A 54-year old man with asymptomtic, tiny, multiple, flesh-colored papules on both cheeks () was referred to us from the cardiothoracic surgery department, where he had been treated for recurrent pneumothorax of the left lung. He did not remember the onset of the lesions, but stated that the number was increasing. He had no special medical or family history. The papules were thought to be sebaceous hyperplasia or verruca plana and a punch biopsy was performed. The specimen showed an epithelial cord and fibrous stroma in the dermis and an anastomosing band from follicular epithelium (). A diagnosis of fibrofolliculoma was made, which is the major feature of BHDS.\nThere was no family history of the skin lesions, lung disease, and of benign or malignant tumors. Furthermore, multiple variable-sized lung cysts were found on his chest following computed tomographic scan and a right renal cyst 2 cm in diameter was found on abdominal sonography (). Molecular analysis of FLCN was performed after informed consent from the patient. Sequencing revealed a single nucleotide frameshift duplication occurring within the polycytosine tract located in exon 11, c.1285dupC (p.H429Pfs*27), resulting in a change of the 429th amino acid from histidine to proline in the FLCN gene product. Based on this, it is possible to accurately diagnose BHDS.\nHis pneumothorax was treated with thoracostomy and pleurodesis, and active treatment was not required for the skin lesions, lung cysts and renal cyst. He is on regular follow-up because renal and colorectal cancer can occur in this syndrome.
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.