Granulomatous and lymphocytic interstitial lung disease: a spectrum of pulmonary histopathologic lesions in common variable immunodeficiency—histologic and immunohistochemical analyses of 16 cases

Abstract

Common Variable Immunodeficiency (CVID) is a primary immunodeficiency of unknown etiology characterized by low serum IgG, a decreased ability to make specific antibodies, and variable T cell defects. Approximately 20% of patients with CVID develop clinical evidence of a diffuse parenchymal lung disease with a constellation of histopathological findings termed granulomatous and lymphocytic interstitial lung disease (GLILD). In this study, we characterized the histological and immunohistochemical features in a series of 16 cases diagnosed by open lung biopsy. Peribronchiolar and interstitial lymphocytic infiltration, granulomatous inflammation and organizing pneumonia were consistent features; interstitial fibrosis with architectural remodeling was also found in a subgroup of patients. By immunohistochemistry, a predominance of CD4+ T lymphocytes with variable numbers of CD8+ T cells and B cells were present, with a striking absence of FOXP3 positive T regulatory cells. This heretofore unrecognized immunohistochemical finding, needs further investigation for a potential role in the pathogenesis of the condition. The presence of interstitial fibrosis with or without architectural remodeling in a subset of patients also needs additional study, for effect on prognosis.

Granulomatous-Lymphocytic Interstitial Lung Disease in 22q11.2 Deletion Syndrome: a Case Report and Literature Review

“…These features are consistent with the FB and LIP patterns that had been ascribed to GLILD a decade prior [2••]. In addition to lymphocytic inflammation, non-necrotizing granulomata were also present in 15/16 cases examined [22•]. These were randomly distributed throughout the lung parenchyma in a basilar distribution, varied from being well-formed to poorly formed and consisted of epithelioid histiocytes with occasional multinucleated giant cells.…”

“…Recently, Rao and colleagues thoroughly detailed the histopathological and immunohistochemical features of VATS-guided or open lung biopsies obtained from 16 CVID patients with GLILD [22•]. Nodular peribronchiolar and diffuse interstitial lymphocytic inflammation was demonstrated in all cases with expansion of the interstitium occurring in severe cases.…”

“…Immunohistochemical staining identified CD3+CD4+ T cells as the predominant lymphocyte present within the peribronchial and interstitial inflammation with B cells representing only a minor component [22•]. In contrast, CD20+ and PAX5+ B cells surrounded by a small ring of CD4+ T cells characterized the nodular components of GLILD.…”

Infectious and Noninfectious Pulmonary Complications in Patients With Primary Immunodeficiency Disorders

“…The presence of GLILD in PID patients points to a poorer prognosis and increases the prevalence of lymphoproliferative disorders [110]. The finding of interstitial fibrosis (with or without architectural remodeling) requires additional study for its effect on prognosis [111]. The typical imaging pattern of ILD in PAD is a generalized diffuse reticular change and consolidation, with or without a groundglass appearance, predominantly in the lower lobe.…”

“…Rao et al [111] evaluated CVID patients and reported OP in 87.5%, mostly in mild forms of the disease. Pulmonary function tests reveal a mild-to-moderate restrictive pattern.…”