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Neuroendocrine Tumors (NETs) of the Minor Papilla/Ampulla

Analysis of 16 Cases Underlines Homology With Major Ampulla NETs and Differences From Extra-Ampullary Duodenal NETs

Vanoli, Alessandro, MD, PhD*,†; Albarello, Luca, MD; Uncini, Stefania, MD*; Fassan, Matteo, MD, PhD§; Grillo, Federica, MD∥,¶; Di Sabatino, Antonio, MD#; Martino, Michele, BSc#; Pasquali, Claudio, MD**; Milanetto, Anna C., MD**; Falconi, Massimo, MD††; Partelli, Stefano, MD, PhD††; Doglioni, Claudio, MD; Schiavo-Lena, Marco, MD; Brambilla, Tatiana, MD‡‡; Pietrabissa, Andrea, MD, PhD§§; Sessa, Fausto, MD∥∥; Capella, Carlo, MD∥∥; Rindi, Guido, MD, PhD¶¶,##; La Rosa, Stefano, MD***; Solcia, Enrico, MD*; Paulli, Marco, MD, PhD*,†

The American Journal of Surgical Pathology: June 2019 - Volume 43 - Issue 6 - p 725–736
doi: 10.1097/PAS.0000000000001234
Original Articles
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Neuroendocrine tumors (NETs) of the minor papilla/ampulla (MIPA) are rare and poorly studied. Only individual case reports and no comprehensive analysis are available from the literature. We collected 16 MIPA NETs and investigated their clinicopathologic and immunohistochemical features, including markers such as somatostatin, pancreatic polypeptide, gastrin, serotonin, MUC1, cytokeratin 7, and somatostatin receptors type 2A and 5. The median age at diagnosis was 57.5 years, and the female-to-male ratio was 2.2:1. The median NET size was 1.45 cm, and most (94%) were low-grade (G1) tumors. Similarly to what was observed in the major ampulla, 3 histotypes were found: (i) ampullary-type somatostatin-producing tumors (ASTs, 10 cases), characterized by somatostatin expression in most tumor cells, focal-to-extensive tubulo-acinar structures, often with psammoma bodies, MUC1 reactivity, and no or rare membranous reactivity for somatostatin receptor type 2A; (ii) gangliocytic paragangliomas (3 cases), characterized by the coexistence of 3 tumor cell types: epithelioid, often reactive for pancreatic polypeptide, ganglion-like cells, and S100 reactive sustentacular/stromal cells; and (iii) ordinary nonfunctioning NETs (3 cases), resembling those more commonly observed in the extra-ampullary duodenum. Comparable histotypes could also be recognized among the 30 MIPA NETs from the literature. No NET-related patient death among MIPA cases was observed during a median follow-up of 38 months; however, MIPA ASTs showed lymph node metastases and invasion of the duodenal muscularis propria or beyond in 44% and 40% of cases, respectively. In conclusion, MIPA NETs closely resemble tumors arising in the major ampulla, with predominance of ASTs.

*Department of Molecular Medicine, Unit of Anatomic Pathology, University of Pavia

#First Department of Internal Medicine, IRCCS San Matteo Hospital Foundation, University of Pavia

Anatomic Pathology, IRCCS San Matteo Hospital Foundation, Pavia

§§Department of Clinical-Surgical, Diagnostic and Pediatric Sciences, Unit of General Surgery 2, University of Pavia and IRCCS San Matteo Hospital Foundation, Pavia

Pathology Unit, IRCCS San Raffaele Scientific Institute

††Pancreatic Surgery Unit, Pancreas Translational & Clinical Research Center, San Raffaele Scientific Institute, “Vita-Salute” University

‡‡Pathology Unit, Humanitas Research Hospital, Humanitas University, Rozzano, Milan

§Department of Medicine (DIMED), Surgical Pathology & Cytopathology Unit

**Department of Surgery 1 Pancreatic and Endocrine Digestive Surgical Unit, University of Padua, Padua

Department of Surgical Science and Integrated Diagnostics (DISC), Pathology Unit, University of Genoa

San Martino Hospital, Genoa

∥∥Department of Medicine and Surgery, Anatomic Pathology Unit, University of Insubria, Varese

¶¶Institute of Anatomic Pathology

##Rome ENETS Center of Excellence, University Hospital Foundation A. Gemelli IRCCS-Catholic University of Sacred Heart, Rome, Italy

***Service of Clinical Pathology, Institute of Pathology, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland

This publication is distributed under the terms of open access policies implemented by the the Italian Ministry of Education, University and Research (MIUR).

Conflicts of Interest and Source of Funding: Supported by a Grant of the Italian Ministry of Education, University and Research (MIUR) to the Department of Molecular Medicine of the University of Pavia under the initiative “Dipartimenti di Eccellenza (2018–2022).” This study was also partly supported by Grants from Fondazione Cariplo (grant No. 2012-0529) to Fondazione IRCCS Policlinico San Matteo and from Associazione Italiana Ricerca sul Cancro—AIRC IG 2013-14696 to G.R. A.V. declares that he has received speaker’s fee by Novartis Pharma. G.R. declares that he has received consultant honoraria by Advanced Accelerator Applications SA, Bracco Imaging, Ipsen Pharma, and speaker’s fee by Novartis Pharma and Ipsen Pharma. M.F. declares that he has received consultant honoraria by Advanced Accelerator Applications SA, Ipsen Pharma, and speaker’s fee by Novartis Pharma and Ipsen Pharma. The remaining authors none were declared.

Correspondence: Alessandro Vanoli, MD, PhD, Department of Molecular Medicine, Unit of Anatomic Pathology, University of Pavia, Via Forlanini, 16, Pavia 27100, Italy (e-mail: alessandro.vanoli@unipv.it).

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