Pathology and genetics of tumours of the urinary system and male genital organs

The 2016 WHO Classification of Tumours of the Urinary System and Male Genital Organs-Part A: Renal, Penile, and Testicular Tumours.

Approximately 95 percent of malignant tumors arising in the testis are germ-cell tumors, a term that indicates their origin in primordial germ cells. Germ-cell tumors also occasionally arise in extragonadal primary sites, and their management follows that of testicular germ-cell tumors. More than 90 percent of patients with newly diagnosed germ-cell tumors are cured, and delay in diagnosis correlates with a higher stage at presentation for treatment.1,2 Management has changed substantially in the past 20 years, largely because of the ability of cisplatin-containing combination chemotherapy to cure advanced disease.3 In this review, we discuss recent developments in our understanding . . .

https://www.nejm.org/doi/pdf/10.1056/NEJM199707243370406

Testicular Germ-Cell Cancer

Pathogenesis of adult testicular germ-cell tumors - a cytogenetic model

Clinical observations and epidemiological evidence suggest that important aetiopathological events that cause neoplastic transformation of the male germ cell may occur in fetal life or early infancy. The incidence of germ cell neoplasia is high in individuals with various disorders of gonadal development and sexual differentiation, such as gonadal dysgenesis or androgen insensitivity syndrome. Increased risk has also been noted in individuals with trisomy 21, idiopathic infertility and low birth weight. Infertility is sometimes associated with small aberrations of sex chromosomes (e.g. low frequency mosaicism XY/XO) which can also be found in patients with testicular cancer. The variety of conditions that predispose to testicular neoplasia and the rise in its incidence in many countries speaks for the influence of environmental factors which may affect genetically predisposed individuals. We hypothesise that if the development of the testis is disturbed or delayed, primordial germ cells or gonocytes undergo maturation delay or differentiation arrest which may render them susceptible to neoplastic transformation. Morphologically homogenous premalignant carcinoma in situ (CIS) cells have the potential to differentiate into a variety of histological forms of overt testicular tumours. Analysis of cell surface antigens expressed by CIS cells found in the vicinity of pure and mixed tumours demonstrates that CIS cells are phenotypically heterogeneous. Comparison of the phenotypes of CIS cells, primordial germ cells, human embryonal carcinoma cells and closely related primate embryonal stem cells reveals various similarities but also differences. We speculate that phenotypical heterogeneity of CIS cells may be associated with their potential to give rise to different tumour types, and may be related to the developmental stage of the early germ cell which has undergone malignant transformation.

Developmental arrest of germ cells in the pathogenesis of germ cell neoplasia

The spermatocytic seminoma has clinical and histological characteristics which differ from those of other germ cell tumours of the testis. Classical seminomas and teratomas are believed to originate from intratubular carcinoma-in-situ (CIS), which is almost invariably found adjacent to these neoplasms. In addition, DNA analysis of these tumours and the surrounding CIS has shown both to have an aneuploid distribution. In order to throw light on the origin of the spermatocytic seminoma, we have examined the testicular tissue adjacent to fifteen spermatocytic seminomas for the presence of CIS and assessed the DNA content of the tumour cells densitometrically. In twelve specimens seminiferous tubules were present adjacent to the tumour, and in none of these cases was CIS seen. Nuclear DNA measurements were possible in eleven tumours and in five cases the distribution was diploid, in three cases tetraploid, and only in three cases aneuploid. Therefore, we suggest that the spermatocytic seminoma has a different cell of origin from that of other germ cell tumours of the testis.

The spermatocytic seminoma: views on pathogenesis.

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The spermatocytic seminoma: views on pathogenesis.