A 62-year-old Asian man who had diffusive discomfort in the middle upper abdomen, accompanied by brown urine, mild yellow sclera, and occasional malaise was admitted to our hospital on November 2, 2020. Timeline of events is shown in Fig. 1.
Routine blood test (November 3, 2020) showed abnormal liver function: total bilirubin 43.00 umol/L↑(≤ 26.0 umol/L), direct bilirubin 41.0 umol/L↑(≤ 8.0 umol/L), total bile acid 61.0 umol/L↑(0-10.0 umol/L), glycocholic acid 64.5 mg/L↑(0-10.0mg/L), alanine aminotransferase 559U/L↑ (9-50 U/L), aspartate aminotransferase 401U/L↑ (15-40 U/L), AST mitochondrial isozyme 32.3 U/L↑ (≤15 U/L), alkaline phosphatase 808 U/L↑(45-125 U/L), γ-glutamyl transpeptidase 1799 U/L↑(10-60 U/L), lactate dehydrogenase 327 U/L↑ (120-250 U/L), and superoxide dismutase 259 U/mL↑ (129-216 U/mL). Serum tumor marker test showed elevated CA199 43.9 U/ml↑(≤30 U/ml). Hepatitis B and hepatitis C tests were negative. Serum IgG4 testing was performed to screen for autoimmune hepatitis, and the result was 4.830g/L↑ (< 2.01g/L).
Routine abdominal ultrasound (November 4, 2020) showed diffusive slight enlargement of the pancreas, dilated intra-/extra-hepatic bile duct, and enlarged gallbladder; space-occupying lesion at pancreas was detected.
Endoscopic ultrasound (EUS) and MRI were performed on November 9, 2020. EUS showed uneven echo in pancreatic neck adjacent to the portal vein and superior mesenteric vein (size about 2.0×2.5 cm2) with clear boundary. No obvious expansion of the main pancreatic duct in the body and tail pancreas was found. Possible malignancy was considered (Fig. 2). EUS-guided fine needle aspiration (FNA) was performed on the lesions at the neck of the pancreas via a transgastric approach. A small amount of white substance and some dark red suspension were collected. Cytological smear, liquid-based cytology, and histopathological examinations were performed respectively. Enhanced abdominal MRI and magnetic resonance cholangiopancreatography (MRCP) showed that the intrahepatic bile duct was slightly dilated, common bile duct was dilated, inflammation of lower segment of common bile duct was suspected, and the malignancy could still not be ruled out (Fig. 3).
In order to identify the nature of pancreatic lesions, further thin-slice enhanced CT and 18F-FDG PET/CT were performed on November 13, 2020. CT showed the suspected lesion in uncinate process of pancreas with intrahepatic and extrahepatic bile duct dilatation, suggesting possible malignancy (Fig. 4). 18F-FDG PET/CT showed the uncinate process of pancreas was mildly enlarged with bile duct tree dilated, the FDG metabolism was slightly increased in uncinate process and head of pancreas (SUVmax=4.07, SUVmean=2.25, 2.4cm × 1.8cm), and the possibility of malignant tumor was considered (Fig. 5).
On November 13, the result of FNA of pancreatic neck lesion turned out to be malignant negative, no evidence of neoplastic cell was seen in cytology and histopathological examination, and re-examination of serum IgG4 was 4.410 g/L↑ (< 2.01 g/L).
Up to this point, common pathogenesis for abnormal liver function (such as alcoholic, viral, pharmacological, genetic factors) was excluded. Based on elevated IgG4 and negative biopsy histology, IgG4-related disease was considered. Meanwhile, various imaging modalities were highly suggestive of underlying malignant tumor lesions. For further differentiation, the patient was enrolled in the clinical trial of 68Ga-FAPI PET/MR imaging approved by the institutional review board in our hospital, and written informed consent was obtained from the patient. From 68Ga-FAPI PET/MR, homogenously elevated radioactivity uptake was found in the entire pancreas (SUVmax=11.04, SUVmean=6.15) and increased radioactivity was also found around dilated intrahepatic and extrahepatic bile duct (SUVmax=3.61, SUVmean=1.92) (Fig. 6). These findings provided evidence for diagnosis of IgG4-RD involving pancreas and biliary tract.
Hormone therapy was initiated thereafter. Specifically, the patient was treated with methylprednisolone and prednisolone, as well as medication for liver protection, bile evacuation, and nutritional support.
After 2 weeks’ treatment, the patient’s blood test was as follows: total bilirubin 17.20 umol/L (≤26.0 umol/L), direct bilirubin 14.3 umol/L↑ (≤8.0 umol/L), total bile acids 11.7 umol/L↑(0–10.0 umol/L), glycocholic acid 6.6 mg/L (0–10.0 mg/L), alanine aminotransferase 41 U/L (9–50 U/L), aspartate aminotransferase 18 U/L (15–40 U/L), AST mitochondrial isoenzyme 1.7 U/L (≤15 U/L), alkaline phosphatase 338 U/L↑ ( 45–125 U/L), γ-glutamyl transpeptidase 478 U/L↑ (10–60 U/L), lactate dehydrogenase 116 U/l (120–250 U/l), and superoxide dismutase 192 U/mL (129–216 U/mL). Tumor marker CA199 was 10.4 U/ml (≤30 U/ml) and IgG4 was 4.220 g/L↑ (<2.01 g/L). The patient’s clinical symptoms improved significantly and liver function improved, so he was discharged on December 9, 2020.