3. EPIDEMIOLOGY AETIOLOGY PATHOLOGY
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
General:
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