Clinicopathologic Findings and Genetic Alterations

● Context.—Birt-Hogg-Dubé (BHD) syndrome is a rare clinicopathologic condition transmitted in an autosomal dominant fashion. This complex entity is characterized by cutaneous fibrofolliculomas, kidney tumors, pulmonary cysts, and spontaneous pneumothorax. Recently, the gene possibly responsible for the clinical manifestations of BHD syndrome has been cloned and characterized. The few reviews of BHD syndrome found in the English literature mostly focus on the skin lesions or genetics, with limited information on other pathologic changes, particularly the kidney lesions. Objective.—To review the literature on this subject with a special emphasis on BHD syndrome-associated renal pathology as well as recent advances in molecular genetic discovery of the BHD syndrome. Data Sources.—We used all data available after performing a literature search using MEDLINE and searching under the headings ‘‘Birt-Hogg-Dubé,’’ ‘‘hybrid oncocytic tumors,’’ and ‘‘folliculin.’’ Conclusions.—The presence of BHD syndrome should be investigated in any patient with multiple bilateral kidney tumors, especially if the predominant histologic type is chromophobe renal cell carcinoma or the so-called hybrid oncocytic tumor. The genetic alteration for BHD syndrome has been mapped to chromosome 17p12q11, and the gene in this region has been cloned and believed to be responsible for the BHD syndrome. The function of the BHD product, called folliculin, is still unknown, although it is speculated to be a tumor suppressor gene. Numerous mutations have been described in the BHD gene. Studies are ongoing to determine the relationship between the BHD gene and development of sporadic renal cell carcinoma and other lesions. (Arch Pathol Lab Med. 2006;130:1865–1870)