Isolated variant of IgG4-sclerosing cholangitis masquerading as hilar cholangiocarcinoma — an enigmatic entity

Egyptian Liver Journal (2023) 13:23 Ravi et al. Egyptian Liver Journal https://doi.org/10.1186/s43066-023-00256-w Open Access CASE REPORT Isolated variant of IgG4‑sclerosing cholangitis masquerading as hilar cholangiocarcinoma — an enigmatic entity Soundarya Ravi1* , Srinivas Bheemanathi Hanuman1, Senthil Gnanasekhran2 and Biju Pottakkat2 Abstract Background IgG4-mediated sclerosing cholangitis (IgG4-SC) is an autoimmune disease that generally occurs in association with type 1 autoimmune pancreatitis (AIP). However, an isolated variant of IgG4-SC is a rare disease that can occur without concurrent AIP and closely mimics extrahepatic cholangiocarcinoma both clinically and radiologically. Case presentation Here, we report a case of an isolated variant of IgG4-SC, which was pre-operatively diagnosed as hilar cholangiocarcinoma. Pathological and immunohistochemical examination revealed features suggestive of IgG4SC, which was confirmed by elevated serum IgG4 levels measured postoperatively. Conclusion Therefore, IgG4-SC should be carefully ruled out in patients presenting with isolated bile duct obstruction, before performing morbid surgical procedures. Keywords Autoimmune, Cholangitis, IgG4 related disease Background IgG4-related disease (IgG4-RD) is a systemic immunemediated chronic inflammatory disease, commonly affecting middle-aged to elderly men, and is characterized by IgG4 type of plasma cell infiltration accompanied by dense fibrosis of the affected organs [1]. IgG4-mediated sclerosing cholangitis (IgG4-SC) is the biliary manifestation of this disease in which the patients present with obstructive jaundice and weight loss. It usually occurs in association with type 1 autoimmune pancreatitis (AIP) [2]. Isolated variant of IgG4-SC is a rare disease that occurs without concurrent AIP. The closest differential *Correspondence: Soundarya Ravi 1 Present Address: Department of Pathology (Histopathology Section), Jawaharlal Institute of Postgraduate Medical Education and Research, Pondicherry, India 2 Present Address: Department of Surgical Gastroenterology, Jawaharlal Institute of Postgraduate Medical Education and Research, Pondicherry, India diagnosis for isolated IgG4-SC is extra-hepatic/ hilar cholangiocarcinoma (CCA), as both these entities have overlapping clinical and radiological findings. However, the management and prognosis of both these entities are entirely different. Case presentation A 57-year-old male, farmer by occupation and non-alcoholic, presented with dull aching upper abdominal pain and vomiting for 3 months associated with progressive yellowish painless discoloration of sclera, generalized pruritis, and significant weight loss noted in the past 2 weeks. He did not have a fever, abdominal distension, hematemesis, melena, clay-colored stools, chest and bony pain, or breathlessness. The patient was a chronic smoker for the past 30 years and a known hypertensive for the past 15 years on treatment. On examination, the patient was icteric and malnourished with multiple scratch marks on the skin. On abdominal examination, he had palpable hepatomegaly, 3 cm from the right costal margin. His liver function tests (LFT) suggested an obstructive pattern of jaundice. LFT values were as follows: total © The Author(s) 2023. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. Ravi et al. Egyptian Liver Journal (2023) 13:23 bilirubin, 7.73 mg/dl; direct bilirubin, 5 mg/dl; alanine aminotransferase (ALT), 53 IU/L; aspartate aminotransferase (AST), 41 IU/L; alkaline phosphatase (ALP), 280 IU/L; and gamma-glutamyl transferase (GGT), 41 IU/L. His CA19-9 levels were elevated (CA19-9, 80 U/mL; reference range: 0–37U/mL) Contrast-enhanced computed tomography (CECT) in the abdomen showed enlargement of the liver with intra-hepatic biliary radicle dilatation (IHBRD). There was asymmetrical circumferential wall thickening of the common bile duct in the hilum, causing proximal bilobar IHBRD with few enlarged lymph nodes in the retro portal and peripancreatic region (Fig. 1). Pancreas and main pancreatic duct (MPD) appeared unremarkable. These findings were confirmed by Magnetic resonance cholangiopancreatography (MRCP). Correlating with clinical findings, LFT, serum CA19-9 levels, and imaging, a clinical diagnosis of hilar CCA was rendered. A staging laparotomy was performed, which showed a hard stricturous lesion of length 2.5 cm in the hilum extending to both right and left hepatic ducts proximally. He underwent open segment I and IV resection of the liver with extra-hepatic bile duct resection and standard lymphadenectomy followed by Roux-en-Y anastomosis. The resected tissue was submitted for histopathological examination. Histopathological examination of the gross thickening present at the confluence of the hepatic and bile duct showed diffuse fibrosis of the duct wall with accentuation around the peri-biliary glands. There was a dense transmural inflammatory infiltrate as well as around the ductules comprising predominantly of plasma cells, lymphocytes, and few eosinophils with perineural extension (Fig. 2). However, there was no evidence of dysplasia or invasive malignancy in the biliary epithelium. Sections from the liver showed portal expansion by moderate lymphoplasmacytic infiltrates in the portal Fig 1 MRI axial cuts at the level of hilum showing bilobar IHBRD with the absence of formation of the primary confluence Page 2 of 5 tracts, mild bile ductular reaction along with porto-portal bridging fibrosis. Lobular hepatocytes showed feathery degeneration with canalicular cholestasis. There was no obliterative cholangitis, peri-ductal onion skin fibrosis, or ductopenia. One of the hilar lymph nodes also showed paracortical expansion by plasma cells. The plasma cells in the hilar stricture and the hilar lymph node were highlighted by IgG and IgG4 immunostains. There were around 30 IgG4-positive plasma cells per high power field with an IgG4/IgG ratio of more than 40% (Fig. 3). Correlating with the morphological and immunohistochemical findings, a diagnosis of IgG4-mediated sclerosing cholangitis (IgG4-SC) was favored. Retrospectively, postoperative serum IgG4 level wa (...truncated)