A rare clinical case of a patient with mixed neuroendocrine-non-neuroendocrine neoplasms of the ampulla of vater

Background. Neuroendocrine tumors are rare neoplasias accounting for 1 % of all digestive malignancies. In 2010, mixed neuroendocrine-non-neuroendocrine neoplasms (MiNENs) were classified by the World Health Organization This type of tumor is extremely rare and most commonly occurs in the appendix, colon, and rectum. To date, only 30 clinical cases of MINEN of the major duodenal papilla (MDP) have been described in the available world literature, while we have not found a description of this pathology in the domestic literature.

Description of the clinical case. We present a case of a 64-year-old male patient with MiNEN MDP. The first clinical manifestation of the disease was obstructive jaundice. To eliminate the jaundice, papillosphincterotomy, transpapillary stenting of the choledochus with a plastic stent was performed. MDP tumor was verifed as adenocarcinoma by histological examination. The patient underwent gastropancreatoduodenal resection. Postoperative immunohistochemical examination showed the expression of antibodies in tumor cells: Synaptophysin (clone 27G12) +++, Chromogranin A (5H7) +, CD 57 (NK-1) ++, Ki 67 (Mib 1) 80 %.

Conclusion: mixed neuroendocrine (G3) non-neuroendocrine carcinoma (G2) of the major duodenal papilla with growth within the wall of the duodenum; metastases of the neuroendocrine component in three lymph nodes, adenocarcinoma metastasis in 1 out of 15 lymph nodes examined; pT2N2M0, MiNEN high grade (classified by S. La Rosa). Conclusion. Mixed neuroendocrine-non-neuroendocrine tumors of MDP are an extremely rare pathology. The accuracy of preoperative morphological diagnostics is not high, therefore, this diagnosis can be easily missed at the preoperative stage. In the morphological study of malignant tumors of MDP, a pathologist should take into account the feasibility of a combination of a neuroendocrine tumor with adenocarcinoma. 

1. Lepage C., Bouvier A.M., Faivre J. Endocrine tumours: epidemiology of malignant digestive neuroendocrine tumours. Eur J Endocrinol. 2013; 168(4): 77–83. doi: 10.1530/EJE-12-0418.

2. Kim J.Y., Hong S.M., Ro J.Y. Recent updates on grading and classifcation of neuroendocrine tumors. Ann Diagn Pathol. 2017; 29: 11–6. doi: 10.1016/j.anndiagpath.2017.04.005.

3. Holmager P., Langer S.W., Kjaer A., Ringholm L., Garbyal R.S., Pommergaard H.C., Hansen C.P., Federspiel B., Andreassen M., Knigge U. Surgery in Patients with Gastro-Entero-Pancreatic Neuroendocrine Carcinomas, Neuroendocrine Tumors G3 and High Grade Mixed Neuroendocrine-Non-Neuroendocrine Neoplasms. Curr Treat Options Oncol. 2022; 23(6): 806–17. doi: 10.1007/s11864-022-00969-x.

4. La Rosa S. Challenges in High-grade Neuroendocrine Neoplasms and Mixed Neuroendocrine/Non-neuroendocrine Neoplasms. Endocr Pathol. 2021; 32(2): 245–57. doi: 10.1007/s12022-021-09676-z.

5. Ren X., Jiang H., Sun K., Qin X., Qu Y., Xia T., Chen Y. Mixed neuroendocrine-non-neuroendocrine neoplasm of the gallbladder: case report and literature review. Diagn Pathol. 2022; 17(1): 51. doi: 10.1186/s13000-022-01231-6.

6. Dobrodeev А.Yu., Gorokhovskaya V.I., Kostromitsky D.N., Afanasyev S.G., Avdeenko Т.V., Bondar L.N., Tarasova A.S., Аvgustinovich А.V. Mixed neuroendocrinenon-neuroendocrine neoplasm of the colon: case report. Experimental and Clinical Gastroenterology. 2021; 11(195): 97–99. (in Russian). doi: 10.31146/1682-8658-ecg-195-11-97-99.

7. Zhang L., DeMay R.M. Cytological features of mixed adenoneuroendocrine carcinoma of the ampulla: two case reports with review of literature. Diagn Cytopathol. 2014; 42(12): 1075–84. doi: 10.1002/dc.23107.

8. de Mestier L., Cros J., Neuzillet C., Hentic O., Egal A., Muller N., Bouché O., Cadiot G., Ruszniewski P., Couvelard A., Hammel P. Digestive System Mixed Neuroendocrine-Non-Neuroendocrine Neoplasms. Neuroendocrinology. 2017; 105(4): 412–25. doi: 10.1159/000475527.

9. Minaya-Bravo A.M., Garcia Mahillo J.C., Mendoza Moreno F., Noguelares Fraguas F., Granell J. Large cell neuroendocrine – Adenocarcinona mixed tumour of colon: Collision tumour with peculiar behaviour. What do we know about these tumours? Ann Med Surg (Lond). 2015; 4(4): 399–403. doi: 10.1016/j.amsu.2015.10.004.

10. Frizziero M., Chakrabarty B., Nagy B., Lamarca A., Hubner R.A., Valle J.W., McNamara M.G. Mixed Neuroendocrine Non-Neuroendocrine Neoplasms: A Systematic Review of a Controversial and Underestimated Diagnosis. J Clin Med. 2020; 9(1): 273. doi: 10.3390/jcm9010273.