Teaching Case

A 71-year-old male presented to the General Medicine department with complaints of vague abdominal pain and nausea. Laboratory investigations revealed deranged liver function tests (including raised bilirubin, SGOT, SGPT, ALP, and GGT). The patient had a history of diabetes mellitus with present HbA1c levels of 7.3%. ESR was also elevated.

A contrast-enhanced computed tomography (CECT) of the abdomen revealed a delayed enhancing hypodense area encasing the body and tail of the pancreas with minimal peri-pancreatic fat stranding (Figure 1). Enhancing soft tissue thickening was also seen in the proximal common bile duct/common hepatic duct region, along with mild intrahepatic biliary radicals dilatation (Figures 2 and 3). Non-enhancing soft tissue thickening was seen along the para-aortic and para-iliac regions (Figure 4). A few mildly prominent upper retroperitoneal lymph nodes were also noted. An autoimmune spectrum involving the retroperitoneum, pancreas, and biliary tree was suspected.

Later, a magnetic resonance cholangiopancreatography (MRCP) was done, which revealed T1 and T2-isointense soft tissue, thickening along the proximal common hepatic duct, biliary confluence, and left hepatic duct with resulting marked luminal narrowing/stricture and associated mild bilobar intrahepatic biliary radicals dilatation (Figure 6). The MRCP revealed the possibility of sclerosing cholangitis and a less likely differential of cholangiocarcinoma. A T1 and T2-hypointense area was noted along the peripheral pancreatic parenchyma (Figure 5). The MRI findings complemented the aforementioned CT-based diagnosis. Immunoglobulin G4 (IgG4) levels were also found to be elevated.

IgG4-related disease is an auto-immune, multi-systemic disorder, with diffuse fibro-inflammatory infiltrates, including IgG4-containing plasma cells (Figure 7). It can mimic various neoplastic and other inflammatory diseases, making it important to differentiate and diagnose early. The IgG4-related disease can affect multiple organs, including the biliary system, retro-peritoneum, kidneys, prostate, testicles, thyroid, salivary and lacrimal glands, lungs, breasts, and pituitary. Hence, clinical features of IgG4-related disease are based on the organ affected, and the presentation is usually sub-acute to chronic, with many cases found incidentally on imaging.

A good clinical examination with laboratory and radiological workup aids in narrowing down the diagnosis, with immunohistochemistry and histopathology being the gold standard. Serum IgG4 levels are also elevated in IgG4-related disease, although normal IgG4 levels cannot rule out its possibility. Hence, imaging workup (CT, MRI, or 18F-FDG PET/CT) is vital to complement clinical and laboratory findings.

IgG4-related disease frequently involves the abdomen, with the biliary system and pancreas being most commonly affected. IgG4-related autoimmune pancreatitis presents as either diffuse uniform enlargement of the pancreas with loss of the normal pancreatic clefts (“sausage pancreas”) or as focal mass-like enlargement [1,2]. The pancreas appears diffusely or focally hypoechoic on ultrasonography, mildly hypodense on CT with loss of pancreatic clefts, and a peripheral halo of low-attenuation on delayed-contrast-enhanced CT. On MRI, the pancreas appears mildly hyperintense on T2-weighted MR images and hypointense on T1-weighted images, with delayed parenchymal enhancement of post-contrast images. It also shows diffusion restriction on DWI and ADC mapping.

IgG4-related sclerosing cholangitis can affect both the intrahepatic and extrahepatic biliary tree, resulting in focal or diffuse duct wall thickening with or without stenosis and upstream dilatation [2,3]. MRI shows T1 and T2-isointense soft tissue thickening along the biliary duct with or without delayed post-contrast enhancement.

The majority of retroperitoneal fibrosis is related to the IgG4 spectrum. On CT, IgG4-related retroperitoneal fibrosis is seen as a para-aortic or a periureteral soft tissue mass, with or without delayed post-contrast enhancement. On MRI, the mass typically appears hypo-isointense on T1-weighted images, with variable signal intensity on T2-weighted images depending on the extent of fibrosis, and with or without post-contrast enhancement.

IgG4-related disease being autoimmune and immune-mediated, responds well to immunosuppression therapy, including corticosteroids. Hence, early diagnosis can prevent the patient from unnecessary medical and surgical interventions, as IgG-4 disease can mimic malignancy.

All patient data have been completely anonymised throughout the entire manuscript and related files.