9,334 worldwide and ~440 in the US — with a 5-year relative survival of 94.9% (vs prostate 97.5%, bladder 77.1%, kidney 75.6%).
Risk Factors
Inherited:
- Family history of GCT.
- Germ cell neoplasia in situ (GCNIS) — formerly intratubular germ cell neoplasia (ITGCN), unclassified. It develops before birth from an arrested gonocyte, and all adult invasive GCTs arise from GCNIS except spermatocytic seminoma. Risk of invasive GCT is ≈50% at 5 years.
- Race — Caucasian risk > African-American.
Acquired:
- Cryptorchidism — ipsilateral relative risk 4–6× (falls to 2–3× if orchidopexy is performed before puberty); contralateral testis slightly increased (RR ~1.74×).
- Personal history of GCT.
Genetics — an increased copy number of the short arm of chromosome 12 (i(12p)) is a universal finding in testicular and extra-gonadal GCTs.
Classification
- Pathological: GCNIS-derived vs non-GCNIS-derived.
- Clinical: seminoma vs non-seminoma GCT (NSGCT) — based on differences in management and outcome. Any tumour containing both seminoma and NSGCT elements is classified as NSGCT.
Histologic Subtypes
Seminoma — the most common GCT (52–56% of GCTs; NSGCT 44–48%). Occurs at an older average age (4th–5th decade), arises from GCNIS, and is the common precursor for the NSGCT subtypes.
Non-seminoma subtypes:
| Subtype | Key features | Markers |
|---|---|---|
| Embryonal carcinoma (EC) | Most undifferentiated NSGCT, totipotent (can differentiate into other NSGCT types including teratoma); aggressive with a high metastatic rate, often despite normal markers | Usually normal |
| Choriocarcinoma | Rare, aggressive, spreads hematogenously | Markedly elevated hCG |
| Yolk sac tumour | — | Almost always elevated AFP; no hCG |
| Teratoma | Histologically benign; contains well- or incompletely-differentiated elements of ≥2 of 3 germ layers (endoderm, mesoderm, ectoderm); chemoresistant; no clinical distinction between mature and immature; rare somatic malignant transformation (rhabdomyosarcoma, adenocarcinoma, PNET) | Normal; may mildly elevate AFP |
Spermatocytic seminoma — accounts for <1% of GCTs. It has a distinct pathogenesis and cell of origin: it does not arise from GCNIS, is not associated with cryptorchidism or bilaterality, does not demonstrate i(12p), and does not occur within mixed GCTs. It is benign and almost always cured with orchiectomy.
Natural History & Metastatic Spread
GCTs are rapidly growing. 70–80% of metastases spread lymphatically from the primary to the retroperitoneal lymph nodes (the most common site) and then to distant sites — the exception is choriocarcinoma, which favours hematogenous dissemination.
- Lymph nodes: retroperitoneal (most common) → supraclavicular, mediastinal; inguinal nodes only with prior scrotal violation.
- Visceral: lung is the second most common metastatic site overall and the most common visceral site. Pulmonary metastases reflect hematogenous spread, whereas mediastinal/cervical disease reflects lymphatic spread. Thoracic disease without retroperitoneal involvement or marker elevation is uncommon. Liver is also involved in advanced disease.
At diagnosis, metastasis (regional or distant) is present in 33% of NSGCT and 15% of pure seminoma.