Clinical and genetic characteristics in two cases of Birt-Hogg-Dubé syndrome associated with papillary renal cell carcinoma and rare Folliculin (FLCN) variants.

Abstract

Birt-Hogg-Dubé syndrome (BHDS) is characterized by autosomal dominant alterations in the Folliculin (FLCN) gene, resulting in cutaneous, pulmonary, and renal abnormalities. In particular, affected individuals are susceptible to the development of renal cell carcinoma (RCC), which most frequently present as chromophobe tumors or hybrid cancers with features of oncocytoma and chromophobe RCC. Type 1 and type 2 papillary neoplasms have rarely been described in the setting of BHDS, and we present two additional cases. Utilizing next-generation sequencing, the patients were found to harbor germline FLCN variants that are not well-documented in the medical literature. While RCCs associated with BHDS are thought to portend a better prognosis compared to their non-syndromic counterparts, the patients described here experienced variable clinical outcomes-one developed locally aggressive disease, distant metastases, and quickly succumbed to his disease.