Carcinoid tumor arising in the cystic duct is exceedingly rare. Over a period of 32 years, since 1984, when Goodman et al. [1] described the first case, only 22 cases of the cystic ductal carcinoid tumors have been reported. We present another similar case followed by review of literature. This is the first case reported from the Middle East.

A 68-year-old female had undergone laparoscopic cholecystectomy for symptomatic gallstones in another hospital, was referred for incidentally discovered carcinoid tumor in the cystic duct. She was a known case of diabetes mellitus, hypertension and osteoporosis. Her symptom was post-prandial right upper quadrant pain for one year. At the time of her presentation to our hospital, she was asymptomatic with unremarkable examination. Her complete blood count, liver function tests and serum chromogranin A, serotonin and octreotide levels were within normal range. Imaging of her abdomen and chest by computed tomography (CT), magnetic resonance (MRI) and positron emission tomography (PET) did not reveal any metastatic deposit.

Macroscopic review of the gallbladder revealed a nodular tumor in the cystic duct which was 0.7 cm in diameter. Microscopic examination showed nests, cords and trabeculae of small cells with granular chromatin which were positive for synaptophysin, chromogranin, and CD56 on immunohistochemistry (Figure 1). The tumor invaded the perineural and muscle tissue. This was consistent with well-differentiated carcinoid tumor.

The patient underwent resection of the cystic duct stump, liver segments 4B and 5 and clearance of hepatoduodenal lymph nodes. Appendectomy was also done because of a nodule in the mesoappendix which turned out to be benign fibrosis. No residual tumor was found on frozen and permanent sections. Her postoperative recovery was unremarkable. At 16th month follow-up, she is doing well with no evidence of recurrent disease on MRI and PET scans.

Carcinoid tumors, arising from the enterochromaffin cells, are extremely rare and account for 0.49% of all malignancies [2]. Only 0.2–2.0% of carcinoid tumors are found in the extra-hepatic bile ducts [3]. Cystic duct carcinoid tumors represent 11–20% of all extra-hepatic bile duct carcinoid tumors [3], highlighting the rarity of this particular tumor at this particular site. Ours is the 23rd case reported in English literature (Table 1) [1] [2] [4][5][6][7][8] [9][10][11][12][13] [14][15][16][17][18] [19][20][21].

Review of the reported cases demarcates the clinical presentation into two groups. Isolated cystic duct involvement usually presents with clinical picture similar to symptomatic gallstones. Gallstones were present in two-thirds of the reported cases. When main hepatic/bile duct gets involved then obstructive jaundice is the usual presentation. Endocrine symptoms are rare and only one patient, who had multiple carcinoid tumors at various locations as part of the multiple endocrine neoplasia type-I (MEN-I) syndrome, presented with Zollinger-Ellison syndrome [17]. Majority of the patients were in their fifth and sixth decades and were females. All cases with isolated cystic duct carcinoid tumor were diagnosed incidentally after cholecystectomy on histological examination. The yield of endoscopic retrograde cholangiopancreatography (ERCP) and biopsy in cases that presented with obstructive jaundice was low and only one patient was diagnosed correctly preoperatively [13].

One-third of the patients had evidence of metastasis. Synchronous spread to the regional lymph nodes was seen in four patients [1][2] [11][21]. Synchronous liver deposits were present in two patients [13] [17]. Metachronous liver metastasis occurred in two patients [10] [16]. It is important to note that the locations of liver metastasis were away from the gallbladder bed which requires re-assessment of the value of adding the resection of liver segments 4 and 5 in the primary clearance.

Complete surgical resection is the best treatment for the fit patient. Isolated cystic duct carcinoid tumor requires clearance of the cystic duct stump and the hepatoduodenal lymph nodes. This can be achieved with open or laparoscopic approaches [20]. Involvement of the main hepatic/bile ducts requires excision of the extra-hepatic bile ducts, clearance of the lymph nodes and reconstruction with hepaticojejunostomy. Liver metastasis can be treated by locoregional modalities such as radio frequency ablation, ethanol injection and chemoembolization. Hormone therapy with somatostatin analogues may be considered in frail patients and those with endocrine symptoms. Radiotherapy and chemotherapy should be reserved for surgically unfit, recurrent or metastatic disease.

During the reported follow-up that ranged between 6 and 49 months, one patient died at sixth month due to liver metastasis [10]. Due to their malignant potential, the patients ought to be followed-up by imaging.

In conclusion, cystic duct carcinoid tumor is a rare tumor which presents either with biliary symptoms or obstructive jaundice. The preoperative diagnosis is difficult. Radical surgical resection is the best treatment. Follow-up is recommended because of relatively low but definite malignant potential.

We would like to acknowledge Dr. Miral Mohammed Mashhour, Department of Pathology, King Fahad Specialist Hospital, Dammam, Saudi Arabia for kindly providing the photomicrographs of the histological slides.

1. Goodman ZD, Albores-Saavedra J, Lundblad DM. Somatostatinoma of the cystic duct. Cancer 1984 Feb 1;53(3):498–502.   [CrossRef]   [Pubmed]    
2. Liew EW, Usatoff V. Cystic duct carcinoid tumor with ensuing lymph node metastasis. Surgical Practice 2011;15:145–7.    
3. Michalopoulos N, Papavramidis TS, Karayannopoulou G, Pliakos I, Papavramidis ST, Kanellos I. Neuroendocrine tumors of extrahepatic biliary tract. Pathol Oncol Res 2014 Oct;20(4):765–75.   [CrossRef]   [Pubmed]    
4. Nicolescu PG, Popescu A. Carcinoid tumor of the cystic duct. Morphol Embryol (Bucur) 1986 Oct-Dec;32(4):275–7.   [Pubmed]    
5. Chittal SM, Ra PM. Carcinoid of the cystic duct. Histopathology 1989 Dec;15(6):643–6.   [CrossRef]   [Pubmed]    
6. Rugge M, Sonego F, Militello C, Guido M, Ninfo V. Primary carcinoid tumor of the cystic and common bile ducts. Am J Surg Pathol 1992 Aug;16(8):802–7.   [CrossRef]   [Pubmed]    
7. Ishibashi T, Nagai H, Yasuda Y, Furuta K, Saito K, Kanazawa K. Multiple carcinoid tumors of the gallbladder and cystic duct. J Hep Bil Pancr Surg 1995;2(1):77–84.   [CrossRef]    
8. Meyer CN, Geerdsen J, Christensen N. Limited surgical excision of a localized carcinoid tumor of the cystic duct. Dig Surg 1997;14:423–5.    
9. Shah IA, Schlageter MO, Wong SX, Gani OS. Carcinoid tumor of the cystic duct. Dig Surg 1998;15(4):372–3.   [CrossRef]   [Pubmed]    
10. Oikawa I, Hirata K, Katsuramaki T, Mukaiya M, Sasaki K, Satoh M. Neuroendocrine carcinoma of the extrahepatic biliary tract with positive immunostaining for gastrin-releasing peptide: report of a case. Surg Today 1998;28(11):1192–5.   [CrossRef]   [Pubmed]    
11. Hermina M, Starling J, Warner TF. Carcinoid tumor of the cystic duct. Pathol Res Pract 1999;195(10):707–9; discussion 710.   [CrossRef]   [Pubmed]    
12. Aronsky D, Z'graggen K, Stauffer E, Lange J, Klaiber C. Primary neuroendocrine tumors of the cystic duct. Digestion 1999 Sep-Oct;60(5):493–6.   [CrossRef]   [Pubmed]    
13. Hubert C, Sempoux C, Berquin A, Deprez P, Jamar F, Gigot JF. Bile duct carcinoid tumors: an uncommon disease but with a good prognosis? Hepatogastroenterology 2005 Jul-Aug;52(64):1042–7.   [Pubmed]    
14. Stavridi F, Chong H, Chan S, Goldsmith C, Reddy M, Glees J, Benepal T. Neuroendocrine tumour of the cystic duct: a case report and literature review. J Gastrointest Cancer 2007;38(1):32–3.   [CrossRef]   [Pubmed]    
15. Sethi H, Madanur M, Srinivasan P, Portmann B, Heaton N, Rela M. Non-functioning well-differentiated neuroendocrine tumor of the extrahepatic bile duct: an unusual suspect? Hepatobiliary Pancreat Dis Int 2007 Oct;6(5):549–52.   [Pubmed]    
16. Felekouras E, Petrou A, Bramis K, et al. Malignant carcinoid tumor of the cystic duct: a rare cause of bile duct obstruction. Hepatobiliary Pancreat Dis Int 2009 Dec;8(6):640–6.   [Pubmed]    
17. Price TN, Thompson GB, Lewis JT, Lloyd RV, Young WF. Zollinger-Ellison syndrome due to primary gastrinoma of the extrahepatic biliary tree: three case reports and review of literature. Endocr Pract 2009 Nov-Dec;15(7):737–49.   [CrossRef]   [Pubmed]    
18. Ioannidis O, Cheva A, Paraskevas G, et al. Neuroendocrine tumor of the cystic duct. Acta Gastroenterol Belg 2012 Sep;75(3):357–60.   [Pubmed]    
19. Lim HU, Chan CC, Knotts FB. An incidental finding of carcinoid tumor of the cystic duct. J Surg Case Rep 2013 Apr 4;2013(4). pii: rjt021.   [CrossRef]   [Pubmed]    
20. Garland J, O'Leary E, Haggerty J, Zorc TG. Carcinoid tumor of the cystic duct: case report, literature review and comparison of surgical approaches. Case Rep Oncol 2014 Sep 3;7(3):621–4.   [CrossRef]   [Pubmed]    
21. Hong N, Kim HJ, Byun JH, Neuroendocrine neoplasms of the extrahepatic bile duct: radiologic and clinical characteristics. Abdom Imaging 2015 Jan;40(1):181–91.   [CrossRef]   [Pubmed]