Primary Neuroendocrine Tumor of the Left Hepatic Duct: A Case Report with Review of the Literature

Primary Biliary Tract Neuroendocrine tumors (NET) are extremely rare tumors with only 77 cases been reported in the literature till now. We describe a case of a left hepatic duct NET and review the literature for this rare malignancy. To the best of our knowledge the present case is the first reported case of a left hepatic duct NET in the literature. In spite of availability of advanced diagnostic tools like Computerized Tomography (CT) Scan and Endoscopic Retrograde Cholangio Pancreaticography (ERCP) a definitive diagnosis of these tumors is possible only after an accurate histopathologic diagnosis of operative specimens with immunohistochemistry and electron microscopy. Though surgical excision remains the gold standard treatment for such tumors, patients with unresectable tumors have good survival with newer biologic agents like Octreotride.


Introduction
NET is derived from the embryonal neural crest cells called Argentaffin or Kulchitsky cells and have a potential for secreting serotonin. This tumor can arise anywhere in the distribution of the Argentaffin cell system. In addition to the most common sites of occurrence, namely, ileum and appendix these tumors have reported to occur in bladder, prostate, rectum, stomach, bronchi, pancreas, and biliary tree.
The Literature documents about 77 cases of neuroendocrine tumor arising from the biliary tree which includes common bile duct, common hepatic duct, cystic duct, and hilar confluence.
We report a case of Primary Biliary NET arising from the left hepatic duct. An extensive search of the literature has yielded no reference regarding a NET arising from the left Hepatic ducts. The present case is the first reported case of a NET arising in the left hepatic duct.    taken from the mass and procedure was abandoned in view of inoperability. Histopathology showed typical rosette appearance of a neuroendocrine tumor ( Figure 4) and immunohistochemistry positive for CD56, Chromogranin and Synaptophysin ( Figure 5). Ultrastructural study of the cell with electron microscopy ( Figure 6) showed the presence of multiple neurosecretory granules with muscle tissue.

Case Report
A whole body Positron Emission Tomography (PET) scan and an Octreotride labeled radionulceotide scan showed

Discussion
Primary Biliary-tract NETs are very rare. They account for 0.2-2% of all gastrointestinal NET [1,2] reason being the paucity of enterochromaffin cells from which NETs arise in this area. Chronic inflammation of the bile duct epithelium is responsible for metaplasia of these enterochromaffin cells and formation of NET. Davies [3] in 1959 reported NET of the distal bile duct and pancreatic duct which represented more of a periampullary NET rather than a biliary tract. Pilz [4] in 1961 was credited to report the first case of a Biliary Tract NET. After an extensive search of the Medline only 77 cases of Biliary Tract NET have been reported so far in the literature since 1961 (Table 1).
Till now no NET in the literature has been reported in the isolated left hepatic duct possibly making our case the first reported case of an isolated left hepatic duct NET.   The most common site of malignancy in the biliary tract was common bile duct (57.14%) followed by the hilar confluence (27.28%), the cystic duct (9.1%), common hepatic duct (5.12%) and finally the left hepatic duct (1.23%).
The mean age of presentation was 47 years (range 6 years to 79 years).
The male to female ratio is 1 : 1. 23 showing that the biliary NET has a preponderance for female.
By far the most common symptom in patients of Biliary tract NET is Jaundice (63.4%) followed by Pain (14.1%), jaundice with pain (12.7%) and remaining nonspecific symptoms like weight loss.
The incidence of a Carcinoid syndrome in patients of Biliary Tract NET is very rare. Only 4 cases which include a single case published by Nesi et al. [51] in 2006 with symptoms of diarrhea due to secretion of serotonin and 3 cases by Price et al. [65] in 2009 with features of Zollinger Ellison syndrome due to secretion of gastrin from tumor in CBD.

Conclusion
Biliary Tract NET are rare tumors that typically present with jaundice and pain. As compared to its counterpart Cholangiocarcinoma Biliary NET occurs in a younger age group with a female preponderance [39]. Biliary NET usually are nonsecreting tumor. Preoperative diagnosis of these tumors require a high index of suspicion and accurate histopathological diagnosis which must include a immunohistochemistry study and electron microscopy. Biliary tract NET are slowgrowing indolent tumor which have a limited propensity for local and metastatic spread. Surgical resection aimed at complete tumor excision with bilio-enteric continuity offers the best cure and high survival rates. Patients who have undergone resection have a long term survival. Even in inoperable patients chemotherapy with newer biologic agents like Octreotride have a favorable outcome on the patient's survival.