Cystic pulmonary parenchymal disorders: Expanding differential considerations

Birt-Hogg-Dubé (BHD) syndrome is a rare, autosomal dominant genodermatosis resulting from mutations in the folliculin (FLCN) tumor suppressor gene coding for the protein FLCN. BHD syndrome usually presents in adulthood and is characterized by the development of skin lesions, renal tumors, and pulmonary cysts, the latter of which may predispose to spontaneous pneumothorax, which may be the presenting feature of this disorder. Although the pulmonary cysts of BHD syndrome may resemble a number of other diffuse pulmonary cystic diseases at thoracic computed tomography, particularly lymphangioleiomyomatosis and lymphocytic interstitial pneumonia, several morphologic features of the pulmonary cysts in BHD patients may suggest the diagnosis of this disorder at thoracic computed tomography, which may be important as not all patients with BHD have all 3 components of the syndrome, and pulmonary cysts may be the first manifestation of BHD syndrome in some patients. The diagnosis of BHD syndrome should be specifically considered when pulmonary cysts are seen in combination with solid, non-fat-containing renal lesions. The detection of fibrofolliculomas at dermatologic examination strongly suggests the diagnosis of BHD syndrome as these lesions are rarely encountered outside this setting. The histopathologic features of BHD syndrome differ from other cystic pulmonary diseases, and genetic testing for derangements in the FLCN gene may confirm the diagnosis of BHD syndrome.