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pancreatic intraepithelial neoplasia

Friday 12 June 2009

PanIN; PanINs; 1998


Definition: Most common precursor lesions of pancreatic ductal adenocarcinoma are microscopic papillary or flat, non-invasive epithelial neoplasms that are usually @<@ 5 mm and confined to pancreatic ducts. It is composed of columnar to cuboidal cells with variable mucin, and divided into three grades according to degree of cytological and architectural atypia (WHO).

Other precursor lesions are IPMN ( intraductal papillary mucinous neoplasm ) and MCN ( mucinous cystic neoplasm ).


- PanIN ( pancreatic intraepithelial neoplasia ) / PanINs


- PanIN-1A (Pancreatic Intraepithelial Neoplasia 1-A)

  • These are flat epithelial lesions composed of tall columnar cells with basally located nuclei and abundant supranuclear mucin.
  • The nuclei are small and round to oval in shape.
  • When oval the nuclei are oriented perpendicular to the basement membrane.
  • It is recognized that there is considerable histologic overlap between non-neoplastic flat hyperplastic lesions and flat neoplastic lesions without atypia.
  • Therefore, some may choose to designate these lesions with the modifier lesion ("PanIN/[L]-1A") to reflect the fact that the neoplastic nature of many cases of PanIn-1A has not been established.

- PanIN-1B (Pancreatic Intraepithelial Neoplasia 1-B)

  • These epithelial lesions have a papillary, micropapillary or basally pseudostratified architecture, but are otherwise identical to PanIN-1A.

- PanIN-2 (Pancreatic Intraepithelial Neoplasia 2)

  • Architecturally these mucinous epithelial lesions may be flat or papillary.
  • Cytologically, by definition, these lesions must have some nuclear abnormalities.
  • These abnormalities may include some loss of polarity, nuclear crowding, enlarged nuclei, pseudo-stratification and hyperchromatism.
  • These nuclear abnormalities fall short of those seen in PanIN-3.
  • Mitoses are rare, but when present are non-luminal (not apical) and not atypical.
  • True cribriforming luminal necrosis and marked cytologic abnormalities are generally not seen, and when present should suggest the diagnosis of PanIN-3.

- PanIN-3 (Pancreatic Intraepithelial Neoplasia 3)

  • Architecturally, these lesions are usually papillary or micropapillary, however, they may rarely be flat.
  • True cribriforming, budding off of small clusters of epithelial cells into the lumen and luminal necroses should all suggest the diagnosis of PanIN-3.
  • Cytologically, these lesions are characterized by a loss of nuclear polarity, dystrophic goblet cells (goblet cells with nuclei oriented towards the lumen and mucinous cytoplasm oriented toward the basement membrane), mitoses which may occasionally be abnormal, nuclear irregularities and prominent (macro) nucleoli.

Mimickers of PanIN

1. Cancerization of ducts

It was recognized that infiltrating carcinomas can extend into pancreatic ducts and ductules. When they do, they may mimic PanIN-3. An infiltrating carcinoma in close proximately to a duct lesion and an abrupt transition from a highly atypical lesion to normal duct epithelium should both suggest the possibility of cancerization of the duct or ductule. In these cases, serial (step) sections may be helpful in defining the relationship of the duct lesion to the infiltrating carcinoma.

2. Intraductal Papillary Mucinous Neoplasms (IPMNs)

IPMNs are mucinous epithelial neoplasms which involve the main pancreatic duct or its major branches. They are larger than PanINs and therefore usually visible grossly or by radiologic imaging. IPMNs may extend into small ducts. In these cases serial (step) sections may be helpful in defining the relationship of the two lesions.

3. Mucinous cystic neoplasms

Mucinous cystic neoplasms are characterized by the presence of ovarian stroma and the absence of a connection to the duct system. These features and the larger size of mucinous cystic neoplasms help distinguish mucinous cystic neoplasms from PanINs.

4. Reactive changes

Reactive changes may mimic PanINs. The presence of significant inflammatory cell infiltrates, particularly when there are numerous polymorphonuclear leukocytes, should raise the possibility of reactive changes.

Molecular biology

- Widespread activation of the DNA damage response in human pancreatic intraepithelial neoplasia. (19668150)


- Nomenclature for Classification of Duct Lesions in the Pancreas (NCI, 1999) at Hopkins

Open references

- Widespread activation of the DNA damage response in human pancreatic intraepithelial neoplasia. Koorstra JB, Hong SM, Shi C, Meeker AK, Ryu JK, Offerhaus GJ, Goggins MG, Hruban RH, Maitra A. Mod Pathol. 2009 Nov;22(11):1439-45. doi : 10.1038/modpathol.2009.114
PMID: 19668150


- Hruban RH, Adsay NV, Albores-Saavedra J, Compton C, Garrett E, Goodman SN, Kern SE, Klimstra DS, Kloppel G, Longnecker DS, Luttges J, Offerhaus GJA. Pancreatic intraepithelial neoplasia (PanIN): A New nomenclature and classification system for pancreatic duct lesions. Am J Surg Pathol