Histological evidence of testicular dysgenesis in contralateral biopsies from 218 patients with testicular germ cell cancer

Abstract

This study was prompted by a hypothesis that testicular germ cell cancer may be aetiologically linked to other male reproductive abnormalities as a part of the so-called 'testicular dysgenesis syndrome' (TDS). To corroborate the hypothesis of a common association of germ cell cancer with testicular dysgenesis, microscopic dysgenetic features were quantified in contralateral testicular biopsies in patients with a testicular germ cell tumour. Two hundred and eighty consecutive contralateral testicular biopsies from Danish patients with testicular cancer diagnosed in 1998-2001 were evaluated retrospectively. Two hundred and eighteen specimens were subsequently included in this study, after 63 patients who did not meet inclusion criteria had to be excluded. The presence of carcinoma in situ (which is believed to originate from transformed gonocytes) was detected in 8.7% of biopsies. The incidence of other dysgenetic features was immature tubules with undifferentiated Sertoli cells, 4.6%; microcalcifications (microliths), 6.0%; and the presence of a Sertoli-cell-only pattern in at least a few tubules, 13.8%. The cumulative incidence of one or more signs of testicular dysgenesis was 25.2%. In a few patients, areas with immature and morphologically distorted tubules were also noted. Spermatogenesis was qualitatively normal in 51.4%, whereas 11.5% had very poor or absent spermatogenesis. It is concluded that microscopic testicular dysgenesis is a frequent feature in contralateral biopsies from patients presenting with testicular germ cell neoplasms of the adolescent and young type. The findings therefore support the hypothesis that this cancer is part of a testicular dysgenesis syndrome. The presence of contralateral carcinoma in situ was higher in the present study than previously reported.

Diagnostic markers for germ cell neoplasms: from placental-like alkaline phosphatase to micro-RNAs

“…It is important for the understanding of the pathogenesis of GCNIS-derived TGCT that even though most of the patients are normally virilised males, these neoplasms are associated with disturbed early development of the testis, often manifested in adulthood as clusters of poorly formed tubules, undifferentiated Sertoli cells, microlithiasis and Leydig cells micronodules [9]. Among the risk factors for GCNIS/TGCT, cryptorchidism, genital malformations, low percentage sex chromosome aneuploidy and some forms of infertility, are also linked to disturbed foetal development, hence all these conditions have been grouped within testicular dysgenesis syndrome (TDS) [10].…”

Origins and molecular biology of testicular germ cell tumors

“…[37][38][39][40][41][42] 43 have shown a strong correlation between the presence of the Y chromosome and the severity of the gonadal dysgenesis. Gonadoblastoma acts as an 'in situ' precursor in these patients.…”

“…Gonadoblastoma acts as an 'in situ' precursor in these patients. Recently, Skakkebaek and co-workers 37,42 suggested that many patients with testicular GCT have some evidence of gonadal dysgenesis in the contralateral gonad, be it microlithiasis, Sertoli-cell-only tubules, seminiferous tubules with undifferentiated Sertoli cells or IGCNU. If this is true, it suggests that a specific genetic mutation may not be required to initiate the process of tumor development, but rather environmental factors are sufficient as initiating events.…”

Expressing urine from a gel disposable diaper for biomonitoring using phthalates as an example

“…Subsequent research demonstrated a coordinated, dosedependent reduction in expression of key genes and proteins involved in cholesterol transport and steroidogenesis and a corresponding reduction in testosterone in the fetal testes (Lehmann et al, 2004). In humans, similar dysgenetic changes in the histology of the testis have been found in patients with testicular cancer, subfertility, or cryptorchidism (Sohval, 1954(Sohval, , 1956Berthelsen & Skakkebaek, 1983;Hoei-Hansen et al, 2003;Skakkebaek et al, 2003). Furthermore, men with rare genetic abnormalities that cause testicular dysgenesis (e.g.…”