Cytological features of mixed adenoneuroendocrine carcinoma of the ampulla of Vater: A case report with immunocytochemical analyses

Diagn Cytopathol. 2018 Jun;46(6):540-546. doi: 10.1002/dc.23891. Epub 2018 Jan 16.


Mixed adenoneuroendocrine carcinoma (MANEC) is defined as a tumor that has morphologically recognizable both adenocarcinoma and neuroendocrine carcinoma components comprising at least 30% of either components. MANEC occurring in the ampulla of Vater is extremely rare, and only 16 cases have been reported in the English language literature. In the present report, we describe the first case of MANEC of the ampulla of Vater with immunocytochemical analyses. An 82-year-old Japanese male was incidentally found to have a tumorous lesion in the ampulla of Vater. Endoscopic ultrasound-fine needle aspiration (EUS-FNA) of the tumor was performed. The Papanicolaou smear demonstrated the presence of different three components. The most dominant component was cohesive clusters of small round cells with round to oval nuclei with powdery chromatin and scant cytoplasm, which corresponded to small cell carcinoma. The second component was an adenocarcinoma, which was composed of irregularly overlapping clusters of tall columnar cells with large round to oval nuclei containing conspicuous nucleoli. The third component was an adenoma, which was comprised of flat cohesive clusters of columnar cells without atypia. Immunocytochemical analyses demonstrated that synaptophysin was expressed in the small round cells, and cdx-2 was expressed in all three components. Accordingly, a cytodiagnosis of MANEC with adenoma component was made. Preoperative diagnosis of ampullary MANEC is difficult. However, this report clearly demonstrates three different components in the EUS-FNA cytological specimen. Therefore, we suggest that cytological examination is a useful method for diagnosis of MANEC of the ampulla of Vater.

Keywords: ampulla of Vater; intestinal-type adenoma; mixed adenoneuroendocrine carcinoma; small cell carcinoma.

Publication types

  • Case Reports

MeSH terms

  • Aged, 80 and over
  • Ampulla of Vater / pathology*
  • Biomarkers, Tumor / metabolism
  • Carcinoma, Neuroendocrine / pathology*
  • Common Bile Duct Neoplasms / pathology*
  • Endoscopic Ultrasound-Guided Fine Needle Aspiration
  • Humans
  • Male


  • Biomarkers, Tumor