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Synchronous Appearance of a High-Grade Neuroendocrine Carcinoma of the Ampulla Vater and Sigmoid Colon Adenocarcinoma

Synchronous Appearance of a High-Grade Neuroendocrine Carcinoma of the Ampulla Vater and Sigmoid... Hindawi Publishing Corporation Case Reports in Oncological Medicine Volume 2013, Article ID 930359, 4 pages http://dx.doi.org/10.1155/2013/930359 Case Report Synchronous Appearance of a High-Grade Neuroendocrine Carcinoma of the Ampulla Vater and Sigmoid Colon Adenocarcinoma 1 1 2 Suna Cokmert, Lutfiye Demir, Aysegul Akder Sari, 1 1 1 1 Yuksel Kucukzeybek, Alper Can, Murat Akyol, Ibrahim Vedat Bayoglu, 1 1 1 Ahmet Dirican, Cigdem Erten, and Mustafa Oktay Tarhan Department of Medical Oncology, Izmir Ataturk Training and Research Hospital, Izmir Katip Celebi University, 35600Izmir,Turkey Department of Pathology, Izmir Ataturk Training and Research Hospital, Izmir Katip Celebi University, 35600 Izmir, Turkey Correspondence should be addressed to Suna Cokmert; sunacok@gmail.com Received 29 September 2013; Accepted 27 October 2013 Academic Editors: J. I. Mayordomo and O. Ozyilkan Copyright © 2013 Suna Cokmert et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Neuroendocrine carcinoma is a relatively rare tumor and its coexistence with other primary cancers is very exceptional. We present a case of a 63-year-old woman with biliary obstruction due to a high-grade neuroendocrine carcinoma located in ampulla of Vater who was found to have a synchronous sigmoid colon adenocarcinoma while undergoing staging laparotomy and pancreas head resection. Medical history was significant only for basal cel l skin cancer. Immunohistochemical examination revealed the concurrence of histologically proved neuroendocrine carcinoma (chromogranin A, synaptophysin, and CD56 were positive) and Stage II (T3, N0, and M0) according to the TNM staging classification of colorectal cancer. eTh coexistence of neuroendocrine tumors with either synchronous or metachronous unrelated cancer is increasingly recognized. eTh patients with neuroendocrine carcinoma should be evaluated for secondary primary malignancies. 1. Introduction tract. Neuroendocrine carcinoma of the ampulla of Vater very rarely coexist with other primary sporadic cancers. Neuroendocrine tumors (NETs) are a rare and heterogeneous Here, we present a patient with an ampulla of Vater mass, group of neoplasms [1] that can arise from neuroendocrine diagnosed as a high-grade neuroendocrine carcinoma, and a cells localized anywhere in the body [1, 2]. In the duode- synchronous sigmoid colon adenocarcinoma coincidentally num, NETs constitute 5.7 to 7.9% of the neuroendocrine diagnosed during the operation for the ampulla of Vater neoplasms of the gastroenteropancreatic tract [3]. In the tumor. English language literature, fewer than 120 cases of NETs of the ampulla of Vater have been described. Furthermore, most neuroendocrine tumors of the duodenum are of carci- 2. Case Report noid origin and only a few case reports of neuroendocrine carcinomas (NEC) of the ampulla have been documented A 63-year-old woman presented with a one-month history of [4–10]. progressive upper abdominal pain and jaundice. On physical Neuroendocrine tumors are associated with synchronous examination both sclerae appeared yellow. Abdominal or metachronous secondary primary malignancies. Rates of examination revealed mild tenderness in the right upper secondary primary malignancies are up to 55% in neuroen- abdominal quadrant, but no mass was palpable. er Th e were docrine tumors [11]. Secondary primary malignancies are no changes in her bowel movements. Medical history was mainly localized in the gastrointestinal and genitourinary insignificant except for basal cell skin cancer for which 2 Case Reports in Oncological Medicine (a) (b) (c) (d) (e) Figure 1: Neuroendocrine carcinoma of ampulla of Vater. (a)-(b) Neuro endocrine tumor invading muscularis propria in the ampulla, (c) focal necrosis centres and moderate atypia in the tumor, (d) Ki-67 proliferation index above 20%, (e) focal positivity with synaptophysin. she had undergone surgery sixteen years ago. Blood tests of Vater. Endoscopic biopsy was taken from mass lesion and showed mildly impaired liver function tests (total bilirubin: showed a poorly differentiated neuroendocrine carcinoma. 1.9 (0-1 mg/dL), direct bilirubin: 1.1 (0–0.3 mg/dL), AST: 22 As the patient had no hormone-related symptoms, octre- (0–32 IU/L), ALT: 18 (0–32 IU/L), ALP: 189 (40–129 IU/L), oscan was not used and a decision was made to perform and GGT: 44 (10–60 U/L)). Hemogram results revealed resection. A pancreatoduodenectomy was done. During microcytic, hypochromic anemia, with hematocrit 24.2% surgery, a mass in the sigmoid colon was incidentally found. (reference range 36–46%), hemoglobin 7.65 g/dL (reference Left colectomy and a lymphadenectomy were performed. range 12–18 g/dL), mean corpuscular volume 69.2 fL (refer- Histopathological examination showed a poorly differenti- ence range 80–97 fL), mean corpuscular hemoglobin 22 pg ated neuroendocrine carcinoma of ampulla of Vater (Figures (reference range 27–31 pg), mean corpuscular hemoglobin 1(a)–1(c)), 1.2 cm in diameter, with a mitotic rate of nine concentration 31.8 g/dL (reference range 32–36 g/dL), and mitoses per 10 high power elds fi and a Ki-67 proliferative serum ferrum and ferritin levels of 23𝜇 g/dL (reference range index of 40% (Figure 1(d)). Immunohistochemistry chro- 70–180𝜇 g/dL) and 80𝜇 g/L (reference range 30–400𝜇 g/L), mogranin A, synaptophysin (Figure 1(e)), and CD56 were respectively. eTh tumor markers alpha-fetoprotein (AFP), positive. er Th e was no metastasis to periampullary lymph carcinoembryonic antigen (CEA), and CA19-9 were all nodes. Furthermore, there was a sigmoid colon adenocarci- within normal ranges. Ultrasonographic examination of noma with local invasion into the subserosa (pT3) (Figure 2). the abdomen showed a dilation of choledocal duct but None of the 8 resected pericolic lymph nodes were involved. no gallstones. Abdominal computed tomography showed All microscopic margins were clear. Treatment with 5-FU and no enlargement of the pancreatic head. An endoscopic leucovorin plus cisplatin to treat both tumors was suggested retrograde cholangiography revealed a mass in the ampulla postoperatively. Case Reports in Oncological Medicine 3 the literature, making this the rfi st case report of this scenario. Prommegger et al. reviewed 14 patients with NET and SPM, and, among those patients, a NET of duodenum localization was detected in only two patients whose SPM were basal cell carcinoma of skin and colon carcinoma. Five patients had synchronous SPM including two colon cancers with one double colon cancer, one gastric cancer, one bladder cancer, and one ovarian cancer and nine metachronous SPM includ- ingtwo basalcellcarcinomas, onecolon cancer,two breast cancer, one gastric MALT-lymphomas, one ductal pancreatic adenocarcinoma, one bladder cancer, and one hepatocellular carcinoma [20]. In addition, a case was reported of a woman treated initially for a synchronous squamous cell carcinoma Figure 2: Adenocarcinoma in sigmoid colon. of the cervix and a basal cell carcinoma of the skin, who developed a third malignancy described as a neuroendocrine carcinoma of an unknown primary site [21]. Our patient has been diagnosed with basal cell skin carcinoma 15 years prior 3. Discussion to the initial diagnosis of the synchronously described colon Neuroendocrine tumors (NETs) may be localized throughout adenocarcinoma and neuroendocrine carcinoma. In this report, we present an interesting case with high- the human body [1] and relatively rarely in theduodenum [2, 3]. In an analysis of 13,715 neuroendocrine tumors reported grade neuroendocrine carcinoma of ampulla of Vater and over a 50-year period to the Surveillance, Epidemiology, and asymptomatic synchronous sigmoid colon adenocarcinoma End Results Program of the National Cancer Institute, only incidentally detected at the operation. Multiple primary 360 cases involved the duodenum or ampulla [9, 12]. A tumors seen synchronously and/or metachronously, with neuroendocrine carcinomas, are an increasingly encountered series from Memorial Sloan-Kettering Cancer Center showed only 14 high-grade neuroendocrine carcinomas out of 215 phenomenon. es Th e patients must be extensively evaluated ampullary carcinomas [13]. Carter et al. reported 7 patients for SPM during the workup and follow-up period. We recommend that a whole body CT scan and endoscopic with NET of ampulla of Vater and, among those patients, a high-grade neuroendocrine carcinoma was detected in only investigation of the gastrointestinal tract be performed. one patient [9]. Based on these reports, it can be postu- Further studies are required to clarify the mechanisms of lated that high-grade neuroendocrine carcinoma localized in carcinogenesis associated with neuroendocrine carcinomas ampulla of Vater is very rare. and synchronous tumors. Neuroendocrine tumors are associated with secondary primary malignancies. In 1944, Pearson and Fitzgerald reported, for the rfi st time, a high incidence of carcinoid Authors’ Contribution tumors with secondary primary malignancies (SPM) [14]. Suna Cokmert, Yuksel Kuc¸ukzeybek, Lutyfi e Demir, and Many reports demonstrated NET-associated SPM in up to Aysegul Akder Sari contributed equally to this work; 55% [3–10] of patients. The situation of NET-associated SPM Suna Cokmert, Yuksel Kuc¸ukzeybek, and Lutyfi e Demir can be explained with the eld-eff fi ect theory. Accordingly, designed the research; Suna Cokmert, Aysegul Akder Sari, a common carcinogenic eeff ct stimulates the growth of neuroendocrine and SPM cancer cells [11, 15]. Additionally, Lutyfi e Demir, Yuksel Kuc ¸ukzeybek, Murat Akyol, Alper Can, Ibrahim Vedat Bayoglu, and Ahmet Dirican per- NETs produce and secrete various neuropeptides or non- formed the research; Suna Cokmert, Cigdem Erten, Yuksel neuropeptides, many of which have specific growth factor Kuc¸ukzeybek, and Mustafa Oktay Tarhan analyzed the data; properties [16]. For example, gastrin and cholecystokinin Suna Cokmert wrote the paper. (CCK) can stimulate gastric mucosal and pancreatic cell growth [17]. Recently, receptors for CCK and gastrin were detected in large amounts in the tissues of lung, ovarian, thyroid, and brain tumors [18]. Although there are several References reports on the increased risk for a second primary malig- [1] K. Oberg, U. Knigge, D. Kwekkeboom, and A. Perren, “Neu- nancy (SPM) in patients with carcinoid tumors [15, 17, 19], roendocrine gastro-entero-pancreatic tumors: ESMO Clinical the rate of secondary primary malignancies for high-grade Practice Guidelines for diagnosis, treatment and follow-up,” neuroendocrine carcinoma is unknown. In our patient, there Annals of Oncology, vol. 23, supplement 7, pp. vii124–vii130, was a high-grade neuroendocrine carcinoma located in the ampulla of Vater. Her colon tumor was asymptomatic and her abdominal CT showed no abnormal finding, and the [2] I. M. Modlin, M. Kidd, R. Pfragner, G. N. Eick, and M. C. mass in the sigmoid colon was coincidentally found during Champaneria, “eTh functional characterization of normal and surgery. Synchronous double primary tumors involving high- neoplastic human enterochromaffin cells,” Journal of Clinical grade neuroendocrine carcinoma of ampulla of Vater and Endocrinology and Metabolism,vol.91, no.6,pp. 2340–2348, sigmoid colon adenocarcinomas have not been reported in 2006. 4 Case Reports in Oncological Medicine [3] L. Bornstein-Quevedo and A. Gamboa-Domnguez, “Carcinoid [19] N. Habal, C. Sims, and A. J. Bilchik, “Gastrointestinal carcinoid tumors of the duodenum and ampulla of vater: a clinicomor- tumors and second primary malignancies,” Journal of Surgical phologic, immunohistochemical, and cell kinetic comparison,” Oncology,vol.75, no.4,pp. 310–316, 2000. Human Pathology, vol. 32, no. 11, pp. 1252–1256, 2001. [20] R. Prommegger, C. Ensinger, P. Steiner, T. Sauper, C. Profan- [4] E.Hatzitheoklitos,M.W.Buchler,H.Friessetal.,“Carcinoidof ter, and R. Margreiter, “Neuroendocrine tumors and second the ampulla of Vater: clinical characteristics and morphologic primary malignancy—a relationship with clinical impact?” features,” Cancer,vol.73, no.6,pp. 1580–1588, 1994. Anticancer Research,vol.24, no.2,pp. 1049–1051, 2004. [5] M.Hartel, M. N. Wente, B. Sido,H.Friess, andM.W.Buc ¨ hler, [21] M. Mesmoudi, S. Boutayeb, T. Mahfoud et al., “Triple malig- “Carcinoid of the ampulla of Vater,” JournalofGastroenterology nancy in a single patient including a cervical carcinoma, a basal and Hepatology, vol. 20, no. 5, pp. 676–681, 2005. cell carcinoma of the skin and a neuroendocrine carcinoma from an unknown primary site: a case report and review of the [6] J. Waisberg, L. L. de Matos, D. R. Waisberg, H. V. B. dos Santos, literature,” Journal of Medical Case Reports,vol.5,article 462, S. M. Fernezlian, and V. L. Capelozzi, “Carcinoid of the minor duodenal papilla associated with pancreas divisum: case report and review of the literature,” Clinics,vol.61, no.4,pp. 365–368, [7] J.M.Dixon,R.W.Chapman,and A. R. Berry, “Carcinoid tumour of the ampulla of Vater presenting as acute pancreatitis,” Gut,vol.28, no.10, pp.1296–1297,1987. [8] R.E.Emory Jr., T. S. Emory, J. R. Goellner,C.S.Grant,and D. M. Nagorney, “Neuroendocrine ampullary tumors: spectrum of disease including the first report of a neuroendocrine carcinoma of non-small cell type,” Surgery, vol. 115, no. 6, pp. 762–766, 1994. [9] J. T. Carter, J. P. Grenert, L. Rubenstein, L. Stewart, and L. W. Way, “Neuroendocrine tumors of the ampulla of vater: biological behavior and surgical management,” Archives of Surgery,vol.144,no. 6, pp.527–531,2009. [10] E. Selvakumar,S.Rajendran,T.G.Balachandar et al., “Neu- roendocrine carcinoma of the ampulla of Vater: a clinico- pathologic evaluation,” Hepatobiliary and Pancreatic Diseases International,vol.7,no. 4, pp.422–425,2008. [11] N. Habal, C. Sims, and A. J. Bilchik, “Gastrointestinal carcinoid tumors and second primary malignancies,” Journal of Surgical Oncology,vol.75, no.4,pp. 310–316, 2000. [12] I. M. Modlin, K. D. Lye, and M. Kidd, “A 5-decade analysis of 13,715 carcinoid tumors,” Cancer,vol.97, no.4,pp. 934–959, [13] H. Nassar, J. Albores-Saavedra, and D. S. Klimstra, “High- grade neuroendocrine carcinoma of the ampulla of vater: a clinicopathologic and immunohistochemical analysis of 14 cases,” American Journal of Surgical Pathology,vol.29, no.5,pp. 588–594, 2005. [14] C. M. Pearson and P. J. Fitzgerald, “Carcinoid tumors—a re- emphasis of their malignant nature. Review of 140 cases,” Cancer,vol.2,no. 6, pp.1005–1026,1949. [15] K. A. Zucker, W. E. Longo, I. M. Modlin, A. J. Bilchik, and T. E. Adrian, “Malignant diathesis from jejunal-ileal carcinoids,” American JournalofGastroenterology,vol.84, no.2,pp. 182–186, [16] K. Oberg, “Expression of growth factors and their receptors in neuroendocrine gut and pancreatic tumors, and prognostic factors for survival,” Annals of the New York Academy of Sciences, vol. 733, pp.46–55,1994. [17] J. T. Gerstle, G. L. Kauffman Jr., and W. A. Koltun, “eTh incidence, management, and outcome of patients with gastroin- testinal carcinoids and second primary malignancies,” Journal of the American College of Surgeons,vol.180,no. 4, pp.427–432, [18] J. C. Reubi, J.-C. Schaer, and B. Waser, “Cholecystokinin (CCK)- A and CCK-B/gastrin receptors in human tumors,” Cancer Research,vol.57, no.7,pp. 1377–1386, 1997. 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Synchronous Appearance of a High-Grade Neuroendocrine Carcinoma of the Ampulla Vater and Sigmoid Colon Adenocarcinoma

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Copyright © 2013 Suna Cokmert et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
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Hindawi Publishing Corporation Case Reports in Oncological Medicine Volume 2013, Article ID 930359, 4 pages http://dx.doi.org/10.1155/2013/930359 Case Report Synchronous Appearance of a High-Grade Neuroendocrine Carcinoma of the Ampulla Vater and Sigmoid Colon Adenocarcinoma 1 1 2 Suna Cokmert, Lutfiye Demir, Aysegul Akder Sari, 1 1 1 1 Yuksel Kucukzeybek, Alper Can, Murat Akyol, Ibrahim Vedat Bayoglu, 1 1 1 Ahmet Dirican, Cigdem Erten, and Mustafa Oktay Tarhan Department of Medical Oncology, Izmir Ataturk Training and Research Hospital, Izmir Katip Celebi University, 35600Izmir,Turkey Department of Pathology, Izmir Ataturk Training and Research Hospital, Izmir Katip Celebi University, 35600 Izmir, Turkey Correspondence should be addressed to Suna Cokmert; sunacok@gmail.com Received 29 September 2013; Accepted 27 October 2013 Academic Editors: J. I. Mayordomo and O. Ozyilkan Copyright © 2013 Suna Cokmert et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Neuroendocrine carcinoma is a relatively rare tumor and its coexistence with other primary cancers is very exceptional. We present a case of a 63-year-old woman with biliary obstruction due to a high-grade neuroendocrine carcinoma located in ampulla of Vater who was found to have a synchronous sigmoid colon adenocarcinoma while undergoing staging laparotomy and pancreas head resection. Medical history was significant only for basal cel l skin cancer. Immunohistochemical examination revealed the concurrence of histologically proved neuroendocrine carcinoma (chromogranin A, synaptophysin, and CD56 were positive) and Stage II (T3, N0, and M0) according to the TNM staging classification of colorectal cancer. eTh coexistence of neuroendocrine tumors with either synchronous or metachronous unrelated cancer is increasingly recognized. eTh patients with neuroendocrine carcinoma should be evaluated for secondary primary malignancies. 1. Introduction tract. Neuroendocrine carcinoma of the ampulla of Vater very rarely coexist with other primary sporadic cancers. Neuroendocrine tumors (NETs) are a rare and heterogeneous Here, we present a patient with an ampulla of Vater mass, group of neoplasms [1] that can arise from neuroendocrine diagnosed as a high-grade neuroendocrine carcinoma, and a cells localized anywhere in the body [1, 2]. In the duode- synchronous sigmoid colon adenocarcinoma coincidentally num, NETs constitute 5.7 to 7.9% of the neuroendocrine diagnosed during the operation for the ampulla of Vater neoplasms of the gastroenteropancreatic tract [3]. In the tumor. English language literature, fewer than 120 cases of NETs of the ampulla of Vater have been described. Furthermore, most neuroendocrine tumors of the duodenum are of carci- 2. Case Report noid origin and only a few case reports of neuroendocrine carcinomas (NEC) of the ampulla have been documented A 63-year-old woman presented with a one-month history of [4–10]. progressive upper abdominal pain and jaundice. On physical Neuroendocrine tumors are associated with synchronous examination both sclerae appeared yellow. Abdominal or metachronous secondary primary malignancies. Rates of examination revealed mild tenderness in the right upper secondary primary malignancies are up to 55% in neuroen- abdominal quadrant, but no mass was palpable. er Th e were docrine tumors [11]. Secondary primary malignancies are no changes in her bowel movements. Medical history was mainly localized in the gastrointestinal and genitourinary insignificant except for basal cell skin cancer for which 2 Case Reports in Oncological Medicine (a) (b) (c) (d) (e) Figure 1: Neuroendocrine carcinoma of ampulla of Vater. (a)-(b) Neuro endocrine tumor invading muscularis propria in the ampulla, (c) focal necrosis centres and moderate atypia in the tumor, (d) Ki-67 proliferation index above 20%, (e) focal positivity with synaptophysin. she had undergone surgery sixteen years ago. Blood tests of Vater. Endoscopic biopsy was taken from mass lesion and showed mildly impaired liver function tests (total bilirubin: showed a poorly differentiated neuroendocrine carcinoma. 1.9 (0-1 mg/dL), direct bilirubin: 1.1 (0–0.3 mg/dL), AST: 22 As the patient had no hormone-related symptoms, octre- (0–32 IU/L), ALT: 18 (0–32 IU/L), ALP: 189 (40–129 IU/L), oscan was not used and a decision was made to perform and GGT: 44 (10–60 U/L)). Hemogram results revealed resection. A pancreatoduodenectomy was done. During microcytic, hypochromic anemia, with hematocrit 24.2% surgery, a mass in the sigmoid colon was incidentally found. (reference range 36–46%), hemoglobin 7.65 g/dL (reference Left colectomy and a lymphadenectomy were performed. range 12–18 g/dL), mean corpuscular volume 69.2 fL (refer- Histopathological examination showed a poorly differenti- ence range 80–97 fL), mean corpuscular hemoglobin 22 pg ated neuroendocrine carcinoma of ampulla of Vater (Figures (reference range 27–31 pg), mean corpuscular hemoglobin 1(a)–1(c)), 1.2 cm in diameter, with a mitotic rate of nine concentration 31.8 g/dL (reference range 32–36 g/dL), and mitoses per 10 high power elds fi and a Ki-67 proliferative serum ferrum and ferritin levels of 23𝜇 g/dL (reference range index of 40% (Figure 1(d)). Immunohistochemistry chro- 70–180𝜇 g/dL) and 80𝜇 g/L (reference range 30–400𝜇 g/L), mogranin A, synaptophysin (Figure 1(e)), and CD56 were respectively. eTh tumor markers alpha-fetoprotein (AFP), positive. er Th e was no metastasis to periampullary lymph carcinoembryonic antigen (CEA), and CA19-9 were all nodes. Furthermore, there was a sigmoid colon adenocarci- within normal ranges. Ultrasonographic examination of noma with local invasion into the subserosa (pT3) (Figure 2). the abdomen showed a dilation of choledocal duct but None of the 8 resected pericolic lymph nodes were involved. no gallstones. Abdominal computed tomography showed All microscopic margins were clear. Treatment with 5-FU and no enlargement of the pancreatic head. An endoscopic leucovorin plus cisplatin to treat both tumors was suggested retrograde cholangiography revealed a mass in the ampulla postoperatively. Case Reports in Oncological Medicine 3 the literature, making this the rfi st case report of this scenario. Prommegger et al. reviewed 14 patients with NET and SPM, and, among those patients, a NET of duodenum localization was detected in only two patients whose SPM were basal cell carcinoma of skin and colon carcinoma. Five patients had synchronous SPM including two colon cancers with one double colon cancer, one gastric cancer, one bladder cancer, and one ovarian cancer and nine metachronous SPM includ- ingtwo basalcellcarcinomas, onecolon cancer,two breast cancer, one gastric MALT-lymphomas, one ductal pancreatic adenocarcinoma, one bladder cancer, and one hepatocellular carcinoma [20]. In addition, a case was reported of a woman treated initially for a synchronous squamous cell carcinoma Figure 2: Adenocarcinoma in sigmoid colon. of the cervix and a basal cell carcinoma of the skin, who developed a third malignancy described as a neuroendocrine carcinoma of an unknown primary site [21]. Our patient has been diagnosed with basal cell skin carcinoma 15 years prior 3. Discussion to the initial diagnosis of the synchronously described colon Neuroendocrine tumors (NETs) may be localized throughout adenocarcinoma and neuroendocrine carcinoma. In this report, we present an interesting case with high- the human body [1] and relatively rarely in theduodenum [2, 3]. In an analysis of 13,715 neuroendocrine tumors reported grade neuroendocrine carcinoma of ampulla of Vater and over a 50-year period to the Surveillance, Epidemiology, and asymptomatic synchronous sigmoid colon adenocarcinoma End Results Program of the National Cancer Institute, only incidentally detected at the operation. Multiple primary 360 cases involved the duodenum or ampulla [9, 12]. A tumors seen synchronously and/or metachronously, with neuroendocrine carcinomas, are an increasingly encountered series from Memorial Sloan-Kettering Cancer Center showed only 14 high-grade neuroendocrine carcinomas out of 215 phenomenon. es Th e patients must be extensively evaluated ampullary carcinomas [13]. Carter et al. reported 7 patients for SPM during the workup and follow-up period. We recommend that a whole body CT scan and endoscopic with NET of ampulla of Vater and, among those patients, a high-grade neuroendocrine carcinoma was detected in only investigation of the gastrointestinal tract be performed. one patient [9]. Based on these reports, it can be postu- Further studies are required to clarify the mechanisms of lated that high-grade neuroendocrine carcinoma localized in carcinogenesis associated with neuroendocrine carcinomas ampulla of Vater is very rare. and synchronous tumors. Neuroendocrine tumors are associated with secondary primary malignancies. In 1944, Pearson and Fitzgerald reported, for the rfi st time, a high incidence of carcinoid Authors’ Contribution tumors with secondary primary malignancies (SPM) [14]. Suna Cokmert, Yuksel Kuc¸ukzeybek, Lutyfi e Demir, and Many reports demonstrated NET-associated SPM in up to Aysegul Akder Sari contributed equally to this work; 55% [3–10] of patients. The situation of NET-associated SPM Suna Cokmert, Yuksel Kuc¸ukzeybek, and Lutyfi e Demir can be explained with the eld-eff fi ect theory. Accordingly, designed the research; Suna Cokmert, Aysegul Akder Sari, a common carcinogenic eeff ct stimulates the growth of neuroendocrine and SPM cancer cells [11, 15]. Additionally, Lutyfi e Demir, Yuksel Kuc ¸ukzeybek, Murat Akyol, Alper Can, Ibrahim Vedat Bayoglu, and Ahmet Dirican per- NETs produce and secrete various neuropeptides or non- formed the research; Suna Cokmert, Cigdem Erten, Yuksel neuropeptides, many of which have specific growth factor Kuc¸ukzeybek, and Mustafa Oktay Tarhan analyzed the data; properties [16]. For example, gastrin and cholecystokinin Suna Cokmert wrote the paper. (CCK) can stimulate gastric mucosal and pancreatic cell growth [17]. Recently, receptors for CCK and gastrin were detected in large amounts in the tissues of lung, ovarian, thyroid, and brain tumors [18]. Although there are several References reports on the increased risk for a second primary malig- [1] K. Oberg, U. Knigge, D. Kwekkeboom, and A. Perren, “Neu- nancy (SPM) in patients with carcinoid tumors [15, 17, 19], roendocrine gastro-entero-pancreatic tumors: ESMO Clinical the rate of secondary primary malignancies for high-grade Practice Guidelines for diagnosis, treatment and follow-up,” neuroendocrine carcinoma is unknown. In our patient, there Annals of Oncology, vol. 23, supplement 7, pp. vii124–vii130, was a high-grade neuroendocrine carcinoma located in the ampulla of Vater. Her colon tumor was asymptomatic and her abdominal CT showed no abnormal finding, and the [2] I. M. Modlin, M. Kidd, R. Pfragner, G. N. Eick, and M. C. mass in the sigmoid colon was coincidentally found during Champaneria, “eTh functional characterization of normal and surgery. Synchronous double primary tumors involving high- neoplastic human enterochromaffin cells,” Journal of Clinical grade neuroendocrine carcinoma of ampulla of Vater and Endocrinology and Metabolism,vol.91, no.6,pp. 2340–2348, sigmoid colon adenocarcinomas have not been reported in 2006. 4 Case Reports in Oncological Medicine [3] L. Bornstein-Quevedo and A. Gamboa-Domnguez, “Carcinoid [19] N. Habal, C. Sims, and A. J. Bilchik, “Gastrointestinal carcinoid tumors of the duodenum and ampulla of vater: a clinicomor- tumors and second primary malignancies,” Journal of Surgical phologic, immunohistochemical, and cell kinetic comparison,” Oncology,vol.75, no.4,pp. 310–316, 2000. Human Pathology, vol. 32, no. 11, pp. 1252–1256, 2001. [20] R. Prommegger, C. Ensinger, P. Steiner, T. Sauper, C. Profan- [4] E.Hatzitheoklitos,M.W.Buchler,H.Friessetal.,“Carcinoidof ter, and R. 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