Primary neuroendocrine tumourof the common hepatic duct: an unexpected Klatskin-like lesion

Bacha Dhouha |

La tunisie chirurgicale - 2021 ; Vol 2021


Neuroendocrine tumours (NETs) arising in the extrahepatic biliary system are exceedingly rare and only account for 0.2 to 2% of all gastrointestinalNETs. Among them, the common bile duct is the most common location, nearly representing 60% of the cases. The perihilar region, the common hepatic duct and the cystic duct are uncommon sites of NETs. Therefore, they may have overlapping clinical and radiological features with a Klatskin tumour. Herein, we report an unusual case of a NET grade 2 of the common hepatic duct in a 64-year-old female patient.

Mots Clés

Neuroendocrine tumours, Klaskin, Immunohistochemistry, Grade

Introduction :

Neuroendocrine tumours (NETs) arising inthe extrahepatic biliary system are exceedingly rare and only account for 0.2 to 2% of all gastrointestinalNETs (1).Among them, the common bile duct is the most common location, nearly representing60% of the cases(2). The perihilar region, the common hepatic duct and the cystic duct are uncommon sites of NETs. Therefore, they may have overlapping clinical and radiological features with a Klatskin tumour. Herein, we report an unusual case of a NET grade 2 of the common hepatic duct.



Case report

A 64-year-old female patient was referred to the surgical department for a two-month history of epigastralgia and vomiting. She hasbeen treated for hypertension, asthma, diabetes mellitus and had a prior surgery for umbilical hernia. Physical examination revealed a good general condition and a slight tenderness in the right hypochondrium. No jaundice was noted. Abnormal laboratory findings includedelevated transaminase levels (AST/ALT:105/188IU/l), hyperbilirubinemia (TB/DB: 36.2/14.3 μmol/l) and cholestasis (Gamma-GT:975IU/l). An abdominal ultrasound revealed a dilatation of the intra and extrahepatic biliary system and a normal appearance of the liver. A subsequent biliary MRI was performed. It showed dilated right and left hepatic ducts upstream a well-defined and heterogeneous hilar lesion, measuring 33.5x16.5 mm. These findings suggested a Klatskin tumour, Bismuth type II. Tumour markers including CA 19-9, CEA and AFP as well as screening for distant metastases were negative. The patient was therefore scheduled for surgery consisting ina bile duct resection including the superior biliary confluence and a possible concomitant segment I resection. Intraoperatively, there was a heterogeneous and stenosing mass arising from the common hepatic duct which measured 3 cm in greatest diameter.No invasion of contiguous organs was noted. The liver and the stomach were normal and there was no evidence of peritoneal carcinomatosis. The gallbladder as well as the whole extrahepatic biliary tree were removed with up to 1-cm surgical margins. Biliary continuing was restored by a Roux-en-Y hepaticojejunostomy. The patient had an uneventful postoperative course and was discharged 11 days later.

On cut surface, the tumour measured 4x3 cm and was nodular, well-defined, fleshy and encompassed the common hepatic duct. Histologically, the tumour was composed of monomorphic cuboidal cells arranged in trabecular and acinar structures within a rich vascular network. The cytoplasm was inconspicuous, eosinophilic and finely granular. Nuclei were uniform, round with a salt-and-pepper chromatin. Tumour cells were immunoreactive for synaptophysin and chromogranin A. Ki67 immunostaining revealed a proliferative index of 6%. Tumour infiltrated the wall of the common hepatic ductbut remained 2-mm distant from the epithelial layer. Surgical margins were negative. These pathological and immunohistochemical findings were consistent with a well-differentiatedgrade 2 NETof the common hepatic duct, according to the WHO criteria for the classification of gastroenteropancreatic neuroendocrine tumours. It was classified pT2 according to the TNM classification (7th edition). Two-month follow-up showed no evidence of recurrent disease and no further adjuvant therapy was necessary.



Most extrahepatic bile duct tumours are adenocarcinomas (80%), with other types of tumours being rare(3). Of them, NETs of the extrahepatic bile duct are exceedingly rare; this may be explained by the scarcity of enterochromaffin cells in the bile duct mucosa(4).

Patients are aged between 19 and 79 years old with a peak incidence in the fifth decade (5). Unlike adenocarcinomas, NETs of the extrahepatic biliary system have a female predilection(4).

These tumours are typically non-functioning and lack specific symptoms at the time of presentation. According to the exhaustive systematic review of the literature performed from 1959 to 2014 by Michalopoulos et al., only 7 (9%) patients with an extrahepatic biliary NET presented with hormone-related symptoms (6). As our case report, patients rather exhibit symptoms related to biliary obstruction, among which neoplastic jaundice and pruritusare the most common. A preoperative diagnosis of biliary NETs is thus challenging and instead, raise a strong suspicion ofKlatskin tumours. In fact, the diagnosis of biliary NETs wasmade preoperatively in only 4 (5.12%) out of 78 cases: two from biopsies obtained during an endoscopic retrograde cholangiopancreatography and two by elevated blood serotonin levels(6).

Neuroendocrine tumours of the gastrointestinal and pancreatobiliary tract are a heterogeneous group of neoplastic proliferations which exhibit clinical, histological and biological heterogeneity with some well-differentiated NETs being more aggressive than grade 3 NETs.In fact, we have all noticed in our daily practice that well-differentiated NETs grade 1 or 2 behave as malignant tumours and have been proven to be metastatic. Consequently, these tumours of all grades are considered malignant, except for precursor-type minute lesions (7). However, ki67 labeling indexseems to be a reliable prognostic marker and correlates significantly and independently with clinical outcome(8,9). The best method for determining ki67 labeling index is the manual count of positive cells on camera-captured/printed image of the hotspot area. The whole neuroendocrine cells can be crossed-off and positive cells can be circled so that an exact percentage of ki67can be determined. We used a printed image of the hotspot area to count the ki67 index which was 6% and consistent with a grade 2 NET. This method has been well-developed in pancreatic NETs and is reported to be the most effective with a very high practicality and accuracy and the best inter-observer agreement (10). Neither eye-balling nor automated system counting are recommended(10).

NETsof the extrahepatic bile ducts are most commonly well-differentiated grade 1 and 2 NETs.

Neuroendocrine carcinomas (NECs) are much less common, accounting for only 0.19% of extrahepatic bile duct tumours(11). They tend to be more distally located in the extrahepatic biliary system than grade 1 and 2 NETs(12).Either small or large cell type, the prognosis of NECs is very poor and 50% of them present with a disseminated disease(3). No long-term follow-up is reported in literature for the biliary tract location of grade1/2 NETs so assessment of prognostic markers cannot be determined as for pancreatic counterparts.

A complete surgical excision of the tumour is the gold standard of treatment for two-thirds of patients with a biliary NET, who present without evidence of metastases. Their 5-year survival varies from 60% to 100%(1). However, the remaining one third presentingat the time of diagnosis with lymph node (19.23%) or liver (16.7%) metastases have a worse prognosis(6). For this category, only an aggressive surgical therapy can increase their chance of recovery. 



Neuroendocrine tumours of the common hepatic duct are exceedingly rare among the biliary tract system primaries. It is a Klatskin-like tumour lesion in clinical presentation and imaging features which makes preoperative diagnosis challenging. Histologically, they commonly present as well-differentiated grade 1 and 2 NETs. Long-term follow-up for this special location is not well-documented in literature as case reports are the most common type of publication. Therefore, assessmentof the malignant behaviour of the biliary NETs grade 1 and 2cannot be determined like for pancreatic counterparts.






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