Pulmonary Cystic Lung Disease in Birt-Hogg-Dube Syndrome: Can Histology Discriminate from Bullous Emphysema?
Aurelie Fabre, Raphael Borie, Marie Pierre Debray, Bruno Crestani, Claire Danel. St Vincent's University Hospital, Dublin, Ireland; Hopital Bichat-Claude Bernard, APHP, HUPNVS, Paris, France
Background: Birt-Hogg-Dubé syndrome (BHDS) is an autosomal dominantly inherited genodermatosis, which predisposes to fibrofolliculomas, renal neoplasms and lung cysts that can lead to spontaneous pneumothorax.
Design: We report a study of 5 cases (1 man, 4 women) with genetically confirmed BHDS who presented with pneumothorax, where surgical resection of pulmonary tissue confirmed cystic lung disease, including 2 cases who had recurrent pneumothorax (interval 1-2 years). We compared these series to a cohort of 6 control cases (primary spontaneous pneumothorax, BHDS negative) matched for sex, age and bulla topography. We reviewed smoking status, and HRCT findings.
Results: This retrospective study of histological surgical material included 1 man (mean age at surgery= 32) and 4 women (mean age at surgery =42 [37-50]) with BHDS. When histological surgical material was available (n=7 including two recurrent cases), 4/5 had a history of recurrent pneumothorax and 5/7 involved the right side. Ex-smoking was noted in 3 BHDS case. Histological analysis showed that compared to controls, BHDS- cysts were either subpleural but in all cases peribronchiolar (“punch-out aspect”) and lacked inflammation or fibrosis. There were lined by flat or hyperplastic TTF-1+ pneumocytes. There was no relationship to the terminal bronchiole or pulmonary artery. In BHDS cases, pleura was thickened but lacked apical cap-like fibroelastotic scars, as seen in 3/6 controls. In all cases there was reactive eosinophilic pleuritis from the pneumothorax. One BHDS case with recurrent pneumothorax had fibroblastic hemosiderin laden nodules in the cyst wall and evidence of peri-cystic hemorrhage. Granulomas were not seen. BHDS cases did not show any evidence of respiratory bronchiolitis but this was seen in 4/6 control cases (5/6 current smokers, one ex-smoker, mean pack-years: 14.8) and for all controls, CT showed bullous emphysema. In all BHD, CT showed true cystic lung disease with thin walled oval-shaped cysts in subpleural areas cases where the diagnosis was suggested.
Conclusions: While the features of BHD are histologically non specific, their “punch-out” appearance close to the broncho-vascular bundles, in the context of scannographic cystic lung disease and non/ex-smoking, may suggest the diagnosis of BHD.
Tuesday, March 5, 2013 2:15 PM
Proffered Papers: Section D, Tuesday Afternoon