Multiple Myeloma in a Patient with Birt-Hogg-Dubé Syndrome

Birt-Hogg-Dubé syndrome (BHDS) is an autosomal dominant disease caused by germline folliculin (FLCN) mutations and it is characterized by skin folliculomas, pulmonary cysts, and renal cell carcinomas (RCC). We herein report the first case of a female patient with BHDS who was diagnosed with multiple myeloma. Daratumumab-based treatment was effective, and the patient remained responsive for over three years. Whole-exome sequencing confirmed an FLCN germline mutation and nine somatic mutations, including an MPDZ mutation, which is a component of the tumor-suppressive Hippo-YAP pathway. Considering the reported association between the Hippo-YAP pathway and RCC with BHDS, an MPDZ mutation may contribute to carcinogenesis in patients with BHDS.