A 37-year-old man presented with an asymptomatic right renal mass detected by ultrasonography and CT (Fig. a). No apparent cutaneous lesions were found by careful inspection and palpation of the skin. The patient had a history of spontaneous pneumothorax on both sides and underwent pulmonary bullectomy on the right side at the age of 30. His father had a history of recurrent spontaneous pneumothorax starting at the age of 28 and died of stoke at the age of 63. His uncle had a history of recurrent spontaneous pneumothorax starting at the age of 24 and died of an accident at the age of 56. Open partial nephrectomy was performed on the patient. Histopathologic examination revealed that the tumor was chromophobe RCC, nuclear grade G2, and 2.2 cm × 2.0 cm × 2.0 cm in size (Fig. b).\nGenomic DNA was extracted from blood samples collected from the patient and his family members. Mutation examination revealed that the proband carried a deletion of three bases (CCT) at nucleotides c.770-772 in exon 7 (c.770-772delCCT) (Fig. c), resulting in deletion of the 257th serine residue (p.257delS). No FLCN mutations were found in any other members of the patient’s family.
A 25-year-old woman visited our hospital because of bilateral pneumothorax detected on a chest X-ray taken during a health screening (Figure ). She had neither chest-related symptoms nor a rash on her body or face. She was a non-smoker and had no history of major diseases. However, she had a family history of spontaneous pneumothorax that included her father, paternal uncle, and paternal aunt.\nA chest computed tomography (CT) scan taken at our hospital showed right-sided pneumothorax as well as almost healed left-sided pneumothorax (Figure ). It also showed multiple cystic lesions throughout both lungs.\nWe performed video-assisted thoracic surgery (VATS) on the patient's right lung. Repetition of pneumothorax was suspected because pleural adhesion and thick pleura were found in her thorax. Many bullas were found at the surface of the lung; therefore, resection and ablation of bullas were performed, followed by stapling of the staple lines and reinforcement of ablated sites using a polyglycolic acid (PGA) sheet and fibrin glue. The patient's post-operative course was uneventful.\nOne month after the operation, she visited our hospital again complaining of respiratory discomfort. Chest X-ray and CT scan showed left-sided pneumothorax. Therefore, we performed VATS on the left lung. Again, many minuscule bullas appeared throughout the whole lung, and pleural adhesion and thick pleura were observed as before in the right lung. The surgery was performed following the same methods used for the right lung. Again, the patient's post-operative course was uneventful, and the recurrence of pneumothorax was not observed in either lung at 6 months after the second operation.\nHistopathological examination showed that the inner surfaces of cysts were lined with epithelial cells, and the cysts occasionally contained internal septa consisting of alveolar walls (Figure ). There were no special pathological findings of lymphangioleiomyomatosis (LAM) or catamenial pneumothorax, including LAM cell clusters or formation of chocolate-like endometriotic cysts.\nBecause the patient was young and a non-smoker with prominent family history of pneumothorax and multiple cystic lesions were observed throughout her whole lung, we suspected congenital disease and particularly BHD, despite the absence of fibrofolliculomas. We presented this case to a special research team focusing on BHD, which was formed as a specialized disease treatment research program by the Japanese government. The patient was diagnosed as having BHD via a DNA analysis, which showed two deletions of bases in exon 12 of the BHD gene (Figure ). No renal tumors were observed by abdominal ultrasonography.