Guidelines

Testicular Cancer

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 [6]. Its incidence has increased during recent decades, particularly in industrialised countries [7,8], and continues to rise. At diagnosis, 1-2% of cases are bilateral and the predominant histology is germ cell tumours (GCT) (90-95% of cases) [6]. The peak incidence is in the third decade of life for non-seminoma testis (NST) and mixed GCT patients, and in the fourth decade for seminoma testis (ST) patients. In 5% of TGCT patients the primary site is at an extragonadal location [9].

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

Non-related GCNIS tumours include pre-pubertal type teratoma and yolk sac (Type I), diagnosed at early paediatric age, and spermatocytic tumours (Type III), diagnosed in the elderly. Although there is overlapping histology between the pre-pubertal teratoma/yolk sac and the teratoma and yolk sac elements in the GCNIS-related non-seminomas, they have a separate and independent pathogenesis [10].

Overall, type II TGCT have a low mutational burden and few somatic changes. A specific recurrent genetic marker – an isochromosome of the short arm of chromosome 12 – (i12p) – is over-represented in most invasive GCNIS-related TGCTs [10,11] but not found in GCNIS [12]. However, some type II TGCTs, mostly seminomas, appear to lack a gain of 12p and present preferential cKIT mutations. Without occurrence of these mutations GCNIS will not progress to invasive GCTs [10]. Other significant chromosomal aberrations in type II TGCTs are gain of 7, 8, 21 and loss of chromosomes 1p, 11, 13 and 18 [13].

Epidemiological risk factors for the development of TC are components of the testicular dysgenesis syndrome (which encompasses cryptorchidism), hypospadias, decreased spermatogenesis and impaired fertility [14-16] or disorders/differences of sex development [17]. Additional risk factors include family history of TC among first-degree relatives and the presence of a contralateral testicular tumour or GCNIS [14,18-24]. Recent genome-wide association studies revealed detectable susceptibility loci leading to an increased relative risk to develop TC [25].

3.2. Histological classification

General:

The recommended pathological classification shown below is based on the 2016 update of the World Health Organization (WHO) pathological classification [26].

1.Germ cell tumours

Germ cell neoplasia in situ (GCNIS)

2.Derived from GCNIS

Seminoma
Embryonal carcinoma
Yolk sac tumour, post-pubertal type
Trophoblastic tumours
Teratoma, post-pubertal type
Teratoma with somatic malignant components
Mixed germ cell tumours

3.Germ cell tumours unrelated to GCNIS

Spermatocytic tumour
Yolk sac tumour, pre-pubertal type
Mixed germ cell tumour, pre-pubertal type

4.Sex cord/stromal tumours

Leydig cell tumour
Malignant Leydig cell tumour
Sertoli cell tumour
Malignant Sertoli cell tumour
Large cell calcifying Sertoli cell tumour
Intratubular large cell hyalinising Sertoli cell neoplasia
Granulosa cell tumour
Adult type
Juvenile type
Thecoma/fibroma group of tumours
Other sex cord/gonadal stromal tumours
Mixed
Unclassified
Tumours containing both germ cell and sex cord/gonadal stromal
Gonadoblastoma

5.Miscellaneous non-specific stromal tumours

Ovarian epithelial tumours
Tumours of the collecting ducts and rete testis
Adenoma
Carcinoma
Tumours of paratesticular structures
Adenomatoid tumour
Mesothelioma (epithelioid, biphasic)
Epididymal tumours
Cystadenoma of the epididymis
Papillary cystadenoma
Adenocarcinoma of the epididymis
Mesenchymal tumours of the spermatic cord and testicular adnexae