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Lower gastrointestinal neuroendocrine neoplasms associated with hereditary cancer syndromes: a case series

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Abstract

Lower gastrointestinal (GI) neuroendocrine neoplasms (NENs) of the colon and rectum are uncommon and not traditionally associated with hereditary GI cancer syndromes. However, with widespread implementation of colorectal cancer screening programs, lower GI NENs are being identified with increasing frequency. We report the first case series of six patients with lower GI NENs who were diagnosed with hereditary GI cancer syndromes by germline testing. Two patients presented with poorly differentiated rectal neuroendocrine carcinoma (NECs) with colonic polyposis and were found to have Familial Adenomatous Polyposis and MYH-Associated Polyposis, respectively. Three patients with colorectal NENs (one well differentiated neuroendocrine tumor, NET, and two NECs), all of which displayed abnormal immunohistochemistry for mismatch repair proteins, were diagnosed with Lynch syndrome. One patient with a goblet cell carcinoid was diagnosed with CHEK2 mutations. All patients met genetic testing guidelines and the diagnosis was made utilizing next generation sequencing gene panel tests. Lower GI NETs should therefore be considered a potential hereditary GI cancer syndrome-associated malignancy in patients who otherwise meet criteria for genetic evaluation.

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References

  1. Syngal S, Brand RE, Church JM, Giardiello FM, Hampel HL, Burt RW, American College of G (2015) ACG clinical guideline: genetic testing and management of hereditary gastrointestinal cancer syndromes. Am J Gastroenterol 110:223–262

    Article  PubMed  PubMed Central  Google Scholar 

  2. Siegel R, Ma J, Zou Z, Jemal A (2014) Cancer statistics, 2014. CA Cancer J Clin 64:9–29

    Article  PubMed  Google Scholar 

  3. Yao JC, Hassan M, Phan A, Dagohoy C, Leary C, Mares JE, Abdalla EK, Fleming JB, Vauthey JN, Rashid A, Evans DB (2008) One hundred years after “carcinoid”: Epidemiology of and prognostic factors for neuroendocrine tumors in 35,825 cases in the united states. J Clin Oncol 26:3063–3072

    Article  PubMed  Google Scholar 

  4. Tsikitis VL, Wertheim BC, Guerrero MA (2012) Trends of incidence and survival of gastrointestinal neuroendocrine tumors in the United States: A seer analysis. J Cancer 3:292–230

    Article  PubMed  PubMed Central  Google Scholar 

  5. Basuroy R, Haji A, Ramage JK, Quaglia A, Srirajaskanthan R (2016) Review article: The investigation and management of rectal neuroendocrine tumours. Aliment Pharmacol Ther 44:332–345

    Article  CAS  PubMed  Google Scholar 

  6. Klimstra DS, Modlin IR, Coppola D, Lloyd RV, Suster S (2010) The pathologic classification of neuroendocrine tumors: a review of nomenclature, grading, and staging systems. Pancreas 39:707–712

    Article  PubMed  Google Scholar 

  7. Kidd M, Modlin I, Oberg K (2016) Towards a new classification of gastroenteropancreatic neuroendocrine neoplasms. Nat Rev Clin Oncol 13:691–705

    Article  CAS  PubMed  Google Scholar 

  8. Bernick PE, Klimstra DS, Shia J, Minsky B, Saltz L, Shi W, Thaler H, Guillem J, Paty P, Cohen AM, Wong WD (2004) Neuroendocrine carcinomas of the colon and rectum. Dis Colon Rectum 47:163–169

    Article  CAS  PubMed  Google Scholar 

  9. Hall MJ, Forman AD, Pilarski R, Wiesner G, Giri VN (2014) Gene panel testing for inherited cancer risk. J Natl Compr Canc Netw 12:1339–1346

    Article  PubMed  Google Scholar 

  10. Hansen MF, Johansen J, Sylvander AE, Bjornevoll I, Talseth-Palmer BA, Lavik LA, Xavier A, Engebretsen LF, Scott RJ, Drablos F, Sjursen W (2017) Use of multigene-panel identifies pathogenic variants in several crc-predisposing genes in patients previously tested for lynch syndrome. Clin Genet. doi:10.1111/cge.12994

    PubMed  Google Scholar 

  11. Pearlman R, Frankel WL, Swanson B et al (2016) Prevalence and spectrum of germline cancer susceptibility gene mutations among patients with early-onset colorectal cancer. JAMA Oncol. doi:10.1001/jamaoncol.2016.5194

    Google Scholar 

  12. Yadav S, Reeves A, Campian S et al (2016) Outcomes of retesting brca negative patients using multigene panels. Fam Cancer. doi:10.1007/s10689-016-9956-7

    Google Scholar 

  13. LaDuca H, Stuenkel AJ, Dolinsky JS, Keiles S, Tandy S, Pesaran T, Chen E, Gau CL, Palmaer E, Shoaepour K, Shah D, Speare V, Gandomi S, Chao E (2014) Utilization of multigene panels in hereditary cancer predisposition testing: analysis of more than 2,000 patients. Genet Med 16:830–837

    Article  PubMed  PubMed Central  Google Scholar 

  14. Mauer CB, Pirzadeh-Miller SM, Robinson LD, Euhus DM (2014) The integration of next-generation sequencing panels in the clinical cancer genetics practice: an institutional experience. Genet Med 16:407–412

    Article  PubMed  Google Scholar 

  15. Kurian AW, Hare EE, Mills MA, Kingham KE, McPherson L, Whittemore AS, McGuire V, Ladabaum U, Kobayashi Y, Lincoln SE, Cargill M, Ford JM (2014) Clinical evaluation of a multiple-gene sequencing panel for hereditary cancer risk assessment. J Clin Oncol 32:2001–2009

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Yousef I, Siyam F, Layfield L, Freter C, Sowers JR (2014) Cervical neuroendocrine tumor in a young female with lynch syndrome. Neuro Endocrinol Lett 35:89–94

    PubMed  PubMed Central  Google Scholar 

  17. Sorscher S, Saroya B (2013) A molecularly confirmed neuroendocrine tumor resulting from lynch syndrome. J Gastrointest Oncol 4:95–96

    PubMed  PubMed Central  Google Scholar 

  18. Miquel C, Sabourin JC, Elias D, Grandjouan S, Viguier J, Ducreux M, Duvillard P, Praz F (2004) An appendix carcinoid tumor in a patient with hereditary nonpolyposis colorectal cancer. Hum Pathol 35:1564–1567

    Article  PubMed  Google Scholar 

  19. Estrella JS, Taggart MW, Rashid A, Abraham SC (2014) Low-grade neuroendocrine tumors arising in intestinal adenomas: evidence for alterations in the adenomatous polyposis coli/beta-catenin pathway. Hum Pathol 45:2051–2058

    Article  CAS  PubMed  Google Scholar 

  20. July LV, Northcott KA, Yoshida EM, Carr DM, Owen DA (1999) Coexisting carcinoid tumors in familial adenomatous polyposis-associated upper intestinal adenomas. Am J Gastroenterol 94:1010–1091

    Article  Google Scholar 

  21. Giardiello FM, Allen JI, Axilbund JE et al (2014) 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 109:1159–1179

    Article  PubMed  Google Scholar 

  22. Stelow EB, Moskaluk CA, Mills SE (2006) The mismatch repair protein status of colorectal small cell neuroendocrine carcinomas. Am J Surg Pathol 30:1401–1404

    Article  PubMed  Google Scholar 

  23. Kloppel G, Rindi G, Anlauf M, Perren A, Komminoth P (2007) Site-specific biology and pathology of gastroenteropancreatic neuroendocrine tumors. Virchows Arch 451(Suppl 1):S9–S27

    Article  PubMed  Google Scholar 

  24. Oberg K (2013) The genetics of neuroendocrine tumors. Semin Oncol 40:37–44

    Article  PubMed  Google Scholar 

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Authors and Affiliations

  1. Division of Gastroenterology, University of California, San Francisco, San Francisco, CA, USA

    Trilokesh D. Kidambi & Jonathan P. Terdiman

  2. Hereditary GI Cancer Prevention Program, Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA, USA

    Christina Pedley, Amie Blanco, Emily K. Bergsland & Jonathan P. Terdiman

  3. Division of Medical Oncology, University of California, San Francisco, San Francisco, CA, USA

    Emily K. Bergsland

  4. Clinical Medicine and Surgery, University of California, San Francisco, 1701 Divisadero, San Francisco, CA, 94115, USA

    Jonathan P. Terdiman

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  1. Trilokesh D. Kidambi
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  2. Christina Pedley
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  3. Amie Blanco
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  4. Emily K. Bergsland
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Correspondence to Jonathan P. Terdiman.

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Kidambi, T.D., Pedley, C., Blanco, A. et al. Lower gastrointestinal neuroendocrine neoplasms associated with hereditary cancer syndromes: a case series. Familial Cancer 16, 537–543 (2017). https://doi.org/10.1007/s10689-017-9979-8

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