Two Japanese cases of birt-hogg-dubé syndrome with pulmonary cysts, fibrofolliculomas, and renal cell carcinomas

Abstract

Birt-Hogg-Dubé syndrome (BHD) is a rare autosomal dominant inherited disease caused by a germline mutation in the folliculin gene mapped in the region of chromosome 17p11.2. BHD predisposes the patient to cutaneous fibrofolliculomas (FFs), pulmonary cysts (PCs), and renal cell carcinoma (RC). Here, we present two cases of BHD in Japanese patients. One patient was a 37-year-old female, and the other a 35-year-old male. Each of the patients was affected by all three symptoms of BHD. Both patients had unremarkable FFs, asymptomatic PCs, and asymptomatic RC. The presence of RC was revealed by abdominal ultrasonic examination. We also summarized the data from 62 Asian cases of BHD from the available literature and found that their FFs were unremarkable. In addition, the proportion of BHD patients with FF is smaller for Asian patients than it is for Caucasian patients. We also found that it is rare for BHD patients in Asia to show all three symptoms of BHD. Careful inspection of the skin as well as skin biopsies are important for the early detection of BHD cases in Asia.

Keywords: Birt-Hogg-Dubé syndrome; Fibrofolliculoma; Pulmonary cyst; Renal cell carcinoma.

Fig. 1

The abdominal CT revealed a low-density area on the left kidney of a 37-year-old female with BHD (a), which was histopathologically diagnosed as clear cell carcinoma. On gross examination, the resected kidney contained a partially hemorrhagic, yellowish, solid tumor (b). The tumor was composed of cells with clear to acidophilic cytoplasm (hematoxylin-eosin stain; c), which were positive for vimentin stain (d; 200× magnification). The thoracic CT revealed bilateral, multiple PCs in the basilar and mediastinal regions (e). Microscopic findings for the lung revealed that the septum of the cyst wall contained capillaries and was lined by pneumocytes on both surfaces (f; 200× magnification). Quiet, skin-colored papules were present on the patient's face (g). There were few pinkish-colored, verrucous papules on the scalp (h). Histopathological images (hematoxylin-eosin) of the FF. The stoma was rich in fibroblasts and was oriented in parallel bundles of root sheath-like fibers and neighboring enlarged hair follicles [20× magnification (i) and 200× magnification (j)] positive for factor 13a (k) and c-kit (l; 400× magnification).

Fig. 2

The abdominal CT revealed a low-density area on the right kidney of a 35-year-old male with BHD (a). The tumor was composed of cells with eosinophilic cytoplasm (hematoxylin-eosin; b), was partially positive for CK7 (c; 200× magnification) and colloidal iron (d; 400× magnification), and histopathologically diagnosed as chromophobe cell carcinoma. A thoracic CT revealed the presence of bilateral, basally located, multiple PCs (e). Pedigrees of the families affected with recurrent pneumothorax (f). Skin-colored papules were present on the nose (g). Histopathological images (hematoxylin-eosin) of the FFs [40× magnification (h) and 200× magnification (i)] positive for factor 13a (j) and c-kit (k; 400× magnification).