A 68-year-old Asian male presented at a local hospital with a 3-month history of high fever, loss of appetite, and 10-kg weight loss. He had no relevant medical history. Laboratory data showed leukocytosis, with a leukocyte count of 17,500/mm3, and an elevated serum C-reactive protein (CRP) concentration of 13.2 mg/dl. Computed tomography (CT) showed a mass of 50 mm in diameter at the tail of the pancreas. One week later, during which his symptoms had continued, he was transferred to our hospital for further examination.
Blood chemical findings in our hospital showed a leukocyte count of 14,900/mm3 and a CRP concentration of 13.5 mg/dl. His serum concentrations of aspartate aminotransferase, alanine aminotransferase, lactate dehydrogenase, creatinine, and amylase were within normal levels, but his serum alkaline phosphatase, leucine aminopeptidase, and gamma-glutamyl transpeptidase concentrations were elevated to 979, 125, and 266 U/l, respectively. Serum levels of carcinoembryonic antigen and pancreas cancer-associated antigen DUPAN-2 were within normal limits, whereas his carbohydrate antigen 19–9 concentration was elevated at 118.0 U/ml. Bacteriological examination showed no signs of infection.
Contrast-enhanced CT showed a heterogeneously stained tumor, 72 mm in diameter, at the tail of the pancreas (Fig. 1). 18 F-2-fluoro-2-deoxyglucose positron-emission tomography/computed tomography (FDG PET/CT) showed FDG accumulation in the tail of the pancreas (SUV max, 17.1), but at no other sites in his body (Fig. 2). Abdominal T2-weighted magnetic resonance imaging, performed 14 days after contrast-enhanced CT, showed a heterogeneous mass at the tail of the pancreas (Fig. 3); the tumor was twice as large as in the initial CT image. Dilatation of the main pancreatic and bile ducts was not detected (Fig. 3). Gastrointestinal endoscopy showed no signs of malignancy.
The rapid growth of the tumor, along with the continuous high fever, elevated leukocyte count, and elevated CRP, in the absence of infection, suggested that the mass was a G-CSF producing pancreatic cancer. The rapid growth of the tumor limited the time required to make a differential diagnosis. We therefore decided to resect the tumor, basing subsequent treatment on histopathological diagnosis. Three weeks after first presenting at our hospital, the patient underwent a distal pancreatectomy with splenectomy. Examination of frozen sections of the tumor indicated that it was an adenocarcinoma. There was no evidence of lymph node swelling or peritoneal dissemination. Intraoperative ultrasonography showed no space occupying lesion in the liver. The diameter of the resected specimen was 154 mm, three times as large as in the initial image (Fig. 4). Macroscopically curative resection was performed, despite the tumor invading the transverse mesocolon. The patient’s leukocyte count rapidly decreased from 26,800/mm3 on the day before the operation to 5,100/mm3 on postoperative day three, and his body temperature was rapidly reduced soon after the operation. He recovered well and was discharged from our hospital 2 weeks after the operation.
Histopathological examination identified the tumor as an anaplastic carcinoma of the pancreas, composed of a ductal carcinoma component, along with bizarre giant cells and spindle-cell differentiation (Fig. 5a). Immunohistochemical examination of the resected specimen showed G-CSF expression (Fig. 5b–d), which, together with his preoperative serum G-CSF concentration of 355 pg/ml (normal range <39 pg/ml), confirmed that the tumor was a G-CSF producing pancreatic cancer. On postoperative day 48, the patient returned to our hospital with a high fever and loss of appetite. CT showed tumor recurrence. He was started immediately on tegafur-gimeracil-oteracil potassium combination S-1 (TS-1) and steroid (betamethasone) 1 mg/day. Despite administration of steroid and nonsteroidal anti-inflammatory drugs, high fever remained unaltered. Serial leukocyte counts, granulocyte counts, and body temperature are shown in Fig. 6. Two weeks after starting on TS-1, he was admitted to our hospital. Contrast-enhanced CT showed peritoneal dissemination and liver metastases (Fig. 7). His leukocyte count and serum CRP concentration increased. He was continued on steroid and TS-1 for 3 weeks, but his condition worsened, and he died on postoperative day 83.