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  • Surgical Pathology Criteria

    Intraductal Tubular Carcinoma of the Pancreas


    • Cytologically atypical nodular pancreatic intraductal epithelial proliferation with a predominantly tubular architecture

    Alternate/Historical Names

    • Intraductal and cystic tubulopapillary adenocarcinoma
    • Intraductal tubular carcinoma
    • Intraductal tubular neoplasm with high grade dysplasia
    • Intraductal tubular tumor
    • Microcystic tubulopapillary carcinoma
    • Intraductal tubulopapillary neoplasm (WHO 2010 preferred term)

    Diagnostic Criteria

    • Nodular intraductal growth
      • Duct dilated locally
        • May fill and obliterate duct lining
      • Upstream pancreas may be atrophic
    • Tubular growth pattern predominates
      • Tightly packed tubules
      • Variable sized tubules
      • May be cribriform
      • May be focally to predominantly papillary
    • Cuboidal to columnar cells resembling normal pancreatic duct cells
      • Scant to moderate amount of cytoplasm
        • Eosinophilic to amphophilic cytoplasm
        • Scant to absent cytoplasmic mucin
      • No evidence of mucin secretion
      • No distension of ducts by mucin
      • No goblet cells
    • No acinar differentiation
    • Moderate to marked cytologic atypia
      • Frequent mitotic figures
      • Frequent necrosis
    • May be associated with invasive carcinoma
      • Metastases reported to local nodes, liver and peritoneum
      • Even in the presence of metastases, behavior of carcinoma appears better than for conventional pancreatic carcinoma, with few deaths
    • Intraductal tubular adenoma does not appear to be related to intraductal tubular carcinoma

    Robert V Rouse MD
    Department of Pathology
    Stanford University School of Medicine
    Stanford CA 94305-5342

    Original posting : August 25, 2009

    Supplemental studies

    CK7 Pos
    CK19 Pos
    MUC1 Pos luminal border
    MUC2 Neg
    MUC5AC Neg
    MUC6 Pos
    SMAD4 Pos
    Trypsin Neg
    Fascin Neg

    • KRAS and BRAF wild type by PCR
    • Mucin stains negative to faint/scant positive

    Differential Diagnosis

    Intraductal Tubular Adenoma Intraductal Tubular Carcinoma
    Composed of mucin positive pyloric type cells Generally mucin poor or negative
    Frequent goblet cells No goblet cells
    Low grade atypia High grade atypia
    Mitotic rate 1-5/50 hpf Mitotic rate frequently >5/50 hpf
    No necrosis Frequent necrosis
    Not associated with invasive carcinoma May have associated invasive carcinoma
    Intraductal tubular adenoma and carcinoma do not appear to be related

    Intraductal Tubular Carcinoma Mucinous Cystic Neoplasm of the Pancreas
    Nodular intraductal growth Mucin filled cyst or cysts
    Males and females affected Nearly all female
    Involves segments of ducts Does not communicate with ducts
    Extensive tubule formation No tubules
    No ovarian type stroma Ovarian type stroma

    Intraductal Tubular Carcinoma PanIN
    Usually clinically detectable Usually not clinically detectable
    Grossly visible Not grossly visible
    Well formed tubules No well formed tubules

    Intraductal Tubular Carcinoma Intraductal Papillary Mucinous Neoplasm
    Nodular indtraductal growth dilates duct locally Distended ducts filled with mucin
    Tubular or tubulopapillary pattern Papillary pattern
    Cuboidal to columnar cells without cytoplasmic mucin Columnar mucin filled cells (may lose mucin if high grade)
    Uniform high grade atypia Atypia may vary from low to high
    Necrosis common Necrosis rare
    No goblet, neuroendocrine or paneth cells May have scattered goblet, neuroendocrine or paneth cells
    MUC2, MUC5AC, Fascin negative MUC2, MUC5AC, Fascin positive
    KRAS wild type KRAS frequently mutated

    Intraductal Tubular Carcinoma Intraductal Oncocytic Papillary Neoplasm
    Tubular or tubulopapillary pattern Papillary and solid patterns
    Lacks granular cytoplasm Eosinophilic granular cytoplasm
    No goblet cells Goblet cells frequently present
    PASd negative or weak PASd positive
    MUC2, MUC5AC negative MUC2, MUC5AC positive

    Intraductal Tubular Adenoma Acinar Cell Carcinoma of the Pancreas (Intraductal Variant)
    Trypsin negative Trypsin positive
    PASd negative to weak/focal PASd positive
    These may be indistinguishable by standard microscopy


    Cystic Pancreatic Lesions


    • Bosman FT, Carneiro F, Hruban RH, Thiese ND (Eds). WHO Classifiication of Tumors of the Digestive System, IARC, Lyon 2010.
    • Yamaguchi H, Shimizu M, Ban S, Koyama I, Hatori T, Fujita I, Yamamoto M, Kawamura S, Kobayashi M, Ishida K, Morikawa T, Motoi F, Unno M, Kanno A, Satoh K, Shimosegawa T, Orikasa H, Watanabe T, Nishimura K, Ebihara Y, Koike N, Furukawa T. Intraductal tubulopapillary neoplasms of the pancreas distinct from pancreatic intraepithelial neoplasia and intraductal papillary mucinous neoplasms. Am J Surg Pathol. 2009 Aug;33(8):1164-72.
    • Königsrainer I, Glatzle J, Klöppel G, Königsrainer A, Wehrmann M. Intraductal and cystic tubulopapillary adenocarcinoma of the pancreas--a possible variant of  intraductal tubular carcinoma. Pancreas. 2008 Jan;36(1):92-5.
    • Esposito I, Bauer A, Hoheisel JD, Kleeff J, Friess H, Bergmann F, Rieker RJ, Otto HF, Klöppel G, Penzel R. Microcystic tubulopapillary carcinoma of the pancreas: a new tumor entity? Virchows Arch. 2004 May;444(5):447-53.
    • Tajiri T, Tate G, Inagaki T, Kunimura T, Inoue K, Mitsuya T, Yoshiba M, Morohoshi T. Intraductal tubular neoplasms of the pancreas: histogenesis and differentiation. Pancreas. 2005 Mar;30(2):115-21.
    • Suda K, Hirai S, Matsumoto Y, Mogaki M, Oyama T, Mitsui T, Fujibayashi M, Kumazawa K, Kajiwara T. Variant of intraductal carcinoma (with scant mucin production) is of main pancreatic duct origin: a clinicopathological study of four patients. Am J Gastroenterol. 1996 Apr;91(4):798-800.
    • Katabi N, Klimstra DS. Intraductal papillary mucinous neoplasms of the pancreas: clinical and pathological features and diagnostic approach. J Clin Pathol. 2008 Dec;61(12):1303-13.
    • Albores-Saavedra J, Sheahan K, O'Riain C, Shukla D. Intraductal tubular adenoma, pyloric type, of the pancreas: additional observations on a new type of  pancreatic neoplasm. Am J Surg Pathol. 2004 Feb;28(2):233-8.
    • Nakayama Y, Inoue H, Hamada Y, Takeshita M, Iwasaki H, Maeshiro K, Iwanaga S, Tani H, Ryu S, Yasunami Y, Ikeda S. Intraductal tubular adenoma of the pancreas, pyloric gland type: a clinicopathologic and immunohistochemical study of 6 cases. Am J Surg Pathol. 2005 May;29(5):607-16.
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