Histological features of sporadic and familial testicular germ cell tumors compared and analysis of age-related changes of histology

Andreas Stang, Mary L. McMaster*, Isabell A. Sesterhenn, Elizabeth Rapley, Robert Huddart, Ketil Heimdal, Katherine A. McGlynn, Jan Wolter Oosterhuis, Mark H. Greene

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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This study aimed to compare histological features of familial and sporadic testicular germ cell tumors (TGCTs) and surrounding parenchyma, since discriminating features might be etiologi-cally 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 infil-tration, 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.

Original languageEnglish
Article number1652
Issue number7
Publication statusPublished - 1 Apr 2021

Bibliographical note

Funding Information:
Funding: The research activities of M.L.M, K.A.M. and M.H.G. were supported by the Intramural Research Program, Division of Cancer Epidemiology and Genetics, National Cancer Institute, as well as support services contracts HHSN261200655004C and HHSN261201300003C with Westat, Inc. A.S. was funded by the German Federal Ministry of Education and Science (BMBF), grant number 01ER1305.

Publisher Copyright:
© 2021 by the authors. Licensee MDPI, Basel, Switzerland.


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