Birt-Hogg-Dubé syndrome

Abstract

Birt-Hogg-Dubé syndrome (BHD) is a rare inherited autosomal dominant disorder caused by germline mutations in the tumour suppressor gene FLCN, encoding the protein folliculin. Its clinical expression typically includes multiple pulmonary cysts, recurrent spontaneous pneumothoraces, cutaneous fibrofolliculomas and renal tumours of various histological types. BHD has no sex predilection and tends to manifest in the third or fourth decade of life. Multiple bilateral pulmonary cysts are found on chest computed tomography in >80% of patients and more than half experience one or more episodes of pneumothorax. A family history of pneumothorax is an important clue, which suggests the diagnosis of BHD. Unlike other cystic lung diseases such as lymphangioleiomyomatosis and pulmonary Langerhans cell histiocytosis, BHD does not lead to progressive loss of lung function and chronic respiratory insufficiency. Renal tumours affect about 30% of patients during their lifetime, and can be multiple and recurrent. The diagnosis of BHD is based on a combination of genetic, clinical and/or skin histopathological criteria. Management mainly consists of early pleurodesis in the case of pneumothorax, periodic renal imaging for tumour detection, and diagnostic work-up in search of BHD in relatives of the index patient.

FIGURE 1

Chest computed tomography in Birt–Hogg–Dubé syndrome. a) A few pulmonary cysts of uneven distribution, size and shape in predominantly basal and paramediastinal location (arrows). b) Frontal plane reconstruction showing multiple cysts adjacent to blood vessels, fissures and visceral pleura, with predominantly basal and paramediastinal location (arrows).

FIGURE 2

Fibrofolliculomas in Birt–Hogg–Dubé syndrome. Multiple skin-coloured tiny papules of the paranasal area can be seen.

FIGURE 3

Abdominal computed tomography scan of a patient with chromophobe renal cell carcinoma after injection of contrast media. The left kidney shows an irregular edge and a homogenous mass indicated by the arrow. The tumour was removed by robot-assisted laparoscopic surgery.

FIGURE 4

Example of a chromophobe renal cell carcinoma. a) Macroscopic appearance (scale in centimetres). b) Haematoxylin and Eosin staining (× 400). c) Staining with anti-cytokeratin-7 antibodies (× 100). d) CD10 staining (× 100). All images courtesy of Prof. La Rosa (Lausanne University Hospital, Lausanne, Switzerland)

FIGURE 5

Histopathology of a fibrofolliculoma with fibroblast-rich mesenchymal tissue in the whole dermal space (Haematoxylin and Eosin stain, ×100). Copyright of this figure belongs to D. Hohl.