Frequency and Markers of Precursor Lesions and Implications for the Pathogenesis of Testicular Germ Cell Tumors

The recent World Health Organization classification of urologic cancer 2016 describes 3 precursor lesions for testicular germ cell tumor type II (TGCT); germ cell neoplasia in situ is the initial precursor lesion. Intratubular seminoma (ITSE) and intratubular embryonal carcinoma (ITEC) are 2 other noninvasive intermediate precursor lesions. Microinvasive germ cell tumor (MGCT) is an invasive precursor lesion. We undertook a retrospective cohort study in Denmark to evaluate the frequency of the precursor lesions concomitant with a macroscopically overt TGCT. We examined 63 testes with TGCT. ITSE as well as MGCT were relatively frequent but we did not find ITEC. Most precursor lesions had a seminomatous immunophenotype, positive for octamer-binding transcription factor 4 and CD117 and negative for CD30. We conclude that MGCT is a frequent intermediate precursor lesion. Background: The World Health Organization classification of urologic cancer 2016 describes 3 noninvasive precursor lesions for testicular germ cell tumor type II (TGCT) of young adults. Germ cell neoplasia in situ is the initial precursor lesion. Intratubular seminoma (ITSE), and intratubular embryonal carcinoma (ITEC) are 2 intermediate precursor lesions. Microinvasive testicular germ cell tumor (MGCT) is an invasive precursor lesion. Materials and Methods: We undertook a retrospective study of testes obtained using orchiectomy for TGCT and examined precursor lesions. The examinations included immunohistochemical staining of the precursor lesions for octamer-binding transcription factor 4 (OCT4), CD117, and CD30. We examined 63 consecutive and evaluable patients. Results: Of the patients, 44 had seminoma and 19 had a nonseminomatous TGCT. MGCT was more frequent than ITSE (P = .002; chi(2) test). None of the testes had ITEC. Immunohistochemistry showed that 72 of 77 precursor lesions (93%) stained positive for OCT4 and CD117 and negative for CD30. The pattern represents a seminomatous immunophenotype. A meta-analysis of the published studies regarding precursor lesions included 1007 patients. Overall, the pooled rate of ITSE was 29% (95% confidence interval [CI], 18%-40%) and the pooled rate of MGCT was 21% (95% CI, 15%-27%). Conclusion: MGCT is a frequent intermediate precursor lesion. (C) 2017 The Authors. Published by Elsevier Inc.