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IgG4-Related Disease
Bronwyn E. Hamilton, MD
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KEY FACTS

  • Terminology

    • Imaging

      • Top Differential Diagnoses

        • Pathology

          • Clinical Issues

            • Diagnostic Checklist

              TERMINOLOGY

              • Abbreviations

                • IgG4-related disease (IgG4-RD)
              • Synonyms

                • Historical terms in various locations include Küttner tumor (submandibular gland), Mikuliçz syndrome (parotid & submandibular), Riedel thyroiditis
                • Orbit involvement previously grouped with nonspecific idiopathic orbital inflammation [(IOI), a.k.a. pseudotumor] but now recognized as separate entity
                • Skull base "pseudotumor" can be due to IgG4-RD
              • Definitions

                • Systemic immune-mediated disease with fibroinflammatory lesions at nearly any anatomic site (likely autoimmune)
                • Requires clinical, radiologic, serologic, & histopathologic correlation; immunohistochemistry has improved characterization of this disease

              IMAGING

              • General Features

                • Radiographic Findings

                  • CT Findings

                    • MR Findings

                      • Ultrasonographic Findings

                        • Imaging Recommendations

                          DIFFERENTIAL DIAGNOSIS

                            PATHOLOGY

                            • General Features

                              • Staging, Grading, & Classification

                                • Gross Pathologic & Surgical Features

                                  • Microscopic Features

                                    CLINICAL ISSUES

                                    • Presentation

                                      • Demographics

                                        • Natural History & Prognosis

                                          • Treatment

                                            • Complications

                                              DIAGNOSTIC CHECKLIST

                                              • Consider

                                                • Image Interpretation Pearls

                                                  Selected References

                                                  1. Behzadi F et al: Imaging of IgG4-related disease in the head and neck: a systematic review, case series, and pathophysiology update. J Neuroradiol. ePub, 2021
                                                  2. Dragan AD et al: Imaging of IgG4-related disease in the extracranial head and neck. Eur J Radiol. 136:109560, 2021
                                                  3. Kaur K et al: Sinonasal IgG4-related disease: a rare and emerging entity broadening the differential diagnosis in the sinonasal universe. Eur Arch Otorhinolaryngol.278(8):2883-90, 2021
                                                  4. Elkhamary SM et al: Involvement of multiple trigeminal nerve branches in IgG4-related orbital disease. Ophthalmic Plast Reconstr Surg. 37(2):176-8, 2020
                                                  5. Ishikawa Y et al: Genetic analysis of IgG4-related disease. Mod Rheumatol. 30(1):17-23, 2020
                                                  6. Lanzillotta M et al: Advances in the diagnosis and management of IgG4 related disease. BMJ. 369:m1067, 2020
                                                  7. Lee MJ et al: Non-specific orbital inflammation: current understanding and unmet needs. Prog Retin Eye Res. 100885, 2020
                                                  8. Savino G et al: Clinical-radiological patterns and histopathological outcomes in non-thyroid extraocular muscle enlargement: retrospective case series and current concepts. Ophthalmic Plast Reconstr Surg. 36(3):284-91, 2020
                                                  9. Strainiene S et al: Multi-organ IgG4-related disease continues to mislead clinicians: a case report and literature review. World J Clin Cases. 8(15):3267-79, 2020
                                                  10. Yoo RE et al: CT and MR imaging findings of ocular adnexal mucosa-associated lymphoid tissue lymphoma associated with IgG4-related disease: multi-institutional case series. Int J Ophthalmol. 13(8):1231-7, 2020
                                                  11. Yuan WH et al: Evaluate the differences in CT features and serum IgG4 levels between lymphoma and immunoglobulin G4-related disease of the orbit. J Clin Med. 9(8), 2020
                                                  12. Zabotti A et al: Ultrasound-guided core needle biopsy compared with open biopsy: a new diagnostic approach to salivary gland enlargement in Sjögren's syndrome? Rheumatology (Oxford). 60(3):1282-90, 2020
                                                  13. Ikeda R et al: Malignancies in patients with IgG4-related diseases in head and neck regions. Tohoku J Exp Med. 249(4):285-90, 2019
                                                  14. Jinkala SR et al: IgG4-related lymphadenopathy masquerading as Hodgkin lymphoma: lessons from a pathologist's desk. BMJ Case Rep. 12(9), 2019
                                                  15. Kurowecki D et al: Cross-sectional pictorial review of IgG4-related disease. Br J Radiol. 92(1103):20190448, 2019
                                                  16. Maehara T et al: Clinical features and mechanistic insights regarding IgG4-related dacryoadenitis and sialoadenitis: a review. Int J Oral Maxillofac Surg. 48(7):908-16, 2019
                                                  17. Rotondi M et al: Diagnosis of endocrine disease: IgG4-related thyroid autoimmune disease. Eur J Endocrinol. 180(5):R175-83, 2019
                                                  18. Sakamoto M et al: The diagnostic utility of submandibular gland sonography and labial salivary gland biopsy in IgG4-related dacryoadenitis and sialadenitis: Its potential application to the diagnostic criteria. Mod Rheumatol. 1-6, 2019
                                                  19. Uccella S et al: Disease heterogeneity in IgG4-related hypophysitis: report of two histopathologically proven cases and review of the literature. Virchows Arch. 475(3):373-81, 2019
                                                  20. Zhao Z et al: IgG4-related disease of the thyroid gland requiring emergent total thyroidectomy: a case report. Head Neck Pathol. 13(3):523-7, 2019
                                                  21. Fujita A: Imaging of Sjögren syndrome and immunoglobulin G4-related disease of the salivary glands. Neuroimaging Clin N Am. 28(2):183-97, 2018
                                                  22. Oyama-Manabe N et al: IgG4-related cardiovascular disease from the aorta to the coronary arteries: Multidetector CT and PET/CT. Radiographics. 38(7):1934-48, 2018
                                                  23. Berti A et al: Quantitative measurement of 18F-FDG PET/CT uptake reflects the expansion of circulating plasmablasts in IgG4-related disease. Rheumatology (Oxford). 56(12):2084-92, 2017
                                                  24. Kawaguchi M et al: Imaging findings of primary immunoglobulin G4-related cervical lymphadenopathy. Neuroradiology. 59(11):1111-9, 2017
                                                  25. Narayan AK et al: Sonographic findings of IgG4-related disease of the salivary glands: case report and review of the literature. J Clin Ultrasound.46(1):73-7, 2017
                                                  26. Thompson A et al: Imaging of IgG4-related disease of the head and neck. Clin Radiol. 73(1):106-20, 2017
                                                  27. Wu A et al: Bilateral IgG4-related ophthalmic disease: a strong indication for systemic imaging. Br J Ophthalmol. 100(10):1409-11, 2016
                                                  28. Inoue D et al: IgG4-related disease: dataset of 235 consecutive patients. Medicine (Baltimore). 94(15):e680, 2015
                                                  29. Ginat DT et al: Radiographic patterns of orbital involvement in IgG4-related disease. Ophthalmic Plast Reconstr Surg. 29(4):261-6, 2013
                                                  30. Fujita A et al: IgG4-related disease of the head and neck: CT and MR imaging manifestations. Radiographics. 32(7):1945-58, 2012
                                                  31. Toyoda K et al: MR imaging of IgG4-related disease in the head and neck and brain. AJNR Am J Neuroradiol. 33(11):2136-9, 2012
                                                  Related Anatomy
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                                                  Related Differential Diagnoses
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                                                  References
                                                  Tables

                                                  Tables

                                                  KEY FACTS

                                                  • Terminology

                                                    • Imaging

                                                      • Top Differential Diagnoses

                                                        • Pathology

                                                          • Clinical Issues

                                                            • Diagnostic Checklist

                                                              TERMINOLOGY

                                                              • Abbreviations

                                                                • IgG4-related disease (IgG4-RD)
                                                              • Synonyms

                                                                • Historical terms in various locations include Küttner tumor (submandibular gland), Mikuliçz syndrome (parotid & submandibular), Riedel thyroiditis
                                                                • Orbit involvement previously grouped with nonspecific idiopathic orbital inflammation [(IOI), a.k.a. pseudotumor] but now recognized as separate entity
                                                                • Skull base "pseudotumor" can be due to IgG4-RD
                                                              • Definitions

                                                                • Systemic immune-mediated disease with fibroinflammatory lesions at nearly any anatomic site (likely autoimmune)
                                                                • Requires clinical, radiologic, serologic, & histopathologic correlation; immunohistochemistry has improved characterization of this disease

                                                              IMAGING

                                                              • General Features

                                                                • Radiographic Findings

                                                                  • CT Findings

                                                                    • MR Findings

                                                                      • Ultrasonographic Findings

                                                                        • Imaging Recommendations

                                                                          DIFFERENTIAL DIAGNOSIS

                                                                            PATHOLOGY

                                                                            • General Features

                                                                              • Staging, Grading, & Classification

                                                                                • Gross Pathologic & Surgical Features

                                                                                  • Microscopic Features

                                                                                    CLINICAL ISSUES

                                                                                    • Presentation

                                                                                      • Demographics

                                                                                        • Natural History & Prognosis

                                                                                          • Treatment

                                                                                            • Complications

                                                                                              DIAGNOSTIC CHECKLIST

                                                                                              • Consider

                                                                                                • Image Interpretation Pearls

                                                                                                  Selected References

                                                                                                  1. Behzadi F et al: Imaging of IgG4-related disease in the head and neck: a systematic review, case series, and pathophysiology update. J Neuroradiol. ePub, 2021
                                                                                                  2. Dragan AD et al: Imaging of IgG4-related disease in the extracranial head and neck. Eur J Radiol. 136:109560, 2021
                                                                                                  3. Kaur K et al: Sinonasal IgG4-related disease: a rare and emerging entity broadening the differential diagnosis in the sinonasal universe. Eur Arch Otorhinolaryngol.278(8):2883-90, 2021
                                                                                                  4. Elkhamary SM et al: Involvement of multiple trigeminal nerve branches in IgG4-related orbital disease. Ophthalmic Plast Reconstr Surg. 37(2):176-8, 2020
                                                                                                  5. Ishikawa Y et al: Genetic analysis of IgG4-related disease. Mod Rheumatol. 30(1):17-23, 2020
                                                                                                  6. Lanzillotta M et al: Advances in the diagnosis and management of IgG4 related disease. BMJ. 369:m1067, 2020
                                                                                                  7. Lee MJ et al: Non-specific orbital inflammation: current understanding and unmet needs. Prog Retin Eye Res. 100885, 2020
                                                                                                  8. Savino G et al: Clinical-radiological patterns and histopathological outcomes in non-thyroid extraocular muscle enlargement: retrospective case series and current concepts. Ophthalmic Plast Reconstr Surg. 36(3):284-91, 2020
                                                                                                  9. Strainiene S et al: Multi-organ IgG4-related disease continues to mislead clinicians: a case report and literature review. World J Clin Cases. 8(15):3267-79, 2020
                                                                                                  10. Yoo RE et al: CT and MR imaging findings of ocular adnexal mucosa-associated lymphoid tissue lymphoma associated with IgG4-related disease: multi-institutional case series. Int J Ophthalmol. 13(8):1231-7, 2020
                                                                                                  11. Yuan WH et al: Evaluate the differences in CT features and serum IgG4 levels between lymphoma and immunoglobulin G4-related disease of the orbit. J Clin Med. 9(8), 2020
                                                                                                  12. Zabotti A et al: Ultrasound-guided core needle biopsy compared with open biopsy: a new diagnostic approach to salivary gland enlargement in Sjögren's syndrome? Rheumatology (Oxford). 60(3):1282-90, 2020
                                                                                                  13. Ikeda R et al: Malignancies in patients with IgG4-related diseases in head and neck regions. Tohoku J Exp Med. 249(4):285-90, 2019
                                                                                                  14. Jinkala SR et al: IgG4-related lymphadenopathy masquerading as Hodgkin lymphoma: lessons from a pathologist's desk. BMJ Case Rep. 12(9), 2019
                                                                                                  15. Kurowecki D et al: Cross-sectional pictorial review of IgG4-related disease. Br J Radiol. 92(1103):20190448, 2019
                                                                                                  16. Maehara T et al: Clinical features and mechanistic insights regarding IgG4-related dacryoadenitis and sialoadenitis: a review. Int J Oral Maxillofac Surg. 48(7):908-16, 2019
                                                                                                  17. Rotondi M et al: Diagnosis of endocrine disease: IgG4-related thyroid autoimmune disease. Eur J Endocrinol. 180(5):R175-83, 2019
                                                                                                  18. Sakamoto M et al: The diagnostic utility of submandibular gland sonography and labial salivary gland biopsy in IgG4-related dacryoadenitis and sialadenitis: Its potential application to the diagnostic criteria. Mod Rheumatol. 1-6, 2019
                                                                                                  19. Uccella S et al: Disease heterogeneity in IgG4-related hypophysitis: report of two histopathologically proven cases and review of the literature. Virchows Arch. 475(3):373-81, 2019
                                                                                                  20. Zhao Z et al: IgG4-related disease of the thyroid gland requiring emergent total thyroidectomy: a case report. Head Neck Pathol. 13(3):523-7, 2019
                                                                                                  21. Fujita A: Imaging of Sjögren syndrome and immunoglobulin G4-related disease of the salivary glands. Neuroimaging Clin N Am. 28(2):183-97, 2018
                                                                                                  22. Oyama-Manabe N et al: IgG4-related cardiovascular disease from the aorta to the coronary arteries: Multidetector CT and PET/CT. Radiographics. 38(7):1934-48, 2018
                                                                                                  23. Berti A et al: Quantitative measurement of 18F-FDG PET/CT uptake reflects the expansion of circulating plasmablasts in IgG4-related disease. Rheumatology (Oxford). 56(12):2084-92, 2017
                                                                                                  24. Kawaguchi M et al: Imaging findings of primary immunoglobulin G4-related cervical lymphadenopathy. Neuroradiology. 59(11):1111-9, 2017
                                                                                                  25. Narayan AK et al: Sonographic findings of IgG4-related disease of the salivary glands: case report and review of the literature. J Clin Ultrasound.46(1):73-7, 2017
                                                                                                  26. Thompson A et al: Imaging of IgG4-related disease of the head and neck. Clin Radiol. 73(1):106-20, 2017
                                                                                                  27. Wu A et al: Bilateral IgG4-related ophthalmic disease: a strong indication for systemic imaging. Br J Ophthalmol. 100(10):1409-11, 2016
                                                                                                  28. Inoue D et al: IgG4-related disease: dataset of 235 consecutive patients. Medicine (Baltimore). 94(15):e680, 2015
                                                                                                  29. Ginat DT et al: Radiographic patterns of orbital involvement in IgG4-related disease. Ophthalmic Plast Reconstr Surg. 29(4):261-6, 2013
                                                                                                  30. Fujita A et al: IgG4-related disease of the head and neck: CT and MR imaging manifestations. Radiographics. 32(7):1945-58, 2012
                                                                                                  31. Toyoda K et al: MR imaging of IgG4-related disease in the head and neck and brain. AJNR Am J Neuroradiol. 33(11):2136-9, 2012