Less advanced testicular dysgenesis is associated by a higher prevalence of germ cell neoplasia

Abstract

There is a theory that the more evident clinical signs of testicular dysgenesis, the more frequent the neoplastic lesions are. The aim of this study was to relate the incidence of testicular germ cell neoplastic lesions (overt germ cell tumours--GCT or testicular carcinoma in situ) to the intensity of testicular organogenesis disturbances (dysgenesis). Biopsies were taken from 154 testes of the following patients: 23 patients with GCT in the contralateral gonad (CGCT), 41 patients with undescended testes operated in childhood (UDT), 90 with azoo-/oligozoospermia (A/O) diagnosed because of infertility. Assessment of seminiferous epithelium, number of Leydig cells, areal fraction of intertubular space (IS), morphometric analysis of seminiferous tubules diameter and thickness of tubular wall were performed. Monoclonal antibodies against placental like alkaline phosphatase and cytokeratin 18 were applied. Germ cell neoplastic lesions were detected in 7.1% of testes and were associated with disturbed spermatogenesis. Among testes with disturbed spermatogenesis they were found the most frequently in CGCT (22.2% vs. 11.1% in UDT and 3.8% in A/O), where spermatogenesis had the highest score (5.7 +/- 3.8 points vs. 4.2 +/- 2.7 in UDT and 4.6 +/- 2.9 in A/O). In CGCT, signs of testicular dysgenesis were less advanced: the highest tubular diameter was 164.4 +/- 32.3 microm vs. 163.5 +/- 28.6 in UDT and 161.4 +/- 31.5 in A/O, the lowest thickness of tubular wall was 8.9 +/- 3.2 microm vs. 10.2 +/- 3.6 in UDT and 10.2 +/- 3.2 in A/O, lowest IS was 36.9 +/- 14.9% vs. 47.9 +/- 18.0 in UDT and 46.5 +/- 18.5 in A/O, and the lowest percentage of tubules with immature Sertoli cells was 0.1 +/- 0.4% vs. 4.9 +/- 7.0 in UDT and 5.2 +/- 9.7 in A/O. Results indicate that neoplastic lesions appear only in testes with disturbed spermatogenesis. Worse condition of spermatogenesis is associated by the presence of other dysgenetic features, but neoplastic lesions appear more frequently in testes with the less advanced features of testicular dysgenesis.

Estrogen receptor alpha localization in the testes of men with normal spermatogenesis

“…The number of Leydig cells in the triangular intertubular spaces was assessed on a scale of 1-5 according to Guminska et al [33]. Based on observations from our own and other studies, a number of Leydig cells higher than 2 points was considered to be abnormal [34].…”

“…Sections of ovarian tissues from postmenopausal women served as positive control [31]. [32], presented in a previous study [33]. A score of 10 points was considered to be full, intact spermatogenesis, while a lower score indicated a deteriorating seminiferous epithelium.…”

“…The assessment of the spermatogenesis score and Leydig cell score, as well as the morphometric analysis of testicular structure, revealed values typical for normal adult testes (Table 1) [33,36,37].…”

“…The following values were recognized as abnormal: tubular diameter < 150 μm, thickness of tubular wall > 10 μm, IS > 40%. The normal values of the diameter of seminiferous tubules, thickness of tubular wall and interstitial spaces were defined based on previous reports [33,34,36,37].…”

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

“…Depending on the degree of masculinisation of the gonad, either GCNIS or gonadoblastoma, or a mixture of both, may be present. GCNIS is enclosed in better masculinised tubules, while gonadoblastoma resides in nests of granulosa-resembling cells, but the neoplastic germ cells have essentially the same phenotypic features [5][6][7]. A good marker for more masculinised Sertoli cells is SOX9, whereas granulosa-like cells surrounding gonadoblastoma cells express FOXL2 [8].…”