Clinicopathologic features of Granulomatous-Lymphocytic Interstitial Lung Disease (GLILD) vs. sarcoidosis

Background: Patients referred to our Sarcoidosis Center receive an alternate diagnosis in 17% of the cases after the pathology is reviewed. One such alternative diagnosis is granulomatous-lymphocytic interstitial lung disease (GLILD). This is an interstitial lung disease (ILD) that has been described in a subset of patients with common variable immunodefi ciency (CVID) and has pathologic features that can overlap signifi cantly with those of sarcoidosis. We conducted a histopathologic comparison between a group of patients with documented GLILD arising in the setting of CVID and a matched group of patients with sarcoidosis. Design: Cases histologically and clinically suspicious for GLILD were reviewed from the authors' case fi les. 8 cases consistent with GLILD and 8 cases of pulmonary sarcoidosis were identifi ed and H&E slides from pulmonary specimens were reviewed. Tissue stains for microorganisms (Grocott methenamine silver -GMS- for fungus and Ziehl-Neelsen acid fast -ZN/AFB- for mycobacteria), immunohistochemical stains (CD3, CD4, CD8, CD20 and HHV-8) as well as in situ hybridization for EBV were performed. Whole slide imaging (WSI, Aperio AT scanner) and a Positive Pixel Count Aperio Algorithm were used to estimate the percentage of tissue B and T lymphocyte and CD4 and CD8 T lymphocytes in GLILD and sarcoidosis. Results: Pulmonary tissue sections from GLILD cases showed more prominent interstitial inflammation with increased areas of organizing pneumonia when compared to the pulmonary sarcoidosis cases. In addition, the granulomas in both GLILD and sarcoidosis cases were non-necrotizing. However, the GLILD granulomas were not in a lymphatic distribution as seen in sarcoidosis, and were more loosely formed. Special stains for microorganisms (GMS and ZN-AFB), immunohistochemistry for HHV-8 and in situ hybridization for EBV were negative in both groups. The difference in tissue CD3:CD20 lymphocyte ratio and the CD4:CD8 ratio between the two groups was not statistically signifi cant. Conclusions: The histopathologic features that distinguish GLILD from sarcoidosis include a brisk interstitial inflammatory infi ltrate with areas of organizing pneumonia and more loosely formed non-necrotizing granulomas. Immunohistochemical stains for B and T lymphocytes and their subsets reveal no signifi cant difference in the ratio of these lymphocytes in GLILD and sarcoidosis.