A 32-year-old female presented with an incidentally found pneumothorax during a workup for a vocal cord mass, after having experienced the symptom of voice change for several months. A chest X-ray and high-resolution chest tomography (HRCT) scan showed a left-side pneumothorax with a small amount of pleural effusion. In addition, several variably-sized thin-walled air cysts were found, mostly located on the basal or medial side of the bilateral lungs (). However, she had neither a history of smoking nor of pneumothorax. She had no history of underlying disease, such as an immunologic or collagen vascular disorder. Of note, her maternal relatives had a family history of pneumothorax. Because the multiple cysts in the bilateral lungs could increase the risk of recurrence, surgical repair was planned.\nVideo-assisted thoracoscopic surgery (VATS) was done for the single-stage resection of bilateral multiple cystic lesions. A double-lumen endotracheal tube was placed for bilateral sequential one-lung ventilation under general anaesthesia. The patient was placed in the lateral decubitus position, and 2-ports VATS exploration was performed using a 30° thoracoscope (Karl Storz endoscope; Karl Storz, Tuttlingen, Germany) for multiple wedge resections using endostaplers. Both bulla plication and ligation were also performed to remove multiple discrete small lesions, and sequential VATS for the contralateral side was conducted. There were multiple large cysts, especially at the base of the lower lobes, and some cysts were assessed as being at the stage of impending rupture (). After a air-leak test using saline solution, 20-Fr chest tubes were placed in the bilateral pleural space through the scope ports. Mechanical pleurodesis was not performed. The examination of the gross specimen revealed multiple, variably-sized subpleural cysts on both lungs, and the largest one measured up to 6.5×4.6 cm.\nThe HRCT and operative findings were uncommon; it is rare for young females to present with numerous thin-walled cysts in the bilateral lungs, especially in the lower lung fields. Furthermore, her grandmother had a history of pneumothorax at a relatively young age. After obtaining an informed consent for a genetic analysis with the suspicion of Birt-Hogg-Dubé syndrome (BHDS), genomic DNA was isolated from peripheral blood leukocytes using the QIAmp DNA Mini Kit (Qiagen, Hamburg, Germany). Polymerase chain reaction (PCR) was carried out using gene-specific primers for all coding exons and splice junctions of FLCN as previously described []. PCR amplicons were bidirectionally sequenced using a BigDye Terminator version 3.1 cycle sequencing kit (Applied Biosystems, Foster City, CA, USA) on an ABI PRISM 3100 Genetic Analyzer (Applied Biosystems). The chromatograms were analyzed using Sequencher ver. 5.0 (Gene Codes, Ann Arbor, MI, USA) and all mutations were described according to the Human Genome Variation Society nomenclature []. The RefSeq ID NM_144997.5 was used for alignment. Direct sequencing of the PCR products revealed a heterozygous, novel nonsense mutation, c.1135A>T; p.Arg379* in exon 10 of FLCN. This mutation has not been previously reported and is absent from locus-specific databases [,] as well as public databases (HGMD; ExAC; 1000 Genomes; dbSNP; and the ethnically specific Korean Reference Genome database, KRGDB). A subsequent familial genetic study was performed in both parents and an older brother of the proband, revealing an identical heterozygous mutation in the proband’s mother ().\nThe bilateral chest tubes were removed on postoperative day 1, and the patient was discharged on postoperative day 2 with complete resolution of the pneumothorax. The vocal cord mass was excised a month later, and was confirmed as a glomus tumor, measuring 2.0×1.2 cm. The patient has been followed for 12 months after the operation, and neither recurrence of pneumothorax nor other symptoms have been noted.
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.