Birt–Hogg–Dubé syndrome in a patient with melanoma and a novel mutation in the FCLN gene

Abstract

Birt-Hogg-Dubé syndrome (BHDS) is an autosomal dominant genodermatosis characterized by the presence of three skin tumors (fibrofolliculomas, trichodiscomas, and acrochordons), together with an increased risk for other tumors, especially renal tumors, caused by a mutation in folliculin, an oncogene suppressor protein. The association of this syndrome with melanoma is very unusual. We report the case of a 54-year-old man with a history of melanoma who had multiple white facial papules. His son also presented similar facial lesions. Histopathologic study showed fibrofolliculomas. These clinical and histopathologic features suggested the diagnosis of BHDS. Genetic study revealed a novel heterozygous mutation p.S185P in exon 6 of the FLCN gene. To date, the association between melanoma and BHDS has rarely been described. As the pathogenic mechanism responsible for melanoma seems to be the same as that responsible for neoplasms in BHDS, the authors consider the melanoma a manifestation of BHDS. Thus, during the periodic follow-up of patients with BHDS, we recommend periodic exhaustive skin examination and excisional biopsy of any suspicious pigmented lesion.