Immunoglobulin G4-related disease (IgG4-RD) is a multiorgan immune-mediated fibro inflammatory condition that mimics many malignant, infectious, and inflammatory disorders.¹ Manifestation of this disease with subacute development of a mass in the affected organ or diffuse enlargement of an organ has been demonstrated in nearly every organ system.^1–3 Diffuse or focal lesions, usually in the form of a mass or swelling, are characteristic imaging findings.⁴ Pancreaticobiliary manifestations often present as mass lesions that mimic malignancy. These patients undergo radical surgery with a preliminary diagnosis of pancreatic adenocarcinoma and the surgical pathology results as IgG4-related autoimmune pancreatitis (AIP). Here, a patient who underwent total pancreatoduodenectomy, total gastrectomy, and total splenectomy due to the misdiagnosis of pancreatic adenocarcinoma and who developed severe morbidities afterward is presented.

A 42-year-old female had been seen at another hospital because of stomach and back pain. Computed tomography (CT) revealed two pancreatic mass lesions in the pancreatic uncinate process and tail (Fig. 1A); the pancreatic duct diameter was 2 mm and enlarged. Magnetic resonance imaging showed that the mass lesions exhibited low intensity on T1-weighted images (Fig. 1B) and slightly hyperintense on T2-weighted images. In a positron emission tomography (PET) scanning study of the left-axillary lymph node (maximal standard uptake value [SUVmax]: 5.36), a mass lesion in the head of the pancreas (SUVmax: 8.87) (Fig. 1C), a mass lesion of 26 mm × 21 mm in the tail of the pancreas (SUVmax: 7.71) (Fig. 1D), increased activity involvement in the uterus (SUVmax: 14.35) were detected. She had no medical history of autoimmune disease or excessive alcohol intake. On laboratory examination, the serum levels of total bilirubin, alkaline phosphatase, and γ-glutamyl transpeptidase were normal range. The level of the tumor markers carcinoembryonic antigen and carbohydrate antigen 19-9 (CA19-9) were in the normal ranges. A preoperative diagnosis of pancreatic malignancy was considered based on the imaging profile. No preoperative tissue diagnosis was made. The possibility of malignant tumors could not be ruled out because of the imaging profile; therefore, in September 2021, the Whipple procedure, total gastrectomy, and total splenectomy were applied to the patient. Histopathological examination revealed granulocytic epithelial lesions in a few areas (Fig. 2A, 2B), intense lymphoplasmacytic inflammation surrounding the pancreatic duct structures (Fig. 2C, 2D), storiform fibrosis in some areas (Fig. 2E), peripancreatitis (Fig. 2F) perineuritis, occasionally follicle-like aggregates, perivenular inflammation, and 30 IgG4+ plasma cells/HPF.

Figure 1. (A) Computed tomography (CT) scan showing hypodense solid nodular mass with the size of approximately 28 mm × 25 mm expanding towards the hilus of the splen which showing exophitic extension in the tail cut of the pancreas (arrow). (B) Magnetic resonance imaging showing T1a hypointense mass lesion of approximately 27 mm × 21 mm in the tail section of the pancreas (arrow). (C) Positron emission tomography (PET)-CT showing fluorodeoxyglucose F 18 (18-FDG)-avid mass lesion (arrow) in the head of the pancreas (maximal standard uptake value [SUVmax]: 8.87). (D) PET-CT showing 18-FDG-avid mass lesion of 26 mm × 21 mm (arrow) in the tail of the pancreas (SUVmax: 7.71).

Figure 2. (A, B) Granulocytic epithelial lesion. Duct epithelium is detached and lies in the lumen. There is dense inflammatory inflitration, including neutrophils (H&E, ×10). (C) Periductular inflammation in autoimmune pancreatitis (AIP). Dense inflammatory cell infiltration is present around a pancreatic duct. Pancreatic duct shows star-shaped deformation and luminal narrowing (H&E, ×10). (D) Periductal inflammation in AIP. Dense inflammatory cell infiltration is present around irregular pancreatic ducts showing luminal narrowing. Periductal inflammation extends into the surrounding parenchyma (H&E, ×10). (E) Storiform fibrosis in AIP. Storiform fibrosis is infiltrated by numerous lymphocytes (H&E, ×4). (F) Peripancreatitis. Chronic inflammatory cell infiltration and fibrosis extend into peripancreatic fat tissue (H&E, ×10).

The patient was referred to our rheumatology clinic with the current pathological findings. The IgG4 level was 1.97 g/L (normal range 0.03–2.10 g/L). According to these pathological findings, we diagnosed the patient with IgG4-related AIP. Methotrexate subcutaneous administration of 15 mg (once a week) and methylprednisolone 32 mg (with 4 mg reduction per week) treatment was started. The patient had developed a 30-kg weight loss and diarrhea after the surgery. Postoperation brittle diabetes mellitus had developed, and quadruple insulin therapy was started. The patient had developed morbidities such as blood sugar dysregulation, loss of appetite, diarrhea, and weight loss. She is being followed up in our clinic.

Two AIP subtypes exist, only one of which (type 1) is associated with IgG4-RD, also denoted as lymphoplasmacytic sclerosing pancreatitis.⁵ AIP frequently presents as painless obstructive jaundice or as a pancreatic mass and can be mimicking for pancreatic cancer. Abdominal pain associated with IgG4-related AIP can be seen in a broad spectrum, from mild dyspeptic complaints to severe abdominal pain associated with pancreatitis. Our patient had stomach and back pain.

Elevations of the bilirubin level and biliary tract enzymes are frequently observed, indicating obstructive jaundice, a common clinical presentation of IgG4-related AIP. In the presented patient, bilirubin level and biliary tract enzyme levels were normal. On diagnostic imaging, some patients show diffuse pancreatic swelling, and others show localized swelling or pancreatic mass formation, leading to concern for pancreatic adenocarcinoma.⁶ The imaging profile revealed enlargement of the pancreatic duct, two pancreatic mass lesions in the pancreatic uncinate process, and the pancreatic tail in the presented patient. The possibility of pancreatic adenocarcinoma could not be ruled out because of the two mass lesions but enlargement in the pancreatic duct could be predictive of AIP.

In a study of 33 patients who underwent pancreaticoduodenectomy and left pancreatic resection with the preliminary diagnosis of pancreatic carcinoma, by Ráty et al,⁷ histopathologically IgG4 staining consistent with type 1 AIP was found in the specimens of 10 patients. Our patient has also applied a very aggressive surgical treatment due to the pre-diagnose of pancreas adenocarcinoma. The outcome of this study demonstrates that by focusing on the preoperative diagnosis of AIP, possibly unnecessary surgery can be prevented.

In a study by van Heerde et al,⁸ CA19-9 and IgG4 levels were measured in 33 patients with AIP. Fifty-three pancreatic carcinoma, 145 other pancreaticobiliary diseases and lower levels of CA19-9 were found in patients with AIP compared to pancreatic adenocarcinoma. According to this study, when the two tests are combined, assuming an upper limit of 74 U/mL for the CA19-9 test and a lower limit of 1.0 g/L for the IgG4 test, distinguishes patients with AIP from pancreatic cancer patients with 94% sensitivity and 100% specificity. In the presented case, the IgG4 level was 1.97 g/L and the CA19-9 test was 14.2 U/mL.

To exclude pancreatic cancer, histopathological diagnosis can be made with endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) or EUS fine needle biopsy (EUS-FNB).⁹ In the presented case, EUS-FNA was unfortunately not performed to diagnose pancreatic mass lesions.

Wu et al¹⁰ suggested some clinical strategies to distinguish between IgG4-related AIP and malignant tumors to avoid unnecessary surgical resection. According to this algorithm for patients considered malignancy, a review of the imaging data is essential if γ-globulin level rises. If the typical imaging features of AIP are shown, a serum IgG4 test should be performed. Patients with increased serum IgG4 levels can be confirmed as AIP and given steroid therapy instead of surgery. To avoid surgery, patients with an insignificant risk of malignancy could receive diagnostic steroid treatment. None of the recommendations in this algorithm was applied to the patient presented here.

In conclusion, IgG4-Associated AIP is a rare disease that presents multiple mass lesions in the pancreas, mimics pancreatic adenocarcinoma, and responds very well to steroid therapy. In the literature, many patients diagnosed with AIP after surgery with a preliminary diagnosis of pancreatic adenocarcinoma, but the patient presented here was treated more aggressively than the surgeries applied to patients in the literature, and total gastrectomy and total splenectomy were performed in addition to total pancreatoduodenectomy. Misdiagnosis of pancreatic adenocarcinoma leads to radical surgeries that cause serious patient morbidity. As a result of these surgeries, the patient developed severe weight loss, chronic diarrhea, and brittle diabetes mellitus. If EUS-FNA, FNB, or explorative laparotomy had been performed or if the patient had been given diagnostic steroid therapy such an aggressive surgical treatment would not have been applied. In patients with multiple masses in the pancreas, considering the possibility of AIP, although it is rare, and performing the necessary diagnostic procedures for exclusion will protect patients from unnecessary surgeries that may lead to severe morbidities.

This paper was presented as an poster in 22nd National Rheumatology Congress, 26-30 October 2022, Glroia Golf Hotel Antalya.

None.

No potential conflict of interest relevant to this article was reported.