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

Alessandro Vanoli, Luca Albarello, Stefania Uncini, Matteo Fassan, Federica Grillo, Antonio Di Sabatino, Michele Martino, Claudio Pasquali, Anna C. Milanetto, Massimo Falconi, Stefano Partelli, Claudio Doglioni, Marco Schiavo-Lena, Tatiana Brambilla, Andrea Pietrabissa, Fausto Sessa, Carlo Capella, Guido Rindi, Stefano La Rosa, Enrico SolciaMarco Paulli

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Abstract

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.

Original languageEnglish
Pages (from-to)725-736
Number of pages12
JournalAmerican Journal of Surgical Pathology
Volume43
Issue number6
DOIs
Publication statusPublished - Jun 1 2019

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Neuroendocrine Tumors
Somatostatin
Pancreatic Polypeptide
Neoplasms
Keratin-7
Paraganglioma
Epithelioid Cells
Gastrins
Stromal Cells
Duodenum
Ganglia
Serotonin
Lymph Nodes
Neoplasm Metastasis

Keywords

  • ampullary-type somatostatin producing tumor
  • gangliocytic paraganglioma
  • MUC1
  • nonfunctioning neuroendocrine tumor
  • somatostatin receptor

ASJC Scopus subject areas

  • Anatomy
  • Surgery
  • Pathology and Forensic Medicine

Cite this

@article{e64dcbae93dc4891b89b225cd4be8300,
title = "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",
abstract = "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.",
keywords = "ampullary-type somatostatin producing tumor, gangliocytic paraganglioma, MUC1, nonfunctioning neuroendocrine tumor, somatostatin receptor",
author = "Alessandro Vanoli and Luca Albarello and Stefania Uncini and Matteo Fassan and Federica Grillo and {Di Sabatino}, Antonio and Michele Martino and Claudio Pasquali and Milanetto, {Anna C.} and Massimo Falconi and Stefano Partelli and Claudio Doglioni and Marco Schiavo-Lena and Tatiana Brambilla and Andrea Pietrabissa and Fausto Sessa and Carlo Capella and Guido Rindi and {La Rosa}, Stefano and Enrico Solcia and Marco Paulli",
year = "2019",
month = "6",
day = "1",
doi = "10.1097/PAS.0000000000001234",
language = "English",
volume = "43",
pages = "725--736",
journal = "American Journal of Surgical Pathology",
issn = "0147-5185",
publisher = "Lippincott Williams and Wilkins",
number = "6",

}

TY - JOUR

T1 - Neuroendocrine Tumors (NETs) of the Minor Papilla/Ampulla

T2 - Analysis of 16 Cases Underlines Homology With Major Ampulla NETs and Differences From Extra-Ampullary Duodenal NETs

AU - Vanoli, Alessandro

AU - Albarello, Luca

AU - Uncini, Stefania

AU - Fassan, Matteo

AU - Grillo, Federica

AU - Di Sabatino, Antonio

AU - Martino, Michele

AU - Pasquali, Claudio

AU - Milanetto, Anna C.

AU - Falconi, Massimo

AU - Partelli, Stefano

AU - Doglioni, Claudio

AU - Schiavo-Lena, Marco

AU - Brambilla, Tatiana

AU - Pietrabissa, Andrea

AU - Sessa, Fausto

AU - Capella, Carlo

AU - Rindi, Guido

AU - La Rosa, Stefano

AU - Solcia, Enrico

AU - Paulli, Marco

PY - 2019/6/1

Y1 - 2019/6/1

N2 - 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.

AB - 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.

KW - ampullary-type somatostatin producing tumor

KW - gangliocytic paraganglioma

KW - MUC1

KW - nonfunctioning neuroendocrine tumor

KW - somatostatin receptor

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DO - 10.1097/PAS.0000000000001234

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VL - 43

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EP - 736

JO - American Journal of Surgical Pathology

JF - American Journal of Surgical Pathology

SN - 0147-5185

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