Testicular Cancer and Germ Cell Tumors

Testicular cancer is the most common solid malignancy in young men, typically presenting between adolescence and the fourth decade of life. The overwhelming majority of cases are germ cell tumours, which are broadly divided into seminomas and non-seminomatous germ cell tumours. Despite often presenting with disease that has already spread, testicular germ cell tumours are among the most treatable of solid cancers because of their marked sensitivity to platinum-based chemotherapy.

Definition

Testicular cancer comprises malignant neoplasms of the testis, of which germ cell tumours (seminomas and non-seminomatous germ cell tumours) are by far the most common; they are classified histologically under the WHO scheme and characterised by serum tumour markers and TNM stage.

Scope

This entry covers the epidemiology, risk factors, and classification of testicular cancer and germ cell tumours: the seminoma versus non-seminoma distinction, the role of serum tumour markers, and the WHO histological framework. It is a reference-educational overview and does not provide diagnostic or treatment recommendations.

Core questions

• What are the main types of testicular germ cell tumour and how are they distinguished?
• Which serum tumour markers are associated with testicular cancer?
• What are the established risk factors, such as cryptorchidism?
• Why is testicular germ cell tumour considered highly curable?

Key concepts

• Germ cell tumour
• Seminoma
• Non-seminomatous germ cell tumour
• Germ cell neoplasia in situ (precursor lesion)
• Serum tumour markers (AFP, beta-hCG, LDH)
• Cryptorchidism as a risk factor
• Platinum sensitivity and curability

Mechanisms

Most testicular germ cell tumours are thought to arise from a common precursor, germ cell neoplasia in situ, derived from fetal germ cells, and the majority of cases harbour an isochromosome 12p (Cheng, 2018). Tumours are divided into seminomas, which resemble undifferentiated germ cells, and non-seminomatous tumours, which show embryonic or extra-embryonic differentiation (embryonal carcinoma, yolk sac tumour, choriocarcinoma, teratoma); this histological distinction is captured by the WHO classification (Moch, 2016). Serum tumour markers—alpha-fetoprotein, beta-human chorionic gonadotropin, and lactate dehydrogenase—reflect tumour biology and are incorporated into staging.

Clinical relevance

Testicular cancer most often presents as a painless testicular lump or swelling in a young man, and serum tumour markers are a distinctive feature used in characterising and staging the disease (Cheng, 2018). The seminoma versus non-seminoma distinction and the marker profile are the principal descriptors clinicians use. This entry describes how the disease is classified and is not a basis for individual diagnostic or treatment decisions.

Epidemiology

Testicular cancer is relatively uncommon overall but is the most frequent solid cancer in men aged roughly 15-40 years, with the highest incidence in populations of European ancestry and a long-term rising trend in many countries (Bray, 2024; Cheng, 2018). The strongest established risk factors are a history of cryptorchidism (undescended testis), a personal or family history of testicular germ cell tumour, and prior germ cell neoplasia in situ (Cheng, 2018).

Evidence & guidelines

Histological classification follows the WHO classification of tumours of the urinary system and male genital organs (Moch, 2016), and anatomical extent plus serum tumour markers are combined in the TNM (S-category) staging system. Disease-specific guidelines are published by professional bodies such as the European Association of Urology and the American Urological Association; readers should consult the current versions.

Seminal works

• cheng-2018
• moch-2016

Frequently asked questions

What are the two main categories of testicular germ cell tumour?

Seminomas, which resemble undifferentiated germ cells, and non-seminomatous germ cell tumours, which show embryonic or extra-embryonic differentiation; the distinction is fundamental to how the disease is classified and staged.

Which conditions increase the risk of testicular cancer?

A history of an undescended testis (cryptorchidism), a personal or family history of testicular germ cell tumour, and the precursor lesion germ cell neoplasia in situ are the strongest established risk factors.