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WHO Classification of Tumours
Pancreatic intraepithelial neoplasia, grade 3 (PanIN-3)


Pancreatic intraepithelial neoplasias (PanINs) are the most common precursor lesions of pancreatic ductal adenocarcinoma. Less frequently, macroscopic (cystic) precursor lesions, including mucinous cystic neoplasms (MCNs) with low- or intermediate-grade dysplasia or with high-grade dysplasia and intraductal papillary mucinous neoplasms (IPMNs) with low- or intermediate dysplasia or with high grade dysplasia , may also progress to ductal adenocarcinoma.

As defined by published consensus guidelines

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Hruban RH, Takaori K, Klimstra DS, Adsay NV, Albores-Saavedra J, Biankin AV, Biankin SA, Compton C, Fukushima N, Furukawa T, Goggins M, Kato Y, Kloppel G, Longnecker DS, Lüttges J, Maitra A, Offerhaus GJ, Shimizu M, Yonezawa S (2004)
An illustrated consensus on the classification of pancreatic intraepithelial neoplasia and intraductal papillary mucinous neoplasms.
Am J Surg Pathol 28: 977-87

, PanINs are microscopic papillary or flat, noninvasive epithelial neoplasms that are usually < 5 mm in diameter and confined to the pancreatic ducts. Composed of columnar to cuboidal cells with varying amounts of mucin, PanINs are divided into three grades according to the degree of cytological and architectural atypia. Lesions with minimal, moderate or marked atypia are designated PanIN-1, PanIN-2, and PanIN-3, respectively. PanIN-1 lesions are further subdivided into flat (PanIN-1A) and papillary types (PanIN-1B) (For more details on morphological features of PanINs, please see histopathology). Multiple lines of evidence support the hypothesis that PanINs are bona fide precursors of infiltrating ductal adenocarcinoma. PanINs (especially higher grade lesions) are more common in pancreata with adenocarcinoma than without
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Andea A, Sarkar F, Adsay VN (2003)
Clinicopathological correlates of pancreatic intraepithelial neoplasia: a comparative analysis of 82 cases with and 152 cases without pancreatic ductal adenocarcinoma.
Mod Pathol 16: 996-1006

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Kozuka S, Sassa R, Taki T, Masamoto K, Nagasawa S, Saga S, Hasegawa K, Takeuchi M (1979)
Relation of pancreatic duct hyperplasia to carcinoma.
Cancer 43: 1418-28

, with at least one study identifying PanIN-3 exclusively in pancreata with an invasive carcinoma
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Cubilla AL, Fitzgerald PJ (1976)
Morphological lesions associated with human primary invasive nonendocrine pancreas cancer.
Cancer Res 36: 2690-8

. As is true for ductal adenocarcinoma, the incidence of PanINs increases with age, and PanINs are more common in the head than in the tail of the pancreas
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Hruban RH, Maitra A, Kern SE, Goggins M (2007)
Precursors to pancreatic cancer.
Gastroenterol Clin North Am 36: 831-49, vi

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Kozuka S, Sassa R, Taki T, Masamoto K, Nagasawa S, Saga S, Hasegawa K, Takeuchi M (1979)
Relation of pancreatic duct hyperplasia to carcinoma.
Cancer 43: 1418-28

. Although rare, patients have been reported who had a residual high grade PanIN lesion at the surgical margin of a partial pancreatectomy for benign disease and then, several months to years after surgery, developed invasive adenocarcinoma in the remnant pancreas
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Brat DJ, Lillemoe KD, Yeo CJ, Warfield PB, Hruban RH (1998)
Progression of pancreatic intraductal neoplasias to infiltrating adenocarcinoma of the pancreas.
Am J Surg Pathol 22: 163-9

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Brockie E, Anand A, Albores-Saavedra J (1998)
Progression of atypical ductal hyperplasia/carcinoma in situ of the pancreas to invasive adenocarcinoma.
Ann Diagn Pathol 2: 286-92

. Perhaps the most compelling evidence comes from the demonstration that PanINs and invasive ductal adenocarcinomas share critical genetic abnormalities
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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


Commentary: Preneoplastic lesions of the digestive system