Mixed (neutrophil-rich) interstitial pneumonitis in biopsy specimens of lung allografts: A clinicopathologic evaluation

Study objectives: Mixed interstitial pneumonitis (MIP), defined herein as a diffuse neutrophil-rich inflammatory infiltrate within the interstitial tissues, is an uncommon finding that is not a standard manifestation of acute or chronic rejection. This study examines the clinical significance of MIP in lung allograft recipients at St. Louis University Hospital. Design: We retrospectively reviewed surgical pathology reports from a selected 50-month period, and identified MIP reported in 13 transbronchial biopsy specimens in lung transplant recipients, representing 4.7% of all lung allograft biopsy specimens seen during this 4-year period. Biopsy specimens with MIP were examined to confirm the presence of a neutrophil-rich interstitial infiltrate and other associated histopathologic findings. The culture results, cytopathologic findings, and clinical charts of the affected patients were also reviewed. Measurements and results: The detection of MIP at some point in a patient's posttransplant course was found to be associated with a significantly shorter (p<0.01) survival, when compared to lung allograft recipients who did not show this finding. A total of seven lung allograft recipients (23% of total) showed MIP at some point in their posttransplant course. Four of the seven (57%) were actively smoking following lung transplantation, compared to 0 of 22 patients who did not show MIP. Six of the 13 MIP biopsy specimens were associated with positive cultures. In no case did MIP coexist with the conventional histologic patterns of acute or chronic rejection. MIP also did not correlate with levels of immunosuppressive therapy or with the incidence of rejection at other times in the patients' posttransplant courses. Conclusions: We found no evidence that MIP represents an unusual form of acute or chronic rejection. Instead, it appears to represent a response to acute injury, similar to other injury patterns (hyaline membranes, organizing pneumonia) in transplant recipients. Exposure to tobacco smoke is likely to have played a role in the development of MIP in at least some cases. Because patients with MIP had a significantly shorter posttransplant survival, MIP may usefully identify lung allograft recipients at risk for an adverse outcome.