Granulocyte colony-stimulating factor-producing hepatocellular carcinoma with abrupt changes

Abstract

Granulocyte colony-stimulating factor (G-CSF)-producing tumor is one of the rare types of cancer clinically characterized by an elevated fever and white blood cell (WBC) increment. Although G-CSF producing tumors have been reported in several types of cancer including those of the lungs, cervix and bladder, G-CSF producing hepatocellular carcinoma is extremely rare. Here, we report the case of a rapidly growing and poorly differentiated hepatocellular carcinoma producing G-CSF. The patient showed symptoms of continuous high fever, stomach pain and cough, and high serum WBC counts, C-reactive protein (CRP) and G-CSF levels were found in laboratory tests. After a radical hepatectomy, the patient completely recovered from the above symptoms and inflammatory state. The serum levels of G-CSF were reduced to normal levels after radical surgery. An immunohistochemical analysis revealed the overexpression of G-CSF in the cytoplasm of certain hepatocellular carcinoma (HCC) cell. The patient's serum WBC, CRP and G-CSF levels remained within normal levels in the six months after surgery without recurrence. This is the 9^th case report of G-CSF producing hepatocellular carcinoma in English literature. We review the clinical characteristics of the G-CSF producing HCC and discuss a possible treatment strategy.

Keywords: Granulocyte colony stimulating factor; Granulocyte colony-stimulating factor producing tumor; Hepatocellular carcinoma; Immunohistochemistry; Sarcomatous changes.

Figure 1

Imaging and macroscopic findings of granulocyte colony-stimulating factor producing hepatocellular carcinoma. A: CT scan one month before operation showed an irregular liver mass located in segment IV, approximately 60 mm in diameter with peripheral enhancement (white arrow head); B: T2-WI MRI one week before operation showed the rapidly growing liver mass with a 100 mm diameter (white arrow head); C: Macroscopic examination showed a large tumor (100 mm × 100 mm) that protruded through segment IV of the liver to the greater omentum; D: The irregular liver tumor in segment IV showed a central necrosis.

Figure 2

Physiological and laboratory changes during the treatment. A: Changes in body temperature during the treatment; B: Laboratory changes during the treatment; 1: Steady state; 2: Admission; 3: Pre operation; 4: Post-operation; 5: Within 2 mo after operation; 6: More than 2 mo after operation; C: White blood cell count, neutrophil proportion and C-reactive protein were collected at various treatment points including “steady-state” (more than six months before admission), “before admission” (within six months of admission), “pre-operation” (from admission until operation), “post-operation” (from operation until discharge), “within two months of surgery” and “more than two months after operation”.

Figure 3

Histopathologic findings. Microscopic findings showed atypical poorly differentiated cells with a sheet structure (A); HCC tumor was also composed of sarcomatous spindle-shaped cells (B); in both samples, a drastic infiltration of the neutrophils was found (H and E, × 20). Immunohistochemical findings showed CAM5.2 positive in the moderately to poorly differentiated HCC lesion (C) and negative in the spindle-shaped cell lesion (D) (CAM5.2, × 20). Immunohistochemical examination showed that G-CSF was positive in the moderately to poorly differentiated HCC lesion (E, F) (G-CSF, × 20 and × 40). G-CSF: Granulocyte colony-stimulating factor; HCC: Hepatocellular carcinoma cell.