Exocrine tumors / carcinomas
PanIN (pancreatic intraepithelial neoplasia)

Topic Completed: 1 August 2012

Revised: 25 June 2019

Copyright: (c) 2002-2019,, Inc.

PubMed Search: PanIN[TI] OR pancreatic intraepithelial neoplasia[TI]

Deepali Jain, M.D.
Page views in 2018: 8,825
Page views in 2019 to date: 7,552
Cite this page: Jain D. PanIN (pancreatic intraepithelial neoplasia). website. Accessed September 19th, 2019.
Definition / general
  • Most common precursor lesions of pancreatic ductal adenocarcinoma (other precursor lesions are IPMN and MCN); are microscopic papillary or flat, noninvasive epithelial neoplasms that are usually < 5 mm and confined to pancreatic ducts; composed of columnar to cuboidal cells with variable mucin and divided into three grades according to degree of cytological and architectural atypia
  • First described in 1998 (Am J Surg Pathol 1998;22:163)
Clinical features

Images hosted on other servers:



  • Normal ductal and ductular epithelium is a cuboidal to low columnar epithelium with amphophilic cytoplasm
  • Mucinous cytoplasm, nuclear crowding and atypia are not seen

Squamous (transitional) metaplasia:
  • Normal cuboidal ductal epithelium is replaced by mature squamous or transitional epithelium without atypia

PanIN 1A:
  • Flat epithelial lesions composed of tall columnar cells with basally located nuclei and abundant supranuclear mucin
  • Nuclei are small, round to oval
  • If oval, the nuclei are perpendicular to the basement membrane
  • Also designated PanIN / L 1A to reflect that the neoplastic nature of many cases is not established
  • May demonstrate KRAS mutations, although they are present in 70% of normal pancreata at autopsy

PanIN 1B:
  • Epithelial lesions with a papillary, micropapillary or basally pseudostratified architecture but otherwise identical to PanIN 1A

PanIN 2:
  • Flat or papillary mucinous epithelial lesions with some nuclear abnormalities (some loss of polarity, nuclear crowding, enlarged nuclei, pseudostratification and hyperchromasia) but less than PanIN 3
  • Rare mitoses are nonluminal (not apical) and not atypical
  • Usually no true cribriforming luminal necrosis or marked cytologic abnormalities

PanIN 3:
  • Papillary or micropapillary, rarely flat
  • True cribriforming, budding off of small clusters of epithelial cells into the lumen and luminal necroses suggests PanIN 3
  • 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 be abnormal, nuclear irregularities and prominent (macro) nucleoli
  • References: Am J Surg Pathol 2001;25:579
Microscopic (histologic) images


Duct is lined by severely atypical epithelium which forms an irregular papillary projection showing a cribriform pattern and lacking a fibrovascular core; this lesion was found near an invasive ductal adenocarcinoma

Severe atypia of duct
epithelium which
abruptly replaces benign
appearing duct cells

Images hosted on other servers:


Squamous (transitional) metaplasia

PanIN 1A

PanIN 1B

PanIN 2

PanIN 3

PanIN 1, 2 and 3

Frozen section margins: PanIN 1, 2 and 3

PanIN 2 and 3

Positive stains
Negative stains
Molecular / cytogenetics description
Differential diagnosis
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