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    • Surgical Pathology Criteria

    Ductal Adenocarcinoma of the Pancreas

    Definition

    • Carcinoma of the pancreas exhibiting ductal differentiation

    Alternate/Historical Names

    • Pancreatic adenocarcinoma
    • Pancreatic carcinoma

    Diagnostic Criteria

    • Irregular glands
      • Usually at least the size of medium sized ducts
        • Small gland carcinomas can be seen
      • Partial / incomplete glands
      • Single infiltrating cells may be seen
    • Haphazard, disorganized invasive pattern
      • Loss of lobular grouping and ductal branching pattern
      • Presence of ducts adjacent to muscular vessels
      • Perineural invasion
        • Has been reported rarely in chronic pancreatitis
      • Bare ducts in fat
        • Only thin rim of fibromuscular tissue
        • 50% sensitive on resection specimens, 2% on biopsies
        • Very specific (reported 100%)
      • May invade into pre-existing ducts
    • Variable nuclear pleomorphism
      • Bland cases rely on architectural features for diagnosis
      • Nuclear variability with at least 4:1 nuclear size ratios is virtually diagnostic
      • Nucleoli >1/4 the diameter of the nucleus are strongly supportive of carcinoma
    • Frequent desmoplastic stromal response
    • Occasional patterns (no clinical significance)
      • Foamy gland
        • Columnar cells with abundant apical microvesicular cytoplasm
          • Mucin negative cytoplasm but apical cytoplasm may show some staining
        • Apical cytoplasmic condensation reminiscent of a brush border
        • Basally located hyperchromatic small cytologically bland nuclei
        • Recognize based on invasive pattern
      • Clear cell
        • Negative for cytoplasmic glycogen and mucin
        • Reminiscent of renal cell carcinoma
        • May form solid areas
        • Mucin scant to negative in most cases
        • A frequent focal pattern in ordinary adenocarcinomas
          • Should be at least 75% clear to be designated clear cell variant
        • One study (Kim) suggests a worse prognosis
      • Cystic papillary (Kelly)
        • Cysts 0.5-1.1 cm
        • Lined by tall mucinous cells
        • Complex papillae
        • Usually mixed with conventional ductal adenocarcinoma
          • May predominate
        • Elastin stain negative (distinguishes from IPMN)
    • The following are considered separately as they may have different behavior or clinically distinct features:

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

    Original posting / last update: 1/4/08, 6/17/12

    Supplemental studies

    Immunohistology

    CK7+20+ 64%
    CK7+20- 28%
    CK7-20+ 5%
    CK7-20- 3%
    • Clear cell variant reported to be positive for hepatocyte nuclear factor-1Beta but sensitivity and specificity do not appear to be useful for diagnosis.

    Differential diagnosis

    Chronic Pancreatitis Ductal Adenocarcinoma of the Pancreas
    Lobular architecture preserved Haphazard infiltrative pattern
    Tubular or oval shape of ducts Irregularly shaped ducts
    Ductal epithelial lining intact Partial / incomplete ducts may be seen
    Ducts accompanied by islets and/or thick fibrous tisue Bare ducts in fat with only thin rim of fibromuscular tissue
    Acini or stroma between ducts and muscular vessels Ducts adjacent to muscular vessels
    Perineural invasion very rare Perineural invasion may be present
    Little variation in nuclear size Nuclear size variation of >4:1 may be seen
    Nucleoli may be moderately enlarged Nucleoli may exceed 1/4 of nuclear diameter

     

    Lymphoplasmacytic Sclerosing Pancreatitis (Autoimmune Type 1) Ductal Adenocarcinoma of the Pancreas
    Prominent lymphoplasmacytic infiltrate Inflammation not a prominent part of mass
    No infiltrative pattern of ducts Infiltrative pattern prominent
    Elevated serum IgG4 No elevation of IgG4
    Immunohistologic demonstration of >30 IgG4 plasma cells per hpf Few IgG4 plasma cells
    More of a gross problem than a microscopic problem

     

    Acinar Cell Carcinoma of the Pancreas Ductal Adenocarcinoma of the Pancreas
    Granular cytoplasm Mucinous cytoplasm
    Nuclei round, usually basal, at most moderately pleomorphic Pleomorphic nuclei, may be variably located
    Usually solid or acinar formations Large, irregular open ductal formations
    Lobular pattern without desmoplastic stroma Desmoplastic stroma
    Single, large, central nucleoli Nucleoli variable
    BCL10, trypsin, chymotrypsin positive BCL10, trypsin, chymotrypsin negative
    Mixed patterns may occur

     

    Pancreatoblastoma Ductal Adenocarcinoma of the Pancreas
    Predominantly pediatric but 1/3 in adults Very rare under age 20
    Foci of squamoid nests No squamoid nests
    Prominent acinar differentiation No acinar differentiation
    Ductal differentiation usually focal Predominant ductal differentiation
    May have primitive round cell component No primitive round cell component

     

    Medullary Carcinoma of the Pancreas Poorly Differentiated Ductal Adenocarcinoma of the Pancreas
    Pushing border Infiltrative border
    Syncitial pattern Usually has more distinct cell borders
    May show microsatellite instability and/or mismatch repair deficiency Not associated with mismatch repair defects

     

    Other periampullary carcinomas

    • Frequently very similar histologic appearance
    • Frequently similar immunophenotype
    • Distinguish based on location of center of mass
    • Identification of an in situ component may be helpful
      • Beware of invasive carcinomas growing along a pre-existing basement membrane

    Clinical

    • Approximately 10% are familial
      • Most are not associated with any known syndrome
      • Some associated with BRCA2 mutations
    • Rare under age 40, very rare under age 20

    Grading/Staging/Report

    • WHO 2010 proposes grading as below, but overally survival is very poor
    Grade Differentiation Mucin Mitoses / HPF Nuclear Cytology
    1 Well differentiated Abundant ≤5 Little polymorphism, polarity preserved
    2 Moderately differentiated, foci of poorly formed glands

    Decreased

    		 6-10 Moderate polymorphism
    3 Poorly differentiated, small irregular glands and single cell infiltration Scant >10 Marked pleomorphism
    Highest score in any category determines the grade

     

    • Staging
      • Use TNM

    Lists

    Pancreatic Carcinomas

    Bibliography

    • Solcia E, Capella C, Kloppel G . Tumors of the Pancreas, Atlas of Tumor Pathology, AFIP Third Series, Fascicle 20, 1997.
    • Hyland C, Kheir SM, Kashlan MB. Frozen section diagnosis of pancreatic carcinoma: a prospective study of 64 biopsies. Am J Surg Pathol. 1981 Mar;5(2):179-91.
    • Cioc AM, Ellison EC, Proca DM, Lucas JG, Frankel WL. Frozen section diagnosis of pancreatic lesions. Arch Pathol Lab Med. 2002 Oct;126(10):1169-73.
    • Weiland LH. Frozen section diagnosis in tumors of the pancreas. Semin Diagn Pathol. 1984 Feb;1(1):54-8.
    • Sharma S, Green KB. The pancreatic duct and its arteriovenous relationship: an underutilized aid in the diagnosis and distinction of pancreatic adenocarcinoma from pancreatic intraepithelial neoplasia. A study of 126 pancreatectomy specimens. Am J Surg Pathol. 2004 May;28(5):613-20.
    • Adsay V, Logani S, Sarkar F, Crissman J, Vaitkevicius V. Foamy gland pattern of pancreatic ductal adenocarcinoma: a deceptively benign-appearing variant. Am J Surg Pathol. 2000 Apr;24(4):493-504.
    • Loos M, Bergmann F, Bauer A, Hoheisel JD, Esposito I, Kleeff J, Schirmacher P, Buchler MW, Kloppel G, Friess H. Solid type clear cell carcinoma of the pancreas: differential diagnosis of an unusual case and review of the literature. Virchows Arch. 2007 Jun;450(6):719-26.
    • Luttges J, Vogel I, Menke M, Henne-Bruns D, Kremer B, Kloppel G. Clear cell carcinoma of the pancreas: an adenocarcinoma with ductal phenotype. Histopathology. 1998 May;32(5):444-8.
    • Ray S, Lu Z, Rajendiran S. Clear cell ductal adenocarcinoma of pancreas: a case report and review of the Arch Pathol Lab Med. 2004 Jun;128(6):693-6.
    • Hruban RH, Fukushima N. Pancreatic adenocarcinoma: update on the surgical pathology of carcinomas of ductal origin and PanINs. Mod Pathol. 2007 Feb;20 Suppl 1:S61-70.
    • Bandyopadhyay S, Basturk O, Coban I, Thirabanajasak D, Liang H, Altinel D, Adsay NV. Isolated solitary ducts (naked ducts) in adipose tissue. A specific but underappreciated finding of pancreatic adenocarcinoma and one of the potential reasons of understaging and high recurrence rate. Am J Surg Pathol. 2009 Mar;33(3):425-9.
    • Klöppel G, Adsay NV. Chronic pancreatitis and the differential diagnosis versus pancreatic cancer. Arch Pathol Lab Med. 2009 Mar;133(3):382-7.
    • Kim L, Liao J, Zhang M, Talamonti M, Bentrem D, Rao S, Yang GY. Clear cell carcinoma of the pancreas: histopathologic features and a unique biomarker: hepatocyte nuclear factor-1beta. Mod Pathol. 2008 Sep;21(9):1075-83.
    • Lüttges J, Schemm S, Vogel I, Hedderich J, Kremer B, Klöppel G. The grade of pancreatic ductal carcinoma is an independent prognostic factor and is superior to the immunohistochemical assessment of proliferation. J Pathol. 2000 Jun;191(2):154-61
    • Kelly PJ, Shinagare S, Sainani N, Hong X, Ferrone C, Yilmaz O, Fernández-del Castillo C, Lauwers GY, Deshpande V. Cystic papillary pattern in pancreatic ductal adenocarcinoma: a heretofore undescribed morphologic pattern that mimics intraductal papillary mucinous carcinoma. Am J Surg Pathol. 2012 May;36(5):696-701
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