Abstract
Recently, the term mixed neuroendocrine non-neuroendocrine neoplasms (MiNEN) has been proposed as an umbrella definition covering different possible combinations of mixed neuroendocrine-exocrine neoplasms. Among these, the adenoma plus neuroendocrine tumor (NET) combination is among the rarest and not formally recognized by the 2019 WHO Classification. In this setting, the debate between either collision tumors or true mixed neoplasms is still unsolved. In this report, a pancreatic intraductal papillary mucinous neoplasm (IPMN) plus a NET is described, and the molecular investigations showed the presence in both populations of the same KRAS, GNAS, and CDKN2A mutations and the amplification of the CCND1 gene. These data prove clonality and support a common origin of both components, therefore confirming the true mixed nature. For this reason, mixed neuroendocrine-exocrine neoplasms, in which the exocrine component is represented by a glandular precursor lesion (adenoma/IPMN) only, should be included into the MiNEN family.
References
WHO (2019) Classification of Tumours Editorial Board, Digestive System Tumours, 5th edn. IARC Press, Lyon
Bosman FT, Carneiro F, Hruban RH, Theise ND (eds) (2010) WHO classification of tumours of the digestive system, 4th edn. IARC Press, Lyon
La Rosa S, Ucella S, Molinari F, Savio A, Mete O et al (2018) Mixed adenoma well-differentiated neuroendocrine tumor (MANET) of the digestive system: an indolent subtype of mixed neuroendocrine-nonneuroendocrine neoplasm (MiNEN). Am J Surg Pathol 42(11):1503–1512
Manuel-Vazquez A, Ramia JM, Latorre-Fraqua R, Valle-Rubio A, Arteaga-Peralta V, Ramiro-Pérez C et al (2018) Pancreatic neuroendocrine tumors and intraductal papillary mucinous neoplasm of the pancreas: a systematic review. Pancreas. 47(5):551–555
Woischke C, Schaaf CW, Yang HM, Vieth M, Veits L, Geddert H, Märkl B, Stömmer P, Schaeffer DF, Frölich M, Blum H, Vosberg S, Greif PA, Jung A, Kirchner T, Horst D (2017) In-depth mutational analyses of colorectal neuroendocrine carcinomas with adenoma or adenocarcinoma components. Mod Pathol 30(1):95–103
Lloyd RV, Osamura RY, Kloppel G, Rosai J (eds) (2017) WHO classification of tumours of endocrine organs, 4th edn. IARC Press, Lyon
Marrache F, Cazals-Hatem D, Kianmanesh R, Palazzo L, Couvelard A, O’Tole D et al (2005) Endocrine tumor and intraductal papillary mucinous neoplasm of the pancreas: a fortuitous association? Pancreas. 31(1):79–83
Kadota Y, Shinoda M, Tanabe M, Tsujikawa H, Ueno A, Masugi Y, Oshima G, Nishiyama R, Tanaka M, Mihara K, Abe Y, Yagi H, Kitago M, Itano O, Kawachi S, Aiura K, Tanimoto A, Sakamaoto M, Kitagawa Y (2013) Concomitant pancreatic endocrine neoplasm and intraductal papillary mucinous neoplasm: a case report and literature review. World J Surg Oncol 11:75
Moriyoshi K, Minamiguchi S, Miyagawa-Hayashino A, Fujimoto M, Kawaguchi M, Haga H (2013) Collision of extensive exocrine and neuroendocrine neoplasms in multiple endocrine neoplasia type 1 revealed by cytogenetic analysis of loss of heterozygosity: a case report. Pathol Int 63(9):469–475
Scarpa A, Chang DK, Nones K, Corbo V, Patch AM, Bailey P et al (2017) Whole-genome landscape of pancreatic neuroendocrine tumours [published correction appears in nature. 2017 Sep 27]. Nature. 543(7643):65–71
Amato E, Dal Molin M, Mafficini A, Yu J, Malleo G, Rusev B et al (2014) Targeted next-generation sequencing of cancer genes dissects the molecular profiles of intraductal papillary neoplasms of the pancreas. J Pathol 233(3):217–227
Roy S, LaFramboise WA, Liu TC, Cao D, Luvison A, Miller C et al (2018) Loss of chromatin-remodeling proteins and/or CDKN2A associates with metastasis of pancreatic neuroendocrine tumors and reduced patient survival times. Gastroenterology 154(8):2060–2063.e8
Chung DC, Brown SB, Graeme-Cook F, Seto M, Warshaw AL, Jensen RT, Arnold A (2000) Overexpression of cyclin D1 occurs frequently in human pancreatic endocrine tumors. J Clin Endocrinol Metab 85(11):4373–4378
Biankin AV, Binakin SA, Kench JG, Morey AL, Lee CS, Head DR et al (2002) Aberrant p16(INK4A) and DPC4/Smad4 expression in intraductal papillary mucinous tumours of the pancreas is associated with invasive ductal adenocarcinoma. Gut. 50(6):861–868
Fritz S, Fernandez-del Castillo C, Mino-Kenudson M, Crippa S, Deshpande V, Lauwers GY, Warshaw AL, Thayer SP, Iafrate AJ (2009) Global genomic analysis of intraductal papillary mucinous neoplasms of the pancreas reveals significant molecular differences compared to ductal adenocarcinoma. Ann Surg 249(3):440–447
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The authors want to thank Dr. Luca Albarello for useful discussion and suggestions, Roberto Cairella and Patricia Ney for their invaluable technical assistance.
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MF and SP were involved in patient care and provided clinical information and specimen. LP and IF performed FISH. RM performed laser capture microdissection. MGC and GG performed sequencing. MSL, AP, and CD wrote the manuscript.
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Schiavo Lena, M., Cangi, M.G., Pecciarini, L. et al. Evidence of a common cell origin in a case of pancreatic mixed intraductal papillary mucinous neoplasm–neuroendocrine tumor. Virchows Arch 478, 1215–1219 (2021). https://doi.org/10.1007/s00428-020-02942-1
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DOI: https://doi.org/10.1007/s00428-020-02942-1