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Germ cell tumour

Germ cell tumour (GCT) is a neoplasm derived from the primordial germ cells, which can be either cancerous or benign. These germ cells typically occur in the gonads (ovary and testis), but GCTs can also originate outside the gonads, often due to developmental errors during embryogenesis.

Classification

Relative incidences of testicular tumours.
Relative incidences of testicular tumours.

GCTs are primarily classified by their histology and are broadly divided into two classes: germinomatous (seminomatous) and nongerminomatous (nonseminomatous) germ-cell tumours. Germinomatous tumours, which include germinoma and its synonyms dysgerminoma and seminoma, tend to grow slower, have a higher sensitivity to radiation, and respond well to chemotherapy. In contrast, nongerminomatous tumours grow faster, have an earlier mean age at diagnosis, and generally have a lower five-year survival rate. However, the prognosis for nongerminomatous tumours has significantly improved with platinum-based chemotherapy regimens.

Germinomatous

  • Germinoma (including dysgerminoma and seminoma):
    • Peak Age: 40–50 years
    • Malignancy: Malignant
    • Histology: Sheets of uniform polygonal cells with cleared cytoplasm; lymphocytes in the stroma
    • Tumour Marker: About 10% have elevated hCG, PLAP

Nongerminomatous

  • Embryonal carcinoma:
    • Peak Age: 20–30 years
    • Malignancy: Malignant
    • Histology: Poorly differentiated, pleomorphic cells in cords, sheets, or papillary formation
    • Tumour Marker: Secrete hCG, AFP
  • Endodermal sinus tumour (yolk sac tumour):
    • Peak Age: 3 years
    • Malignancy: Malignant
    • Histology: Poorly differentiated endothelium-like, cuboidal, or columnar cells
    • Tumour Marker: 100% secrete AFP
  • Choriocarcinoma:
    • Peak Age: 20–30 years
    • Malignancy: Malignant
    • Histology: Cytotrophoblast and syncytiotrophoblast without villus formation
    • Tumour Marker: 100% secrete hCG
  • Teratoma (including mature teratoma, dermoid cyst, immature teratoma, teratoma with malignant transformation):
    • Peak Age: 0–3, 15–30 years
    • Malignancy: Mature teratoma and dermoid cyst usually benign; others usually malignant
    • Histology: Very variable, but "normal" tissues are common
    • Tumour Marker: Pure tumours do not secrete hCG, AFP

Cause

The cause of GCTs remains unclear, but theories suggest abnormal migration of germ cells during embryogenesis or a widespread distribution of germ cells to multiple sites during normal embryogenesis. Extragonadal GCTs were initially thought to be isolated metastases from an undetected primary tumour in a gonad but are now known to be congenital in many cases.

Location

GCTs are found both within and outside the gonads, occurring in locations such as the head (inside the cranium and mouth), neck, mediastinum, and pelvis (particularly sacrococcygeal teratoma). In females, GCTs account for 30% of ovarian tumours, but only 1–3% of ovarian cancers in North America. In younger women and neonates, they are more common and often malignant.

Treatment

For women with benign GCTs such as mature teratomas (dermoid cysts), ovarian cystectomy or oophorectomy is curative. Malignant GCTs often require staging surgery similar to that for epithelial ovarian cancer. Chemotherapy is commonly used, with PEB (or BEP) being the standard regimen, consisting of bleomycin, etoposide, and cisplatin. Targeted treatments like immunotherapy and kinase inhibitors are under evaluation for chemotherapy-resistant tumours.

Prognosis

Prognosis depends on the type and stage of the tumour, with the International Germ Cell Consensus Classification used as a tool for estimating relapse risk. Access to appropriate treatment significantly affects outcomes, and studies show improved five-year survival rates with early diagnosis and treatment at specialised cancer units. Choriocarcinoma of the testicles has the worst prognosis among germ-cell cancers.


Self-assessment MCQs (single best answer)

What is the primary classification criterion for germ cell tumours (GCTs)?



Which type of germ cell tumour is most commonly found in males aged 40-50 years?



Which tumour marker is commonly elevated in seminomas?



What is the typical age range for peak incidence of embryonal carcinoma?



Which histological feature is associated with endodermal sinus tumours?



What percentage of ovarian tumours in females are germ cell tumours?



Which chemotherapy regimen is standard for treating malignant germ cell tumours?



What is the prognosis for choriocarcinoma of the testicles compared to other germ cell tumours?



How do germinomatous tumours generally respond to treatment compared to nongerminomatous tumours?



What is the role of AFP as a tumour marker in germ cell tumours?



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