Primary hepatic carcinoid tumor: A case report and literature review

Introduction: Primary hepatic carcinoid tumor (PHCT) is very rare and difficult to diagnose before biopsy or operation. We report a patient with a small PHCT and review cases in the literature. Case presentation: A 48-year-old Chinese female with underlying hepatitis B virus (HBV) infection was found to have a low echoic hepatic nodule by abdominal ultrasound. Tumor markers were negative. Dynamic liver computed tomography scans showed enhancement of the nodule in the arterial phase and early washout in the portal phase. Hepatocellular carcinoma (HCC) was considered based on the image findings and underlying HBV infection. However, the tumor biopsy revealed a malignant neoplasm that originating from neuroendocrine cells. Pre-operative and intra-operative investigations for the possible other origin of carcinoid tumor were negative, so PHCT was confirmed. Conclusion: A small and asymptomatic PHCT is extremely rare. PHCT should be one of the differential diagnoses in patients with small hepatic tumor, even in regions with high prevalence of HBV infection and HCC. Pre-operative biopsy is necessary to avoid misdiagnosis even when HCC is highly suspected clinically. Introduction: Carcinoid tumors are neuroendocrine origin neoplasm and may produce serotonin or other functional peptide hormones. They are well-differentiated and low-grade malignant neoplasms. Approximately 74% of all carcinoid tumors arise from the gastrointestinal (GI) tract and the liver is a common site for metastases 1 . However, primary hepatic carcinoid tumor (PHCT) is very rare and the first case was documented by Edmondson in 1958 2 . This rarity makes it difficult for clinicians to diagnose accurately before biopsy, resection of tumor, or autopsy 3 . Large-sized tumors are common presentations when they are diagnosed 4 . PHCT presents as a small and single nodule, is extremely rare and is difficult to differentiate from hepatocellular carcinoma (HCC), particularly in a region with high prevalence of HCC. Herein, we report a rare case of small PHCT with underlying HBV infection which was suspected to be a small HCC before operation and also comprehensively review 94 cases of PHCT in the literature. Case presentation A 48-year-old Chinese female with HBV infection for 15 years was regularly followed up at gastroenterology outpatient department by abdominal ultrasound (US) and serum alpha-fetoprotein (AFP) screening every six months. In May 2005, abdominal US demonstrated a low echoic nodule, 1.6 1.6 cm in size in the sixth segment of the liver and mild parenchymal liver disease (Fig.1A). She was asymptomatic and no abnormality was disclosed by physical examination. Noncontrast liver computed tomography (CT) showed a 1.6 1.6 cm well-circumscribed and low density nodule in the same liver segment (Fig.1B). Dynamic CT scans showed enhancement of the nodule in the arterial phase and early washout in the portal phase (Figs.1C and 1D). Serum was positive for hepatitis B surface antigen (HBsAg), but negative for HBeAg. The serum anti-HCV was also negative. AFP and CEA were with normal range. Based on the imaging findings and underlying HBV infection, small HCC was highly suspected and a US-guided liver biopsy was performed for definite diagnosis. However, the pathological finding suggested a malignant neoplasm originating form neuroendocrine cells (Fig. 2A). The result of immunohistochemistric (IHC) stain was positive for neuron-specific enolase (NSE), synaptophysin, and chromogranin A (Fig. 2B). The preoperative 24-hour urine 5-hydroxyindoleacetic acid (5-HIAA) value was within normal limits. We undertook a more thorough investigation to rule out the possibility that the liver tumor was a metastatic carcinoid. This workup included upper and low GI endoscopy, a small bowel series, abdominal US, and chest and abdominal CT scans. All imaging findings were unremarkable. Partial hepatectomy was performed. Small bowel, appendix and large bowel were checked during operation and no tumor was found. No cirrhotic liver was noted. The surgery was performed successfully and the patient recovered well. The resected liver tissue contained a 1.6x1.6x1.5 cm circumscribed tumor (Fig. 3). Histological examination revealed the round or ovoid neoplastic cells arranged in insular pattern with a rosette formation. There was no tumor embolus in the vessel and the resection line was free from tumor invasion. The IHC stains were positive for chromogranin A, cytokeratin, NSE, and synaptophysin. The final diagnosis was PHCT. She was followed up regularly at our hospital and remained disease-free 3 years after operation. Discussion: The origin of PHCT remains unknown. The cells may originate from ectopic pancreatic or adrenal tissue found within the liver or from scattered neuroendocrine cells in the intrahepatic biliary epithelium 5 . Some were observed in animal studies such as those found in the rat liver 6 . The scarcity of such cells may explain the rarity of primary hepatic neuroendocrine tumors. It is also proposed that chronic inflammation in the biliary system may induce intestinal metaplasia that predisposes to the development of neuroendocrine tumor 5 . Including our case, we found 94 cases of PHCT (including primary hepatic neuroendocrine tumor) in the literature 1-5, 7-15 and their clinical characteristics are summarized in Table 1. This type of tumor occurs mainly in middle age (mean age, 49.8 years) and is slightly more frequent in females (58.5%). The most common symptom among 84 cases was abdominal pain (37 cases, 44.0%). Eleven cases were asymptomatic (11.7%). The overall mortality rate was 25.5% (24/94) as shown in