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.