Primary hepatic neuroendocrine carcinoma: report of two cases and literature review
Tóm tắt
Primary hepatic neuroendocrine carcinoma (PHNEC) is extremely rare. The diagnosis of PHNEC remains challenging—partly due to its rarity, and partly due to its lack of unique clinical features. Available treatment options for PHNEC include surgical resection of the liver tumor(s), radiotherapy, liver transplant, transcatheter arterial chemoembolization (TACE), and administration of somatostatin analogues. We report two male PHNEC cases and discuss the diagnosis and treatment options. Both cases presented with abdominal pain; case two also presented with symptoms of jaundice. The initial diagnosis for both cases was poorly differentiated grade 3 small-cell neuroendocrine carcinoma, based on imaging characteristics and the pathology of liver biopsies. Final diagnoses of PHNEC were arrived at by ruling out non-hepatic origins. Case one presented with a large tumor in the right liver lobe, and the patient was treated with TACE. Case two presented with tumors in both liver lobes, invasions into the left branch of hepatic portal vein, and metastasis in the hepatic hilar lymph node. This patient was ineligible for TACE and was allergic to the somatostatin analogue octreotide. This limited treatment options to supportive therapies such as albumin supplementation for liver protection. Patient one and two died at 61 and 109 days, respectively, following initial hospital admission. We diagnosed both cases with poorly differentiated grade 3 small-cell PHNEC through imaging characteristics, immunohistochemical staining of liver biopsies, and examinations to eliminate non-hepatic origins. Neither TACE nor liver protection appeared to significantly extend survival time of the two patients, suggesting these treatments may be inadequate to improve survival of patients with poorly differentiated grade 3 small-cell PHNEC. The prognosis of poorly differentiated grade 3 small-cell PHNEC is poor due to limited and ineffective treatment options.
Tài liệu tham khảo
Park CH, Chung JW, Jang SJ, Chung MJ, Bang S, Park SW, Song SY, Chung JB, Park JY. Clinical features and outcomes of primary hepatic neuroendocrine carcinomas. J Gastroenterol Hepatol. 2012;27(8):1306–11.
Shetty PK, Baliga SV, Balaiah K, Gnana PS. Primary hepatic neuroendocrine tumor: an unusual cystic presentation. Indian J Pathol Microbiol. 2010;53(4):760–2.
Skagias L, Vasou O, Ntinis A, Kondi-Pafiti A, Koureas A, Politi E. Primary hepatic neuroendocrine tumor with exophytic growth: report of a case with diagnosis by fine needle aspiration biopsy. Acta Cytol. 2010;54(2):202–4.
Camargo ES, Viveiros Mde M, Correa Neto IJ, Robles L, Rezende MB. Primary hepatic carcinoid tumor: case report and literature review. Einstein (Sao Paulo). 2014;12(4):505–8.
Oronsky B, PC Ma, Morgensztern D, Carter CA. Nothing But NET: A Review of Neuroendocrine Tumors and Carcinomas. Neoplasia. 2017;19(12):991–1002. https://doi.org/10.1016/j.neo.2017.09.002.
Quartey B: Primary hepatic neuroendocrine tumor: what do we know now?; 2011.
Lin CW, Lai CH, Hsu CC, Hsu CT, Hsieh PM, Hung KC, Chen YS. Primary hepatic carcinoid tumor: a case report and review of the literature. Cases J. 2009;2(1):90.
Knox CD, Anderson CD, Lamps LW, Adkins RB, Pinson CW. Long-term survival after resection for primary hepatic carcinoid tumor. Ann Surg Oncol. 2003;10(10):1171–5.
Zhang A, Xiang J, Zhang M, Zheng S. Primary hepatic carcinoid tumours: clinical features with an emphasis on carcinoid syndrome and recurrence. J Int Med Res. 2008;36(4):848–59.
Akahori T, Sho M, Tanaka T, Nishiofuku H, Kinoshita S, Nagai M, Kichikawa K, Nakajima Y. Significant efficacy of new transcatheter arterial chemoembolization technique for hepatic metastases of pancreatic neuroendocrine tumors. Anticancer Res. 2013;33(8):3355–8.
Bencsikova B. Antiproliferative effect of somatostatin analogs - data analyses and clinical applications in the context of the CLARINET study. Klinicka onkologie. 2016;29(4):253–8.
Chamberlain RS, Canes D, Brown KT, Saltz L, Jarnagin W, Fong Y, Blumgart LH. Hepatic neuroendocrine metastases: does intervention alter outcomes? J Am Coll Surg. 2000;190(4):432–45.
Iwao M, Nakamuta M, Enjoji M, Kubo H, Fukutomi T, Tanabe Y, Nishi H, Taguchi KI, Kotoh K, Nawata H. Primary hepatic carcinoid tumor: case report and review of 53 cases. Med Sci Monit. 2001;7(4):746–50.
Donadon M, Torzilli G, Palmisano A, Del Fabbro D, Panizzo V, Maggioni M, Santambrogio R, Montorsi M. Liver resection for primary hepatic neuroendocrine tumours: report of three cases and review of the literature. Eur J Surg Oncol. 2006;32(3):325–8.
Huang YQ, Xu F, Yang JM, Huang B. Primary hepatic neuroendocrine carcinoma: clinical analysis of 11 cases. Hepatobiliary Pancreat Dis Int. 2010;9(1):44–8.
Rückert R, Rückert J, Dörffel Y, Rudolph B, Müller J. Primary hepatic neuroendocrine tumor: successful hepatectomy in two cases and review of the literature. Digestion. 1999;60(2):110–6.
Akahoshi T, Higashi H, Tsuruta S, Tahara K, Matsumoto T, Takeuchi H, Era S, Fujita F, Muto Y. Primary neuroendocrine carcinoma coexisting with hemangioma in the liver: report of a case. Surg Today. 2010;40(2):185–9.
Modlin IM, Lye KD, Kidd M. A 5-decade analysis of 13,715 carcinoid tumors. Cancer. 2003;97(4):934–59.
Nikfarjam M, Muralidharan V, Christophi C. Primary hepatic carcinoid tumours. HPB (Oxford). 2004;6(1):13–7.
Morishita A, Yoneyama H, Nomura T, Sakamoto T, Fujita K, Tani J, Miyoshi H, Haba R, Masaki T. Primary hepatic neuroendocrine tumor: a case report. Mol Clin Oncol. 2016;4(6):954–6.
Kellock T, Tuong B, Harris AC, Yoshida E. Diagnostic imaging of primary hepatic neuroendocrine tumors: a case and discussion of the literature. Case Rep Radiol. 2014;2014:5.
Elsayes KM, Menias CO, Bowerson M, Osman OM, Alkharouby AM, Hillen TJ. Imaging of carcinoid tumors: spectrum of findings with pathologic and clinical correlation. J Comput Assist Tomogr. 2011;35(1):72–80.
Hasegawa H, Kuzushita N, Nakazuru S, Itoh M, Araki M, Yoshioka C, Suemura S, Ohta M, Yoshio T, Toyama T, et al. Case of primary hepatic neuroendocrine carcinoma diagnosed by needle biopsy. Nihon Shokakibyo Gakkai Zasshi. 2010;107(12):1956–62.
Tamm EP, Kim EE, Ng CS. Imaging of neuroendocrine tumors. Hematol Oncol Clin North Am. 2007;21(3):409–32.
Wang L-X, Liu K, Lin G-W, Jiang T. Primary hepatic neuroendocrine tumors: comparing CT and MRI features with pathology. Cancer Imaging. 2015;15(1):1.
Pilichowska M, Kimura N, Ouchi A, Lin H, Mizuno Y, Nagura H. Primary hepatic carcinoid and neuroendocrine carcinoma: clinicopathological and immunohistochemical study of five cases. Pathol Int. 1999;49(4):318–24.
Sundin A, Eriksson B, Bergström M, Långström B, Öberg K, Örlefors H. PET in the diagnosis of neuroendocrine tumors. Ann N Y Acad Sci. 2004;1014(1):246–57.
Wang LM, An SL, Wu JX. Diagnosis and therapy of primary hepatic neuroendocrine carcinoma: clinical analysis of 10 cases. Asian Pac J Cancer Prev. 2014;15(6):2541–6. https://www.ncbi.nlm.nih.gov/pubmed/24761861.
Ihse I, Persson B, Tibblin S. Neuroendocrine metastases of the liver. World J Surg. 1995;19(1):76–82.
Seemann MD, Meisetschlaeger G, Gaa J, Rummeny EJ. Assessment of the extent of metastases of gastrointestinal carcinoid tumors using whole-body PET, CT, MRI, PET/CT and PET/MRI. Eur J Med Res. 2006;11(2):58–65.
Choi GH, Ann SY, Lee SI, Kim SB, Song IH. Collision tumor of hepatocellular carcinoma and neuroendocrine carcinoma involving the liver: case report and review of the literature. World J Gastroenterol. 2016;22(41):9229–34.
Baker E, Jacobs C, Martinie J, Iannitti DA, Vrochides D, Swan RZ. Mixed hepatocellular carcinoma, neuroendocrine carcinoma of the liver. Am Surg. 2016;82(11):1121–5.
Okumura Y, Kohashi K, Wang H, Kato M, Maehara Y, Ogawa Y, Oda Y. Combined primary hepatic neuroendocrine carcinoma and hepatocellular carcinoma with aggressive biological behavior (adverse clinical course): a case report. Pathol Res Pract. 2017;213(10):1322–6.
Lu JG, Farukhi MA, Mayeda D, French SW. Hepatocellular carcinoma with neuroendocrine differentiation: a case report. Exp Mol Pathol. 2017;103(2):200–3.
Yun EY, Kim TH, Lee SS, Kim HJ, Kim HJ, Jung WT, Lee OJ, Song DH. A case of composite hepatocellular carcinoma and neuroendocrine carcinoma in a patient with liver cirrhosis caused by chronic hepatitis B. Korean J Gastroenterol. 2016;68(2):109–13.
Michalopoulos N, Papavramidis TS, Karayannopoulou G, Pliakos I, Papavramidis ST, Kanellos I. Neuroendocrine tumors of extrahepatic biliary tract. Pathol Oncol Res. 2014;20(4):765–75.
Quartey B. Primary hepatic neuroendocrine tumor: what do we know now? World J Surg Oncol. 2011;2(5):209–16.
Mehta DC, Warner RRP, Parnes I, Weiss M. An 18-year follow-up of primary hepatic carcinoid with carcinoid syndrome. J Clin Gastroenterol. 1996;23(1):60–2.
Sano K, Kosuge T, Yamamoto J, Shimada K, Takayama T, Yamasaki S, Makuuchi M. Primary hepatic carcinoid tumors confirmed with long-term follow-up after resection. Hepato-Gastroenterology. 1998;46(28):2547–50.
Iimuro Y, Deguchi Y, Ueda Y, Tanaka A, Iwasa Y, Ishihara M, Mizuta K, Yamamoto Y, Ikai I, Shimahara Y. Primary hepatic carcinoid tumor with metachronous lymph node metastasis after long-term follow up. J Gastroenterol Hepatol. 2002;17(10):1119–24.
Fenwick SW, Wyatt JI, Toogood GJ, Lodge JP. Hepatic resection and transplantation for primary carcinoid tumors of the liver. Ann Surg. 2004;239(2):210–9.
de Liguori CN, Manzia T, Tariciotti L, Berlanda M, Orlando G, Tisone G. Liver transplantation in primary hepatic carcinoid tumor: case report and literature review. In: Transplantation proceedings: 2009: Elsevier; 2009. p. 1386–9. http://www.transplantation-proceedings.org/article/S0041-1345(09)00398-4/fulltext.
Weiner RE, Thakur ML. Radiolabeled peptides in the diagnosis and therapy of oncological diseases. Appl Radiat Isot. 2002;57(5):749–63.
Bodei L, Kwekkeboom DJ, Kidd M, Modlin IM, Krenning EP. Radiolabeled somatostatin analogue therapy of Gastroenteropancreatic cancer. Semin Nucl Med. 2016;46(3):225–38.
Yang K, Cheng YS, Yang JJ, Jiang X, Guo JX. Primary hepatic neuroendocrine tumor with multiple liver metastases: a case report with review of the literature. World J Gastroenterol. 2015;21(10):3132–8.
Sarmiento JM, Heywood G, Rubin J, Ilstrup DM, Nagorney DM, Que FG. Surgical treatment of neuroendocrine metastases to the liver: a plea for resection to increase survival. J Am Coll Surg. 2003;197(1):29–37.
Jensen RT, Delle Fave G. Promising advances in the treatment of malignant pancreatic endocrine tumors. N Engl J Med. 2011;364(6):564–5.
Yao JC, Shah MH, Ito T, Bohas CL, Wolin EM, Van Cutsem E, Hobday TJ, Okusaka T, Capdevila J, de Vries EG, et al. Everolimus for advanced pancreatic neuroendocrine tumors. N Engl J Med. 2011;364(6):514–23.
Raymond E, Dahan L, Raoul JL, Bang YJ, Borbath I, Lombard-Bohas C, Valle J, Metrakos P, Smith D, Vinik A, et al. Sunitinib malate for the treatment of pancreatic neuroendocrine tumors. N Engl J Med. 2011;364(6):501–13.
Chan DL, Segelov E, Singh S. Everolimus in the management of metastatic neuroendocrine tumours. Ther Adv Gastroenterol. 2017;10(1):132–41.
Mulvey CK, Bergsland EK. Systemic therapies for advanced gastrointestinal carcinoid tumors. Hematol Oncol Clin North Am. 2016;30(1):63–82.
Hentic O, Couvelard A, Rebours V, Zappa M, Dokmak S, Hammel P, Maire F, O'Toole D, Lévy P, Sauvanet A, et al. Ki-67 index, tumor differentiation, and extent of liver involvement are independent prognostic factors in patients with liver metastases of digestive endocrine carcinomas. Endocr Relat Cancer. 2011;18(1):51–9.
Bosman FT, Carneiro F, Hruban RH, Theise ND. WHO classification of Tumours of the digestive system. Fourth ed; 2010.
Yao JC, Hassan M, Phan A, Dagohoy C, Leary C, Mares JE, Abdalla EK, Fleming JB, Vauthey JN, Rashid A, et al. One hundred years after “carcinoid”: epidemiology of and prognostic factors for neuroendocrine tumors in 35,825 cases in the United States. J Clin Oncol. 2008;26(18):3063–72.
Yau T, Yao TJ, Chan P, Epstein RJ, Ng KK, Chok SH, Cheung TT, Fan ST, Poon RT. The outcomes of elderly patients with hepatocellular carcinoma treated with transarterial chemoembolization. Cancer. 2009;115(23):5507–15.
Schwartz G, Colanta A, Gaetz H, Olichney J, Attiyeh F. Primary carcinoid tumors of the liver. World J Surg Oncol. 2008;6:91.
Srivastava A, Hornick JL. Immunohistochemical staining for CDX-2, PDX-1, NESP-55, and TTF-1 can help distinguish gastrointestinal carcinoid tumors from pancreatic endocrine and pulmonary carcinoid tumors. Am J Surg Pathol. 2009;33(4):626–32.