Primary hepatic neuroendocrine carcinoma (ORPHA:100085)
Primary hepatic neuroendocrine carcinoma (PHNEC) is a rare hepatic tumor that may manifest with abdominal pain or fullness, as well as diarrhea or weight loss. More than 10% of cases are asymptomatic and in rare cases a carcinoid syndrome may be observed.
Epidemiology
PHNEC has been estimated to have an incidence of approximately 1/500,000, accounting for <1% of all malignancies. PHNEC is slightly more frequent in females.
Clinical description
The age of onset is variable. In the early stages of PHNEC, patients may exhibit nonspecific symptoms, including upper abdominal pain and distension or fullness, while some may suffer from carcinoid syndrome (paroxysmal flushing, episodes of asthma-like wheezing, right-side heart failure and diarrhea). Progression of PHNEC is accompanied by the symptoms caused by tumor compression to adjacent organs, dyspepsia, weight loss and fatigue. More than 10% of cases are asymptomatic. PHNEC is not associated with cirrhosis or other forms of preexisting liver disease.
Etiology
The etiology of PHNEC is still unknown but it is thought to arise from Kulchitsky cells originating in the neural crest. It is also hypothesized that chronic inflammation in the biliary system may initiate intestinal metaplasia, which predisposes to the development of neuroendocrine tumors. Another possibility is that they originate from ectopic pancreatic or adrenal tissues within the liver.
Diagnostic methods
Diagnosis relies on laboratory findings showing negative serum alpha-fetoprotein levels and negative results for other conventional tumor markers (carcinoembryonic antigen, CA125 and CA19‑9) in addition to non-contrasted computed tomography (CT) scans showing low-density masses, with some having a cystic component. Dynamic contrast CT reveals enhanced masses in the early phase and low density masses in the late phase. On magnetic resonance imaging (MRI), PHNEC usually presents with low intensity on T1-weighted images and high intensity on T2-weighted images, and appears as a large dominant hypervascular mass accompanied by satellite nodules, with rapid washout and capsular enhancement on dynamic MRI and restricted diffusion on diffusion-weighted imaging. An octreoscan is recommended as it may detect small metastatic masses. Histologically, PHNEC appears as a hemorrhagic, non-capsulated mass, with central, irregular fibrosis and hyaline degeneration. The diagnosis may be confirmed by immunohistochemistry where the cells present a strong positivity for neurosecretory markers such as chromogranin, synaptophysin, neuron specific enolase, and S-100 protein.
Differential diagnosis
Differential diagnosis includes hepatic adenoma, hepatocellular carcinoma, cholangiocarcinoma, congenital liver hemangioma (see these terms), focal nodular hyperplasia, primary hepatic angiosarcoma, secondary hepatic neuroendocrine carcinoma, or hepatic metastases from any other primary cancer site.
Management and treatment
Surgery is often the only curative option and provides the most favorable outcome. For ill-defined lesions, a palliative cytoreductive surgery in combination with transcatheter arterial embolization (TACE) and subsequent administration of lanreotide (a long acting somatostatin analogue) may be effective. Targeted radiation therapy, given as either SIRT (selective internal radiation therapy) or PRRT (peptide receptor radiation therapy) is of theoretical benefit.
Prognosis
Early detection and treatment are key in achieving a good prognosis. The prognosis depends on the pathological type, degree of differentiation, and size and boundary of the tumor as well as the presence of metastasis and the physical status of the patient.

                            Last update: 
                            October 2014


                            - Expert reviewer(s): 
                            Pr Graeme POSTON