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The value of positive Oct3/4 and D2-40 immunohistochemical expression in prediction of germ cell neoplasia in prepubertal boys with cryptorchidism

Abstract Objective: Intratubular germ cell neoplasia (ITGCN) is a precursor to testicular germ cell cancer. Adult germ cell cancer immunohistochemical markers fail to detect ITGCN in prepubertal boys with congenital cryptorchidism, because positive immunohistochemistry is commonly seen below 18 months old, where most orchiopexies are performed. The aim of the study was to evaluate the ability of Oct3/4 and D2-40 immunohistochemical markers to detect ITGCN in boys older than 2 years with cryptorchidism. Materials and methods: Histological sections from 309 testicular biopsies from 234 boys aged 1 month to 14 years, 6 months operated on for cryptorchidism were incubated with primary antibodies including anti-placental-like alkaline phosphatase, anti-Oct3/4, anti-C-kit and anti-D2-40 receptor. Results: One 3-year, 8-month-old boy with 45X/46XY disorder of sexual development had ITGCN and all positive markers. Besides this case, none of the 192 testes except one from boys older than 2 years had any Oct3/4- or D2-40-positive germ cells identified. The germ cells of the right testis from a 3-year, 7-month-old boy had weak Oct3/4 expression but were D2-40 negative. The prevalences of Oct3/4- and D2-40-positive staining of germ cells in testicular biopsies were, for each age group: < 6 months, 100% and 50%; 6 months to < 1 year, 65% and 16%; 1 to < 2 years, 15% and 3%; and 2 years to < 14 years, 6 months, 2% and 1%, respectively. Conclusion: Oct3/4 and D2-40 immunohistochemical markers may be beneficial in detecting ITGCN in boys older than 2 years with cryptorchidism. Even when immunohistochemistry is applied, prepubertal ITGCN is so rarely demonstrated in cryptorchid testes that it is not plausible that ITGCN generally originates during fetal development in cryptorchidism.