Gastrointestinal: Pitfalls of an abruptly elevated alpha-fetoprotein in a chronic hepatitis B carrier.

Abstract

A 31-year-old male with a history of diabetes mellitus and viral hepatitis B was admitted to our hospital in March 2021 for epigastric pain, steatorrhea, and increased alpha-fetoprotein (AFP). He had a history of excessive drinking for more than a decade. Two years ago, he was admitted to another institution due to abdominal distention, and computed tomography (CT) showed enlargement of the pancreas. He then received endoscopic ultrasonography-guided fine-needle aspiration (EUS-FNA) and was diagnosed with chronic pancreatitis. Since then, he lost 25 kg, despite relief of associated symptoms after medical treatment, including pancreatic enzyme preparations and prokinetics. Physical examination showed tenderness in the upper abdomen. Laboratory examination revealed the following abnormalities: white blood cell count (11.01 × 109/L), erythrocyte sedimentation rate (120 mm/h), alkaline phosphatase (163 U/L; reference range, 45–125 U/L), γ-glutamyl transpeptidase (223 U/L; reference range, 10–60 U/L), CEA (9.32 ng/mL; reference range, 0–5.00 ng/mL), AFP (3473 ng/mL; reference range, 0–20 ng/mL). Measurements of CA19–9 (21.70 U/mL; reference range, 0–34.00 U/mL) and IgG4 (0.263 g/L, reference range, 0.030–2.100 g/L) were normal. A plain/contrast CT of the abdomen revealed diffuse enlargement of the pancreas with hypodensity, focal coarse calcifications, and a capsule rim sign (Fig. 1a). Positron emission tomography demonstrated an increased uptake of 18F-FDP in the pancreatic head and uncinate process (Fig. 1b). Endoscopic ultrasound examination showed a hypoechoic mass located at the pancreatic head, and fine needle aspiration was performed (Fig. 2a–d). Based on the patient's symptoms and history (male, alcohol consumption, viral hepatitis and significantly increased AFP), the initial consultant doctor focused on screening for hepatocellular carcinoma (HCC). However, CT and positron emission tomography revealed no obvious abnormality of the liver but showed a suspicious pancreatic tumor and chronic pancreatitis (Fig. 1a,b). Though the IgG4 level was normal, considering the “sausage-like” appearance and capsule rim sign of the pancreas revealed by CT, we considered the differential diagnosis of autoimmune pancreatitis. Therefore, EUS-FNA was scheduled for further assessment. Ultrasonographic imaging showed a 4.5 × 4.2 cm hypoechoic mass in the pancreatic head, with an ill-defined border, heterogenous internal echogenicity, and diffusely scattered calcifications (Fig. 2a). Cytological examination revealed the morphology and size of the tumor cells were relatively consistent but moderately enlarged with salt-and-pepper nuclei, which are characteristics of pancreatic neuroendocrine tumors (Fig. 2b). Histopathologic findings showed a heterogenous gland pattern with irregular enlarged nuclei (Fig. 2c). The abnormal cells were found to be positive for CK7 and negative for Hep-par 1 (Fig. 2d), chromogranin A, synaptophysin, or CD56 by immunohistochemical staining (IHS). After a multidisciplinary discussion, final diagnosis was determined as pancreatic ductal adenocarcinoma (PDAC) based on histology and IHS. The patient eventually received chemotherapy consisted of gemcitabine plus capecitabine. After one cycle of treatment, the serum level of AFP rapidly decreased to 1347 ng/mL and related symptoms were relieved significantly. The patient has not returned for follow-up since then. AFP is generally used as a biomarker for HCC, yolk sac tumor, gonadal tumors, and certain types of gastric carcinomas. There are also some reports of AFP-producing pancreatic tumors, usually hepatoid carcinoma and acinar cell carcinoma. The reports of AFP-producing PDAC are rare. One possible explanation for AFP production in pancreatic cancer is the activation of the hepatic gene within the pancreas during carcinogenesis. To identify the diagnosis, histopathology and immunohistochemistry can be crucial. The level of AFP after treatment of the AFP-producing pancreatic tumor may serve as an indicator to monitor therapeutic response and recurrence.