Journal of Pathology and Translational Medicine

Case Studies

Gastric IgG4-related disease presenting as a mass lesion and masquerading as a gastrointestinal stromal tumor: Banumathi Ramakrishna, Rohan Yewale, Kavita Vijayakumar, Patta Radhakrishna, Balakrishnan Siddartha Ramakrishna; J Pathol Transl Med. 2020;54(3):258-262. Published online March 4, 2020; DOI: https://doi.org/10.4132/jptm.2020.02.10

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IgG4-related disease of the stomach is a rare disorder, and only a few cases have been reported. We present two cases that were identified over a 2-month period in our center. Two male patients aged 52 and 48 years presented with mass lesion in the stomach, which were clinically thought to be gastrointestinal stromal tumor, and they underwent excision of the lesion. Microscopic examination revealed marked fibrosis, which was storiform in one case, associated with diffuse lymphoplasmacytic infiltration and an increase in IgG4-positive plasma cells on immunohistochemistry. Serum IgG4 level was markedly elevated. Although rare, IgG4-related disease should be considered in the differential diagnosis of gastric submucosal mass lesions.

Citations

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CGB5, INHBA and TRAJ19 Hold Prognostic Potential as Immune Genes for Patients with Gastric Cancer
Bei Ji, Lili Qiao, Wei Zhai
Digestive Diseases and Sciences.2023; 68(3): 791. CrossRef
IgG4-related diseases of the digestive tract
J.-Matthias Löhr, Miroslav Vujasinovic, Jonas Rosendahl, John H. Stone, Ulrich Beuers
Nature Reviews Gastroenterology & Hepatology.2022; 19(3): 185. CrossRef
Clinicopathological characteristics of gastric IgG4‐related disease: Systematic scoping review
Haruki Sawada, Torrey Czech, Krixie Silangcruz, Landon Kozai, Adham Obeidat, Eric Andrew Wien, Midori Filiz Nishimura, Asami Nishikori, Yasuharu Sato, Yoshito Nishimura
Journal of Gastroenterology and Hepatology.2022; 37(10): 1865. CrossRef
Utility of gastric biopsy in diagnosing IgG4‐related gastrointestinal disease
Kaori Uchino, Kenji Notohara, Takeshi Uehara, Yasuhiro Kuraishi, Junya Itakura, Akihiro Matsukawa
Pathology International.2021; 71(2): 124. CrossRef

A Rare Case of Adenosquamous Carcinoma Arising in the Background of IgG4-Related Lung Disease: Sangjoon Choi, Sujin Park, Man Pyo Chung, Tae Sung Kim, Jong Ho Cho, Joungho Han; J Pathol Transl Med. 2019;53(3):188-191. Published online March 11, 2019; DOI: https://doi.org/10.4132/jptm.2019.02.21

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Abstract PDF

IgG4-related disease is a systemic inflammatory disease and is known as IgG4-related lung disease (IgG4-RLD) when it involves the respiratory system. Primary lung cancer arising from a background of IgG4-RLD is very rare. Herein, we report a case of adenosquamous carcinoma arising from the background of IgG4-RLD and presenting as an interstitial lung disease pattern. A 66-year-old man underwent lobectomy under the impression of primary lung cancer. Grossly, the mass was ill-defined and gray-tan colored, and the background lung was fibrotic. Microscopically, tumor cells showed both squamous and glandular differentiation. Dense lymphoplasmacytic infiltration with fibrosis and obliterative phlebitis were seen in the background lung. IgG4 immunohistochemical stain showed diffuse positivity in infiltrating plasma cells. Primary lung adenosquamous carcinoma has not been reported in a background of IgG4-RLD. Due to the rarity of IgG4-RLD, physicians must follow patients with IgG4-RLD over long periods of time to accurately predict the risk of lung cancer.

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Endometrioid Carcinomas of the Ovaries and Endometrium Involving Endocervical Polyps: Comprehensive Clinicopathological Analyses
Jihee Sohn, Yurimi Lee, Hyun-Soo Kim
Diagnostics.2022; 12(10): 2339. CrossRef
A Case of IgG4-related Disease Composed of a Paravertebral Tumor Alone with Multiple Lung Cancers
Mutsumi Ozasa, Toyomitsu Sawai, Yosuke Harada, Sumako Yoshioka, Nobuko Matsuo, Hiroshi Mukae
Haigan.2021; 61(3): 213. CrossRef
Serous Carcinoma of the Endometrium with Mesonephric-Like Differentiation Initially Misdiagnosed as Uterine Mesonephric-Like Adenocarcinoma: A Case Report with Emphasis on the Immunostaining and the Identification of Splice Site TP53 Mutation
Sangjoon Choi, Yoon Yang Jung, Hyun-Soo Kim
Diagnostics.2021; 11(4): 717. CrossRef
A Case of IgG4-related Thyroiditis Diagnosed by Total Thyroidectomy
Daiki Sakamoto, Masao Yagi, Hiroshi Iwai
Practica Oto-Rhino-Laryngologica.2021; 114(7): 547. CrossRef
Mesonephric-like Differentiation of Endometrial Endometrioid Carcinoma: Clinicopathological and Molecular Characteristics Distinct from Those of Uterine Mesonephric-like Adenocarcinoma
Sujin Park, Go Eun Bae, Jiyoung Kim, Hyun-Soo Kim
Diagnostics.2021; 11(8): 1450. CrossRef
Mesonephric-like Adenocarcinoma of the Uterine Corpus: Comprehensive Immunohistochemical Analyses Using Markers for Mesonephric, Endometrioid and Serous Tumors
Hyunjin Kim, Kiyong Na, Go Eun Bae, Hyun-Soo Kim
Diagnostics.2021; 11(11): 2042. CrossRef
Not Cancer After All: Two Rare Cases of IgG4-Related Lung Disease
Josué Pinto, Carla Damas, António Morais
Archivos de Bronconeumología.2020; 56(1): 53. CrossRef
Not Cancer After All: Two Rare Cases of IgG4-Related Lung Disease
Josuèc) Pinto, Carla Damas, António Morais
Archivos de Bronconeumología (English Edition).2020; 56(1): 52. CrossRef
Axillary lymphadenopathy with IgG4 positive plasma cell infiltration as differential diagnosis of metastatic lung adenocarcinoma
Yutaro Ito, Masanori Harada, Namio Kagoo, Tsutomu Kubota, Koshiro Ichijyo, Eisuke Mochizuki, Masahiro Uehara, Shun Matsuura, Masaru Tsukui, Naoki Koshimizu
Respiratory Medicine Case Reports.2020; 31: 101196. CrossRef

Coexisting Mucinous Cystic Neoplasm of the Pancreas and Type 1 Autoimmune Pancreatitis: Mee-Jeong Kim, Tae Jun Song, Hyoung Jung Kim, Song-Cheol Kim, Myung-Hwan Kim, Seung-Mo Hong; J Pathol Transl Med. 2019;53(2):125-128. Published online November 14, 2018; DOI: https://doi.org/10.4132/jptm.2018.10.25

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Abstract PDF

Type 1 autoimmune pancreatitis (AIP1) is an IgG4-related systemic disease that mimics tumors. We report a rare case of AIP1 accompanied by mucinous cystic neoplasm (MCN). A pancreatic lesion was incidentally detected in a woman in her 60s. After 6 years of follow-up, the lesion abruptly increased in size. Computed tomography showed a 3.5 cm unilocular cyst in the tail of the pancreas and distal pancreatectomy was performed. On microscopic examination, the cyst was lined by mucinous and non-mucinous epithelial cells with mild cytologic atypia. The surrounding stroma comprised ovarian-type spindle cells with progesterone receptor positivity. The pericystic pancreas exhibited multifocal lymphoid follicles, lymphoplasmacytic infiltrations, obliterative phlebitis, and storiform fibrosis. IgG4-positive plasma cell infiltration (215 cells high-power field) and the IgG4/IgG ratio (57%) were increased. Cases of MCN coexisting with AIP1 are extremely rare; only two such cases have been reported in the English-language literature. This third case featured low-grade MCN with AIP1.

Citations

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Histological features of autoimmune pancreatitis and IgG4-related sclerosing cholangitis with a correlation with imaging findings
Kenji NOTOHARA
Choonpa Igaku.2023; 50(1): 55. CrossRef
Imaging Features and Risk Factors of Pancreatic Cystic Lesions Complicating Autoimmune Pancreatitis: A Retrospective Study
Bin-Bin Zhang, Xin-Meng Hou, Yu-Qi Chen, Jian-Wei Huo, Er-Hu Jin
Current Medical Imaging Formerly Current Medical Imaging Reviews.2023;[Epub] CrossRef
Histological features of autoimmune pancreatitis and IgG4-related sclerosing cholangitis with a correlation with imaging findings
Kenji Notohara
Journal of Medical Ultrasonics.2021; 48(4): 581. CrossRef
自己免疫性膵炎診療ガイドライン2020

Suizo.2020; 35(6): 465. CrossRef
Mucinous cystic neoplasm of the pancreas with type-1 autoimmune pancreatitis-like lesion
Kevin Gowing, David F. Schaeffer, Hui-Min Yang
Human Pathology: Case Reports.2019; 18: 200339. CrossRef

IgG4-Related Disease Presented as a Mural Mass in the Stomach: Chang Gok Woo, Jeong Hwan Yook, Ah Young Kim, Jihun Kim; J Pathol Transl Med. 2016;50(1):67-70. Published online September 30, 2015; DOI: https://doi.org/10.4132/jptm.2015.07.28

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84 Download
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21 Crossref

Abstract PDF

Isolated gastric IgG4-related disease (IgG4-RD) is a very rare tumefactive inflammatory condition, with only a few cases reported to date. A 48-year-old woman was incidentally found to have a subepithelial tumor in the stomach. Given a presumptive diagnosis of gastrointestinal stromal tumor or neuroendocrine tumor, she underwent wedge resection. The lesion was vaguely nodular and mainly involved the submucosa and proper muscle layer. Microscopically, all classical features of type I autoimmune pancreatitis including lymphoplasmacytic infiltration, storiform fibrosis, obliterative phlebitis, and numerous IgG4-positive plasma cells were seen. She had no evidence of IgG4-RD in other organs. Although very rare, IgG4-RD should be considered one of the differential diagnoses in the setting of gastric wall thickening or subepithelial mass-like lesion. Deep biopsy with awareness of this entity might avoid unnecessary surgical intervention.

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Value of High‐Frequency Ultrasonography in the Qualitative and Semi‐Quantitative Assessment of Immunoglobulin G4‐Related Submandibular Sialadenitis
Lei Chen, Lin Nong, Jumei Liu, Luzeng Chen, Yuhong Shao, Xiuming Sun
Journal of Ultrasound in Medicine.2023; 42(10): 2235. CrossRef
IgG4-related pseudotumours: a series of 12 cases and a review of the literature
Andrea Maccagno, Bianca Grosser, László Füzesi, Björn Konukiewitz, Dmytro Vlasenko, Dorothea Weckermann, Stephan Raab, Johannes Zenk, Abbas Agaimy, Bruno Märkl
Pathology.2022; 54(5): 563. CrossRef
IgG4-Related Disease With Gastrointestinal Involvement: Case Reports and Literature Review
Xinhe Zhang, Xing Jin, Lin Guan, Xuyong Lin, Xuedan Li, Yiling Li
Frontiers in Immunology.2022;[Epub] CrossRef
Clinicopathological characteristics of gastric IgG4‐related disease: Systematic scoping review
Haruki Sawada, Torrey Czech, Krixie Silangcruz, Landon Kozai, Adham Obeidat, Eric Andrew Wien, Midori Filiz Nishimura, Asami Nishikori, Yasuharu Sato, Yoshito Nishimura
Journal of Gastroenterology and Hepatology.2022; 37(10): 1865. CrossRef
Utility of gastric biopsy in diagnosing IgG4‐related gastrointestinal disease
Kaori Uchino, Kenji Notohara, Takeshi Uehara, Yasuhiro Kuraishi, Junya Itakura, Akihiro Matsukawa
Pathology International.2021; 71(2): 124. CrossRef
A reappraisal of sclerosing nodular and/or polypoid lesions of the gastrointestinal tract rich in IgG4‐positive plasma cells
Runjan Chetty
Histopathology.2020; 76(6): 832. CrossRef
Gastric IgG4-related disease presenting as a mass lesion and masquerading as a gastrointestinal stromal tumor
Banumathi Ramakrishna, Rohan Yewale, Kavita Vijayakumar, Patta Radhakrishna, Balakrishnan Siddartha Ramakrishna
Journal of Pathology and Translational Medicine.2020; 54(3): 258. CrossRef
IgG4-related Sclerosing Disease Forming a Gastric Submucosal Tumor Diagnosed after Laparoscopic Endoscopic Cooperative Surgery—Report of a Case—
Tatsuki ISHIKAWA, Katsunori NAKANO, Masafumi OSAKA, Yayoi KADOTANI, Kaori OKUGAWA, Kiyokazu AKIOKA, Kenta SHIGEMORI, Yohei HOSOKAWA
Nihon Rinsho Geka Gakkai Zasshi (Journal of Japan Surgical Association).2020; 81(2): 254. CrossRef
Calcifying fibrous tumor of the gastrointestinal tract: A clinicopathologic review and update
Donald Turbiville, Xu-Chen Zhang
World Journal of Gastroenterology.2020; 26(37): 5597. CrossRef
A Suspected Case of IgG4-Related Appendiceal Pseudotumor
Yudai Hojo, Yoshiharu Shirakata, Ai Izumi, Jun Matsui, Tokuyuki Yamashita, Hikaru Aoki, Makoto Kurimoto, Masaaki Hirata, Naoki Goda, Hiroaki Ito, Jun Tamura
The Japanese Journal of Gastroenterological Surgery.2020; 53(12): 976. CrossRef
Immunoglobulin G4-related gastric pseudotumor – An impostor: Case report
Manuel Santiago Mosquera, Andrea Suarez Gómez, Hugo Herrera, Karen Moreno-Medina, Alejandro González-Orozco, Carlos J-Perez Rivera
International Journal of Surgery Case Reports.2020; 75: 333. CrossRef
Imaging and pathological features of gastric lesion of immunoglobulin G4-related disease: A case report and review of the recent literature
Dai Inoue, Norihide Yoneda, Kotaro Yoshida, Hiromi Nuka, Jun Kinoshita, Sachio Fushida, Fumihito Toshima, Tetsuya Minami, Masayuki Takahira, Shoko Hamaoka, Hiroko Ikeda, Toshifumi Gabata, Mitsuhiro Kawano
Modern Rheumatology.2019; 29(2): 377. CrossRef
Immunoglobulin G4-Related Gastric Ulcer Mimicking Advanced Stomach Cancer in a Patient with Type I Autoimmune Pancreatitis
Joung Ha Park, Jin Hee Noh, Jang ho Lee, Goeun Lee, Seung-Mo Hong, Kwang Bum Cho, Myung-Hwan Kim
The Korean Journal of Medicine.2019; 94(3): 287. CrossRef
Review of IgG4-related disease
Raquel Sánchez-Oro, Elsa María Alonso-Muñoz, Lidia Martí Romero
Gastroenterología y Hepatología (English Edition).2019; 42(10): 638. CrossRef
Revisión de la enfermedad relacionada con la IgG4
Raquel Sánchez-Oro, Elsa María Alonso-Muñoz, Lidia Martí Romero
Gastroenterología y Hepatología.2019; 42(10): 638. CrossRef
Gastrointestinal manifestation of immunoglobulin G4-related disease: clarification through a multicenter survey
Kenji Notohara, Terumi Kamisawa, Kazushige Uchida, Yoh Zen, Mitsuhiro Kawano, Satomi Kasashima, Yasuharu Sato, Masahiro Shiokawa, Takeshi Uehara, Hajime Yoshifuji, Hiroko Hayashi, Koichi Inoue, Keisuke Iwasaki, Hiroo Kawano, Hiroyuki Matsubayashi, Yukitos
Journal of Gastroenterology.2018; 53(7): 845. CrossRef
IgG4-Related Disease Mimicking Crohn’s Disease: A Case Report and Review of Literature
Fabiana Ciccone, Antonio Ciccone, Mirko Di Ruscio, Filippo Vernia, Gianluca Cipolloni, Gino Coletti, Giuseppe Calvisi, Giuseppe Frieri, Giovanni Latella
Digestive Diseases and Sciences.2018; 63(4): 1072. CrossRef
IgG4-related Disease in the Stomach which Was Confused with Gastrointestinal Stromal Tumor (GIST): Two Case Reports and Review of the Literature
Ho Seok Seo, Yoon Ju Jung, Cho Hyun Park, Kyo Young Song, Eun Sun Jung
Journal of Gastric Cancer.2018; 18(1): 99. CrossRef
Multivisceral IgG4-related disease presenting as recurrent massive gastrointestinal bleeding: a case report and literature review
Xuexue Deng, Ronghua Fang, Jianshu Zhang, Rongqiong Li
BMC Gastroenterology.2018;[Epub] CrossRef
IgG4-Related Sclerosing Disease Presenting as a Gastric Submucosal Tumor
Takashi Masuda, Toshifumi Matsumoto, Yushi Kaishakuji, Hirotada Tajiri, Akinori Egashira, Hirofumi Kawanaka
The Japanese Journal of Gastroenterological Surgery.2018; 51(10): 599. CrossRef
A rare case of IgG4-related disease: a gastric mass, associated with regional lymphadenopathy
Dimitar Bulanov, Elena Arabadzhieva, Sasho Bonev, Atanas Yonkov, Diana Kyoseva, Tihomir Dikov, Violeta Dimitrova
BMC Surgery.2016;[Epub] CrossRef

Original Articles

Idiopathic Duct Centric Pancreatitis in Korea: A Clinicopathological Study of 14 Cases.: Hyo Jeong Kang, Tae Jun Song, Eunsil Yu, Jihun Kim; Korean J Pathol. 2011;45(5):491-497.; DOI: https://doi.org/10.4132/KoreanJPathol.2011.45.5.491

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Abstract PDF: BACKGROUND
Idiopathic duct centric pancreatitis (IDCP) is a subtype of autoimmune pancreatitis (AIP) that is histologically characterized by granulocytic epithelial lesion and scarce IgG4-positive cells. This subtype of AIP has not been documented in Asian countries.
METHODS
We reviewed 38 histologically confirmed AIP cases and classified them into lymphoplasmacytic sclerosing pancreatitis (LPSP) and IDCP. Then, clinicopathological characteristics were compared between LPSP and IDCP.
RESULTS
Fourteen cases (36.8%) were IDCP. IDCP affected younger patients more than LPSP. IDCP was associated with ulcerative colitis in 35.7% of cases, whereas LPSP was associated with IgG4-related sclerosing diseases such as cholangitis, retroperitoneal fibrosis or sialadenitis in 41.7% of cases. IDCP was microscopically characterized by neutrophilic ductoacinitis with occasional granulocytic epithelial lesions, whereas LPSP was characterized by storiform inflammatory cell-rich fibrosis and obliterative phlebitis. IgG4-positive cells were not detected in any IDCP case but more than 20 IgG4-positive cells per high-power-field were invariably detected in LPSP cases. All patients with IDCP responded dramatically to steroids without recurrence, whereas 33.3% of patients with LPSP developed recurrences.
CONCLUSIONS
IDCP is clinicopathologically distinct from LPSP and can be diagnosed when neutrophilic ductoacinitis or granulocytic epithelial lesions are observed in a pancreatic biopsy under the appropriate clinical setting.

Primary Biliary Cirrhosis-Autoimmune Hepatitis Overlap Syndrome.: Jong Yup Bae, Young Nyun Park, Chanil Park; Korean J Pathol. 1997;31(1):87-90.

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Abstract PDF: Cases sharing features of both primary biliary cirrhosis and autoimmune hepatitis have been reported as a mixed type, overlap syndrome, immunocholangitis and autoimmune cholangiopathy. A primary biliary cirrhosis- autoimmune hepatitis overlap syndrome is unusual and characterized by overlapping features; cholestasis, high titer of alkaline phosphatase, bile duct damage and granulomas in the liver biopsy, high antinuclear antibody, increased IgG and IgM and intra-acinar hepatitis with piecemeal necrosis. Autoimmune mechanisms are thought to play a major role in the pathogenesis of the overlapping syndrome and the bases of immunosuppressive therapy. A 58-year-old female patient shows overlapping clinical and laboratory findings, chronic active hepatitis in initial liver biopsy which transits to primary biliary cirrhosis with cholangitis and granulomas. This is a case of hepatobiliary lesion showing overlapping features of both primary biliary cirrhosis and autoimmune hepatitis over 3-year period.

Clinicopathologic Comparison between Autoimmune Cholangitis and Primary Biliary Cirrhosis.: Gyeong Hoon Kang, So Dug Lim, Eun Sil Yu, On Ja Kim, Geun Chan Lee, Neung Hwa Park, Dong Jin Suh; Korean J Pathol. 1998;32(2):115-124.

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Abstract PDF: Primary biliary cirrhosis (PBC) is characterized by histological findings of an immunoinflammatory destruction of small- and medium-sized bile ducts with progressive portal fibrosis, and the presence of anti-mitochondrial antibody (AMA) with a laboratory evidence of chronic cholestasis. The term "autoimmune cholangitis" (AIC) is used for a disease with the clinical and pathologic features of primary biliary cirrhosis (PBC) but with negative AMA and positive anti-nuclear antibody (ANA) tests. Eight cases of AIC and ten cases of PBC were reviewed in order to determine whether there was any difference between two diseases in clinico-pathologic aspects. All of the patients were female and the mean ages of AIC and PBC patients were 48 and 47 years, respectively. ANA test was positive in six of ten PBC paients and their mean titer was lower than that of AIC patients. IgM level was significantly higher in PBC group than in AIC group. No significant difference was found between two groups with respect to biochemical and histopathological features. Since the only consistently distinguishing features between these two conditions are the autoantibody profile (AMA vs ANA) and immunoglobulin level (IgM), these two conditions might be part of a spectrum. PBC can be considered to be the same as AMA-positive AIC or alternatively AIC to be the same as AMA-negative PBC.

Differential Expression of Promyelocytic Leukemia Protein in Autoimmune Liver Diseases.: Hyun Jung Kim, Jung Sun Kim, Yong Sang Lee, Young Hwa Chung, Han Joo Lee, Dong Jin Suh, Chong Jai Kim, Eunsil Yu; Korean J Pathol. 2004;38(6):357-363.

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Abstract PDF: BACKGROUND
Promyelocytic leukemia protein (PML) is a primary biliary cirrhosis (PBC)-specific autoantigen. Anti-PML antibody is analyzed using cultured cells with patient sera, however, PML expression has rarely been examined in liver tissues.
METHODS
In the present study, PML expression was examined immunohistochemically in paraffin embedded liver needle biopsy specimens obtained from 20 cases of PBC, 10 cases of autoimmune cholangitis, 36 cases of autoimmune hepatitis and from 5 cases of noninflammatory livers.
RESULTS
Variable PML immunopositivity was detected in the bile duct epithelial cells of 18 (90.0%) of 20 PBC cases and in all 10 cases (100.0%) of autoimmune cholangitis, whereas it was only present in 6 (16.7%) of 36 cases of autoimmune hepatitis (p<0.001). In contrast, hepatocyte PML immunopositivity was higher in autoimmune hepatitis (33/36 cases, 90.8%), than in PBC (10/20 cases, 50.0%) or autoimmune cholangitis (3/10 cases, 30.0%) (p<0.05).
CONCLUSION
Our data indicate that the differential expression of PML is closely related to autoimmune liver diseases type, and suggest that the overexpression of PML protein in bile duct cells is associated with the development of autoantibodies in patients with PBC or autoimmune cholangitis. Furthermore, PML immunoreactivity may be useful for the diagnosis of autoimmune cholangitis and overlap syndrome.

Liver in Systemic Lupus Erythematous: Clinicopathological analysis of 8 cases.: Young Nyun Park, Chan Il Park, Yoon Sok Chung, Si Young Song, Chein Soo Hong; Korean J Pathol. 1992;26(5):445-450.

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Abstract PDF: Hepatic changes in eight cases of systemic lupus erythematosus(SLE), were studied to evaluate the nature of hepatic injury of SLE and its relation to lupoid hepatitis. Common histologic changes of the liver in SLE included intralobular necro-inflammatory activities, fatty change, canalicular bile stasis and mild perivenular and Disse space fibrosis. The fatty change and intralobular fibrosis were thought not to be due to SLE itself but associated with steroid administration or chronic alcoholic consumption. The necro-inflammatory changes were usually mild and features of chronic active hepatitis with periportal destruction occured in one case. Symptoms related to the involvement of many other organs than the liver appeared much frequently in patients with SLE than lupoid hepatitis, suggesting that the SLE involving liver and the lupoid hepatitis are different diseases.

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