Histologic findings in lung biopsies in patients with suspected graft-versus-host disease

Abstract

The histopathologic features of pulmonary graft-versus-host disease (GVHD) status post-bone marrow transplant are not well described. Lung biopsies from patients with clinically suspected GVHD were studied. There were 17 biopsies from 9 men and 5 women. Alveolar changes were classified as acute lung injury with intra-alveolar fibrin, organizing pneumonia (OP), and chronic interstitial pneumonia (CIP). Intraepithelial bronchiolar T cells were increased in 16 of 17 biopsies within bronchiolar mucosa (56 ± 30 per 100 epithelial cells). Atypical pneumocytes were present in 10 biopsies, and atypia was marked in 2 biopsies. Reactive bronchiolar cells were also seen in all 3 groups and showed mild atypia in 5 and marked atypia in 1, mimicking viral cytopathic effect. Apoptosis of bronchiolar epithelium and interstitium was seen in all but 1 case and was most marked in the acute injury and OP patterns. Perivenular cuffing was present in 11 of 17 biopsies. All 3 patients with acute injury died of acute respiratory distress syndrome; 1 patient with OP died of systemic GVHD; and 1 patient with CIP pattern died of opportunistic infection. Obstructive lung disease with obliterative bronchiolitis developed in 3 patients, all of whom stabilized with treatment and were alive at last follow-up (mean, 25 months). All 3 histologic patterns of pulmonary GVHD are characterized by intrabronchiolar T cells, apoptosis, and perivenulitis, which help to distinguish GVHD from infections. The acute lung injury pattern has a poor prognosis, and bronchiolitis obliterans syndrome develops in a subset of patients with CIP histologic pattern.