Mixed Adeno-Neuroendocrine Carcinoma; Case Series of Ten Patients with Review of the Literature

Abstract

Aims: Mixed adeno-neuroendocrine carcinoma is a rare entity, diagnosed with immunohistochemical studies. Literature mainly includes case reports and series which are very few. In our study, we aimed to report a case series from a tertiary hospital with demographics of the patients, detailed tumor and clinical findings and follow-up plus survival conditions.Methods: Pathology database was explored for patients with the pathological diagnosis of ‘mixed adeno-neuroendocrine carcinoma’ and patients were identified retrospectively and evaluated in means of demographics, histopathological examination, tumor properties.Results:  Ten patients had been diagnosed with mixed adeno-neuroendocrine carcinoma in our center, diagnosed at a mean age of 64.7.  Stomach was found to be the most common localization. Five patients (50%) were diagnosed as grade 3. Following surgery, median follow-up was 15 months with a median survival time of 20.6 months.Conclusion: This case series may contribute to the literature on the pathological and clinical aspects of the mixed adenoneuroendocrine carcinoma of the gastrointestinal system.

Keywords

• Digestive system, mixed adenoneuroendocrine carcinoma, neuroendocrine neoplasm, prognosis

References

1. 1. Rindi G, Arnold R, Bosman FT, Capella C, Klimstra DS, Klöppel G, et al. Nomenclature and classification of neuroendocrine neoplasms of the digestive system. In: Bosman FT, Carneiro F, Hruban RH, Theise ND, editors. WHO Classification of Tumours of the Digestive System. 4th ed. Lyon, France: IARC Press; 2010:13-4.
2. 2. Cordier R. Les cellules argentaffines dans les tumeurs intestinales. Arch Int Med Exp 1924;1:5.
3. 3. Lewin K. Carcinoid tumors and the mixed (composite) glandular-endocrine cell carcinomas. Am J Surg Pathol 1987;11(Suppl 1):71-86.
4. 4. La Rosa S, Marando A, Sessa F, Capella C. Mixed adenoneuroendocrine carcinomas (MANECs) of the gastrointestinal tract: an update. Cancers (Basel) 2012;4:11-30.
5. 5. Harada K, Sato Y, Ikeda H, Maylee H, Igarashi S, Okamura A, et al. Clinicopathologic study of mixed adenoneuroendocrine carcinomas of heptobiliary organs. Wirchows Arch 2012;460:281-9.
6. 6. Gurzu S, Kadar Z, Bara T, Bara T Jr, Tamasi A, Azamfirei L, et al. Mixed adenoneuroendocrine carcinoma of gastrointestinal tract: report of two cases. World J Gastroenterol 2015;21:1329-33.
7. 7. Liu XJ, Feng JS, Xiang WY, Kong B, Wang LM, Zeng JC, et al. Clinicopathological features of an ascending colon mixed adenoneuroendocrine carcinoma with clinical serosal invasion. Int J Clin Exp Pathol 2014;7:6395-8.
8. 8. Acosta AM, Hamedani FS, Kajdacsy-Balla A, Wiley EL. Primary Mixed Adenoneuroendocrine Carcinoma of the Gallbladder in a 55-Year-Old Female Patient: A Case Report and Review of the Literature. Int J Surg Pathol 2015;23:414-8.

9. 9. Solcia E, Klöppel G, Sobin LH. Histopathological Typing of Endocrine Tumours. 2nd ed. Berlin, Germany: Springer; 2000.
10. 10. Mahansaria SS, Agrawal N, Arora A, Bihari C, Appukuttan M, Chattopadhyay TK. Ampullary mixed adenoneuroendocrine carcinoma: surprise histology, familiar management. Int J Surg Pathol 2017;7:585-91.
11. 11. Acosta AM, Wiley EL. Primary biliary mixed adenoneuroendocrine carcinoma (MANEC). A short review. Arch Pathol Lab Med 2016;140:1157-62.
12. 12. Chen MH, Kuo YJ, Yeh YC, Lin YC, Tzeng CH, Liu CY, et al. High neuroendocrine component is a factor for poor prognosis in gastrointestinal high-grade malignant mixed adenoneuroendocrine neoplasms. J Chin Med Assoc 2015;78:454-9.
13. 13. Scholzen T, Gerdes J. The Ki-67 protein: from the known and the unknown. J Cell Physiol 2000;182:311-22.
14. 14. Brathwaite S, Rock J, Yearsley MM, Bekaii-Saab T, Wei L, Frankel WL, et al. Mixed adeno-neuroendocrine carcinoma: an aggressive clinical entity. Ann Surg Oncol 2016;23:2281-6.
15. 15. Song W, Chen W, Zhang S, Peng J, He Y. Successful treatment of gallbladder mixed adenoneuroendocrine carcinoma with neo-adjuvant chemotherapy. Diagn Pathol 2012;7:163.
16. 16. Murata M, Takahashi H, Yamada M, Song M, Hiratsuka M. A case of mixed adenoneuroendocrine carcinoma of the pancreas. Immunohistochemical analysis for histogenesis. Medicine (Baltimore) 2017;96:e6225.
17. 17. La Rosa S, Marando A, Furlan D, Sahnane N, Capella C. Colorectal poorly differentiated neuroendocrine carcinomas and mixed aenoneuroendocrine carcinomas: insights into the diagnostic immunophenotype, assesment of methylation profile, and search for prognostic markers. Am J Surg Pathol 2012;36:601-11.
18. 18. Juanmartinena JF, Fernandez-Urien I, Cordoba A, Miranda C, Borda A. Mixed adenoneuroendocrine carcinoma (MANEC) of the gastroesophageal junction: a case report and review of the literature. Rev Esp Enferm Dig 2017;109:160-2.
19. 19. Veits L, Lang-Schwarz C, Volkholz H, Falkeis C, Vieth M, Schulz H. Mixed adenoneuroendocrine carcinoma (MANEC) of the esophagogastric junction predominantly consisting of poorly differentiated neuroendocrine carcinoma. Endoscopy 2013;45(Suppl 2):16-7.
20. 20. 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. Wirchows Arch 2006;449:499-506.