Heterogeneous distribution of ITGCNU in an adult testis: consequences for biopsy-based diagnosis

Carcinoma in situ (CIS) of the testis, also referred to as intratubular germ cell neoplasia unclassified (ITGCNU), is currently accepted as the common precursor for all malignant germ cell tumors of adolescents and adults- that is, the seminomatous and nonseminoma cancers. These preinvasive cells have specific cellular characteristics, which can be used for the early diagnosis-routinely done by morphological analysis, sometimes supported by immunohistochemistry-of tissue obtained by an open surgical biopsy. False-negative biopsy results can occur mostly because of the nonrandom distribution of ITGCNU within the testis, misdiagnosis, or suboptimal tissue treatment and analysis. In this article, we demonstrate the potential pitfalls in the diagnosis of ITGCNU. The results support the use of the highly specific and sensitive immunohistochemical marker OCT3/4 for the diagnosis of ITGCNU and provide evidence for the nonrandom distribution of ITGCNU, which is a significant limitation in the diagnosis of this preinvasive lesion.