Genes associated with testicular germ cell tumors and testicular dysgenesis in patients with testicular microlithiasis

Today it is noted that the most cases of the hypospadias, cryptorchidism, testicular microlithiasis, as well as problems of semen quality and testicular germ cell tumours can be a clinical manifestation of testicular dysgenesis syndrome caused by abnormal development of reproductive organs. In the last decade, technological progress in the molecular genetics has made possible to carry out a directed search for genetic factors associated with reproductive disorders in men. In the review we attempted to analyze available literature data on the testicular dysgenesis syndrome and its constituent condition and also to consider the risk factors associated with its development. We give particular attention to the consideration of genetic factors that determine the manifestation of testicular microlithiasis, cryptorchidism and testicular germ cell tumors, both individual clinical conditions and in the syndrome of testicular dysgenesis. Knowledge of the genetic aspects of reproductive damage will allow us to characterize the complex interconnection of the human genome with the clinical phenotype, clarify the role of unfavorable factors of the environment and the lifestyle of the individual, and suggest new approaches to treatment.

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Histological Features of Sporadic and Familial Testicular Germ Cell Tumors Compared and Analysis of Age-Related Changes of Histology

Cancers ◽

10.3390/cancers13071652 ◽

2021 ◽

Vol 13 (7) ◽

pp. 1652

Author(s):

Andreas Stang ◽

Mary L. McMaster ◽

Isabell A. Sesterhenn ◽

Elizabeth Rapley ◽

Robert Huddart ◽

...

Keyword(s):

Germ Cell ◽

Germ Cell Tumors ◽

Lymphocytic Infiltration ◽

Testicular Germ Cell Tumors ◽

Testicular Microlithiasis ◽

Testicular Germ Cell ◽

Histological Features ◽

Age Related ◽

Infiltrating Lymphocytes ◽

Surrounding Parenchyma

This study aimed to compare histological features of familial and sporadic testicular germ cell tumors (TGCTs) and surrounding parenchyma, since discriminating features might be etiologically relevant and clinically useful. The study of parenchyma was prompted by reports claiming a higher prevalence of testicular microlithiasis in familial cases. Histological features of TGCTs and surrounding parenchyma of 296 sporadic and 305 familial cases were compared. For each case, one representative hematoxylin and eosin-stained slide was available. Slides were independently scored by two expert pathologists using a semi-quantitative data abstract. Discrepancies were resolved by consensus. A logistic regression model was used to assess the ability to discriminate between sporadic and familial GCT. The histological composition of a tumor, amount of lymphocytic infiltration, amount of germ cell neoplasia in situ (GCNIS), and presence of testicular microlithiasis (TM) did not discriminate between sporadic and familial GCT (area under the curve 0.56, 95%CI 0.51–0.61). Novel observations included increasing lymphocytic infiltration and decreasing GCNIS and TM with increasing age at diagnosis. The presence of tubules with infiltrating lymphocytes was mainly associated with pure seminomas and nonseminomas with a seminoma component. Among seminomas, tubules with infiltrating lymphocytes decreased with increasing age. No discernable differences between sporadic and familial TGCTs were found. The age-related changes in the tumors and surrounding parenchyma in these groups combined are consistent with a host response building up over time predominantly affecting seminomas, the seminoma-component of nonseminomas and GCNIS. TM may gradually dissolve with age. Our hypothesis that histological differences between sporadic and familial TGCT might identify genetically distinct disease subsets was not supported.

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