title: No definite clinical features of immunoglobulin G4-related disease in patients with pulmonary nodular lymphoid hyperplasia.
abstract: Pulmonary nodular lymphoid hyperplasia (PNLH) may show heavy lymphoplasmacytic infiltrates with increased immunoglobulin G4 (IgG4)-positive plasma cells as in IgG4-related disease (IgG4-RD). However, it is unclear whether PNLH could be a manifestation of IgG4-RD. A recent study reported the presence of Epstein-Barr virus (EBV) in IgG4-related lymphadenopathy. We postulated that a subset of PNLH might represent IgG4-related lung disease with EBV-positive lymphocytes as has been reported in IgG4-related lymphadenopathy. IgG and IgG4 immunohistochemistries were performed on 26 PNLH cases in our files (1994-2014) and on 9 controls including diffuse lymphoid hyperplasia of the lung without nodularity (n=2), usual interstitial pneumonia with increased lymphoplasmacytic infiltrates (n=5), and thoracic lymphadenopathy (n=2). EBV in situ hybridization was performed in the cases with the highest IgG4+ count (n=15). Median IgG4+ plasma cell count in PNLH was 36 cells per high-power field (interquartile range, 7-65) with median IgG4+/IgG+ ratio of 0.24 (interquartile range, 0.12-0.37). Three of 26 cases had a markedly increased IgG4+ count (range, 55-139) and IgG4+/IgG+ ratio (>0.4). Serum IgG4 level available in 1 of these cases was not elevated, and all 3 patients had alternate medical diagnoses. Absolute counts of IgG4+ plasma cells in PNLH did not significantly differ from the other control groups. Result of EBV in situ hybridization was negative in all cases tested. In conclusion, most PNLH cases had low IgG4+ cells, and there was no clinical evidence of IgG4-RD or EBV among those with increased IgG4+ cells.
authors.affiliation: Division of Anatomic Pathology, Mayo Clinic, Rochester, MN 55905.
authors.forename: Melanie C
authors.initials: MC
authors.lastname: Bois
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Mayo Clinic, Rochester, MN 55905.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Sekiguchi
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Mayo Clinic, Rochester, MN 55905.
authors.forename: Jay H
authors.initials: JH
authors.lastname: Ryu
authors.affiliation: Division of Anatomic Pathology, Mayo Clinic, Rochester, MN 55905. Electronic address: yi.joanne@mayo.edu.
authors.forename: Eunhee S
authors.initials: ES
authors.lastname: Yi
mesh_terms: D000328:Adult; D000368:Aged; D001327:Autoimmune Diseases / Q000097:blood / Q000276:immunology* / Q000473:pathology; D015415:Biomarkers / Q000032:analysis / Q000097:blood; D001706:Biopsy; D016022:Case-Control Studies; D020031:Epstein-Barr Virus Infections / Q000276:immunology / Q000473:pathology; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000032:analysis* / Q000097:blood; D007150:Immunohistochemistry; D008168:Lung / Q000276:immunology* / Q000473:pathology; D008171:Lung Diseases / Q000097:blood / Q000276:immunology* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D008910:Minnesota; D010950:Plasma Cells / Q000276:immunology* / Q000473:pathology; D019310:Pseudolymphoma / Q000097:blood / Q000276:immunology* / Q000473:pathology
chemical_list: D015415:Biomarkers; D007074:Immunoglobulin G
keywords: EBV; IgG4-related disease; IgG4-related lung disease; Pulmonary nodular lymphoid hyperplasia; Usual interstitial pneumonia