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

Authors: Ajay H. Bhandarwar; Taher A. Shaikh; Ashok D. Borisa; Jaydeep H. Palep; Arun S. Patil; Aditya A. Manke
Journal: Case Reports in Surgery
 (2012)

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## Abstract

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.


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## Body

## 1. 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.Primary Biliary Tract NETs are rare and account for 0.2%–2% [1, 2] of all gastrointestinal neuroendocrine tumors.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.


## 2. Case Report

A 69-years-old female presented with colicky pain in the right hypochondrium since 3 years. She had past history of open cholecystectomy done for gall stones 15 years back. On physical examination the patient was anicteric with soft abdomen. An Ultrasonography (USG) of the abdomen showed a hypoechoic lesion of size 3.5 cm × 4 cm in segment 4 of the liver. Computerized Tomography (CT) of the abdomen showed a 4.1 × 3.7 cm heterogeneously enhancing mass lesion in segment IV of liver abutting the left branch of portal vein (Figure1). A Magnetic Resonance Imaging (MRI) of upper abdomen with Magnetic Resonance CholagioPancreaticography (MRCP) showed a filling defect in the left hepatic duct with lesion in the adjacent part of liver in segment IV, suggestive of a left hepatic duct tumor with infiltration in the liver (Figure 2). Tumor marker serum alfa fetoprotein was mildly raised. Patient was worked up for left hepatectomy. Intraopertaively a lesion arising from the left hepatic duct involving the left branch of portal vein and extending upto the portal confluence was found (Figure 3) rendering the tumor unresectable. A biopsy was 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.Figure 1
CT scan showing mass lesion in segment 4 abutting the left branch of portal vein.Figure 2
MRCP showing a filling defect in the left hepatic duct.Figure 3
Intraoperative picture showing tumor arising from the left hepatic duct. CBD hooked in yellow, hepatic artery in red, and portal vein in blue.Figure 4
Histopathology showing a typical rosette appearance of neuroendocrine tumor.Immunohistochemistry staining positive for Chromogranin (a) and Synaptophysin (b).
(a)
(b)Figure 6
Electron microscopy picture showing multiple granules of varying sizes.A whole body Positron Emission Tomography (PET) scan and an Octreotride labeled radionulceotide scan showed somatostatin receptor expressing lesion in the hepatobiliary system (Figure7).PET Scan (a) and Octreotride labelled (b) scan showing tumor limited to the hepatobiliary system.
(a)
(b)The patient was started on long-acting Octreotride therapy single dose every month. The patient has received 12 of such doses and is doing well after a 1-year followup without any complications. A follow up MRI (Figure8) upper abdomen with MRCP at 1 year showed the absence of filling defect in the Left hepatic duct that was seen previously which showed tumor regression.Figure 8
Follow up MRCP at 1 year showing absence of any filling defect in the left hepatic duct.


## 3. 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).Table 1
Showing study of reported cases of Biliary tract NET.
No.
Case reference
Age
Sex
Complaint
Location
(1)
Pilz, [4]  1961
55
F
Weakness
CBD
(2)
Little et al., [5]  1968
41
F
RUQ pain, jaundice,
Hilar
(3)
Bergdahl, [6]  1976
79
F
Autopsy finding
Distal CBD
(4)
Judge et al., [7]  1976
19
M
Jaundice, pain
Hilar
(5)
Gerlock and Muhletaler [8]  1979
32
M
Jaundice
CBD
(6)
Vitaux et al., [9]  1981
24
M
Jaundice
Distal CBD
(7)
Nakamuara et al. [10]  1981
58
F
Jaundice
CBD
(8)
Abe et al., [11]  1983
64
M
RUQ pain
CBD
(9)
Goodman et al., [12]  1984
28
F
RUQ Pain
Cystic duct
(10)
Jutte et al., [13]  1986
62
M
Back Pain
CHD
(11)
Nicolescu and Popescu, [14]  1986
50
F
RUQ pain
CBD
(12)
Alexander et al., [15]  1986
64
F
Hematemesis
CBD
(13)
Gastinger et al. [16]  1987
65
F
Jaundice, Pain
Hilar
(14)
Reinhardt et al. [17]  1988
71
F
Jaundice, fever
CBD
(15)
Chittal and Ra, [18] 1989
46
F
RUQ pain
Cystic duct
(16)
Fujita et al., [19] 1989
55
F
RUQ pain
CBD
(17)
Bickerstaff and Ross [20]  1989
57
F
Jaundice
CBD
(18)
Brown et al., [21] 1990
35
F
Jaundice
Hilar
(19)
Bumin et al., [22] 1990
38
F
Jaundice
CBD
(20)
Fellows et al. [23] 1990
30
M
Jaundice
CBD
(21)
Besznyák et al. [24]
13
F
Jaundice
Hilar
(22)
Angeles-Angeles et al., [25] 1991
39
F
Jaundice
CBD
(23)
Barron-Rodriguez et al., [26] 1991
36
M
Jaundice, RUQ pain
CBD
(24)
Newman et al., 1992 [27]
15
F
N/A
CBD
(25)
Dixon et al., 1992 [28]
60
F
RUQ pain
CBD
(26)
Rugge et al., [29] 1992
64
F
Jaundice, RUQ pain
Cysticduct, CBD
(27)
Gembala et al., [30] 1993
28
M
Jaundice
Hilar
(28)
Mandujano-Vera et al., [31] 1995
53
F
Jaundice
CBD
(29)
Sankary et al., [32] 1995
47
F
Jaundice
Hilar
(30)
Hao et al., [33] 1996
47
M
Incidental finding
CBD
(31)
Kopelman et al., [34] 1996
44
M
Jaundice
CBD
(32)
Belli et al., [35] 1996 CBD
78
M
Jaundice
CBD
(33)
Bembenek et al., [36] 1998
12
F
Jaundice
Hilar
(34)
Nahas et al., [37] 1998
61
F
Jaundice
Hilar
(35)
Ross et al., [38] 1999
65
F
Jaundice
CBD
(36)
Chamberlain and Blumgart [39] 1999
37
F
Itching
Hilar
(37)
Chamberlain and Blumgart [39] 1999
67
F
Itching
Hilar
(38)
Hermina et al., [40] 1999
69
M
RUQ pain
Cystic duct
(39)
Perakath et al. [42] 1999
36
F
Jaundice, Pain
CHD
(40)
Chan et al [41] 2000
14
M
Jaundice
Hilar
(41)
Maitra et al., [42] 2000
53
F
Jaundice,
CBD
(42)
Maitra et al., [42] 2000
61
F
Jaundice, itching
Hilar
(43)
Juturi et al., [43] 2000
43
M
Jaundice, itching
CBD
(44)
Turrión et al., [44] 2002
51
F
Jaundice, itching
Hilar
(45)
Pawlik et al., [45] 2003
59
M
Jaundice
Hilar
(46)
Podnos et al., [46] 2003
65
F
Cholecystitis
CBD
(47)
Podnos et al., [46] 2003
27
M
Jaundice, itching
CBD
(48)
Volpe et al., [47] 2003
19
M
Jaundice, pain
CBD
(49)
Menezes et al., [48]
30
M
Jaundice
CHD
(50)
Ligato et al., [49] 2005
33
F
Irritable bowel
Hilar
(51)
Hubert et al., [50]  2005
NA
M
Jaundice
CBD
(52)
Hubert et al., [50]  2005
NA
M
Jaundice
CBD
(53)
Hubert et al., [50]  2005
NA
F
Jaundice
CBD
(54)
Nesi et al., [51] 2006
30
M
Jaundice, iarrhoea
CBD
(55)
Kim et al., [52] 2006
67
F
Jaundice
CBD
(56)
Caglikulekci et al., [53] 2006
40
F
Jaundice
Hilar
(57)
Honda et al., [54] 2006
76
M
Jaundice, pain
CBD
(58)
Todorki et al., [55] 2007
73
M
Jaundice, Fever
CBD
(59)
Sethi et al., [56] 2007
51
M
ERCP finding
CHD with Cystic
(60)
Stavridi et al., [57] 2007
NA
NA
NA
Cystic duct
(61)
Jiménez et al., [58] 2007
60
M
Jaundice
Hilar
(62)
Ferrone et al., [59] 2007
NA
NA
NA
NA
(63)
Nafidi  et al., [60] 2008
31
F
RUQ pain
CBD
(64)
Gusani et al., [61] 2008
NA
NA
NA
CBD
(65)
Schmitt et al., [62] 2008
NA
NA
NA
Hilar
(66)
Costantini et al., [63] 2008
NA
NA
NA
CHD
(67)
Felekouras et al., [64] 2009
60
F
Jaundice
Cystic duct
(68)
Price et al., [65] 2009
NA
NA
Jaundice
CBD
(69)
Price et al., [65] 2009
NA
NA
Jaundice
CBD
(70)
Price et al., [65] 2009
NA
NA
Jaundice
Hilar
(71)
Tonnhofer et al., [66]
6
F
Jaundice
CBD
(72)
Zhan et al. [67] 2010
10
M
NA
CBD
(73)
Squillaci et al., [68] 2010
52
M
Jaundice
CBD
(74)
Squillaci et al.,  [68] 2010
70
M
Jaundice
CBD
(75)
Tsalis et al., [69] 2010
77
M
Incidental
Hilar
(76)
Lee et al., [70] 2011
59
M
Jaundice
CBD
(77)
Athanasopoulos et al., [71] 2011
43
M
Jaundice
CBD
(78)
Present case
69
F
Pain
Left hepatic duct
CHD: common hepatic duct, CBD: common bile duct,  Hilar  at the common bile duct bifurcation.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.


## 4. 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 slow-growing 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.



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