title: Characterization of pulmonary cysts in Birt-Hogg-Dubé syndrome: histopathological and morphometric analysis of 229 pulmonary cysts from 50 unrelated patients.
abstract: OBJECTIVE
  To characterize the pathological features of pulmonary cysts, and to elucidate the possible mechanism of cyst formation in the lungs of patients with Birt-Hogg-Dubé syndrome (BHDS), a tumour suppressor gene syndrome, using histological and morphometric analyses.
  
  
  RESULTS
  We evaluated 229 lung cysts from 50 patients with BHDS and 117 from 34 patients with primary spontaneous pneumothorax (PSP) for their number, size, location and absence or presence of inflammation. The BHDS cysts abutted on interlobular septa (88.2%) and had intracystic septa (13.6%) or protruding venules (39.5%) without cell proliferation or inflammation. The frequencies of these histological characteristics differed significantly from those seen in the lungs of patients with PSP (P < 0.05). Although the intrapulmonary BHDS cysts were smaller than the subpleural BHDS cysts (P < 0.001), there was no difference in size between them when there was no inflammation. The number of cysts diminished logarithmically and the proportion of cysts with inflammation increased as their individual sizes became greater (P < 0.05).
  
  
  CONCLUSIONS
  These results imply that the BHDS cysts are likely to develop in the periacinar region, an anatomically weak site in a primary lobule, where alveoli attach to connective tissue septa. We hypothesize that the BHDS cysts possibly expand in size as the alveolar walls disappear at the alveolar-septal junction, and grow even larger when several cysts fuse.
authors.affiliation: Department of Pathology, Japanese Red Cross Medical Centre, Tokyo, Japan; The Study Group of Pneumothorax and Cystic Lung Diseases, Tokyo, Japan.
authors.forename: Toshio
authors.initials: T
authors.lastname: Kumasaka
authors.forename: Takuo
authors.initials: T
authors.lastname: Hayashi
authors.forename: Keiko
authors.initials: K
authors.lastname: Mitani
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Kataoka
authors.forename: Mika
authors.initials: M
authors.lastname: Kikkawa
authors.forename: Kazunori
authors.initials: K
authors.lastname: Tobino
authors.forename: Etsuko
authors.initials: E
authors.lastname: Kobayashi
authors.forename: Yoko
authors.initials: Y
authors.lastname: Gunji
authors.forename: Makiko
authors.initials: M
authors.lastname: Kunogi
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Kurihara
authors.forename: Kuniaki
authors.initials: K
authors.lastname: Seyama
mesh_terms: D000328:Adult; D058249:Birt-Hogg-Dube Syndrome / Q000235:genetics / Q000473:pathology*; D003560:Cysts / Q000235:genetics / Q000473:pathology*; D005260:Female; D006801:Humans; D008171:Lung Diseases / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D011518:Proto-Oncogene Proteins / Q000235:genetics; D025521:Tumor Suppressor Proteins / Q000235:genetics
chemical_list: C476078:FLCN protein, human; D011518:Proto-Oncogene Proteins; D025521:Tumor Suppressor Proteins
keywords: TGF-β; alveolar-septal junction; cell-matrix interaction; folliculin; mechanical stresses