Available online 15 November 2023

Author links open overlay panelABSTRACT

The recognition of immunoglobulin G4-related disease (IgG4-RD) as an entity in the pancreaticobiliary tract was followed by a slew of papers describing inflammation and fibrosis containing IgG4-positive plasma cells in a variety of sites including the respiratory tract, leading to the hypothesis that these abnormalities were attributable to IgG4-RD. Predictably, pathologists began to see requests from clinicians to perform IgG4 immunohistochemistry in lung biopsies “to rule out IgG4-RD”. Several years later, the notion that IgG4-RD would prove to be the underlying cause of a wide array of fibroinflammatory lesions in the lung has not panned out as promised. To the contrary, it has become clear that IgG4-positive plasma cells are not specific for IgG4-RD, and that large numbers of IgG4-positive plasma cells can be encountered in other well-defined entities, including inflammatory myofibroblastic tumor and nodular lymphoid hyperplasia, as well as in lymphoplasmacytic infiltrates in other entities, including connective tissue disease and idiopathic forms of interstitial lung disease. It has also become clear that raised serum IgG4 levels can occur in settings other than IgG4-RD. These observations suggest that true IgG4-RD of the lung is far less common than previously surmised. Pathologists must familiarize themselves with mimics of IgG4-RD in the lung and exercise caution before attributing lymphoplasmacytic infiltrates in the lung to IgG4-RD.

Section snippetsINTRODUCTION

IgG4-related disease (IgG4-RD) is an uncommon systemic disorder characterized by mass-like sclerosing lesions in the pancreas, salivary glands, lacrimal glands and other tissues.1, 2, 3, 4 The recognition of raised serum IgG4 levels1 and increased tissue IgG4-positive plasma cells5 in patients with sclerosing pancreatitis was followed by several studies describing increased IgG4-positive plasma cells in lung biopsies and resections.6, 7, 8, 9, 10, 11, 12, 13, 14, 15 Although the clinical and

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Declaration of Competing Interest

I have no financial or other conflicts of interest to declare

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