Gonadoblastoma: an immunohistochemical study and comparison to S ertoli cell nodule with intratubular germ cell neoplasia, with pathogenetic implications

Aims To investigate the immunohistochemical properties of the sex cord cells of gonadoblastoma and Sertoli cell nodule with intratubular germ cell neoplasia unclassified ( IGCNU ) as a means of objective distinction and to provide insight into the pathogenesis. Methods and results Immunohistochemical stains for SOX 9, F ox L 2 and SF ‐1 were performed on 10 gonadoblastomas (all phenotypical females) and 14 S ertoli cell nodules with IGCNU in normal phenotypical males with coexisting germ cell tumours. The sex cord cells of gonadoblastomas showed strong, diffuse F ox L 2 and SF ‐1 positivity and focal weak to moderate SOX 9 reactivity, whereas those of S ertoli cell nodules with IGCNU were uniformly, strongly positive for SOX 9 and SF ‐1, while negative for F ox L 2. Conclusions Coexpression of SOX 9 and F ox L 2 in the sex cord cells of gonadoblastomas provides evidence that these morphologically ambiguous sex cord cells are incompletely differentiated. The strong, diffuse SOX 9 and SF ‐1 positivity and absence of F ox L 2 reactivity in the S ertoli cell nodules with IGNCU support full S ertoli cell differentiation of the sex cord cells and distinguish them from gonadoblastomas. Deficient SOX 9 expression in gonadoblastoma supports a current model of pathogenesis where immature germ cells, in the absence of well‐formed S ertoli cells, retain a fetal phenotype and susceptibility to malignant transformation.