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

Abstract

Simple Summary Testicular germ cell tumors (TGCT) are highly heritable, and earlier studies reported a higher prevalence of certain microscopic features in familial cases compared with sporadic cases. Reasoning by analogy relative to different causal genes for different histologic subtypes of familial kidney cancer, we searched for etiologically informative histopathology associations in familial testicular germ cell cancer. We conducted a detailed, blinded pathology review of familial and sporadic TGCT cases to investigate whether we could identify differences between these two patient subsets and to study the effect of age at diagnosis on histologic features in both groups combined. Our results show no specific histologic differences between familial and sporadic TGCTs. However, we observed histologic features that varied with age at diagnosis among the two groups combined. Thus, our results suggest that there are no histological differences between familial and sporadic TGCT that might identify genetically distinct disease subsets. Abstract 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.