Annals of Surgical Oncology

, Volume 23, Issue 7, pp 2281–2286 | Cite as

Mixed Adeno-neuroendocrine Carcinoma: An Aggressive Clinical Entity

  • Shayna Brathwaite
  • Jonathan Rock
  • Martha M. Yearsley
  • Tanios Bekaii-Saab
  • Lai Wei
  • Wendy L. Frankel
  • John Hays
  • Christina Wu
  • Sherif Abdel-Misih
Colorectal Cancer



Mixed adeno-neuroendocrine carcinoma (MANEC) is a rare pathologic diagnosis recently defined by the World Health Organization in 2010. Due to poor understanding of MANEC as a clinical entity, there is significant variation in the management of these patients. The purpose of our study was to characterize MANEC to develop evidence-based treatment strategies.


The Ohio State University patient database was queried for the diagnosis of MANEC and 46 patients were identified. For comparison, the database also was queried for goblet cell carcinoid (GCC) of the appendix, signet ring cell carcinoma, and carcinoid/neuroendocrine tumor of the appendix. Charts were then retrospectively reviewed for clinicopathologic characteristics, patient treatment, and survival data.


The mean age of diagnosis of MANEC was 54 years. Eighty-seven percent of MANEC arose from the appendix, with 28 % of patients undergoing appendectomy and 35 % undergoing right hemicolectomy as their index operation. Immunohistochemical staining was positive for chromogranin (82 %), synaptophysin (97 %), and CD56 (67 %). Sixty-seven percent of patients presented with stage IV disease and 41 % had nodal metastases. Overall survival was 4.1 years, which was statistically significantly different (p ≤ 0.05) compared with carcinoid tumors (13.4 years), GCC (15.4 years), and signet ring carcinoma (2.2 years).


MANEC is a more aggressive clinical entity than both GCC of the appendix and carcinoid/neuroendocrine tumors of the appendix. Based on these findings, we recommend patients with MANEC tumors undergo aggressive multidisciplinary cancer management and close surveillance.


Overall Survival Carcinoid Tumor Signet Ring Cell Carcinoma Appendiceal Tumor Goblet Cell Carcinoid 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



The authors have no disclosures.


  1. 1.
    Komminoth PA, Capella C, Klimstra DS, Klöppel G, Solcia E, Rindi G. Neuroendocrine neoplasms of the appendix. In: WHO classification of tumours of the digestive system. 4th ed. Lyon: IARC Press; 2010.Google Scholar
  2. 2.
    Rindi G, Bordi C, La Rosa S, et al. Gastroenteropancreatic (neuro)endocrine neoplasms: the histology report. Dig Liver Dis. 2011;43 Suppl 4:S356–60.CrossRefPubMedGoogle Scholar
  3. 3.
    Lewin K. Carcinoid tumors and the mixed (composite) glandular-endocrine cell carcinomas. Am J Surg Pathol. 1987;11 Suppl 1:71–86.CrossRefPubMedGoogle Scholar
  4. 4.
    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
  5. 5.
    Holt N, Gronbaek H. Goblet cell carcinoids of the appendix. Sci World J. 2013;2013:543696–702.CrossRefGoogle Scholar
  6. 6.
    Roy P, Chetty R. Goblet cell carcinoid tumors of the appendix: an overview. World J Gastrointest Oncol. 2010;2(6):251–8.CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    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.CrossRefPubMedGoogle Scholar
  8. 8.
    Power DG, Asmis TR, Tang LH, Brown K, Kemeny NE. High-grade neuroendocrine carcinoma of the colon, long-term survival in advanced disease. Med Oncol. 2011;28 Suppl 1:S169–74.CrossRefPubMedGoogle Scholar
  9. 9.
    Shia J, Tang LH, Weiser MR, et al. Is nonsmall cell type high-grade neuroendocrine carcinoma of the tubular gastrointestinal tract a distinct disease entity? Am J Surg Pathol. 2008;32(5):719–31.CrossRefPubMedGoogle Scholar
  10. 10.
    La Rosa S, Marando A, Sessa F, Capella C. Mixed adenoneuroendocrine carcinomas (MANECs) of the gastrointestinal tract: an update. Cancers. 2012;4(1):11–30.CrossRefPubMedPubMedCentralGoogle Scholar
  11. 11.
    Scholzen T, Gerdes J. The Ki-67 protein: from the known and the unknown. J Cell Physiol. 2000;182(3):311–22.CrossRefPubMedGoogle Scholar
  12. 12.
    Lowe K, Khithani A, Liu E, et al. Ki-67 labeling: a more sensitive indicator of malignant phenotype than mitotic count or tumor size? J Surg Oncol. 2012;106(6):724–7.CrossRefPubMedGoogle Scholar
  13. 13.
    Hamilton SR, Aaltonen LA, (eds.). World Health Organization Classification of Tumours. Pathology and Genetics of Tumours of the Digestive System. Lyon: IARC Press; 2000.Google Scholar
  14. 14.
    Goede AC, Caplin ME, Winslet MC. Carcinoid tumour of the appendix. Br J Surg. 2003;90(11):1317–22.CrossRefPubMedGoogle Scholar
  15. 15.
    Nussbaum DP, Speicher PJ, Gulack BC, et al. Management of 1- to 2-cm carcinoid tumors of the appendix: using the national cancer data base to address controversies in general surgery. J Am Coll Surg. 2015;220(5):894–903.CrossRefPubMedGoogle Scholar
  16. 16.
    Mullen JT, Savarese DM. Carcinoid tumors of the appendix: a population-based study. J Surg Oncol. 2011;104(1):41–4.CrossRefPubMedGoogle Scholar
  17. 17.
    Benedix F, Reimer A, Gastinger I, et al. Primary appendiceal carcinoma—epidemiology, surgery and survival: results of a German multi-center study. Eur J Surg Oncol. 2010;36(8):763–71.CrossRefPubMedGoogle Scholar
  18. 18.
    Moertel CG, Weiland LH, Nagorney DM, Dockerty MB. Carcinoid tumor of the appendix: treatment and prognosis. N Engl J Med. 1987;317(27):1699–701.CrossRefPubMedGoogle Scholar
  19. 19.
    Murray SE, Lloyd RV, Sippel RS, Chen H, Oltmann SC. Postoperative surveillance of small appendiceal carcinoid tumors. Am J Surg. 2014;207(3):342–5; discussion 345.Google Scholar
  20. 20.
    Kulke MH, Shah MH, Benson AB, et al. Neuroendocrine tumors, version 1.2015. J Natl Compr Canc Netw. 2015;13(1):78–108.PubMedGoogle Scholar
  21. 21.
    McCusker ME, Cote TR, Clegg LX, Sobin LH. Primary malignant neoplasms of the appendix: a population-based study from the surveillance, epidemiology and end-results program, 1973–1998. Cancer. 2002;94(12):3307–12.CrossRefPubMedGoogle Scholar

Copyright information

© Society of Surgical Oncology 2016

Authors and Affiliations

  • Shayna Brathwaite
    • 1
  • Jonathan Rock
    • 2
  • Martha M. Yearsley
    • 2
  • Tanios Bekaii-Saab
    • 3
  • Lai Wei
    • 4
  • Wendy L. Frankel
    • 2
  • John Hays
    • 3
  • Christina Wu
    • 3
  • Sherif Abdel-Misih
    • 5
  1. 1.Department of General SurgeryThe Ohio State University Wexner Medical CenterColumbusUSA
  2. 2.Department of PathologyThe Ohio State University Wexner Medical CenterColumbusUSA
  3. 3.Department of Internal MedicineThe Ohio State University Wexner Medical CenterColumbusUSA
  4. 4.Center for BiostatisticsThe Ohio State University Wexner Medical CenterColumbusUSA
  5. 5.Division of Surgical OncologyThe Ohio State University Wexner Medical CenterColumbusUSA

Personalised recommendations