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IgG4 disease: The great masquerader
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Clinics and Research in Hepatology and Gastroenterology (2015) xxx, xxx.e1—xxx.e3
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CASE REPORT
IgG4 disease: The great masquerader Divya Yadav a, Xiuli Liu b, Prabhleen Chahal a,∗ a
Department of Gastroenterology and Hepatology, Digestive Disease Institute, Cleveland Clinic, Cleveland, Ohio, United States b Department of Anatomic Pathology, Cleveland Clinic, Cleveland, Ohio, United States
Summary Systemic IgG4 disease can have a wide spectrum of clinical presentation, which can mimic several other disease entities. In this report, we describe a series of two patients with IgG4-related disease who were referred to us initially with the diagnosis of acute cholecystitis and the second patient with metastatic pancreatic adenocarcinoma with peritoneal metastasis respectively. © 2015 Elsevier Masson SAS. All rights reserved.
A 68-year-old male was referred to us with new onset of jaundice, right-sided abdominal pain with 20-pound weight loss in past 3 months. He underwent ERCP at a local hospital and was found to have a distal biliary stricture. A plastic biliary stent was inserted and brush cytology from the distal biliary stricture was reportedly negative for cancer. Couple days after the procedure, patient complained of mild tenderness in his right upper quadrant without fever or any other new symptoms. A computed tomography (CT) scan of the abdomen revealed prominent head of the pancreas concerning for malignancy, thickened gall bladder wall with pericholecystic fluid. He was given the diagnosis of acute cholecystitis with possible pancreatic head adenocarcinoma. He was placed on oral ciprofloxacin and referred to us for further management. Upon arrival, his physical
∗ Corresponding author at: Department of Gastroenterology and Hepatology, Digestive Disease Institute, A31, The Cleveland Clinic, 9500 Euclid Avenue, Cleveland, Ohio 44195, United States. Tel.: +(216) 444 6521; fax: +(216) 444 6284. E-mail address: [email protected] (P. Chahal).
examination revealed an afebrile, anicteric man with a firm palpable right submandibular gland and an anterior cervical lymph node. Laboratory data showed IgG4 level of 164 mg/dL (reference range: 2.4—121.0 mg/dL). Endoscopic ultrasound (EUS) revealed a diffusely hypoechoic pancreas without a discrete mass and a focal mildly echogenic circumferential thickening of the distal bile duct without mass lesion. The entire clinical scenario was suspicious of systemic IgG4-related disease and thus biopsy of the right submandibular gland and lymph node was obtained. It showed fibroinflammatory infiltrates with non-necrotizing granulomata (Fig. 1A and B) and an increase in IgG4 positive plasma cells (Fig. 1C) consistent with IgG4-related chronic sclerosing sialadenitis but negative for neoplasm. Due to the CT finding of acute cholecystitis and persistent right upper quadrant pain, patient underwent cholecystectomy. During cholecystectomy his gallbladder was found to be diffusely erythematous with thickened wall up to 0.9 cm. Sections of the gallbladder showed extensive surface erosion and mucosal and mural neutrophilic and eosinophilic inflammation on a background of storiform cellular fibrosis (Fig. 1D) and lymphocytic phlebitis (Fig. 1E). Immunohistochemical
http://dx.doi.org/10.1016/j.clinre.2015.06.003 2210-7401/© 2015 Elsevier Masson SAS. All rights reserved.
Please cite this article in press as: Yadav D, et al. IgG4 disease: The great masquerader. Clin Res Hepatol Gastroenterol (2015), http://dx.doi.org/10.1016/j.clinre.2015.06.003
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Figure 1 A. Histology and immunohistochemical stain for IgG4 of the submandibular gland showed dense lymphoplasmacytic infiltrate with gland atrophy and fibrosis. B. Histology and immunohistochemical stain for IgG4 of the submandibular gland noncaseating granuloma (H&E stain, 200×). C. Histology and immunohistochemical stain for IgG4 of the submandibular gland showed increase in IgG4 positive plasma cells. D. Histology and immunohistochemical stain for IgG4 of the gallbladder erosion, acute cholecystitis on a background of storiform cellular fibrosis (H&E stain, 40×). E. Histology and immunohistochemical stain for IgG4 of the gallbladder showed lymphocytic phlebitis (H&E stain, 200×). F. Immunohistochemical stain for IgG4, 200× showed increase in IgG4 positive plasma cells.
stain for IgG4 revealed the presence of up to 27 IgG4 positive plasma cells (Fig. 1F). The overall histologic features of the gallbladder were consistent with IgG4-related sclerosing cholangitis with obstructive cholecystitis. Patient was placed on tapering course of prednisone 40 mg daily and at 4 months follow-up had complete resolution of his bile duct stricture, enlarged cervical node, enlarged salivary glands and mass like appearance of his pancreas. He remains asymptomatic at 2-year follow-up. A 58-year-old male was referred to us with new onset of painless obstructive jaundice, diabetes with 25-pound
weight loss in past 3 months. A computed tomography (CT) scan done at outside facility demonstrated a mass in the pancreatic head and body, dilated biliary tree, left hepatic lesion as well 2 peritoneal nodules. He was diagnosed with metastatic pancreatic adenocarcinoma with peritoneal carcinomatosis and was referred to us for further management. Upon arrival, his physical exam was largely unremarkable apart from visible icterus. We performed EUS, which showed circumferential thickening of distal bile duct wall, diffuse hypoechoic changes in the entire pancreas suggestive of autoimmune pancreatitis with mass like appearance
Please cite this article in press as: Yadav D, et al. IgG4 disease: The great masquerader. Clin Res Hepatol Gastroenterol (2015), http://dx.doi.org/10.1016/j.clinre.2015.06.003
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ARTICLE IN PRESS
IgG4 disease: The great masquerader
Figure 2
Figure 3
Sausage-shaped enlargement.
Low-attenuation pancreatic head.
of pancreatic head. Fine needle aspiration of pancreatic head was done and it showed granulomatous inflammation and stromal fragments, negative for malignant cells. CT scan was repeated revealing sausage-shaped enlargement of the pancreas with thin hypo-enhancing rim around the parenchyma (Fig. 2). Laboratory data showed IgG4 level of 564 mg/dL (reference range: 2.4—121.0 mg/dL) suggestive of autoimmune pancreatitis. Diagnosis of IgG4-related disease was confirmed by a peritoneal nodule biopsy. He was started on tapering course of prednisone 40 mg orally and at 6-week follow-up. Repeat CT scan showed improvement with a decrease in the size of pancreatic enlargement and peritoneal nodules. Multiple more conspicuous focal low-attenuation renal lesions (Figs. 3 and 4) were identified which was suggestive of IgG4 interstitial nephritis. He continued tapering dose of prednisone and eventually maintained at 5 mg per day with addition of 150 mg daily of oral
xxx.e3
Figure 4
Attenuation of right kidney.
Azathioprine as his maintenance regimen. Patient remains asymptomatic at 18 months follow-up. Discussion: IgG4-related disease is a great masquerader with a hugely varied clinical presentation. It is a multi-organ syndrome characterized by typical histological features of lymphoplasmacytic sclerosing chronic inflammation in affected organs, frequent elevations of serum IgG4, and abundant IgG4 + plasma cells in affected organs. However, patients with systemic IgG4-related disease may not exhibit all of the above features. This leads to often seen misdiagnosis and delay in reaching the correct diagnosis in this unique subset of patients [1,2]. Our two cases highlight this challenging aspect of this disease entity apart from their intriguing clinical presentation. To our knowledge, there has been only one previous report of IgG4-related disease presenting with the pancreatic mass, obstructive jaundice and peritoneal nodules. Clinicians should be aware of these diverse spectrums of presentation of this enigmatic disease entity.
Disclosure of interest The authors declare that they have no conflicts of interest concerning this article. Financial support: none.
References [1] Leise MD, Smyrk TC, Takahashi N, Sweetser SR, Vege SS, Chari ST. IgG4-associated cholecystitis: another clue in the diagnosis of autoimmune pancreatitis. Dig Dis Sci 2011;56(5):1290—4, http://dx.doi.org/10.1007/s10620-010-1478-9. e P, Dvoˇrᡠcková J, Novotn´ y I, Floreánová K, [2] Bojková M, Dítˇ Kianiˇ cka B, et al. Immunoglobulin G4, autoimmune pancreatitis and pancreatic cancer. Dig Dis 2015;33:86—90.
Please cite this article in press as: Yadav D, et al. IgG4 disease: The great masquerader. Clin Res Hepatol Gastroenterol (2015), http://dx.doi.org/10.1016/j.clinre.2015.06.003
ARTICLE IN PRESS
Clinics and Research in Hepatology and Gastroenterology (2015) xxx, xxx.e1—xxx.e3
Available online at
ScienceDirect www.sciencedirect.com
CASE REPORT
IgG4 disease: The great masquerader Divya Yadav a, Xiuli Liu b, Prabhleen Chahal a,∗ a
Department of Gastroenterology and Hepatology, Digestive Disease Institute, Cleveland Clinic, Cleveland, Ohio, United States b Department of Anatomic Pathology, Cleveland Clinic, Cleveland, Ohio, United States
Summary Systemic IgG4 disease can have a wide spectrum of clinical presentation, which can mimic several other disease entities. In this report, we describe a series of two patients with IgG4-related disease who were referred to us initially with the diagnosis of acute cholecystitis and the second patient with metastatic pancreatic adenocarcinoma with peritoneal metastasis respectively. © 2015 Elsevier Masson SAS. All rights reserved.
A 68-year-old male was referred to us with new onset of jaundice, right-sided abdominal pain with 20-pound weight loss in past 3 months. He underwent ERCP at a local hospital and was found to have a distal biliary stricture. A plastic biliary stent was inserted and brush cytology from the distal biliary stricture was reportedly negative for cancer. Couple days after the procedure, patient complained of mild tenderness in his right upper quadrant without fever or any other new symptoms. A computed tomography (CT) scan of the abdomen revealed prominent head of the pancreas concerning for malignancy, thickened gall bladder wall with pericholecystic fluid. He was given the diagnosis of acute cholecystitis with possible pancreatic head adenocarcinoma. He was placed on oral ciprofloxacin and referred to us for further management. Upon arrival, his physical
∗ Corresponding author at: Department of Gastroenterology and Hepatology, Digestive Disease Institute, A31, The Cleveland Clinic, 9500 Euclid Avenue, Cleveland, Ohio 44195, United States. Tel.: +(216) 444 6521; fax: +(216) 444 6284. E-mail address: [email protected] (P. Chahal).
examination revealed an afebrile, anicteric man with a firm palpable right submandibular gland and an anterior cervical lymph node. Laboratory data showed IgG4 level of 164 mg/dL (reference range: 2.4—121.0 mg/dL). Endoscopic ultrasound (EUS) revealed a diffusely hypoechoic pancreas without a discrete mass and a focal mildly echogenic circumferential thickening of the distal bile duct without mass lesion. The entire clinical scenario was suspicious of systemic IgG4-related disease and thus biopsy of the right submandibular gland and lymph node was obtained. It showed fibroinflammatory infiltrates with non-necrotizing granulomata (Fig. 1A and B) and an increase in IgG4 positive plasma cells (Fig. 1C) consistent with IgG4-related chronic sclerosing sialadenitis but negative for neoplasm. Due to the CT finding of acute cholecystitis and persistent right upper quadrant pain, patient underwent cholecystectomy. During cholecystectomy his gallbladder was found to be diffusely erythematous with thickened wall up to 0.9 cm. Sections of the gallbladder showed extensive surface erosion and mucosal and mural neutrophilic and eosinophilic inflammation on a background of storiform cellular fibrosis (Fig. 1D) and lymphocytic phlebitis (Fig. 1E). Immunohistochemical
http://dx.doi.org/10.1016/j.clinre.2015.06.003 2210-7401/© 2015 Elsevier Masson SAS. All rights reserved.
Please cite this article in press as: Yadav D, et al. IgG4 disease: The great masquerader. Clin Res Hepatol Gastroenterol (2015), http://dx.doi.org/10.1016/j.clinre.2015.06.003
+Model CLINRE-767; No. of Pages 3
ARTICLE IN PRESS
xxx.e2
D. Yadav et al.
Figure 1 A. Histology and immunohistochemical stain for IgG4 of the submandibular gland showed dense lymphoplasmacytic infiltrate with gland atrophy and fibrosis. B. Histology and immunohistochemical stain for IgG4 of the submandibular gland noncaseating granuloma (H&E stain, 200×). C. Histology and immunohistochemical stain for IgG4 of the submandibular gland showed increase in IgG4 positive plasma cells. D. Histology and immunohistochemical stain for IgG4 of the gallbladder erosion, acute cholecystitis on a background of storiform cellular fibrosis (H&E stain, 40×). E. Histology and immunohistochemical stain for IgG4 of the gallbladder showed lymphocytic phlebitis (H&E stain, 200×). F. Immunohistochemical stain for IgG4, 200× showed increase in IgG4 positive plasma cells.
stain for IgG4 revealed the presence of up to 27 IgG4 positive plasma cells (Fig. 1F). The overall histologic features of the gallbladder were consistent with IgG4-related sclerosing cholangitis with obstructive cholecystitis. Patient was placed on tapering course of prednisone 40 mg daily and at 4 months follow-up had complete resolution of his bile duct stricture, enlarged cervical node, enlarged salivary glands and mass like appearance of his pancreas. He remains asymptomatic at 2-year follow-up. A 58-year-old male was referred to us with new onset of painless obstructive jaundice, diabetes with 25-pound
weight loss in past 3 months. A computed tomography (CT) scan done at outside facility demonstrated a mass in the pancreatic head and body, dilated biliary tree, left hepatic lesion as well 2 peritoneal nodules. He was diagnosed with metastatic pancreatic adenocarcinoma with peritoneal carcinomatosis and was referred to us for further management. Upon arrival, his physical exam was largely unremarkable apart from visible icterus. We performed EUS, which showed circumferential thickening of distal bile duct wall, diffuse hypoechoic changes in the entire pancreas suggestive of autoimmune pancreatitis with mass like appearance
Please cite this article in press as: Yadav D, et al. IgG4 disease: The great masquerader. Clin Res Hepatol Gastroenterol (2015), http://dx.doi.org/10.1016/j.clinre.2015.06.003
+Model CLINRE-767; No. of Pages 3
ARTICLE IN PRESS
IgG4 disease: The great masquerader
Figure 2
Figure 3
Sausage-shaped enlargement.
Low-attenuation pancreatic head.
of pancreatic head. Fine needle aspiration of pancreatic head was done and it showed granulomatous inflammation and stromal fragments, negative for malignant cells. CT scan was repeated revealing sausage-shaped enlargement of the pancreas with thin hypo-enhancing rim around the parenchyma (Fig. 2). Laboratory data showed IgG4 level of 564 mg/dL (reference range: 2.4—121.0 mg/dL) suggestive of autoimmune pancreatitis. Diagnosis of IgG4-related disease was confirmed by a peritoneal nodule biopsy. He was started on tapering course of prednisone 40 mg orally and at 6-week follow-up. Repeat CT scan showed improvement with a decrease in the size of pancreatic enlargement and peritoneal nodules. Multiple more conspicuous focal low-attenuation renal lesions (Figs. 3 and 4) were identified which was suggestive of IgG4 interstitial nephritis. He continued tapering dose of prednisone and eventually maintained at 5 mg per day with addition of 150 mg daily of oral
xxx.e3
Figure 4
Attenuation of right kidney.
Azathioprine as his maintenance regimen. Patient remains asymptomatic at 18 months follow-up. Discussion: IgG4-related disease is a great masquerader with a hugely varied clinical presentation. It is a multi-organ syndrome characterized by typical histological features of lymphoplasmacytic sclerosing chronic inflammation in affected organs, frequent elevations of serum IgG4, and abundant IgG4 + plasma cells in affected organs. However, patients with systemic IgG4-related disease may not exhibit all of the above features. This leads to often seen misdiagnosis and delay in reaching the correct diagnosis in this unique subset of patients [1,2]. Our two cases highlight this challenging aspect of this disease entity apart from their intriguing clinical presentation. To our knowledge, there has been only one previous report of IgG4-related disease presenting with the pancreatic mass, obstructive jaundice and peritoneal nodules. Clinicians should be aware of these diverse spectrums of presentation of this enigmatic disease entity.
Disclosure of interest The authors declare that they have no conflicts of interest concerning this article. Financial support: none.
References [1] Leise MD, Smyrk TC, Takahashi N, Sweetser SR, Vege SS, Chari ST. IgG4-associated cholecystitis: another clue in the diagnosis of autoimmune pancreatitis. Dig Dis Sci 2011;56(5):1290—4, http://dx.doi.org/10.1007/s10620-010-1478-9. e P, Dvoˇrᡠcková J, Novotn´ y I, Floreánová K, [2] Bojková M, Dítˇ Kianiˇ cka B, et al. Immunoglobulin G4, autoimmune pancreatitis and pancreatic cancer. Dig Dis 2015;33:86—90.
Please cite this article in press as: Yadav D, et al. IgG4 disease: The great masquerader. Clin Res Hepatol Gastroenterol (2015), http://dx.doi.org/10.1016/j.clinre.2015.06.003