Colon adenocarcinoma and Birt-Hogg-Dubé syndrome in a young patient: case report and exploration of pathologic implications.

Birt-Hogg-Dubé syndrome (BHD) is an autosomal dominant disorder caused by germline mutations in the folliculin gene () that result in the functional loss of the tumor suppressor folliculin. It is classically associated with cutaneous hamartomas, pulmonary cysts with spontaneous pneumothorax, and various renal cancers. In this case, we present a patient initially diagnosed with chromophobe renal cell carcinoma and subsequently found to have colorectal cancer (CRC). The presence of two separate malignancies in a young patient with a strong family history of CRC (father and paternal grandfather) led to genetic testing, which revealed an c.1177-5_1177-3del mutation, and a diagnosis of BHD was made. Out of the more than 300 known unique mutations of the coding region, the c.1285dupC mutation on exon 11 has been the only one convincingly associated with CRC thus far. While larger cohort studies are needed to further clarify this association, we present the first patient with CRC to our knowledge with an c.1177-5_1177-3del mutation and loss of heterozygosity implicating it as an initiating factor in tumorigenesis. We further explore the studies supporting and refuting the connection between BHD and CRC and highlight the molecular signaling pathways that may play a role in pathogenesis.