The Birt-Hogg-Dube syndrome: dermatological features and internal malignancies.

A 56-year-old Caucasian male presented with a fast-growing subcutaneous tumour on the right shoulder over the last 6 months. On examination, this was a mobile and firm tumour of 4 cm diameter (Figure 1). The patient was also concerned about cosmetic disfigurement from multiple small facial papules. These had been growing gradually over the last 3 years. The past medical history revealed six episodes of spontaneous pneumothoraces, treated with a right-sided surgical pleurectomy at the age of 28 years, with no recurrence since. Interestingly, his mother had developed identical lesions over her face a few years before she died from an undetermined internal cancer. Examination revealed dozens of firm whitish small papules distributed on his face (Figure 2), neck and upper trunk. Skin biopsies were consistent with the diagnosis of fibrofolliculomas. Histopathology of the tumour from the right shoulder showed bland myofibroblastic-looking spindle cells dispersed in a myxoid and collagenous stroma, but elsewhere with an ill-defined storiform pattern and scattered mast cells (Figure 3). Immunostains were negative in lesional cells for S100 protein, epithelial membrane antigen, CD34 cell surface antigen, neurofilaments, desmin, smooth muscle actin antigen, cytokeratin AE1-3, and the MIB-1 proliferation index was low. There was focal nuclear positivity for b-catenin. Overall, the lesion was considered to represent a superficial fibromatosis. Suspecting a diagnosis of Birt–Hogg–Dubé (BHD), a rare autosomal dominantly inherited genodermatosis, an ultrasound of the abdomen and pelvis was ordered. A mass was identified in the left kidney. Subsequent abdominal and thoracic computed tomography established a 4.5 cm diameter mass at the lower pole of the left kidney (Figure 4) and multiple paraseptal cystic changes throughout the lungs (Figure 4). The patient underwent a successful partial nephrectomy of the left kidney. The histology was consistent with renal cell adenocarcinoma. The presence of the superficial fibromatosis, a variant of the desmoid tumour described in familial adenomatous polyposis and previous studies showing a link between BHD, colonic polyps and cancer, prompted a colonoscopy. This revealed several tubular adenomas at the sigmoid and caecum with three in the caecum exhibiting severely dysplastic changes. Genetic studies confirmed a mutation of folliculin, a novel protein with tumour suppressor effects.