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WHO Classification of Tumours
Mixed adenoneuroendocrine carcinoma
Colon and rectum


Definition

Mixed adenoneuroendocrine carcinomas (MANEC) have a phenotype that is morphologically recognizable as both gland-forming epithelial and neuroendocrine, and are defined as carcinomas since both components are malignant and should be graded. A component of squamous cell carcinoma is rare. Arbitrarily, at least 30% of either component should be identified to qualify for this definition. The identification in adenocarcinoma of scattered neuroendocrine cells by immunohistochemistry does not qualify for this definition
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Bosman FT, Carneiro F, Hruban RH, Theise ND (Eds.)
WHO Classification of Tumours of the Digestive System.
4th Edition
International Agency for Research on Cancer: Lyon 2010



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Commentary: Neuroendocrine tumours of the digestive system

Although examples have been reported of NETs or neuroendocrine micronests arising in adenomatous polyps

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Lyda MH, Fenoglio-Preiser CM (1998)
Adenoma-carcinoid tumors of the colon.
Arch Pathol Lab Med 122: 262-5




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Pulitzer M, Xu R, Suriawinata AA, Waye JD, Harpaz N (2006)
Microcarcinoids in large intestinal adenomas.
Am J Surg Pathol 30: 1531-6



, NETs arising in association with adenocarcinomas are exceedingly rare
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Anagnostopoulos GK, Arvanitidis D, Sakorafas G, Pavlakis G, Kolilekas L, Arkoumani E, Stefanou D (2004)
Combined carcinoid-adenocarcinoma tumour of the anal canal.
Scand J Gastroenterol 39: 198-200




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Hock YL, Scott KW, Grace RH (1993)
Mixed adenocarcinoma/carcinoid tumour of large bowel in a patient with Crohn's disease.
J Clin Pathol 46: 183-5




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Jiao YF, Nakamura S, Arai T, Sugai T, Uesugi N, Habano W, Suzuki M, Tazawa H, Goukon Y (2003)
Adenoma, adenocarcinoma and mixed carcinoid-adenocarcinoma arising in a small lesion of the colon.
Pathol Int 53: 457-62




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Knight BK, Hayes MM (1987)
Mixed adenocarcinoma and carcinoid tumour of the colon. A report of 4 cases with postulates on histogenesis.
S Afr Med J 72: 708-10



. Thus, most bona fide MANECs of the large bowel consist of components of adenocarcinoma (or, in the anal canal, squamous cell carcinoma) mixed with high-grade NEC, which can be either small cell or large cell
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Makino A, Serra S, Chetty R (2006)
Composite adenocarcinoma and large cell neuroendocrine carcinoma of the rectum.
Virchows Arch 448: 644-7




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Shia J, Tang LH, Weiser MR, Brenner B, Adsay NV, Stelow EB, Saltz LB, Qin J, Landmann R, Leonard GD, Dhall D, Temple L, Guillem JG, Paty PB, Kelsen D, Wong WD, Klimstra DS (2008)
Is nonsmall cell type high-grade neuroendocrine carcinoma of the tubular gastrointestinal tract a distinct disease entity?
Am J Surg Pathol 32: 719-31



. In fact, as mentioned above, many highgrade NECs have minor exocrine components, and an origin in association with adenomatous polyps is frequent
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Mills SE, Allen MS, Cohen AR (1983)
Small-cell undifferentiated carcinoma of the colon. A clinicopathological study of five cases and their association with colonic adenomas.
Am J Surg Pathol 7: 643-51



. Conversely, immunohistochemically detectable neuroendocrine cells are found in up to 41% of colorectal adenocarcinomas, most of which have no morphological suggestion of a discrete neuroendocrine component
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Indinnimeo M, Cicchini C, Memeo L, Stazi A, Provenza C, Ricci F, Mingazzini PL (2002)
Correlation between chromogranin-A expression and pathological variables in human colon carcinoma.
Anticancer Res 22: 395-8




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Sun MH (2004)
Neuroendocrine differentiation in sporadic CRC and hereditary nonpolyosis colorectal cancer.
Dis Markers 20: 283-8




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Yao GY, Zhou JL, Lai MD, Chen XQ, Chen PH (2003)
Neuroendocrine markers in adenocarcinomas: an investigation of 356 cases.
World J Gastroenterol 9: 858-61



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A neoplasm with morphologically recognizable adeno- and neuroendocrine phenotypes is defined as carcinoma since both components are malignant and should be graded. The identification of scattered neuroendocrine cells by immunohistochemistry in adenocarcinoma does not qualify for this definition. A squamous cell carcinoma component is rare

Click for details
Bosman FT, Carneiro F, Hruban RH, Theise ND (Eds.)
WHO Classification of Tumours of the Digestive System.
4th Edition
International Agency for Research on Cancer: Lyon 2010



.