Testicular Cancer


3.1. Epidemiology and Aetiology

Testicular cancer represents 1% of adult neoplasms and 5% of urological tumours, with three to ten new cases per 100,000 males/per year in Western societies [4]. The incidence of TC has increased during recent decades, predominantly in industrialised countries [5-8], and it continues to rise. At diagnosis, 1-2% are bilateral and 90-95% of cases are germ cell tumours (GCT) [4]. The peak incidence is in the third decade of life for non-seminomatous germ cell tumour (NSGCT) and mixed GCT patients, and in the fourth decade for seminoma testis (ST) patients. In 5% of GCT patients, the primary site is at an extragonadal location [9].

There are two fundamental categories of GCTs based on their development and epigenetic features. Most malignant post-pubertal GCTs originate from germ cell neoplasia “in situ” (GCNIS). Histologically and clinically, these are subdivided into seminomas and non-seminomas, the latter encompassing somatic and extra-embryonal elements of embryonal carcinoma, yolk sac, choriocarcinoma and post-pubertal teratoma [10].

Non GCNIS derived tumours include pre-pubertal type teratoma and yolk sac tumour, which occur in early childhood, and spermatocytic tumours which usually occurs in older men. Although there is overlapping histology between the pre-pubertal type teratoma/yolk sac and the teratoma and yolk sac tumour elements in the GCNIS-derived NSGCT, these have a separate and independent pathogenesis [10].

Risk factors for GCNIS-derived GCTs are components of the testicular dysgenesis syndrome, which encompasses cryptorchidism, hypospadias, decreased spermatogenesis and impaired fertility [11-13] or disorders of sex development [14]. Additional risk factors include a family history of TC among first-degree relatives and the presence of a contralateral testicular tumour or GCNIS [15-23] although the risk was lower if TC patients previously had received platinum-based chemotherapy [24,25]. Genome-wide association studies revealed detectable susceptibility loci leading to an increased relative risk to develop TC [26].

3.2. Histological classification


The recommended pathological classification shown below is based on the 2022 update of the World Health Organization (WHO) pathological classification [27].

1. Germ cell tumours derived from germ cell neoplasia in situ

  • Non-invasive germ cell neoplasia
    - Germ cell neoplasia in situ
    - Specific forms of intratubular germ cell neoplasia
    - Gonadoblastoma
  • The germinoma family of tumours
    - Seminoma
  • Non-seminomatous germ cell tumours
    - Embryonal carcinoma
    - Yolk sac tumour, postpubertal-type
    - Choriocarcinoma
    - Placental site trophoblastic tumour
    - Epithelioid trophoblastic tumour
    - Cystic trophoblastic tumour
    - Teratoma, postpubertal-type
    - Teratoma with somatic-type malignancy
  • Mixed germ cell tumours of the testis
    - Mixed germ cell tumours
  • Germ cell tumours of unknown type
    - Regressed germ cell tumours

2. Germ cell tumours unrelated to germ cell neoplasia in situ

- Spermatocytic tumour
- Teratoma, prepubertal-type
- Yolk sac tumour, prepubertal-type
- Testicular neuroendocrine tumour, prepubertal-type
- Mixed teratoma and yolk sac tumour, prepubertal-type

3. Sex cord stromal tumours of the testis

  • Leydig cell tumour
    - Leydig cell tumour
  • Sertoli cell tumours
    - Sertoli cell tumour
    - Large cell calcifying Sertoli cell tumour
  • Granulosa cell tumours
    - Adult granulosa cell tumour
    - Juvenile granulosa cell tumour
  • The fibroma thecoma family of tumours
    - Tumours in the fibroma thecoma group
  • Mixed and other sex cord stromal tumours
    - Mixed sex cord stromal tumour
    - Signet ring stromal tumour
    - Myoid gonadal stromal tumour
  • Sex cord stromal tumour NOS

4. Tumours of the testicular adnexa

  • Ovarian-type tumours of the collecting ducts and rete testis
    - Serous cystadenoma
    - Serous tumour of borderline malignancy
    - Serous cystadenocarcinoma
    - Mucinous cystadenoma
    - Mucinous borderline tumour
    - Mucinous cystadenocarcinoma
    - Endometrioid tumours
    - Clear cell adenocarcinoma
    - Brenner tumour
  • Tumours of the collecting ducts and rete testis
    - Adenoma of the collecting ducts and rete testis
    - Adenocarcinoma of the collecting ducts and rete testis
  • Paratesticular mesothelial tumours
    - Adenomatoid tumour
    - Well-differentiated papillary mesothelial tumour
    - Mesothelioma
  • Tumours of the epididymis
    - Cystadenoma of the epididymis
    - Papillary cystadenoma of the epididymis
    - Adenocarcinoma of the epididymis
    - Squamous cell carcinoma of the epididymis
    - Melanotic neuroectodermal tumour of the epididymis