Granulomatous and Lymphocytic Interstitial Lung Disease (GLILD) in Common Variable Immunodeficiency (CVID) – Histological and Immunohistochemical Analysis of 12 Cases of a Rare Entity
Nagarjun Rao, Nicole Chase, John M Routes, Alexander C Mackinnon. Medical College of Wisconsin, Milwaukee, WI
Background: CVID is a primary immunodeficiency of unknown etiology characterized by low serum IgG, inability to make specific antibodies and variable T cell defects. Up to 20% of patients with CVID can develop clinical evidence of a progressive restrictive diffuse parenchymal lung disease called GLILD. The constellation of pulmonary changes in GLILD have not been described comprehensively in the pathology literature. We present the histological and immunohistochemical features in a series of 12 cases of this rare entity.
Design: Twelve (12) cases of GLILD form the basis of the study. Open lung (11) and transbronchial (1) biopsies were evaluated for interstitial and alveolar inflammation, lymphoid aggregates with or without germinal centers, granulomata, organizing pneumonia and interstitial fibrosis. Immunohistochemical stains were performed on six cases for a panel of antibodies including CD3, CD 20, CD4, CD8, Human Herpes Virus-8 (HHV-8), and CD 68. The proportion of T and B lymphocytes and CD4+ and CD8+ subsets of T cells were calculated by image analysis.
Results: Follicular bronchiolitis (12/12 cases), lymphoid interstitial pneumonia (LIP) (11/12) and granulomatous inflammation (11/12) were consistent features; organizing pneumonia (7/12) and interstitial fibrosis (6/12) were also seen, although architectural remodeling reminiscent of the usual interstitial pneumonia (UIP) pattern was seen only in 1 case. Epithelioid cell granulomata bore some resemblance to sarcoidosis with circumscription and absent necrosis but without the distinct lymphangitic distribution pattern. Quantitative immunohistochemical analysis showed that CD3+ T cells comprised 69.7 – 98.9% of all lymphocytes (mean – 81.7%); and CD4+ cells comprised 58.2 – 94.2% of all T lymphocytes (mean – 71.8%). HHV-8 was negative in all cases and CD68 highlighted numerous histiocytes, including mononuclear epithelioid histiocytes comprising the granulomata.
Conclusions: We have characterized the pathologic features of GLILD, a rare entity occurring in patients with CVID. Consistent histologic features include follicular bronchiolitis, LIP and sarcoid-like granulomata. Organizing pneumonia and interstitial fibrosis can be seen, and the latter may portend poor prognosis. The histologic overlap, and the predominance of CD4 positive cells, point to a T helper cell driven immune process somewhat analogous to sarcoidosis.
Tuesday, March 5, 2013 2:00 PM
Proffered Papers: Section D, Tuesday Afternoon