Generally speaking, in contrast to the HCC plus cholangiocarcinoma type in the liver, the concurrent occurrence of HCC and NEC is rarer because the incidence of primary hepatic NEC is very rare in contrast to occasional intrahepatic metastasis of NEC. Diagnosis requires a comprehensive histopathological evaluation together with immunohistochemistry. The rare occurrence of these tumors necessitates more reported cases in order to fully understand their clinical characteristics, behaviors and treatments. We present a case of a liver tumor with features of both classical HCC and NEC. In this case, the patient is young, male, and has a history of hepatitis B, which is consistent with the previous literature [5, 6, 7], which all featured male patients with underlying liver disease, involving chronic hepatitis or cirrhosis of unknown cause, sometime a fat component [8].
On immunohistochemistry, this tumor composed with a cell carcinoma with features of a small neuroendocrine carcinoma. It was strongly positive HCC marker of HEPA and GPC-3, and positive neuroendocrine markers of chromogranin, synaptophysin, CD56, and GPC-3. The tumors were separated from each other by broad fibrous bands. No transition areas were present. Even in the areas of closest proximity the tumors were sharply demarcated and were compressing, rather than infiltrating. In terms of genes, ERIN BAKER et al [9] reported through genetic analysis, both tumor components contained gene mutations in CTNNB1 gene (S33F located in exon 3), and also shared mutations in PD-1, PGP, and SMO in the genes. The nonneoplastic liver showed liver cirrhosis and portal fibrosis.
Combined hepatocellular and neuroendocrine carcinoma, on the one hand, is similar to hepatocellular carcinoma in terms of hematology and imaging tests, such as hepatitis B and C virus infection status, blood AFP level, and presence or absence of combined liver cirrhosis; on the other hand, vascular and extrahepatic metastasis of mixed liver carcinoma are similar to cholangiocarcinoma, so it is quite difficult to obtain a precise diagnosis before surgery. In this case, we found our patient with solid tumor with cystic changes on ultrasonography. Further research is needed to confirm the idea that whether it differs from the colliquation necrosis in HCC and is helpful for differential diagnosis [10, 11]. The contrast-enhanced ultrasound performance of the type mixed tumor was reported for the first time. The manifestation of CEUS of the tumor (homogeneously hyper-enhanced in the arterial phase, heterogenous mild enhancement in the portal phase and hypo-enhanced in the parenchymal phase) is similar to that of HCC, so it is believed that this may be the reason for the misdiagnosis. Another important problem to be solved in making a diagnosis of concurrent HCC and NEC is the discrimination of primary NEC and from metastatic NEC [12], as the liver is the most frequent site of metastasis for NEC. Therefore other primary sites should be examined when an NEC is suspected in the liver. In our case, there were no other neoplastic lesions found besides in the liver.
The prognosis and treatment of HCC accompanied by NEC are uncertain due to the small number of cases studied. This observation suggested that NEC components strongly affect the aggressive behavior of the tumor and it is proposed that the NEC component may be responsible for the poor prognosis in these patients. The treatment is also a comprehensive treatment based on hepatectomy, combining with multiple treatment modes including radical resection, lymph node dissection, and adjuvant treatment in order to improve the efficacy and prolong survival time. Other treatment such as transcatheter arterial chemoembolization (TACE) and percutuneors ethanol injectiontherapy (PEIT) can be considered as well, especially when a tumor recurs.
In conclusion, the rare occurrence of HCC-NEC and the lack of diagnostic clinical signs and symptoms do not exclude their consideration in the differential diagnosis of liver tumors, especially in patients with the chronic liver disease, regardless of the presence of cirrhosis. Since HCC-NEC is easy to confuse with hepatocellular carcinoma, careful screening of symptoms is needed to avoid misdiagnosis. Resection is the first choice of treatment for HCC-NEC and provides the most favorable outcomes including long-term survival. We hope that our report will increase awareness of this combined entity in the liver and that further experience contributes in the establishment of prompt and accurate diagnoses in future cases.