IgG4-related meningeal disease: clinico-pathological features and proposal for diagnostic criteria

Acta Neuropathol. 2010 Dec;120(6):765-76. doi: 10.1007/s00401-010-0746-2. Epub 2010 Sep 16.


IgG4-related disease has evolved from originally being recognized as a form of pancreatitis to encompass diseases of numerous organs including the hypophysis and one reported case of dural involvement. A search of the University of Virginia, Division of Neuropathology files for 10 years identified ten cases of unexplained lymphoplasmacytic meningeal inflammation that we then evaluated using immunohistochemical stains for IgG4 and IgG. Ten control cases including sarcoidosis (4), tuberculosis (1), bacterial abscess (2), Langerhans cell histiocytosis (2), and foreign body reaction (1) were also examined. The number of IgG4-positive plasma cells was counted in five high power fields (HPFs) and an average per HPF was calculated. Cases that contained greater than ten IgG4-positive cells/HPF were considered to be IgG4-related. Five of the study cases met these criteria, including one case of leptomeningeal inflammation. All cases exhibited the typical histological features of IgG4-related disease including lymphoplasmacytic inflammation, fibrosis, and phlebitis. The dural-based lesions appear to represent a subset of the cases historically diagnosed as idiopathic hypertrophic pachymeningitis. While the leptomeningeal process most closely resembles non-vasculitic autoimmune inflammatory meningoencephalitis. Given these findings, IgG4-related meningitis should be considered in the differential diagnosis of meningeal inflammatory lesions after stringent clinical and histologic criteria are used to rule out other possible diagnoses.

Publication types

  • Case Reports
  • Review

MeSH terms

  • Autoimmune Diseases of the Nervous System / diagnosis*
  • Autoimmune Diseases of the Nervous System / immunology
  • Autoimmune Diseases of the Nervous System / pathology*
  • Diagnosis, Differential
  • Humans
  • Immunoglobulin G / biosynthesis*
  • Meninges / immunology
  • Meninges / pathology*
  • Meningitis / diagnosis*
  • Meningitis / immunology
  • Meningitis / pathology*
  • Meningitis, Aseptic / diagnosis*
  • Meningitis, Aseptic / immunology
  • Meningitis, Aseptic / pathology*
  • Plasma Cells / immunology
  • Plasma Cells / metabolism
  • Plasma Cells / pathology
  • Retrospective Studies


  • Immunoglobulin G