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  • Surgical Pathology Criteria

    Pancreatic Intraepithelial Neoplasia


    • Microscopic noninvasive epithelial neoplasm arising in the pancreatic ducts

    Alternate/Historical Names

    • Pancreatic intraepithelial lesion (sometimes used for grade 1 or 2 lesions)
    • PanIN

    Diagnostic Criteria

    • Microscopic finding
      • Not grossly visible
    • Usually involves ducts <5 mm in diameter
      • Measure largest cross-section from basement membrane
      • Do not include periductal lesions or fibrosis
      • Measure entire duct even if only partially involved
      • Involved ducts >5 mm may be due to obstruction
    • Lined by columnar to cuboidal mucinous cells
      • Mucin may be depleted in high grade lesions
    • Varying degrees of cytologic atypia and architectural complexity

    Reetesh Pai MD
    Department of Pathology
    Stanford University School of Medicine
    Stanford CA 94305-5342

    Original posting : February 1, 2007

    Supplemental studies


    • MUC2 and CDX2 negative

    Differential Diagnosis

    Normal Duct PanIN
    Cuboidal to low columnar lining Tall columnar lining
    Amphophilic cytoplasm Abundant supranuclear mucin
    Regular bland nuclei May show nuclear crowding and atypia

    Reactive Duct PanIN
    Round smooth nuclei Nuclei may show irregularity
    Basally oriented nuclei May have pseudostratified or stratified nuclei
    Eosinophilic cytoplasm Abundant supranuclear mucin
    No micropapillary architecture May be micropapillary

    Cancerization of Duct by Invasive Ductal Carcinoma PanIN, Grade 3
    Abrupt transition of neoplastic to normal Gradual transition
    May be continuous with invasive carcinoma Not continuous with invasive carcinoma

    Intraductal Papillary Mucinous Neoplasm PanIN
    Usually clinically detectable Usually not clinically detectable
    Grossly visible Not grossly visible
    May have well formed papillae No well formed papillae
    May be associated with colloid carcinoma No association with colloid carcinoma
    MUC2 or CDX2 may be positive MUC2 and CDX2 negative


    • PanIN 1A and 1B are common incidental findings
      • May be found in up to 40% of noncancerous pancreata
    • Natural history of PanIN 2 and 3 is not known
    • PanIN 3, at least, may be a precursor to invasive ductal carcinoma
      • Rare in noncancerous pancreata
      • Present in 30-50% of pancreata with invasive carcinomas
      • Associated with usual ductal type adenocarcinoma
        • No association with colloid (mucinous) carcinoma
    • Margin involvement in cases with resected invasive carcinoma
      • PanIN 1 and 2 require no further therapy
      • PanIN 3
        • Older patient
          • No clear benefit as resection may deplete pancreatic reserves
        • Young patient
          • May benefit from additional resection to prevent progression to invasive carcinoma

    Grading / Staging / Report

    • Grading
      • PanIN 1A
        • Flat
        • Tall columnar cells
        • Bland, basal nuclei
        • Abundant supranuclear mucin
      • PanIN 1B
        • Micropapillary architecture or
        • Basally stratified architecture
        • Otherwise identical to PanIN 1A
      • PanIN 2
        • Usually papillary but may be flat
        • Mild cytologic atypia
          • Loss of polarity
          • Nuclear crowding
          • Pseudostratification
          • Hyperchromasia
          • Mitotic figures rare, not atypical
        • No necrosis or cribriform architecture
      • PanIN 3
        • Architectural atypia
          • Cribriform or
          • Budding off of small clusters of cells into lumen
          • Lumenal necrosis
            • Diagnostic if present
        • Significant cytologic atypia
          • Loss of nuclear polarity
          • Dystrophic (upside down) goblet cells
          • Prominent nucleoli
          • Frequent mitotic figures
            • May be atypical
    • Staging
      • Not relevant unless invasive carcinoma is present
    • Report
      • Grade
      • Presence or absence of invasive carcinoma
        • Give type and size


    Mucinous Pancreatic Lesions


    • 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, Luttges J, Maitra A, Offerhaus GJ, Shimizu M, Yonezawa S. An illustrated consensus on the classification of pancreatic intraepithelial neoplasia and intraductal papillary mucinous neoplasms. Am J Surg Pathol. 2004 Aug;28(8):977-87.
    • Maitra A, Fukushima N, Takaori K, Hruban RH. Precursors to invasive pancreatic cancer. Adv Anat Pathol. 2005 Mar;12(2):81-91.
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