Table 1 Comparison of clinical, pathological and histological features of intrahepatic carcinomas
Hepatocellular carcinoma | Cholangiocarcinoma | Biliary neuroendocrine carcinoma | Mixed adeno-neuroendocrine carcinoma | |
|---|---|---|---|---|
Common site | Liver parenchyma | Extrahepatic biliary tract | Very rare, perihilar and extrahepatic bile ducts [6] | |
No previous reports of intrahepatic MANEC | ||||
Laboratory abnormalities | Raised hepatitic enzymes | Intrahepatic—typically raised ALP and GGT, normal or mildly elevated bilirubin | Raised ALP and GGT | As cholangiocarcinoma and BNET |
Tumour markers—AFP [31] | Tumour markers CA19-9 and CEA may be raised, but lack sensitivity and specificity [12–14] | |||
Radiological features | Hyper-attenuating in arterial phase with portal venous phase washout on dual-phase contrast CT | Hypo or iso-attentuating compared to background liver on dual-phase contrast CT in both venous and arterial phases | Similar radiological findings to cholangiocarcinoma | As cholangiocarcinoma and BNET |
Increased T2 intensity on MRI | Evidence of biliary tract obstruction with proximal dilatation | |||
Invasion of portal vein | ||||
Histological features | Neoplastic cells resembling hepatocytes. It can have different type of architecture such as trabecular, acinar, pseudoglandular, compact and scirrhous | Invasive adenocarcinoma with variable sized tubular structures, formation of acini or micropapillary structures. The intraductal growth in the extrahepatic biliary tree can present as BilIN or IPNB [32]. It does not express chromogranin and synaptophysin extensively | These tumours are composed of cells superimposable to those of gut and pancreas endocrine cell and show diffuse positivity for Chromogranin A and synaptophysin without any other differentiation [5] | Adenocarcinoma component typically on tumour surface, with stromal, vascular and local lymph node invasion involving neuroendocrine components [6] |
Positive Hep-Par1 staining [28] | Neuroendocrine component usually shows higher proliferative activity [6] | |||
Prognosis | Highly variable dependent on staging, grading, presence or absence of cirrhosis [33] | Better outcomes in intrahepatic tumours For R0-resected intrahepatic tumours—median survival 80 months, 5-year survival 63 % [9] | Dependent on grade (mitotic index and Ki-67 proliferation index) [7] | Dependent on proliferative activity of neuroendocrine component [6] |
Appears to have better long-term survival rate compared with other biliary tract malignancies [34] | 45 month survival in one case [29] |