What are the Histopathologic Findings in Pulmonary Allografts with Graft Failure?

Abstract

Purpose The goal of this study was to investigate the pathology of graft failure in a series of explants and autopsies with special emphasis on chronic lung allograft dysfunction (CLAD). Methods Histopathologic evaluation was performed on a series of pulmonary allografts, received either at the time of re-transplantation or at autopsy, from patients with primary lung allograft failure, over a 13-year period. The findings were categorized as acute and organizing alveolar injury, obliterative bronchiolitis (OB), restrictive CLAD (including acute fibrinoid organizing pneumonia [AFOP]/interstitial-pleuroparenchymal fibrosis), mixed obliterative and restrictive, and other. Results Twenty-two lungs were examined retrospectively. Of these, 19 (86%) were explants and 3 (14%) were from autopsies. Fourteen patients were male (64%) and 8 were female (36%). For men, the average age was 58 ± 4 years at transplant, while the average age for females was 48 ± 5 at transplant. The median duration of transplant was 468 days. Eight cases showed acute and organizing alveolar injury (36%, mean 300 days post-transplant), 4 showed pure OB (18%, mean 1400 days post-transplant), zero showed pure restrictive CLAD, 6 showed mixed obliterative and restrictive disease (27%, mean 1076 days post-transplant), and 4 were categorized as other (18%, mean 375 days post-transplant). The latter 4 allografts showed aspiration, HPE, bronchiectasis, and acute cellular rejection. Of the restrictive CLAD allografts, 5 showed AFOP with interstitial fibrosis, while 1 was primarily pleuroparenchymal fibroelastosis. One of 4 allografts with OB and 4 of 6 allografts with mixed CLAD + OB had focal acute and organizing alveolar injury. Vasculitis was present in 3 of 6 allografts with mixed CLAD + OB and 1 of 4 allografts with pure OB. Irregular scars with plasma cell infiltrates seen in 2 of 6 allografts with mixed CLAD + OB and in 1 of 4 allografts with pure OB. Conclusion CLAD and acute alveolar injury are the most common causes of graft failure. Alveolar injury is usually soon after transplant but may also occur late. Restrictive CLAD was not seen in the absence of OB in this study. The median graft survival was similar in the pure OB and mixed CLAD groups.