title: FOXL2 mutations in granulosa cell tumors occurring in males.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
authors: Division of Anatomic Pathology, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota, USA. felipelima.joema@mayo.edu
authors: Joema F
authors: JF
authors: Lima
authors: Long
authors: L
authors: Jin
authors: Ana Rose C
authors: AR
authors: de Araujo
authors: Michele R
authors: MR
authors: Erikson-Johnson
authors: Andre M
authors: AM
authors: Oliveira
authors: Thomas J
authors: TJ
authors: Sebo
authors: Gary L
authors: GL
authors: Keeney
authors: Fabiola
authors: F
authors: Medeiros
mesh_terms: D000328:Adult; D000368:Aged; D004252:DNA Mutational Analysis; D000074842:Forkhead Box Protein L2; D051858:Forkhead Transcription Factors / Q000235:genetics*; D006106:Granulosa Cell Tumor / Q000235:genetics* / Q000473:pathology; D006801:Humans; D007223:Infant; D007265:Inhibins / Q000235:genetics; D008297:Male; D009154:Mutation; D013736:Testicular Neoplasms / Q000235:genetics* / Q000473:pathology
chemical_list: C421604:FOXL2 protein, human; D000074842:Forkhead Box Protein L2; D051858:Forkhead Transcription Factors; D007265:Inhibins