title: Ovarian cellular fibromas lack FOXL2 mutations: a useful diagnostic adjunct in the distinction from diffuse adult granulosa cell tumor.
abstract: Ovarian cellular fibromas are uncommon neoplasms, which may result in considerable diagnostic confusion with diffuse adult granulosa cell tumor. This is an important distinction, as the former usually exhibits benign behavior, whereas the latter is a low-grade malignant neoplasm capable of recurrence and metastasis. FOXL2 mutation (402C→G) has been demonstrated in >95% of ovarian adult granulosa cell tumors, only rarely in other ovarian sex cord-stromal neoplasms, and never in ovarian fibromas. In this study, we evaluated a series of ovarian cellular fibromas or mitotically active cellular fibromas (n=22), 3 with minor sex cord elements, for FOXL2 mutation. These were mostly received in consultation, often with a differential diagnosis of diffuse adult granulosa cell tumor. Immunohistochemically, 10 of 10 cases tested exhibited nuclear staining with FOXL2. FOXL2 (402C→G) mutation was not demonstrated in any of the 22 cellular or mitotically active cellular fibromas. Three additional neoplasms composed of cellular nodules of epithelioid cells in a background fibrous stroma, raising the possibility of adult granulosa cell tumor with a prominent fibrothecomatous component, were also tested; 2 of these were mutation negative, and 1 contained a FOXL2 mutation. FOXL2 mutation analysis is a useful adjunct in distinguishing between diffuse adult granulosa cell tumor (mutation present) and cellular fibroma (mutation absent). Mutation testing should be considered in problematic cases, as this will provide prognostic information for the patient.
authors.affiliation: *Department of Pathology, Belfast Health and Social Care Trust, Belfast †Department of Pathology, Barts Health NHS Trust, London, United Kingdom ‡Centre for Translational and Applied Genomics §Department of Pathology, University of British Columbia ∥Department of Pathology, Vancouver General Hospital, Vancouver, BC, Canada.
authors.forename: W Glenn
authors.initials: WG
authors.lastname: McCluggage
authors.forename: Naveena
authors.initials: N
authors.lastname: Singh
authors.forename: Stefan
authors.initials: S
authors.lastname: Kommoss
authors.forename: David G
authors.initials: DG
authors.lastname: Huntsman
authors.forename: C Blake
authors.initials: CB
authors.lastname: Gilks
mesh_terms: D014408:Biomarkers, Tumor / Q000032:analysis / Q000235:genetics*; D001706:Biopsy; D004252:DNA Mutational Analysis; D003937:Diagnosis, Differential; D005260:Female; D005350:Fibroma / Q000737:chemistry / Q000235:genetics* / Q000473:pathology; D000074842:Forkhead Box Protein L2; D051858:Forkhead Transcription Factors / Q000032:analysis / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D006106:Granulosa Cell Tumor / Q000737:chemistry / Q000235:genetics* / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D008938:Mitosis; D009154:Mutation; D010051:Ovarian Neoplasms / Q000737:chemistry / Q000235:genetics* / Q000473:pathology; D010641:Phenotype; D011237:Predictive Value of Tests
chemical_list: D014408:Biomarkers, Tumor; C421604:FOXL2 protein, human; D000074842:Forkhead Box Protein L2; D051858:Forkhead Transcription Factors