Chikako Iwabuchi1, Hiroki Ebana2, Akira Ishiko3, Azusa Negishi4, Teruaki Mizobuchi5, Toshio Kumasaka6, Masatoshi Kurihara5, Kuniaki Seyama7. 1. Department of Dermatology, Nissan Tamagawa Hospital, Tokyo, Japan; Department of Dermatology, Toho University School of Medicine, Faculty of Medicine, Tokyo, Japan; The Study Group for Pneumothorax and Cystic Lung Diseases, Tokyo, Japan. Electronic address: bry89chikako@yahoo.co.jp. 2. Pneumothorax Research Center and Division of Thoracic Surgery, Nissan Tamagawa Hospital, Tokyo, Japan; Division of Respiratory Medicine, Juntendo University Faculty of Medicine and Graduate School of Medicine, Tokyo, Japan; The Study Group for Pneumothorax and Cystic Lung Diseases, Tokyo, Japan. 3. Department of Dermatology, Toho University School of Medicine, Faculty of Medicine, Tokyo, Japan. 4. Department of Dermatology, Nissan Tamagawa Hospital, Tokyo, Japan; Department of Dermatology, Toho University School of Medicine, Faculty of Medicine, Tokyo, Japan. 5. Pneumothorax Research Center and Division of Thoracic Surgery, Nissan Tamagawa Hospital, Tokyo, Japan; The Study Group for Pneumothorax and Cystic Lung Diseases, Tokyo, Japan. 6. Department of Pathology, Japanese Red Cross Medical Center, Tokyo, Japan; The Study Group for Pneumothorax and Cystic Lung Diseases, Tokyo, Japan. 7. Division of Respiratory Medicine, Juntendo University Faculty of Medicine and Graduate School of Medicine, Tokyo, Japan; The Study Group for Pneumothorax and Cystic Lung Diseases, Tokyo, Japan.
Abstract
BACKGROUND: Birt-Hogg-Dubé syndrome (BHDS) (OMIM #135150) is an autosomal dominant disease, characterized by fibrofolliculomas (FFs) of the skin, pulmonary cysts with/without pneumothorax, and renal tumors. The prevalence of skin manifestations reported for Japanese BHDS patients is lower (<30%) compared with that of Western countries (75∼90%), which appear to be underestimated. OBJECTIVE: To precisely examine the prevalence of skin lesions with dermoscopy and histopathology with reference to genetic analyses. METHODS: We studied 31 patients (47.0±13.2years old, range 15-71) consisting of 26 unrelated families consecutively from May 2013 to June 2015 specifically for skin-colored papules on their faces and cervicothoracic regions. Patients initially suspected of BHDS from multiple pulmonary cysts that resulted in pneumothorax (30/31; 96.8%) received dermoscopic examinations and skin biopsies if applicable. The diagnosis of BHDS was established by folliculin (FLCN) genetic testing, and the results were compared to the histopathological findings of FFs or trichodiscomas (TDs). RESULTS: FLCN germline mutation was demonstrated in 25/26 (96.2%) unrelated families tested and 28/29 patients (96.6%) tested. Skin lesions were recognized in 26/31 patients (83.9%); skin biopsies were performed in 23 patients of whom FFs and/or TDs were histologically demonstrated in 17 (73.9%). Although our study population included patients whose skin manifestations were evaluated prior to or after FLCN genetic testing, skin lesions were clearly prevalent and recognizable irrespective of whether genetic testing was or wasn't done. When examined with dermoscopy, distinct FFs appeared as well-demarcated areas of pallor with central follicular openings in 13 of 15 FF-bearing patients (86.7%); however, those manifestations were not recognized for TD. CONCLUSIONS: Skin lesions appear to be more prevalent than previously reported (<30% vs.73.9%) in Japanese BHDS patients. Dermoscopy is a useful diagnostic aid for finding FFs.
BACKGROUND: Birt-Hogg-Dubé syndrome (BHDS) (OMIM #135150) is an autosomal dominant disease, characterized by fibrofolliculomas (FFs) of the skin, pulmonary cysts with/without pneumothorax, and renal tumors. The prevalence of skin manifestations reported for Japanese BHDS patients is lower (<30%) compared with that of Western countries (75∼90%), which appear to be underestimated. OBJECTIVE: To precisely examine the prevalence of skin lesions with dermoscopy and histopathology with reference to genetic analyses. METHODS: We studied 31 patients (47.0±13.2years old, range 15-71) consisting of 26 unrelated families consecutively from May 2013 to June 2015 specifically for skin-colored papules on their faces and cervicothoracic regions. Patients initially suspected of BHDS from multiple pulmonary cysts that resulted in pneumothorax (30/31; 96.8%) received dermoscopic examinations and skin biopsies if applicable. The diagnosis of BHDS was established by folliculin (FLCN) genetic testing, and the results were compared to the histopathological findings of FFs or trichodiscomas (TDs). RESULTS:FLCN germline mutation was demonstrated in 25/26 (96.2%) unrelated families tested and 28/29 patients (96.6%) tested. Skin lesions were recognized in 26/31 patients (83.9%); skin biopsies were performed in 23 patients of whom FFs and/or TDs were histologically demonstrated in 17 (73.9%). Although our study population included patients whose skin manifestations were evaluated prior to or after FLCN genetic testing, skin lesions were clearly prevalent and recognizable irrespective of whether genetic testing was or wasn't done. When examined with dermoscopy, distinct FFs appeared as well-demarcated areas of pallor with central follicular openings in 13 of 15 FF-bearing patients (86.7%); however, those manifestations were not recognized for TD. CONCLUSIONS:Skin lesions appear to be more prevalent than previously reported (<30% vs.73.9%) in Japanese BHDS patients. Dermoscopy is a useful diagnostic aid for finding FFs.
Authors: Kiril Trpkov; Ondrej Hes; Sean R Williamson; Anthony J Gill; Adebowale J Adeniran; Abbas Agaimy; Reza Alaghehbandan; Mahul B Amin; Pedram Argani; Ying-Bei Chen; Liang Cheng; Jonathan I Epstein; John C Cheville; Eva Comperat; Isabela Werneck da Cunha; Jennifer B Gordetsky; Sounak Gupta; Huiying He; Michelle S Hirsch; Peter A Humphrey; Payal Kapur; Fumiyoshi Kojima; Jose I Lopez; Fiona Maclean; Cristina Magi-Galluzzi; Jesse K McKenney; Rohit Mehra; Santosh Menon; George J Netto; Christopher G Przybycin; Priya Rao; Qiu Rao; Victor E Reuter; Rola M Saleeb; Rajal B Shah; Steven C Smith; Satish Tickoo; Maria S Tretiakova; Lawrence True; Virginie Verkarre; Sara E Wobker; Ming Zhou Journal: Mod Pathol Date: 2021-03-04 Impact factor: 8.209