GCNIS

GCNIS, or germ cell neoplasia in situ, is a premalignant lesion of the gonads and the principal precursor to most testicular germ cell tumors, including seminoma and non-seminomatous germ cell tumors. It is believed to arise from gonocytes that fail to differentiate properly during fetal development and persists in the seminiferous tubules into puberty and adulthood. GCNIS cells are typically noninvasive but clonally related to invasive germ cell tumors, and their presence indicates a risk of progression to cancer if not monitored or treated.

Pathologically, GCNIS is characterized by atypical germ cells within the basement membrane of seminiferous tubules. These cells often show enlarged nuclei, prominent nucleoli, and pale cytoplasm, and they may be arranged in clusters or individual cells along the tubular walls. Immunohistochemically, GCNIS cells commonly express markers such as OCT3/4 and placental-like alkaline phosphatase (PLAP), supporting a germ cell origin; they usually lack markers of mature spermatogenesis.

Risk factors associated with GCNIS include cryptorchidism, testicular dysgenesis, infertility, and a family history of testicular cancer. It can be found in the contralateral testis of men with a germ cell tumor in one testis, and it may be identified incidentally in surgical specimens or biopsies performed for other indications.

Clinical management depends on the clinical context. In men with known GCNIS, surveillance for progression to invasive cancer is common, while adjuvant or targeted therapy may be considered in higher-risk situations or in the presence of concomitant invasive germ cell tumors. If progression occurs, treatment follows standard regimens for testicular germ cell tumors, which can include orchiectomy followed by radiotherapy or chemotherapy, depending on tumor type and stage. Prognosis is favorable when invasive cancer is detected and treated early, but untreated GCNIS carries a risk of progression to cancer over time.