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Beuers U, Trampert DC. IgG4-Related Cholangitis. Semin Liver Dis 2025. [PMID: 40342085 DOI: 10.1055/a-2588-3875] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 05/11/2025]
Abstract
IgG4-related cholangitis (IRC) is a rare fibroinflammatory disease of the biliary tree and liver and presents the major hepatobiliary manifestation of IgG4-related systemic disease (IgG4-RD). IRC also includes the IgG4-related inflammatory pseudotumor of the liver and IgG4-related cholecystitis. IRC mimics other cholangiopathies such as primary sclerosing cholangitis or cholangiocarcinoma. IRC may be found in 30 to 60% of cases with type 1 autoimmune pancreatitis, the most frequent manifestation of IgG4-RD. The pathogenesis of IRC (and IgG4-RD) is incompletely understood. Genetic predisposition, environmental factors, oligoclonal glucocorticosteroid-sensitive expansion of IgG4+ B cells/plasmablasts in blood and affected tissue and blocking autoantibody formation against protective IgG4-specific autoantigens such as annexin A11 and laminin 511-E8 with impaired protection of biliary epithelia against toxic bile acids have been described in IRC. Specific T cell subtypes are involved in the inflammatory process. The diagnosis of IRC is made according to HISORt criteria comprising histopathology, imaging, serology, other organ manifestations, and response to therapy. Treatment of IRC aiming to prevent organ failure and improve symptoms includes remission induction with highly effective glucocorticosteroids and long-term maintenance of remission with immunomodulators such as glucocorticosteroid sparing additives or B cell depleting approaches.
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Affiliation(s)
- Ulrich Beuers
- Department of Gastroenterology and Hepatology, Tytgat Institute for Liver and Intestinal Research, AGEM, Amsterdam University Medical Center, Amsterdam, The Netherlands
| | - David C Trampert
- Department of Gastroenterology and Hepatology, Tytgat Institute for Liver and Intestinal Research, AGEM, Amsterdam University Medical Center, Amsterdam, The Netherlands
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2
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Aouadi SE, Imrani K, Naggar A, Bahha S, Billah NM, Nassar I. IgG4-related disease revealed by acute pancreatitis: A case report and literature review. Radiol Case Rep 2025; 20:2315-2322. [PMID: 40129846 PMCID: PMC11930517 DOI: 10.1016/j.radcr.2025.01.078] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/17/2024] [Revised: 01/14/2025] [Accepted: 01/23/2025] [Indexed: 03/26/2025] Open
Abstract
IgG4-related disease is a systemic autoimmune disorder characterized by multiorgan involvement, often presenting with pancreatic, renal, biliary, and salivary gland abnormalities. Diagnosis relies on clinical, serological, imaging, and occasionally histological findings. This report describes a 65-year-old male presenting with acute pancreatitis, bilateral renal lesions, and biliary strictures. Elevated serum IgG4 levels (3.76 g/L) confirmed the diagnosis using the 2019 ACR/EULAR and 2020 Comprehensive Diagnostic Criteria despite the lack of histological confirmation. Corticosteroid therapy led to rapid clinical and biochemical improvement, underscoring the importance of integrating multiple diagnostic modalities in managing IgG4-related disease and demonstrating the effectiveness of early intervention.
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Affiliation(s)
- Salma El Aouadi
- Central Radiology Department, Ibn Sina University Hospital, Rabat, Morocco
| | - Kaoutar Imrani
- Central Radiology Department, Ibn Sina University Hospital, Rabat, Morocco
| | - Amine Naggar
- Central Radiology Department, Ibn Sina University Hospital, Rabat, Morocco
| | - Soukaina Bahha
- Central Radiology Department, Ibn Sina University Hospital, Rabat, Morocco
| | | | - Ittimade Nassar
- Central Radiology Department, Ibn Sina University Hospital, Rabat, Morocco
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Farrokh F, Rimmer RA. Sinonasal Presentations of Immunoglobulin G4-Related Disease: A Scoping Review. Laryngoscope 2025. [PMID: 40231759 DOI: 10.1002/lary.32196] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/29/2024] [Revised: 03/10/2025] [Accepted: 03/24/2025] [Indexed: 04/16/2025]
Abstract
OBJECTIVE Immunoglobulin G4 related disease (IgG4RD) is a recently identified systematic immune disease that may manifest in various organ systems. The latest classification criteria from 2019 combine data from 11 "typical" organ systems for diagnosis, notably excluding the sinonasal region. As sinonasal involvement is not included in this criteria, we performed a scoping review to better clarify sinonasal presentations of IgG4RD. DATA SOURCES We conducted a literature search in three bibliographic resources: Pubmed, Scopus, and Web of science. REVIEW METHODS All the databases' results were reviewed by two authors utilizing Endnote and Rayyan platforms. Articles were included if they presented a case (or cases) with sinonasal IgG4RD. Critical appraisal of all included articles was performed according to JBI guidelines. RESULTS Eighty articles containing 145 patients with sinonasal manifestations of IgG4RD were included. Ages ranged from 13 to 83 years (mean 54.57 ± 15.85 years). The most common clinical symptoms were nasal (63.4%) and visual/orbital (37.9%) complaints. The most frequent sites of involvement were maxillary sinus (N = 75), ethmoid sinus (N = 65) and nasal cavity (N = 59). Seventy-three percent of patients had involvement of at least one other organ system outside the sinonasal region. CONCLUSION Sinonasal manifestations have been described despite not being considered a typical organ system eligible for the recent classification criteria of IgG4RD; however, simultaneous involvement of other organ systems outside the sinonasal region is common. Familiarity with common presentations of IgG4RD and related diagnostic elements is critical to the diagnosis and management of all involved sites. LEVEL OF EVIDENCE N/A.
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Affiliation(s)
- Fatemeh Farrokh
- Otorhinolaryngology Research Center, Imam Khomeini Hospital Complex, Tehran University of Medical Sciences, Tehran, Iran
| | - Ryan A Rimmer
- Division of Otolaryngology, Yale School of Medicine, New Haven, Connecticut, USA
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Hawkins N, Sun D, Pornkul P, Bae K, Ben David M. Hilar and Extrahepatic Inflammatory Pseudotumour: A Case Report and Systematic Literature Review. Cureus 2025; 17:e79727. [PMID: 40017578 PMCID: PMC11865861 DOI: 10.7759/cureus.79727] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 02/22/2025] [Indexed: 03/01/2025] Open
Abstract
Inflammatory pseudotumor (IPT) is a benign inflammatory lesion that is exceptionally rare in the biliary tree. Its clinical and radiological presentation mimics neoplastic disease, so diagnosis often relies on histology. Surgical resection is the mainstay of treatment. A case of histologically confirmed IPT in a 52-year-old female, successfully managed with surgical resection, is presented. A systematic literature review was conducted following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines to identify case reports and case series of IPT involving the extrahepatic bile ducts and liver hilum. Searches of PubMed and Embase (from January 1960 to December 2024) yielded 23 original articles that met inclusion criteria. Data on clinical presentation, management, and outcomes were analyzed. A total of 33 cases of hilar and extrahepatic IPT have been reported in the literature. Obstructive jaundice was the most common presentation (79% n=26/32) accompanied by biochemical elevation of liver function tests (91% n=21/23) and bilirubin (77% n=17/22). Surgical resection was the most common treatment (82% n=27/33) with excellent outcomes and only one case of recurrence. However, the follow-up period was relatively short (median of one year). Of five cases initially treated with steroids, three were successfully managed with steroids alone. The other two cases proceeded to surgical resection due to disease progression. Serum immunoglobulin-G4 was high in successfully managed cases and not reported in failed cases. Hilar and extrahepatic IPT is a rare pathology with a similar presentation to neoplastic disease, which can make diagnosis and management challenging. Surgical resection is the mainstay of management, however, in select cases, preoperative biopsy may help avoid unnecessary surgical intervention. Further studies with extended follow-up are needed to optimize diagnostic and therapeutic strategies.
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Affiliation(s)
- Nicole Hawkins
- General Surgery, Townsville University Hospital, Townsville, AUS
| | - David Sun
- General Surgery, Townsville University Hospital, Townsville, AUS
| | - Panuwat Pornkul
- General Surgery, Townsville University Hospital, Townsville, AUS
| | - Kaeun Bae
- General Surgery, Townsville University Hospital, Townsville, AUS
| | - Matan Ben David
- Upper Gastrointestinal and Hepatobiliary Surgery, Townsville University Hospital, Townsville, AUS
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Liang MX, Chen Y, He Y, He YH. Journey to diagnosis: An unfinished exploration of IgG4-related sclerosing cholangitis. World J Clin Cases 2024; 12:6608-6612. [PMID: 39600477 PMCID: PMC11514334 DOI: 10.12998/wjcc.v12.i33.6608] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/04/2024] [Revised: 08/19/2024] [Accepted: 08/23/2024] [Indexed: 09/27/2024] Open
Abstract
IgG4-related sclerosing cholangitis (IgG4-SC) is an inflammatory disease that leads to bile duct stricture, characterized by the infiltration of IgG4-positive plasma cells into the bile duct wall, thickening of the bile duct wall, and narrowing of the lumen. The differential diagnosis of IgG4-SC mainly includes primary sclerosing cholangitis, cholangiocarcinoma, and pancreatic cancer. IgG4-SC is often associated with autoimmune pancreatitis and can be accurately diagnosed based on clinical diagnostic criteria. However, isolated IgG4-SC is difficult to distinguish from biliary tumors. Given the significant differences in biological behavior, treatment, and prognosis between these diseases, accurately identifying isolated IgG4-SC has very important clinical significance.
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Affiliation(s)
- Ming-Xing Liang
- Department of Infectious Diseases, Affiliated Hospital of Zunyi Medical University, Zunyi 563000, Guizhou Province, China
| | - Ya Chen
- Department of Infectious Diseases, Affiliated Hospital of Zunyi Medical University, Zunyi 563000, Guizhou Province, China
| | - Ya He
- Department of Infectious Diseases, Affiliated Hospital of Zunyi Medical University, Zunyi 563000, Guizhou Province, China
| | - Yi-Huai He
- Department of Infectious Diseases, Affiliated Hospital of Zunyi Medical University, Zunyi 563000, Guizhou Province, China
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Toh C, Morita S, Takeda N, Yamazaki F, Yokoyama K, Sato M, Kumaki D, Sakai T, Funakoshi K, Tsuneyama K. Immunoglobulin G4-related autoimmune hepatitis following type 1 autoimmune pancreatitis: A case report and literature review. Intern Med 2024:4687-24. [PMID: 39522990 DOI: 10.2169/internalmedicine.4687-24] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/16/2024] Open
Abstract
We herein report a case of IgG4-related autoimmune hepatitis (AIH) in a patient with a history of type 1 autoimmune pancreatitis. A 56-year-old man presented with fatigue and jaundice at our hospital. A blood biochemistry analysis revealed significant liver dysfunction, positive results for antinuclear antibodies, and high serum IgG4 levels. A histopathological examination revealed interface hepatitis marked by IgG4-positive plasma cell infiltration in the portal area, leading to liver cell depletion and necrosis. Based on the diagnosis of IgG4-related AIH, prednisolone treatment was initiated, which led to the rapid resolution of liver dysfunction and jaundice. An accurate diagnosis of IgG4-related AIH is crucial to prevent secondary manifestations.
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Affiliation(s)
- Chiharu Toh
- Department of Gastroenterology and Hepatology, Niigata Prefectural Central Hospital, Japan
| | - Shinichi Morita
- Department of Gastroenterology and Hepatology, Niigata Prefectural Central Hospital, Japan
| | - Nobutaka Takeda
- Department of Gastroenterology and Hepatology, Niigata Prefectural Central Hospital, Japan
| | - Fusako Yamazaki
- Department of Gastroenterology and Hepatology, Niigata Prefectural Central Hospital, Japan
| | - Kunihiko Yokoyama
- Department of Gastroenterology and Hepatology, Niigata Prefectural Central Hospital, Japan
| | - Masatoshi Sato
- Department of Gastroenterology and Hepatology, Niigata Prefectural Central Hospital, Japan
| | - Daisuke Kumaki
- Department of Gastroenterology and Hepatology, Niigata Prefectural Central Hospital, Japan
| | - Takeshi Sakai
- Department of Pathology, Niigata Prefectural Central Hospital, Japan
| | - Kazuhiro Funakoshi
- Department of Gastroenterology and Hepatology, Niigata Prefectural Central Hospital, Japan
| | - Koichi Tsuneyama
- Department of Pathology and Laboratory Medicine, Tokushima University Graduate School of Biomedical Science, Japan
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7
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Wan Q, Xu Z, Liu X, Wu Z, Zhong Q, Wu C. A case report of IgG4-related hepatic inflammatory pseudotumor in a 3-year old boy. Front Immunol 2024; 15:1376276. [PMID: 38745658 PMCID: PMC11091244 DOI: 10.3389/fimmu.2024.1376276] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/25/2024] [Accepted: 04/19/2024] [Indexed: 05/16/2024] Open
Abstract
Background Hepatic Inflammatory Pseudotumor (IPT) is an infrequent condition often masquerading as a malignant tumor, resulting in misdiagnosis and unnecessary surgical resection. The emerging concept of IgG4-related diseases (IgG4-RD) has gained widespread recognition, encompassing entities like IgG4-related hepatic IPT. Clinically and radiologically, corticosteroids and immunosuppressive therapies have proven effective in managing this condition. Case Presentation A 3-year-old Chinese boy presented to the clinic with an 11-month history of anemia, fever of unknown origin, and a tender hepatic mass. Blood examinations revealed chronic anemia (Hb: 6.4 g/L, MCV: 68.6 fl, MCH: 19.5 pg, reticulocytes: 1.7%) accompanied by an inflammatory reaction and an elevated serum IgG4 level (1542.2 mg/L). Abdominal contrast-enhanced computed tomography unveiled a 7.6 cm low-density mass in the right lateral lobe, while magnetic resonance imaging demonstrated slight hypointensity on T1-weighted images and slight hyperintensity on T2-weighted images, prompting suspicion of hepatic malignancy. A subsequent liver biopsy revealed a mass characterized by fibrous stroma and dense lymphoplasmacytic infiltration. Immunohistochemical analysis confirmed the presence of IgG4-positive plasma cells, leading to the diagnosis of IgG4-related hepatic IPT. Swift resolution occurred upon initiation of corticosteroid and mycophenolate mofetil therapies. Conclusion This study underscores the diagnostic approach to hepatic IPT, utilizing histopathology, immunostaining, imaging, serology, organ involvement, and therapeutic response. Early histological examination plays a pivotal role in clinical guidance, averting misdiagnosis as a liver tumor and unnecessary surgical interventions.
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Affiliation(s)
- Qian Wan
- Department of Hematology, Jiangxi Provincial Children’s Hospital, Nanchang, China
| | - Zhongjin Xu
- Department of Hematology, Jiangxi Provincial Children’s Hospital, Nanchang, China
| | - Xiaohui Liu
- Department of Rheumatology and Immunology, Jiangxi Provincial Children’s Hospital, Nanchang, China
| | - Zhuqiang Wu
- Nuclear Magnetic Resonance Room, Jiangxi Provincial Children’s Hospital, Nanchang, China
| | - Qingmei Zhong
- Department of Pathology, The Ninth Hospital of Nanchang, Nanchang, China
| | - Chongjun Wu
- Department of Hematology, Jiangxi Provincial Children’s Hospital, Nanchang, China
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Park BU, Lee HE, Zhang L. Mimickers of immunoglobulin G4-related hepatobiliary disease on biopsy. Semin Diagn Pathol 2024; 41:95-107. [PMID: 38238218 DOI: 10.1053/j.semdp.2024.01.009] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/11/2023] [Revised: 01/04/2024] [Accepted: 01/05/2024] [Indexed: 03/24/2024]
Abstract
With the growing recognition of IgG4-related hepatobiliary disease, establishing a definitive diagnosis relies mainly on a combination of clinical findings, serological markers, and imaging modalities. However, the role of histopathological evaluation remains indispensable, particularly in cases necessitating differential diagnosis or malignancy exclusion. While diagnosing IgG4-related hepatobiliary disease through surgical resection specimens is often straightforward, pathologists encounter substantial challenges when evaluating biopsies. The increasing rarity of surgical interventions exacerbates this due to improved disease recognition and suspicion. Numerous confounding factors, including the absence of the characteristic histologic features, limited tissue sample size, biopsy artifacts, and the limited value of IgG4 counts, further complicate the diagnostic process. Additionally, many other disorders exhibit clinical and histological features that overlap with IgG4-related disease, intensifying the complexity of interpreting biopsy specimens. This article explores the clinical and histomorphologic features of IgG4-related hepatobiliary disease and its potential mimickers. It offers valuable insights for pathologists and clinicians when confronted with biopsy specimens from hepatobiliary organs.
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Affiliation(s)
- Byoung Uk Park
- Division of Anatomic Pathology, Mayo Clinic, Rochester, MN 55905, United States
| | - Hee Eun Lee
- Division of Anatomic Pathology, Mayo Clinic, Rochester, MN 55905, United States
| | - Lizhi Zhang
- Division of Anatomic Pathology, Mayo Clinic, Rochester, MN 55905, United States.
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9
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Mukhopadhyay S. Differential diagnosis of IgG4-positive plasma cells in the lung. Semin Diagn Pathol 2024; 41:72-78. [PMID: 37993385 DOI: 10.1053/j.semdp.2023.11.006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/24/2023] [Accepted: 11/14/2023] [Indexed: 11/24/2023]
Abstract
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.
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Affiliation(s)
- Sanjay Mukhopadhyay
- Department of Pathology, Pathology and Laboratory Medicine Institute, Cleveland Clinic, 9500 Euclid Avenue/L25, Cleveland, OH 44195, United States.
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Gialanella JP, Steidl T, Korpela K, Grandhi MS, Langan RC, Alexander HR, Hudacko RM, Ecker BL. Hepatic pseudotumor associated with Strongyloides infection: A case report. World J Hepatol 2023; 15:1338-1343. [PMID: 38223414 PMCID: PMC10784808 DOI: 10.4254/wjh.v15.i12.1338] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/13/2023] [Revised: 10/21/2023] [Accepted: 11/29/2023] [Indexed: 12/25/2023] Open
Abstract
BACKGROUND Strongyloides sterocoralis is a parasitic infection caused by a roundworm that is transmitted through soil contaminated with larvae. It can infrequently cause hepatic abscesses in immunocompromised patients and is rarely reported to form hepatic lesions in immunocompetent hosts. CASE SUMMARY We present a case study of a 45-year-old female who presented with right upper quadrant abdominal pain and constitutional symptoms for several weeks. Cross-sectional imaging identified several malignant-appearing liver masses. Further investigation, including serological testing and histopathologic examination, revealed the presence of serum Strongyloides antibodies and hepatic granulomas with extensive necrosis. Following treatment with ivermectin for 2 wk, there was complete resolution of the liver lesions and associated symptoms. CONCLUSION This case highlights the importance of considering parasitic infections, such as Strongyloides, in the differential diagnosis of hepatic masses. Early recognition and appropriate treatment can lead to a favorable outcome and prevent unnecessary invasive procedures. Increased awareness among clinicians is crucial to ensure the timely diagnosis and management of such cases.
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Affiliation(s)
- Jessica P Gialanella
- Department of Surgical Oncology, Rutgers Cancer Institute of New Jersey, New Brunswick, NJ 08901, United States
| | - Tyler Steidl
- Rutgers New Jersey Medical School, Newark, NJ 07103, United States
| | - Kokkola Korpela
- Department of Infectious Disease, Cooperman Barnabas Medical Center, Livingston, NJ 07039, United States
| | - Miral S Grandhi
- Department of Surgical Oncology, Rutgers Cancer Institute of New Jersey, New Brunswick, NJ 08901, United States
| | - Russell C Langan
- Department of Surgical Oncology, Rutgers Cancer Institute of New Jersey, New Brunswick, NJ 08901, United States
| | - H Richard Alexander
- Department of Surgical Oncology, Rutgers Cancer Institute of New Jersey, New Brunswick, NJ 08901, United States
| | - Rachel M Hudacko
- Department of Pathology and Labratory Medicine, Rutgers Robert Wood Johnson Medical School, New Brunswick, NJ 08901, United States
| | - Brett L Ecker
- Department of Surgical Oncology, Rutgers Cancer Institute of New Jersey, New Brunswick, NJ 08901, United States.
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Hideshima K, Suzuki T, Oe S, Shinohara N, Matuhashi N, Ichii O, Tai M, Ejiri Y, Miyagawa K, Harada M. IgG4-related hepatic inflammatory pseudotumor in a patient with serum IgG4-negative type 1 autoimmune pancreatitis. Clin J Gastroenterol 2023; 16:895-900. [PMID: 37794288 DOI: 10.1007/s12328-023-01861-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/17/2023] [Accepted: 09/05/2023] [Indexed: 10/06/2023]
Abstract
IgG4-related disease (IgG4-RD) can cause heterogeneous lesion in various organs. Serum IgG4 levels are useful in monitoring patients with IgG4-RD; however, when it is negative, more careful observation is required. A 58-year-old woman who had been diagnosed with serum IgG4-negative type 1 autoimmune pancreatitis (AIP) 3 years prior visited our hospital for the evaluation of a liver tumor. She had visited a nearby hospital 1 month prior with complaints of a swelling in her right neck, and histological examinations were suggestive of IgG4-related sialadenitis. A positron emission tomography scan showed fluoro-deoxy-glucose accumulation in her right liver lobe; therefore, she was referred to our hospital. Liver tumor biopsy showed inflammatory cell infiltration and storiform fibrosis, without histological findings indicative of a malignancy. Many IgG4-positive cells were detected in immunostaining; thus, an IgG4-related hepatic inflammatory pseudo-tumor was diagnosed. After increasing in steroid dosage, the patient remained recurrence-free with 2 years. To our knowledge, this is the first report of mass-forming IPT for serum IgG4-negative type 1 AIP. Occasionally, IgG4-related IPT may appear in the periphery of the liver, and serum IgG4-negative cases should be more carefully observed because serum IgG4 is not an indicator.
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Affiliation(s)
- Kosuke Hideshima
- The Third Department of Internal Medicine, University of Occupational and Environmental Health, 1-1 Iseigaoka, Yahatanishi-ku, Kitakyushu, 807-8555, Japan.
- Department of Gastroenterology, Fukushima Rosai Hospital, 3 Numaziri, Uchigo Tsuzuri-machi, Iwaki, Japan.
| | - Tomohiro Suzuki
- Department of Gastroenterology, Fukushima Rosai Hospital, 3 Numaziri, Uchigo Tsuzuri-machi, Iwaki, Japan
| | - Shinji Oe
- The Third Department of Internal Medicine, University of Occupational and Environmental Health, 1-1 Iseigaoka, Yahatanishi-ku, Kitakyushu, 807-8555, Japan
| | - Nobuhiko Shinohara
- The Third Department of Internal Medicine, University of Occupational and Environmental Health, 1-1 Iseigaoka, Yahatanishi-ku, Kitakyushu, 807-8555, Japan
| | - Nobuo Matuhashi
- Department of Gastroenterology, Fukushima Rosai Hospital, 3 Numaziri, Uchigo Tsuzuri-machi, Iwaki, Japan
| | - Osamu Ichii
- Department of Gastroenterology, Fukushima Rosai Hospital, 3 Numaziri, Uchigo Tsuzuri-machi, Iwaki, Japan
| | - Mayumi Tai
- Department of Gastroenterology, Fukushima Rosai Hospital, 3 Numaziri, Uchigo Tsuzuri-machi, Iwaki, Japan
| | - Yutaka Ejiri
- Department of Gastroenterology, Fukushima Rosai Hospital, 3 Numaziri, Uchigo Tsuzuri-machi, Iwaki, Japan
| | - Koichiro Miyagawa
- The Third Department of Internal Medicine, University of Occupational and Environmental Health, 1-1 Iseigaoka, Yahatanishi-ku, Kitakyushu, 807-8555, Japan
| | - Masaru Harada
- The Third Department of Internal Medicine, University of Occupational and Environmental Health, 1-1 Iseigaoka, Yahatanishi-ku, Kitakyushu, 807-8555, Japan
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12
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Kersten R, Trampert DC, Herta T, Hubers LM, Maillette de Buy Wenniger LJ, Verheij J, van de Graaf SFJ, Beuers U. IgG4-related cholangitis - a mimicker of fibrosing and malignant cholangiopathies. J Hepatol 2023; 79:1502-1523. [PMID: 37598939 DOI: 10.1016/j.jhep.2023.08.005] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/12/2023] [Revised: 07/24/2023] [Accepted: 08/14/2023] [Indexed: 08/22/2023]
Abstract
IgG4-related cholangitis (IRC) is the major hepatobiliary manifestation of IgG4-related disease (IgG4-RD), a systemic fibroinflammatory disorder. The pathogenesis of IgG4-RD and IRC is currently viewed as multifactorial, as there is evidence of a genetic predisposition while environmental factors, such as blue-collar work, are major risk factors. Various autoantigens have been described in IgG4-RD, including annexin A11 and laminin 511-E8, proteins which may exert a partially protective function in cholangiocytes by enhancing secretion and barrier function, respectively. For the other recently described autoantigens, galectin-3 and prohibitin 1, a distinct role in cholangiocytes appears less apparent. In relation to these autoantigens, oligoclonal expansions of IgG4+ plasmablasts are present in patients with IRC and disappear upon successful treatment. More recently, specific T-cell subtypes including regulatory T cells, follicular T helper 2 cells, peripheral T helper cells and cytotoxic CD8+ and CD4+ SLAMF7+ T cells have been implicated in the pathogenesis of IgG4-RD. The clinical presentation of IRC often mimics other biliary diseases such as primary sclerosing cholangitis or cholangiocarcinoma, which may lead to inappropriate medical and potentially invalidating surgical interventions. As specific biomarkers are lacking, diagnosis is made according to the HISORt criteria comprising histopathology, imaging, serology, other organ manifestations and response to therapy. Treatment of IRC aims to prevent or alleviate organ damage and to improve symptoms and consists of (i) remission induction, (ii) remission maintenance and (iii) long-term management. Glucocorticosteroids are highly effective for remission induction, after which immunomodulators can be introduced for maintenance of remission as glucocorticosteroid-sparing alternatives. Increased insight into the pathogenesis of IRC will lead to improved diagnosis and novel therapeutic strategies in the future.
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Affiliation(s)
- Remco Kersten
- Department of Gastroenterology & Hepatology, Tytgat Institute for Liver and Intestinal Research, AGEM, Amsterdam University Medical Centers, Amsterdam, the Netherlands
| | - David C Trampert
- Department of Gastroenterology & Hepatology, Tytgat Institute for Liver and Intestinal Research, AGEM, Amsterdam University Medical Centers, Amsterdam, the Netherlands
| | - Toni Herta
- Department of Gastroenterology & Hepatology, Tytgat Institute for Liver and Intestinal Research, AGEM, Amsterdam University Medical Centers, Amsterdam, the Netherlands; Division of Hepatology, Department of Medicine II, Leipzig University Medical Center, Leipzig, Germany
| | - Lowiek M Hubers
- Department of Gastroenterology & Hepatology, Tytgat Institute for Liver and Intestinal Research, AGEM, Amsterdam University Medical Centers, Amsterdam, the Netherlands
| | | | - Joanne Verheij
- Department of Pathology, Amsterdam University Medical Centers, the Netherlands
| | - Stan F J van de Graaf
- Department of Gastroenterology & Hepatology, Tytgat Institute for Liver and Intestinal Research, AGEM, Amsterdam University Medical Centers, Amsterdam, the Netherlands
| | - Ulrich Beuers
- Department of Gastroenterology & Hepatology, Tytgat Institute for Liver and Intestinal Research, AGEM, Amsterdam University Medical Centers, Amsterdam, the Netherlands.
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13
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Kim SR, Kim SK, Koma YI, Sasaki M, Asai A, Nishikawa H. Hepatic Inflammatory Pseudotumor-Focusing on Its Heterogeneity. Diagnostics (Basel) 2023; 13:2857. [PMID: 37685395 PMCID: PMC10486865 DOI: 10.3390/diagnostics13172857] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2023] [Revised: 08/16/2023] [Accepted: 09/01/2023] [Indexed: 09/10/2023] Open
Abstract
Hepatic inflammatory pseudotumors (IPTs) are defined as benign, non-malignant, non-metastasizing tumors characterized by the presence of myofibroblastic spindle cells, hetorogenous populations of inflammatory cells, particularly plasma cells, lymphocytes and macrophages, as well as locations of fibrosis and necrosis without cellular anaplasia or atypical mitoses. Despite subsequent reports in the references, hepatic IPT remains difficult to diagnose; while posing major issues specifically for its differential diagnosis compared with that of other various benign diseases and malignant hepatic tumors. Histopathological findings are always a requisite for confirming the diagnosis, particularly given that the pathogenesis of IPT remains ambiguous to date. Hepatic IPT is a heterogeneous entity in terms of its clinical features, pathological findings, and pathogenesis. Once the diagnosis is confirmed, however, needless surgery such as wedge resection and lobectomy should be avoided. Here, we discuss the heterogeneity of hepatic IPT, its clinical features, pathological findings, and pathogenesis, and describe its differential diagnosis.
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Affiliation(s)
- Soo Ryang Kim
- Department of Gastroenterology, Kobe Asahi Hospital, Kobe 653-0801, Japan;
| | - Soo Ki Kim
- Department of Gastroenterology, Kobe Asahi Hospital, Kobe 653-0801, Japan;
| | - Yu-ichiro Koma
- Department of Pathology, Kobe University Graduate School of Medicine, Kobe 650-0017, Japan
| | - Motoko Sasaki
- Department of Human Pathology, Kanazawa University Graduate School of Medicine, Kanazawa 920-8640, Japan
| | - Akira Asai
- The Second Department of Internal Medicine, Osaka Medical and Pharmaceutical University, Takatsuki 569-8686, Japan
| | - Hiroki Nishikawa
- The Second Department of Internal Medicine, Osaka Medical and Pharmaceutical University, Takatsuki 569-8686, Japan
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Abstract
Hepatic inflammatory pseudotumor (IPT) describes a mass lesion composed of fibroblasts or myofibroblasts with a dense inflammatory infiltrate comprising lymphocyte, plasma cells, and histiocytes. These lesions are presumed to be an exuberant response to an infectious organism, although in most cases the causative agent is unknown. In specific circumstances, pathologists should consider ancillary techniques to exclude specific infections, such as mycobacteria, Candida, or syphilis. IgG4-related disease may cause a plasma-cell rich IPT. Finally, true neoplasms can mimic IPTs and must be excluded with appropriate ancillary studies, including inflammatory myofibroblastic tumor, follicular dendritic cell tumor, inflammatory angiomyolipoma, Hodgkin lymphoma, and inflammatory hepatocellular carcinoma.
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Affiliation(s)
- Donghai Wang
- Department of Pathology, New York University Grossman School of Medicine, NYU Langone Health, 560 First Avenue TH-483, New York, NY 10016, USA
| | - Joseph Misdraji
- Department of Pathology, Yale School of Medicine, Yale New Haven Hospital, 20 York Street EP2-611, New Haven, CT 06510, USA.
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15
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Naik M, Hesni S, Tamimi A, Hameed M, Tomlinson J, Poo S, Tam F, Strickland N, Barwick TD, Harvey CJ. Imaging manifestations of IgG4-related disease. Clin Radiol 2023; 78:555-564. [PMID: 37217396 DOI: 10.1016/j.crad.2023.03.003] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/27/2021] [Revised: 02/07/2023] [Accepted: 03/06/2023] [Indexed: 05/24/2023]
Abstract
IgG4-related disease is a multisystem immune-mediated disorder associated with lesions manifesting an IgG4-rich plasma cell infiltrate and often raised serum IgG4 concentrations. The disease can mimic neoplastic, infective, and inflammatory processes due to features such as development of masses or organ enlargement. Prompt consideration of this diagnosis is essential to avoid unnecessary investigations and offer appropriate treatments, which can include steroids and other immunosuppressive agents. Although histology is typically diagnostic, imaging is critical to assess disease burden, determine biopsy targets, and evaluate response to treatment. Characteristic imaging features can also point towards the diagnosis in the absence of biopsy. This review highlights these features, as well as more atypical findings, grouped by organ or system. Differential diagnoses are emphasised. The full spectrum of imaging methods is discussed. Whole-body imaging with integrated 2-[18F]-fluoro-2-deoxy-d-glucose (FDG) positron-emission tomography (PET)/computed tomography (CT) has an evolving role in the detection of multi-organ involvement and subsequent follow-up.
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Affiliation(s)
- M Naik
- Department of Radiology, Hammersmith Hospital, Du Cane Road, London W12 0HS, UK
| | - S Hesni
- Department of Radiology, Hammersmith Hospital, Du Cane Road, London W12 0HS, UK
| | - A Tamimi
- Department of Radiology, Hammersmith Hospital, Du Cane Road, London W12 0HS, UK
| | - M Hameed
- Department of Radiology, Hammersmith Hospital, Du Cane Road, London W12 0HS, UK
| | - J Tomlinson
- Department of Renal Medicine, Hammersmith Hospital, Du Cane Road, London W12 0HS, UK
| | - S Poo
- Department of Renal Medicine, Hammersmith Hospital, Du Cane Road, London W12 0HS, UK
| | - F Tam
- Department of Renal Medicine, Hammersmith Hospital, Du Cane Road, London W12 0HS, UK
| | - N Strickland
- Department of Radiology, Hammersmith Hospital, Du Cane Road, London W12 0HS, UK
| | - T D Barwick
- Department of Radiology, Hammersmith Hospital, Du Cane Road, London W12 0HS, UK
| | - C J Harvey
- Department of Radiology, Hammersmith Hospital, Du Cane Road, London W12 0HS, UK.
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16
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Dike CR, Sun QK, Rahib L, Golden M, Abu-El-Haija M. Extra-pancreatic manifestations reported in association with pancreatitis; an international survey report. PLoS One 2023; 18:e0288337. [PMID: 37432930 DOI: 10.1371/journal.pone.0288337] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/16/2023] [Accepted: 06/23/2023] [Indexed: 07/13/2023] Open
Abstract
BACKGROUND/OBJECTIVES Local and systemic manifestations have been reported in association with pancreatitis, anecdotally. However, a systematic collection on the prevalence of each of these symptoms in pancreatitis is lacking. We aimed to determine the prevalence of symptoms and diagnoses reported by a cohort of patients with pancreatitis, refer to as "extra pancreatic manifestation of pancreatitis". METHODS Cross-sectional study approved by the IRB and administered through a REDCap survey by "Mission: Cure", a nonprofit organization. RESULTS Of the 225 respondents analyzed; 89% were adults, 69% females, 89% Caucasians with 74% residing in the USA. 42% of children and 50% of adults reported exocrine pancreatic insufficiency while 8% of children and 26% of adults reported DM. Type 3c DM was reported in all children and 45% of adult DM cases. Children were diagnosed with genetic or hereditary pancreatitis more frequently compared to adults (33.3% versus 8%; p = <0.001). Significantly more symptoms and diagnoses were reported by adults when compared to children including nighttime sweats, bloating, or cramping, greasy or oily stools, feeling cold and GERD with p values of 0.002, 0.006, 0.046, 0.002 and 0.003 respectively. CONCLUSIONS Adults with pancreatitis frequently report symptoms not known to be associated with pancreatitis. Studies investigating mechanisms for these associated symptoms should be explored.
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Affiliation(s)
- Chinenye R Dike
- Department of Pediatrics, Division of Pediatric Gastroenterology, Hepatology and Nutrition, University of Nebraska Medical Center and Children's Hospital & Medical Center, Omaha, NE, United States of America
- Department of Pediatrics, Division of Pediatric Gastroenterology, Hepatology and Nutrition, University of Alabama at Birmingham, Birmingham, AL, United States of America
| | - Qin Kiki Sun
- Department of Pediatrics, Division of Biostatistics and Epidemiology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, United States of America
| | - Lola Rahib
- Mission: Cure, New York, New York, United States of America
| | - Megan Golden
- Mission: Cure, New York, New York, United States of America
| | - Maisam Abu-El-Haija
- Department of Pediatrics, Division of Pediatric Gastroenterology, Hepatology and Nutrition, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, United States of America
- University of Cincinnati, Department of Pediatrics, Division of Pediatric Gastroenterology, Hepatology and Nutrition, Cincinnati, OH, United States of America
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17
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Caverenne L, Weichselbaum L, Van Hoof M, Deltenre P. An unusual cause of extrahepatic cholestasis associated with solid liver lesions: a case report. Acta Gastroenterol Belg 2023; 86:490-492. [PMID: 37814566 DOI: 10.51821/86.3.10393] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/11/2023]
Abstract
IgG4-related sclerosing cholangitis is a special type of cholangiopathy often associated with autoimmune pancreatitis. In this article, we report an unusual case of IgG4-SC limited to the common hepatic duct and associated with pseudo tumoral liver lesions, but without evidence of pancreatic involvement. Corticosteroid therapy was rapidly effective and allowed normalization of liver tests.
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Affiliation(s)
- L Caverenne
- Department of Gastroenterology and Hepatology, Clinique St Luc, Bouge, Belgium
| | - L Weichselbaum
- Department of Gastroenterology and Hepatology, Clinique St Luc, Bouge, Belgium
| | - M Van Hoof
- Department of Gastroenterology and Hepatology, Clinique St Luc, Bouge, Belgium
| | - P Deltenre
- Department of Gastroenterology and Hepatology, Clinique St Luc, Bouge, Belgium
- Department of Gastroenterology, Hepatopancreatology, and Digestive Oncology, C.U.B. Hôpital Erasme, Université Libre de Bruxelles, Brussels, Belgium
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18
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Cho SH, Song TJ, Park JS, Yoon JH, Yang MJ, Yoon SB, Lee JM, Lee YN, Kim SH, Choi EK, Park SW, Oh D, Park DH, Lee SS, Seo DW, Lee SK, Kim MH. Comparison of the long-term outcomes between proximal and distal IgG4-related sclerosing cholangitis: A multicenter cohort study. J Gastroenterol Hepatol 2023; 38:648-655. [PMID: 36710432 DOI: 10.1111/jgh.16136] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/22/2022] [Revised: 01/11/2023] [Accepted: 01/27/2023] [Indexed: 01/31/2023]
Abstract
BACKGROUND AND AIMS Immunoglobulin G4-related sclerosing cholangitis (IgG4-SC) is considered a biliary manifestation of IgG4-related diseases. However, there has been a controversy on the clinical outcomes according to the location of the involved bile duct. We therefore compared the clinical outcomes and long-term prognosis of IgG4-SC with proximal bile duct involvement (proximal IgG4-SC) and IgG4-SC with distal bile duct involvement (distal IgG4-SC). METHODS We reviewed the data of patients with IgG4-SC that were prospectively collected at 10 tertiary centers between March 2002 and October 2020. Clinical manifestations, outcomes, association with autoimmune pancreatitis (AIP), steroid-responsiveness, and relapse of IgG4-SC were evaluated. RESULTS A total of 148 patients (proximal IgG4-SC, n = 59; distal IgG4-SC, n = 89) were analyzed. The median age was 65 years (IQR, 56.25-71), and 86% were male. The two groups were similar in terms of jaundice at initial presentation (51% vs 65%; P = 0.082) and presence of elevated serum IgG4 (66% vs 70%; P = 0.649). The two groups showed significant differences in terms of steroid-responsiveness (91% vs 100%; P = 0.008), association with AIP (75% vs 99%; P = 0.001), and occurrence of liver cirrhosis (9% vs 1%; P = 0.034). During a median follow-up of 64 months (IQR, 21.9-84.7), the cumulative relapse-free survival was significantly different between the two groups (67% vs 79% at 5 years; P = 0.035). CONCLUSIONS Relapse of IgG4-SC frequently occurred during follow-up. Proximal IgG4-SC and distal IgG4-SC had different long-term outcomes in terms of steroid-responsiveness, occurrence of liver cirrhosis, and recurrence. It may be advantageous to determine the therapeutic and follow-up strategies according to the location of bile duct involvement.
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Affiliation(s)
- Sung Hyun Cho
- Department of Gastroenterology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, South Korea
| | - Tae Jun Song
- Department of Gastroenterology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, South Korea
| | - Jin-Seok Park
- Division of Gastroenterology, Department of Internal Medicine, Inha University School of Medicine, Incheon, South Korea
| | - Jai Hoon Yoon
- Division of Gastroenterology, Department of Internal medicine, Hanyang University Hospital, Hanyang University College of Medicine, Seoul, South Korea
| | - Min Jae Yang
- Department of Gastroenterology, Ajou University School of Medicine, Suwon, South Korea
| | - Seung Bae Yoon
- Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, South Korea
| | - Jae Min Lee
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Korea University College of Medicine, Seoul, South Korea
| | - Yun Nah Lee
- Department of Gastroenterology, Soonchunhyang University School of Medicine, Bucheon, South Korea
| | - Seong-Hun Kim
- Division of Gastroenterology, Department of Internal Medicine, Jeonbuk National University Medical School, Research Institute of Clinical Medicine of Jeonbuk National University-Biomedical Research Institute of Jeonbuk National University Hospital, Jeonju, South Korea
| | - Eun Kwang Choi
- Department of Internal Medicine, Jeju National University School of Medicine, Jeju, South Korea
| | - Se Woo Park
- Division of Gastroenterology, Department of Internal Medicine, Hallym University Dongtan Sacred Heart Hospital, Hallym University College of Medicine, Gyeonggi-do, South Korea
| | - Dongwook Oh
- Department of Gastroenterology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, South Korea
| | - Do Hyun Park
- Department of Gastroenterology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, South Korea
| | - Sang Soo Lee
- Department of Gastroenterology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, South Korea
| | - Dong-Wan Seo
- Department of Gastroenterology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, South Korea
| | - Sung Koo Lee
- Department of Gastroenterology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, South Korea
| | - Myung-Hwan Kim
- Department of Gastroenterology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, South Korea
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Omer Mirghani M, Zia Z, Haytham Mawardi M, Almansouri Z, Ahmad N. IgG4-related inflammatory pseudotumor of the liver presenting as an incidental solitary liver mass. INTERNATIONAL JOURNAL OF HEPATOBILIARY AND PANCREATIC DISEASES 2023. [DOI: 10.5348/100101z04mm2023cr] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 03/06/2023]
Abstract
Inflammatory pseudotumor is increasingly being recognized as a definitive pathological entity affecting many organ systems and often difficult to distinguish from malignancy. We report a case of a 48-year-old female who presented with right hypochondrial pain associated with nausea and vomiting and recent weight loss. An ultrasound scan demonstrated gallstones without evidence of cholecystitis and an incidental 1.5 cm mass in the left liver lobe. A computed tomography (CT) and a magnetic resonance imaging (MRI) scan described the mass suspicious of a malignant tumour. An ultrasound-guided biopsy confirmed a benign inflammatory mass with lymphoplasmacytic infiltration staining for IgG4 and no evidence of malignancy. The patient had an elevated serum IgG4 levels. The patient was kept under surveillance. She underwent a laparoscopic cholecystectomy and at 18 months following the initial presentation the patient remains asymptomatic with stable liver lesion on ultrasound scan.
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Affiliation(s)
- Mohammed Omer Mirghani
- Department of Surgery, Section of Hepatobiliary and Transplantation Surgery, King Faisal Specialist Hospital and Research Centre, Jeddah, Saudi Arabia
| | - Zergham Zia
- Department of Radiology, King Faisal Specialist Hospital and Research Centre, Jeddah, Saudi Arabia
| | - Mohammad Haytham Mawardi
- Department of Medicine, King Faisal Specialist Hospital and Research Centre, Jeddah, Saudi Arabia
| | - Zuhoor Almansouri
- Department of Anatomic Pathology, King Faisal Specialist Hospital and Research Centre, Jeddah, Saudi Arabia
| | - Niaz Ahmad
- Departmet of Surgery, Section of Hepatobiliary and Transplantation Surgery, King Faisal Specialist Hospital and Research Centre, Jeddah, Saudi Arabia
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20
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Xu J, Bettendorf B, D'Oria M, Sharafuddin MJ. Multidisciplinary diagnosis and management of inflammatory aortic aneurysms. J Vasc Surg 2022:S0741-5214(22)02645-3. [PMID: 36565773 DOI: 10.1016/j.jvs.2022.12.024] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/05/2022] [Revised: 12/07/2022] [Accepted: 12/13/2022] [Indexed: 12/24/2022]
Abstract
BACKGROUND Inflammatory abdominal aortic aneurysms (IAAAs) are a variant involving a distinct immunoinflammatory process, with nearly one half believed to be associated with IgG4-related disease (IgG4-RD). METHODS MEDLINE and Google Scholar searches were conducted for English-language publications relevant to inflammatory aortic aneurysms from January 1970 onward. The search terms included inflammatory aortic aneurysms, aortitis, periaortitis, IgG4-related disease, and retroperitoneal fibrosis. Relevant studies were selected for review based on their relevance. RESULTS Morphologically, IAAAs are characterized by a thickened aneurysm wall often displaying contrast enhancement and elevated metabolic activity on fluorine-18 fluorodeoxyglucose-positron emission tomography imaging. A strong association exists with perianeurysmal and retroperitoneal fibrosis. Although the rupture risk appears lower with IAAAs than with noninflammatory abdominal aortic aneurysms (AAAs), the currently recommended diameter threshold for operative management is the same. Open repair has been associated with increased morbidity compared with noninflammatory AAAs, and a retroperitoneal approach or minimal dissection transperitoneal approach has been recommended to avoid duodenal and retroperitoneal structural injuries. Endovascular aneurysm repair has been increasingly used, especially for patients unfit for open surgery. It is important to exclude an infectious etiology before the initiation of immunosuppressive therapy or operative repair. Multimodality imaging follow-up is critical to monitor disease activity and secondary involvement of retroperitoneal structures by the associated fibrotic process. Maintenance of immunosuppressive therapy will be needed postoperatively for most patients with active systemic disease, especially those with IgG4-RD and those with persistent symptoms. Additional interventions aimed at ureteral decompression could also be required, and lifelong follow-up is mandatory. CONCLUSIONS Preoperative multimodality imaging is a diagnostic cornerstone for assessment of the disease extent and activity. IgG4-RD is an increasingly recognized category of IAAAs, with implications for tailoring adjunctive medical therapy. Open surgical repair remains the procedure of choice, although endovascular aneurysm repair is increasingly being offered. Maintenance immunosuppressive therapy can be offered according to the disease activity as assessed by follow-up imaging studies.
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Affiliation(s)
- Jun Xu
- Division of Vascular Surgery, University of Iowa Carver College of Medicine, Iowa City, IA
| | - Brittany Bettendorf
- Department of Internal Medicine, University of Iowa Carver College of Medicine, Iowa City, IA
| | - Mario D'Oria
- Division of Vascular and Endovascular Surgery, Cardiovascular Department, University Hospital of Trieste, Trieste, Italy
| | - Mel J Sharafuddin
- Division of Vascular Surgery, University of Iowa Carver College of Medicine, Iowa City, IA.
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21
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Patel N, Das P, Jain D. Systemic Manifestations of Gastrointestinal Tract Diseases and Systemic Diseases Involving the Gastrointestinal Tract. SURGICAL PATHOLOGY OF THE GASTROINTESTINAL SYSTEM 2022:521-572. [DOI: 10.1007/978-981-16-6395-6_14] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
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22
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Drazilova S, Veseliny E, Lenartova PD, Drazilova D, Gazda J, Grgurevic I, Janicko M, Jarcuska P. IgG4-Related Sclerosing Cholangitis: Rarely Diagnosed, but not a Rare Disease. Can J Gastroenterol Hepatol 2021; 2021:1959832. [PMID: 34970512 PMCID: PMC8714375 DOI: 10.1155/2021/1959832] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/10/2021] [Revised: 11/08/2021] [Accepted: 12/01/2021] [Indexed: 11/30/2022] Open
Abstract
IgG4-related sclerosing cholangitis, a biliary manifestation of an IgG4-related disease, belongs to the spectrum of sclerosing cholangiopathies which result in biliary stenosis. It presents with signs of cholestasis and during differential diagnosis it should be distinguished from cholangiocarcinoma or from other forms of sclerosing cholangitis (primary and secondary sclerosing cholangitis). Despite increasing information and recently established diagnostic criteria, IgG4-related sclerosing cholangitis remains underdiagnosed in routine clinical practice. The diagnosis is based on a combination of the clinical picture, laboratory parameters, histological findings, and a cholangiogram. Increased serum IgG4 levels are nonspecific but are indeed a part of the diagnostic criteria proposed by the Japan Biliary Association and the HISORt criteria for IgG4-SC. High serum IgG4 retains clinical utility depending on the magnitude of elevation. Approximately 90% of patients have concomitant autoimmune pancreatitis, while 10% present with isolated biliary involvement only. About 26% of patients have other organ involvement, such as IgG4-related dacryoadenitis/sialadenitis, IgG4-related retroperitoneal fibrosis, or IgG4-related renal lesions. A full-blown histological finding characterized by IgG4-enriched lymphoplasmacytic infiltrates, obliterative phlebitis, and storiform fibrosis is difficult to capture in practice because of its subepithelial localization. However, the histological yield is increased by immunohistochemistry, with evidence of IgG4-positive plasma cells. Based on a cholangiogram, IgG-4 related sclerosing cholangitis is classified into four subtypes according to the localization of stenoses. The first-line treatment is corticosteroids. The aim of the initial treatment is to induce clinical and laboratory remission and cholangiogram normalization. Even though 30% of patients have a recurrent course, in the literature data, there is no consensus on chronic immunosuppressive maintenance therapy. The disease has a good prognosis when diagnosed early.
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Affiliation(s)
- Sylvia Drazilova
- 2 Department of Internal Medicine, PJ Safarik University in Kosice and L. Pasteur University Hospital, Trieda SNP 1, 040 11 Kosice, Slovakia
| | - Eduard Veseliny
- 2 Department of Internal Medicine, PJ Safarik University in Kosice and L. Pasteur University Hospital, Trieda SNP 1, 040 11 Kosice, Slovakia
| | - Patricia Denisa Lenartova
- Department of Infectology and Travel Medicine, PJ Safarik University in Kosice and L. Pasteur University Hospital, Rastislavova 43, 040 01 Kosice, Slovakia
| | - Dagmar Drazilova
- 1 Faculty of Medicine, Charles University, Katerinska 1660/32, 121 08 Nove Mesto, Prague, Czech Republic
| | - Jakub Gazda
- 2 Department of Internal Medicine, PJ Safarik University in Kosice and L. Pasteur University Hospital, Trieda SNP 1, 040 11 Kosice, Slovakia
| | - Ivica Grgurevic
- Department of Gastroenterology, Hepatology and Clinical Nutrition, University of Zagreb School of Medicine and University Hospital Dubrava, Avenija Gojka Suska 6, 10000 Zagreb, Croatia
| | - Martin Janicko
- 2 Department of Internal Medicine, PJ Safarik University in Kosice and L. Pasteur University Hospital, Trieda SNP 1, 040 11 Kosice, Slovakia
| | - Peter Jarcuska
- 2 Department of Internal Medicine, PJ Safarik University in Kosice and L. Pasteur University Hospital, Trieda SNP 1, 040 11 Kosice, Slovakia
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23
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Notohara K. Histological features of autoimmune pancreatitis and IgG4-related sclerosing cholangitis with a correlation with imaging findings. J Med Ultrason (2001) 2021; 48:581-594. [PMID: 34669070 DOI: 10.1007/s10396-021-01148-5] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/06/2021] [Accepted: 09/03/2021] [Indexed: 12/12/2022]
Abstract
Autoimmune pancreatitis (AIP) is characterized by a tumefactive inflammatory lesion resembling pancreatic carcinoma. Type 1 AIP is a pancreatic manifestation of IgG4-related disease characterized by unique histological features that can be identified on imaging. The capsule-like rim, which is a collar of hypertrophic lesion surrounding the pancreas, consists of lymphoplasmacytic infiltration and fibrosis, and storiform fibrosis is often identified. Hypertrophic lesions of various microscopic architectures such as the ducts, veins (obliterative phlebitis), arteries (periarteritis), and nerves are observed without parenchymal damage. The pancreatic lobules keep their contours, but the acinar cells are diminished and replaced by numerous inflammatory cells. These features provide clues to arrive at a diagnosis of type 1 AIP and to distinguish it from pancreatic carcinoma on imaging. In contrast, type 2 AIP is an epithelium-centered inflammation involving the ducts and lobules. Neutrophilic infiltration in the epithelium and/or lumens (granulocytic epithelial lesion) is a characteristic finding. Lobular swelling due to inflammation is the cause of pancreatic enlargement. IgG4-related sclerosing cholangitis is histologically similar to the hypertrophic ductal lesion in type 1 AIP and characterized by wall thickening due to inflammation and luminal stenosis. The epithelium is intact, which is different from bile duct carcinomas and primary sclerosing cholangitis, the latter of which is characterized by inflammation targeting the epithelium. Although the histological features of type 1 AIP and IgG4-related sclerosing cholangitis are unique, the biopsy diagnosis of these diseases has limitations, which should be recognized by clinicians.
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Affiliation(s)
- Kenji Notohara
- Department of Anatomic Pathology, Kurashiki Central Hospital, 1-1-1 Miwa, Kurashiki, 710-8602, Japan.
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Abstract
Autoimmune pancreatitis (AIP) has attracted much attention in the last two decades, and due to the diagnostic value of immunoglobulin G4 (IgG4), the number of cases diagnosed in clinical practice has markedly increased. However, in contrast to prototypic IgG4-related type 1 AIP, a minor subtype of AIP, referred to as type 2 AIP, is less widely known and has thus not yet been characterized in detail. Type 2 AIP is unrelated to IgG4 and is a completely distinct entity from type 1 AIP. One confusing factor is that the two types of AIP share patterns of clinical presentation (e.g., acute pancreatitis and painless jaundice) and imaging abnormalities (e.g., diffuse or segmental enlargement). Since there are currently no established serum markers, the diagnosis of type 2 AIP is highly challenging and requires the tissue confirmation of neutrophilic injury to the pancreatic ducts, a finding designated as a granulocytic epithelial lesion. Approximately one-third of cases are associated with inflammatory bowel disease, particularly ulcerative colitis; however, the pathological relationship between these two conditions has not yet been clarified. Unanswered questions relate to its pathophysiology, the potential development of a similar granulocytic injury in other organs, and the characteristics of pediatric cases. This review summarizes consensus and controversies surrounding type 2 AIP, with the aim of increasing awareness and highlighting the unmet needs of this underrecognized condition.
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Affiliation(s)
- Yoh Zen
- Institute of Liver Studies, King's College Hospital & King's College London, London, UK
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25
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Song S, Jo S. Isolated mass-forming IgG4-related sclerosing cholangitis masquerading as extrahepatic cholangiocarcinoma: A case report. World J Clin Cases 2021; 9:8773-8781. [PMID: 34734055 PMCID: PMC8546832 DOI: 10.12998/wjcc.v9.i29.8773] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/26/2021] [Revised: 07/20/2021] [Accepted: 07/29/2021] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND IgG4-related sclerosing cholangitis (IgG4-RSC) is an uncommon benign disease, and its rarer, isolated and mass-forming subtype poses a significant challenge to differential diagnosis from cholangiocarcinoma of the extrahepatic bile duct. We herein report a case of isolated IgG4-RSC with an obstructing bile duct mass, for which extrahepatic bile duct resection was performed under the impression of proximal common bile duct (CBD) cancer.
CASE SUMMARY A 79-year-old male was admitted for jaundice that had developed 1 mo prior. There was no family history for autoimmune diseases or biliary cancer. Computed tomography (CT) and magnetic resonance cholangiopancreaticography revealed a short segmental concentric wall thickening of the proximal CBD with diffuse dilatation of the bile duct to the periphery. The endoscopic biopsy specimen showed no malignant cells. Positron emission tomography-CT showed a focal hypermetabolic lesion (SUVmax 4.2) in and around the proximal CBD area. With the impression of proximal CBD cancer, we performed segmental resection of the extrahepatic bile duct. Histopathology demonstrated marked sclerosis with diffuse lymphoplasmacytic infiltration and some eosinophils. Immunohistochemical staining for IgG4 showed increased positivity in some areas (up to 30/high-power field) and IgG4+/IgG+ cell ratio as 30%-50%. Pathologists’ impression was IgG4-related sclerosing disease. Follow-up serum IgG4 levels were continuously elevated; however, no evidence of relapse or other organ involvement related to IgG4-RSC presented.
CONCLUSION Isolated and mass-forming IgG4-RSC displays striking similarity with cholangiocarcinoma. To avoid unnecessary major surgery, high index of suspicion is needed.
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Affiliation(s)
- Sanghyun Song
- Department of Surgery, Dankook University Hospital, Cheonan 31116, Chungnam Province, South Korea
| | - Sungho Jo
- Department of Surgery, Dankook University Hospital, Cheonan 31116, Chungnam Province, South Korea
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Komori T, Inoue D, Izumozaki A, Sugiura T, Terada K, Yoneda N, Toshima F, Yoshida K, Kitao A, Kozaka K, Takahira M, Kawano M, Kobayashi S, Gabata T. Ultrasonography of IgG4-related dacryoadenitis and sialadenitis: Imaging features and clinical usefulness. Mod Rheumatol 2021; 32:986-993. [PMID: 34918161 DOI: 10.1093/mr/roab063] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/09/2021] [Revised: 06/27/2021] [Accepted: 08/12/2021] [Indexed: 11/13/2022]
Abstract
OBJECTIVES To clarify the ultrasonographic features of immunoglobulin G4 (IgG4)-related dacryoadenitis and sialadenitis (IgG4-DS) and their usefulness in clinical diagnostic sessions. METHODS By re-evaluating 96 consecutive patients with IgG4-related disease, we identified 54 patients (male:female = 37:17; median age, 69.5 years) who underwent lacrimal or submandibular gland (LG or SG, respectively) ultrasonography and computed tomography (CT). Their clinical and ultrasonographic features were retrospectively analysed. Radio-pathological correlations were also examined in LG (23 cases) and SG lesions (20 cases). Additionally, the diagnostic accuracy of CT for LG/SG lesions was evaluated. RESULTS Abnormal ultrasonographic findings were detected in 33 (LGs) and 38 (SGs) patients, and most of them were observed bilaterally. All lesions were well demarcated and demonstrated diffuse low-echoic areas (rocky pattern) or multiple low-echoic nodules surrounded by high-echoic linear shadows (cobblestone pattern) corresponding to intra-lobular inflammation and inter-lobular fibrosis. Moreover, 42% (LGs; 14/33) and 42% (SGs; 16/38) patients had glandular lesions without clinical symptoms associated with the affected glands. The diagnostic accuracy of CT was ∼80% for LG and 55% for SG. CONCLUSIONS Ultrasonographic findings in IgG4-DS included diffuse or nodular low-echoic areas with linear high-echoic structures corresponding to inflamed lobules and inter-lobular fibrosis. These findings can help detect IgG4-DS.
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Affiliation(s)
- Takahiro Komori
- Department of Radiology, Kanazawa University Graduate School of Medical Science, Kanazawa, Japan
| | - Dai Inoue
- Department of Radiology, Kanazawa University Graduate School of Medical Science, Kanazawa, Japan
| | - Akira Izumozaki
- Department of Radiology, Kanazawa University Graduate School of Medical Science, Kanazawa, Japan
| | - Takumi Sugiura
- Department of Radiology, Kanazawa University Graduate School of Medical Science, Kanazawa, Japan
| | - Kanako Terada
- Department of Radiology, Kanazawa University Graduate School of Medical Science, Kanazawa, Japan
| | - Norihide Yoneda
- Department of Radiology, Kanazawa University Graduate School of Medical Science, Kanazawa, Japan
| | - Fumihito Toshima
- Department of Radiology, Kanazawa University Graduate School of Medical Science, Kanazawa, Japan
| | - Kotaro Yoshida
- Department of Radiology, Kanazawa University Graduate School of Medical Science, Kanazawa, Japan
| | - Azusa Kitao
- Department of Radiology, Kanazawa University Graduate School of Medical Science, Kanazawa, Japan
| | - Kazuto Kozaka
- Department of Radiology, Kanazawa University Graduate School of Medical Science, Kanazawa, Japan
| | - Masayuki Takahira
- Department of Ophthalmology, Kanazawa University Graduate School of Medical Science, Kanazawa, Japan
| | - Mitsuhiro Kawano
- Division of Rheumatology, Department of Internal Medicine, Kanazawa University Graduate School of Medical Science, Kanazawa, Japan
| | - Satoshi Kobayashi
- Department of Radiology, Kanazawa University Graduate School of Medical Science, Kanazawa, Japan.,Department of Quantum Medical Imaging, Kanazawa University Graduate School of Medical Sciences, Kanazawa, Japan
| | - Toshifumi Gabata
- Department of Radiology, Kanazawa University Graduate School of Medical Science, Kanazawa, Japan
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IgG4-related hepatic inflammatory pseudotumor mimicking cholangiolocellular carcinoma. Clin J Gastroenterol 2021; 14:1733-1739. [PMID: 34570358 DOI: 10.1007/s12328-021-01526-z] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/07/2021] [Accepted: 09/22/2021] [Indexed: 10/20/2022]
Abstract
Inflammatory pseudotumor (IPT) is a benign tumor mass composed of chronic infiltration of inflammatory cells and fibrous tissue. IgG4-RD (related disease) in the hepatobiliary system has been widely recognized and includes IgG4-related hepatic IPT. This report describes a patient with IgG4-related hepatic IPT with sclerosing cholangitis. A 75-year-old woman was admitted to our hospital for the treatment of rectal cancer. Abdominal contrast-enhanced computed tomography revealed a low-density mass, 2.5 cm in diameter, in the left lateral lobe. Magnetic resonance imaging showed that the mass was slightly hypointense on T1-weighted images and slightly hyperintense on T2-weighted images. Based on these results, we made a diagnosis of cholangiolocellular carcinoma, and we performed a left hepatectomy. Histopathological examination showed that the mass was composed of fibrous stroma with dense lymphoplasmacytic infiltration. Immunohistochemically, IgG4-positive plasma cells were observed. The final diagnosis was IgG4-related hepatic IPT with sclerosing cholangitis. IgG4-related IPT is a relatively rare disease that can occur in any organ of the body. Although the accurate diagnosis of IgG4-related hepatic IPT remains difficult, IgG4-RD should be included in the differential diagnosis of liver tumors and histological analysis performed.
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28
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Okaniwa S. Role of transabdominal ultrasound in the diagnosis of autoimmune pancreatitis. J Med Ultrason (2001) 2021; 48:525-536. [PMID: 34476654 DOI: 10.1007/s10396-021-01133-y] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/28/2021] [Accepted: 07/20/2021] [Indexed: 01/05/2023]
Abstract
The most important thing in the diagnosis of autoimmune pancreatitis (AIP) is to suspect the possibility of AIP. In the acute phase, diffuse pancreatic enlargement is a highly specific finding of AIP compared to focal enlargement. Though the sensitivity is low, high-frequency transducers can detect the capsule-like rim sign and penetrating duct sign. Those findings are characteristic of AIP and useful for differential diagnosis with pancreatic carcinoma. In focal AIP, both contrast-enhanced US showing iso/hypervascularity and elastography showing increased stiffness not only in the focal enlargement but also in the surrounding parenchyma are also useful for differential diagnosis. Furthermore, changes over time after the two-week steroid trial, such as resolution or measurable reduction in parenchymal enlargement and a decrease in the mean shear-wave velocity on elastography, are also cardinal features of AIP. Since AIP is a pancreatic manifestation in immunoglobulin G4-related disease, evaluation of other organs, including the biliary tract and salivary glands, is particularly useful in focal AIP. A characteristic US finding of bile ducts is three-layered (high-low-high pattern) wall thickening with a markedly thickened middle layer. US can also detect wall thickening of bile ducts, which show no abnormalities on cholangiography. These findings are useful for differential diagnosis with cholangiocarcinoma. Multiple hypoechoic areas in submandibular glands are characteristic US findings of sialadenitis in type 1 AIP, and the sensitivity is higher than that of physical examination. US can further contribute to the diagnosis of AIP by employing elastography and contrast-enhanced US in addition to high-frequency transducers.
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Affiliation(s)
- Shinji Okaniwa
- Department of Gastroenterology, Iida Municipal Hospital, 438 Yawata-machi, Iida, Nagano, 395-8502, Japan.
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29
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Fibrohistiocytic Variant of Hepatic Pseudotumor: An Antibiotic Responsive Tumefactive Lesion. Am J Surg Pathol 2021; 45:1314-1323. [PMID: 34334689 DOI: 10.1097/pas.0000000000001767] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
Inflammatory pseudotumor is a term used to designate inflammation-rich tumefactive lesions. Following the exclusion of specific entities such as IgG4-related disease and other neoplastic entities previously included in this entity, the majority of hepatic pseudotumors show a prominent fibrohistiocytic inflammatory reaction and have been previously categorized as fibrohistiocytic variant of hepatic pseudotumor (FHVHPT). The goal of this study was to examine the clinical, radiologic, histologic, and etiologic aspects of this entity. After excluding neoplastic diseases, we identified 30 patients with FHVHPT from 3 institutions between 2009 and 2019. We extracted demographic and clinical data, liver function tests as well as culture results and radiologic information. Hematoxylin and eosin-stained slides were reviewed for pattern of inflammation as well as its cellular composition. Immunohistochemistry for IgG4 and IgG was performed in all cases. The mean age of the 30 lesions characterized as FHVHPT was 56 years (range: 23 to 79 y). Nineteen patients showed solitary lesions; 11 were multiple. The mean size of the lesion was 3.8 cm (range: 1 to 7.5 cm). On imaging, a neoplastic process or metastasis was the leading diagnostic consideration (n=15, 50%). The most common symptom was abdominal pain (n=14/30); 8 patients presented with symptoms compatible with an infectious process, including fever. The inflammatory infiltrate was dominated by lymphocytes and plasma cells, and in most cases, a prominent histiocytic infiltrate (22/30). Neutrophils were identified in 12 cases, with microabscess noted in 8. Storiform pattern of fibrosis was seen in 14/30 cases; obliterative phlebitis was not identified. Culture identified a microorganism in 4 of 9 cases evaluated. The mean IgG4 count was 9.3 per HPF (range: 0 to 51) with 9 of the 26 (35%) biopsies showing >10 IgG4 positive plasma cells per HPF. The mean IgG4 to IgG ratio was 8% (range: 8% to 46%). A hepatectomy was performed in 4 cases. On broad spectrum antibiotics (n=14) the lesions either resolved or decreased in size. Eight patients did not receive specific therapy, nevertheless, the lesion(s) resolved spontaneously in 6 cases, remained stable or decreased in size in 2 cases. Notably, none of these patients showed evidence of a hepatic recurrence. FHVHPT, a tumefactive lesion that mimics hepatic neoplasia, is histologically characterized by a fibrohistiocytic infiltrate. In the majority of patients FHVHPT represents the organizing phase of hepatic abscess and can be successfully managed with antibiotic therapy.
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30
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Nojima T, Nonaka M, Seo Y, Yamamura Y, Mukai M. Increased Expression of Activation-Induced Cytidine Deaminase in Sinus Mucosa from IgG4-Related Disease Patients with Comorbid Chronic Rhinosinusitis. ORL J Otorhinolaryngol Relat Spec 2021; 83:286-294. [PMID: 34077941 DOI: 10.1159/000515797] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/15/2021] [Accepted: 03/10/2021] [Indexed: 11/19/2022]
Abstract
OBJECTIVE IgG4-related disease (IgG4-RD) is a systemic condition characterized by an elevated serum IgG4 level, localized infiltration of IgG4-positive plasma cells, and lesions in various organs. IgG4-RD also shows high rates of complication with allergic diseases and is often accompanied by elevated serum IgE levels. Reports in recent years have also shown high rates of complication with chronic rhinosinusitis (CRS) and its characteristic nasal manifestations. Accordingly, we speculate that there may be a distinct form of CRS that, as an IgG4-RD, differs from other CRS. Here, we investigated whether the elevated levels of factors that are thought to be important in the pathogenesis of IgG4-RD are also seen in the sinus mucosa of IgG4-RD-associated CRS patients. METHODS Ethmoid sinus mucosa specimens from 9 IgG4-RD (6 Mikulicz disease and 3 Küttner's tumor) patients with elevated serum IgG4 and IgE and from 22 control CRS patients were examined immunohistochemically for Treg cytokines (IL-10 and TGF-β), activation-induced cytidine deaminase (AID), and immunocompetent cells. The 22 control CRS patients were divided into 3 subgroups based on the serological findings for IgG4 and IgE. Quantitative real-time PCR was performed to examine the expression of AID. RESULTS The ethmoid sinus mucosa from patients with IgG4-RD-associated CRS showed, in comparison with the 3 CRS control subgroups, significantly elevated AID production. Their mucosa also showed significantly increased infiltration of CD-20-positive immunocompetent cells compared with the controls. On the other hand, immunohistochemical examination found no significant differences in the number of IL-10- or TGF-β-positive cells. CONCLUSION Ethmoid sinus mucosa from IgG4-RD-associated CRS patients showed clearly increased AID production, suggesting AID involvement in class-switching to IgG4 in those local sites. This implies the existence of a distinct form of CRS that is an IgG4-RD.
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Affiliation(s)
- Tomohito Nojima
- Department of Otolaryngology, Tokyo Women's Medical University, Tokyo, Japan
| | - Manabu Nonaka
- Department of Otolaryngology, Tokyo Women's Medical University, Tokyo, Japan
| | - Yukako Seo
- Department of Otolaryngology, Tokyo Women's Medical University, Tokyo, Japan
| | - Yukie Yamamura
- Department of Otolaryngology, Tokyo Women's Medical University, Tokyo, Japan
| | - Masayoshi Mukai
- Department of Otolaryngology, Tokyo Women's Medical University, Tokyo, Japan
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31
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Kurita Y, Fujita Y, Sekino Y, Watanabe S, Iwasaki A, Kagawa K, Tanida E, Yagi S, Hasegawa S, Sato T, Hosono K, Kato S, Kobayashi N, Ichikawa Y, Endo I, Nakajima A, Kubota K. IgG4-related sclerosing cholangitis may be a risk factor for cancer. JOURNAL OF HEPATO-BILIARY-PANCREATIC SCIENCES 2021; 28:524-532. [PMID: 33931982 DOI: 10.1002/jhbp.957] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/14/2020] [Revised: 02/16/2021] [Accepted: 03/26/2021] [Indexed: 12/22/2022]
Abstract
BACKGROUND/PURPOSE The relationship between autoimmune pancreatitis (AIP) and malignancy has been reported. However, the potential risk for cancer in patients with immunoglobulin 4 (IgG4)-related sclerosing cholangitis (IgG4-SC) is unclear. The present study aimed to evaluate the incidence of cancer in IgG4-SC patients. METHODS We retrospectively collected clinical data for 121 patients diagnosed with IgG4-SC from 7 hospitals. We calculated the standardized incidence ratio (SIR) of cancer in IgG4-SC patients based on the national cancer rates. The SIR of the period after the diagnosis of IgG4-SC were calculated. RESULTS The mean follow-up period was 6.4 years, with 121 IgG4-SC patients. During the follow-up period, 26 patients had cancer, and 29 cancers were diagnosed. The SIR of cancer after the diagnosis of IgG4-SC was 1.90 (95% confidence interval [CI] 1.67-2.21). The SIR of pancreatic and bile duct cancer was 10.30 and 8.88, respectively. The SIR of cancer in <1 year, 1-5 years, and >5 years after diagnosis of IgG4-SC were 2.58, 1.01, and 2.44, respectively. CONCLUSIONS IgG4-SC patients have a high risk of cancer including pancreatic and bile duct cancer. The risk of cancer was high less <1 year and >5 years after diagnosis of IgG4-SC. Therefore, IgG4-SC patients may require careful long-term follow-up.
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Affiliation(s)
- Yusuke Kurita
- Department of Gastroenterology and Hepatology, Yokohama City University Hospital, Yokohama, Japan
| | - Yuji Fujita
- Department of Hepato-Biliary-Pancreatic Medicine, NTT Medical Center Tokyo, Tokyo, Japan
| | - Yusuke Sekino
- Department of Gastroenterology, Yokohama Rosai Hospital, Yokohama, Japan
| | - Seitaro Watanabe
- Department of Gastroenterology, Yokohama Sakae Kyosai Hospital, Yokohama, Japan
| | - Akito Iwasaki
- Department of Gastroenterology, Hiratsuka City Hospital, Hiratsuka, Japan
| | - Koichi Kagawa
- Department of Gastroenterology, Keiyu Hospital, Yokohama, Japan
| | - Emiko Tanida
- Department of Gastroenterology, Machida Municipal Hospital, Tokyo, Japan
| | - Shin Yagi
- Department of Gastroenterology and Hepatology, Yokohama City University Hospital, Yokohama, Japan
| | - Sho Hasegawa
- Department of Gastroenterology and Hepatology, Yokohama City University Hospital, Yokohama, Japan
| | - Takamitsu Sato
- Department of Gastroenterology and Hepatology, Yokohama City University Hospital, Yokohama, Japan
| | - Kunihiro Hosono
- Department of Gastroenterology and Hepatology, Yokohama City University Hospital, Yokohama, Japan
| | - Shingo Kato
- Department of Gastroenterology and Hepatology, Yokohama City University Hospital, Yokohama, Japan
| | | | - Yasushi Ichikawa
- Department of Oncology, Yokohama City University Hospital, Yokohama, Japan
| | - Itaru Endo
- Department of Gastroenterological Surgery, Yokohama City University Hospital, Yokohama, Japan
| | - Atsushi Nakajima
- Department of Gastroenterology and Hepatology, Yokohama City University Hospital, Yokohama, Japan
| | - Kensuke Kubota
- Department of Gastroenterology and Hepatology, Yokohama City University Hospital, Yokohama, Japan
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32
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Mukai K, Nishida T, Adachi S, Matsumoto K, Osugi N, Sugimoto A, Nakamatsu D, Yamamoto M, Fukui K, Tamura H, Inada M. Immunoglobulin G4-Hepatopathy with Acute Hepatitis-Like Onset and Marked Centrilobular Necrosis: Clinicopathologically Unique Pattern of Hepatic Injury Related to Immunoglobulin G4-Related Disease. Case Rep Gastroenterol 2021; 15:720-728. [PMID: 34594172 PMCID: PMC8436635 DOI: 10.1159/000516313] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/25/2021] [Accepted: 03/19/2021] [Indexed: 11/22/2022] Open
Abstract
A 69-year-old man presented with jaundice and appetite loss. Blood analyses showed elevated aminotransferase levels, hyperbilirubinemia, positivity for antinuclear antibody, elevated immunoglobulin (Ig) G4 levels, and negativity for hepatitis virus markers. Additionally, computed tomography revealed a focal enlargement of the pancreatic body and enhancement of the peripheral bile ducts. Liver biopsy showed interface hepatitis, supporting a clinical diagnosis of autoimmune hepatitis (AIH). Immunohistochemistry revealed that IgG4-bearing plasma cells accounted for more than 60% of the IgG-bearing plasma cells in the portal area. Then, we started oral prednisolone therapy. After tapering, serum transaminase levels became elevated again, and we had to adjust the dose. Azathioprine maintenance therapy was necessary to prevent relapse. We herein report a case of IgG4-hepatopathy with a clinical course similar to that of AIH with acute onset.
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Affiliation(s)
- Kaori Mukai
- Department of Gastroenterology and Hepatology, Toyonaka Municipal Hospital, Toyonaka, Japan
| | - Tsutomu Nishida
- Department of Gastroenterology and Hepatology, Toyonaka Municipal Hospital, Toyonaka, Japan
| | - Shiro Adachi
- Department of Pathology, Toyonaka Municipal Hospital, Toyonaka, Japan
| | - Kengo Matsumoto
- Department of Gastroenterology and Hepatology, Toyonaka Municipal Hospital, Toyonaka, Japan
| | - Naoto Osugi
- Department of Gastroenterology and Hepatology, Toyonaka Municipal Hospital, Toyonaka, Japan
| | - Aya Sugimoto
- Department of Gastroenterology and Hepatology, Toyonaka Municipal Hospital, Toyonaka, Japan
| | - Dai Nakamatsu
- Department of Gastroenterology and Hepatology, Toyonaka Municipal Hospital, Toyonaka, Japan
| | - Masashi Yamamoto
- Department of Gastroenterology and Hepatology, Toyonaka Municipal Hospital, Toyonaka, Japan
| | - Koji Fukui
- Department of Gastroenterology and Hepatology, Toyonaka Municipal Hospital, Toyonaka, Japan
| | - Hiromi Tamura
- Department of Pathology, Toyonaka Municipal Hospital, Toyonaka, Japan
| | - Masami Inada
- Department of Gastroenterology and Hepatology, Toyonaka Municipal Hospital, Toyonaka, Japan
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Nakazawa T, Kamisawa T, Okazaki K, Kawa S, Tazuma S, Nishino T, Inoue D, Naitoh I, Watanabe T, Notohara K, Kubota K, Ohara H, Tanaka A, Takikawa H, Masamune A, Unno M. Clinical diagnostic criteria for IgG4-related sclerosing cholangitis 2020: (Revision of the clinical diagnostic criteria for IgG4-related sclerosing cholangitis 2012). JOURNAL OF HEPATO-BILIARY-PANCREATIC SCIENCES 2021; 28:235-242. [PMID: 33586343 DOI: 10.1002/jhbp.913] [Citation(s) in RCA: 33] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/07/2020] [Revised: 12/15/2020] [Accepted: 02/07/2021] [Indexed: 12/24/2022]
Abstract
Several years have passed since the clinical diagnostic criteria for IgG4-related sclerosing cholangitis 2012 were published. New findings and knowledge have accumulated since then. The Research Committees for IgG4-related Diseases and for Intractable Diseases of the Liver and Biliary Tract, in association with the Ministry of Health, Labor, and Welfare of Japan and the Japan Biliary Association, have established a working group consisting of researchers specializing in IgG4-SC and have drawn up new clinical diagnostic criteria for IgG4-SC 2020. The diagnosis of IgG4-SC is based on a combination of the following six criteria: (a) narrowing of the intra- or extrahepatic bile duct; (b) thickening of the bile duct wall; (c) serological findings; (d) pathological findings; (e) other organ involvement; and (f) effectiveness of steroid therapy. These new diagnostic criteria for IgG4-SC are useful in practice for general physicians and other non-specialists.
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Affiliation(s)
- Takahiro Nakazawa
- Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan
| | - Terumi Kamisawa
- Department of Internal Medicine, Tokyo Metropolitan, Komagome Hospital, Tokyo, Japan
| | - Kazuichi Okazaki
- Department of Internal Medicine, Kansai Medical University Kori Hospital, Neyagawa, Japan
| | - Shigeyuki Kawa
- Department of Internal Medicine, Matsumoto Dental University, Shiojiri, Japan
| | - Susumu Tazuma
- Department of General Internal Medicine, Hiroshima University Graduate School of Biomedical & Health Science, Hiroshima, Japan
| | - Takayoshi Nishino
- Department of Gastroenterology, Tokyo Womens' Medical University Yachiyo Medical Center, Yachiyo, Japan
| | - Dai Inoue
- Department of Radiology, Kanazawa University Graduate School of Medical Sciences, Kanazawa, Japan
| | - Itaru Naitoh
- Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan
| | - Takayuki Watanabe
- Department of Medicine, Gastroenterology, Shinshu University, Matsumoto, Nagano, Japan
| | - Kenji Notohara
- Department of Anatomic Pathology, Kurashiki Central Hospital, Kurashiki, Japan
| | - Kensuke Kubota
- Department of Endoscopy, Yokohama City University Hospital, Yokohama, Japan
| | - Hirotaka Ohara
- Department of Community-Based Medical Education, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan
| | - Atsushi Tanaka
- Department of Medicine, Teikyo University School of Medicine, Tokyo, Japan
| | - Hajime Takikawa
- Department of Medicine, Teikyo University School of Medicine, Tokyo, Japan
| | - Atsushi Masamune
- Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai, Japan
| | - Michiaki Unno
- Division of Hepato-Biliary Pancreatic Surgery, Tohoku University Graduate School of Medicine, Sendai, Japan
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Nasser R, Gilshtein H, Mansour S, Yasin K, Borzellino G, Khuri S. Isolated Type Immunoglobulin G4 Sclerosing Cholangitis: The Misdiagnosed Cholangiocarcinoma. J Clin Med Res 2021; 13:75-81. [PMID: 33747321 PMCID: PMC7935625 DOI: 10.14740/jocmr4428] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/14/2021] [Accepted: 01/21/2021] [Indexed: 12/13/2022] Open
Abstract
Immunoglobulin G4 sclerosing cholangitis (IgG4-SC), firstly described in 2004, is the biliary manifestation of a recently described multisystem immune-mediated disease known as IgG4-related disease. IgG4-SC is a unique and rare type of cholangitis of unknown etiology and its precise prevalence rate is still unclear. It is characterized by bile duct wall thickening and high levels of systemic serum IgG4 plasma cells. Differential diagnoses for IgG4-SC include benign (primary sclerosing cholangitis) as well as malignant (extra-hepatic cholangiocarcinoma) diseases. Discrimination between these entities is very important, due to the fact that they have different biological behaviors and different therapeutic strategies. The rare IgG4-SC subgroup with its puzzling manifestations carries a hefty diagnostic challenge for the treating physicians, and inaccurate diagnosis can lead to unnecessary morbid surgical procedures. With the paucity and relative weakness of available data in the current literature, one needs to carefully review all available parameters. A low threshold of suspicion is required to try and prevent missing IgG4-SC. IgG4-SC is highly responsive to steroid treatment, especially during the early inflammatory phase, while delay in management could lead to fibrosis and organ dysfunction. On the other hand, cholangiocarcinoma is treated by means of surgery and/or chemotherapeutic agents.
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Affiliation(s)
- Roni Nasser
- Gastroenterology and Hepatology Department, Rambam Health Care Campus, Haifa, Israel
| | - Hayim Gilshtein
- Colorectal Surgery Unit, General Surgery Department, Rambam Health Care Campus, Haifa, Israel
| | - Subhi Mansour
- HPB and Surgical Oncology Unit, General Surgery Department, Rambam Health Care Campus, Haifa, Israel
| | - Kamel Yasin
- Gastroenterology and Hepatology Department, Rambam Health Care Campus, Haifa, Israel
| | | | - Safi Khuri
- HPB and Surgical Oncology Unit, General Surgery Department, Rambam Health Care Campus, Haifa, Israel
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35
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Zhang Z, Guan W, Lin Q, Yu W. Thoracic paravertebral involvement in patients with IgG4-related disease: CT and MR imaging findings. Rheumatology (Oxford) 2021; 59:3878-3885. [PMID: 32556185 DOI: 10.1093/rheumatology/keaa254] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/06/2019] [Revised: 03/19/2020] [Indexed: 11/14/2022] Open
Abstract
OBJECTIVES To retrospectively evaluate CT and magnetic resonance (MR) imaging thoracic paravertebral findings at baseline and follow-up in patients with IgG4-related disease. METHODS The study consisted of 36 patients with IgG4-related disease involving thoracic paravertebral regions (32 men and four women; mean age, 58 years; range, 25-78 years). A total of 36 patients underwent CT or MR imaging at baseline; 20 patients underwent follow-up. CT and MR images were reviewed and analysed in consensus by two radiologists for the various features of thoracic paravertebral lesions. RESULTS All lesions were located around two or more thoracic vertebrae, particularly the lower thoracic vertebrae (n = 36). The right side of vertebrae was predominantly affected in all cases (n = 36). Radiologically, IgG4-related thoracic paravertebral lesions were categorized into three types: solitary or multiple saddle-like masses type (32 patients); multiple nodules type (three patients); and invasively irregular mass type (three patients). All the types showed soft-tissue density on CT images, isointense on T1- and T2-weighted images, and homogeneous enhancement with penetration of small arteries in the lesions on contrast-enhanced CT and MR images. Steroid therapy administered to 20 patients dramatically diminished the mean maximum thickness in 18 patients. One patient with T7-12 vertebrae involved improved after steroid therapy. CONCLUSION IgG4-related paravertebral lesions occur mainly around the right side of the lower thoracic vertebrae and manifest as three major patterns of CT and MR imaging findings. Recognition of these diagnostic features will assist in the diagnosis and treatment of IgG4-related disease.
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Affiliation(s)
- Zaizhu Zhang
- Department of Radiology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China
| | - Wenmin Guan
- Department of Radiology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China
| | - Qiang Lin
- Department of Radiology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China
| | - Wei Yu
- Department of Radiology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China
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Goyal S, Sakhuja P. Autoimmune pancreatitis: Current perspectives. INDIAN J PATHOL MICR 2021; 64:S149-S159. [PMID: 34135159 DOI: 10.4103/ijpm.ijpm_59_21] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022] Open
Abstract
Over the last two decades, our knowledge and understanding regarding the pathogenesis and biology of autoimmune pancreatitis (AIP) have improved tremendously. Type 1 AIP or IgG4-related pancreatitis (IgG4-RP) is now believed to be the prototype of the multisystemic IgG4-related disease. In view of clinical features like obstructive jaundice and mass-forming lesions in the pancreas in elderly men, type 1 AIP often mimics pancreatic cancer. IgG4-related sclerosing cholangitis concomitantly involving the extrahepatic and intrahepatic biliary tree is the most common extrapancreatic involvement seen in up to 80% of these patients, which needs to distinguish from cholangiocarcinoma. Histology is characterised by lymphoplasmacytic inflammation, abundant IgG4 positive plasma cell infiltration, storiform fibrosis and obliterative phlebitis. Apart from histology, high serum IgG4 levels, pancreatic parenchymal and duct imaging findings and other organ involvement aid in diagnosis especially in cases where definitive histology is not evident. Also, these parameters lay the foundation of various diagnostic criteria proposed over last few years. On the contrary, histology alone is the mainstay for establishing diagnosis of idiopathic duct-centric pancreatitis (IDCP) as it lacks any specific serological marker or imaging. Since both types of AIP respond dramatically to corticosteroid treatment, a biopsy is crucial to establish the preoperative diagnosis and to exclude malignancy so as to avoid unnecessary surgery. This review discusses the morphologic spectrum, treatment and prognosis of IgG4-RP and IDCP with an emphasis on approach to diagnosis with relevant histologic features, differential diagnoses and the challenges faced during biopsy interpretation.
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Affiliation(s)
- Surbhi Goyal
- Department of Pathology, GIPMER, New Delhi, India
| | - Puja Sakhuja
- Department of Pathology, GIPMER, New Delhi, India
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Akyol S, Öz Atalay F, Hasdemir S, Yerci Ö. IgG4-Related Disease of the Ovary. Turk Patoloji Derg 2021; 37:63-66. [PMID: 32779156 PMCID: PMC10508929 DOI: 10.5146/tjpath.2020.01500] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/08/2020] [Accepted: 07/19/2020] [Indexed: 11/18/2022] Open
Abstract
Immunoglobulin G4-related disease is characterized by dense fibrosis, obliterative phlebitis, and lymphoplasmacytic infiltration that contains abundant IgG4 positive plasma cells. It causes tumefactive lesions in the involved organs and is most commonly seen in the salivary glands, pancreas, and retroperitoneum. Ovarian involvement has been reported in only two cases. In our case, a 58-year-old female patient presented with abdominal distention and pain. Pelvic computed tomography revealed a soft tissue lesion compatible with the omental cake, several intraabdominal implants, and bilateral adnexal fullness. A laparotomy was performed under suspicion of peritoneal carcinomatosis secondary to bilateral adnexal mass. In the histopathologic examination, abundant lymphoplasmacytic infiltration and dense fibrosis were observed in both ovaries and the peritoneum. In the areas of greatest density, the density of IgG4-positive plasma cells was found to range from 40 to 50 per high-power field. The patient was accepted as suffering from probable IgG4-related disease because of the bilateral involvement of the ovaries and the histopathological findings. In conclusion, we present this case to draw attention to the fact that IgG4-related disease can also be seen in the ovary.
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Affiliation(s)
- Sevda Akyol
- Department of Pathology, Bursa Uludag University Faculty of Medicine, Bursa, Turkey
| | - Fatma Öz Atalay
- Department of Pathology, Bursa Uludag University Faculty of Medicine, Bursa, Turkey
| | - Secil Hasdemir
- Department of Pathology, Bursa Uludag University Faculty of Medicine, Bursa, Turkey
| | - Ömer Yerci
- Department of Pathology, Bursa Uludag University Faculty of Medicine, BURSA, TURKEY
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Mačinga P, Jarošová J, Špičák J, Hucl T. [Immunoglobulin G4-related disease in gastroenterology]. VNITRNI LEKARSTVI 2021; 67:76-83. [PMID: 34074105 DOI: 10.36290/vnl.2021.018] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/02/2025]
Abstract
IgG4-related disease is a recently defined clinical entity that can manifest itself in any organ. The most common gastrointestinal manifestations are diseases of the pancreas (autoimmune pancreatitis type 1) and biliary tree (IgG4-associated cholangitis); involvement of liver parenchyma is uncommon and the affection of tubular organs is very rare. IgG4-related pancreatitis and cholangitis can mimic malignancies in their clinical presentation. Diagnosis is often difficult and requires careful evaluation of the combination of symptoms, serology and imaging findings, while adhering to the established diagnostic criteria. The first line of treatment is the administration of corticoids and the remission is achieved in the vast majority of patients. In case of contraindication, intolerance or failure of corticotherapy, patients should receive B cell depletion therapy (rituximab). Based on the available knowledge, monotherapy with other immunosuppressants is not considered to be sufficiently effective. Some patients may benefit from maintenance treatment to prevent relapse, which is otherwise common in both IgG4-related pancreatitis and cholangitis. Recognized IgG4-related disease has a good prognosis, but some patients develop irreversible fibrotic changes in the affected organ with consequent dysfunction; the possible association of the disease with a higher risk of malignancy has not yet been reliably elucidated.
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39
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Song J, Li Y, Bowlus CL, Yang G, Leung PSC, Gershwin ME. Cholangiocarcinoma in Patients with Primary Sclerosing Cholangitis (PSC): a Comprehensive Review. Clin Rev Allergy Immunol 2020; 58:134-149. [PMID: 31463807 DOI: 10.1007/s12016-019-08764-7] [Citation(s) in RCA: 55] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Cholangiocarcinoma (CCA) is the most common malignancy in patients with primary sclerosing cholangitis (PSC) and carries a high rate of mortality. Although the pathogenesis of CCA in PSC is largely unknown, inflammation-driven carcinogenesis concomitant with various genetic and epigenetic abnormalities are underlying factors. The majority of CCA cases develop from a dominant stricture (DS), which is defined as a stricture with a diameter < 1.5 mm in the common bile duct or < 1.0 mm in the hepatic duct. In PSC patients presenting with an abrupt aggravation of jaundice, pain, fatigue, pruritus, weight loss, or worsening liver biochemistries, CCA should be suspected and evaluated utilizing a variety of diagnostic modalities. However, early recognition of CCA in PSC remains a major challenge. Importantly, 30-50% of CCA in PSC patients are observed within the first year following the diagnosis of PSC followed by an annual incidence ranging from 0.5 to 1.5 per 100 persons, which is nearly 10 to 1000 times higher than that in the general population. Cumulative 5-year, 10-year, and lifetime incidences are 7%, 8-11%, and 9-20%, respectively. When PSC-associated CCA is diagnosed, most tumors are unresectable, and no effective medications are available. Given the poor therapeutic outcome, the surveillance and management of PSC patients who are at an increased risk of developing CCA are of importance. Such patients include older males with large-duct PSC and possibly concurrent ulcerative colitis. Thus, more attention should be paid to patients with these clinical features, in particular within the first year after PSC diagnosis. In contrast, CCA is less frequently observed in pediatric or female PSC patients or in those with small-duct PSC or concurrent Crohn's disease. Recently, new biomarkers such as antibodies to glycoprotein 2 have been found to be associated with an increased risk of developing CCA in PSC. Herein, we review the literature on the pathogenesis, incidence, clinical features, and risk factors, with a focus on various diagnostic modalities of PSC-associated CCA.
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Affiliation(s)
- Junmin Song
- Department of Gastroenterology, Shengjing Hospital of China Medical University, No. 36 Sanhao Street, Heping District, Shenyang, 110004, Liaoning, People's Republic of China.,Division of Rheumatology, Allergy and Clinical Immunology, University of California, 451 Health Science Drive, Suite 6510, Davis, CA, 95616, USA
| | - Yang Li
- Department of Intensive Care Unit (ICU), Shengjing Hospital of China Medical University, No. 36 Sanhao Street, Heping District, Shenyang, Liaoning, 110004, People's Republic of China
| | - Christopher L Bowlus
- Division of Gastroenterology and Hepatology, University of California, 451 Health Sciences Drive, Suite 6510, Davis, CA, 95616, USA
| | - GuoXiang Yang
- Division of Rheumatology, Allergy and Clinical Immunology, University of California, 451 Health Science Drive, Suite 6510, Davis, CA, 95616, USA
| | - Patrick S C Leung
- Division of Rheumatology, Allergy and Clinical Immunology, University of California, 451 Health Science Drive, Suite 6510, Davis, CA, 95616, USA.
| | - M Eric Gershwin
- Division of Rheumatology, Allergy and Clinical Immunology, University of California, 451 Health Science Drive, Suite 6510, Davis, CA, 95616, USA.
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Perugino CA, Stone JH. IgG4-related disease: an update on pathophysiology and implications for clinical care. Nat Rev Rheumatol 2020; 16:702-714. [PMID: 32939060 DOI: 10.1038/s41584-020-0500-7] [Citation(s) in RCA: 206] [Impact Index Per Article: 41.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 08/21/2020] [Indexed: 12/14/2022]
Abstract
IgG4-related disease (IgG4-RD) has only existed as a unique disease entity since 2003, yet remarkable progress has already been achieved in describing the essential features of the disease. A framework for systematic clinical studies has been created by the development of a quantitative disease activity tool (the IgG4-RD Responder Index) and the validation of classification criteria, both of which were the products of international, multi-centre investigations. In addition, substantial strides have been made in understanding the pathophysiology of IgG4-RD. In particular, the central role of B cells in the disease has been demonstrated by both the robust clinical responsiveness of IgG4-RD to B cell depletion and by the identification of multiple self-antigens that promote B cell expansion. CD4+ T cells have also been investigated in detail; CD4+ cytotoxic T lymphocytes (suspected of promoting disease) and a specific T follicular helper cell subset that contributes to IgG4 isotype switching have both been defined by multiple groups. The mechanisms by which these immune cells converge on target tissues, interact with fibroblasts and promote tissue remodelling are beginning to be understood and will be an important research focus in the coming years.
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Affiliation(s)
- Cory A Perugino
- Massachusetts General Hospital, Division of Rheumatology, Allergy and Immunology, Boston, MA, USA.,Ragon Institute of MGH, MIT and Harvard, Cambridge, MA, USA
| | - John H Stone
- Massachusetts General Hospital, Division of Rheumatology, Allergy and Immunology, Boston, MA, USA.
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Ishii Y, Serikawa M, Tsuboi T, Kawamura R, Tsushima K, Nakamura S, Hirano T, Fukiage A, Ikemoto J, Kiyoshita Y, Saeki S, Tamura Y, Chayama K. Usefulness of peroral cholangioscopy in the differential diagnosis of IgG4-related sclerosing cholangitis and extrahepatic cholangiocarcinoma: a single-center retrospective study. BMC Gastroenterol 2020; 20:287. [PMID: 32831026 PMCID: PMC7445926 DOI: 10.1186/s12876-020-01429-2] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/18/2020] [Accepted: 08/17/2020] [Indexed: 02/08/2023] Open
Abstract
BACKGROUND In the diagnosis of IgG4-related sclerosing cholangitis (IgG4-SC), differentiation from extrahepatic cholangiocarcinoma (ECC) is extremely important but is still a clinical challenge. This study aimed to elucidate the usefulness of peroral cholangioscopy (POCS) for the differential diagnosis between IgG4-SC and ECC. METHODS POCS findings for bile duct stricture were retrospectively evaluated in 17 patients with IgG4-SC diagnosed at the Hiroshima University Hospital and 53 patients with surgically resected infiltrating ECC. Mucosal surface, dilated vessels (tortuosity, caliber alteration, and disruption), and easily bleeding were compared between the groups. RESULTS The stricture sites of IgG4-SC evaluated by POCS were 10 extrapancreatic bile ducts and 9 intrapancreatic bile ducts. In patients with IgG4-SC, smooth mucosal surface was observed in 89% (17/19), dilated vessels in 58% (11/19) [tortuosity 82% (9/11), caliber alteration 18% (2/11), and disruption 9% (1/11)], and easily bleeding in 0%. Irregular mucosal surface and easily bleeding were observed significantly more frequently in ECC (both P < 0.001). The frequency of caliber alteration and disruption of dilated vessels was significantly less in IgG4-SC (P < 0.001 and 0.005, respectively). The sensitivity and specificity of POCS in the diagnosis of ECC were 96 and 89%, respectively. Dilated vessels in IgG4-SC were observed significantly more frequently in the extrapancreatic bile duct, especially the hilar bile duct (P = 0.006). Concerning image evaluation, the interobserver agreement was κ = 0.719, and the intraobserver agreement was κ = 0.768 and 0.754. CONCLUSIONS Characteristic POCS findings of the stricture sites in IgG4-SC were smooth mucosal surface, dilated vessels without caliber alteration and disruption, and lack of easily bleeding. These POCS findings are extremely useful for distinguishing between IgG4-SC and ECC.
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Affiliation(s)
- Yasutaka Ishii
- Department of Gastroenterology and Metabolism, Graduate School of Biomedical & Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan.
| | - Masahiro Serikawa
- Department of Gastroenterology and Metabolism, Graduate School of Biomedical & Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan
| | - Tomofumi Tsuboi
- Department of Gastroenterology and Metabolism, Graduate School of Biomedical & Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan
| | - Ryota Kawamura
- Department of Gastroenterology and Metabolism, Graduate School of Biomedical & Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan
| | - Ken Tsushima
- Department of Gastroenterology and Metabolism, Graduate School of Biomedical & Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan
| | - Shinya Nakamura
- Department of Gastroenterology and Metabolism, Graduate School of Biomedical & Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan
| | - Tetsuro Hirano
- Department of Gastroenterology and Metabolism, Graduate School of Biomedical & Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan
| | - Ayami Fukiage
- Department of Gastroenterology and Metabolism, Graduate School of Biomedical & Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan
| | - Juri Ikemoto
- Department of Gastroenterology and Metabolism, Graduate School of Biomedical & Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan
| | - Yusuke Kiyoshita
- Department of Gastroenterology and Metabolism, Graduate School of Biomedical & Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan
| | - Sho Saeki
- Department of Gastroenterology and Metabolism, Graduate School of Biomedical & Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan
| | - Yosuke Tamura
- Department of Gastroenterology and Metabolism, Graduate School of Biomedical & Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan
| | - Kazuaki Chayama
- Department of Gastroenterology and Metabolism, Graduate School of Biomedical & Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan
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Abstract
Autoimmune liver diseases comprise a spectrum of progredient idiopathic inflammatory diseases. Typical histological features of autoimmune hepatitis (AIH) include the pattern of chronic hepatitis with predominant plasma cell-rich interface activity, rosetting of hepatocytes, and emperipolesis. Florid bile duct lesions are the key feature of primary biliary cholangitis (PBC); onion-like periductal fibrosis characterizes the primary sclerosing cholangitis (PSC). Variants of AIH, or overlap syndromes, show intersecting histomorphologic findings with PBC or PSC. The diagnosis of the different autoimmune inflammatory liver diseases is based on clinical presentation, a hepatitic or cholestatic pattern of liver enzymes, immuno-serological findings, image analysis in PSC, and liver biopsy as a facultative or obligatory adjunct. Liver biopsy plays a major role in the diagnosis of AIH, small-duct PSC, AMA-negative PBC, IgG4-related diseases, overlap syndrome, and in the recognition of concurrent liver diseases, especially drug-induced liver diseases. Herewith pathologists can help clinicians find adequate therapy for different autoimmune inflammatory liver diseases.
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Affiliation(s)
- Hans-Peter Fischer
- Institut für Pathologie, Universität Bonn, Venusberg-Campus 1, 53127, Bonn, Deutschland.
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IgG4-related disease in the abdomen and pelvis: atypical findings, pitfalls, and mimics. Abdom Radiol (NY) 2020; 45:2485-2499. [PMID: 32300834 DOI: 10.1007/s00261-020-02526-2] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
IgG4-related disease (IgG4-RD) is a systemic, autoimmune, fibroinflammatory disease that can cause multi-organ damage. Although there have been many trials and studies since its recognition in 2003, there is still much that is unknown. Furthermore, IgG4-RD can affect any organ in the body and often has many mimics and alternative diagnoses, which can make for a challenging workup. Imaging plays a substantial role in the diagnosis of IgG4-RD and is often the first occasion where IgG4-RD comes into consideration. Thus, knowledge about the imaging findings of various manifestations of IgG4-RD can aid in the diagnosis and have a significant impact on patient management. In this article, we review the wide array of imaging findings, both typical and atypical, as well as possible mimics of IgG4-RD in the abdomen and pelvis.
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Löhr JM, Beuers U, Vujasinovic M, Alvaro D, Frøkjær JB, Buttgereit F, Capurso G, Culver EL, de-Madaria E, Della-Torre E, Detlefsen S, Dominguez-Muñoz E, Czubkowski P, Ewald N, Frulloni L, Gubergrits N, Duman DG, Hackert T, Iglesias-Garcia J, Kartalis N, Laghi A, Lammert F, Lindgren F, Okhlobystin A, Oracz G, Parniczky A, Mucelli RMP, Rebours V, Rosendahl J, Schleinitz N, Schneider A, van Bommel EFH, Verbeke CS, Vullierme MP, Witt H. European Guideline on IgG4-related digestive disease - UEG and SGF evidence-based recommendations. United European Gastroenterol J 2020; 8:637-666. [PMID: 32552502 PMCID: PMC7437085 DOI: 10.1177/2050640620934911] [Citation(s) in RCA: 128] [Impact Index Per Article: 25.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/29/2020] [Accepted: 05/04/2020] [Indexed: 12/12/2022] Open
Abstract
The overall objective of these guidelines is to provide evidence-based recommendations for the diagnosis and management of immunoglobulin G4 (IgG4)-related digestive disease in adults and children. IgG4-related digestive disease can be diagnosed only with a comprehensive work-up that includes histology, organ morphology at imaging, serology, search for other organ involvement, and response to glucocorticoid treatment. Indications for treatment are symptomatic patients with obstructive jaundice, abdominal pain, posterior pancreatic pain, and involvement of extra-pancreatic digestive organs, including IgG4-related cholangitis. Treatment with glucocorticoids should be weight-based and initiated at a dose of 0.6-0.8 mg/kg body weight/day orally (typical starting dose 30-40 mg/day prednisone equivalent) for 1 month to induce remission and then be tapered within two additional months. Response to initial treatment should be assessed at week 2-4 with clinical, biochemical and morphological markers. Maintenance treatment with glucocorticoids should be considered in multi-organ disease or history of relapse. If there is no change in disease activity and burden within 3 months, the diagnosis should be reconsidered. If the disease relapsed during the 3 months of treatment, immunosuppressive drugs should be added.
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Affiliation(s)
- J-Matthias Löhr
- Department of Upper Gastrointestinal Diseases, Karolinska University Hospital, Stockholm, Sweden and Department of Clinical Science, Intervention and Technology (CLINTEC), Karolinska Institutet, Stockholm, Sweden
| | - Ulrich Beuers
- Department of Gastroenterology and Hepatology, Amsterdam University Medical Centers, location AMC, Amsterdam, the Netherlands
| | - Miroslav Vujasinovic
- Department of Upper Gastrointestinal Diseases, Karolinska University Hospital, Stockholm, Sweden and Department of Medicine Huddinge, Karolinska Institutet, Stockholm, Sweden
| | - Domenico Alvaro
- Department of Translational and Precision Medicine, Sapienza University of Rome, Rome, Italy
| | | | - Frank Buttgereit
- Department of Rheumatology and Clinical Immunology, Charité University Medicine Berlin, Berlin, Germany
| | - Gabriele Capurso
- PancreatoBiliary Endoscopy and EUS Division Pancreas Translational and Clinical Research Center IRCCS San Raffaele Scientific Institute, Milan, Italy
| | - Emma L Culver
- Translational Gastroenterology Unit, John Radcliffe Hospital and Nuffield Department of Medicine, University of Oxford, Oxford, UK
| | - Enrique de-Madaria
- Gastroenterology Department, Alicante University General Hospital, ISABIAL, Alicante, Spain
| | - Emanuel Della-Torre
- School of Medicine, Vita-Salute San Raffaele University, Milan, Italy; Unit of Immunology, Rheumatology, Allergy and Rare Disease (UnIRAR), IRCCS San Raffaele Scientific Institute, Milan, Italy
| | - Sönke Detlefsen
- Department of Pathology, Odense Pancreas Center (OPAC), Odense University Hospital, Odense, Denmark
| | - Enrique Dominguez-Muñoz
- Department of Gastroenterology and Hepatology, University Hospital of Santiago de Compostela, Santiago de Compostela, Spain
| | - Piotr Czubkowski
- Department of Gastroenterology, Hepatology, Nutritional Disorders and Pediatrics, The Children’s Memorial Health Institute, Warsaw, Poland
| | - Nils Ewald
- Institute of Endocrinology, Diabetology and Metabolism, Johannes Wesling University hospital, Minden, Germany and Justus Liebig University Giessen, Giessen, Germany
| | - Luca Frulloni
- Department of Medicine, Pancreas Institute, University of Verona, Verona, Italy
| | - Natalya Gubergrits
- Department of Internal Medicine, Donetsk National Medical University, Lyman, Ukraine
| | - Deniz Guney Duman
- Department of Gastroenterology, School of Medicine, Marmara University, Istanbul, Turkey
| | - Thilo Hackert
- Department of General, Visceral and Transplantation Surgery, University of Heidelberg, Heidelberg, Germany
| | - Julio Iglesias-Garcia
- Department of Gastroenterology and Hepatology, University Hospital of Santiago de Compostela, Santiago de Compostela, Spain
| | - Nikolaos Kartalis
- Department of Abdominal Radiology, Karolinska University Hospital, Stockholm, Sweden
| | - Andrea Laghi
- Department of Surgical and Medical Sciences and Translational Medicine, Sapienza University of Rome, Sant’Andrea Hospital, Rome, Italy
| | - Frank Lammert
- Department of Medicine II, Saarland University Medical Center, Homburg, Germany
| | - Fredrik Lindgren
- Department of Pediatric Gastroenterology, Hepatology and Nutrition, Karolinska University Hospital, Stockholm, Sweden
| | | | - Grzegorz Oracz
- Department of Gastroenterology, Hepatology, Nutritional Disorders and Pediatrics, The Children’s Memorial Health Institute, Warsaw, Poland
| | - Andrea Parniczky
- Institute for Translational Medicine, Szentágothai Research Centre, Medical School, University of Pécs, Pécs, Hungary; Heim Pál National Insitute of Pediatrics, Budapest, Hungary
| | | | - Vinciane Rebours
- Pancreatology Department, Beaujon Hospital, Clichy, Université de Paris, France
| | - Jonas Rosendahl
- Department of Internal Medicine I, Martin Luther University, Halle, Germany
| | - Nicolas Schleinitz
- Département de Médicine Interne Timone, Assistance Publique-Hôpitaux de Marseille, Aix-Marseille Université, Marseille, France
| | - Alexander Schneider
- Department of Gastroenterology and Hepatology, Klinikum Bad Hersfeld, Bad Hersfeld, Germany
| | - Eric FH van Bommel
- Department of Internal Medicine, Dutch National Center of Expertise Retroperitoneal Fibrosis, Albert Schweitzer hospital, Dordrecht, the Netherlands
| | | | | | - Heiko Witt
- Else Kröner-Fresenius-Zentrum für Ernährungsmedizin, Paediatric Nutritional Medicine, Technische Universität München, Freising, Germany
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Liver atrophy in IgG4-related disease: An autopsy case. HUMAN PATHOLOGY: CASE REPORTS 2020. [DOI: 10.1016/j.ehpc.2020.200355] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022] Open
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Nakata R, Uehara T, Iwaya M, Asaka S, Kobayashi S, Sugano M, Higuchi K, Kusama Y, Nakazawa K, Nakaguro M, Kobayashi M, Tateishi A, Makino M, Kawaguchi K, Maejima T, Ishii K, Sano K, Shimojo H, Hori A, Otsuki T, Hamano H, Kawa S, Ota H. Immunostaining With Immunoglobulin G Subclass Antibody Cocktail for Diagnosis of Type 1 Autoimmune Pancreatitis. Int J Surg Pathol 2020; 28:844-849. [PMID: 32456567 DOI: 10.1177/1066896920924781] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022]
Abstract
BACKGROUND. Immunoglobulin (Ig) G4-related diseases (RDs) are systemic diseases in which serum IgG4 levels are frequently elevated. They can cause diffuse or focal tumor formation, organ swelling, and tissue thickening in organs infiltrated by IgG4+ plasma cells. The diagnostic criteria for IgG4-RDs include an IgG4/IgG ratio >40%, but counting IgG+ cells can be difficult because of the weakness of IgG staining density. We hypothesized that an antibody cocktail of mixed IgG1, IgG2, IgG3, and IgG4 (AC-IgG) might give immunohistochemistry results comparable with those of IgG in IgG4-RD. METHODS. We compared AC-IgG reactivity with IgG expression in type 1 autoimmune pancreatitis (AIP), a representative IgG4-RD. We compared immunohistochemistry results using AC-IgG and IgG-only in 10 cases of AIP. The coefficient of variation (Cv) was used to analyze differences between AC-IgG and IgG findings in AIP by 13 board-certified pathologists. RESULTS. Although mean values for IgG+ cells did not significantly differ between AC-IgG (34.3; range = 27.4-37.1) and IgG (30.0; range = 23.0-45.6; P = .6254), Cv was lower for AC-IgG (33.4%) than for IgG (51.4%; regression equation; y[IgG] = 0.988x + 0.982; correlation coefficient = 0.907). The data showed that the results of both methods were largely consistent. CONCLUSION. AC-IgG could replace IgG to count IgG+ cells because of its lower Cv.
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Affiliation(s)
- Rie Nakata
- 168943Matsumoto Kyoritsu Hospital, Matsumoto, Japan
| | | | - Mai Iwaya
- 13056Shinshu University, Matsumoto, Japan
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- 36910Iida Municipal Hospital, Iida, Japan
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Management of biliary stricture in patients with IgG4-related sclerosing cholangitis. PLoS One 2020; 15:e0232089. [PMID: 32353060 PMCID: PMC7192452 DOI: 10.1371/journal.pone.0232089] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/02/2020] [Accepted: 04/07/2020] [Indexed: 02/07/2023] Open
Abstract
Background We aimed to determine the optimal approach with endoscopic biliary drainage (EBD) and corticosteroid (CS) for the treatment of IgG4-related sclerosing cholangitis (ISC). Methods To evaluate the safety of EBD for treatment of biliary stricture caused by ISC, we assessed the risk of stent dislodgement and sought to determine the most appropriate time for stent removal. We also assessed the safety of treatment with CS alone for patients with obstructive jaundice, and the rate of and risk factors for biliary tract complications. Results Sixty-nine patients with ISC treated with CS were enrolled. Twenty-eight patients (40.6%) were treated with EBD for biliary stricture before CS initiation. Intentional stent removal was performed in thirteen (46.4%) after confirming CS-induced improvement. Eleven of thirteen patients (84.6%) underwent stent removal within 1 month after CS initiation and all their stent removals were safely carried out without early (within two weeks) recurrence of obstructive jaundice. Ten of twenty-eight patients (35.7%) experienced spontaneous stent dislodgement after CS initiation, and seven (70%) of them developed stent dislodgement two weeks to two months after CS initiation. Among forty-one patients treated with CS alone without EBD, 10 patients had obstructive jaundice at the time of CS initiation and all of them achieved clinical improvement without biliary tract infection. During the follow-up, three patients (4.3%), all of whom had undergone EBD, developed bile-duct stones, while none of those treated with CS alone developed bile-duct stones (p = 0.032). Long-term biliary stenting was a risk factor for bile-duct stones. Conclusions Biliary stent removal should be carried out within 2 weeks after CS initiation if biliary stricture improves to prevent stent dislodgement. Obstructive jaundice can be treated safely with CS alone in patients without infection. Clinicians should be aware of the possibility of bile-duct stones in patients treated with EBD.
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Eosinophilic pancreatitis versus pancreatitis associated with eosinophilic gastroenteritis - a systematic review regarding clinical features and diagnosis. ACTA ACUST UNITED AC 2020; 57:284-295. [PMID: 31120859 DOI: 10.2478/rjim-2019-0012] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/01/2019] [Indexed: 01/16/2023]
Abstract
BACKGROUND Over the past years, eosinophil infiltration involving the gastrointestinal tract and pancreas leading to eosinophilic pancreatitis, eosinophilic gastroenteritis and hypereosinophilic syndrome has been reported in the literature. We aimed to analyze and compare the features involving patients with eosinophilic pancreatitis and pancreatitis associated with eosinophilic gastroenteritis and to determine if there is a connection between the two disorders or if they in fact meet the diagnostic criteria for hypereosinophilic syndrome. MATERIAL AND METHODS The following search was performed in March 2019 on PubMed (MEDLINE) database using the medical terms "pancreatitis", "eosinophilic pancreatitis", "eosinophilic gastroenteritis" and "hypereosinophilic syndrome". RESULTS The search revealed 119 publications from 1970 onwards. A total of 83 papers were excluded, and the remaining 36 publications, consisting in case reports and case series, were analyzed. From 45 patients, 20 subjects with eosinophilic gastroenteritis developed pancreatitis, 20/45 had eosinophilic pancreatitis, and 5/45 hypereosinophilic syndrome involving the pancreas. There was no significant difference regarding clinical, laboratory and imaging features between the three groups, despite the multiple theories that explain the association of pancreatic and gastrointestinal eosinophilic infiltration. Although there was a strong resemblance between the three groups, histological evidence of eosinophilic gastrointestinal infiltration guided the treatment towards a less invasive way, while subjects with eosinophilic pancreatitis underwent pancreatic surgery to exclude potentially malignant lesions. CONCLUSION Although there are various theories that explain pancreatitis development in patients with eosinophilic gastroenteritis, hypereosinophilia diagnostic work-up should be taken into account in all patients with high number of blood eosinophils, even in those with eosinophilic pancreatitis in order to establish the diagnosis using a minimally invasive approach and to apply an adequate treatment.
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Thanage R, Jain S, Sonthalia N, Udgirkar S, Chandnani S, Contractor Q, Rathi P. An Enigmatic Liver Mass in a Child. Euroasian J Hepatogastroenterol 2020; 9:104-107. [PMID: 32117700 PMCID: PMC7047306 DOI: 10.5005/jp-journals-10018-1307] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/23/2022] Open
Abstract
Hepatic space occupying lesions in childhood are a diagnostic challenge, as they are caused by a variety of malignant and nonmalignant disorders with a different prognosis and, of course, treatment. They are often misdiagnosed or diagnosed only after surgical resection. A 14-year-old boy presented with abdominal pain, evening-rise fever with loss of appetite and weight. The patient also developed jaundice after 2 months of above symptoms. Ultrasound of the abdomen showed an irregular infiltrative mass in segment IV of the liver. Gadobenate disodium magnetic resonance imaging done showed T1 hypointense and T2 hyperintense lesions in segment VIII of the liver with extension into porta with delayed enhancement suggestive of fibrous tumor. Liver biopsy showed extensive liver parenchymal fibrosis with a mixed inflammatory infiltrate with eosinophils. Bacterial, tubercular, and fungal culture of liver biopsy were negative. Although serum IgG4 levels were 7.88 g/L (N =1.9 g/L), IgG4 staining of liver biopsy was negative. The patient was started on prednisolone 1 mg/kg considering the diagnosis of inflammatory pseudotumor (IPT). Twenty days after starting the steroid, mass lesions were converted into multicystic abscess requiring antibiotics and pigtail drainage. On follow-up, patient had improved symptoms with mass lesions turned into small-sized abscess cavity. Hepatic IPTs are difficult to differentiate from malignant tumors, as they are rare and can have variable imaging findings. To avoid inadvertent surgery, histological confirmation of the hepatic mass is essential. Steroids should be used with caution with close follow-up to prevent iatrogenic complications, such as a chronic liver abscess.
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Affiliation(s)
- Ravi Thanage
- Department of Gastroenterology, Topiwala National Medical College and BYL Nair Hospital, Mumbai, Maharashtra, India
| | - Shubham Jain
- Department of Gastroenterology, Topiwala National Medical College and BYL Nair Hospital, Mumbai, Maharashtra, India
| | - Nikhil Sonthalia
- Department of Gastroenterology, Topiwala National Medical College and BYL Nair Hospital, Mumbai, Maharashtra, India
| | - Suhas Udgirkar
- Department of Gastroenterology, Topiwala National Medical College and BYL Nair Hospital, Mumbai, Maharashtra, India
| | - Sanjay Chandnani
- Department of Gastroenterology, Topiwala National Medical College and BYL Nair Hospital, Mumbai, Maharashtra, India
| | - Qais Contractor
- Department of Gastroenterology, Topiwala National Medical College and BYL Nair Hospital, Mumbai, Maharashtra, India
| | - Pravin Rathi
- Department of Gastroenterology, Topiwala National Medical College and BYL Nair Hospital, Mumbai, Maharashtra, India
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Maehara T, Moriyama M, Nakamura S. Review of a novel disease entity, immunoglobulin G4-related disease. J Korean Assoc Oral Maxillofac Surg 2020; 46:3-11. [PMID: 32158675 PMCID: PMC7049757 DOI: 10.5125/jkaoms.2020.46.1.3] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/06/2019] [Accepted: 01/06/2020] [Indexed: 12/20/2022] Open
Abstract
Immunoglobulin G4 (IgG4)-related dacryoadenitis and sialoadenitis (IgG4-DS) are part of a multiorgan fibroinflammatory condition of unknown etiology termed IgG4-related disease (IgG4-RD), which has been recognized as a single diagnostic entity for less than 15 years. Histopathologic examination is critical for diagnosis of IgG4-RD. CD4+ T and B cells, including IgG4-expressing plasma cells, constitute the major inflammatory cell populations in IgG4-RD and are thought to cause organ damage and tissue fibrosis. Patients with IgG4-RD who have active, untreated disease exhibit significant increase of IgG4-secreting plasmablasts in the blood. Considerable insight into the immunologic mechanisms of IgG4-RD has been achieved in the last decade using novel molecular biology approaches, including next-generation and single-cell RNA sequencing. Exploring the interactions between CD4+ T cells and B lineage cells is critical for understanding the pathophysiology of IgG4-RD. Establishment of pathogenic T cell clones and identification of antigens specific to these clones constitutes the first steps in determining the pathogenesis of the disease. Herein, the clinical features and mechanistic insights regarding pathogenesis of IgG4-RD were reviewed.
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Affiliation(s)
- Takashi Maehara
- Section of Oral and Maxillofacial Oncology, Division of Maxillofacial Diagnostic and Surgical Sciences, Faculty of Dental Science, Kyushu University, Fukuoka, Japan
| | - Masafumi Moriyama
- Section of Oral and Maxillofacial Oncology, Division of Maxillofacial Diagnostic and Surgical Sciences, Faculty of Dental Science, Kyushu University, Fukuoka, Japan
| | - Seiji Nakamura
- Section of Oral and Maxillofacial Oncology, Division of Maxillofacial Diagnostic and Surgical Sciences, Faculty of Dental Science, Kyushu University, Fukuoka, Japan
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