Consensus statement on the pathology of IgG4-related disease

Published on Sep 1, 2012in Modern Pathology5.988
· DOI :10.1038/MODPATHOL.2012.72
Vikram Deshpande100
Estimated H-index: 100
(Harvard University),
Yoh Zen69
Estimated H-index: 69
(University of Cambridge)
+ 38 AuthorsJohn H. Stone76
Estimated H-index: 76
(Harvard University)
IgG4-related disease is a newly recognized fibro-inflammatory condition characterized by several features: a tendency to form tumefactive lesions in multiple sites; a characteristic histopathological appearance; and—often but not always—elevated serum IgG4 concentrations. An international symposium on IgG4-related disease was held in Boston, MA, on 4–7 October 2011. The organizing committee comprising 35 IgG4-related disease experts from Japan, Korea, Hong Kong, the United Kingdom, Germany, Italy, Holland, Canada, and the United States, including the clinicians, pathologists, radiologists, and basic scientists. This group represents broad subspecialty expertise in pathology, rheumatology, gastroenterology, allergy, immunology, nephrology, pulmonary medicine, oncology, ophthalmology, and surgery. The histopathology of IgG4-related disease was a specific focus of the international symposium. The primary purpose of this statement is to provide practicing pathologists with a set of guidelines for the diagnosis of IgG4-related disease. The diagnosis of IgG4-related disease rests on the combined presence of the characteristic histopathological appearance and increased numbers of IgG4+ plasma cells. The critical histopathological features are a dense lymphoplasmacytic infiltrate, a storiform pattern of fibrosis, and obliterative phlebitis. We propose a terminology scheme for the diagnosis of IgG4-related disease that is based primarily on the morphological appearance on biopsy. Tissue IgG4 counts and IgG4:IgG ratios are secondary in importance. The guidelines proposed in this statement do not supplant careful clinicopathological correlation and sound clinical judgment. As the spectrum of this disease continues to expand, we advocate the use of strict criteria for accepting newly proposed entities or sites as components of the IgG4-related disease spectrum.
Figures & Tables
📖 Papers frequently viewed together
261 Citations
2,772 Citations
346 Citations
#1Seth B. Krantz (NU: Northwestern University)H-Index: 13
#2Mario A. Shields (NU: Northwestern University)H-Index: 13
Last. David J. Bentrem (NU: Northwestern University)H-Index: 67
view all 5 authors...
Pancreatic adenocarcinoma remains among the most lethal of human malignancies. Overall 5-y survival is less than 5%, and only 20% of patients presenting with localized disease amenable to surgical resection. Even in patients who undergo resection, long-term survival remains extremely poor. A major contributor to the aggressiveness of multiple cancers, and pancreatic cancer in particular, is the process of epithelial-to-mesenchymal transition (EMT). This review highlights the growing evidence of ...
71 CitationsSource
#1Hisanori Umehara (Kanazawa Medical University)H-Index: 43
#2Kazuichi Okazaki (Kansai Medical University)H-Index: 68
Last. Dai Inoue (Kanazawa University)H-Index: 5
view all 22 authors...
IgG4-related disease (IgG4RD) is a novel clinical disease entity characterized by elevated serum IgG4 concentration and tumefaction or tissue infiltration by IgG4-positive plasma cells. IgG4RD may be present in a certain proportion of patients with a wide variety of diseases, including Mikulicz’s disease, autoimmune pancreatitis, hypophysitis, Riedel thyroiditis, interstitial pneumonitis, interstitial nephritis, prostatitis, lymphadenopathy, retroperitoneal fibrosis, inflammatory aortic aneurysm...
509 CitationsSource
#1Hisanori Umehara (Kanazawa Medical University)H-Index: 43
#2Kazuichi Okazaki (Kansai Medical University)H-Index: 68
Last. Hirotaka Ohara (Nagoya City University)H-Index: 42
view all 26 authors...
Background IgG4-related disease (IgG4-RD) is a novel clinical disease entity characterized by elevated serum IgG4 concentration and tumefaction or tissue infiltration by IgG4+ plasma cells. Although IgG4-RD is not rare and is clinically important, its clinical diagnostic criteria have not been established. Comprehensive diagnostic criteria for IgG4-RD, including the involvement of various organs, are intended for the practical use of general physicians and nonspecialists.
1,049 CitationsSource
#1Skye C. Mayo (Johns Hopkins University)H-Index: 25
#2Marta M. Gilson (Johns Hopkins University)H-Index: 13
Last. Timothy M. Pawlik (Johns Hopkins University)H-Index: 93
view all 10 authors...
Background Surgical resection remains the only potentially curative option for patients with pancreatic adenocarcinoma (PAC). Advances in surgical technique and perioperative care have reduced perioperative mortality; however, temporal trends in perioperative morbidity and the use of adjuvant therapy on a population basis remain ill-defined. Study Design Using Surveillance, Epidemiology, and End Results–Medicare data, 2,461 patients with resected PAC were identified from 1991 to 2005. We examine...
91 CitationsSource
27 CitationsSource
#1Mitsuhiro Kawano (Kanazawa University)H-Index: 21
#1Mitsuhiro Kawano (Kanazawa University)H-Index: 20
Last. Takao Saito (Fukuoka University)H-Index: 33
view all 15 authors...
Background IgG4-related disease has attracted wide attention recently. It is characterized by a high level of serum IgG4 and dense infiltration of IgG4-positive plasma cells into multiple organs, with the kidney being one representative target. Although several sets of diagnostic criteria for autoimmune pancreatitis (AIP) are available and renal lesion is recognized as an extra-pancreatic manifestation of AIP, it is difficult to differentiate IgG4-related tubulointerstitial nephritis (TIN) witho...
275 CitationsSource
#1Yassaman Raissian (Mayo Clinic)H-Index: 5
#2Samih H. NasrH-Index: 52
Last. Lynn D. CornellH-Index: 46
view all 13 authors...
IgG4-related systemic disease is an autoimmune disease that was first recognized in the pancreas but also affects other organs. This disease may manifest as tubulointerstitial nephritis (IgG4-TIN), but its clinicopathologic features in the kidney are not well described. Of the 35 patients with IgG4-TIN whose renal tissue specimens we examined, 27 (77%) had acute or progressive chronic renal failure, 29 (83%) had involvement of other organ systems, and 18 of 23 (78%) had radiographic abnormalitie...
228 CitationsSource
#1Vikram Deshpande (Harvard University)H-Index: 100
#2Arezou KhosroshahiH-Index: 30
Last. John H. StoneH-Index: 76
view all 5 authors...
BackgroundEosinophilic angiocentric fibrosis (EAF) is an uncommon tumefactive lesion of the orbit and upper respiratory tract of unknown etiology. The condition is characterized histologically by concentric layers of fibrosis around small-caliber arteries and a mixed inflammatory infiltrate dominate
81 CitationsSource
#1Kensuke Kubota (YCU: Yokohama City University)H-Index: 30
#2Shingo Kato (YCU: Yokohama City University)H-Index: 21
Last. Atsushi Nakajima (YCU: Yokohama City University)H-Index: 63
view all 14 authors...
Background and study aims Expression of the forkhead/winged helix family of transcription factor P3+ regulatory T cells (FOXP3+ Treg), a master gene of regulatory T cells (Treg) is observed in patients with autoimmune pancreatitis (AIP). We investigated the usefulness of detection of FOXP3+ Treg in the main duodenal papilla for differential diagnosis between AIP and pancreatic cancer (Pca).
10 CitationsSource
#1Hideaki MotekiH-Index: 16
#2Masanori YasuoH-Index: 23
Last. Shin-ichi UsamiH-Index: 45
view all 5 authors...
Abstract Conclusion: IgG4-related disease involves nasal manifestations with chronic rhinosinusitis (CRS). This type of sinusitis is a new clinical entity of nasal disease associated with a high level of serum IgG4 for which steroid therapy is effective. Objectives. To confirm whether IgG4-related disease has distinctive chronic rhinosinusitis. Methods: We compared serum IgG4 levels as well as nasal computed tomography (CT) and clinicopathological findings before and after glucocorticoid treatme...
63 CitationsSource
Cited By1429
#1Karen Thomas (Houston Methodist Hospital)H-Index: 2
Last. Jae Y. Ro (Cornell University)H-Index: 87
view all 5 authors...
Abstract Background Rosai-Dorfman disease (RDD) is a rare entity characterized by lymphadenopathy with dilated lymph node sinuses containing lymphocytes, plasma cells, and histiocytes exhibiting emperipolesis. IgG4-related disease (IgG4-RD) is relatively more common and is characterized by mass-forming lesions with dense lymphoplasmacytic infiltration, numerous IgG4 positive cells, fibrosis which is at least focally storiform, and obliterative phlebitis. Concomitant RDD and IgG4-RD is rare, and ...
#1Byung-Woo Yoo (Yonsei University)H-Index: 2
#2Sang-Won Lee (Yonsei University)H-Index: 23
Last. Seung Min Jung (Catholic University of Korea)H-Index: 12
view all 5 authors...
2 CitationsSource
#1Miji Lee (Gyeongsang National University)
#2Kyeong Hwa Ryu (Gyeongsang National University)H-Index: 6
Last. In Chul Nam (Gyeongsang National University)
view all 7 authors...
RATIONALE Rosai-Dorfman disease (RDD) is a rare and self-limiting condition caused by the non-neoplastic proliferation of histiocytes/phagocytes in the sinusoids of lymph nodes and in extranodal tissues. Of the extranodal involvement, laryngeal involvement is extremely rare. Because of its rarity and nonspecific clinicoradiologic features, RDD is often difficult to differentiate from other benign or malignant lymphoproliferative diseases. We present a case of RDD with infiltration of IgG4-bearin...
#1Marco Lanzillotta (UniSR: Vita-Salute San Raffaele University)H-Index: 14
#2Andreu Fernández-Codina (UWO: University of Western Ontario)H-Index: 9
Last. Emanuel Della-Torre (UniSR: Vita-Salute San Raffaele University)H-Index: 25
view all 7 authors...
INTRODUCTION Awareness of IgG4-related disease (IgG4-RD) is increasing worldwide and specialists are now familiar with most of its clinical manifestations and mimickers. IgG4-RD promptly responds to glucocorticoids and repeated courses are typically used to induce and maintain remission because the disease relapses in most patients. If left untreated it can lead to organ dysfunction, organ failure and death. Advancement in our understanding of IgG4-RD pathogenesis is leading to the identificatio...
#1Frederike C. Oertel (Humboldt University of Berlin)H-Index: 12
#2Michael Scheel (Humboldt University of Berlin)H-Index: 28
Last. Friedemann Paul (Humboldt University of Berlin)H-Index: 67
view all 6 authors...
Myelitis is an acute or subacute inflammatory syndrome of the spinal cord. Myelopathy, often used as a synonym and presenting with similar symptoms in clinical practice, can be caused by numerous, not primarily inflammatory etiologies and might also show a progressive disease course. Within the last decade the spectrum of autoimmune myelitis was significantly broadened as was the spectrum of diagnostic methods. Apart from the characteristic example of multiple sclerosis with short-length myeliti...
#1Michael B. Green (BU: Boston University)H-Index: 1
#2Mary K. Daly (BU: Boston University)H-Index: 11
Last. Daniel R. Lefebvre (Harvard University)H-Index: 11
view all 4 authors...
Abstract Purpose To present a case of adult onset asthma with periocular xanthogranuloma (AAPOX), and discuss existing literature on adult orbital xanthogranulomatous diseases (AOXGDs) and their treatment. Observations A 63 year old male presented with progressive bilateral eyelid swelling with overlying yellow plaques associated with asthma. CT scan showed periorbital swelling with enlargement of the superior and lateral rectus muscles bilaterally. Biopsy demonstrated orbital xanthogranulomatou...
#1Samuel J. Cler (WashU: Washington University in St. Louis)
#2Nima Sharifai (WashU: Washington University in St. Louis)H-Index: 3
Last. Michael R. Chicoine (WashU: Washington University in St. Louis)H-Index: 35
view all 9 authors...
Abstract Objective IgG4-Related Disease (IgG4-RD) is an inflammatory process that uncommonly can present in the skull base and calvarium and mimic a tumor but the nature of this condition is not well summarized in the neurosurgical literature. Methods A review of 2 cases of IgG4-RD in the skull base highlighting the diagnostic challenges with assessment of these skull base lesions was performed, and a systematic review of relevant literature summarized. Results A systematic review of literature ...
#1Haruaki Hino (Kansai Medical University)H-Index: 1
#2Noriyuki Tanaka (Kansai Medical University)H-Index: 1
Last. Tomohiro Murakawa (Kansai Medical University)H-Index: 23
view all 9 authors...
BACKGROUND Immunoglobulin G4-related disease (IgG4-RD) is a multi-organ disorder predominantly occurring in middle-aged to elderly male patients characterized by multi-organ fibrosis, specific pathological findings of storiform fibrosis with IgG4-positive plasma cell infiltration, and elevated serum IgG4 level. We herein report a rare presentation of IgG4-RD forming an isolated mass in the middle mediastinum mimicking a mediastinal tumor and discuss the clinical significance of mediastinal IgG4-...
1 CitationsSource
#1Utako Ishimoto (Jikei University School of Medicine)H-Index: 1
#2Akiyoshi Kinoshita (Jikei University School of Medicine)H-Index: 10
Last. Tooru Harada (Jikei University School of Medicine)
view all 5 authors...