FOXL2-associated granulosa cell tumor

FOXL2 mutation (402C→G) has been demonstrated in >95% of ovarian adult granulosa cell tumors.

Diagnostic use

 Differential diagnosis with ovarian cellular fibroma

• 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.
• 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.

References

 Ovarian Cellular Fibromas Lack FOXL2 Mutations: A Useful Diagnostic Adjunct in the Distinction From Diffuse Adult Granulosa Cell Tumor. McCluggage WG, Singh N, Kommoss S, Huntsman DG, Gilks CB. Am J Surg Pathol. 2013 Jun 14. PMID: 23774170
See also

 FOXs

• FOXLs

References

 Adult-type granulosa cell tumors and FOXL2 mutation. Köbel M, Gilks CB, Huntsman DG. Cancer Res. 2009 Dec 15;69(24):9160-2. PMID: 19996294

 The specificity of the FOXL2 c.402C>G Somatic mutation: a survey of solid tumors. Schrader KA, Gorbatcheva B, Senz J, Heravi-Moussavi A, Melnyk N, Salamanca C, Maines-Bandiera S, Cooke SL, Leung P, Brenton JD, Gilks CB, Monahan J, Huntsman DG. PLoS One. 2009 Nov 24;4(11):e7988. PMID: 19956657

 The forkhead factor FOXL2: A novel tumor suppressor? Benayoun BA, Kalfa N, Sultan C, Veitia RA. Biochim Biophys Acta. 2009 Sep 10. PMID: 19747961

 The new molecular biology of granulosa cell tumors of the ovary. Kalfa N, Veitia RA, Benayoun BA, Boizet-Bonhoure B, Sultan C. Genome Med. 2009 Aug 25;1(8):81. PMID: 19725933

 Mutation of FOXL2 in granulosa-cell tumors of the ovary. Shah SP, Köbel M, Senz J, Morin RD, Clarke BA, Wiegand KC, Leung G, Zayed A, Mehl E, Kalloger SE, Sun M, Giuliany R, Yorida E, Jones S, Varhol R, Swenerton KD, Miller D, Clement PB, Crane C, Madore J, Provencher D, Leung P, DeFazio A, Khattra J, Turashvili G, Zhao Y, Zeng T, Glover JN, Vanderhyden B, Zhao C, Parkinson CA, Jimenez-Linan M, Bowtell DD, Mes-Masson AM, Brenton JD, Aparicio SA, Boyd N, Hirst M, Gilks CB, Marra M, Huntsman DG. N Engl J Med. 2009 Jun 25;360(26):2719-29. PMID: 19516027