FOXL2 mutations in granulosa cell tumors occurring in males

Context. - Granulosa cell tumors comprise less than 5% of ovarian tumors in women and are much rarer in men, with only about 20 cases reported, to our knowledge. Recently, a somatic mutation of FOXL2 was reported in virtually all adult-type granulosa cell tumors in women. Objective. - To investigate FOXL2 mutations in granulosa cell tumors occurring in males. Design. - Five cases of an adult-type granulosa cell tumor from males were selected from the files of the Mayo Clinic. Nine other testicular tumors (1 juvenile granulosa cell tumor, 5 Leydig cell tumors, and 3 Sertoli- Leydig cell tumors) were evaluated for comparison. Inhibin immunostain was performed in all cases. DNA was extracted from formalin-fixed, paraffin-embedded tissue, followed by polymerase chain reaction and direct sequencing of FOXL2. Results. - All 5 cases had classic histopathologic features of the adult-type granulosa cell tumor. Inhibin was diffusely positive in all cases. FOXL2 402C→G (C134W) was identified in 40% (2 of 5) of the male, adult-type granulosa cell tumors. Of the 2 tumors positive for the mutation, 1 occurred in the testis of a man, and the other one affected the abdominal ovaries of a phenotypically male patient. All other testicular tumors were negative for the mutation. Conclusions. - The FOXL2 402C→G (C134W) mutation is also present in adult-type granulosa cell tumors occurring in men, although in a smaller proportion when compared with the rates reported in women. FOXL2 mutational analysis can be a helpful in the diagnosis of granulosa cell tumors of the testis.