We report here a case of a primary hepatic carcinoid tumour (PHCT) associated with a Zollinger Ellison syndrome. The primary hepatic carcinoid tumours are uncommon [3
] and represent an intriguing diagnosis to solve. The demonstration of the hepatic origin of a neuroendocrine tumour is difficult since the liver is a frequent site for metastases of different types of tumours: intestinal carcinoids, primary tumours (hepatocarcinoma, etc) and benign pathology (nodular focal hyperplasia, etc).
Carcinoid tumours have their origin in neuroendocrine stem cells (known as enterochromaffin cells or APUD cells (Amine Precursor Uptake Decarboxilase) derived from the embrionary neuronal crest. Cells that migrated from the neuronal crest can give rise to gastrointestinal carcinoid tumours to foregut, midgut and hindgut, being the most common localization the appendix and the small bowel [4
]. Liver has few or none enterochromaffin cells, unlike other organs (pancreas, for example).
Some theories for the origin of PHCTs have been proposed. The most accepted thories are: (i) ectopic cells of pancreatic or adrenal tissue, (ii) neuroectodermal origin cells, (iii) neuroendocrine programmed ectoblasts [5
]. It is believed that, during the early stages of regeneration, the bile ducts epithelium displays neuroendocrine characteristics and cytoplasmatic chromogranin A expression, due to chronic inflammation [6
In general, PHCT may vary in size, ranging from 1 cm to 20 cm [7
] and their aspect is of a unique mass [3
] completely separated from the surrounding liver tissue. Females tend to be affected more often than males (1.4:1) and the age of presentation may range between 18 to 84 years, with an average of 50 years [3
The clinical presentation is atypical, with symptoms like upper abdominal pain or discomfort like fullness, as well as diarrhoea or weight loss [3
]. Only a small percent (7%-13%) of patients accuses symptoms of a typical carcinoid syndrome [3
The radiology diagnosis has poor specificity as the appearance on ultrasound, CT or MRI is of a solid mass with cystic areas and hyperechoic or mixed pattern, with central or peripheral calcifications and fibrous scars. The majority are intense, hypervascularised tumours, which explains the contrast enhancement in ultrasound and CT images, in a similar fashion as the hepatocarcinoma. [9
]. When diagnosing a neuroendocrine tumour, an octreoscan is always recommended since it may detect small metastasic deposits. PET scan may visualize somatostatin receptor type 2 lacking neuroendocrine tumours which are impossible to detect on somatostatin receptor scintigraphy.
The gold standard for diagnosis is the liver biopsy since it may differentiate the lesion from other types of tumours. Cautions must be taken in order to avoid complications like carcinoid crisis as a recent case report shows [10
]. From the histologic point of view the hepatic carcinoma appears as a hemorrhagic, not capsulated mass, with central, irregular fibrosis and hyaline degeneration. The tumoural cells display an eosinophilic cytoplasm and irregular, hyperchromic nucleus. In inmunohistochemistry these cells present a strong positivity for neurosecretory markers as chromogranin, synaptophysin, neuron specific enolase meanwhile markers as serotonin, pancreatic polypeptide or gastrin are inconsistently positive [8
The treatment is the surgical resection, when possible. Almost 85% of primary hepatic carcinoid tumour patients may have a resectable disease [11
]. Survival and recurrence tares five years after surgery are of 80-92.5% [8
] and 18% respectively [14
]. When a not well defined lesion is observed, a palliative cyto-reductive surgery in combination with transcatheter arterial embolization (TACE) and subsequent administration of lanreotide (long acting somatostatin analogue) might be effective, as Touloumis et al. showed recently [12
In our patient’s case, the immunohistochemistry result corresponded to a type A carcinoid tumour (APUDOMA). The moderate staining for gastrin pointed to gastrin secreting PHCT, associated thus with a Zollinger Ellison syndrome. In a recent review, gastrin was the most common hormone secreted of all cases (7/69) of primary hepatic carcinoid published till date [3
Primary hepatic carcinoid tumours are rare entities that sometimes may be associated with syndromes like ZES, carcinoid, etc. induced by neuroendocrine hormones secretion (gastrin, 5-HIAA, ACTH; etc). An early and pertinent diagnosis offers the possibility of surgery resection, with a good 5 early survival rate and a poor relapse rate.