Tumors of the Gastrointestinal System Including the Pancreas

  • Melissa W. TaggartEmail author
  • Wai Chin Foo
  • Sun Mi Lee


The chapter on the gastrointestinal tract focuses on neoplasms arising in the esophagus, stomach, small intestine, appendix, colon, and anus. An overview of concepts common to the gastrointestinal tract, such as neoplasia arising in inflammatory conditions and hereditary conditions, and an overview of neuroendocrine neoplasms, is provided in the introductory section. A brief review of normal histology of the organs is presented. Most of the tumors presented in this chapter represent epithelial neoplasms, and thus, mesenchymal tumors and lymphomas are reviewed in their respective chapters. The features of the neoplasms are presented, including descriptions of pertinent precursor lesions, pathogenesis, macroscopic and microscopic features as well as tumor subtypes and histologic prognostic features, and immunohistochemical profiles. Common diagnostic dilemmas, predictive and prognostic factors, and molecular abnormalities are discussed. Changes to the current American Joint Commission on Cancer staging guidelines are highlighted.


Gastrointestinal Carcinoma Adenocarcinoma Squamous cell carcinoma Neuroendocrine Adenoma Precursor Dysplasia 


  1. 1.
    Balkwill F, Mantovani A. Inflammation and cancer: back to Virchow? Lancet. 2001;357(9255):539–45.PubMedGoogle Scholar
  2. 2.
    O’Sullivan KE, Phelan JJ, O’Hanlon C, Lysaght J, O’Sullivan JN, Reynolds JV. The role of inflammation in cancer of the esophagus. Expert Rev Gastroenterol Hepatol. 2014;8(7):749–60.PubMedGoogle Scholar
  3. 3.
    Park YH, Kim N. Review of atrophic gastritis and intestinal metaplasia as a premalignant lesion of gastric cancer. J Cancer Prev. 2015;20(1):25–40.PubMedPubMedCentralGoogle Scholar
  4. 4.
    Correa P, Piazuelo MB. Helicobacter pylori infection and gastric adenocarcinoma. US Gastroenterol Hepatol Rev. 2011;7(1):59–64.PubMedPubMedCentralGoogle Scholar
  5. 5.
    Ullman TA, Itzkowitz SH. Intestinal inflammation and cancer. Gastroenterology. 2011;140(6):1807–16.PubMedGoogle Scholar
  6. 6.
    Axelrad JE, Lichtiger S, Sethi A. Treatment of Crohn’s disease anastomotic stricture with a Lumen-apposing metal stent. Clin Gastroenterol Hepatol. 2018;16(3):A25–6.PubMedGoogle Scholar
  7. 7.
    Ng DW, Ching Tan GH, Teo MC. Malignancy arising in a 41-year-old colonic interposition graft. Asian J Surg. 2016;39(1):45–7.PubMedGoogle Scholar
  8. 8.
    Iwamoto M, Kawada K, Hida K, Hasegawa S, Sakai Y. Adenocarcinoma arising at a colostomy site with inguinal lymph node metastasis: report of a case. Jpn J Clin Oncol. 2015;45(2):217–20.PubMedGoogle Scholar
  9. 9.
    Boland CR, Goel A. Microsatellite instability in colorectal cancer. Gastroenterology. 2010;138(6):2073–87. e3.PubMedPubMedCentralGoogle Scholar
  10. 10.
    Tutlewska K, Lubinski J, Kurzawski G. Germline deletions in the EPCAM gene as a cause of lynch syndrome – literature review. Hered Cancer Clin Pract. 2013;11(1):9.PubMedPubMedCentralGoogle Scholar
  11. 11.
    Giardiello FM, Allen JI, Axilbund JE, Boland CR, Burke CA, Burt RW, et al. Guidelines on genetic evaluation and management of lynch syndrome: a consensus statement by the US multi-society task force on colorectal cancer. Am J Gastroenterol. 2014;109(8):1159–79.PubMedGoogle Scholar
  12. 12.
    Vasen HF, Mecklin JP, Khan PM, Lynch HT. The International Collaborative Group on hereditary non-polyposis colorectal Cancer (ICG-HNPCC). Dis Colon Rectum. 1991;34(5):424–5.PubMedGoogle Scholar
  13. 13.
    Vasen HF, Watson P, Mecklin JP, Lynch HT. New clinical criteria for hereditary nonpolyposis colorectal cancer (HNPCC, Lynch syndrome) proposed by the International Collaborative group on HNPCC. Gastroenterology. 1999;116(6):1453–6.PubMedGoogle Scholar
  14. 14.
    Parry S, Win AK, Parry B, Macrae FA, Gurrin LC, Church JM, et al. Metachronous colorectal cancer risk for mismatch repair gene mutation carriers: the advantage of more extensive colon surgery. Gut. 2011;60(7):950–7.PubMedGoogle Scholar
  15. 15.
    Umar A, Boland CR, Terdiman JP, Syngal S, de la Chapelle A, Ruschoff J, et al. Revised Bethesda Guidelines for hereditary nonpolyposis colorectal cancer (Lynch syndrome) and microsatellite instability. J Natl Cancer Inst. 2004;96(4):261–8.PubMedPubMedCentralGoogle Scholar
  16. 16.
    Sepulveda AR, Hamilton SR, Allegra CJ, Grody W, Cushman-Vokoun AM, Funkhouser WK, et al. Molecular biomarkers for the evaluation of colorectal cancer: guideline from the American Society for Clinical Pathology, College of American Pathologists, Association for Molecular Pathology, and American Society of Clinical Oncology. Arch Pathol Lab Med. 2017;141(5):625–57.PubMedGoogle Scholar
  17. 17.
    Network NCC. Colon cancer (Version 2.2017 – March 13, 2017). Available from:
  18. 18.
    Network NCC. Rectal cancer (Version 3.2017 – March 13, 2017). Available from:
  19. 19.
    Evaluation of Genomic Applications in P, Prevention Working G. Recommendations from the EGAPP Working Group: genetic testing strategies in newly diagnosed individuals with colorectal cancer aimed at reducing morbidity and mortality from Lynch syndrome in relatives. Genet Med. 2009;11(1):35–41.Google Scholar
  20. 20.
    Ladabaum U, Wang G, Terdiman J, Blanco A, Kuppermann M, Boland CR, et al. Strategies to identify the lynch syndrome among patients with colorectal cancer: a cost-effectiveness analysis. Ann Intern Med. 2011;155(2):69–79.PubMedPubMedCentralGoogle Scholar
  21. 21.
    Rubenstein JH, Enns R, Heidelbaugh J, Barkun A, Clinical Guidelines C. American Gastroenterological Association Institute guideline on the diagnosis and management of Lynch syndrome. Gastroenterology. 2015;149(3):777–82. quiz e16–7.PubMedGoogle Scholar
  22. 22.
    Bartley AN, Luthra R, Saraiya DS, Urbauer DL, Broaddus RR. Identification of cancer patients with Lynch syndrome: clinically significant discordances and problems in tissue-based mismatch repair testing. Cancer Prev Res (Phila). 2012;5(2):320–7.Google Scholar
  23. 23.
    Blake C, Tsao JL, Wu A, Shibata D. Stepwise deletions of polyA sequences in mismatch repair-deficient colorectal cancers. Am J Pathol. 2001;158(5):1867–70.PubMedPubMedCentralGoogle Scholar
  24. 24.
    Kuan SF, Ren B, Brand R, Dudley B, Pai RK. Neoadjuvant therapy in microsatellite-stable colorectal carcinoma induces concomitant loss of MSH6 and Ki-67 expression. Hum Pathol. 2017;63:33–9.PubMedGoogle Scholar
  25. 25.
    Bao F, Panarelli NC, Rennert H, Sherr DL, Yantiss RK. Neoadjuvant therapy induces loss of MSH6 expression in colorectal carcinoma. Am J Surg Pathol. 2010;34(12):1798–804.PubMedGoogle Scholar
  26. 26.
    Shia J. Immunohistochemistry versus microsatellite instability testing for screening colorectal cancer patients at risk for hereditary nonpolyposis colorectal cancer syndrome. Part I. The utility of immunohistochemistry. J Mol Diagn. 2008;10(4):293–300.PubMedPubMedCentralGoogle Scholar
  27. 27.
    Zhang L. Immunohistochemistry versus microsatellite instability testing for screening colorectal cancer patients at risk for hereditary nonpolyposis colorectal cancer syndrome. Part II. The utility of microsatellite instability testing. J Mol Diagn. 2008;10(4):301–7.PubMedPubMedCentralGoogle Scholar
  28. 28.
    Buhard O, Lagrange A, Guilloux A, Colas C, Chouchene M, Wanherdrick K, et al. HSP110 T17 simplifies and improves the microsatellite instability testing in patients with colorectal cancer. J Med Genet. 2016;53(6):377–84.PubMedGoogle Scholar
  29. 29.
    Niu B, Ye K, Zhang Q, Lu C, Xie M, McLellan MD, et al. MSIsensor: microsatellite instability detection using paired tumor-normal sequence data. Bioinformatics. 2014;30(7):1015–6.Google Scholar
  30. 30.
    Salipante SJ, Scroggins SM, Hampel HL, Turner EH, Pritchard CC. Microsatellite instability detection by next generation sequencing. Clin Chem. 2014;60(9):1192–9.Google Scholar
  31. 31.
    Nowak JA, Yurgelun MB, Bruce JL, Rojas-Rudilla V, Hall DL, Shivdasani P, et al. Detection of mismatch repair deficiency and microsatellite instability in colorectal adenocarcinoma by targeted next-generation sequencing. J Mol Diagn. 2017;19(1):84–91.PubMedPubMedCentralGoogle Scholar
  32. 32.
    Funkhouser WK Jr, Lubin IM, Monzon FA, Zehnbauer BA, Evans JP, Ogino S, et al. Relevance, pathogenesis, and testing algorithm for mismatch repair-defective colorectal carcinomas: a report of the association for molecular pathology. J Mol Diagn. 2012;14(2):91–103.PubMedGoogle Scholar
  33. 33.
    Boland CR, Thibodeau SN, Hamilton SR, Sidransky D, Eshleman JR, Burt RW, et al. A National Cancer Institute workshop on microsatellite instability for cancer detection and familial predisposition: development of international criteria for the determination of microsatellite instability in colorectal cancer. Cancer Res. 1998;58(22):5248–57.PubMedGoogle Scholar
  34. 34.
    Deschoolmeester V, Baay M, Wuyts W, Van Marck E, Van Damme N, Vermeulen P, et al. Detection of microsatellite instability in colorectal cancer using an alternative multiplex assay of quasi-monomorphic mononucleotide markers. J Mol Diagn. 2008;10(2):154–9.PubMedPubMedCentralGoogle Scholar
  35. 35.
    Rodriguez-Soler M, Perez-Carbonell L, Guarinos C, Zapater P, Castillejo A, Barbera VM, et al. Risk of cancer in cases of suspected lynch syndrome without germline mutation. Gastroenterology. 2013;144(5):926–32 e1. quiz e13–4.PubMedGoogle Scholar
  36. 36.
    Haraldsdottir S, Hampel H, Tomsic J, Frankel WL, Pearlman R, de la Chapelle A, et al. Colon and endometrial cancers with mismatch repair deficiency can arise from somatic, rather than germline, mutations. Gastroenterology. 2014;147(6):1308–16. e1.PubMedPubMedCentralGoogle Scholar
  37. 37.
    Mensenkamp AR, Vogelaar IP, van Zelst-Stams WA, Goossens M, Ouchene H, Hendriks-Cornelissen SJ, et al. Somatic mutations in MLH1 and MSH2 are a frequent cause of mismatch-repair deficiency in Lynch syndrome-like tumors. Gastroenterology. 2014;146(3):643–6. e8.PubMedGoogle Scholar
  38. 38.
    Castillejo A, Vargas G, Castillejo MI, Navarro M, Barbera VM, Gonzalez S, et al. Prevalence of germline MUTYH mutations among Lynch-like syndrome patients. Eur J Cancer. 2014;50(13):2241–50.PubMedGoogle Scholar
  39. 39.
    Morak M, Heidenreich B, Keller G, Hampel H, Laner A, de la Chapelle A, et al. Biallelic MUTYH mutations can mimic lynch syndrome. Eur J Hum Genet. 2014;22(11):1334–7.PubMedPubMedCentralGoogle Scholar
  40. 40.
    Carethers JM. Differentiating Lynch-like from Lynch syndrome. Gastroenterology. 2014;146(3):602–4.PubMedPubMedCentralGoogle Scholar
  41. 41.
    Carethers JM, Stoffel EM. Lynch syndrome and Lynch syndrome mimics: the growing complex landscape of hereditary colon cancer. World J Gastroenterol. 2015;21(31):9253–61.PubMedPubMedCentralGoogle Scholar
  42. 42.
    Shia J. Evolving approach and clinical significance of detecting DNA mismatch repair deficiency in colorectal carcinoma. Semin Diagn Pathol. 2015;32(5):352–61.PubMedPubMedCentralGoogle Scholar
  43. 43.
    Bakry D, Aronson M, Durno C, Rimawi H, Farah R, Alharbi QK, et al. Genetic and clinical determinants of constitutional mismatch repair deficiency syndrome: report from the constitutional mismatch repair deficiency consortium. Eur J Cancer. 2014;50(5):987–96.PubMedGoogle Scholar
  44. 44.
    Jasperson K, Burt RW. The genetics of colorectal cancer. Surg Oncol Clin N Am. 2015;24(4):683–703.PubMedGoogle Scholar
  45. 45.
    Newton KF, Mallinson EK, Bowen J, Lalloo F, Clancy T, Hill J, et al. Genotype-phenotype correlation in colorectal polyposis. Clin Genet. 2012;81(6):521–31.PubMedGoogle Scholar
  46. 46.
    Knudsen AL, Bulow S, Tomlinson I, Moslein G, Heinimann K, Christensen IJ, et al. Attenuated familial adenomatous polyposis: results from an international collaborative study. Colorectal Dis. 2010;12(10 Online):e243–9.PubMedGoogle Scholar
  47. 47.
    Burt RW, Leppert MF, Slattery ML, Samowitz WS, Spirio LN, Kerber RA, et al. Genetic testing and phenotype in a large kindred with attenuated familial adenomatous polyposis. Gastroenterology. 2004;127(2):444–51.PubMedGoogle Scholar
  48. 48.
    Aretz S, Uhlhaas S, Caspari R, Mangold E, Pagenstecher C, Propping P, et al. Frequency and parental origin of de novo APC mutations in familial adenomatous polyposis. Eur J Hum Genet. 2004;12(1):52–8.PubMedGoogle Scholar
  49. 49.
    Bulow S, Bjork J, Christensen IJ, Fausa O, Jarvinen H, Moesgaard F, et al. Duodenal adenomatosis in familial adenomatous polyposis. Gut. 2004;53(3):381–6.PubMedPubMedCentralGoogle Scholar
  50. 50.
    Gardner EJ. Follow-up study of a family group exhibiting dominant inheritance for a syndrome including intestinal polyps, osteomas, fibromas and epidermal cysts. Am J Hum Genet. 1962;14:376–90.PubMedPubMedCentralGoogle Scholar
  51. 51.
    Vogt S, Jones N, Christian D, Engel C, Nielsen M, Kaufmann A, et al. Expanded extracolonic tumor spectrum in MUTYH-associated polyposis. Gastroenterology. 2009;137(6):1976–85. e1–10.PubMedGoogle Scholar
  52. 52.
    Nielsen M, Morreau H, Vasen HF, Hes FJ. MUTYH-associated polyposis (MAP). Crit Rev Oncol Hematol. 2011;79(1):1–16.PubMedGoogle Scholar
  53. 53.
    Al-Tassan N, Chmiel NH, Maynard J, Fleming N, Livingston AL, Williams GT, et al. Inherited variants of MYH associated with somatic G:C-->T:a mutations in colorectal tumors. Nat Genet. 2002;30(2):227–32.PubMedGoogle Scholar
  54. 54.
    Borras E, Taggart MW, Lynch PM, Vilar E. Establishing a diagnostic road map for MUTYH-associated polyposis. Clin Cancer Res. 2014;20(5):1061–3.PubMedPubMedCentralGoogle Scholar
  55. 55.
    Guarinos C, Juarez M, Egoavil C, Rodriguez-Soler M, Perez-Carbonell L, Salas R, et al. Prevalence and characteristics of MUTYH-associated polyposis in patients with multiple adenomatous and serrated polyps. Clin Cancer Res. 2014;20(5):1158–68.PubMedGoogle Scholar
  56. 56.
    Church J, Kravochuck S. The “studded” rectum: phenotypic evidence of MYH-associated polyposis. Dis Colon Rectum. 2016;59(6):565–9.PubMedGoogle Scholar
  57. 57.
    Palles C, Cazier JB, Howarth KM, Domingo E, Jones AM, Broderick P, et al. Germline mutations affecting the proofreading domains of POLE and POLD1 predispose to colorectal adenomas and carcinomas. Nat Genet. 2013;45(2):136–44.PubMedGoogle Scholar
  58. 58.
    Bellido F, Pineda M, Aiza G, Valdes-Mas R, Navarro M, Puente DA, et al. POLE and POLD1 mutations in 529 kindred with familial colorectal cancer and/or polyposis: review of reported cases and recommendations for genetic testing and surveillance. Genet Med. 2016;18(4):325–32.PubMedGoogle Scholar
  59. 59.
    Mehenni H, Blouin JL, Radhakrishna U, Bhardwaj SS, Bhardwaj K, Dixit VB, et al. Peutz-Jeghers syndrome: confirmation of linkage to chromosome 19p13.3 and identification of a potential second locus, on 19q13.4. Am J Hum Genet. 1997;61(6):1327–34.PubMedPubMedCentralGoogle Scholar
  60. 60.
    Jenne DE, Reimann H, Nezu J, Friedel W, Loff S, Jeschke R, et al. Peutz-Jeghers syndrome is caused by mutations in a novel serine threonine kinase. Nat Genet. 1998;18(1):38–43.PubMedGoogle Scholar
  61. 61.
    Karuman P, Gozani O, Odze RD, Zhou XC, Zhu H, Shaw R, et al. The Peutz-Jegher gene product LKB1 is a mediator of p53-dependent cell death. Mol Cell. 2001;7(6):1307–19.PubMedGoogle Scholar
  62. 62.
    Alessi DR, Sakamoto K, Bayascas JR. LKB1-dependent signaling pathways. Annu Rev Biochem. 2006;75:137–63.PubMedGoogle Scholar
  63. 63.
    Jass JR, Williams CB, Bussey HJ, Morson BC. Juvenile polyposis--a precancerous condition. Histopathology. 1988;13(6):619–30.PubMedGoogle Scholar
  64. 64.
    Bouraoui S, Azouz H, Kechrid H, Lemaiem F, Mzabi-Regaya S. Peutz-Jeghers’ syndrome with malignant development in a hamartomatous polyp: report of one case and review of the literature. Gastroenterol Clin Biol. 2008;32(3):250–4.PubMedGoogle Scholar
  65. 65.
    Heald B, Mester J, Rybicki L, Orloff MS, Burke CA, Eng C. Frequent gastrointestinal polyps and colorectal adenocarcinomas in a prospective series of PTEN mutation carriers. Gastroenterology. 2010;139(6):1927–33.PubMedPubMedCentralGoogle Scholar
  66. 66.
    Beggs AD, Latchford AR, Vasen HF, Moslein G, Alonso A, Aretz S, et al. Peutz-Jeghers syndrome: a systematic review and recommendations for management. Gut. 2010;59(7):975–86.PubMedGoogle Scholar
  67. 67.
    Gammon A, Jasperson K, Kohlmann W, Burt RW. Hamartomatous polyposis syndromes. Best Pract Res Clin Gastroenterol. 2009;23(2):219–31.PubMedPubMedCentralGoogle Scholar
  68. 68.
    Menko FH, Kneepkens CM, de Leeuw N, Peeters EA, Van Maldergem L, Kamsteeg EJ, et al. Variable phenotypes associated with 10q23 microdeletions involving the PTEN and BMPR1A genes. Clin Genet. 2008;74(2):145–54.PubMedGoogle Scholar
  69. 69.
    Brosens LA, van Hattem A, Hylind LM, Iacobuzio-Donahue C, Romans KE, Axilbund J, et al. Risk of colorectal cancer in juvenile polyposis. Gut. 2007;56(7):965–7.PubMedPubMedCentralGoogle Scholar
  70. 70.
    Eng C. PTEN: one gene, many syndromes. Hum Mutat. 2003;22(3):183–98.Google Scholar
  71. 71.
    Eng C, Thiele H, Zhou XP, Gorlin RJ, Hennekam RC, Winter RM. PTEN mutations and proteus syndrome. Lancet. 2001;358(9298):2079–80.PubMedGoogle Scholar
  72. 72.
    Stanich PP, Owens VL, Sweetser S, Khambatta S, Smyrk TC, Richardson RL, et al. Colonic polyposis and neoplasia in Cowden syndrome. Mayo Clin Proc. 2011;86(6):489–92.PubMedPubMedCentralGoogle Scholar
  73. 73.
    Tan C, Du X. KRAS mutation testing in metastatic colorectal cancer. World J Gastroenterol. 2012;18(37):5171–80.PubMedPubMedCentralGoogle Scholar
  74. 74.
    Mocellin S, Nitti D. Gastrointestinal carcinoid: epidemiological and survival evidence from a large population-based study (n = 25 531). Ann Oncol. 2013;24(12):3040–4.PubMedGoogle Scholar
  75. 75.
    AJCC cancer staging manual. 8 ed. New York: Springer Science+Business Media; 2016. pages cm p.Google Scholar
  76. 76.
    Pinchot SN, Holen K, Sippel RS, Chen H. Carcinoid tumors. Oncologist. 2008;13(12):1255–69.PubMedPubMedCentralGoogle Scholar
  77. 77.
    Raut CP, Kulke MH, Glickman JN, Swanson RS, Ashley SW. Carcinoid tumors. Curr Probl Surg. 2006;43(6):383–450.PubMedGoogle Scholar
  78. 78.
    Yao JC, Hassan M, Phan A, Dagohoy C, Leary C, Mares JE, 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.PubMedGoogle Scholar
  79. 79.
    Williams ED, Siebenmann RE, Sobin LH. Histological typing of endocrine tumours. 1st ed. Geneva: World Health Organization. International Histological Classification of Tumours; 1980. p. 69.Google Scholar
  80. 80.
    Solcia E, Kloppel G, Sobin LH. Histological typing of endocrine tumours. 2nd ed. Berlin Heidelberg: Springer; 2000.Google Scholar
  81. 81.
    Hamilton SR, Aaltonen LA, Organization WH, Cancer IAfRo. Pathology and genetics of tumours of the digestive system. Lyon: IARC Press; 2000.Google Scholar
  82. 82.
    Lloyd RV, Osamura R, Kloppel G, Rosai J, editors. WHO classification of tumours of endocrine organs. 4th ed. Lyon: International Agency for Research on Cancer; 2017.Google Scholar
  83. 83.
    Bosman FT, World Health Organization, International Agency for Research on Cancer. WHO classification of tumours of the digestive system. 4th ed. Lyon: International Agency for Research on Cancer; 2010. p. 417.Google Scholar
  84. 84.
    Tang LH, Gonen M, Hedvat C, Modlin IM, Klimstra DS. Objective quantification of the Ki67 proliferative index in neuroendocrine tumors of the gastroenteropancreatic system: a comparison of digital image analysis with manual methods. Am J Surg Pathol. 2012;36(12):1761–70.PubMedGoogle Scholar
  85. 85.
    Reid MD, Bagci P, Ohike N, Saka B, Erbarut Seven I, Dursun N, et al. Calculation of the Ki67 index in pancreatic neuroendocrine tumors: a comparative analysis of four counting methodologies. Mod Pathol. 2015;28(5):686–94.PubMedGoogle Scholar
  86. 86.
    Adsay V. Ki67 labeling index in neuroendocrine tumors of the gastrointestinal and pancreatobiliary tract: to count or not to count is not the question, but rather how to count. Am J Surg Pathol. 2012;36(12):1743–6.PubMedGoogle Scholar
  87. 87.
    McCall CM, Shi C, Cornish TC, Klimstra DS, Tang LH, Basturk O, et al. Grading of well-differentiated pancreatic neuroendocrine tumors is improved by the inclusion of both Ki67 proliferative index and mitotic rate. Am J Surg Pathol. 2013;37(11):1671–7.PubMedPubMedCentralGoogle Scholar
  88. 88.
    Matsukuma K, Olson KA, Gui D, Gandour-Edwards R, Li Y, Beckett L. Synaptophysin-Ki67 double stain: a novel technique that improves interobserver agreement in the grading of well-differentiated gastrointestinal neuroendocrine tumors. Mod Pathol. 2017;30(4):620–9.PubMedPubMedCentralGoogle Scholar
  89. 89.
    Benafif S, Eeles R. Diagnosis and management of hereditary carcinoids. Recent Results Cancer Res. 2016;205:149–68.PubMedGoogle Scholar
  90. 90.
    Sei Y, Zhao X, Forbes J, Szymczak S, Li Q, Trivedi A, et al. A hereditary form of small intestinal carcinoid associated with a germline mutation in inositol polyphosphate multikinase. Gastroenterology. 2015;149(1):67–78.PubMedPubMedCentralGoogle Scholar
  91. 91.
    Katdare MV, Fichera A, Heimann TM. Familial rectal carcinoid: report of two first-degree relatives with rectal carcinoid and review of the literature. Tech Coloproctol. 2006;10(2):143–6.PubMedGoogle Scholar
  92. 92.
    Doi M, Ikawa O, Taniguchi H, Kawamura T, Katsura K. Multiple rectal carcinoid tumors in monozygotic twins. Clin J Gastroenterol. 2016;9(4):215–21.PubMedGoogle Scholar
  93. 93.
    Hiripi E, Bermejo JL, Sundquist J, Hemminki K. Familial gastrointestinal carcinoid tumours and associated cancers. Ann Oncol. 2009;20(5):950–4.PubMedGoogle Scholar
  94. 94.
    Hassan C, Repici A, Rex DK. Serrated polyposis syndrome: risk stratification or reduction? Gut. 2016;65(7):1070–2.PubMedGoogle Scholar
  95. 95.
    Heetfeld M, Chougnet CN, Olsen IH, Rinke A, Borbath I, Crespo G, et al. Characteristics and treatment of patients with G3 gastroenteropancreatic neuroendocrine neoplasms. Endocr Relat Cancer. 2015;22(4):657–64.PubMedGoogle Scholar
  96. 96.
    Velayoudom-Cephise FL, Duvillard P, Foucan L, Hadoux J, Chougnet CN, Leboulleux S, et al. Are G3 ENETS neuroendocrine neoplasms heterogeneous? Endocr Relat Cancer. 2013;20(5):649–57.PubMedGoogle Scholar
  97. 97.
    Coriat R, Walter T, Terris B, Couvelard A, Ruszniewski P. Gastroenteropancreatic well-differentiated grade 3 neuroendocrine tumors: review and position statement. Oncologist. 2016;21(10):1191–9.PubMedPubMedCentralGoogle Scholar
  98. 98.
    Basturk O, Yang Z, Tang LH, Hruban RH, Adsay V, McCall CM, et al. The high-grade (WHO G3) pancreatic neuroendocrine tumor category is morphologically and biologically heterogeneous and includes both well differentiated and poorly differentiated neoplasms. Am J Surg Pathol. 2015;39(5):683–90.PubMedPubMedCentralGoogle Scholar
  99. 99.
    Reid MD, Balci S, Saka B, Adsay NV. Neuroendocrine tumors of the pancreas: current concepts and controversies. Endocr Pathol. 2014;25(1):65–79.PubMedGoogle Scholar
  100. 100.
    Sorbye H, Welin S, Langer SW, Vestermark LW, Holt N, Osterlund P, et al. Predictive and prognostic factors for treatment and survival in 305 patients with advanced gastrointestinal neuroendocrine carcinoma (WHO G3): the NORDIC NEC study. Ann Oncol. 2013;24(1):152–60.PubMedGoogle Scholar
  101. 101.
    Tang LH, Basturk O, Sue JJ, Klimstra DS. A practical approach to the classification of WHO grade 3 (G3) well-differentiated neuroendocrine tumor (WD-NET) and poorly differentiated neuroendocrine carcinoma (PD-NEC) of the pancreas. Am J Surg Pathol. 2016;40(9):1192–202.PubMedPubMedCentralGoogle Scholar
  102. 102.
    Smith JD, Reidy DL, Goodman KA, Shia J, Nash GM. A retrospective review of 126 high-grade neuroendocrine carcinomas of the colon and rectum. Ann Surg Oncol. 2014;21(9):2956–62.PubMedPubMedCentralGoogle Scholar
  103. 103.
    Rindi G, Kloppel G, Couvelard A, Komminoth P, Korner M, Lopes JM, et al. TNM staging of midgut and hindgut (neuro) endocrine tumors: a consensus proposal including a grading system. Virchows Arch. 2007;451(4):757–62.PubMedGoogle Scholar
  104. 104.
    Rindi G, Petrone G, Inzani F. The 2010 WHO classification of digestive neuroendocrine neoplasms: a critical appraisal four years after its introduction. Endocr Pathol. 2014;25(2):186–92.PubMedGoogle Scholar
  105. 105.
    La Rosa S, Marando A, Sessa F, Capella C. Mixed adenoneuroendocrine carcinomas (MANECs) of the gastrointestinal tract: an update. Cancers (Basel). 2012;4(1):11–30.PubMedPubMedCentralGoogle Scholar
  106. 106.
    La Rosa S, Marando A, Furlan D, Sahnane N, Capella C. Colorectal poorly differentiated neuroendocrine carcinomas and mixed adenoneuroendocrine carcinomas: insights into the diagnostic immunophenotype, assessment of methylation profile, and search for prognostic markers. Am J Surg Pathol. 2012;36(4):601–11.PubMedGoogle Scholar
  107. 107.
    Capella C, La Rosa S, Uccella S, Billo P, Cornaggia M. Mixed endocrine-exocrine tumors of the gastrointestinal tract. Semin Diagn Pathol. 2000;17(2):91–103.PubMedGoogle Scholar
  108. 108.
    Volante M, Rindi G, Papotti M. The grey zone between pure (neuro)endocrine and non-(neuro)endocrine tumours: a comment on concepts and classification of mixed exocrine-endocrine neoplasms. Virchows Arch. 2006;449(5):499–506.PubMedGoogle Scholar
  109. 109.
    Lewin K. Carcinoid tumors and the mixed (composite) glandular-endocrine cell carcinomas. Am J Surg Pathol. 1987;11(Suppl 1):71–86.PubMedGoogle Scholar
  110. 110.
    Volante M, Righi L, Asioli S, Bussolati G, Papotti M. Goblet cell carcinoids and other mixed neuroendocrine/nonneuroendocrine neoplasms. Virchows Arch. 2007;451(Suppl 1):S61–9.PubMedGoogle Scholar
  111. 111.
    Hervieu V, Scoazec JY. Mixed endocrine tumors. Ann Pathol. 2005;25(6):511–28.PubMedGoogle Scholar
  112. 112.
    Weissferdt A, Tang X, Wistuba II, Moran CA. Comparative immunohistochemical analysis of pulmonary and thymic neuroendocrine carcinomas using PAX8 and TTF-1. Mod Pathol. 2013;26(12):1554–60.PubMedPubMedCentralGoogle Scholar
  113. 113.
    Lin X, Saad RS, Luckasevic TM, Silverman JF, Liu Y. Diagnostic value of CDX-2 and TTF-1 expressions in separating metastatic neuroendocrine neoplasms of unknown origin. Appl Immunohistochem Mol Morphol. 2007;15(4):407–14.PubMedGoogle Scholar
  114. 114.
    Ordonez NG. Value of PAX 8 immunostaining in tumor diagnosis: a review and update. Adv Anat Pathol. 2012;19(3):140–51.PubMedGoogle Scholar
  115. 115.
    Graham RP, Shrestha B, Caron BL, Smyrk TC, Grogg KL, Lloyd RV, et al. Islet-1 is a sensitive but not entirely specific marker for pancreatic neuroendocrine neoplasms and their metastases. Am J Surg Pathol. 2013;37(3):399–405.PubMedGoogle Scholar
  116. 116.
    Schmitt AM, Riniker F, Anlauf M, Schmid S, Soltermann A, Moch H, et al. Islet 1 (Isl1) expression is a reliable marker for pancreatic endocrine tumors and their metastases. Am J Surg Pathol. 2008;32(3):420–5.PubMedGoogle Scholar
  117. 117.
    Agaimy A, Erlenbach-Wunsch K, Konukiewitz B, Schmitt AM, Rieker RJ, Vieth M, et al. ISL1 expression is not restricted to pancreatic well-differentiated neuroendocrine neoplasms, but is also commonly found in well and poorly differentiated neuroendocrine neoplasms of extrapancreatic origin. Mod Pathol. 2013;26(7):995–1003.PubMedGoogle Scholar
  118. 118.
    Yang EJ, Kong CS, Longacre TA. Vulvar and anal intraepithelial neoplasia: terminology, diagnosis, and ancillary studies. Adv Anat Pathol. 2017;24(3):136–50.PubMedGoogle Scholar
  119. 119.
    Koo J, Mertens RB, Mirocha JM, Wang HL, Dhall D. Value of islet 1 and PAX8 in identifying metastatic neuroendocrine tumors of pancreatic origin. Mod Pathol. 2012;25(6):893–901.PubMedGoogle Scholar
  120. 120.
    Mehta RS, Song M, Nishihara R, Drew DA, Wu K, Qian ZR, et al. Dietary patterns and risk of colorectal cancer: analysis by tumor location and molecular subtypes. Gastroenterology. 2017;152(8):1944–53. e1.PubMedPubMedCentralGoogle Scholar
  121. 121.
    Kim JY, Hong SM. Recent updates on neuroendocrine tumors from the gastrointestinal and Pancreatobiliary tracts. Arch Pathol Lab Med. 2016;140(5):437–48.PubMedGoogle Scholar
  122. 122.
    Kim KW, Krajewski KM, Nishino M, Jagannathan JP, Shinagare AB, Tirumani SH, et al. Update on the management of gastroenteropancreatic neuroendocrine tumors with emphasis on the role of imaging. AJR Am J Roentgenol. 2013;201(4):811–24.PubMedPubMedCentralGoogle Scholar
  123. 123.
    Koo J, Dhall D. Problems with the diagnosis of metastatic neuroendocrine neoplasms. Which diagnostic criteria should we use to determine tumor origin and help guide therapy? Semin Diagn Pathol. 2015;32(6):456–68.PubMedGoogle Scholar
  124. 124.
    Hallet J, Law CH, Cukier M, Saskin R, Liu N, Singh S. Exploring the rising incidence of neuroendocrine tumors: a population-based analysis of epidemiology, metastatic presentation, and outcomes. Cancer. 2015;121(4):589–97.PubMedGoogle Scholar
  125. 125.
    Dogeas E, Cameron JL, Wolfgang CL, Hirose K, Hruban RH, Makary MA, et al. Duodenal and ampullary carcinoid tumors: size predicts necessity for lymphadenectomy. J Gastrointest Surg. 2017;21(8):1262–9.PubMedGoogle Scholar
  126. 126.
    Brown LM, Devesa SS, Chow WH. Incidence of adenocarcinoma of the esophagus among white Americans by sex, stage, and age. J Natl Cancer Inst. 2008;100(16):1184–7.PubMedPubMedCentralGoogle Scholar
  127. 127.
    Ryerson AB, Eheman CR, Altekruse SF, Ward JW, Jemal A, Sherman RL, et al. Annual Report to the Nation on the Status of Cancer, 1975-2012, featuring the increasing incidence of liver cancer. Cancer. 2016;122(9):1312–37.PubMedPubMedCentralGoogle Scholar
  128. 128.
    Wang HH, Mangano MM, Antonioli DA. Evaluation of T-lymphocytes in esophageal mucosal biopsies. Mod Pathol. 1994;7(1):55–8.PubMedGoogle Scholar
  129. 129.
    De La Pava S, Nigogosyan G, Pickren JW, Cabrera A. Melanosis of the esophagus. Cancer. 1963;16:48–50.Google Scholar
  130. 130.
    Odze RD, Goldblum JR. Odze and Goldblum surgical pathology of the GI tract, liver, biliary tract, and pancreas. Philadelphia: Elsevier - Health Sciences Division; 2014.Google Scholar
  131. 131.
    Crespi M, Munoz N, Grassi A, Qiong S, Jing WK, Jien LJ. Precursor lesions of oesophageal cancer in a low-risk population in China: comparison with high-risk populations. Int J Cancer. 1984;34(5):599–602.PubMedGoogle Scholar
  132. 132.
    Dawsey SM, Lewin KJ, Wang GQ, Liu FS, Nieberg RK, Yu Y, et al. Squamous esophageal histology and subsequent risk of squamous cell carcinoma of the esophagus. A prospective follow-up study from Linxian, China. Cancer. 1994;74(6):1686–92.PubMedGoogle Scholar
  133. 133.
    Lopes AB, Fagundes RB. Esophageal squamous cell carcinoma - precursor lesions and early diagnosis. World J Gastrointest Endosc. 2012;4(1):9–16.PubMedPubMedCentralGoogle Scholar
  134. 134.
    Mandard AM, Marnay J, Gignoux M, Segol P, Blanc L, Ollivier JM, et al. Cancer of the esophagus and associated lesions: detailed pathologic study of 100 esophagectomy specimens. Hum Pathol. 1984;15(7):660–9.PubMedGoogle Scholar
  135. 135.
    Shimizu Y, Yoshida T, Kato M, Hirota J, Ono S, Nakagawa M, et al. Low-grade dysplasia component in early invasive squamous cell carcinoma of the esophagus. J Gastroenterol Hepatol. 2010;25(2):314–8.PubMedGoogle Scholar
  136. 136.
    Wang GQ, Abnet CC, Shen Q, Lewin KJ, Sun XD, Roth MJ, et al. Histological precursors of oesophageal squamous cell carcinoma: results from a 13 year prospective follow up study in a high risk population. Gut. 2005;54(2):187–92.PubMedPubMedCentralGoogle Scholar
  137. 137.
    Takahashi H, Arimura Y, Masao H, Okahara S, Tanuma T, Kodaira J, et al. Endoscopic submucosal dissection is superior to conventional endoscopic resection as a curative treatment for early squamous cell carcinoma of the esophagus (with video). Gastrointest Endosc. 2010;72(2):255–64. 64 e1–2.PubMedGoogle Scholar
  138. 138.
    Hashimoto CL, Iriya K, Baba ER, Navarro-Rodriguez T, Zerbini MC, Eisig JN, et al. Lugol’s dye spray chromoendoscopy establishes early diagnosis of esophageal cancer in patients with primary head and neck cancer. Am J Gastroenterol. 2005;100(2):275–82.PubMedGoogle Scholar
  139. 139.
    Takenaka R, Kawahara Y, Okada H, Hori K, Inoue M, Kawano S, et al. Narrow-band imaging provides reliable screening for esophageal malignancy in patients with head and neck cancers. Am J Gastroenterol. 2009;104(12):2942–8.PubMedGoogle Scholar
  140. 140.
    Tajima Y, Nakanishi Y, Tachimori Y, Kato H, Watanabe H, Yamaguchi H, et al. Significance of involvement by squamous cell carcinoma of the ducts of esophageal submucosal glands. Analysis of 201 surgically resected superficial squamous cell carcinomas. Cancer. 2000;89(2):248–54.PubMedGoogle Scholar
  141. 141.
    Abraham SC, Wang H, Wang KK, Wu TT. Paget cells in the esophagus: assessment of their histopathologic features and near-universal association with underlying esophageal adenocarcinoma. Am J Surg Pathol. 2008;32(7):1068–74.PubMedGoogle Scholar
  142. 142.
    Wang WC, Wu TT, Chandan VS, Lohse CM, Zhang L. Ki-67 and ProExC are useful immunohistochemical markers in esophageal squamous intraepithelial neoplasia. Hum Pathol. 2011;42(10):1430–7.PubMedGoogle Scholar
  143. 143.
    Richter JE. Surgery for reflux disease: reflections of a gastroenterologist. N Engl J Med. 1992;326(12):825–7.PubMedGoogle Scholar
  144. 144.
    Wild CP, Hardie LJ. Reflux, Barrett’s oesophagus and adenocarcinoma: burning questions. Nat Rev Cancer. 2003;3(9):676–84.PubMedGoogle Scholar
  145. 145.
    Westhoff B, Brotze S, Weston A, McElhinney C, Cherian R, Mayo MS, et al. The frequency of Barrett’s esophagus in high-risk patients with chronic GERD. Gastrointest Endosc. 2005;61(2):226–31.PubMedGoogle Scholar
  146. 146.
    Gerson LB, Shetler K, Triadafilopoulos G. Prevalence of Barrett’s esophagus in asymptomatic individuals. Gastroenterology. 2002;123(2):461–7.PubMedGoogle Scholar
  147. 147.
    Cameron AJ. Epidemiology of columnar-lined esophagus and adenocarcinoma. Gastroenterol Clin N Am. 1997;26(3):487–94.Google Scholar
  148. 148.
    Hampel H, Abraham NS, El-Serag HB. Meta-analysis: obesity and the risk for gastroesophageal reflux disease and its complications. Ann Intern Med. 2005;143(3):199–211.PubMedGoogle Scholar
  149. 149.
    Kamat P, Wen S, Morris J, Anandasabapathy S. Exploring the association between elevated body mass index and Barrett’s esophagus: a systematic review and meta-analysis. Ann Thorac Surg. 2009;87(2):655–62.PubMedGoogle Scholar
  150. 150.
    Wang KK, Sampliner RE, Practice Parameters Committee of the American College of G. Updated guidelines 2008 for the diagnosis, surveillance and therapy of Barrett’s esophagus. Am J Gastroenterol. 2008;103(3):788–97.PubMedGoogle Scholar
  151. 151.
    Sampliner RE. Practice guidelines on the diagnosis, surveillance, and therapy of Barrett’s esophagus. The Practice Parameters Committee of the American College of Gastroenterology. Am J Gastroenterol. 1998;93(7):1028–32.PubMedGoogle Scholar
  152. 152.
    Riddell RH. The biopsy diagnosis of gastroesophageal reflux disease, “carditis,” and Barrett’s esophagus, and sequelae of therapy. Am J Surg Pathol. 1996;20(Suppl 1):S31–50.PubMedGoogle Scholar
  153. 153.
    Sharma P, McQuaid K, Dent J, Fennerty MB, Sampliner R, Spechler S, et al. A critical review of the diagnosis and management of Barrett’s esophagus: the AGA Chicago Workshop. Gastroenterology. 2004;127(1):310–30.PubMedGoogle Scholar
  154. 154.
    Odze RD. Unraveling the mystery of the gastroesophageal junction: a pathologist’s perspective. Am J Gastroenterol. 2005;100(8):1853–67.PubMedGoogle Scholar
  155. 155.
    Playford RJ. New British Society of Gastroenterology (BSG) guidelines for the diagnosis and management of Barrett’s oesophagus. Gut. 2006;55(4):442.PubMedPubMedCentralGoogle Scholar
  156. 156.
    Ogiya K, Kawano T, Ito E, Nakajima Y, Kawada K, Nishikage T, et al. Lower esophageal palisade vessels and the definition of Barrett’s esophagus. Dis Esophagus. 2008;21(7):645–9.PubMedGoogle Scholar
  157. 157.
    Gatenby PA, Ramus JR, Caygill CP, Shepherd NA, Watson A. Relevance of the detection of intestinal metaplasia in non-dysplastic columnar-lined oesophagus. Scand J Gastroenterol. 2008;43(5):524–30.PubMedGoogle Scholar
  158. 158.
    Kelty CJ, Gough MD, Van Wyk Q, Stephenson TJ, Ackroyd R. Barrett’s oesophagus: intestinal metaplasia is not essential for cancer risk. Scand J Gastroenterol. 2007;42(11):1271–4.PubMedGoogle Scholar
  159. 159.
    Glickman JN, Wang H, Das KM, Goyal RK, Spechler SJ, Antonioli D, et al. Phenotype of Barrett’s esophagus and intestinal metaplasia of the distal esophagus and gastroesophageal junction: an immunohistochemical study of cytokeratins 7 and 20, Das-1 and 45 MI. Am J Surg Pathol. 2001;25(1):87–94.PubMedGoogle Scholar
  160. 160.
    Conio M, Filiberti R, Blanchi S, Ferraris R, Marchi S, Ravelli P, et al. Risk factors for Barrett’s esophagus: a case-control study. Int J Cancer. 2002;97(2):225–9.PubMedGoogle Scholar
  161. 161.
    Ofman JJ, Shaheen NJ, Desai AA, Moody B, Bozymski EM, Weinstein WM. The quality of care in Barrett’s esophagus: endoscopist and pathologist practices. Am J Gastroenterol. 2001;96(3):876–81.PubMedGoogle Scholar
  162. 162.
    Iftikhar SY, James PD, Steele RJ, Hardcastle JD, Atkinson M. Length of Barrett’s oesophagus: an important factor in the development of dysplasia and adenocarcinoma. Gut. 1992;33(9):1155–8.PubMedPubMedCentralGoogle Scholar
  163. 163.
    Sikkema M, Looman CW, Steyerberg EW, Kerkhof M, Kastelein F, van Dekken H, et al. Predictors for neoplastic progression in patients with Barrett’s Esophagus: a prospective cohort study. Am J Gastroenterol. 2011;106(7):1231–8.PubMedGoogle Scholar
  164. 164.
    Avidan B, Sonnenberg A, Schnell TG, Chejfec G, Metz A, Sontag SJ. Hiatal hernia size, Barrett’s length, and severity of acid reflux are all risk factors for esophageal adenocarcinoma. Am J Gastroenterol. 2002;97(8):1930–6.PubMedGoogle Scholar
  165. 165.
    Rudolph RE, Vaughan TL, Storer BE, Haggitt RC, Rabinovitch PS, Levine DS, et al. Effect of segment length on risk for neoplastic progression in patients with Barrett esophagus. Ann Intern Med. 2000;132(8):612–20.PubMedGoogle Scholar
  166. 166.
    Hornick JL, Blount PL, Sanchez CA, Cowan DS, Ayub K, Maley CC, et al. Biologic properties of columnar epithelium underneath reepithelialized squamous mucosa in Barrett’s esophagus. Am J Surg Pathol. 2005;29(3):372–80.PubMedGoogle Scholar
  167. 167.
    Mino-Kenudson M, Ban S, Ohana M, Puricelli W, Deshpande V, Shimizu M, et al. Buried dysplasia and early adenocarcinoma arising in Barrett esophagus after porfimer-photodynamic therapy. Am J Surg Pathol. 2007;31(3):403–9.PubMedGoogle Scholar
  168. 168.
    Shaheen NJ, Sharma P, Overholt BF, Wolfsen HC, Sampliner RE, Wang KK, et al. Radiofrequency ablation in Barrett’s esophagus with dysplasia. N Engl J Med. 2009;360(22):2277–88.PubMedGoogle Scholar
  169. 169.
    Weinstein WM, Ippoliti AF. The diagnosis of Barrett’s esophagus: goblets, goblets, goblets. Gastrointest Endosc. 1996;44(1):91–5.PubMedGoogle Scholar
  170. 170.
    Srivastava A, Odze RD, Lauwers GY, Redston M, Antonioli DA, Glickman JN. Morphologic features are useful in distinguishing Barrett esophagus from carditis with intestinal metaplasia. Am J Surg Pathol. 2007;31(11):1733–41.PubMedGoogle Scholar
  171. 171.
    Antonioli DA, Wang HH. Morphology of Barrett’s esophagus and Barrett’s-associated dysplasia and adenocarcinoma. Gastroenterol Clin N Am. 1997;26(3):495–506.Google Scholar
  172. 172.
    Odze RD. Diagnosis and grading of dysplasia in Barrett’s oesophagus. J Clin Pathol. 2006;59(10):1029–38.PubMedPubMedCentralGoogle Scholar
  173. 173.
    Wang HH, Zeroogian JM, Spechler SJ, Goyal RK, Antonioli DA. Prevalence and significance of pancreatic acinar metaplasia at the gastroesophageal junction. Am J Surg Pathol. 1996;20(12):1507–10.PubMedGoogle Scholar
  174. 174.
    Chen YY, Wang HH, Antonioli DA, Spechler SJ, Zeroogian JM, Goyal R, et al. Significance of acid-mucin-positive nongoblet columnar cells in the distal esophagus and gastroesophageal junction. Hum Pathol. 1999;30(12):1488–95.PubMedGoogle Scholar
  175. 175.
    Shields HM, Rosenberg SJ, Zwas FR, Ransil BJ, Lembo AJ, Odze R. Prospective evaluation of multilayered epithelium in Barrett’s esophagus. Am J Gastroenterol. 2001;96(12):3268–73.PubMedGoogle Scholar
  176. 176.
    Hahn HP, Shahsafaei A, Odze RD. Vascular and lymphatic properties of the superficial and deep lamina propria in Barrett esophagus. Am J Surg Pathol. 2008;32(10):1454–61.PubMedGoogle Scholar
  177. 177.
    Reid BJ, Haggitt RC, Rubin CE, Roth G, Surawicz CM, Van Belle G, et al. Observer variation in the diagnosis of dysplasia in Barrett’s esophagus. Hum Pathol. 1988;19(2):166–78.PubMedGoogle Scholar
  178. 178.
    Schlemper RJ, Riddell RH, Kato Y, Borchard F, Cooper HS, Dawsey SM, et al. The Vienna classification of gastrointestinal epithelial neoplasia. Gut. 2000;47(2):251–5.PubMedPubMedCentralGoogle Scholar
  179. 179.
    Lomo LC, Blount PL, Sanchez CA, Li X, Galipeau PC, Cowan DS, et al. Crypt dysplasia with surface maturation: a clinical, pathologic, and molecular study of a Barrett’s esophagus cohort. Am J Surg Pathol. 2006;30(4):423–35.PubMedGoogle Scholar
  180. 180.
    Brown IS, Whiteman DC, Lauwers GY. Foveolar type dysplasia in Barrett esophagus. Mod Pathol. 2010;23(6):834–43.PubMedGoogle Scholar
  181. 181.
    Souza RF, Morales CP, Spechler SJ. Review article: a conceptual approach to understanding the molecular mechanisms of cancer development in Barrett’s oesophagus. Aliment Pharmacol Ther. 2001;15(8):1087–100.PubMedGoogle Scholar
  182. 182.
    Hornick JL, Odze RD. Neoplastic precursor lesions in Barrett’s esophagus. Gastroenterol Clin N Am. 2007;36(4):775–96. v.Google Scholar
  183. 183.
    Thurberg BL, Duray PH, Odze RD. Polypoid dysplasia in Barrett’s esophagus: a clinicopathologic, immunohistochemical, and molecular study of five cases. Hum Pathol. 1999;30(7):745–52.PubMedGoogle Scholar
  184. 184.
    Buttar NS, Wang KK, Sebo TJ, Riehle DM, Krishnadath KK, Lutzke LS, et al. Extent of high-grade dysplasia in Barrett’s esophagus correlates with risk of adenocarcinoma. Gastroenterology. 2001;120(7):1630–9.PubMedGoogle Scholar
  185. 185.
    Reid BJ, Blount PL, Feng Z, Levine DS. Optimizing endoscopic biopsy detection of early cancers in Barrett’s high-grade dysplasia. Am J Gastroenterol. 2000;95(11):3089–96.PubMedGoogle Scholar
  186. 186.
    Asthana N, Mandich D, Ligato S. Esophageal polypoid dysplasia of gastric foveolar phenotype with focal intramucosal carcinoma associated with Barrett’s esophagus. Am J Surg Pathol. 2008;32(10):1581–5.PubMedGoogle Scholar
  187. 187.
    Montgomery E, Bronner MP, Greenson JK, Haber MM, Hart J, Lamps LW, et al. Are ulcers a marker for invasive carcinoma in Barrett's esophagus? Data from a diagnostic variability study with clinical follow-up. Am J Gastroenterol. 2002;97(1):27–31.PubMedGoogle Scholar
  188. 188.
    Montgomery E, Bronner MP, Goldblum JR, Greenson JK, Haber MM, Hart J, et al. Reproducibility of the diagnosis of dysplasia in Barrett esophagus: a reaffirmation. Hum Pathol. 2001;32(4):368–78.PubMedGoogle Scholar
  189. 189.
    Zhang X, Huang Q, Goyal RK, Odze RD. DNA ploidy abnormalities in basal and superficial regions of the crypts in Barrett’s esophagus and associated neoplastic lesions. Am J Surg Pathol. 2008;32(9):1327–35.PubMedGoogle Scholar
  190. 190.
    Rucker-Schmidt RL, Sanchez CA, Blount PL, Ayub K, Li X, Rabinovitch PS, et al. Nonadenomatous dysplasia in Barrett esophagus: a clinical, pathologic, and DNA content flow cytometric study. Am J Surg Pathol. 2009;33(6):886–93.PubMedPubMedCentralGoogle Scholar
  191. 191.
    Mahajan D, Bennett AE, Liu X, Bena J, Bronner MP. Grading of gastric foveolar-type dysplasia in Barrett’s esophagus. Mod Pathol. 2010;23(1):1–11.PubMedGoogle Scholar
  192. 192.
    Naini BV, Souza RF, Odze RD. Barrett’s esophagus: a comprehensive and contemporary review for pathologists. Am J Surg Pathol. 2016;40(5):e45–66.PubMedPubMedCentralGoogle Scholar
  193. 193.
    Cook MB, Chow WH, Devesa SS. Oesophageal cancer incidence in the United States by race, sex, and histologic type, 1977–2005. Br J Cancer. 2009;101(5):855–9.PubMedPubMedCentralGoogle Scholar
  194. 194.
    Bosman FT, World Health Organization, International Agency for Research on Cancer. WHO classification of tumours of the digestive system. Lyon: IARC Press; 2010. p. 417.Google Scholar
  195. 195.
    Ina H, Shibuya H, Ohashi I, Kitagawa M. The frequency of a concomitant early esophageal cancer in male patients with oral and oropharyngeal cancer. Screening results using Lugol dye endoscopy. Cancer. 1994;73(8):2038–41.PubMedGoogle Scholar
  196. 196.
    Takubo K, Aida J, Sawabe M, Kurosumi M, Arima M, Fujishiro M, et al. Early squamous cell carcinoma of the oesophagus: the Japanese viewpoint. Histopathology. 2007;51(6):733–42.PubMedGoogle Scholar
  197. 197.
    Lin DC, Du XL, Wang MR. Protein alterations in ESCC and clinical implications: a review. Dis Esophagus. 2009;22(1):9–20.PubMedGoogle Scholar
  198. 198.
    Lu YK, Li YM, Gu YZ. Cancer of esophagus and esophagogastric junction: analysis of results of 1,025 resections after 5 to 20 years. Ann Thorac Surg. 1987;43(2):176–81.PubMedGoogle Scholar
  199. 199.
    Ide H, Nakamura T, Hayashi K, Endo T, Kobayashi A, Eguchi R, et al. Esophageal squamous cell carcinoma: pathology and prognosis. World J Surg. 1994;18(3):321–30.PubMedGoogle Scholar
  200. 200.
    Sarbia M, Porschen R, Borchard F, Horstmann O, Willers R, Gabbert HE. Incidence and prognostic significance of vascular and neural invasion in squamous cell carcinomas of the esophagus. Int J Cancer. 1995;61(3):333–6.PubMedGoogle Scholar
  201. 201.
    Sarbia M, Bittinger F, Porschen R, Dutkowski P, Willers R, Gabbert HE. Prognostic value of histopathologic parameters of esophageal squamous cell carcinoma. Cancer. 1995;76(6):922–7.PubMedGoogle Scholar
  202. 202.
    Amin MB, Edge SB, American Joint Committee on Cancer. AJCC cancer staging manual. 8th ed. Switzerland: Springer; 2017. p. xvii. 1024 pages.Google Scholar
  203. 203.
    Shimada H, Kitabayashi H, Nabeya Y, Okazumi S, Matsubara H, Funami Y, et al. Treatment response and prognosis of patients after recurrence of esophageal cancer. Surgery. 2003;133(1):24–31.PubMedGoogle Scholar
  204. 204.
    Mori M, Matsuda H, Kuwano H, Matsuura H, Sugimachi K. Oesophageal squamous cell carcinoma with lymphoid stroma. A case report. Virchows Arch A Pathol Anat Histopathol. 1989;415(5):473–9.PubMedGoogle Scholar
  205. 205.
    Takubo K, Takai A, Takayama S, Sasajima K, Yamashita K, Fujita K. Intraductal spread of esophageal squamous cell carcinoma. Cancer. 1987;59(10):1751–7.PubMedGoogle Scholar
  206. 206.
    Tsang WY, Chan JK, Lee KC, Leung AK, Fu YT. Basaloid-squamous carcinoma of the upper aerodigestive tract and so-called adenoid cystic carcinoma of the oesophagus: the same tumour type? Histopathology. 1991;19(1):35–46.PubMedGoogle Scholar
  207. 207.
    Kobayashi Y, Nakanishi Y, Taniguchi H, Sekine S, Igaki H, Tachimori Y, et al. Histological diversity in basaloid squamous cell carcinoma of the esophagus. Dis Esophagus. 2009;22(3):231–8.PubMedGoogle Scholar
  208. 208.
    Osborn NK, Keate RF, Trastek VF, Nguyen CC. Verrucous carcinoma of the esophagus: clinicopathophysiologic features and treatment of a rare entity. Dig Dis Sci. 2003;48(3):465–74.PubMedGoogle Scholar
  209. 209.
    Lauwers GY, Grant LD, Scott GV, Carr NJ, Sobin LH. Spindle cell squamous carcinoma of the esophagus: analysis of ploidy and tumor proliferative activity in a series of 13 cases. Hum Pathol. 1998;29(8):863–8.PubMedGoogle Scholar
  210. 210.
    Hanada M, Nakano K, Ii Y, Yamashita H. Carcinosarcoma of the esophagus with osseous and cartilagenous production. A combined study of keratin immunohistochemistry and electron microscopy. Acta Pathol Jpn. 1984;34(3):669–78.PubMedGoogle Scholar
  211. 211.
    Boone J, van Hillegersberg R, Offerhaus GJ, van Diest PJ, Borel Rinkes IH, Ten Kate FJ. Targets for molecular therapy in esophageal squamous cell carcinoma: an immunohistochemical analysis. Dis Esophagus. 2009;22(6):496–504.PubMedGoogle Scholar
  212. 212.
    Sawada G, Niida A, Hirata H, Komatsu H, Uchi R, Shimamura T, et al. An integrative analysis to identify driver genes in esophageal squamous cell carcinoma. PLoS One. 2015;10(10):e0139808.PubMedPubMedCentralGoogle Scholar
  213. 213.
    Montesano R, Hollstein M, Hainaut P. Genetic alterations in esophageal cancer and their relevance to etiology and pathogenesis: a review. Int J Cancer. 1996;69(3):225–35.PubMedGoogle Scholar
  214. 214.
    Lagergren J, Bergstrom R, Nyren O. Association between body mass and adenocarcinoma of the esophagus and gastric cardia. Ann Intern Med. 1999;130(11):883–90.PubMedGoogle Scholar
  215. 215.
    Gatenby PA, Caygill CP, Ramus JR, Charlett A, Fitzgerald RC, Watson A. Short segment columnar-lined oesophagus: an underestimated cancer risk? A large cohort study of the relationship between Barrett's columnar-lined oesophagus segment length and adenocarcinoma risk. Eur J Gastroenterol Hepatol. 2007;19(11):969–75.PubMedGoogle Scholar
  216. 216.
    Lagergren J, Bergstrom R, Adami HO, Nyren O. Association between medications that relax the lower esophageal sphincter and risk for esophageal adenocarcinoma. Ann Intern Med. 2000;133(3):165–75.PubMedGoogle Scholar
  217. 217.
    Pohl H, Welch HG. The role of overdiagnosis and reclassification in the marked increase of esophageal adenocarcinoma incidence. J Natl Cancer Inst. 2005;97(2):142–6.PubMedGoogle Scholar
  218. 218.
    Vizcaino AP, Moreno V, Lambert R, Parkin DM. Time trends incidence of both major histologic types of esophageal carcinomas in selected countries, 1973-1995. Int J Cancer. 2002;99(6):860–8.PubMedGoogle Scholar
  219. 219.
    Corley DA, Levin TR, Habel LA, Weiss NS, Buffler PA. Surveillance and survival in Barrett’s adenocarcinomas: a population-based study. Gastroenterology. 2002;122(3):633–40.PubMedGoogle Scholar
  220. 220.
    Smith RR, Hamilton SR, Boitnott JK, Rogers EL. The spectrum of carcinoma arising in Barrett’s esophagus. A clinicopathologic study of 26 patients. Am J Surg Pathol. 1984;8(8):563–73.PubMedGoogle Scholar
  221. 221.
    Hamilton SR, Smith RR. The relationship between columnar epithelial dysplasia and invasive adenocarcinoma arising in Barrett’s esophagus. Am J Clin Pathol. 1987;87(3):301–12.PubMedGoogle Scholar
  222. 222.
    Chejfec G, Jablokow VR, Gould VE. Linitis plastica carcinoma of the esophagus. Cancer. 1983;51(11):2139–43.PubMedGoogle Scholar
  223. 223.
    Donahue JM, Nichols FC, Li Z, Schomas DA, Allen MS, Cassivi SD, et al. Complete pathologic response after neoadjuvant chemoradiotherapy for esophageal cancer is associated with enhanced survival. Ann Thorac Surg. 2009;87(2):392–8. discussion 8-9.PubMedPubMedCentralGoogle Scholar
  224. 224.
    Hornick JL, Farraye FA, Odze RD. Prevalence and significance of prominent mucin pools in the esophagus post neoadjuvant chemoradiotherapy for Barrett’s-associated adenocarcinoma. Am J Surg Pathol. 2006;30(1):28–35.PubMedGoogle Scholar
  225. 225.
    Torres C, Turner JR, Wang HH, Richards W, Sugarbaker D, Shahsafaei A, et al. Pathologic prognostic factors in Barrett’s associated adenocarcinoma: a follow-up study of 96 patients. Cancer. 1999;85(3):520–8.PubMedGoogle Scholar
  226. 226.
    Rice TW, Patil DT, Blackstone EH. 8th edition AJCC/UICC staging of cancers of the esophagus and esophagogastric junction: application to clinical practice. Ann Cardiothorac Surg. 2017;6(2):119–30.PubMedPubMedCentralGoogle Scholar
  227. 227.
    Hamilton K, Chiappori A, Olson S, Sawyers J, Johnson D, Washington K. Prevalence and prognostic significance of neuroendocrine cells in esophageal adenocarcinoma. Mod Pathol. 2000;13(5):475–81.PubMedGoogle Scholar
  228. 228.
    Yachida S, Nakanishi Y, Shimoda T, Nimura S, Igaki H, Tachimori Y, et al. Adenosquamous carcinoma of the esophagus. Clinicopathologic study of 18 cases. Oncology. 2004;66(3):218–25.PubMedGoogle Scholar
  229. 229.
    Gowryshankar A, Nagaraja V, Eslick GD. HER2 status in Barrett’s esophagus & esophageal cancer: a meta analysis. J Gastrointest Oncol. 2014;5(1):25–35.PubMedPubMedCentralGoogle Scholar
  230. 230.
    Bartley AN, Washington MK, Ventura CB, Ismaila N, Colasacco C, Benson AB 3rd, et al. HER2 testing and clinical decision making in gastroesophageal adenocarcinoma: guideline from the College of American Pathologists, American Society for Clinical Pathology, and American Society of Clinical Oncology. Arch Pathol Lab Med. 2016;140(12):1345–63.PubMedGoogle Scholar
  231. 231.
    Bang YJ, Van Cutsem E, Feyereislova A, Chung HC, Shen L, Sawaki A, et al. Trastuzumab in combination with chemotherapy versus chemotherapy alone for treatment of HER2-positive advanced gastric or gastro-oesophageal junction cancer (ToGA): a phase 3, open-label, randomised controlled trial. Lancet. 2010;376(9742):687–97.PubMedGoogle Scholar
  232. 232.
    Hofmann M, Stoss O, Shi D, Buttner R, van de Vijver M, Kim W, et al. Assessment of a HER2 scoring system for gastric cancer: results from a validation study. Histopathology. 2008;52(7):797–805.PubMedGoogle Scholar
  233. 233.
    Ajani JA, Bentrem DJ, Besh S, D’Amico TA, Das P, Denlinger C, et al. Gastric cancer, version 2.2013: featured updates to the NCCN Guidelines. J Natl Compr Cancer Netw. 2013;11(5):531–46.Google Scholar
  234. 234.
    Bell-Thomson J, Haggitt RC, Ellis FH Jr. Mucoepidermoid and adenoid cystic carcinomas of the esophagus. J Thorac Cardiovasc Surg. 1980;79(3):438–46.PubMedGoogle Scholar
  235. 235.
    Woodard BH, Shelburne JD, Vollmer RT, Postlethwait RW. Mucoepidermoid carcinoma of the esophagus: a case report. Hum Pathol. 1978;9(3):352–4.PubMedGoogle Scholar
  236. 236.
    Sasajima K, Watanabe M, Takubo K, Takai A, Yamashita K, Onda M. Mucoepidermoid carcinoma of the esophagus: report of two cases and review of the literature. Endoscopy. 1990;22(3):140–3.PubMedGoogle Scholar
  237. 237.
    Akagi I, Miyashita M, Makino H, Nomura T, Ohkawa K, Tajiri T. Basaloid squamous cell carcinoma of the esophagus: report of two cases. J Nippon Med Sch. 2008;75(6):354–60.PubMedGoogle Scholar
  238. 238.
    Kabuto T, Taniguchi K, Iwanaga T, Terasawa T, Sano M, Tateishi R, et al. Primary adenoid cystic carcinoma of the esophagus: report of a case. Cancer. 1979;43(6):2452–6.PubMedGoogle Scholar
  239. 239.
    Hoda SA, Hajdu SI. Small cell carcinoma of the esophagus. Cytology and immunohistology in four cases. Acta Cytol. 1992;36(2):113–20.PubMedGoogle Scholar
  240. 240.
    Modlin IM, Shapiro MD, Kidd M. An analysis of rare carcinoid tumors: clarifying these clinical conundrums. World J Surg. 2005;29(1):92–101.PubMedGoogle Scholar
  241. 241.
    Takubo K, Nakamura K, Sawabe M, Arai T, Esaki Y, Miyashita M, et al. Primary undifferentiated small cell carcinoma of the esophagus. Hum Pathol. 1999;30(2):216–21.PubMedGoogle Scholar
  242. 242.
    Cary NR, Barron DJ, McGoldrick JP, Wells FC. Combined oesophageal adenocarcinoma and carcinoid in Barrett’s oesophagitis: potential role of enterochromaffin-like cells in oesophageal malignancy. Thorax. 1993;48(4):404–5.PubMedPubMedCentralGoogle Scholar
  243. 243.
    Chong FK, Graham JH, Madoff IM. Mucin-producing carcinoid (“composite tumor”) of upper third of esophagus: a variant of carcinoid tumor. Cancer. 1979;44(5):1853–9.PubMedGoogle Scholar
  244. 244.
    Maru DM, Khurana H, Rashid A, Correa AM, Anandasabapathy S, Krishnan S, et al. Retrospective study of clinicopathologic features and prognosis of high-grade neuroendocrine carcinoma of the esophagus. Am J Surg Pathol. 2008;32(9):1404–11.PubMedGoogle Scholar
  245. 245.
    Siegal A, Swartz A. Malignant carcinoid of oesophagus. Histopathology. 1986;10(7):761–5.PubMedGoogle Scholar
  246. 246.
    Nawroz IM. Malignant carcinoid tumour of oesophagus. Histopathology. 1987;11(8):879–80.PubMedGoogle Scholar
  247. 247.
    Kloppel G, Rindi G, Anlauf M, Perren A, Komminoth P. Site-specific biology and pathology of gastroenteropancreatic neuroendocrine tumors. Virchows Arch. 2007;451(Suppl 1):S9–27.PubMedGoogle Scholar
  248. 248.
    Chuah SK, Hu TH, Kuo CM, Chiu KW, Kuo CH, Wu KL, et al. Upper gastrointestinal carcinoid tumors incidentally found by endoscopic examinations. World J Gastroenterol. 2005;11(44):7028–32.PubMedPubMedCentralGoogle Scholar
  249. 249.
    Modlin IM, Sandor A. An analysis of 8305 cases of carcinoid tumors. Cancer. 1997;79(4):813–29.PubMedGoogle Scholar
  250. 250.
    Yun JP, Zhang MF, Hou JH, Tian QH, Fu J, Liang XM, et al. Primary small cell carcinoma of the esophagus: clinicopathological and immunohistochemical features of 21 cases. BMC Cancer. 2007;7:38.PubMedPubMedCentralGoogle Scholar
  251. 251.
    Lu J, Xue LY, Lu N, Zou SM, Liu XY, Wen P. Superficial primary small cell carcinoma of the esophagus: clinicopathological and immunohistochemical analysis of 15 cases. Dis Esophagus. 2010;23(2):153–9.PubMedGoogle Scholar
  252. 252.
    Travis WD, Linnoila RI, Tsokos MG, Hitchcock CL, Cutler GB Jr, Nieman L, et al. Neuroendocrine tumors of the lung with proposed criteria for large-cell neuroendocrine carcinoma. An ultrastructural, immunohistochemical, and flow cytometric study of 35 cases. Am J Surg Pathol. 1991;15(6):529–53.PubMedGoogle Scholar
  253. 253.
    Travis WD, Brambilla E, Nicholson AG, Yatabe Y, Austin JHM, Beasley MB, et al. The 2015 World Health Organization classification of lung tumors: impact of genetic, clinical and radiologic advances since the 2004 classification. J Thorac Oncol. 2015;10(9):1243–60.PubMedGoogle Scholar
  254. 254.
    Briggs JC, Ibrahim NB. Oat cell carcinomas of the oesophagus: a clinico-pathological study of 23 cases. Histopathology. 1983;7(2):261–77.PubMedGoogle Scholar
  255. 255.
    Ho KJ, Herrera GA, Jones JM, Alexander CB. Small cell carcinoma of the esophagus: evidence for a unified histogenesis. Hum Pathol. 1984;15(5):460–8.PubMedGoogle Scholar
  256. 256.
    Correa P. A human model of gastric carcinogenesis. Cancer Res. 1988;48(13):3554–60.PubMedGoogle Scholar
  257. 257.
    Ito H, Hata J, Yokozaki H, Nakatani H, Oda N, Tahara E. Tubular adenoma of the human stomach. An immunohistochemical analysis of gut hormones, serotonin, carcinoembryonic antigen, secretory component, and lysozyme. Cancer. 1986;58(10):2264–72.PubMedGoogle Scholar
  258. 258.
    Oberhuber G, Stolte M. Gastric polyps: an update of their pathology and biological significance. Virchows Arch. 2000;437(6):581–90.PubMedGoogle Scholar
  259. 259.
    Domizio P, Talbot IC, Spigelman AD, Williams CB, Phillips RK. Upper gastrointestinal pathology in familial adenomatous polyposis: results from a prospective study of 102 patients. J Clin Pathol. 1990;43(9):738–43.PubMedPubMedCentralGoogle Scholar
  260. 260.
    Nakamura T, Nakano G. Histopathological classification and malignant change in gastric polyps. J Clin Pathol. 1985;38(7):754–64.PubMedPubMedCentralGoogle Scholar
  261. 261.
    Abraham SC, Park SJ, Lee JH, Mugartegui L, Wu TT. Genetic alterations in gastric adenomas of intestinal and foveolar phenotypes. Mod Pathol. 2003;16(8):786–95.PubMedGoogle Scholar
  262. 262.
    Ito H, Yasui W, Yoshida K, Nakayama H, Tahara E. Depressed tubular adenoma of the stomach: pathological and immunohistochemical features. Histopathology. 1990;17(5):419–26.PubMedGoogle Scholar
  263. 263.
    Lauwers GY, Riddell RH. Gastric epithelial dysplasia. Gut. 1999;45(5):784–90.PubMedPubMedCentralGoogle Scholar
  264. 264.
    Tosi P, Baak JP, Luzi P, Miracco C, Lio R, Barbini P. Morphometric distinction of low- and high-grade dysplasias in gastric biopsies. Hum Pathol. 1989;20(9):839–44.PubMedGoogle Scholar
  265. 265.
    Lansdown M, Quirke P, Dixon MF, Axon AT, Johnston D. High grade dysplasia of the gastric mucosa: a marker for gastric carcinoma. Gut. 1990;31(9):977–83.PubMedPubMedCentralGoogle Scholar
  266. 266.
    Vieth M, Kushima R, Borchard F, Stolte M. Pyloric gland adenoma: a clinico-pathological analysis of 90 cases. Virchows Arch. 2003;442(4):317–21.PubMedGoogle Scholar
  267. 267.
    Chen ZM, Scudiere JR, Abraham SC, Montgomery E. Pyloric gland adenoma: an entity distinct from gastric foveolar type adenoma. Am J Surg Pathol. 2009;33(2):186–93.PubMedGoogle Scholar
  268. 268.
    Stewart BW, Wild CP. World cancer report 2014. Lyon: International Agency for Research on Cancer; 2014.Google Scholar
  269. 269.
    Locke GR 3rd, Talley NJ, Carpenter HA, Harmsen WS, Zinsmeister AR, Melton LJ 3rd. Changes in the site- and histology-specific incidence of gastric cancer during a 50-year period. Gastroenterology. 1995;109(6):1750–6.PubMedGoogle Scholar
  270. 270.
    Kuipers EJ. Helicobacter pylori and the risk and management of associated diseases: gastritis, ulcer disease, atrophic gastritis and gastric cancer. Aliment Pharmacol Ther. 1997;11(Suppl 1):71–88.PubMedGoogle Scholar
  271. 271.
    Henson DE, Dittus C, Younes M, Nguyen H, Albores-Saavedra J. Differential trends in the intestinal and diffuse types of gastric carcinoma in the United States, 1973-2000: increase in the signet ring cell type. Arch Pathol Lab Med. 2004;128(7):765–70.PubMedGoogle Scholar
  272. 272.
    Cameron AJ, Lomboy CT, Pera M, Carpenter HA. Adenocarcinoma of the esophagogastric junction and Barrett’s esophagus. Gastroenterology. 1995;109(5):1541–6.PubMedGoogle Scholar
  273. 273.
    Wijnhoven BP, Siersema PD, Hop WC, van Dekken H, Tilanus HW. Adenocarcinomas of the distal oesophagus and gastric cardia are one clinical entity. Rotterdam Oesophageal Tumour Study Group. Br J Surg. 1999;86(4):529–35.PubMedGoogle Scholar
  274. 274.
    Siewert JR, Stein HJ. Classification of adenocarcinoma of the oesophagogastric junction. Br J Surg. 1998;85(11):1457–9.PubMedGoogle Scholar
  275. 275.
    Allum WH, Powell DJ, McConkey CC, Fielding JW. Gastric cancer: a 25-year review. Br J Surg. 1989;76(6):535–40.PubMedGoogle Scholar
  276. 276.
    Capella C, Frigerio B, Cornaggia M, Solcia E, Pinzon-Trujillo Y, Chejfec G. Gastric parietal cell carcinoma--a newly recognized entity: light microscopic and ultrastructural features. Histopathology. 1984;8(5):813–24.PubMedGoogle Scholar
  277. 277.
    Bonar SF, Sweeney EC. The prevalence, prognostic significance and hormonal content of endocrine cells in gastric cancer. Histopathology. 1986;10(1):53–63.PubMedGoogle Scholar
  278. 278.
    Ueyama H, Yao T, Nakashima Y, Hirakawa K, Oshiro Y, Hirahashi M, et al. Gastric adenocarcinoma of fundic gland type (chief cell predominant type): proposal for a new entity of gastric adenocarcinoma. Am J Surg Pathol. 2010;34(5):609–19.PubMedGoogle Scholar
  279. 279.
    Singhi AD, Lazenby AJ, Montgomery EA. Gastric adenocarcinoma with chief cell differentiation: a proposal for reclassification as oxyntic gland polyp/adenoma. Am J Surg Pathol. 2012;36(7):1030–5.PubMedGoogle Scholar
  280. 280.
    Ooi A, Nakanishi I, Itoh T, Ueda H, Mai M. Predominant Paneth cell differentiation in an intestinal type gastric cancer. Pathol Res Pract. 1991;187(2–3):220–5.PubMedGoogle Scholar
  281. 281.
    Fiocca R, Villani L, Tenti P, Solcia E, Cornaggia M, Frigerio B, et al. Characterization of four main cell types in gastric cancer: foveolar, mucopeptic, intestinal columnar and goblet cells. An histopathologic, histochemical and ultrastructural study of “early” and “advanced” tumours. Pathol Res Pract. 1987;182(3):308–25.PubMedGoogle Scholar
  282. 282.
    Setala LP, Kosma VM, Marin S, Lipponen PK, Eskelinen MJ, Syrjanen KJ, et al. Prognostic factors in gastric cancer: the value of vascular invasion, mitotic rate and lymphoplasmacytic infiltration. Br J Cancer. 1996;74(5):766–72.PubMedPubMedCentralGoogle Scholar
  283. 283.
    Tanaka A, Watanabe T, Okuno K, Yasutomi M. Perineural invasion as a predictor of recurrence of gastric cancer. Cancer. 1994;73(3):550–5.PubMedGoogle Scholar
  284. 284.
    Ming SC. Gastric carcinoma. A pathobiological classification. Cancer. 1977;39(6):2475–85.PubMedGoogle Scholar
  285. 285.
    Lauren P. The two histological main types of gastric carcinoma: diffuse and so-called intestinal-type carcinoma. An attempt at a histo-clinical classification. Acta Pathol Microbiol Scand. 1965;64:31–49.PubMedGoogle Scholar
  286. 286.
    Roy P, Piard F, Dusserre-Guion L, Martin L, Michiels-Marzais D, Faivre J. Prognostic comparison of the pathological classifications of gastric cancer: a population-based study. Histopathology. 1998;33(4):304–10.PubMedGoogle Scholar
  287. 287.
    Berlth F, Bollschweiler E, Drebber U, Hoelscher AH, Moenig S. Pathohistological classification systems in gastric cancer: diagnostic relevance and prognostic value. World J Gastroenterol. 2014;20(19):5679–84.PubMedPubMedCentralGoogle Scholar
  288. 288.
    Mori M, Sakaguchi H, Akazawa K, Tsuneyoshi M, Sueishi K, Sugimachi K. Correlation between metastatic site, histological type, and serum tumor markers of gastric carcinoma. Hum Pathol. 1995;26(5):504–8.PubMedGoogle Scholar
  289. 289.
    Carneiro F, Huntsman DG, Smyrk TC, Owen DA, Seruca R, Pharoah P, et al. Model of the early development of diffuse gastric cancer in E-cadherin mutation carriers and its implications for patient screening. J Pathol. 2004;203(2):681–7.PubMedGoogle Scholar
  290. 290.
    Fiocca R, Villani L, Tenti P, Cornaggia M, Finzi G, Riva C, et al. The foveolar cell component of gastric cancer. Hum Pathol. 1990;21(3):260–70.PubMedGoogle Scholar
  291. 291.
    Machado JC, Nogueira AM, Carneiro F, Reis CA, Sobrinho-Simoes M. Gastric carcinoma exhibits distinct types of cell differentiation: an immunohistochemical study of trefoil peptides (TFF1 and TFF2) and mucins (MUC1, MUC2, MUC5AC, and MUC6). J Pathol. 2000;190(4):437–43.PubMedGoogle Scholar
  292. 292.
    Oda K, Tamaru J, Takenouchi T, Mikata A, Nunomura M, Saitoh N, et al. Association of Epstein-Barr virus with gastric carcinoma with lymphoid stroma. Am J Pathol. 1993;143(4):1063–71.PubMedPubMedCentralGoogle Scholar
  293. 293.
    Matsunou H, Konishi F, Hori H, Ikeda T, Sasaki K, Hirose Y, et al. Characteristics of Epstein-Barr virus-associated gastric carcinoma with lymphoid stroma in Japan. Cancer. 1996;77(10):1998–2004.PubMedGoogle Scholar
  294. 294.
    Minamoto T, Mai M, Watanabe K, Ooi A, Kitamura T, Takahashi Y, et al. Medullary carcinoma with lymphocytic infiltration of the stomach. Clinicopathologic study of 27 cases and immunohistochemical analysis of the subpopulations of infiltrating lymphocytes in the tumor. Cancer. 1990;66(5):945–52.PubMedGoogle Scholar
  295. 295.
    Nakamura S, Ueki T, Yao T, Ueyama T, Tsuneyoshi M. Epstein-Barr virus in gastric carcinoma with lymphoid stroma. Special reference to its detection by the polymerase chain reaction and in situ hybridization in 99 tumors, including a morphologic analysis. Cancer. 1994;73(9):2239–49.PubMedGoogle Scholar
  296. 296.
    dos Santos NR, Seruca R, Constancia M, Seixas M, Sobrinho-Simoes M. Microsatellite instability at multiple loci in gastric carcinoma: clinicopathologic implications and prognosis. Gastroenterology. 1996;110(1):38–44.PubMedGoogle Scholar
  297. 297.
    Hisamichi S. Screening for gastric cancer. World J Surg. 1989;13(1):31–7.PubMedGoogle Scholar
  298. 298.
    Marubashi S, Yano H, Monden T, Tateishi H, Kanoh T, Iwazawa T, et al. Primary squamous cell carcinoma of the stomach. Gastric Cancer. 1999;2(2):136–41.PubMedGoogle Scholar
  299. 299.
    Mori M, Iwashita A, Enjoji M. Adenosquamous carcinoma of the stomach. A clinicopathologic analysis of 28 cases. Cancer. 1986;57(2):333–9.PubMedGoogle Scholar
  300. 300.
    Yoshida K, Manabe T, Tsunoda T, Kimoto M, Tadaoka Y, Shimizu M. Early gastric cancer of adenosquamous carcinoma type: report of a case and review of literature. Jpn J Clin Oncol. 1996;26(4):252–7.PubMedGoogle Scholar
  301. 301.
    Robey-Cafferty SS, Grignon DJ, Ro JY, Cleary KR, Ayala AG, Ordonez NG, et al. Sarcomatoid carcinoma of the stomach. A report of three cases with immunohistochemical and ultrastructural observations. Cancer. 1990;65(7):1601–6.PubMedGoogle Scholar
  302. 302.
    Randjelovic T, Filipovic B, Babic D, Cemerikic V, Filipovic B. Carcinosarcoma of the stomach: a case report and review of the literature. World J Gastroenterol. 2007;13(41):5533–6.PubMedPubMedCentralGoogle Scholar
  303. 303.
    Ikeda Y, Kosugi S, Nishikura K, Ohashi M, Kanda T, Kobayashi T, et al. Gastric carcinosarcoma presenting as a huge epigastric mass. Gastric Cancer. 2007;10(1):63–8.PubMedGoogle Scholar
  304. 304.
    Dundas SA, Slater DN, Wagner BE, Mills PA. Gastric adenocarcinoleiomyosarcoma: a light, electron microscopic and immunohistological study. Histopathology. 1988;13(3):347–50.PubMedGoogle Scholar
  305. 305.
    Nakayama Y, Murayama H, Iwasaki H, Iwanaga S, Kikuchi M, Ikeda S, et al. Gastric carcinosarcoma (sarcomatoid carcinoma) with rhabdomyoblastic and osteoblastic differentiation. Pathol Int. 1997;47(8):557–63.PubMedGoogle Scholar
  306. 306.
    Yamazaki K. A gastric carcinosarcoma with neuroendocrine cell differentiation and undifferentiated spindle-shaped sarcoma component possibly progressing from the conventional tubular adenocarcinoma; an immunohistochemical and ultrastructural study. Virchows Arch. 2003;442(1):77–81.PubMedGoogle Scholar
  307. 307.
    Sato Y, Shimozono T, Kawano S, Toyoda K, Onoe K, Asada Y, et al. Gastric carcinosarcoma, coexistence of adenosquamous carcinoma and rhabdomyosarcoma: a case report. Histopathology. 2001;39(5):543–4.PubMedGoogle Scholar
  308. 308.
    Kallakury BV, Bui HX, del Rosario A, Wallace J, Solis OG, Ross JS. Primary gastric adenosarcoma. Arch Pathol Lab Med. 1993;117(3):299–301.PubMedGoogle Scholar
  309. 309.
    Inagawa S, Shimazaki J, Hori M, Yoshimi F, Adachi S, Kawamoto T, et al. Hepatoid adenocarcinoma of the stomach. Gastric Cancer. 2001;4(1):43–52.PubMedGoogle Scholar
  310. 310.
    Yamazawa S, Ushiku T, Shinozaki-Ushiku A, Hayashi A, Iwasaki A, Abe H, et al. Gastric cancer with primitive enterocyte phenotype: an aggressive subgroup of intestinal-type adenocarcinoma. Am J Surg Pathol. 2017;41(7):989–97.PubMedGoogle Scholar
  311. 311.
    Liu X, Cheng Y, Sheng W, Lu H, Xu X, Xu Y, et al. Analysis of clinicopathologic features and prognostic factors in hepatoid adenocarcinoma of the stomach. Am J Surg Pathol. 2010;34(10):1465–71.PubMedGoogle Scholar
  312. 312.
    Ishikura H, Kirimoto K, Shamoto M, Miyamoto Y, Yamagiwa H, Itoh T, et al. Hepatoid adenocarcinomas of the stomach. An analysis of seven cases. Cancer. 1986;58(1):119–26.PubMedGoogle Scholar
  313. 313.
    Motoyama T, Aizawa K, Watanabe H, Fukase M, Saito K. Alpha-fetoprotein producing gastric carcinomas: a comparative study of three different subtypes. Acta Pathol Jpn. 1993;43(11):654–61.PubMedGoogle Scholar
  314. 314.
    Ming SC. Cellular and molecular pathology of gastric carcinoma and precursor lesions: a critical review. Gastric Cancer. 1998;1(1):31–50.PubMedGoogle Scholar
  315. 315.
    Petrella T, Montagnon J, Roignot P, Van Nieuvanhuyse A, Matagrin C, Michiels-Marzais D, et al. Alphafetoprotein-producing gastric adenocarcinoma. Histopathology. 1995;26(2):171–5.PubMedGoogle Scholar
  316. 316.
    Byrne D, Holley MP, Cuschieri A. Parietal cell carcinoma of the stomach: association with long-term survival after curative resection. Br J Cancer. 1988;58(1):85–7.PubMedPubMedCentralGoogle Scholar
  317. 317.
    Hayashi I, Muto Y, Fujii Y, Morimatsu M. Mucoepidermoid carcinoma of the stomach. J Surg Oncol. 1987;34(2):94–9.PubMedGoogle Scholar
  318. 318.
    Amrikachi M, Ro JY, Ordonez NG, Ayala AG. Adenocarcinomas of the gastrointestinal tract with prominent rhabdoid features. Ann Diagn Pathol. 2002;6(6):357–63.PubMedGoogle Scholar
  319. 319.
    Oda, Kondo H, Yamao T, Saito D, Ono H, Gotoda T, et al. Metastatic tumors to the stomach: analysis of 54 patients diagnosed at endoscopy and 347 autopsy cases. Endoscopy. 2001;33(6):507–10.PubMedGoogle Scholar
  320. 320.
    Kim GH, Ahn JY, Jung HY, Park YS, Kim MJ, Choi KD, et al. Clinical and endoscopic features of metastatic tumors in the stomach. Gut Liver. 2015;9(5):615–22.PubMedGoogle Scholar
  321. 321.
    Yang Y, Lu S, Zeng W, Xie S, Xiao S. GATA3 expression in clinically useful groups of breast carcinoma: a comparison with GCDFP15 and mammaglobin for identifying paired primary and metastatic tumors. Ann Diagn Pathol. 2017;26:1–5.PubMedGoogle Scholar
  322. 322.
    O’Connell FP, Wang HH, Odze RD. Utility of immunohistochemistry in distinguishing primary adenocarcinomas from metastatic breast carcinomas in the gastrointestinal tract. Arch Pathol Lab Med. 2005;129(3):338–47.PubMedGoogle Scholar
  323. 323.
    Lau SK, Weiss LM, Chu PG. Differential expression of MUC1, MUC2, and MUC5AC in carcinomas of various sites: an immunohistochemical study. Am J Clin Pathol. 2004;122(1):61–9.PubMedGoogle Scholar
  324. 324.
    Patel DS, Khandeparkar SGS, Joshi AR, Kulkarni MM, Dhande B, Lengare P, et al. Immunohistochemical Study of MUC1, MUC2 and MUC5AC expression in primary breast carcinoma. J Clin Diagn Res. 2017;11(4):EC30–EC4.PubMedPubMedCentralGoogle Scholar
  325. 325.
    Brito MJ, Williams GT, Thompson H, Filipe MI. Expression of p53 in early (T1) gastric carcinoma and precancerous adjacent mucosa. Gut. 1994;35(12):1697–700.PubMedPubMedCentralGoogle Scholar
  326. 326.
    Milne AN, Carvalho R, Morsink FM, Musler AR, de Leng WW, Ristimaki A, et al. Early-onset gastric cancers have a different molecular expression profile than conventional gastric cancers. Mod Pathol. 2006;19(4):564–72.PubMedGoogle Scholar
  327. 327.
    Lee JH, Abraham SC, Kim HS, Nam JH, Choi C, Lee MC, et al. Inverse relationship between APC gene mutation in gastric adenomas and development of adenocarcinoma. Am J Pathol. 2002;161(2):611–8.PubMedPubMedCentralGoogle Scholar
  328. 328.
    Park K, Kim SJ, Bang YJ, Park JG, Kim NK, Roberts AB, et al. Genetic changes in the transforming growth factor beta (TGF-beta) type II receptor gene in human gastric cancer cells: correlation with sensitivity to growth inhibition by TGF-beta. Proc Natl Acad Sci U S A. 1994;91(19):8772–6.PubMedPubMedCentralGoogle Scholar
  329. 329.
    Hara T, Ooi A, Kobayashi M, Mai M, Yanagihara K, Nakanishi I. Amplification of c-myc, K-sam, and c-met in gastric cancers: detection by fluorescence in situ hybridization. Lab Investig. 1998;78(9):1143–53.PubMedGoogle Scholar
  330. 330.
    Lee JH, Han SU, Cho H, Jennings B, Gerrard B, Dean M, et al. A novel germ line juxtamembrane met mutation in human gastric cancer. Oncogene. 2000;19(43):4947–53.PubMedGoogle Scholar
  331. 331.
    Boku N. HER2-positive gastric cancer. Gastric Cancer. 2014;17(1):1–12.PubMedGoogle Scholar
  332. 332.
    Jardim DL, de Melo GD, Falchook GS, Janku F, Zinner R, Wheler JJ, et al. MET aberrations and c-MET inhibitors in patients with gastric and esophageal cancers in a phase I unit. Oncotarget. 2014;5(7):1837–45.PubMedPubMedCentralGoogle Scholar
  333. 333.
    Metzger ML, Behrens HM, Boger C, Haag J, Kruger S, Rocken C. MET in gastric cancer--discarding a 10% cutoff rule. Histopathology. 2016;68(2):241–53.PubMedGoogle Scholar
  334. 334.
    Ha SY, Lee J, Kang SY, Do IG, Ahn S, Park JO, et al. MET overexpression assessed by new interpretation method predicts gene amplification and poor survival in advanced gastric carcinomas. Mod Pathol. 2013;26(12):1632–41.PubMedGoogle Scholar
  335. 335.
    Lee HE, Kim MA, Lee HS, Jung EJ, Yang HK, Lee BL, et al. MET in gastric carcinomas: comparison between protein expression and gene copy number and impact on clinical outcome. Br J Cancer. 2012;107(2):325–33.PubMedPubMedCentralGoogle Scholar
  336. 336.
    Yildiz Y, Sokmensuer C, Yalcin S. Evaluation of c-Met, HGF, and HER-2 expressions in gastric carcinoma and their association with other clinicopathological factors. Onco Targets Ther. 2016;9:5809–17.PubMedPubMedCentralGoogle Scholar
  337. 337.
    Wu MS, Lee CW, Shun CT, Wang HP, Lee WJ, Chang MC, et al. Distinct clinicopathologic and genetic profiles in sporadic gastric cancer with different mutator phenotypes. Genes Chromosomes Cancer. 2000;27(4):403–11.PubMedGoogle Scholar
  338. 338.
    Chung DC, Yoon SS, Lauwers GY, Patel D. Case records of the Massachusetts General Hospital. Case 22-2007. A woman with a family history of gastric and breast cancer. N Engl J Med. 2007;357(3):283–91.PubMedGoogle Scholar
  339. 339.
    Pedrazzani C, Corso G, Marrelli D, Roviello F. E-cadherin and hereditary diffuse gastric cancer. Surgery. 2007;142(5):645–57.PubMedGoogle Scholar
  340. 340.
    Caldas C, Carneiro F, Lynch HT, Yokota J, Wiesner GL, Powell SM, et al. Familial gastric cancer: overview and guidelines for management. J Med Genet. 1999;36(12):873–80.PubMedPubMedCentralGoogle Scholar
  341. 341.
    Blair V, Martin I, Shaw D, Winship I, Kerr D, Arnold J, et al. Hereditary diffuse gastric cancer: diagnosis and management. Clin Gastroenterol Hepatol. 2006;4(3):262–75.PubMedGoogle Scholar
  342. 342.
    Keller G, Vogelsang H, Becker I, Hutter J, Ott K, Candidus S, et al. Diffuse type gastric and lobular breast carcinoma in a familial gastric cancer patient with an E-cadherin germline mutation. Am J Pathol. 1999;155(2):337–42.PubMedPubMedCentralGoogle Scholar
  343. 343.
    Huntsman DG, Carneiro F, Lewis FR, MacLeod PM, Hayashi A, Monaghan KG, et al. Early gastric cancer in young, asymptomatic carriers of germ-line E-cadherin mutations. N Engl J Med. 2001;344(25):1904–9.PubMedGoogle Scholar
  344. 344.
    Rogers WM, Dobo E, Norton JA, Van Dam J, Jeffrey RB, Huntsman DG, et al. Risk-reducing total gastrectomy for germline mutations in E-cadherin (CDH1): pathologic findings with clinical implications. Am J Surg Pathol. 2008;32(6):799–809.PubMedGoogle Scholar
  345. 345.
    Aarnio M, Salovaara R, Aaltonen LA, Mecklin JP, Jarvinen HJ. Features of gastric cancer in hereditary non-polyposis colorectal cancer syndrome. Int J Cancer. 1997;74(5):551–5.PubMedGoogle Scholar
  346. 346.
    Abraham SC, Nobukawa B, Giardiello FM, Hamilton SR, Wu TT. Fundic gland polyps in familial adenomatous polyposis: neoplasms with frequent somatic adenomatous polyposis coli gene alterations. Am J Pathol. 2000;157(3):747–54.PubMedPubMedCentralGoogle Scholar
  347. 347.
    Hofgartner WT, Thorp M, Ramus MW, Delorefice G, Chey WY, Ryan CK, et al. Gastric adenocarcinoma associated with fundic gland polyps in a patient with attenuated familial adenomatous polyposis. Am J Gastroenterol. 1999;94(8):2275–81.PubMedGoogle Scholar
  348. 348.
    Zwick A, Munir M, Ryan CK, Gian J, Burt RW, Leppert M, et al. Gastric adenocarcinoma and dysplasia in fundic gland polyps of a patient with attenuated adenomatous polyposis coli. Gastroenterology. 1997;113(2):659–63.PubMedGoogle Scholar
  349. 349.
    Cancer Genome Atlas Research N. Comprehensive molecular characterization of gastric adenocarcinoma. Nature. 2014;513(7517):202–9.Google Scholar
  350. 350.
    Cristescu R, Lee J, Nebozhyn M, Kim KM, Ting JC, Wong SS, et al. Molecular analysis of gastric cancer identifies subtypes associated with distinct clinical outcomes. Nat Med. 2015;21(5):449–56.PubMedGoogle Scholar
  351. 351.
    Lei Z, Tan IB, Das K, Deng N, Zouridis H, Pattison S, et al. Identification of molecular subtypes of gastric cancer with different responses to PI3-kinase inhibitors and 5-fluorouracil. Gastroenterology. 2013;145(3):554–65.PubMedGoogle Scholar
  352. 352.
    Setia N, Agoston AT, Han HS, Mullen JT, Duda DG, Clark JW, et al. A protein and mRNA expression-based classification of gastric cancer. Mod Pathol. 2016;29(7):772–84.PubMedGoogle Scholar
  353. 353.
    Liu Z, Mira JL, Cruz-Caudillo JC. Primary gastric choriocarcinoma: a case report and review of the literature. Arch Pathol Lab Med. 2001;125(12):1601–4.PubMedGoogle Scholar
  354. 354.
    Imai Y, Kawabe T, Takahashi M, Matsumura M, Komatsu Y, Hamada E, et al. A case of primary gastric choriocarcinoma and a review of the Japanese literature. J Gastroenterol. 1994;29(5):642–6.PubMedGoogle Scholar
  355. 355.
    Namikawa T, Kobayashi M, Okabayashi T, Ozaki S, Nakamura S, Yamashita K, et al. Primary gastric small cell carcinoma: report of a case and review of the literature. Med Mol Morphol. 2005;38(4):256–61.PubMedGoogle Scholar
  356. 356.
    Matsui K, Jin XM, Kitagawa M, Miwa A. Clinicopathologic features of neuroendocrine carcinomas of the stomach: appraisal of small cell and large cell variants. Arch Pathol Lab Med. 1998;122(11):1010–7.PubMedGoogle Scholar
  357. 357.
    Kusayanagi S, Konishi K, Miyasaka N, Sasaki K, Kurahashi T, Kaneko K, et al. Primary small cell carcinoma of the stomach. J Gastroenterol Hepatol. 2003;18(6):743–7.PubMedGoogle Scholar
  358. 358.
    Modlin IM, Kidd M, Latich I, Zikusoka MN, Shapiro MD. Current status of gastrointestinal carcinoids. Gastroenterology. 2005;128(6):1717–51.PubMedGoogle Scholar
  359. 359.
    Laine L, Ahnen D, McClain C, Solcia E, Walsh JH. Review article: potential gastrointestinal effects of long-term acid suppression with proton pump inhibitors. Aliment Pharmacol Ther. 2000;14(6):651–68.PubMedGoogle Scholar
  360. 360.
    La Rosa S, Inzani F, Vanoli A, Klersy C, Dainese L, Rindi G, et al. Histologic characterization and improved prognostic evaluation of 209 gastric neuroendocrine neoplasms. Hum Pathol. 2011;42(10):1373–84.PubMedGoogle Scholar
  361. 361.
    Rindi G, Bordi C, Rappel S, La Rosa S, Stolte M, Solcia E. Gastric carcinoids and neuroendocrine carcinomas: pathogenesis, pathology, and behavior. World J Surg. 1996;20(2):168–72.PubMedGoogle Scholar
  362. 362.
    Thomas RM, Baybick JH, Elsayed AM, Sobin LH. Gastric carcinoids. An immunohistochemical and clinicopathologic study of 104 patients. Cancer. 1994;73(8):2053–8.PubMedGoogle Scholar
  363. 363.
    Borch K, Renvall H, Kullman E, Wilander E. Gastric carcinoid associated with the syndrome of hypergastrinemic atrophic gastritis. A prospective analysis of 11 cases. Am J Surg Pathol. 1987;11(6):435–44.PubMedGoogle Scholar
  364. 364.
    Solcia E, Capella C, Fiocca R, Rindi G, Rosai J. Gastric argyrophil carcinoidosis in patients with Zollinger-Ellison syndrome due to type 1 multiple endocrine neoplasia. A newly recognized association. Am J Surg Pathol. 1990;14(6):503–13.PubMedGoogle Scholar
  365. 365.
    Ooi A, Ota M, Katsuda S, Nakanishi I, Sugawara H, Takahashi I. An unusual case of multiple gastric carcinoids associated with diffuse endocrine cell hyperplasia and parietal cell hypertrophy. Endocr Pathol. 1995;6(3):229–37.PubMedGoogle Scholar
  366. 366.
    Rindi G, Azzoni C, La Rosa S, Klersy C, Paolotti D, Rappel S, et al. ECL cell tumor and poorly differentiated endocrine carcinoma of the stomach: prognostic evaluation by pathological analysis. Gastroenterology. 1999;116(3):532–42.PubMedGoogle Scholar
  367. 367.
    Carney JA, Go VL, Fairbanks VF, Moore SB, Alport EC, Nora FE. The syndrome of gastric argyrophil carcinoid tumors and nonantral gastric atrophy. Ann Intern Med. 1983;99(6):761–6.PubMedGoogle Scholar
  368. 368.
    Muller J, Kirchner T, Muller-Hermelink HK. Gastric endocrine cell hyperplasia and carcinoid tumors in atrophic gastritis type A. Am J Surg Pathol. 1987;11(12):909–17.PubMedGoogle Scholar
  369. 369.
    Pandol SJ. The exocrine pancreas. Colloquium series on integrated systems physiology: from molecule to function to disease. San Rafael: Morgan & Claypool Life Sciences; 2010.Google Scholar
  370. 370.
    Stelow EB, Adams RB, Moskaluk CA. The prevalence of pancreatic intraepithelial neoplasia in pancreata with uncommon types of primary neoplasms. Am J Surg Pathol. 2006;30(1):36–41.PubMedGoogle Scholar
  371. 371.
    Brockie E, Anand A, Albores-Saavedra J. Progression of atypical ductal hyperplasia/carcinoma in situ of the pancreas to invasive adenocarcinoma. Ann Diagn Pathol. 1998;2(5):286–92.PubMedGoogle Scholar
  372. 372.
    Brat DJ, Lillemoe KD, Yeo CJ, Warfield PB, Hruban RH. Progression of pancreatic intraductal neoplasias to infiltrating adenocarcinoma of the pancreas. Am J Surg Pathol. 1998;22(2):163–9.PubMedGoogle Scholar
  373. 373.
    Basturk O, Hong SM, Wood LD, Adsay NV, Albores-Saavedra J, Biankin AV, et al. A revised classification system and recommendations from the Baltimore consensus meeting for neoplastic precursor lesions in the pancreas. Am J Surg Pathol. 2015;39(12):1730–41.PubMedPubMedCentralGoogle Scholar
  374. 374.
    Hruban RH, Takaori K, Klimstra DS, Adsay NV, Albores-Saavedra J, Biankin AV, et al. An illustrated consensus on the classification of pancreatic intraepithelial neoplasia and intraductal papillary mucinous neoplasms. Am J Surg Pathol. 2004;28(8):977–87.PubMedGoogle Scholar
  375. 375.
    Chen J, Baithun SI. Morphological study of 391 cases of exocrine pancreatic tumours with special reference to the classification of exocrine pancreatic carcinoma. J Pathol. 1985;146(1):17–29.PubMedGoogle Scholar
  376. 376.
    Adsay V, Logani S, Sarkar F, Crissman J, Vaitkevicius V. Foamy gland pattern of pancreatic ductal adenocarcinoma: a deceptively benign-appearing variant. Am J Surg Pathol. 2000;24(4):493–504.PubMedGoogle Scholar
  377. 377.
    Bagci P, Andea AA, Basturk O, Jang KT, Erbarut I, Adsay V. Large duct type invasive adenocarcinoma of the pancreas with microcystic and papillary patterns: a potential microscopic mimic of non-invasive ductal neoplasia. Mod Pathol. 2012;25(3):439–48.PubMedGoogle Scholar
  378. 378.
    Dursun N, Feng J, Basturk O, Bandyopadhyay S, Cheng JD, Adsay VN. Vacuolated cell pattern of pancreatobiliary adenocarcinoma: a clinicopathological analysis of 24 cases of a poorly recognized distinctive morphologic variant important in the differential diagnosis. Virchows Arch. 2010;457(6):643–9.PubMedPubMedCentralGoogle Scholar
  379. 379.
    Zerbi A, De Nardi P, Braga M, Radice F, Sironi M, Di Carlo V. An oncocytic carcinoma of the pancreas with pulmonary and subcutaneous metastases. Pancreas. 1993;8(1):116–9.PubMedGoogle Scholar
  380. 380.
    Bandyopadhyay S, Basturk O, Coban I, Thirabanjasak D, Liang H, Altinel D, et al. Isolated solitary ducts (naked ducts) in adipose tissue: a specific but underappreciated finding of pancreatic adenocarcinoma and one of the potential reasons of understaging and high recurrence rate. Am J Surg Pathol. 2009;33(3):425–9.PubMedGoogle Scholar
  381. 381.
    Luttges J, Schemm S, Vogel I, Hedderich J, Kremer B, Kloppel G. The grade of pancreatic ductal carcinoma is an independent prognostic factor and is superior to the immunohistochemical assessment of proliferation. J Pathol. 2000;191(2):154–61.PubMedGoogle Scholar
  382. 382.
    Adsay NV, Basturk O, Bonnett M, Kilinc N, Andea AA, Feng J, et al. A proposal for a new and more practical grading scheme for pancreatic ductal adenocarcinoma. Am J Surg Pathol. 2005;29(6):724–33.PubMedGoogle Scholar
  383. 383.
    Giulianotti PC, Boggi U, Fornaciari G, Bruno J, Rossi G, Giardino D, et al. Prognostic value of histological grading in ductal adenocarcinoma of the pancreas. Kloppel vs TNM grading. Int J Pancreatol. 1995;17(3):279–89.PubMedGoogle Scholar
  384. 384.
    Duval JV, Savas L, Banner BF. Expression of cytokeratins 7 and 20 in carcinomas of the extrahepatic biliary tract, pancreas, and gallbladder. Arch Pathol Lab Med. 2000;124(8):1196–200.PubMedGoogle Scholar
  385. 385.
    Lee MJ, Lee HS, Kim WH, Choi Y, Yang M. Expression of mucins and cytokeratins in primary carcinomas of the digestive system. Mod Pathol. 2003;16(5):403–10.PubMedGoogle Scholar
  386. 386.
    Luttges J, Zamboni G, Longnecker D, Kloppel G. The immunohistochemical mucin expression pattern distinguishes different types of intraductal papillary mucinous neoplasms of the pancreas and determines their relationship to mucinous noncystic carcinoma and ductal adenocarcinoma. Am J Surg Pathol. 2001;25(7):942–8.PubMedGoogle Scholar
  387. 387.
    Andrianifahanana M, Moniaux N, Schmied BM, Ringel J, Friess H, Hollingsworth MA, et al. Mucin (MUC) gene expression in human pancreatic adenocarcinoma and chronic pancreatitis: a potential role of MUC4 as a tumor marker of diagnostic significance. Clin Cancer Res. 2001;7(12):4033–40.PubMedGoogle Scholar
  388. 388.
    Monges GM, Mathoulin-Portier MP, Acres RB, Houvenaeghel GF, Giovannini MF, Seitz JF, et al. Differential MUC 1 expression in normal and neoplastic human pancreatic tissue. An immunohistochemical study of 60 samples. Am J Clin Pathol. 1999;112(5):635–40.PubMedGoogle Scholar
  389. 389.
    Moy AP, Arora K, Deshpande V. Albumin expression distinguishes bile duct adenomas from metastatic adenocarcinoma. Histopathology. 2016;69(3):423–30.PubMedGoogle Scholar
  390. 390.
    Wilentz RE, Su GH, Dai JL, Sparks AB, Argani P, Sohn TA, et al. Immunohistochemical labeling for dpc4 mirrors genetic status in pancreatic adenocarcinomas : a new marker of DPC4 inactivation. Am J Pathol. 2000;156(1):37–43.PubMedPubMedCentralGoogle Scholar
  391. 391.
    Tascilar M, Offerhaus GJ, Altink R, Argani P, Sohn TA, Yeo CJ, et al. Immunohistochemical labeling for the Dpc4 gene product is a specific marker for adenocarcinoma in biopsy specimens of the pancreas and bile duct. Am J Clin Pathol. 2001;116(6):831–7.PubMedGoogle Scholar
  392. 392.
    Adsay NV, Pierson C, Sarkar F, Abrams J, Weaver D, Conlon KC, et al. Colloid (mucinous noncystic) carcinoma of the pancreas. Am J Surg Pathol. 2001;25(1):26–42.PubMedGoogle Scholar
  393. 393.
    Seidel G, Zahurak M, Iacobuzio-Donahue C, Sohn TA, Adsay NV, Yeo CJ, et al. Almost all infiltrating colloid carcinomas of the pancreas and periampullary region arise from in situ papillary neoplasms: a study of 39 cases. Am J Surg Pathol. 2002;26(1):56–63.PubMedGoogle Scholar
  394. 394.
    Kardon DE, Thompson LD, Przygodzki RM, Heffess CS. Adenosquamous carcinoma of the pancreas: a clinicopathologic series of 25 cases. Mod Pathol. 2001;14(5):443–51.PubMedGoogle Scholar
  395. 395.
    Yamaguchi K, Enjoji M. Adenosquamous carcinoma of the pancreas: a clinicopathologic study. J Surg Oncol. 1991;47(2):109–16.PubMedGoogle Scholar
  396. 396.
    Hruban RH, Pitman MB, Klimstra DS, American Registry of Pathology, Armed Forces Institute of Pathology (U.S.). Tumors of the pancreas. Washington, D.C.: American Registry of Pathology in collaboration with the Armed Forces Institute of Pathology; 2007. xviii, 422 p.Google Scholar
  397. 397.
    Paal E, Thompson LD, Frommelt RA, Przygodzki RM, Heffess CS. A clinicopathologic and immunohistochemical study of 35 anaplastic carcinomas of the pancreas with a review of the literature. Ann Diagn Pathol. 2001;5(3):129–40.PubMedGoogle Scholar
  398. 398.
    Alguacil-Garcia A, Weiland LH. The histologic spectrum, prognosis, and histogenesis of the sarcomatoid carcinoma of the pancreas. Cancer. 1977;39(3):1181–9.PubMedGoogle Scholar
  399. 399.
    Dhall D, Klimstra DS. The cellular composition of osteoclastlike giant cell-containing tumors of the pancreatobiliary tree. Am J Surg Pathol. 2008;32(2):335–7. author response 7.PubMedGoogle Scholar
  400. 400.
    Dworak O, Wittekind C, Koerfgen HP, Gall FP. Osteoclastic giant cell tumor of the pancreas. An immunohistological study and review of the literature. Pathol Res Pract. 1993;189(2):228–31. discussion 32-4.PubMedGoogle Scholar
  401. 401.
    Han SS, Jang JY, Kim SW, Kim WH, Lee KU, Park YH. Analysis of long-term survivors after surgical resection for pancreatic cancer. Pancreas. 2006;32(3):271–5.PubMedGoogle Scholar
  402. 402.
    Banville N, Geraghty R, Fox E, Leahy DT, Green A, Keegan D, et al. Medullary carcinoma of the pancreas in a man with hereditary nonpolyposis colorectal cancer due to a mutation of the MSH2 mismatch repair gene. Hum Pathol. 2006;37(11):1498–502.PubMedGoogle Scholar
  403. 403.
    Wilentz RE, Goggins M, Redston M, Marcus VA, Adsay NV, Sohn TA, et al. Genetic, immunohistochemical, and clinical features of medullary carcinoma of the pancreas: a newly described and characterized entity. Am J Pathol. 2000;156(5):1641–51.PubMedPubMedCentralGoogle Scholar
  404. 404.
    Nakata B, Wang YQ, Yashiro M, Nishioka N, Tanaka H, Ohira M, et al. Prognostic value of microsatellite instability in resectable pancreatic cancer. Clin Cancer Res. 2002;8(8):2536–40.PubMedGoogle Scholar
  405. 405.
    Hruban RH, Molina JM, Reddy MN, Boitnott JK. A neoplasm with pancreatic and hepatocellular differentiation presenting with subcutaneous fat necrosis. Am J Clin Pathol. 1987;88(5):639–45.PubMedGoogle Scholar
  406. 406.
    Marchegiani G, Gareer H, Parisi A, Capelli P, Bassi C, Salvia R. Pancreatic hepatoid carcinoma: a review of the literature. Dig Surg. 2013;30(4–6):425–33.PubMedGoogle Scholar
  407. 407.
    Adsay NV, Klimstra DS, Compton CC. Cystic lesions of the pancreas. Introduction. Semin Diagn Pathol. 2000;17(1):1–6.PubMedGoogle Scholar
  408. 408.
    Albores-Saavedra J, Gould EW, Angeles-Angeles A, Henson DE. Cystic tumors of the pancreas. Pathol Annu. 1990;25(Pt 2):19–50.PubMedGoogle Scholar
  409. 409.
    Adsay NV, Klimstra DS. Cystic forms of typically solid pancreatic tumors. Semin Diagn Pathol. 2000;17(1):81–8.PubMedGoogle Scholar
  410. 410.
    Compton CC. Serous cystic tumors of the pancreas. Semin Diagn Pathol. 2000;17(1):43–55.PubMedGoogle Scholar
  411. 411.
    Egawa N, Maillet B, Klöppel G, Schröder S, Mukai K. Serous oligocystic and ill-demarcated adenoma of the pancreas: a variant of serous cystic adenoma. Virchows Arch. 1994;424(1):13–7.PubMedGoogle Scholar
  412. 412.
    Lewandrowski K, Warshaw A, Compton C. Macrocystic serous cystadenoma of the pancreas: a morphologic variant differing from microcystic adenoma. Hum Pathol. 1992;23(8):871–5.PubMedGoogle Scholar
  413. 413.
    Tseng JF, Warshaw AL, Sahani DV, Lauwers GY, Rattner DW, Fernandez-del CC. Serous cystadenoma of the pancreas: tumor growth rates and recommendations for treatment. Ann Surg. 2005;242(3):413–9. discussion 9-21.PubMedPubMedCentralGoogle Scholar
  414. 414.
    King JC, Ng TT, White SC, Cortina G, Reber HA, Hines OJ. Pancreatic serous cystadenocarcinoma: a case report and review of the literature. J Gastrointest Surg. 2009;13(10):1864–8.PubMedPubMedCentralGoogle Scholar
  415. 415.
    Bramis K, Petrou A, Papalambros A, Manzelli A, Mantonakis E, Brennan N, et al. Serous cystadenocarcinoma of the pancreas: report of a case and management reflections. World J Surg Oncol. 2012;10:51.PubMedPubMedCentralGoogle Scholar
  416. 416.
    Girelli R, Bassi C, Falconi M, De Santis L, Bonora A, Caldiron E, et al. Pancreatic cystic manifestations in von Hippel-Lindau disease. Int J Pancreatol. 1997;22(2):101–9.PubMedGoogle Scholar
  417. 417.
    Hough DM, Stephens DH, Johnson CD, Binkovitz LA. Pancreatic lesions in von Hippel-Lindau disease: prevalence, clinical significance, and CT findings. AJR Am J Roentgenol. 1994;162(5):1091–4.PubMedGoogle Scholar
  418. 418.
    Panarelli NC, Park KJ, Hruban RH, Klimstra DS. Microcystic serous cystadenoma of the pancreas with subtotal cystic degeneration: another neoplastic mimic of pancreatic pseudocyst. Am J Surg Pathol. 2012;36(5):726–31.PubMedGoogle Scholar
  419. 419.
    Thirabanjasak D, Basturk O, Altinel D, Cheng JD, Adsay NV. Is serous cystadenoma of the pancreas a model of clear-cell-associated angiogenesis and tumorigenesis? Pancreatology. 2009;9(1–2):182–8.PubMedGoogle Scholar
  420. 420.
    Perez-Ordonez B, Naseem A, Lieberman PH, Klimstra DS. Solid serous adenoma of the pancreas. The solid variant of serous cystadenoma? Am J Surg Pathol. 1996;20(11):1401–5.PubMedGoogle Scholar
  421. 421.
    Kosmahl M, Wagner J, Peters K, Sipos B, Kloppel G. Serous cystic neoplasms of the pancreas: an immunohistochemical analysis revealing alpha-inhibin, neuron-specific enolase, and MUC6 as new markers. Am J Surg Pathol. 2004;28(3):339–46.PubMedGoogle Scholar
  422. 422.
    Yasuhara Y, Sakaida N, Uemura Y, Senzaki H, Shikata N, Tsubura A. Serous microcystic adenoma (glycogen-rich cystadenoma) of the pancreas: study of 11 cases showing clinicopathological and immunohistochemical correlations. Pathol Int. 2002;52(4):307–12.PubMedGoogle Scholar
  423. 423.
    Wu J, Jiao Y, Dal Molin M, Maitra A, de Wilde RF, Wood LD, et al. Whole-exome sequencing of neoplastic cysts of the pancreas reveals recurrent mutations in components of ubiquitin-dependent pathways. Proc Natl Acad Sci U S A. 2011;108(52):21188–93.PubMedPubMedCentralGoogle Scholar
  424. 424.
    Wu J, Matthaei H, Maitra A, Dal Molin M, Wood LD, Eshleman JR, et al. Recurrent GNAS mutations define an unexpected pathway for pancreatic cyst development. Sci Transl Med. 2011;3(92):92ra66.PubMedPubMedCentralGoogle Scholar
  425. 425.
    Moore PS, Zamboni G, Brighenti A, Lissandrini D, Antonello D, Capelli P, et al. Molecular characterization of pancreatic serous microcystic adenomas: evidence for a tumor suppressor gene on chromosome 10q. Am J Pathol. 2001;158(1):317–21.PubMedPubMedCentralGoogle Scholar
  426. 426.
    Thompson LD, Becker RC, Przygodzki RM, Adair CF, Heffess CS. Mucinous cystic neoplasm (mucinous cystadenocarcinoma of low-grade malignant potential) of the pancreas: a clinicopathologic study of 130 cases. Am J Surg Pathol. 1999;23(1):1–16.PubMedGoogle Scholar
  427. 427.
    Compagno J, Oertel JE. Mucinous cystic neoplasms of the pancreas with overt and latent malignancy (cystadenocarcinoma and cystadenoma). A clinicopathologic study of 41 cases. Am J Clin Pathol. 1978;69(6):573–80.PubMedGoogle Scholar
  428. 428.
    Wilentz RE, Albores-Saavedra J, Hruban RH. Mucinous cystic neoplasms of the pancreas. Semin Diagn Pathol. 2000;17(1):31–42.PubMedGoogle Scholar
  429. 429.
    Zamboni G, Scarpa A, Bogina G, Iacono C, Bassi C, Talamini G, et al. Mucinous cystic tumors of the pancreas: clinicopathological features, prognosis, and relationship to other mucinous cystic tumors. Am J Surg Pathol. 1999;23(4):410–22.PubMedGoogle Scholar
  430. 430.
    Izumo A, Yamaguchi K, Eguchi T, Nishiyama K, Yamamoto H, Yonemasu H, et al. Mucinous cystic tumor of the pancreas: immunohistochemical assessment of “ovarian-type stroma”. Oncol Rep. 2003;10(3):515–25.PubMedGoogle Scholar
  431. 431.
    Hara T, Kawashima H, Ishigooka M, Kashiyama M, Takanashi S, Yamazaki S, et al. Mucinous cystic tumors of the pancreas. Surg Today. 2002;32(11):965–9.PubMedGoogle Scholar
  432. 432.
    Ridder GJ, Maschek H, Flemming P, Nashan B, Klempnauer J. Ovarian-like stroma in an invasive mucinous cystadenocarcinoma of the pancreas positive for inhibin. A hint concerning its possible histogenesis. Virchows Arch. 1998;432(5):451–4.PubMedGoogle Scholar
  433. 433.
    Hirano H, Morita K, Tachibana S, Okimura A, Fujisawa T, Ouchi S, et al. Undifferentiated carcinoma with osteoclast-like giant cells arising in a mucinous cystic neoplasm of the pancreas. Pathol Int. 2008;58(6):383–9.PubMedGoogle Scholar
  434. 434.
    Zamboni G, Terris B, Scarpa A, Kosmahl M, Capelli P, Klimstra DS, et al. Acinar cell cystadenoma of the pancreas: a new entity? Am J Surg Pathol. 2002;26(6):698–704.PubMedGoogle Scholar
  435. 435.
    Luttges J, Feyerabend B, Buchelt T, Pacena M, Kloppel G. The mucin profile of noninvasive and invasive mucinous cystic neoplasms of the pancreas. Am J Surg Pathol. 2002;26(4):466–71.PubMedGoogle Scholar
  436. 436.
    Yoshizawa K, Nagai H, Sakurai S, Hironaka M, Morinaga S, Saitoh K, et al. Clonality and K-ras mutation analyses of epithelia in intraductal papillary mucinous tumor and mucinous cystic tumor of the pancreas. Virchows Arch. 2002;441(5):437–43.PubMedGoogle Scholar
  437. 437.
    Jimenez RE, Warshaw AL, Z’Graggen K, Hartwig W, Taylor DZ, Compton CC, et al. Sequential accumulation of K-ras mutations and p53 overexpression in the progression of pancreatic mucinous cystic neoplasms to malignancy. Ann Surg. 1999;230(4):501–9. discussion 9-11.PubMedPubMedCentralGoogle Scholar
  438. 438.
    Adsay V, Mino-Kenudson M, Furukawa T, Basturk O, Zamboni G, Marchegiani G, et al. Pathologic evaluation and reporting of intraductal papillary mucinous neoplasms of the pancreas and other tumoral intraepithelial neoplasms of pancreatobiliary tract: recommendations of verona consensus meeting. Ann Surg. 2016;263(1):162–77.PubMedPubMedCentralGoogle Scholar
  439. 439.
    Matthaei H, Wu J, Dal Molin M, Shi C, Perner S, Kristiansen G, et al. GNAS sequencing identifies IPMN-specific mutations in a subgroup of diminutive pancreatic cysts referred to as “incipient IPMNs”. Am J Surg Pathol. 2014;38(3):360–3.PubMedPubMedCentralGoogle Scholar
  440. 440.
    Adsay NV, Conlon KC, Zee SY, Brennan MF, Klimstra DS. Intraductal papillary-mucinous neoplasms of the pancreas: an analysis of in situ and invasive carcinomas in 28 patients. Cancer. 2002;94(1):62–77.PubMedGoogle Scholar
  441. 441.
    Azar C, Van de Stadt J, Rickaert F, Deviere M, Baize M, Kloppel G, et al. Intraductal papillary mucinous tumours of the pancreas. Clinical and therapeutic issues in 32 patients. Gut. 1996;39(3):457–64.PubMedPubMedCentralGoogle Scholar
  442. 442.
    Kloppel G. Clinicopathologic view of intraductal papillary-mucinous tumor of the pancreas. Hepato-Gastroenterology. 1998;45(24):1981–5.PubMedGoogle Scholar
  443. 443.
    Loftus EV Jr, Olivares-Pakzad BA, Batts KP, Adkins MC, Stephens DH, Sarr MG, et al. Intraductal papillary-mucinous tumors of the pancreas: clinicopathologic features, outcome, and nomenclature. Members of the Pancreas Clinic, and Pancreatic Surgeons of Mayo Clinic. Gastroenterology. 1996;110(6):1909–18.PubMedGoogle Scholar
  444. 444.
    Paal E, Thompson LD, Przygodzki RM, Bratthauer GL, Heffess CS. A clinicopathologic and immunohistochemical study of 22 intraductal papillary mucinous neoplasms of the pancreas, with a review of the literature. Mod Pathol. 1999;12(5):518–28.PubMedGoogle Scholar
  445. 445.
    Furukawa T, Kloppel G, Volkan Adsay N, Albores-Saavedra J, Fukushima N, Horii A, et al. Classification of types of intraductal papillary-mucinous neoplasm of the pancreas: a consensus study. Virchows Arch. 2005;447(5):794–9.PubMedGoogle Scholar
  446. 446.
    Adsay NV, Merati K, Andea A, Sarkar F, Hruban RH, Wilentz RE, et al. The dichotomy in the preinvasive neoplasia to invasive carcinoma sequence in the pancreas: differential expression of MUC1 and MUC2 supports the existence of two separate pathways of carcinogenesis. Mod Pathol. 2002;15(10):1087–95.PubMedGoogle Scholar
  447. 447.
    Adsay NV, Longnecker DS, Klimstra DS. Pancreatic tumors with cystic dilatation of the ducts: intraductal papillary mucinous neoplasms and intraductal oncocytic papillary neoplasms. Semin Diagn Pathol. 2000;17(1):16–30.PubMedGoogle Scholar
  448. 448.
    Nakayama Y, Inoue H, Hamada Y, Takeshita M, Iwasaki H, Maeshiro K, et al. Intraductal tubular adenoma of the pancreas, pyloric gland type: a clinicopathologic and immunohistochemical study of 6 cases. Am J Surg Pathol. 2005;29(5):607–16.PubMedGoogle Scholar
  449. 449.
    Albores-Saavedra J, Sheahan K, O’Riain C, Shukla D. Intraductal tubular adenoma, pyloric type, of the pancreas: additional observations on a new type of pancreatic neoplasm. Am J Surg Pathol. 2004;28(2):233–8.PubMedGoogle Scholar
  450. 450.
    Kato N, Akiyama S, Motoyama T. Pyloric gland-type tubular adenoma superimposed on intraductal papillary mucinous tumor of the pancreas. Pyloric gland adenoma of the pancreas. Virchows Arch. 2002;440(2):205–8.PubMedGoogle Scholar
  451. 451.
    Bakotic BW, Robinson MJ, Sturm PD, Hruban RH, Offerhaus GJ, Albores-Saavedra J. Pyloric gland adenoma of the main pancreatic duct. Am J Surg Pathol. 1999;23(2):227–31.PubMedGoogle Scholar
  452. 452.
    Adsay NV, Merati K, Basturk O, Iacobuzio-Donahue C, Levi E, Cheng JD, et al. Pathologically and biologically distinct types of epithelium in intraductal papillary mucinous neoplasms: delineation of an “intestinal” pathway of carcinogenesis in the pancreas. Am J Surg Pathol. 2004;28(7):839–48.PubMedGoogle Scholar
  453. 453.
    Ishida M, Egawa S, Aoki T, Sakata N, Mikami Y, Motoi F, et al. Characteristic clinicopathological features of the types of intraductal papillary-mucinous neoplasms of the pancreas. Pancreas. 2007;35(4):348–52.PubMedGoogle Scholar
  454. 454.
    Basturk O, Tan M, Bhanot U, Allen P, Adsay V, Scott SN, et al. The oncocytic subtype is genetically distinct from other pancreatic intraductal papillary mucinous neoplasm subtypes. Mod Pathol. 2016;29(9):1058–69.PubMedPubMedCentralGoogle Scholar
  455. 455.
    Schaberg KB, DiMaio MA, Longacre TA. Intraductal papillary mucinous neoplasms often contain epithelium from multiple subtypes and/or are unclassifiable. Am J Surg Pathol. 2016;40(1):44–50.PubMedGoogle Scholar
  456. 456.
    Tanaka M, Fernandez-del Castillo C, Adsay V, Chari S, Falconi M, Jang JY, et al. International consensus guidelines 2012 for the management of IPMN and MCN of the pancreas. Pancreatology. 2012;12(3):183–97.PubMedGoogle Scholar
  457. 457.
    Terada T, Ohta T, Kitamura Y, Ashida K, Matsunaga Y. Cell proliferative activity in intraductal papillary-mucinous neoplasms and invasive ductal adenocarcinomas of the pancreas: an immunohistochemical study. Arch Pathol Lab Med. 1998;122(1):42–6.PubMedGoogle Scholar
  458. 458.
    Nagai E, Ueki T, Chijiiwa K, Tanaka M, Tsuneyoshi M. Intraductal papillary mucinous neoplasms of the pancreas associated with so-called “mucinous ductal ectasia”. Histochemical and immunohistochemical analysis of 29 cases. Am J Surg Pathol. 1995;19(5):576–89.PubMedGoogle Scholar
  459. 459.
    Basturk O, Khayyata S, Klimstra DS, Hruban RH, Zamboni G, Coban I, et al. Preferential expression of MUC6 in oncocytic and pancreatobiliary types of intraductal papillary neoplasms highlights a pyloropancreatic pathway, distinct from the intestinal pathway, in pancreatic carcinogenesis. Am J Surg Pathol. 2010;34(3):364–70.PubMedPubMedCentralGoogle Scholar
  460. 460.
    Lee JH, Kim Y, Choi JW, Kim YS. KRAS, GNAS, and RNF43 mutations in intraductal papillary mucinous neoplasm of the pancreas: a meta-analysis. Springerplus. 2016;5(1):1172.PubMedPubMedCentralGoogle Scholar
  461. 461.
    Satoh K, Shimosegawa T, Moriizumi S, Koizumi M, Toyota T. K-ras mutation and p53 protein accumulation in intraductal mucin-hypersecreting neoplasms of the pancreas. Pancreas. 1996;12(4):362–8.PubMedGoogle Scholar
  462. 462.
    Z’Graggen K, Rivera JA, Compton CC, Pins M, Werner J, Fernandez-del Castillo C, et al. Prevalence of activating K-ras mutations in the evolutionary stages of neoplasia in intraductal papillary mucinous tumors of the pancreas. Ann Surg. 1997;226(4):491–8. discussion 8-500.PubMedPubMedCentralGoogle Scholar
  463. 463.
    Chadwick B, Willmore-Payne C, Tripp S, Layfield LJ, Hirschowitz S, Holden J. Histologic, immunohistochemical, and molecular classification of 52 IPMNs of the pancreas. Appl Immunohistochem Mol Morphol. 2009;17(1):31–9.PubMedGoogle Scholar
  464. 464.
    Biankin AV, Biankin SA, Kench JG, Morey AL, Lee CS, Head DR, et al. Aberrant p16(INK4A) and DPC4/Smad4 expression in intraductal papillary mucinous tumours of the pancreas is associated with invasive ductal adenocarcinoma. Gut. 2002;50(6):861–8.PubMedPubMedCentralGoogle Scholar
  465. 465.
    Sato N, Rosty C, Jansen M, Fukushima N, Ueki T, Yeo CJ, et al. STK11/LKB1 Peutz-Jeghers gene inactivation in intraductal papillary-mucinous neoplasms of the pancreas. Am J Pathol. 2001;159(6):2017–22.PubMedPubMedCentralGoogle Scholar
  466. 466.
    Tsai JH, Liau JY, Yuan CT, Cheng ML, Yuan RH, Jeng YM. RNF43 mutation frequently occurs with GNAS mutation and mucin hypersecretion in intraductal papillary neoplasms of the bile duct. Histopathology. 2017;70(5):756–65.PubMedGoogle Scholar
  467. 467.
    Zauber P, Marotta S, Sabbath-Solitare M. GNAS mutations are associated with mucin production in low-grade appendiceal mucinous neoplasms, villous adenomas, and carcinomas. Hum Pathol. 2015;46(2):339.PubMedGoogle Scholar
  468. 468.
    Komatsu H, Tanji E, Sakata N, Aoki T, Motoi F, Naitoh T, et al. A GNAS mutation found in pancreatic intraductal papillary mucinous neoplasms induces drastic alterations of gene expression profiles with upregulation of mucin genes. PLoS One. 2014;9(2):e87875.PubMedPubMedCentralGoogle Scholar
  469. 469.
    Adsay NV, Adair CF, Heffess CS, Klimstra DS. Intraductal oncocytic papillary neoplasms of the pancreas. Am J Surg Pathol. 1996;20(8):980–94.PubMedGoogle Scholar
  470. 470.
    Basturk O, Chung SM, Hruban RH, Adsay NV, Askan G, Iacobuzio-Donahue C, et al. Distinct pathways of pathogenesis of intraductal oncocytic papillary neoplasms and intraductal papillary mucinous neoplasms of the pancreas. Virchows Arch. 2016;469(5):523–32.PubMedPubMedCentralGoogle Scholar
  471. 471.
    Patel SA, Adams R, Goldstein M, Moskaluk CA. Genetic analysis of invasive carcinoma arising in intraductal oncocytic papillary neoplasm of the pancreas. Am J Surg Pathol. 2002;26(8):1071–7.PubMedGoogle Scholar
  472. 472.
    Konigsrainer I, Glatzle J, Kloppel G, Konigsrainer A, Wehrmann M. Intraductal and cystic tubulopapillary adenocarcinoma of the pancreas--a possible variant of intraductal tubular carcinoma. Pancreas. 2008;36(1):92–5.PubMedGoogle Scholar
  473. 473.
    Yamaguchi H, Shimizu M, Ban S, Koyama I, Hatori T, Fujita I, et al. Intraductal tubulopapillary neoplasms of the pancreas distinct from pancreatic intraepithelial neoplasia and intraductal papillary mucinous neoplasms. Am J Surg Pathol. 2009;33(8):1164–72.PubMedGoogle Scholar
  474. 474.
    Schlitter AM, Jang KT, Kloppel G, Saka B, Hong SM, Choi H, et al. Intraductal tubulopapillary neoplasms of the bile ducts: clinicopathologic, immunohistochemical, and molecular analysis of 20 cases. Mod Pathol. 2015;28(9):1249–64.PubMedGoogle Scholar
  475. 475.
    Tajiri T, Tate G, Kunimura T, Inoue K, Mitsuya T, Yoshiba M, et al. Histologic and immunohistochemical comparison of intraductal tubular carcinoma, intraductal papillary-mucinous carcinoma, and ductal adenocarcinoma of the pancreas. Pancreas. 2004;29(2):116–22.PubMedGoogle Scholar
  476. 476.
    Tajiri T, Tate G, Inagaki T, Kunimura T, Inoue K, Mitsuya T, et al. Intraductal tubular neoplasms of the pancreas: histogenesis and differentiation. Pancreas. 2005;30(2):115–21.PubMedGoogle Scholar
  477. 477.
    Yamaguchi H, Kuboki Y, Hatori T, Yamamoto M, Shiratori K, Kawamura S, et al. Somatic mutations in PIK3CA and activation of AKT in intraductal tubulopapillary neoplasms of the pancreas. Am J Surg Pathol. 2011;35(12):1812–7.PubMedGoogle Scholar
  478. 478.
    Basturk O, Berger MF, Yamaguchi H, Adsay V, Askan G, Bhanot UK, et al. Pancreatic intraductal tubulopapillary neoplasm is genetically distinct from intraductal papillary mucinous neoplasm and ductal adenocarcinoma. Mod Pathol. 2017;30(12):1760–72.PubMedGoogle Scholar
  479. 479.
    Chatelain D, Paye F, Mourra N, Scoazec JY, Baudrimont M, Parc R, et al. Unilocular acinar cell cystadenoma of the pancreas an unusual acinar cell tumor. Am J Clin Pathol. 2002;118(2):211–4.PubMedGoogle Scholar
  480. 480.
    Albores-Saavedra J. Acinar cystadenoma of the pancreas: a previously undescribed tumor. Ann Diagn Pathol. 2002;6(2):113–5.PubMedGoogle Scholar
  481. 481.
    Khor TS, Badizadegan K, Ferrone C, Fernandez-del Castillo C, Desai GS, Saenz A, et al. Acinar cystadenoma of the pancreas: a clinicopathologic study of 10 cases including multilocular lesions with mural nodules. Am J Surg Pathol. 2012;36(11):1579–91.PubMedGoogle Scholar
  482. 482.
    Singhi AD, Norwood S, Liu TC, Sharma R, Wolfgang CL, Schulick RD, et al. Acinar cell cystadenoma of the pancreas: a benign neoplasm or non-neoplastic ballooning of acinar and ductal epithelium? Am J Surg Pathol. 2013;37(9):1329–35.PubMedGoogle Scholar
  483. 483.
    Couvelard A, Terris B, Hammel P, Palazzo L, Belghiti J, Levy P, et al. Acinar cystic transformation of the pancreas (or acinar cell cystadenoma), a rare and recently described entity. Ann Pathol. 2002;22(5):397–400.PubMedGoogle Scholar
  484. 484.
    Klimstra DS, Heffess CS, Oertel JE, Rosai J. Acinar cell carcinoma of the pancreas. A clinicopathologic study of 28 cases. Am J Surg Pathol. 1992;16(9):815–37.PubMedGoogle Scholar
  485. 485.
    Hoorens A, Lemoine NR, McLellan E, Morohoshi T, Kamisawa T, Heitz PU, et al. Pancreatic acinar cell carcinoma. An analysis of cell lineage markers, p53 expression, and Ki-ras mutation. Am J Pathol. 1993;143(3):685–98.PubMedPubMedCentralGoogle Scholar
  486. 486.
    La Rosa S, Adsay V, Albarello L, Asioli S, Casnedi S, Franzi F, et al. Clinicopathologic study of 62 acinar cell carcinomas of the pancreas: insights into the morphology and immunophenotype and search for prognostic markers. Am J Surg Pathol. 2012;36(12):1782–95.PubMedGoogle Scholar
  487. 487.
    Shorter NA, Glick RD, Klimstra DS, Brennan MF, MP LQ. Malignant pancreatic tumors in childhood and adolescence: the Memorial Sloan-Kettering experience, 1967 to present. J Pediatr Surg. 2002;37(6):887–92.PubMedGoogle Scholar
  488. 488.
    Burns WA, Matthews MJ, Hamosh M, Weide GV, Blum R, Johnson FB. Lipase-secreting acinar cell carcinoma of the pancreas with polyarthropathy. A light and electron microscopic, histochemical, and biochemical study. Cancer. 1974;33(4):1002–9.PubMedGoogle Scholar
  489. 489.
    Holen KD, Klimstra DS, Hummer A, Gonen M, Conlon K, Brennan M, et al. Clinical characteristics and outcomes from an institutional series of acinar cell carcinoma of the pancreas and related tumors. J Clin Oncol. 2002;20(24):4673–8.PubMedGoogle Scholar
  490. 490.
    Vakiani E, Young RH, Carcangiu ML, Klimstra DS. Acinar cell carcinoma of the pancreas metastatic to the ovary: a report of 4 cases. Am J Surg Pathol. 2008;32(10):1540–5.PubMedGoogle Scholar
  491. 491.
    Sigel CS, Klimstra DS. Cytomorphologic and immunophenotypical features of acinar cell neoplasms of the pancreas. Cancer Cytopathol. 2013;121(8):459–70.PubMedGoogle Scholar
  492. 492.
    Lowery MA, Klimstra DS, Shia J, Yu KH, Allen PJ, Brennan MF, et al. Acinar cell carcinoma of the pancreas: new genetic and treatment insights into a rare malignancy. Oncologist. 2011;16(12):1714–20.PubMedPubMedCentralGoogle Scholar
  493. 493.
    Cantrell BB, Cubilla AL, Erlandson RA, Fortner J, Fitzgerald PJ. Acinar cell cystadenocarcinoma of human pancreas. Cancer. 1981;47(2):410–6.PubMedGoogle Scholar
  494. 494.
    Labate AM, Klimstra DL, Zakowski MF. Comparative cytologic features of pancreatic acinar cell carcinoma and islet cell tumor. Diagn Cytopathol. 1997;16(2):112–6.PubMedGoogle Scholar
  495. 495.
    Klimstra DS, Rosai J, Heffess CS. Mixed acinar-endocrine carcinomas of the pancreas. Am J Surg Pathol. 1994;18(8):765–78.PubMedGoogle Scholar
  496. 496.
    Ohike N, Kosmahl M, Kloppel G. Mixed acinar-endocrine carcinoma of the pancreas. A clinicopathological study and comparison with acinar-cell carcinoma. Virchows Arch. 2004;445(3):231–5.PubMedGoogle Scholar
  497. 497.
    Askan G, Deshpande V, Klimstra DS, Adsay V, Sigel C, Shia J, et al. Expression of markers of hepatocellular differentiation in pancreatic acinar cell neoplasms: a potential diagnostic pitfall. Am J Clin Pathol. 2016;146(2):163–9.PubMedPubMedCentralGoogle Scholar
  498. 498.
    Ting DT, Deshpande V. Expression of albumin mRNA in primary hepatic neoplasms and acinar cell carcinoma. Am J Surg Pathol. 2015;39(8):1157–8.PubMedGoogle Scholar
  499. 499.
    Wang L, Basturk O, Chmielecki J, Ross J, Stephens P, Adsay V, et al. Development of BRAF FISH assay for the detection of BRAF gene rearrangements identified in pancreatic acinar cell carcinomas. Lab Investig. 2015-02-01;95(Supplemental 1):132–40.Google Scholar
  500. 500.
    Liu W, Shia J, Gönen M, Lowery MA, O’Reilly EM, Klimstra DS. DNA mismatch repair abnormalities in acinar cell carcinoma of the pancreas: frequency and clinical significance. Pancreas. 2014;43(8):1264–70.PubMedGoogle Scholar
  501. 501.
    Karamurzin Y, Zeng Z, Stadler ZK, Zhang L, Ouansafi I, Al-Ahmadie HA, et al. Unusual DNA mismatch repair-deficient tumors in Lynch syndrome: a report of new cases and review of the literature. Hum Pathol. 2012;43(10):1677–87.PubMedGoogle Scholar
  502. 502.
    Terhune PG, Heffess CS, Longnecker DS. Only wild-type c-ki-ras codons 12, 13, and 61 in human pancreatic acinar cell carcinomas. Mol Carcinog. 1994;10(2):110–4.PubMedGoogle Scholar
  503. 503.
    Moore PS, Orlandini S, Zamboni G, Capelli P, Rigaud G, Falconi M, et al. Pancreatic tumours: molecular pathways implicated in ductal cancer are involved in ampullary but not in exocrine nonductal or endocrine tumorigenesis. Br J Cancer. 2001;84(2):253–62.PubMedPubMedCentralGoogle Scholar
  504. 504.
    Abraham SC, Wu TT, Hruban RH, Lee JH, Yeo CJ, Conlon K, et al. Genetic and immunohistochemical analysis of pancreatic acinar cell carcinoma: frequent allelic loss on chromosome 11p and alterations in the APC/beta-catenin pathway. Am J Pathol. 2002;160(3):953–62.PubMedPubMedCentralGoogle Scholar
  505. 505.
    Furlan D, Sahnane N, Bernasconi B, Frattini M, Tibiletti MG, Molinari F, et al. APC alterations are frequently involved in the pathogenesis of acinar cell carcinoma of the pancreas, mainly through gene loss and promoter hypermethylation. Virchows Arch. 2014;464(5):553–64.PubMedGoogle Scholar
  506. 506.
    La Rosa S, Bernasconi B, Frattini M, Tibiletti MG, Molinari F, Furlan D, et al. TP53 alterations in pancreatic acinar cell carcinoma: new insights into the molecular pathology of this rare cancer. Virchows Arch. 2016;468(3):289–96.PubMedGoogle Scholar
  507. 507.
    Klimstra DS, Wenig BM, Adair CF, Heffess CS. Pancreatoblastoma. A clinicopathologic study and review of the literature. Am J Surg Pathol. 1995;19(12):1371–89.PubMedGoogle Scholar
  508. 508.
    Palosaari D, Clayton F, Seaman J. Pancreatoblastoma in an adult. Arch Pathol Lab Med. 1986;110(7):650–2.PubMedGoogle Scholar
  509. 509.
    Dunn JL, Longnecker DS. Pancreatoblastoma in an older adult. Arch Pathol Lab Med. 1995;119(6):547–51.PubMedGoogle Scholar
  510. 510.
    Hoorens A, Gebhard F, Kraft K, Lemoine NR, Kloppel G. Pancreatoblastoma in an adult: its separation from acinar cell carcinoma. Virchows Arch. 1994;424(5):485–90.PubMedGoogle Scholar
  511. 511.
    Drut R, Jones MC. Congenital pancreatoblastoma in Beckwith-Wiedemann syndrome: an emerging association. Pediatr Pathol. 1988;8(3):331–9.PubMedGoogle Scholar
  512. 512.
    Muguerza R, Rodriguez A, Formigo E, Montero M, Vazquez JL, Paramo C, et al. Pancreatoblastoma associated with incomplete Beckwith-Wiedemann syndrome: case report and review of the literature. J Pediatr Surg. 2005;40(8):1341–4.PubMedGoogle Scholar
  513. 513.
    Bien E, Godzinski J, Dall'igna P, Defachelles AS, Stachowicz-Stencel T, Orbach D, et al. Pancreatoblastoma: a report from the European cooperative study group for paediatric rare tumours (EXPeRT). Eur J Cancer. 2011;47(15):2347–52.PubMedGoogle Scholar
  514. 514.
    Morohoshi T, Kanda M, Horie A, Chott A, Dreyer T, Kloppel G, et al. Immunocytochemical markers of uncommon pancreatic tumors. Acinar cell carcinoma, pancreatoblastoma, and solid cystic (papillary-cystic) tumor. Cancer. 1987;59(4):739–47.PubMedGoogle Scholar
  515. 515.
    Cingolani N, Shaco-Levy R, Farruggio A, Klimstra DS, Rosai J. Alpha-fetoprotein production by pancreatic tumors exhibiting acinar cell differentiation: study of five cases, one arising in a mediastinal teratoma. Hum Pathol. 2000;31(8):938–44.PubMedGoogle Scholar
  516. 516.
    Tanaka Y, Kato K, Notohara K, Nakatani Y, Miyake T, Ijiri R, et al. Significance of aberrant (cytoplasmic/nuclear) expression of beta-catenin in pancreatoblastoma. J Pathol. 2003;199(2):185–90.PubMedGoogle Scholar
  517. 517.
    Abraham SC, Wu TT, Klimstra DS, Finn LS, Lee JH, Yeo CJ, et al. Distinctive molecular genetic alterations in sporadic and familial adenomatous polyposis-associated pancreatoblastomas : frequent alterations in the APC/beta-catenin pathway and chromosome 11p. Am J Pathol. 2001;159(5):1619–27.PubMedPubMedCentralGoogle Scholar
  518. 518.
    Stelow EB, Shaco-Levy R, Bao F, Garcia J, Klimstra DS. Pancreatic acinar cell carcinomas with prominent ductal differentiation: mixed acinar ductal carcinoma and mixed acinar endocrine ductal carcinoma. Am J Surg Pathol. 2010;34(4):510–8.PubMedGoogle Scholar
  519. 519.
    Yu R, Jih L, Zhai J, Nissen NN, Colquhoun S, Wolin E, et al. Mixed acinar-endocrine carcinoma of the pancreas: new clinical and pathological features in a contemporary series. Pancreas. 2013;42(3):429–35.PubMedGoogle Scholar
  520. 520.
    Ogbonna OH, Garcon MC, Syrigos KN, Saif MW. Mixed acinar-neuroendocrine carcinoma of the pancreas with neuroendocrine predominance. Case Rep Med. 2013;2013:705092.PubMedPubMedCentralGoogle Scholar
  521. 521.
    Klimstra DS, Wenig BM, Heffess CS. Solid-pseudopapillary tumor of the pancreas: a typically cystic carcinoma of low malignant potential. Semin Diagn Pathol. 2000;17(1):66–80.PubMedGoogle Scholar
  522. 522.
    Kissane JM. Pancreatoblastoma and solid and cystic papillary tumor: two tumors related to pancreatic ontogeny. Semin Diagn Pathol. 1994;11(2):152–64.PubMedGoogle Scholar
  523. 523.
    Kloppel G, Morohoshi T, John HD, Oehmichen W, Opitz K, Angelkort A, et al. Solid and cystic acinar cell tumour of the pancreas. A tumour in young women with favourable prognosis. Virchows Arch A Pathol Anat Histol. 1981;392(2):171–83.PubMedGoogle Scholar
  524. 524.
    Pettinato G, Manivel JC, Ravetto C, Terracciano LM, Gould EW, di Tuoro A, et al. Papillary cystic tumor of the pancreas. A clinicopathologic study of 20 cases with cytologic, immunohistochemical, ultrastructural, and flow cytometric observations, and a review of the literature. Am J Clin Pathol. 1992;98(5):478–88.PubMedGoogle Scholar
  525. 525.
    Stommer P, Kraus J, Stolte M, Giedl J. Solid and cystic pancreatic tumors. Clinical, histochemical, and electron microscopic features in ten cases. Cancer. 1991;67(6):1635–41.PubMedGoogle Scholar
  526. 526.
    Matsunou H, Konishi F, Yamamichi N, Takayanagi N, Mukai M. Solid, infiltrating variety of papillary cystic neoplasm of the pancreas. Cancer. 1990;65(12):2747–57.PubMedGoogle Scholar
  527. 527.
    Kloppel G, Maurer R, Hofmann E, Luthold K, Oscarson J, Forsby N, et al. Solid-cystic (papillary-cystic) tumours within and outside the pancreas in men: report of two patients. Virchows Arch A Pathol Anat Histopathol. 1991;418(2):179–83.PubMedGoogle Scholar
  528. 528.
    Nishihara K, Nagoshi M, Tsuneyoshi M, Yamaguchi K, Hayashi I. Papillary cystic tumors of the pancreas. Assessment of their malignant potential. Cancer. 1993;71(1):82–92.PubMedGoogle Scholar
  529. 529.
    Abraham SC, Klimstra DS, Wilentz RE, Yeo CJ, Conlon K, Brennan M, et al. Solid-pseudopapillary tumors of the pancreas are genetically distinct from pancreatic ductal adenocarcinomas and almost always harbor beta-catenin mutations. Am J Pathol. 2002;160(4):1361–9.PubMedPubMedCentralGoogle Scholar
  530. 530.
    Chetty R, Serra S. Loss of expression of E-cadherin in solid pseudopapillary tumors of the pancreas. Pancreas. 2009;38(3):338. author reply −9.PubMedGoogle Scholar
  531. 531.
    Hibi T, Ojima H, Sakamoto Y, Kosuge T, Shimada K, Sano T, et al. A solid pseudopapillary tumor arising from the greater omentum followed by multiple metastases with increasing malignant potential. J Gastroenterol. 2006;41(3):276–81.PubMedGoogle Scholar
  532. 532.
    Zinner MJ, Shurbaji MS, Cameron JL. Solid and papillary epithelial neoplasms of the pancreas. Surgery. 1990;108(3):475–80.PubMedGoogle Scholar
  533. 533.
    Martin RC, Klimstra DS, Brennan MF, Conlon KC. Solid-pseudopapillary tumor of the pancreas: a surgical enigma? Ann Surg Oncol. 2002;9(1):35–40.PubMedGoogle Scholar
  534. 534.
    Orlando CA, Bowman RL, Loose JH. Multicentric papillary-cystic neoplasm of the pancreas. Arch Pathol Lab Med. 1991;115(9):958–60.PubMedGoogle Scholar
  535. 535.
    Albores-Saavedra J, Simpson KW, Bilello SJ. The clear cell variant of solid pseudopapillary tumor of the pancreas: a previously unrecognized pancreatic neoplasm. Am J Surg Pathol. 2006;30(10):1237–42.PubMedGoogle Scholar
  536. 536.
    Tang LH, Aydin H, Brennan MF, Klimstra DS. Clinically aggressive solid pseudopapillary tumors of the pancreas: a report of two cases with components of undifferentiated carcinoma and a comparative clinicopathologic analysis of 34 conventional cases. Am J Surg Pathol. 2005;29(4):512–9.PubMedGoogle Scholar
  537. 537.
    Tanaka Y, Kato K, Notohara K, Hojo H, Ijiri R, Miyake T, et al. Frequent beta-catenin mutation and cytoplasmic/nuclear accumulation in pancreatic solid-pseudopapillary neoplasm. Cancer Res. 2001;61(23):8401–4.PubMedGoogle Scholar
  538. 538.
    Tiemann K, Heitling U, Kosmahl M, Kloppel G. Solid pseudopapillary neoplasms of the pancreas show an interruption of the Wnt-signaling pathway and express gene products of 11q. Mod Pathol. 2007;20(9):955–60.PubMedGoogle Scholar
  539. 539.
    Serra S, Chetty R. Revision 2: an immunohistochemical approach and evaluation of solid pseudopapillary tumour of the pancreas. J Clin Pathol. 2008;61(11):1153–9.PubMedGoogle Scholar
  540. 540.
    Zamboni G, Bonetti F, Scarpa A, Pelosi G, Doglioni C, Iannucci A, et al. Expression of progesterone receptors in solid-cystic tumour of the pancreas: a clinicopathological and immunohistochemical study of ten cases. Virchows Arch A Pathol Anat Histopathol. 1993;423(6):425–31.PubMedGoogle Scholar
  541. 541.
    Kunz PL, Reidy-Lagunes D, Anthony LB, Bertino EM, Brendtro K, Chan JA, et al. Consensus guidelines for the management and treatment of neuroendocrine tumors. Pancreas. 2013;42(4):557–77.PubMedPubMedCentralGoogle Scholar
  542. 542.
    Sorbye H, Strosberg J, Baudin E, Klimstra DS, Yao JC. Gastroenteropancreatic high-grade neuroendocrine carcinoma. Cancer. 2014;120(18):2814–23.PubMedGoogle Scholar
  543. 543.
    Zee SY, Hochwald SN, Conlon KC, Brennan MF, Klimstra DS. Pleomorphic pancreatic endocrine neoplasms: a variant commonly confused with adenocarcinoma. Am J Surg Pathol. 2005;29(9):1194–200.PubMedGoogle Scholar
  544. 544.
    Gould VE, Wiedenmann B, Lee I, Schwechheimer K, Dockhorn-Dworniczak B, Radosevich JA, et al. Synaptophysin expression in neuroendocrine neoplasms as determined by immunocytochemistry. Am J Pathol. 1987;126(2):243–57.PubMedPubMedCentralGoogle Scholar
  545. 545.
    Lloyd RV, Mervak T, Schmidt K, Warner TF, Wilson BS. Immunohistochemical detection of chromogranin and neuron-specific enolase in pancreatic endocrine neoplasms. Am J Surg Pathol. 1984;8(8):607–14.PubMedGoogle Scholar
  546. 546.
    Jiao Y, Shi C, Edil BH, de Wilde RF, Klimstra DS, Maitra A, et al. DAXX/ATRX, MEN1, and mTOR pathway genes are frequently altered in pancreatic neuroendocrine tumors. Science. 2011;331(6021):1199–203.PubMedPubMedCentralGoogle Scholar
  547. 547.
    Marinoni I, Kurrer AS, Vassella E, Dettmer M, Rudolph T, Banz V, et al. Loss of DAXX and ATRX are associated with chromosome instability and reduced survival of patients with pancreatic neuroendocrine tumors. Gastroenterology. 2014;146(2):453–60. e5.PubMedGoogle Scholar
  548. 548.
    Reyes CV, Wang T. Undifferentiated small cell carcinoma of the pancreas: a report of five cases. Cancer. 1981;47(10):2500–2.PubMedGoogle Scholar
  549. 549.
    Basturk O, Tang L, Hruban RH, Adsay V, Yang Z, Krasinskas AM, et al. Poorly differentiated neuroendocrine carcinomas of the pancreas: a clinicopathologic analysis of 44 cases. Am J Surg Pathol. 2014;38(4):437–47.PubMedPubMedCentralGoogle Scholar
  550. 550.
    Yachida S, Vakiani E, White CM, Zhong Y, Saunders T, Morgan R, et al. Small cell and large cell neuroendocrine carcinomas of the pancreas are genetically similar and distinct from well-differentiated pancreatic neuroendocrine tumors. Am J Surg Pathol. 2012;36(2):173–84.PubMedPubMedCentralGoogle Scholar
  551. 551.
    Gramlich Tea. In: Mills IS, editor. Histology for pathologists. 3rd ed. Philadelphia: Lippincott Williams and Wilkins; 2007. p. 24.Google Scholar
  552. 552.
    Witkiewicz A, Galler A, Yeo CJ, Gross SD. Gangliocytic paraganglioma: case report and review of the literature. J Gastrointest Surg. 2007;11(10):1351–4.PubMedGoogle Scholar
  553. 553.
    Stringer Mea. In: Standring S, editor. Gray’s anatomy: the anatomical basis of clinical practice. 41st ed. Philadelphia: Elsevier; 2013.Google Scholar
  554. 554.
    Costacurta L. Anatomical and functional aspects of the human suspensory muscle of the duodenum. Acta Anat (Basel). 1972;82(1):34–46.Google Scholar
  555. 555.
    Thompson JS, Langnas AN, Pinch LW, Kaufman S, Quigley EM, Vanderhoof JA. Surgical approach to short-bowel syndrome. Experience in a population of 160 patients. Ann Surg. 1995;222(4):600–5. discussion 5-7.PubMedPubMedCentralGoogle Scholar
  556. 556.
    Marsh MN, Rostami K. What is normal intestinal mucosa? Gastroenterology. 2016;151(5):784–8.PubMedGoogle Scholar
  557. 557.
    Rubin W. The epithelial “membrane” of the small intestine. Am J Clin Nutr. 1971;24(1):45–64.PubMedGoogle Scholar
  558. 558.
    Dobbins WO 3rd. Human intestinal intraepithelial lymphocytes. Gut. 1986;27(8):972–85.PubMedPubMedCentralGoogle Scholar
  559. 559.
    Ferguson A, Murray D. Quantitation of intraepithelial lymphocytes in human jejunum. Gut. 1971;12(12):988–94.PubMedPubMedCentralGoogle Scholar
  560. 560.
    Selby WS, Janossy G, Bofill M, Jewell DP. Lymphocyte subpopulations in the human small intestine. The findings in normal mucosa and in the mucosa of patients with adult coeliac disease. Clin Exp Immunol. 1983;52(1):219–28.PubMedPubMedCentralGoogle Scholar
  561. 561.
    Neugut AI, Jacobson JS, Suh S, Mukherjee R, Arber N. The epidemiology of cancer of the small bowel. Cancer Epidemiol Biomark Prev. 1998;7(3):243–51.Google Scholar
  562. 562.
    Siegel RL, Miller KD, Jemal A. Cancer statistics, 2016. CA Cancer J Clin. 2016;66(1):7–30.Google Scholar
  563. 563.
    Haselkorn T, Whittemore AS, Lilienfeld DE. Incidence of small bowel cancer in the United States and worldwide: geographic, temporal, and racial differences. Cancer Causes Control. 2005;16(7):781–7.PubMedGoogle Scholar
  564. 564.
    Howe JR, Karnell LH, Menck HR, Scott-Conner C. The American College of Surgeons Commission on Cancer and the American Cancer Society. Adenocarcinoma of the small bowel: review of the National Cancer Data Base, 1985-1995. Cancer. 1999;86(12):2693–706.PubMedGoogle Scholar
  565. 565.
    Severson RK, Schenk M, Gurney JG, Weiss LK, Demers RY. Increasing incidence of adenocarcinomas and carcinoid tumors of the small intestine in adults. Cancer Epidemiol Biomark Prev. 1996;5(2):81–4.Google Scholar
  566. 566.
    Bilimoria KY, Bentrem DJ, Wayne JD, Ko CY, Bennett CL, Talamonti MS. Small bowel cancer in the United States: changes in epidemiology, treatment, and survival over the last 20 years. Ann Surg. 2009;249(1):63–71.PubMedGoogle Scholar
  567. 567.
    Bonadona V, Bonaiti B, Olschwang S, Grandjouan S, Huiart L, Longy M, et al. Cancer risks associated with germline mutations in MLH1, MSH2, and MSH6 genes in Lynch syndrome. JAMA. 2011;305(22):2304–10.PubMedGoogle Scholar
  568. 568.
    Wright DH. The major complications of coeliac disease. Baillieres Clin Gastroenterol. 1995;9(2):351–69.PubMedGoogle Scholar
  569. 569.
    Howdle PD, Jalal PK, Holmes GK, Houlston RS. Primary small-bowel malignancy in the UK and its association with coeliac disease. QJM. 2003;96(5):345–53.PubMedGoogle Scholar
  570. 570.
    Wheeler JM, Warren BF, Mortensen NJ, Kim HC, Biddolph SC, Elia G, et al. An insight into the genetic pathway of adenocarcinoma of the small intestine. Gut. 2002;50(2):218–23.PubMedPubMedCentralGoogle Scholar
  571. 571.
    Aparicio T, Svrcek M, Zaanan A, Beohou E, Laforest A, Afchain P, et al. Small bowel adenocarcinoma phenotyping, a clinicobiological prognostic study. Br J Cancer. 2013;109(12):3057–66.PubMedPubMedCentralGoogle Scholar
  572. 572.
    Breuhahn K, Singh S, Schirmacher P, Blaker H. Large-scale N-terminal deletions but not point mutations stabilize beta-catenin in small bowel carcinomas, suggesting divergent molecular pathways of small and large intestinal carcinogenesis. J Pathol. 2008;215(3):300–7.PubMedGoogle Scholar
  573. 573.
    Arai M, Shimizu S, Imai Y, Nakatsuru Y, Oda H, Oohara T, et al. Mutations of the Ki-ras, p53 and APC genes in adenocarcinomas of the human small intestine. Int J Cancer. 1997;70(4):390–5.PubMedGoogle Scholar
  574. 574.
    Blaker H, von Herbay A, Penzel R, Gross S, Otto HF. Genetics of adenocarcinomas of the small intestine: frequent deletions at chromosome 18q and mutations of the SMAD4 gene. Oncogene. 2002;21(1):158–64.PubMedGoogle Scholar
  575. 575.
    Laforest A, Aparicio T, Zaanan A, Silva FP, Didelot A, Desbeaux A, et al. ERBB2 gene as a potential therapeutic target in small bowel adenocarcinoma. Eur J Cancer. 2014;50(10):1740–6.PubMedGoogle Scholar
  576. 576.
    Koornstra JJ. Small bowel endoscopy in familial adenomatous polyposis and Lynch syndrome. Best Pract Res Clin Gastroenterol. 2012;26(3):359–68.PubMedGoogle Scholar
  577. 577.
    Vasen HF, Bulow S, Myrhoj T, Mathus-Vliegen L, Griffioen G, Buskens E, et al. Decision analysis in the management of duodenal adenomatosis in familial adenomatous polyposis. Gut. 1997;40(6):716–9.PubMedPubMedCentralGoogle Scholar
  578. 578.
    Halfdanarson TR, McWilliams RR, Donohue JH, Quevedo JF. A single-institution experience with 491 cases of small bowel adenocarcinoma. Am J Surg. 2010;199(6):797–803.PubMedGoogle Scholar
  579. 579.
    Overman MJ, Pozadzides J, Kopetz S, Wen S, Abbruzzese JL, Wolff RA, et al. Immunophenotype and molecular characterisation of adenocarcinoma of the small intestine. Br J Cancer. 2010;102(1):144–50.PubMedGoogle Scholar
  580. 580.
    Svrcek M, Jourdan F, Sebbagh N, Couvelard A, Chatelain D, Mourra N, et al. Immunohistochemical analysis of adenocarcinoma of the small intestine: a tissue microarray study. J Clin Pathol. 2003;56(12):898–903.PubMedPubMedCentralGoogle Scholar
  581. 581.
    Planck M, Ericson K, Piotrowska Z, Halvarsson B, Rambech E, Nilbert M. Microsatellite instability and expression of MLH1 and MSH2 in carcinomas of the small intestine. Cancer. 2003;97(6):1551–7.PubMedGoogle Scholar
  582. 582.
    Diosdado B, Buffart TE, Watkins R, Carvalho B, Ylstra B, Tijssen M, et al. High-resolution array comparative genomic hybridization in sporadic and celiac disease-related small bowel adenocarcinomas. Clin Cancer Res. 2010;16(5):1391–401.PubMedGoogle Scholar
  583. 583.
    Aparicio T, Zaanan A, Svrcek M, Laurent-Puig P, Carrere N, Manfredi S, et al. Small bowel adenocarcinoma: epidemiology, risk factors, diagnosis and treatment. Dig Liver Dis. 2014;46(2):97–104.PubMedGoogle Scholar
  584. 584.
    Palascak-Juif V, Bouvier AM, Cosnes J, Flourie B, Bouche O, Cadiot G, et al. Small bowel adenocarcinoma in patients with Crohn’s disease compared with small bowel adenocarcinoma de novo. Inflamm Bowel Dis. 2005;11(9):828–32.PubMedGoogle Scholar
  585. 585.
    Askling J, Linet M, Gridley G, Halstensen TS, Ekstrom K, Ekbom A. Cancer incidence in a population-based cohort of individuals hospitalized with celiac disease or dermatitis herpetiformis. Gastroenterology. 2002;123(5):1428–35.PubMedGoogle Scholar
  586. 586.
    Green PH, Fleischauer AT, Bhagat G, Goyal R, Jabri B, Neugut AI. Risk of malignancy in patients with celiac disease. Am J Med. 2003;115(3):191–5.PubMedGoogle Scholar
  587. 587.
    Talamonti MS, Goetz LH, Rao S, Joehl RJ. Primary cancers of the small bowel: analysis of prognostic factors and results of surgical management. Arch Surg. 2002;137(5):564–70. discussion 70-1.PubMedGoogle Scholar
  588. 588.
    Masselli G, Polettini E, Casciani E, Bertini L, Vecchioli A, Gualdi G. Small-bowel neoplasms: prospective evaluation of MR enteroclysis. Radiology. 2009;251(3):743–50.PubMedGoogle Scholar
  589. 589.
    Ross A, Mehdizadeh S, Tokar J, Leighton JA, Kamal A, Chen A, et al. Double balloon enteroscopy detects small bowel mass lesions missed by capsule endoscopy. Dig Dis Sci. 2008;53(8):2140–3.PubMedGoogle Scholar
  590. 590.
    Fischer HP, Zhou H. Pathogenesis of carcinoma of the papilla of Vater. J Hepato-Biliary-Pancreat Surg. 2004;11(5):301–9.Google Scholar
  591. 591.
    Law JK. New developments in small bowel enteroscopy. Curr Opin Gastroenterol. 2016;32:387.PubMedGoogle Scholar
  592. 592.
    Saurin JC, Pilleul F, Soussan EB, Maniere T, D'Halluin PN, Gaudric M, et al. Small-bowel capsule endoscopy diagnoses early and advanced neoplasms in asymptomatic patients with lynch syndrome. Endoscopy. 2010;42(12):1057–62.PubMedGoogle Scholar
  593. 593.
    Standards of Practice C, Adler DG, Qureshi W, Davila R, Gan SI, Lichtenstein D, et al. The role of endoscopy in ampullary and duodenal adenomas. Gastrointest Endosc. 2006;64(6):849–54.Google Scholar
  594. 594.
    Meneghetti AT, Safadi B, Stewart L, Way LW. Local resection of ampullary tumors. J Gastrointest Surg. 2005;9(9):1300–6.PubMedGoogle Scholar
  595. 595.
    Zadorova Z, Dvofak M, Hajer J. Endoscopic therapy of benign tumors of the papilla of Vater. Endoscopy. 2001;33(4):345–7.PubMedGoogle Scholar
  596. 596.
    Zhang MQ, Lin F, Hui P, Chen ZM, Ritter JH, Wang HL. Expression of mucins, SIMA, villin, and CDX2 in small-intestinal adenocarcinoma. Am J Clin Pathol. 2007;128(5):808–16.PubMedGoogle Scholar
  597. 597.
    Chen ZM, Ritter JH, Wang HL. Differential expression of alpha-methylacyl coenzyme A racemase in adenocarcinomas of the small and large intestines. Am J Surg Pathol. 2005;29(7):890–6.PubMedGoogle Scholar
  598. 598.
    Fang JY, Richardson BC. The MAPK signalling pathways and colorectal cancer. Lancet Oncol. 2005;6(5):322–7.PubMedGoogle Scholar
  599. 599.
    Benvenuti S, Sartore-Bianchi A, Di Nicolantonio F, Zanon C, Moroni M, Veronese S, et al. Oncogenic activation of the RAS/RAF signaling pathway impairs the response of metastatic colorectal cancers to anti-epidermal growth factor receptor antibody therapies. Cancer Res. 2007;67(6):2643–8.PubMedGoogle Scholar
  600. 600.
    Di Nicolantonio F, Martini M, Molinari F, Sartore-Bianchi A, Arena S, Saletti P, et al. Wild-type BRAF is required for response to panitumumab or cetuximab in metastatic colorectal cancer. J Clin Oncol. 2008;26(35):5705–12.PubMedGoogle Scholar
  601. 601.
    Allegra CJ, Rumble RB, Schilsky RL. Extended RAS gene mutation testing in metastatic colorectal carcinoma to predict response to anti-epidermal growth factor receptor monoclonal antibody therapy: American Society of Clinical Oncology provisional clinical opinion update 2015 summary. J Oncol Pract. 2016;12(2):180–1.PubMedGoogle Scholar
  602. 602.
    Cancer AJCO. AJCC cancer staging manual. 8th ed. Chicago: Springer; 2016.Google Scholar
  603. 603.
    Bakaeen FG, Murr MM, Sarr MG, Thompson GB, Farnell MB, Nagorney DM, et al. What prognostic factors are important in duodenal adenocarcinoma? Arch Surg. 2000;135(6):635–41. discussion 41-2.PubMedGoogle Scholar
  604. 604.
    Howe JR, Klimstra DS, Moccia RD, Conlon KC, Brennan MF. Factors predictive of survival in ampullary carcinoma. Ann Surg. 1998;228(1):87–94.PubMedPubMedCentralGoogle Scholar
  605. 605.
    Kimura W, Futakawa N, Zhao B. Neoplastic diseases of the papilla of Vater. J Hepato-Biliary-Pancreat Surg. 2004;11(4):223–31.Google Scholar
  606. 606.
    He J, Ahuja N, Makary MA, Cameron JL, Eckhauser FE, Choti MA, et al. 2564 resected periampullary adenocarcinomas at a single institution: trends over three decades. HPB (Oxford). 2014;16(1):83–90.Google Scholar
  607. 607.
    Chen SC, Shyr YM, Wang SE. Longterm survival after pancreaticoduodenectomy for periampullary adenocarcinomas. HPB (Oxford). 2013;15(12):951–7.Google Scholar
  608. 608.
    Chandrasegaram MD, Chiam SC, Chen JW, Khalid A, Mittinty ML, Neo EL, et al. Distribution and pathological features of pancreatic, ampullary, biliary and duodenal cancers resected with pancreaticoduodenectomy. World J Surg Oncol. 2015;13:85.PubMedPubMedCentralGoogle Scholar
  609. 609.
    Sperti C, Pasquali C, Piccoli A, Sernagiotto C, Pedrazzoli S. Radical resection for ampullary carcinoma: long-term results. Br J Surg. 1994;81(5):668–71.PubMedGoogle Scholar
  610. 610.
    Talamini MA, Moesinger RC, Pitt HA, Sohn TA, Hruban RH, Lillemoe KD, et al. Adenocarcinoma of the ampulla of Vater. A 28-year experience. Ann Surg. 1997;225(5):590–9. discussion 9-600.PubMedPubMedCentralGoogle Scholar
  611. 611.
    Yeo CJ, Cameron JL, Sohn TA, Lillemoe KD, Pitt HA, Talamini MA, et al. Six hundred fifty consecutive pancreaticoduodenectomies in the 1990s: pathology, complications, and outcomes. Ann Surg. 1997;226(3):248–57. discussion 57-60.PubMedPubMedCentralGoogle Scholar
  612. 612.
    Bouvet M, Gamagami RA, Gilpin EA, Romeo O, Sasson A, Easter DW, et al. Factors influencing survival after resection for periampullary neoplasms. Am J Surg. 2000;180(1):13–7.PubMedGoogle Scholar
  613. 613.
    Chang MC, Chang YT, Tien YW, Sun CT, Wu MS, Lin JT. Distinct chromosomal aberrations of ampulla of Vater and pancreatic head cancers detected by laser capture microdissection and comparative genomic hybridization. Oncol Rep. 2005;14(4):867–72.PubMedGoogle Scholar
  614. 614.
    Ohike N, Kim GE, Tajiri T, Krasinskas A, Basturk O, Coban I, et al. Intra-ampullary papillary-tubular neoplasm (IAPN): characterization of tumoral intraepithelial neoplasia occurring within the ampulla: a clinicopathologic analysis of 82 cases. Am J Surg Pathol. 2010;34(12):1731–48.PubMedPubMedCentralGoogle Scholar
  615. 615.
    Adsay V, Ohike N, Tajiri T, Kim GE, Krasinskas A, Balci S, et al. Ampullary region carcinomas: definition and site specific classification with delineation of four clinicopathologically and prognostically distinct subsets in an analysis of 249 cases. Am J Surg Pathol. 2012;36(11):1592–608.PubMedGoogle Scholar
  616. 616.
    Reid MD, Balci S, Ohike N, Xue Y, Kim GE, Tajiri T, et al. Ampullary carcinoma is often of mixed or hybrid histologic type: an analysis of reproducibility and clinical relevance of classification as pancreatobiliary versus intestinal in 232 cases. Mod Pathol. 2016;29(12):1575–85.PubMedGoogle Scholar
  617. 617.
    Cancer IAfRo. In: Bosman FT, editor. WHO classification of tumors of the digestive system. 4th ed. Lyon: IARC Press; 2010.Google Scholar
  618. 618.
    Chen YY, Li AF, Huang KH, Lan YT, Chen MH, Chao Y, et al. Adenosquamous carcinoma of the stomach and review of the literature. Pathol Oncol Res. 2015;21(3):547–51.PubMedGoogle Scholar
  619. 619.
    Komatsu H, Egawa S, Motoi F, Morikawa T, Sakata N, Naitoh T, et al. Clinicopathological features and surgical outcomes of adenosquamous carcinoma of the pancreas: a retrospective analysis of patients with resectable stage tumors. Surg Today. 2015;45(3):297–304.PubMedGoogle Scholar
  620. 620.
    Masoomi H, Ziogas A, Lin BS, Barleben A, Mills S, Stamos MJ, et al. Population-based evaluation of adenosquamous carcinoma of the colon and rectum. Dis Colon Rectum. 2012;55(5):509–14.PubMedPubMedCentralGoogle Scholar
  621. 621.
    Sreenarasimhaiah J, Hoang MP. Esophageal squamous cell carcinoma with metastasis to the ampulla. Gastrointest Endosc. 2005;62(2):310–1. discussion 1.PubMedGoogle Scholar
  622. 622.
    Lee TH, Park SH, Lee CK, Lee SH, Chung IK, Kim SJ, et al. Ampulla of Vater metastasis from recurrent uterine cervix carcinoma presenting as groove pancreatitis. Gastrointest Endosc. 2011;73(2):362–3.PubMedGoogle Scholar
  623. 623.
    Buyukcelik A, Ensari A, Sarioglu M, Isikdogan A, Icli F. Squamous cell carcinoma of the larynx metastasized to the ampulla of Vater. Report of a case. Tumori. 2003;89(2):199–201.PubMedGoogle Scholar
  624. 624.
    Murakami T, Yao T, Mitomi H, Morimoto T, Ueyama H, Matsumoto K, et al. Clinicopathologic and immunohistochemical characteristics of gastric adenocarcinoma with enteroblastic differentiation: a study of 29 cases. Gastric Cancer. 2016;19(2):498–507.PubMedGoogle Scholar
  625. 625.
    Gardiner GW, Lajoie G, Keith R. Hepatoid adenocarcinoma of the papilla of Vater. Histopathology. 1992;20(6):541–4.PubMedGoogle Scholar
  626. 626.
    Sato Y, Tominaga H, Tangoku A, Hamanaka Y, Yamashita Y, Suzuki T. Alpha-fetoprotein-producing cancer of the ampulla of Vater. Hepato-Gastroenterology. 1992;39(6):566–9.PubMedGoogle Scholar
  627. 627.
    Sakamoto K, Watanabe M, De La Cruz C, Honda H, Ise H, Mitsui K, et al. Primary invasive micropapillary carcinoma of the colon. Histopathology. 2005;47(5):479–84.PubMedGoogle Scholar
  628. 628.
    De la Cruz C, Moriya T, Endoh M, Watanabe M, Takeyama J, Yang M, et al. Invasive micropapillary carcinoma of the breast: clinicopathological and immunohistochemical study. Pathol Int. 2004;54(2):90–6.PubMedGoogle Scholar
  629. 629.
    Michal M, Skalova A, Mukensnabl P. Micropapillary carcinoma of the parotid gland arising in mucinous cystadenoma. Virchows Arch. 2000;437(4):465–8.PubMedGoogle Scholar
  630. 630.
    Amin MB, Tamboli P, Merchant SH, Ordonez NG, Ro J, Ayala AG, et al. Micropapillary component in lung adenocarcinoma: a distinctive histologic feature with possible prognostic significance. Am J Surg Pathol. 2002;26(3):358–64.PubMedGoogle Scholar
  631. 631.
    Roh JH, Srivastava A, Lauwers GY, An J, Jang KT, Park CK, et al. Micropapillary carcinoma of stomach: a clinicopathologic and immunohistochemical study of 11 cases. Am J Surg Pathol. 2010;34(8):1139–46.PubMedGoogle Scholar
  632. 632.
    Khayyata S, Basturk O, Adsay NV. Invasive micropapillary carcinomas of the ampullo-pancreatobiliary region and their association with tumor-infiltrating neutrophils. Mod Pathol. 2005;18(11):1504–11.PubMedGoogle Scholar
  633. 633.
    Fujita T, Konishi M, Gotohda N, Takahashi S, Nakagohri T, Kojima M, et al. Invasive micropapillary carcinoma of the ampulla of Vater with extensive lymph node metastasis: report of a case. Surg Today. 2010;40(12):1197–200.PubMedGoogle Scholar
  634. 634.
    Nassar H, Pansare V, Zhang H, Che M, Sakr W, Ali-Fehmi R, et al. Pathogenesis of invasive micropapillary carcinoma: role of MUC1 glycoprotein. Mod Pathol. 2004;17(9):1045–50.PubMedGoogle Scholar
  635. 635.
    Lee JH, Kim JH, Choi JW, Kim YS. The presence of a micropapillary component predicts aggressive behaviour in early and advanced gastric adenocarcinomas. Pathology. 2010;42(6):560–3.PubMedGoogle Scholar
  636. 636.
    McQuitty E, Ro JY, Truong LD, Shen SS, Zhai Q, Ayala AG. Lymphovascular invasion in micropapillary urothelial carcinoma: a study of 22 cases. Arch Pathol Lab Med. 2012;136(6):635–9.PubMedGoogle Scholar
  637. 637.
    Terada T. Primary signet-ring cell carcinoma of the ampulla of Vater: a case report with an immunohistochemical study. Appl Immunohistochem Mol Morphol. 2012;20(4):427–8.PubMedGoogle Scholar
  638. 638.
    Wakasugi M, Tanemura M, Furukawa K, Murata M, Miyazaki M, Oshita M, et al. Signet ring cell carcinoma of the ampulla of vater: Report of a case and a review of the literature. Int J Surg Case Rep. 2015;12:108–11.PubMedPubMedCentralGoogle Scholar
  639. 639.
    Molberg KH, Heffess C, Delgado R, Albores-Saavedra J. Undifferentiated carcinoma with osteoclast-like giant cells of the pancreas and periampullary region. Cancer. 1998;82(7):1279–87.PubMedGoogle Scholar
  640. 640.
    Hechtman JF, Liu W, Sadowska J, Zhen L, Borsu L, Arcila ME, et al. Sequencing of 279 cancer genes in ampullary carcinoma reveals trends relating to histologic subtypes and frequent amplification and overexpression of ERBB2 (HER2). Mod Pathol. 2015;28(8):1123–9.PubMedPubMedCentralGoogle Scholar
  641. 641.
    Nakai T, Koh K, Kawabe T, Son E, Yoshikawa H, Yasutomi M. Importance of microperineural invasion as a prognostic factor in ampullary carcinoma. Br J Surg. 1997;84(10):1399–401.PubMedGoogle Scholar
  642. 642.
    Willett CG, Warshaw AL, Convery K, Compton CC. Patterns of failure after pancreaticoduodenectomy for ampullary carcinoma. Surg Gynecol Obstet. 1993;176(1):33–8.PubMedGoogle Scholar
  643. 643.
    Klimstra DS, Modlin IR, Coppola D, Lloyd RV, Suster S. The pathologic classification of neuroendocrine tumors: a review of nomenclature, grading, and staging systems. Pancreas. 2010;39(6):707–12.PubMedGoogle Scholar
  644. 644.
    Pavel M, Baudin E, Couvelard A, Krenning E, Oberg K, Steinmuller T, et al. ENETS Consensus Guidelines for the management of patients with liver and other distant metastases from neuroendocrine neoplasms of foregut, midgut, hindgut, and unknown primary. Neuroendocrinology. 2012;95(2):157–76.PubMedGoogle Scholar
  645. 645.
    Vinik AI, Woltering EA, Warner RR, Caplin M, O'Dorisio TM, Wiseman GA, et al. NANETS consensus guidelines for the diagnosis of neuroendocrine tumor. Pancreas. 2010;39(6):713–34.PubMedGoogle Scholar
  646. 646.
    Vinik AI, Anthony L, Boudreaux JP, Go VL, O’Dorisio TM, Ruszniewski P, et al. Neuroendocrine tumors: a critical appraisal of management strategies. Pancreas. 2010;39(6):801–18.PubMedGoogle Scholar
  647. 647.
    Brenner B, Shah MA, Gonen M, Klimstra DS, Shia J, Kelsen DP. Small-cell carcinoma of the gastrointestinal tract: a retrospective study of 64 cases. Br J Cancer. 2004;90(9):1720–6.PubMedPubMedCentralGoogle Scholar
  648. 648.
    Van Landingham SB, Kluppel S, Symmonds R Jr, Snyder SK. Coexisting carcinoid tumor and Crohn’s disease. J Surg Oncol. 1983;24(4):310–4.PubMedGoogle Scholar
  649. 649.
    Moyana TN, Shukoor S. Gastrointestinal endocrine cell hyperplasia in celiac disease: a selective proliferative process of serotonergic cells. Mod Pathol. 1991;4(4):419–23.PubMedGoogle Scholar
  650. 650.
    Di Sabatino A, Giuffrida P, Vanoli A, Luinetti O, Manca R, Biancheri P, et al. Increase in neuroendocrine cells in the duodenal mucosa of patients with refractory celiac disease. Am J Gastroenterol. 2014;109(2):258–69.PubMedGoogle Scholar
  651. 651.
    Anlauf M, Garbrecht N, Henopp T, Schmitt A, Schlenger R, Raffel A, et al. Sporadic versus hereditary gastrinomas of the duodenum and pancreas: distinct clinico-pathological and epidemiological features. World J Gastroenterol. 2006;12(34):5440–6.PubMedPubMedCentralGoogle Scholar
  652. 652.
    Anlauf M, Perren A, Henopp T, Rudolf T, Garbrecht N, Schmitt A, et al. Allelic deletion of the MEN1 gene in duodenal gastrin and somatostatin cell neoplasms and their precursor lesions. Gut. 2007;56(5):637–44.PubMedPubMedCentralGoogle Scholar
  653. 653.
    Perren A, Anlauf M, Henopp T, Rudolph T, Schmitt A, Raffel A, et al. Multiple endocrine neoplasia type 1 (MEN1): loss of one MEN1 allele in tumors and monohormonal endocrine cell clusters but not in islet hyperplasia of the pancreas. J Clin Endocrinol Metab. 2007;92(3):1118–28.PubMedGoogle Scholar
  654. 654.
    Anlauf M, Perren A, Meyer CL, Schmid S, Saremaslani P, Kruse ML, et al. Precursor lesions in patients with multiple endocrine neoplasia type 1-associated duodenal gastrinomas. Gastroenterology. 2005;128(5):1187–98.PubMedGoogle Scholar
  655. 655.
    Kloppel G, Anlauf M, Perren A. Endocrine precursor lesions of gastroenteropancreatic neuroendocrine tumors. Endocr Pathol. 2007;18(3):150–5.PubMedGoogle Scholar
  656. 656.
    Feldman JM. Urinary serotonin in the diagnosis of carcinoid tumors. Clin Chem. 1986;32(5):840–4.PubMedGoogle Scholar
  657. 657.
    Feldman JM. Increased dopamine production in patients with carcinoid tumors. Metabolism. 1985;34(3):255–60.PubMedGoogle Scholar
  658. 658.
    Alumets J, Hakanson R, Ingemansson S, Sundler F. Substance P and 5-HT in granules isolated from an intestinal argentaffin carcinoid. Histochemistry. 1977;52(3):217–22.PubMedGoogle Scholar
  659. 659.
    Oates JA, Pettinger WA, Doctor RB. Evidence for the release of bradykinin in carcinoid syndrome. J Clin Invest. 1966;45(2):173–8.PubMedPubMedCentralGoogle Scholar
  660. 660.
    Theodorsson-Norheim E, Norheim I, Oberg K, Brodin E, Lundberg JM, Tatemoto K, et al. Neuropeptide K: a major tachykinin in plasma and tumor tissues from carcinoid patients. Biochem Biophys Res Commun. 1985;131(1):77–83.PubMedGoogle Scholar
  661. 661.
    Lucas KJ, Feldman JM. Flushing in the carcinoid syndrome and plasma kallikrein. Cancer. 1986;58(10):2290–3.PubMedGoogle Scholar
  662. 662.
    Klimstra DS, Modlin IR, Adsay NV, Chetty R, Deshpande V, Gonen M, et al. Pathology reporting of neuroendocrine tumors: application of the Delphic consensus process to the development of a minimum pathology data set. Am J Surg Pathol. 2010;34(3):300–13.PubMedGoogle Scholar
  663. 663.
    Debas HT, Soon-Shiong P, McKenzie AD, Bogoch A, Greig JH, Dunn WL, et al. Use of secretin in the roentgenologic and biochemical diagnosis of duodenal gastrinoma. Am J Surg. 1983;145(3):408–11.PubMedGoogle Scholar
  664. 664.
    Passaro E Jr, Howard TJ, Sawicki MP, Watt PC, Stabile BE. The origin of sporadic gastrinomas within the gastrinoma triangle: a theory. Arch Surg. 1998;133(1):13–6. discussion 7.PubMedGoogle Scholar
  665. 665.
    Deveney CW, Deveney KE, Stark D, Moss A, Stein S, Way LW. Resection of gastrinomas. Ann Surg. 1983;198(4):546–53.PubMedPubMedCentralGoogle Scholar
  666. 666.
    Friesen SR. The development of endocrinopathies in the prospective screening of two families with multiple endocrine adenopathy, type I. World J Surg. 1979;3(6):753–64.PubMedGoogle Scholar
  667. 667.
    Friesen SR. Update on the diagnosis and treatment of rare neuroendocrine tumors. Surg Clin North Am. 1987;67(2):379–93.PubMedGoogle Scholar
  668. 668.
    Perry RR, Feliberti E, Vinik A. Gastrinoma Zollinger-Ellison-Syndrome. In: De Groot LJ, Chrousos G, Dungan K, Feingold KR, Grossman A, Hershman JM, et al., editors. Endotext. South Dartmouth:; 2000.Google Scholar
  669. 669.
    Kulke MH, Shah MH, Benson AB 3rd, Bergsland E, Berlin JD, Blaszkowsky LS, et al. Neuroendocrine tumors, version 1.2015. J Natl Compr Cancer Netw. 2015;13(1):78–108.Google Scholar
  670. 670.
    Zollinger RM. Gastrinoma: factors influencing prognosis. Surgery. 1985;97(1):49–54.PubMedGoogle Scholar
  671. 671.
    Stabile BE, Passaro E Jr. Benign and malignant gastrinoma. Am J Surg. 1985;149(1):144–50.PubMedGoogle Scholar
  672. 672.
    Maton PN, Vinayek R, Frucht H, McArthur KA, Miller LS, Saeed ZA, et al. Long-term efficacy and safety of omeprazole in patients with Zollinger-Ellison syndrome: a prospective study. Gastroenterology. 1989;97(4):827–36.PubMedGoogle Scholar
  673. 673.
    Yu F, Venzon DJ, Serrano J, Goebel SU, Doppman JL, Gibril F, et al. Prospective study of the clinical course, prognostic factors, causes of death, and survival in patients with long-standing Zollinger-Ellison syndrome. J Clin Oncol. 1999;17(2):615–30.PubMedGoogle Scholar
  674. 674.
    Barreras RF, Mack E, Goodfriend T, Damm M. Resection of gastrinoma in the Zollinger-Ellison syndrome. Gastroenterology. 1982;82(5 Pt 1):953–6.PubMedGoogle Scholar
  675. 675.
    Kloppel G, Anlauf M. Epidemiology, tumour biology and histopathological classification of neuroendocrine tumours of the gastrointestinal tract. Best Pract Res Clin Gastroenterol. 2005;19(4):507–17.PubMedGoogle Scholar
  676. 676.
    Krejs GJ, Orci L, Conlon JM, Ravazzola M, Davis GR, Raskin P, et al. Somatostatinoma syndrome. Biochemical, morphologic and clinical features. N Engl J Med. 1979;301(6):285–92.PubMedGoogle Scholar
  677. 677.
    Ganda OP, Weir GC, Soeldner JS, Legg MA, Chick WL, Patel YC, et al. “Somatostatinoma”: a somatostatin-containing tumor of the endocrine pancreas. N Engl J Med. 1977;296(17):963–7.PubMedGoogle Scholar
  678. 678.
    Garbrecht N, Anlauf M, Schmitt A, Henopp T, Sipos B, Raffel A, et al. Somatostatin-producing neuroendocrine tumors of the duodenum and pancreas: incidence, types, biological behavior, association with inherited syndromes, and functional activity. Endocr Relat Cancer. 2008;15(1):229–41.PubMedGoogle Scholar
  679. 679.
    Crain EL Jr, Thorn GW. Functioning pancreatic islet cell adenomas; a review of the literature and presentation of two new differential tests. Medicine (Baltimore). 1949;28(4):427–47.Google Scholar
  680. 680.
    Suzuki H, Kuwano H, Masuda N, Hashimoto S, Kanoh K, Nomoto K, et al. Diagnostic usefulness of FDG-PET for malignant somatostatinoma of the pancreas. Hepato-Gastroenterology. 2008;55(85):1242–5.PubMedGoogle Scholar
  681. 681.
    Luna IE, Monrad N, Binderup T, Boisen Thoegersen C, Hilsted L, Jensen C, et al. Somatostatin-immunoreactive pancreaticoduodenal neuroendocrine neoplasms: twenty-three cases evaluated according to the WHO 2010 classification. Neuroendocrinology. 2016;103(5):567–77.PubMedGoogle Scholar
  682. 682.
    Tanaka S, Yamasaki S, Matsushita H, Ozawa Y, Kurosaki A, Takeuchi K, et al. Duodenal somatostatinoma: a case report and review of 31 cases with special reference to the relationship between tumor size and metastasis. Pathol Int. 2000;50(2):146–52.PubMedGoogle Scholar
  683. 683.
    Vinik A, Feliberti E, Perry RR. Somatostatinoma. In: De Groot LJ, Chrousos G, Dungan K, Feingold KR, Grossman A, Hershman JM, et al., editors. Endotext. South Dartmouth:; 2000.Google Scholar
  684. 684.
    Angeletti S, Corleto VD, Schillaci O, Marignani M, Annibale B, Moretti A, et al. Use of the somatostatin analogue octreotide to localise and manage somatostatin-producing tumours. Gut. 1998;42(6):792–4.PubMedPubMedCentralGoogle Scholar
  685. 685.
    Gonzalez RS, Liu EH, Alvarez JR, Ayers GD, Washington MK, Shi C. Should mesenteric tumor deposits be included in staging of well-differentiated small intestine neuroendocrine tumors? Mod Pathol. 2014;27(9):1288–95.PubMedPubMedCentralGoogle Scholar
  686. 686.
    Norlen O, Stalberg P, Oberg K, Eriksson J, Hedberg J, Hessman O, et al. Long-term results of surgery for small intestinal neuroendocrine tumors at a tertiary referral center. World J Surg. 2012;36(6):1419–31.PubMedGoogle Scholar
  687. 687.
    Akerstrom G, Makridis C, Johansson H. Abdominal surgery in patients with midgut carcinoid tumors. Acta Oncol. 1991;30(4):547–53.PubMedGoogle Scholar
  688. 688.
    Arnold R, Muller H, Schade-Brittinger C, Rinke A, Klose K, Barth P, et al. Placebo-controlled, double-blind, prospective, randomized study of the effect of octreotide LAR in the control of tumor growth in patients with metastatic neuroendocrine midgut tumors: a report from the PROMID study group. J Clin Oncol. 2009;27(15_suppl):4508.Google Scholar
  689. 689.
    Kvols LK, Oberg KE, O'Dorisio TM, Mohideen P, de Herder WW, Arnold R, et al. Pasireotide (SOM230) shows efficacy and tolerability in the treatment of patients with advanced neuroendocrine tumors refractory or resistant to octreotide LAR: results from a phase II study. Endocr Relat Cancer. 2012;19(5):657–66.PubMedGoogle Scholar
  690. 690.
    Yao JC, Fazio N, Singh S, Buzzoni R, Carnaghi C, Wolin E, et al. Everolimus for the treatment of advanced, non-functional neuroendocrine tumours of the lung or gastrointestinal tract (RADIANT-4): a randomised, placebo-controlled, phase 3 study. Lancet. 2016;387(10022):968–77.PubMedGoogle Scholar
  691. 691.
    Okubo Y, Yokose T, Motohashi O, Miyagi Y, Yoshioka E, Suzuki M, et al. Duodenal rare neuroendocrine tumor: clinicopathological characteristics of patients with gangliocytic paraganglioma. Gastroenterol Res Pract. 2016;2016:5257312.PubMedPubMedCentralGoogle Scholar
  692. 692.
    Park HK, Han HS. Duodenal gangliocytic paraganglioma with lymph node metastasis. Arch Pathol Lab Med. 2016;140(1):94–8.PubMedPubMedCentralGoogle Scholar
  693. 693.
    Okubo Y, Wakayama M, Nemoto T, Kitahara K, Nakayama H, Shibuya K, et al. Literature survey on epidemiology and pathology of gangliocytic paraganglioma. BMC Cancer. 2011;11:187.PubMedPubMedCentralGoogle Scholar
  694. 694.
    Mann CM, Bramhall SR, Buckels JA, Taniere P. An unusual case of duodenal obstruction-gangliocytic paraganglioma. J Hepato-Biliary-Pancreat Surg. 2009;16(4):562–5.Google Scholar
  695. 695.
    Tomic S, Warner T. Pancreatic somatostatin-secreting gangliocytic paraganglioma with lymph node metastases. Am J Gastroenterol. 1996;91(3):607–8.PubMedGoogle Scholar
  696. 696.
    Netter FH. Atlas of human anatomy. 4th ed. Philadelphia: Saunders/Elsevier; 2006. p. 548. 47 p.Google Scholar
  697. 697.
    Mills SE, editor. Histology for pathologists. 4th ed. Philadelphia: Lippincott Williams & Wilkins; 2012.Google Scholar
  698. 698.
    Shamsuddin AM, Phelps PC, Trump BF. Human large intestinal epithelium: light microscopy, histochemistry, and ultrastructure. Hum Pathol. 1982;13(9):790–803.PubMedGoogle Scholar
  699. 699.
    Cheng H, Leblond CP. Origin, differentiation and renewal of the four main epithelial cell types in the mouse small intestine. V. Unitarian theory of the origin of the four epithelial cell types. Am J Anat. 1974;141(4):537–61.PubMedGoogle Scholar
  700. 700.
    Ramachandran A, Madesh M, Balasubramanian KA. Apoptosis in the intestinal epithelium: its relevance in normal and pathophysiological conditions. J Gastroenterol Hepatol. 2000;15(2):109–20.PubMedGoogle Scholar
  701. 701.
    Merker SR, Weitz J, Stange DE. Gastrointestinal organoids: how they gut it out. Dev Biol. 2016;420(2):239–50.PubMedGoogle Scholar
  702. 702.
    He XC, Zhang J, Tong WG, Tawfik O, Ross J, Scoville DH, et al. BMP signaling inhibits intestinal stem cell self-renewal through suppression of Wnt-beta-catenin signaling. Nat Genet. 2004;36(10):1117–21.PubMedGoogle Scholar
  703. 703.
    Symonds DA. Paneth cell metaplasia in diseases of the colon and rectum. Arch Pathol. 1974;97(6):343–7.PubMedGoogle Scholar
  704. 704.
    Donnellan WL. The structure of the colonic mucosa. The epithelium and subepithelial reticulohistiocytic complex. Gastroenterology. 1965;49(5):496–514.PubMedGoogle Scholar
  705. 705.
    Watanabe H, Margulis AR, Harter L. The occurrence of lymphoid nodules in the colon of adults. J Clin Gastroenterol. 1983;5(6):535–9.PubMedGoogle Scholar
  706. 706.
    Azzopardi JG, Evans DJ. Mucoprotein-containing histiocytes (muciphages) in the rectum. J Clin Pathol. 1966;19(4):368–74.PubMedPubMedCentralGoogle Scholar
  707. 707.
    Bethesda, MD: National Cancer Institute; 2017. pp. 1–6, updated November 2016. Available from:
  708. 708.
    Cancer facts and figures London, England: World Cancer Research Fund International; Available from:
  709. 709.
    Cancer Incidence and Mortality Worldwide: IARC CancerBase No.11 [Internet] Lyon, France: International Agency for Research on Cancer; 2013 [Version 1.0]: Available from:
  710. 710.
    Lee YC, Lee YL, Chuang JP, Lee JC. Differences in survival between colon and rectal cancer from SEER data. PLoS One. 2013;8(11):e78709.PubMedPubMedCentralGoogle Scholar
  711. 711.
    Siegel RL, Miller KD, Jemal A. Cancer statistics, 2017. CA Cancer J Clin. 2017;67(1):7–30.PubMedPubMedCentralGoogle Scholar
  712. 712.
    Siegel RL, Fedewa SA, Anderson WF, Miller KD, Ma J, Rosenberg PS, et al. Colorectal cancer incidence patterns in the United States, 1974–2013. J Natl Cancer Inst. 2017;109(8)Google Scholar
  713. 713.
    Ballester V, Rashtak S, Boardman L. Clinical and molecular features of young-onset colorectal cancer. World J Gastroenterol. 2016;22(5):1736–44.PubMedPubMedCentralGoogle Scholar
  714. 714.
    Ahnen DJ, Wade SW, Jones WF, Sifri R, Mendoza Silveiras J, Greenamyer J, et al. The increasing incidence of young-onset colorectal cancer: a call to action. Mayo Clin Proc. 2014;89(2):216–24.PubMedGoogle Scholar
  715. 715.
    Astin M, Griffin T, Neal RD, Rose P, Hamilton W. The diagnostic value of symptoms for colorectal cancer in primary care: a systematic review. Br J Gen Pract. 2011;61(586):e231–43.PubMedPubMedCentralGoogle Scholar
  716. 716.
    Turati F, Bravi F, Di Maso M, Bosetti C, Polesel J, Serraino D, et al. Adherence to the World Cancer Research Fund/American Institute for Cancer Research recommendations and colorectal cancer risk. Eur J Cancer. 2017;85:86–94.PubMedGoogle Scholar
  717. 717.
    Shaukat A, Dostal A, Menk J, Church TR. BMI is a risk factor for colorectal cancer mortality. Dig Dis Sci. 2017;62(9):2511–7.PubMedGoogle Scholar
  718. 718.
    Ferrari P, Jenab M, Norat T, Moskal A, Slimani N, Olsen A, et al. Lifetime and baseline alcohol intake and risk of colon and rectal cancers in the European prospective investigation into cancer and nutrition (EPIC). Int J Cancer. 2007;121(9):2065–72.PubMedGoogle Scholar
  719. 719.
    Chang LC, Wu MS, Tu CH, Lee YC, Shun CT, Chiu HM. Metabolic syndrome and smoking may justify earlier colorectal cancer screening in men. Gastrointest Endosc. 2014;79(6):961–9.PubMedGoogle Scholar
  720. 720.
    Schmid D, Behrens G, Matthews CE, Leitzmann MF. Physical activity and risk of colon cancer in diabetic and nondiabetic US adults. Mayo Clin Proc. 2016;91(12):1693–705.PubMedGoogle Scholar
  721. 721.
    Solomon BL, Whitman T, Wood ME. Contribution of extended family history in assessment of risk for breast and colon cancer. BMC Fam Pract. 2016;17(1):126.PubMedPubMedCentralGoogle Scholar
  722. 722.
    Fuchs CS, Giovannucci EL, Colditz GA, Hunter DJ, Speizer FE, Willett WC. A prospective study of family history and the risk of colorectal cancer. N Engl J Med. 1994;331(25):1669–74.PubMedGoogle Scholar
  723. 723.
    Montazeri Z, Theodoratou E, Nyiraneza C, Timofeeva M, Chen W, Svinti V, et al. Systematic meta-analyses and field synopsis of genetic association studies in colorectal adenomas. Int J Epidemiol. 2016;45(1):186–205.PubMedGoogle Scholar
  724. 724.
    Tarraga Lopez PJ, Albero JS, Rodriguez-Montes JA. Primary and secondary prevention of colorectal cancer. Clin Med Insights Gastroenterol. 2014;7:33–46.PubMedPubMedCentralGoogle Scholar
  725. 725.
    Cole BF, Logan RF, Halabi S, Benamouzig R, Sandler RS, Grainge MJ, et al. Aspirin for the chemoprevention of colorectal adenomas: meta-analysis of the randomized trials. J Natl Cancer Inst. 2009;101(4):256–66.PubMedPubMedCentralGoogle Scholar
  726. 726.
    Bae JM, Kim JH, Kang GH. Molecular subtypes of colorectal cancer and their clinicopathologic features, with an emphasis on the serrated neoplasia pathway. Arch Pathol Lab Med. 2016;140(5):406–12.PubMedGoogle Scholar
  727. 727.
    Stachler MD, Rinehart E, Lindeman N, Odze R, Srivastava A. Novel molecular insights from routine genotyping of colorectal carcinomas. Hum Pathol. 2015;46(4):507–13.PubMedGoogle Scholar
  728. 728.
    East JE, Atkin WS, Bateman AC, Clark SK, Dolwani S, Ket SN, et al. British Society of Gastroenterology position statement on serrated polyps in the colon and rectum. Gut. 2017;66(7):1181–96.PubMedPubMedCentralGoogle Scholar
  729. 729.
    Lengauer C, Kinzler KW, Vogelstein B. Genetic instability in colorectal cancers. Nature. 1997;386(6625):623–7.PubMedGoogle Scholar
  730. 730.
    Weisenberger DJ, Siegmund KD, Campan M, Young J, Long TI, Faasse MA, et al. CpG island methylator phenotype underlies sporadic microsatellite instability and is tightly associated with BRAF mutation in colorectal cancer. Nat Genet. 2006;38(7):787–93.PubMedGoogle Scholar
  731. 731.
    Toyota M, Ahuja N, Ohe-Toyota M, Herman JG, Baylin SB, Issa JP. CpG island methylator phenotype in colorectal cancer. Proc Natl Acad Sci U S A. 1999;96(15):8681–6.PubMedPubMedCentralGoogle Scholar
  732. 732.
    Cancer Genome Atlas N. Comprehensive molecular characterization of human colon and rectal cancer. Nature. 2012;487(7407):330–7.Google Scholar
  733. 733.
    Leggett B, Whitehall V. Role of the serrated pathway in colorectal cancer pathogenesis. Gastroenterology. 2010;138(6):2088–100.PubMedGoogle Scholar
  734. 734.
    Wood LD, Parsons DW, Jones S, Lin J, Sjoblom T, Leary RJ, et al. The genomic landscapes of human breast and colorectal cancers. Science. 2007;318(5853):1108–13.PubMedGoogle Scholar
  735. 735.
    Patel SS, Kilgore ML. Cost effectiveness of colorectal cancer screening strategies. Cancer Control. 2015;22(2):248–58.PubMedGoogle Scholar
  736. 736.
    Winawer SJ, Zauber AG, Fletcher RH, Stillman JS, O'Brien MJ, Levin B, et al. Guidelines for colonoscopy surveillance after polypectomy: a consensus update by the US Multi-Society Task Force on Colorectal Cancer and the American Cancer Society. Gastroenterology. 2006;130(6):1872–85.PubMedGoogle Scholar
  737. 737.
    Mahajan D, Downs-Kelly E, Liu X, Pai RK, Patil DT, Rybicki L, et al. Reproducibility of the villous component and high-grade dysplasia in colorectal adenomas <1 cm: implications for endoscopic surveillance. Am J Surg Pathol. 2013;37(3):427–33.PubMedGoogle Scholar
  738. 738.
    Panarelli NC, Schreiner AM, Brandt SM, Shepherd NA, Yantiss RK. Histologic features and cytologic techniques that aid pathologic stage assessment of colonic adenocarcinoma. Am J Surg Pathol. 2013;37(8):1252–8.PubMedGoogle Scholar
  739. 739.
    Shepherd NA, Bussey HJ, Jass JR. Epithelial misplacement in Peutz-Jeghers polyps. A diagnostic pitfall. Am J Surg Pathol. 1987;11(10):743–9.PubMedGoogle Scholar
  740. 740.
    Backes Y, Moons LM, Novelli MR, van Bergeijk JD, Groen JN, Seerden TC, et al. Diagnosis of T1 colorectal cancer in pedunculated polyps in daily clinical practice: a multicenter study. Mod Pathol. 2017;30(1):104–12.PubMedGoogle Scholar
  741. 741.
    Benizri EI, Bereder JM, Rahili A, Bernard JL, Vanbiervliet G, Filippi J, et al. Additional colectomy after colonoscopic polypectomy for T1 colon cancer: a fine balance between oncologic benefit and operative risk. Int J Color Dis. 2012;27(11):1473–8.Google Scholar
  742. 742.
    Nascimbeni R, Burgart LJ, Nivatvongs S, Larson DR. Risk of lymph node metastasis in T1 carcinoma of the colon and rectum. Dis Colon Rectum. 2002;45(2):200–6.PubMedGoogle Scholar
  743. 743.
    Netzer P, Forster C, Biral R, Ruchti C, Neuweiler J, Stauffer E, et al. Risk factor assessment of endoscopically removed malignant colorectal polyps. Gut. 1998;43(5):669–74.PubMedPubMedCentralGoogle Scholar
  744. 744.
    Seitz U, Bohnacker S, Seewald S, Thonke F, Brand B, Braiutigam T, et al. Is endoscopic polypectomy an adequate therapy for malignant colorectal adenomas? Presentation of 114 patients and review of the literature. Dis Colon Rectum. 2004;47(11):1789–96. discussion 96-7.PubMedGoogle Scholar
  745. 745.
    Pai RK, Chen Y, Jakubowski MA, Shadrach BL, Plesec TP, Pai RK. Colorectal carcinomas with submucosal invasion (pT1): analysis of histopathological and molecular factors predicting lymph node metastasis. Mod Pathol. 2017;30(1):113–22.PubMedGoogle Scholar
  746. 746.
    Rashtak S, Rego R, Sweetser SR, Sinicrope FA. Sessile serrated polyps and colon cancer prevention. Cancer Prev Res (Phila). 2017;10(5):270–8.Google Scholar
  747. 747.
    Yang HM, Mitchell JM, Sepulveda JL, Sepulveda AR. Molecular and histologic considerations in the assessment of serrated polyps. Arch Pathol Lab Med. 2015;139(6):730–41.PubMedGoogle Scholar
  748. 748.
    Choi EY, Appelman HD. A historical perspective and expose on serrated polyps of the colorectum. Arch Pathol Lab Med. 2016;140(10):1079–84.PubMedGoogle Scholar
  749. 749.
    Rex DK, Ahnen DJ, Baron JA, Batts KP, Burke CA, Burt RW, et al. Serrated lesions of the colorectum: review and recommendations from an expert panel. Am J Gastroenterol. 2012;107(9):1315–29. quiz 4, 30.PubMedPubMedCentralGoogle Scholar
  750. 750.
    Yantiss RK, Goldman H, Odze RD. Hyperplastic polyp with epithelial misplacement (inverted hyperplastic polyp): a clinicopathologic and immunohistochemical study of 19 cases. Mod Pathol. 2001;14(9):869–75.PubMedGoogle Scholar
  751. 751.
    Kawasaki K, Kurahara K, Oshiro Y, Yanai S, Kobayashi H, Nakamura S, et al. Clinicopathologic features of inverted serrated lesions of the large bowel. Digestion. 2016;93(4):280–7.PubMedGoogle Scholar
  752. 752.
    He EY, Wyld L, Sloane MA, Canfell K, Ward RL. The molecular characteristics of colonic neoplasms in serrated polyposis: a systematic review and meta-analysis. J Pathol Clin Res. 2016;2(3):127–37.PubMedPubMedCentralGoogle Scholar
  753. 753.
    Network NCC. Anal Carcinoma (Version 2.2017 – April 20, 2017). Available from:
  754. 754.
    Schoen RE, Akpan IM. Whither the hyperplastic and serrated polyp? Gastrointest Endosc. 2016;83(3):563–5.PubMedGoogle Scholar
  755. 755.
    Glatz K, Pritt B, Glatz D, Hartmann A, O’Brien MJ, Blaszyk H. A multinational, internet-based assessment of observer variability in the diagnosis of serrated colorectal polyps. Am J Clin Pathol. 2007;127(6):938–45.PubMedGoogle Scholar
  756. 756.
    Khalid O, Radaideh S, Cummings OW, O’Brien MJ, Goldblum JR, Rex DK. Reinterpretation of histology of proximal colon polyps called hyperplastic in 2001. World J Gastroenterol. 2009;15(30):3767–70.PubMedPubMedCentralGoogle Scholar
  757. 757.
    Vayrynen SA, Vayrynen JP, Klintrup K, Makela J, Tuomisto A, Makinen MJ. Ectopic crypt foci in conventional and serrated colorectal polyps. J Clin Pathol. 2016;69(12):1063–9.PubMedGoogle Scholar
  758. 758.
    Hafezi-Bakhtiari S, Wang LM, Colling R, Serra S, Chetty R. Histological overlap between colorectal villous/tubulovillous and traditional serrated adenomas. Histopathology. 2015;66(2):308–13.PubMedGoogle Scholar
  759. 759.
    Kalimuthu SN, Serra S, Hafezi-Bakhtiari S, Colling R, Wang LM, Chetty R. Mucin-rich variant of traditional serrated adenoma: a distinct morphological variant. Histopathology. 2017;71(2):208–16.Google Scholar
  760. 760.
    Bettington ML, Walker NI, Rosty C, Brown IS, Clouston AD, McKeone DM, et al. A clinicopathological and molecular analysis of 200 traditional serrated adenomas. Mod Pathol. 2015;28(3):414–27.PubMedGoogle Scholar
  761. 761.
    Yantiss RK, Oh KY, Chen YT, Redston M, Odze RD. Filiform serrated adenomas: a clinicopathologic and immunophenotypic study of 18 cases. Am J Surg Pathol. 2007;31(8):1238–45.PubMedGoogle Scholar
  762. 762.
    Chetty R, Vajpeyi R, Penwick JL. Psammomatous melanotic schwannoma presenting as colonic polyps. Virchows Arch. 2007;451(3):717–20.PubMedGoogle Scholar
  763. 763.
    Liu C, Walker NI, Leggett BA, Whitehall VL, Bettington ML, Rosty C. Sessile serrated adenomas with dysplasia: morphological patterns and correlations with MLH1 immunohistochemistry. Mod Pathol. 2017;30:1728.PubMedPubMedCentralGoogle Scholar
  764. 764.
    Rex DK, Boland CR, Dominitz JA, Giardiello FM, Johnson DA, Kaltenbach T, et al. Colorectal cancer screening: recommendations for physicians and patients from the U.S. multi-society task force on colorectal cancer. Gastroenterology. 2017;153(1):307–23.PubMedGoogle Scholar
  765. 765.
    Patel SG, Ahnen DJ. Familial colon cancer syndromes: an update of a rapidly evolving field. Curr Gastroenterol Rep. 2012;14(5):428–38.PubMedPubMedCentralGoogle Scholar
  766. 766.
    Hemminki K, Chen B. Familial risk for colorectal cancers are mainly due to heritable causes. Cancer Epidemiol Biomark Prev. 2004;13(7):1253–6.Google Scholar
  767. 767.
    Esteban-Jurado C, Garre P, Vila M, Lozano JJ, Pristoupilova A, Beltran S, et al. New genes emerging for colorectal cancer predisposition. World J Gastroenterol. 2014;20(8):1961–71.PubMedPubMedCentralGoogle Scholar
  768. 768.
    Da Silva FC, Wernhoff P, Dominguez-Barrera C, Dominguez-Valentin M. Update on hereditary colorectal cancer. Anticancer Res. 2016;36(9):4399–405.Google Scholar
  769. 769.
    Lindor NM, Rabe K, Petersen GM, Haile R, Casey G, Baron J, et al. Lower cancer incidence in Amsterdam-I criteria families without mismatch repair deficiency: familial colorectal cancer type X. JAMA. 2005;293(16):1979–85.PubMedPubMedCentralGoogle Scholar
  770. 770.
    Greenson JK, Huang SC, Herron C, Moreno V, Bonner JD, Tomsho LP, et al. Pathologic predictors of microsatellite instability in colorectal cancer. Am J Surg Pathol. 2009;33(1):126–33.PubMedPubMedCentralGoogle Scholar
  771. 771.
    Domingo E, Freeman-Mills L, Rayner E, Glaire M, Briggs S, Vermeulen L, et al. Somatic POLE proofreading domain mutation, immune response, and prognosis in colorectal cancer: a retrospective, pooled biomarker study. Lancet Gastroenterol Hepatol. 2016;1(3):207–16.PubMedGoogle Scholar
  772. 772.
    Egoavil C, Juarez M, Guarinos C, Rodriguez-Soler M, Hernandez-Illan E, Alenda C, et al. Increased risk of colorectal cancer in patients with multiple serrated polyps and their first-degree relatives. Gastroenterology. 2017;153(1):106–12. e2.PubMedGoogle Scholar
  773. 773.
    IJspeert JE, Rana SA, Atkinson NS, van Herwaarden YJ, Bastiaansen BA, van Leerdam ME, et al. Clinical risk factors of colorectal cancer in patients with serrated polyposis syndrome: a multicentre cohort analysis. Gut. 2017;66(2):278–84.PubMedGoogle Scholar
  774. 774.
    Boparai KS, Mathus-Vliegen EM, Koornstra JJ, Nagengast FM, van Leerdam M, van Noesel CJ, et al. Increased colorectal cancer risk during follow-up in patients with hyperplastic polyposis syndrome: a multicentre cohort study. Gut. 2010;59(8):1094–100.PubMedGoogle Scholar
  775. 775.
    Carballal S, Rodriguez-Alcalde D, Moreira L, Hernandez L, Rodriguez L, Rodriguez-Moranta F, et al. Colorectal cancer risk factors in patients with serrated polyposis syndrome: a large multicentre study. Gut. 2016;65(11):1829–37.PubMedGoogle Scholar
  776. 776.
    Colliver DW, Crawford NP, Eichenberger MR, Zacharius W, Petras RE, Stromberg AJ, et al. Molecular profiling of ulcerative colitis-associated neoplastic progression. Exp Mol Pathol. 2006;80(1):1–10.PubMedGoogle Scholar
  777. 777.
    Tanaka T, Kobunai T, Yamamoto Y, Emoto S, Murono K, Kaneko M, et al. Colitic cancer develops through mutational alteration distinct from that in sporadic colorectal cancer: a comparative analysis of mutational rates at each step. Cancer Genomics Proteomics. 2017;14(5):341–8.PubMedPubMedCentralGoogle Scholar
  778. 778.
    Castano-Milla CCM, Gisbert JP. Systemic review with meta-analysis; the declining risk of colorectal cancer in ulcerative colitis. Aliment Pharmacol Ther. 2014;39(7):645–59.PubMedGoogle Scholar
  779. 779.
    Kinugasa T, Akagi Y. Status of colitis-associated cancer in ulcerative colitis. World J Gastrointest Oncol. 2016;8(4):351–7.PubMedPubMedCentralGoogle Scholar
  780. 780.
    Higashi D, Futami K, Ishibashi Y, Egawa Y, Maekawa T, Matsui T, et al. Clinical course of colorectal cancer in patients with ulcerative colitis. Anticancer Res. 2011;31(7):2499–504.PubMedGoogle Scholar
  781. 781.
    Levi GS, Harpaz N. Intestinal low-grade tubuloglandular adenocarcinoma in inflammatory bowel disease. Am J Surg Pathol. 2006;30(8):1022–9.PubMedGoogle Scholar
  782. 782.
    Hornick JL. Manual of surgical pathology. 3rd ed. Philadelphia: Elsevier Saunders; 2010.Google Scholar
  783. 783.
    Kakar S, Chanjuan S, Berho M, Driman D, Fitzgibbons P, Frankel W, Hill K, Jessup J, Kransinskas A, Washington M. Protocol for the examination of specimens from patients with primary carcinoma of the colon and rectum 2016 []:Available from: - !%40%40%3F_afrLoop%3D63660215376515%26_adf.ctrl-state%3Driqh4s1xm_4.
  784. 784.
    Hav M, Libbrecht L, Ferdinande L, Geboes K, Pattyn P, Cuvelier CA. Pathologic assessment of rectal carcinoma after neoadjuvant radio(chemo)therapy: prognostic implications. Biomed Res Int. 2015;2015:574540.PubMedPubMedCentralGoogle Scholar
  785. 785.
    Birbeck KF, Macklin CP, Tiffin NJ, Parsons W, Dixon MF, Mapstone NP, et al. Rates of circumferential resection margin involvement vary between surgeons and predict outcomes in rectal cancer surgery. Ann Surg. 2002;235(4):449–57.PubMedPubMedCentralGoogle Scholar
  786. 786.
    Glynne-Jones R, Mawdsley S, Novell JR. The clinical significance of the circumferential resection margin following preoperative pelvic chemo-radiotherapy in rectal cancer: why we need a common language. Color Dis. 2006;8(9):800–7.Google Scholar
  787. 787.
    Kapiteijn E, Marijnen CA, Nagtegaal ID, Putter H, Steup WH, Wiggers T, et al. Preoperative radiotherapy combined with total mesorectal excision for resectable rectal cancer. N Engl J Med. 2001;345(9):638–46.PubMedGoogle Scholar
  788. 788.
    Parfitt JR, Driman DK. The total mesorectal excision specimen for rectal cancer: a review of its pathological assessment. J Clin Pathol. 2007;60(8):849–55.PubMedGoogle Scholar
  789. 789.
    Gorog D, Nagy P, Peter A, Perner F. Influence of obesity on lymph node recovery from rectal resection specimens. Pathol Oncol Res. 2003;9(3):180–3.PubMedGoogle Scholar
  790. 790.
    Wijesuriya RE, Deen KI, Hewavisenthi J, Balawardana J, Perera M. Neoadjuvant therapy for rectal cancer down-stages the tumor but reduces lymph node harvest significantly. Surg Today. 2005;35(6):442–5.PubMedGoogle Scholar
  791. 791.
    Betge J, Harbaum L, Pollheimer MJ, Lindtner RA, Kornprat P, Ebert MP, et al. Lymph node retrieval in colorectal cancer: determining factors and prognostic significance. Int J Color Dis. 2017;32(7):991–8.Google Scholar
  792. 792.
    Arnold A, Kloor M, Jansen L, Chang-Claude J, Brenner H, von Winterfeld M, et al. The association between microsatellite instability and lymph node count in colorectal cancer. Virchows Arch. 2017;471(1):57–64.PubMedGoogle Scholar
  793. 793.
    Choi JP, Park IJ, Lee BC, Hong SM, Lee JL, Yoon YS, et al. Variability in the lymph node retrieval after resection of colon cancer: influence of operative period and process. Medicine (Baltimore). 2016;95(31):e4199.Google Scholar
  794. 794.
    Solon JG, Cahalane A, Burke JP, Gibbons D, McCann JW, Martin ST, et al. A radiological and pathological assessment of ileocolic pedicle length as a predictor of lymph node retrieval following right hemicolectomy for caecal cancer. Tech Coloproctol. 2016;20(8):545–50.PubMedGoogle Scholar
  795. 795.
    Lavy R, Hershkovitz Y, Kapiev A, Chikman B, Shapira Z, Poluksht N, et al. A comparative study on two different pathological methods to retrieve lymph nodes following gastrectomy. Int J Surg. 2014;12(7):725–8.PubMedGoogle Scholar
  796. 796.
    Ong ML, Schofield JB. Assessment of lymph node involvement in colorectal cancer. World J Gastrointest Surg. 2016;8(3):179–92.PubMedPubMedCentralGoogle Scholar
  797. 797.
    Rossler O, Betge J, Harbaum L, Mrak K, Tschmelitsch J, Langner C. Tumor size, tumor location, and antitumor inflammatory response are associated with lymph node size in colorectal cancer patients. Mod Pathol. 2017;30(6):897–904.PubMedGoogle Scholar
  798. 798.
    Goldstein NS. Lymph node recoveries from 2427 pT3 colorectal resection specimens spanning 45 years: recommendations for a minimum number of recovered lymph nodes based on predictive probabilities. Am J Surg Pathol. 2002;26(2):179–89.PubMedGoogle Scholar
  799. 799.
    AJCC cancer staging manual. 8th ed. New York: Springer Science+Business Media; 2016. pages cm p.Google Scholar
  800. 800.
    Kalluri R. The biology and function of fibroblasts in cancer. Nat Rev Cancer. 2016;16(9):582–98.PubMedGoogle Scholar
  801. 801.
    Cooper HS, Deppisch LM, Gourley WK, Kahn EI, Lev R, Manley PN, et al. Endoscopically removed malignant colorectal polyps: clinicopathologic correlations. Gastroenterology. 1995;108(6):1657–65.PubMedGoogle Scholar
  802. 802.
    Cooper HS. Pathologic issues in the treatment of endoscopically removed malignant colorectal polyps. J Natl Compr Cancer Netw. 2007;5(9):991–6.Google Scholar
  803. 803.
    Cappellesso R, Luchini C, Veronese N, Lo Mele M, Rosa-Rizzotto E, Guido E, et al. Tumor budding as a risk factor for nodal metastasis in pT1 colorectal cancers: a meta-analysis. Hum Pathol. 2017;65:62–70.PubMedGoogle Scholar
  804. 804.
    Rosty C, Williamson EJ, Clendenning M, Walters RJ, Win AK, Jenkins MA, et al. Should the grading of colorectal adenocarcinoma include microsatellite instability status? Hum Pathol. 2014;45(10):2077–84.PubMedGoogle Scholar
  805. 805.
    Young J, Simms LA, Biden KG, Wynter C, Whitehall V, Karamatic R, et al. Features of colorectal cancers with high-level microsatellite instability occurring in familial and sporadic settings: parallel pathways of tumorigenesis. Am J Pathol. 2001;159(6):2107–16.PubMedPubMedCentralGoogle Scholar
  806. 806.
    Shia J, Ellis NA, Paty PB, Nash GM, Qin J, Offit K, et al. Value of histopathology in predicting microsatellite instability in hereditary nonpolyposis colorectal cancer and sporadic colorectal cancer. Am J Surg Pathol. 2003;27(11):1407–17.PubMedGoogle Scholar
  807. 807.
    Truta B, Chen YY, Blanco AM, Deng G, Conrad PG, Kim YH, et al. Tumor histology helps to identify lynch syndrome among colorectal cancer patients. Familial Cancer. 2008;7(3):267–74.PubMedGoogle Scholar
  808. 808.
    Shia J, Schultz N, Kuk D, Vakiani E, Middha S, Segal NH, et al. Morphological characterization of colorectal cancers in the cancer genome atlas reveals distinct morphology-molecular associations: clinical and biological implications. Mod Pathol. 2017;30(4):599–609.PubMedGoogle Scholar
  809. 809.
    Hugen N, Verhoeven RH, Lemmens VE, van Aart CJ, Elferink MA, Radema SA, et al. Colorectal signet-ring cell carcinoma: benefit from adjuvant chemotherapy but a poor prognostic factor. Int J Cancer. 2015;136(2):333–9.PubMedGoogle Scholar
  810. 810.
    Park PY, Goldin T, Chang J, Markman M, Kundranda MN. Signet-ring cell carcinoma of the colon: a case report and review of the literature. Case Rep Oncol. 2015;8(3):466–71.PubMedPubMedCentralGoogle Scholar
  811. 811.
    Guzinska-Ustymowicz K, Niewiarowska K, Pryczynicz A. Invasive micropapillary carcinoma: a distinct type of adenocarcinomas in the gastrointestinal tract. World J Gastroenterol. 2014;20(16):4597–606.PubMedPubMedCentralGoogle Scholar
  812. 812.
    Pyo JS, Sohn JH, Kang G. Medullary carcinoma in the colorectum: a systematic review and meta-analysis. Hum Pathol. 2016;53:91–6.PubMedGoogle Scholar
  813. 813.
    Makinen MJ. Colorectal serrated adenocarcinoma. Histopathology. 2007;50(1):131–50.PubMedGoogle Scholar
  814. 814.
    Thelin C, Alquist CR, Engel LS, Dewenter T. Primary clear cell adenocarcinoma of the colon: a case report and review. J La State Med Soc. 2014;166(4):143–8.PubMedGoogle Scholar
  815. 815.
    Wang W, Li X, Qu G, Leng T, Geng J. Primary clear cell adenocarcinoma of the colon presenting as a huge extracolic mass: a case report. Oncol Lett. 2014;8(4):1873–5.PubMedPubMedCentralGoogle Scholar
  816. 816.
    Barrera-Maldonado CD, Wiener I, Sim S. Clear cell adenocarcinoma of the colon: a case report and review of the literature. Case Rep Oncol Med. 2014;2014:905478.PubMedPubMedCentralGoogle Scholar
  817. 817.
    Furuya Y, Wakahara T, Akimoto H, Kishimoto T, Hiroshima K, Yanagie H, et al. Clear cell adenocarcinoma with enteroblastic differentiation of the ascending colon. J Clin Oncol. 2011;29(22):e647–9.PubMedGoogle Scholar
  818. 818.
    Oh SK, Kim HW, Kang DH, Choi CW, Choi YY, Lim HK, et al. Primary adenocarcinoma with focal choriocarcinomatous differentiation in the sigmoid colon. Korean J Gastroenterol. 2015;66(5):291–6.PubMedGoogle Scholar
  819. 819.
    Lino-Silva LS, Salcedo-Hernandez RA, Herrera-Gomez A, Padilla-Rosciano A, Ramirez-Jaramillo M, Herrera-Goepfert RE, et al. Colonic cribriform carcinoma, a morphologic pattern associated with low survival. Int J Surg Pathol. 2015;23(1):13–9.PubMedGoogle Scholar
  820. 820.
    Wong HH, Chu P. Immunohistochemical features of the gastrointestinal tract tumors. J Gastrointest Oncol. 2012;3(3):262–84.PubMedPubMedCentralGoogle Scholar
  821. 821.
    Fleming M, Ravula S, Tatishchev SF, Wang HL. Colorectal carcinoma: pathologic aspects. J Gastrointest Oncol. 2012;3(3):153–73.PubMedPubMedCentralGoogle Scholar
  822. 822.
    Saad RS, Silverman JF, Khalifa MA, Rowsell C. CDX2, cytokeratins 7 and 20 immunoreactivity in rectal adenocarcinoma. Appl Immunohistochem Mol Morphol. 2009;17(3):196–201.PubMedGoogle Scholar
  823. 823.
    Hinoi T, Tani M, Lucas PC, Caca K, Dunn RL, Macri E, et al. Loss of CDX2 expression and microsatellite instability are prominent features of large cell minimally differentiated carcinomas of the colon. Am J Pathol. 2001;159(6):2239–48.PubMedPubMedCentralGoogle Scholar
  824. 824.
    McGregor DK, Wu TT, Rashid A, Luthra R, Hamilton SR. Reduced expression of cytokeratin 20 in colorectal carcinomas with high levels of microsatellite instability. Am J Surg Pathol. 2004;28(6):712–8.PubMedGoogle Scholar
  825. 825.
    Ueno H, Price AB, Wilkinson KH, Jass JR, Mochizuki H, Talbot IC. A new prognostic staging system for rectal cancer. Ann Surg. 2004;240(5):832–9.PubMedPubMedCentralGoogle Scholar
  826. 826.
    Lugli A, Kirsch R, Ajioka Y, Bosman F, Cathomas G, Dawson H, et al. Recommendations for reporting tumor budding in colorectal cancer based on the International Tumor Budding Consensus Conference (ITBCC) 2016. Mod Pathol. 2017;30(9):1299–311.PubMedGoogle Scholar
  827. 827.
    Rogers AC, Winter DC, Heeney A, Gibbons D, Lugli A, Puppa G, et al. Systematic review and meta-analysis of the impact of tumour budding in colorectal cancer. Br J Cancer. 2016;115(7):831–40.PubMedPubMedCentralGoogle Scholar
  828. 828.
    Suzuki A, Togashi K, Nokubi M, Koinuma K, Miyakura Y, Horie H, et al. Evaluation of venous invasion by Elastica van Gieson stain and tumor budding predicts local and distant metastases in patients with T1 stage colorectal cancer. Am J Surg Pathol. 2009;33(11):1601–7.PubMedGoogle Scholar
  829. 829.
    Roxburgh CS, McMillan DC, Richards CH, Atwan M, Anderson JH, Harvey T, et al. The clinical utility of the combination of T stage and venous invasion to predict survival in patients undergoing surgery for colorectal cancer. Ann Surg. 2014;259(6):1156–65.PubMedGoogle Scholar
  830. 830.
    Betge J, Pollheimer MJ, Lindtner RA, Kornprat P, Schlemmer A, Rehak P, et al. Intramural and extramural vascular invasion in colorectal cancer: prognostic significance and quality of pathology reporting. Cancer. 2012;118(3):628–38.PubMedGoogle Scholar
  831. 831.
    Cienfuegos JA, Martinez P, Baixauli J, Beorlegui C, Rosenstone S, Sola JJ, et al. Perineural invasion is a major prognostic and predictive factor of response to adjuvant chemotherapy in stage I-II colon cancer. Ann Surg Oncol. 2017;24(4):1077–84.PubMedGoogle Scholar
  832. 832.
    Fujita S, Shimoda T, Yoshimura K, Yamamoto S, Akasu T, Moriya Y. Prospective evaluation of prognostic factors in patients with colorectal cancer undergoing curative resection. J Surg Oncol. 2003;84(3):127–31.PubMed