JSCR 2013; 4 (3 pages) doi:10.1093/jscr/rjt021
Case Report
An incidental finding of carcinoid tumor of the cystic duct Hoang U. Lim1, Cyrus C. Chan2,* and F. Barry Knotts3 1
Department of Surgery, Mercy St. Vincent Medical Center, Toledo, OH, USA, 2Department of Surgery, University of Toledo Medical Center, Toledo, OH, USA and 3Department of Surgery, Mercy St. Vincent Medical Center, Toledo, OH, USA *Correspondence address. Department of Surgery, University of Toledo Medical Center, 3065 Arlington Avenue, Toledo, OH 43614, USA. Tel: þ1-626-757-3009; E-mail: [email protected] Received 1 March 2013; accepted 11 March 2013
INTRODUCTION Carcinoid tumors are most commonly found in the appendix, but can be located anywhere along the gastrointestinal tract, within the ovary and even the lung [1]. Carcinoid tumor of the cystic duct is an extremely rare finding. A review of the literature reveals that there have been only seven previously reported cases [2– 8].
CASE REPORT A 58-year-old Caucasian female presented with episodic right upper quadrant pain for the past 2 weeks. The pain was associated with multiple episodes of nausea, vomiting and diarrhea. She denied any jaundice, weight loss, hematochezia or melena. Physical examination revealed a soft abdomen without a palpable mass. She had tenderness in the right upper quadrant of the abdomen and Murphy’s sign was present. The white blood cell count was 18.8K/ml, hematocrit 41.0%, bilirubin 0.20 mg/ dl, lipase 101 U/l, alkaline phosphatase 70 U/l, alanine aminotransferase 28 U/l and aspartate aminotransferase 30 U/l. Computed tomography of the abdomen showed an enlarged fatty liver, mildly prominent gallbladder and inflammatory changes and edema at the root of the mesentery. Abdominal
ultrasound revealed gallbladder sludge and wall thickness measuring 2 mm. The patient underwent laparoscopic cholecystectomy. Pathology report revealed mild chronic cholecystitis with foci of cholesterolosis and a small 2 mm carcinoid tumor at the cystic duct margin extending into the gallbladder mucosa. Histologically, the tumor demonstrated uniform eosinophilic neoplastic cells with oval nucleus (Fig. 1) and was positive for chromogranin and synaptophysin neuroendocrine markers (Figs 2 and 3). The patient was returned to the operating room 15 days after her first operation for a Roux-en-Y heptaticojejunostomy and excisional biopsy of a large lymph node at the mesenteric root. Her preoperative urine 5-hydroxyindoleacetic acid (5-HIAA), chromogranin A and serotonin levels were all normal. Final pathology report showed no viable tumor identified on the common hepatic and common bile duct margins, focal residual necrotic carcinoid tumor involving the cystic duct margin and one periductal lymph node negative for carcinoid tumor. The mesenteric root lymph node was positive for follicular lymphoma. Post-operative course was unremarkable. Medical oncology was consulted and recommended no chemotherapy at this time. The patient was seen in clinic 10 months post-operatively and remains disease free with normal liver function and humoral secretion tests.
Published by Oxford University Press and JSCR Publishing Ltd. All rights reserved. # The Author 2013. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/ licenses/by-nc/3.0/), which permits non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact [email protected].
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Cystic duct carcinoids are extremely rare tumors. We present a 58-year-old female with carcinoid tumor found within the cystic duct margin following laparoscopic cholecystectomy. She subsequently underwent surgical resection with a Roux-en-Y hepaticojejunostomy. No standard guidelines currently exist regarding surgical excision of these rare tumors. Therefore, we conducted a thorough review of the literature to recommend complete oncologic surgical resection with re-establishment of biliary continuity as the mainstay of definitive treatment; adjuvant therapy currently remains investigational. Long-term prognosis is good with this approach.
Page 2 of 3
H.U. Lim et al.
Figure 1: Carcinoid tumor at the cystic duct margin (H&E, magnification 40).
DISCUSSION Carcinoid tumors arise from enterochromaffin cells (Kulchitsky cells) and usually present in the fifth decade of life. They are most commonly found in the appendix (45%), jejunoileum (28%) and rectum (16%) [1]. The majority of carcinoid tumors are asymptomatic and found incidentally during surgery. They frequently coexist with a second primary adenocarcinoma of the colon. The growth pattern for these tumors is slow with metastatic development after 7 – 14 years. Metastatic potential is dependent upon location, size, depth of invasion and growth pattern. Malignant carcinoid syndrome occurs in ,10% of patients and signifies metastatic disease due to hepatic replacement. The syndrome is characterized by flushing (80%), diarrhea (76%), asthma (25%) and right heart valvular disease (41 – 70%) [1]. The humoral factors that contribute to the syndrome include serotonin, 5-hydroxytryptophan, histamine, dopamine, kallikrein, substance P, prostaglandin and neuropeptide K. The diagnosis for carcinoid syndrome is
highly specific when there are elevated urinary levels of 5-hydroxyindoleacetic acid over 24 h. The treatment for carcinoid tumors is dependent on size and presence of lymph node metastasis. Segmental intestinal resection is adequate for lesions ,1 cm without lymph node involvement. For multifocal tumors or lesions .1 cm with lymph node involvement, standard oncologic resection is required [1]. Carcinoid tumors of the extra-hepatic biliary tract are uncommon and account for 0.2 – 2% of all gastrointestinal tract carcinoids. The etiology is unknown but is thought to be related to chronic inflammation of the biliary tract, which leads to metaplasia of the biliary mucosa. This results in an increased number of Kulchitsky cells and may lead to development of carcinoid tumors [4]. There have been only 70 cases of biliary tract carcinoid tumors reported since it was first discovered in 1959. Of these, the most common anatomic locations are the common bile duct (58%), perihilar duct (28%), cystic duct (11%) and common hepatic duct (3%) [9]. There are currently seven reported cases of cystic duct carcinoid tumor (Table 1) [2 – 8]. The most common main complaints were right upper quadrant pain and jaundice; malignant carcinoid syndrome has not been reported in this group. These tumors occur more often in women, with a female-to-male ratio of 3:1. There does not appear to be a direct correlation between tumor size and metastasis in carcinoid tumor of the cystic duct [7]. The tumors are discovered incidentally after surgical intervention and pathologic analysis. Complete surgical resection in patients with resectable biliary tumor remains the standard of care [1]. Long-term prognosis is good with a 10-year survival rate of 80% for carcinoid tumors of the extra-hepatic biliary tract [10].
Conflict of interest statement We certify that we do not have any affiliation with or financial involvement in any organization or entity with a direct
Downloaded from http://jscr.oxfordjournals.org/ by guest on April 9, 2013
Figure 2: Chromogranin positive neoplastic cells (magnification 20).
Figure 3: Synaptophysin positive neoplastic cells (magnification 20).
Carcinoid tumor of the cystic duct
Page 3 of 3
Table 1: Reported cases of carcinoid tumors of the cystic duct Author
Year
Age
Sex
CC
Size
Mets
Follow up
1
Nicolescu et al.
1986
50
F
RUQ pain
0.5 cm
None
Not reported
2
Chittal and Ra
1989
46
F
RUQ pain
0.8 cm
None
DF, 36 months
3
Rugge et al.
1992
64
M
Jaundice
2 cm
None
DF, 12 months
4
Meyer et al.
1997
56
F
RUQ pain
Small
None
DF, 48 months
5
Shah et al.
1998
52
F
RUQ pain
0.5 cm
None
Not reported
6
Hermina et al.
1999
69
M
RUQ pain
Small
LN
Not reported
7
Felekouras et al.
2007
60
F
Jaundice
2 cm
None
DF, 11 months
8
Present case
2012
58
F
RUQ pain
0.2 cm
None
DF, 10 months
CC, chief complaint; RUQ, right upper quadrant; DF, disease free; LN, lymph node.
financial interest in the subject matter or materials discussed in the manuscript (e.g. employment, consultancies, stock ownership, honoraria and expert testimony). We do not have any commercial or proprietary interest in any drug, device, or equipment mentioned in the article above. No financial support was used for this work.
REFERENCES 1. Townsend CM, Jr, Beauchamp RD, Evers BM, Mattox KL. Sabiston Textbook of Surgery: the Biological Basis of Modern Surgical Practice. Philadelphia: Saunders, 2012:1259–62. 2. Nicolescu PG, Popescu A. Carcinoid tumor of the cystic duct. Morphol Embryol (Bucur) 1986;32:275– 7. 3. Chittal SM, Ra PM. Carcinoid of the cystic duct. Histopathology 1989;15:643–6.
4. 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;16:802– 7. 5. Meyer C, Geerdsen J, Christensen N. Limited surgical excision of a localized carcinoid tumour of the cystic duct. Dig Surg 1997;14:423– 5. 6. Shah IA, Schlageter MO, Wong SX, Gani OS. Carcinoid tumor of the cystic duct. Dig Surg 1998;15:372–3. 7. Hermina M, Starling J, Warner TF. Carcinoid tumor of the cystic duct. Pathol Res Pract 1999;195:707– 9. 8. Felekouras E, Petrou A, Bramis K, Prassas E, Papaconstantinou I, Dimitriou N, et al. Malignant carcinoid tumor of the cystic duct: a rare cause of bile duct obstruction. Hepatobiliary Pancreat Dis Int 2009;8:640–6. 9. Jethava A, Muralidharan V, Mesologites T, Stoica-Mustafa E, Dasanu CA. An unusual presentation of a carcinoid tumor of the common bile duct. JOP 2013;14:85– 7. 10. Albores-Saavedra J, Batich K, Hossain S, Henson D, Schwartz AM. Carcinoid tumors and small-cell carcinomas of the gallbladder and extrahepatic bile ducts: a comparative study based on 221 cases from the Surveillance, Epidemiology, and End Results Program. Ann Diagn Pathol 2009;13:378–83.
Downloaded from http://jscr.oxfordjournals.org/ by guest on April 9, 2013
Case [2– 8]
Copyright of Journal of Surgical Case Reports is the property of Journal of Surgical Case Reports and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use.
Case Report
An incidental finding of carcinoid tumor of the cystic duct Hoang U. Lim1, Cyrus C. Chan2,* and F. Barry Knotts3 1
Department of Surgery, Mercy St. Vincent Medical Center, Toledo, OH, USA, 2Department of Surgery, University of Toledo Medical Center, Toledo, OH, USA and 3Department of Surgery, Mercy St. Vincent Medical Center, Toledo, OH, USA *Correspondence address. Department of Surgery, University of Toledo Medical Center, 3065 Arlington Avenue, Toledo, OH 43614, USA. Tel: þ1-626-757-3009; E-mail: [email protected] Received 1 March 2013; accepted 11 March 2013
INTRODUCTION Carcinoid tumors are most commonly found in the appendix, but can be located anywhere along the gastrointestinal tract, within the ovary and even the lung [1]. Carcinoid tumor of the cystic duct is an extremely rare finding. A review of the literature reveals that there have been only seven previously reported cases [2– 8].
CASE REPORT A 58-year-old Caucasian female presented with episodic right upper quadrant pain for the past 2 weeks. The pain was associated with multiple episodes of nausea, vomiting and diarrhea. She denied any jaundice, weight loss, hematochezia or melena. Physical examination revealed a soft abdomen without a palpable mass. She had tenderness in the right upper quadrant of the abdomen and Murphy’s sign was present. The white blood cell count was 18.8K/ml, hematocrit 41.0%, bilirubin 0.20 mg/ dl, lipase 101 U/l, alkaline phosphatase 70 U/l, alanine aminotransferase 28 U/l and aspartate aminotransferase 30 U/l. Computed tomography of the abdomen showed an enlarged fatty liver, mildly prominent gallbladder and inflammatory changes and edema at the root of the mesentery. Abdominal
ultrasound revealed gallbladder sludge and wall thickness measuring 2 mm. The patient underwent laparoscopic cholecystectomy. Pathology report revealed mild chronic cholecystitis with foci of cholesterolosis and a small 2 mm carcinoid tumor at the cystic duct margin extending into the gallbladder mucosa. Histologically, the tumor demonstrated uniform eosinophilic neoplastic cells with oval nucleus (Fig. 1) and was positive for chromogranin and synaptophysin neuroendocrine markers (Figs 2 and 3). The patient was returned to the operating room 15 days after her first operation for a Roux-en-Y heptaticojejunostomy and excisional biopsy of a large lymph node at the mesenteric root. Her preoperative urine 5-hydroxyindoleacetic acid (5-HIAA), chromogranin A and serotonin levels were all normal. Final pathology report showed no viable tumor identified on the common hepatic and common bile duct margins, focal residual necrotic carcinoid tumor involving the cystic duct margin and one periductal lymph node negative for carcinoid tumor. The mesenteric root lymph node was positive for follicular lymphoma. Post-operative course was unremarkable. Medical oncology was consulted and recommended no chemotherapy at this time. The patient was seen in clinic 10 months post-operatively and remains disease free with normal liver function and humoral secretion tests.
Published by Oxford University Press and JSCR Publishing Ltd. All rights reserved. # The Author 2013. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/ licenses/by-nc/3.0/), which permits non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact [email protected].
Downloaded from http://jscr.oxfordjournals.org/ by guest on April 9, 2013
Cystic duct carcinoids are extremely rare tumors. We present a 58-year-old female with carcinoid tumor found within the cystic duct margin following laparoscopic cholecystectomy. She subsequently underwent surgical resection with a Roux-en-Y hepaticojejunostomy. No standard guidelines currently exist regarding surgical excision of these rare tumors. Therefore, we conducted a thorough review of the literature to recommend complete oncologic surgical resection with re-establishment of biliary continuity as the mainstay of definitive treatment; adjuvant therapy currently remains investigational. Long-term prognosis is good with this approach.
Page 2 of 3
H.U. Lim et al.
Figure 1: Carcinoid tumor at the cystic duct margin (H&E, magnification 40).
DISCUSSION Carcinoid tumors arise from enterochromaffin cells (Kulchitsky cells) and usually present in the fifth decade of life. They are most commonly found in the appendix (45%), jejunoileum (28%) and rectum (16%) [1]. The majority of carcinoid tumors are asymptomatic and found incidentally during surgery. They frequently coexist with a second primary adenocarcinoma of the colon. The growth pattern for these tumors is slow with metastatic development after 7 – 14 years. Metastatic potential is dependent upon location, size, depth of invasion and growth pattern. Malignant carcinoid syndrome occurs in ,10% of patients and signifies metastatic disease due to hepatic replacement. The syndrome is characterized by flushing (80%), diarrhea (76%), asthma (25%) and right heart valvular disease (41 – 70%) [1]. The humoral factors that contribute to the syndrome include serotonin, 5-hydroxytryptophan, histamine, dopamine, kallikrein, substance P, prostaglandin and neuropeptide K. The diagnosis for carcinoid syndrome is
highly specific when there are elevated urinary levels of 5-hydroxyindoleacetic acid over 24 h. The treatment for carcinoid tumors is dependent on size and presence of lymph node metastasis. Segmental intestinal resection is adequate for lesions ,1 cm without lymph node involvement. For multifocal tumors or lesions .1 cm with lymph node involvement, standard oncologic resection is required [1]. Carcinoid tumors of the extra-hepatic biliary tract are uncommon and account for 0.2 – 2% of all gastrointestinal tract carcinoids. The etiology is unknown but is thought to be related to chronic inflammation of the biliary tract, which leads to metaplasia of the biliary mucosa. This results in an increased number of Kulchitsky cells and may lead to development of carcinoid tumors [4]. There have been only 70 cases of biliary tract carcinoid tumors reported since it was first discovered in 1959. Of these, the most common anatomic locations are the common bile duct (58%), perihilar duct (28%), cystic duct (11%) and common hepatic duct (3%) [9]. There are currently seven reported cases of cystic duct carcinoid tumor (Table 1) [2 – 8]. The most common main complaints were right upper quadrant pain and jaundice; malignant carcinoid syndrome has not been reported in this group. These tumors occur more often in women, with a female-to-male ratio of 3:1. There does not appear to be a direct correlation between tumor size and metastasis in carcinoid tumor of the cystic duct [7]. The tumors are discovered incidentally after surgical intervention and pathologic analysis. Complete surgical resection in patients with resectable biliary tumor remains the standard of care [1]. Long-term prognosis is good with a 10-year survival rate of 80% for carcinoid tumors of the extra-hepatic biliary tract [10].
Conflict of interest statement We certify that we do not have any affiliation with or financial involvement in any organization or entity with a direct
Downloaded from http://jscr.oxfordjournals.org/ by guest on April 9, 2013
Figure 2: Chromogranin positive neoplastic cells (magnification 20).
Figure 3: Synaptophysin positive neoplastic cells (magnification 20).
Carcinoid tumor of the cystic duct
Page 3 of 3
Table 1: Reported cases of carcinoid tumors of the cystic duct Author
Year
Age
Sex
CC
Size
Mets
Follow up
1
Nicolescu et al.
1986
50
F
RUQ pain
0.5 cm
None
Not reported
2
Chittal and Ra
1989
46
F
RUQ pain
0.8 cm
None
DF, 36 months
3
Rugge et al.
1992
64
M
Jaundice
2 cm
None
DF, 12 months
4
Meyer et al.
1997
56
F
RUQ pain
Small
None
DF, 48 months
5
Shah et al.
1998
52
F
RUQ pain
0.5 cm
None
Not reported
6
Hermina et al.
1999
69
M
RUQ pain
Small
LN
Not reported
7
Felekouras et al.
2007
60
F
Jaundice
2 cm
None
DF, 11 months
8
Present case
2012
58
F
RUQ pain
0.2 cm
None
DF, 10 months
CC, chief complaint; RUQ, right upper quadrant; DF, disease free; LN, lymph node.
financial interest in the subject matter or materials discussed in the manuscript (e.g. employment, consultancies, stock ownership, honoraria and expert testimony). We do not have any commercial or proprietary interest in any drug, device, or equipment mentioned in the article above. No financial support was used for this work.
REFERENCES 1. Townsend CM, Jr, Beauchamp RD, Evers BM, Mattox KL. Sabiston Textbook of Surgery: the Biological Basis of Modern Surgical Practice. Philadelphia: Saunders, 2012:1259–62. 2. Nicolescu PG, Popescu A. Carcinoid tumor of the cystic duct. Morphol Embryol (Bucur) 1986;32:275– 7. 3. Chittal SM, Ra PM. Carcinoid of the cystic duct. Histopathology 1989;15:643–6.
4. 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;16:802– 7. 5. Meyer C, Geerdsen J, Christensen N. Limited surgical excision of a localized carcinoid tumour of the cystic duct. Dig Surg 1997;14:423– 5. 6. Shah IA, Schlageter MO, Wong SX, Gani OS. Carcinoid tumor of the cystic duct. Dig Surg 1998;15:372–3. 7. Hermina M, Starling J, Warner TF. Carcinoid tumor of the cystic duct. Pathol Res Pract 1999;195:707– 9. 8. Felekouras E, Petrou A, Bramis K, Prassas E, Papaconstantinou I, Dimitriou N, et al. Malignant carcinoid tumor of the cystic duct: a rare cause of bile duct obstruction. Hepatobiliary Pancreat Dis Int 2009;8:640–6. 9. Jethava A, Muralidharan V, Mesologites T, Stoica-Mustafa E, Dasanu CA. An unusual presentation of a carcinoid tumor of the common bile duct. JOP 2013;14:85– 7. 10. Albores-Saavedra J, Batich K, Hossain S, Henson D, Schwartz AM. Carcinoid tumors and small-cell carcinomas of the gallbladder and extrahepatic bile ducts: a comparative study based on 221 cases from the Surveillance, Epidemiology, and End Results Program. Ann Diagn Pathol 2009;13:378–83.
Downloaded from http://jscr.oxfordjournals.org/ by guest on April 9, 2013
Case [2– 8]
Copyright of Journal of Surgical Case Reports is the property of Journal of Surgical Case Reports and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use.
