Presence of c-KIT-positive mast cells in obliterative bronchiolitis from diverse causes

Context. - The mechanism of fibrosis is not clear in patients with obliterative bronchiolitis after a remote injury. Immune-mediated progression may be a reason. c-KIT (CD117)-positive mast cells have been associated with chronic fibrosing diseases and may potentially be treated with imatinib (Gleevec), a c-KIT blocker. Objective. - To evaluate the role of mast cells in fibrosis associated with obliterative bronchiolitis. Design. - Four cases of obliterative bronchiolitis (household cleaner exposure, ammonia exposure, idiopathic, and posttransplantation) were compared with asthma/emphysema. Small and large airways were stained for CD20, CD3, CD4, CD8, CD117, CD34, CD25, stem cell factor (c-KIT ligand) and with toluidine blue, hematoxylin-eosin, and trichrome. c-KIT (CD117)-stained slides were digitally scanned with Aperio ScanScope and stained cells within the epithelium and subepithelium of small and large airways were counted (per millimeter of basement membrane). Results. - Mast cells were concentrated within the involved subepithelium of small airways in obliterative bronchiolitis (122 cells/mm), unlike asthma/emphysema (25 cells/mm). Conversely, there were more mast cells in the epithelium in cases of asthma/emphysema than in obliterative bronchiolitis (7 cells/mm and 2 cells/mm, respectively). Mast cells were significantly increased around involved airways versus uninvolved airways (52 cells/mm vs 14 cells/mm). Large airways in either group had similar c-KIT (CD117) expression. Stem cell factor was not increased. Conclusions. - Mast cells appear to be concentrated in the lesional small-airway subepithelium in obliterative bronchiolitis. The possible role of c-KIT inhibitors such as imatinib (Gleevec) in the progression of fibrosis preceding the development of obliterative bronchiolitis is discussed.