Intratubular germ cell neoplasia of the testis and its associated cancers: the use of novel biomarkers

Recent advances in the understanding of the molecular pathology of testicular tumours have led to the identification of several new immunohistochemical markers for invasive and in situ germ cell neoplasms. OCT3/4 and NANOG are nuclear stains that have high sensitivity and specificity for the identification of intratubular germ cell neoplasia as well as seminoma and embryonal carcinoma. A potential pitfall in their application to the detection of intratubular germ cell neoplasia, as in other markers that represent oncofetal antigens, is their expression in non-neoplastic germ cells with 'delayed maturation'. SALL4, another nuclear stain, is positive for most germ cell tumours as a group and may be especially helpful in the distinction of these tumours from somatic carcinomas in non-testicular sites. Glypican 3 is a more sensitive marker for yolk sac tumour than alpha-fetoprotein. SOX2 and SOX17 may be useful for differentiating seminoma and embryonal carcinoma, especially following chemotherapy as embryonal carcinoma may lose CD30 expression in this setting. This article reviews the application of these immunohistochemical markers and others to the diagnosis of germ cell neoplasia with reference to older immunohistochemical stains when appropriate. Suggested immunohistochemical panels are described for individual tumour types.