IgG4-related disease in the head and neck

Semin Diagn Pathol. 2012 Nov;29(4):235-44. doi: 10.1053/j.semdp.2012.07.008.


Lymphoid infiltrates are relatively common in the ocular adnexa and the salivary glands. They are of a variety of types and include both reactive processes and lymphomas. Within the ocular adnexa in years past, lymphoid proliferations were classified as inflammatory pseudotumor, reactive lymphoid hyperplasia, atypical lymphoid hyperplasia, and lymphoma. With improvements in diagnostic techniques and with advances in lymphoma subclassification, it became clear that many of the dense lymphoid infiltrates, including cases classified as lymphoma and likely some classified as atypical lymphoid hyperplasia, represented low-grade B-cell lymphomas, the most common of which by far were extranodal marginal zone lymphomas of mucosa-associated lymphoid tissue (MALT) lymphomas. Ocular adnexal inflammatory pseudotumor, reactive lymphoid hyperplasia, and chronic sclerosing sialadenitis were recognized, but the focus in diagnosis had been on avoiding misdiagnosis as a neoplastic process and in planning appropriate therapy. Recently, it has become clear that many cases of these reactive processes fall into the spectrum of immunoglobulin G4 (IgG4)-related disease, offering new insight into the pathogenesis of inflammatory lesions occurring in the ocular adnexa and the salivary glands. The majority of entities previously classified as chronic sclerosing sialadenitis, Mikulicz disease, orbital pseudolymphoma, and eosinophilic angiocentric fibrosis are now considered a part of the IgG4-related disease spectrum. In this review, we discuss the histologic and immunohistochemical features of IgG4-related disease of the head and neck and provide guidance for distinguishing this disease from its many mimics.

Publication types

  • Review

MeSH terms

  • Autoimmune Diseases / diagnosis*
  • Autoimmune Diseases / immunology
  • Autoimmune Diseases / metabolism
  • Biomarkers / metabolism
  • Diagnosis, Differential
  • Female
  • Head and Neck Neoplasms / diagnosis
  • Humans
  • Immunoglobulin G / blood*
  • Lymphoma, B-Cell, Marginal Zone / diagnosis
  • Male
  • Orbital Diseases / diagnosis*
  • Orbital Diseases / immunology
  • Orbital Diseases / metabolism
  • Sialadenitis / diagnosis*
  • Sialadenitis / immunology
  • Sialadenitis / metabolism
  • Sjogren's Syndrome / diagnosis


  • Biomarkers
  • Immunoglobulin G