Pancreatic Cancer

  • Diagnosis
  • Screening
  • Monitoring
  • Background
  • Lab Tests
  • References
  • Related Topics
  • Videos

Indications for Testing

  • Patient presenting with jaundice and pancreatic mass
  • Monitoring for tumor recurrence after surgery

Laboratory Testing

  • Liver function testing – may show elevated bilirubin and alkaline phosphatase
  • CA 19-9 serum antigen testing – sensitivity depends on stage of cancer (50-75% sensitivity and 80-85% specificity)
    • May be elevated in benign obstructive jaundice, chronic pancreatitis
    • Should be used in conjunction with imaging studies to diagnose pancreatic cancer
    • Limited use as early screening
    • Levels may be predictive of outcome
  • Other potential markers include MUC-1 antigen (also called CA 15-3 antigen) and carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1), although neither has been sufficiently validated for pancreatic cancer
  • Cystic lesions (small, but palpable chance of malignancy)
    • Increased risk of malignancy when found in a patient with hereditary syndrome associated with increased risk of pancreatic cancer (ACG, 2015)
    • American Gastroenterological Association (AGA) recommendations (2015)
      • Cysts with at least 2 high-risk features (eg, size ≥3 cm, solid component) should be examined by endoscopic ultrasound with fine needle aspiration (EUS-FNA) – see Histology section below
    • Aspirated cystic fluid testing – amylase, carcinoembryonic antigen (CEA), and CA 19-9
      • Levels suggestive of cancer diagnosis
        • Amylase – <250 U/mL
        • CEA – >800 ng/mL
        • CA 19-9 – >37 U/mL
  • Cytology
    • Positive cytology from laparoscopy or laparotomy performed after imaging studies is diagnostic of distant metastatic disease (American Joint Committee on Cancer, 2010)
  • Molecular testing
    • KRAS gene mutation in ductal adenocarcinoma is common
      • May also be useful for cystic lesions with negative cytology and fluid analysis
    • Gene mutation testing (eg, BRCA1, CDKN2A, PRSSI, SPINK1) may be indicated in familial syndromes
      • BRCA1 and BRCA2 – indicated when two or more relatives have diagnosis of breast, ovarian, aggressive prostate, or pancreatic cancer at any age (NCCN, 2014)
      • BRCA1/2, CDKN2A, PALB2, ATM – recommended testing as per ACG, 2015
        • Evaluation for Peutz-Jeghers syndrome (PJS) and Lynch syndrome (LS) should be considered if component of personal or family history meets criteria for testing

Histology

  • Biopsy of tumor with histologic evaluation
    • Fine needle aspiration (FNA) via endoscopic ultrasound (EUS) is initial procedure of choice for diagnosis
      • EUS-FNA is preferred over CT-guided FNA
  • FISH detection of aneuploidy for chromosomes 3, 7, and 17, and loss of the 9p21 locus is helpful in establishing the diagnosis of pancreatic ductal carcinoma in cytologic specimens
  • Histopathology of pancreatic tumors differs between exocrine and neuroendocrine types; see Pancreatic Neuroendocrine Tumors for more information
  • Immunohistochemistry
    • Available stains include cytokeratin 8,18 low molecular weight (CAM 5.2), protein gene product (PGP) 9.5, synaptophysin, epithelial membrane antigen (EMA), p21, and carcinoembryonic antigen polyclonal

Genetic Testing

  • Consider molecular testing in the following (ACMG, 2015)
    • Pancreatic cancer diagnosis at any age if any of the following criteria are met
      • ≥2 cases of pancreatic cancer in close relatives
      • ≥2 cases of breast, ovarian, and/or aggressive prostate cancer in close relatives
      • Ashkenazi Jewish ancestry
    • Pancreatic cancer and ≥1 Peutz-Jeghers syndrome polyp in the same person
    • Pancreatic cancer and 2 additional cases of any LS-associated cancer in the same person or in close relatives
    • ≥3 cases of pancreatic cancer and/or melanoma in close relatives
    • Pancreatic cancer and melanoma in the same person

Imaging Studies

  • CT scan – use pancreatic triphasic protocol (arterial, late arterial, and venous phases)
    • Volume rendering CT scan is most useful
    • Provides diagnosis and helps identify resectable disease
    • Helps assess vascular involvement
  • EUS or endoscopic retrograde cholangiopancreatography (ERCP) to outline extent of ductal involvement; may also use MRI/magnetic resonance cholangiopancreatography (MRCP)

Differential Diagnosis

  • Screening recommendations ( ACG, 2015)
    • Screening should be performed in expert centers
    • High risk patients only and should include endoscopic ultrasound (EUS) and/or MRI (See Genetics in Background section)
    • EUS and/or MRI
      • Annually starting at 50 years or 10 years younger than the earliest relative’s pancreatic cancer
      • PJS – consider starting at 35 years
  • CA 19-9 – serial monitoring recommended to assess follow-up after potentially curative surgery or response to palliative chemotherapy
  • Carcinoembryonic antigen (CEA) – less useful than CA 19-9 for monitoring

Pancreatic cancer, a common cancer in the U.S., has historically been associated with a high mortality rate. It has a low 5-year survival rate due to the typically late stage of cancer at time of diagnosis.

Epidemiology

  • Incidence – 9-10/100,000
  • Age – peak incidence in 60s
  • Sex – M>F
  • Ethnicity – 30-40% higher incidence in African Americans

Risk Factors

Pathophysiology

  • Tumor is usually ductal adenocarcinoma
    • Accounts for >90% of pancreatic cancers
    • 60-70% of tumors located in head of pancreas
    • May also have mucinous cystadenocarcinomic variants
      • Tumors may manifest solely as cysts
  • Uncommon neuroendocrine tumors may also affect the pancreas

Clinical Presentation

  • No specific early warning symptoms
  • Signs and symptoms related to location of tumor
  • Abdominal pain and weight loss – most common
  • Obstructive jaundice if tumor is at the head of the pancreas
  • Late features – ascites, abdominal mass
  • If tumors are neuroendocrine in nature, patient may initially present with an endocrine syndrome (eg, hypoglycemia in insulinoma)

Tests generally appear in the order most useful for common clinical situations. Click on number for test-specific information in the ARUP Laboratory Test Directory.

Hepatic Function Panel 0020416
Method: Quantitative Enzymatic/Quantitative Spectrophotometry

Cancer Antigen-GI (CA 19-9) 0080461
Method: Quantitative Electrochemiluminescent Immunoassay

Limitations

Cannot be interpreted as absolute evidence of the presence or absence of malignant disease

May not be detectable in patients with Lewis-a negative blood group

Results obtained with different methods cannot be used interchangeably

Cancer Antigen-GI (CA 19-9), Body Fluid 0020746
Method: Quantitative Electrochemiluminescent Immunoassay

Limitations

Cannot be interpreted as absolute evidence of the presence or absence of malignant disease

Results obtained with different assay methods or kits cannot be used interchangeably

Pancreatobiliary FISH 2002528
Method: Fluorescence in situ Hybridization/Computer Assisted Analysis/Microscopy

Limitations

Negative results indicate none of the numeric chromosomal abnormalities commonly associated with pancreatic carcinoma were identified in the specimen, but does not exclude the possibility of pancreatic carcinoma

Follow Up

If result is negative and high clinical suspicion exists, additional clinical studies should be considered

Amylase, Body Fluid 0020506
Method: Quantitative Enzymatic

Muc-1 by Immunohistochemistry 2004002
Method: Immunohistochemistry

Carcinoembryonic Antigen, Fluid 0020742
Method: Quantitative Electrochemiluminescent Immunoassay

Cytokeratin 8,18 Low Molecular Weight (CAM 5.2) by Immunohistochemistry 2003493
Method: Immunohistochemistry

Epithelial Membrane Antigen (EMA) by Immunohistochemistry 2003872
Method: Immunohistochemistry

p21 (Waf1/Cip 1) by Immunohistochemistry 2004067
Method: Immunohistochemistry

Protein Gene Product (PGP) 9.5 by Immunohistochemistry 2004091
Method: Immunohistochemistry

Synaptophysin by Immunohistochemistry 2004139
Method: Immunohistochemistry

Carcinoembryonic Antigen, Polyclonal (CEA P) by Immunohistochemistry 2003827
Method: Immunohistochemistry

Guidelines

Diamandis EP, Hoffman BR, Sturgeon CM. National Academy of Clinical Biochemistry Laboratory Medicine Practice Guidelines for the Use of Tumor Markers. Clin Chem. 2008; 54(11): 1935-9. PubMed

Hampel H, Bennett RL, Buchanan A, Pearlman R, Wiesner GL, Guideline Development Group, American College of Medical Genetics and Genomics Professional Practice and Guidelines Committee and National Society of Genetic Counselors Practice Guidelines Committee. A practice guideline from the American College of Medical Genetics and Genomics and the National Society of Genetic Counselors: referral indications for cancer predisposition assessment. Genet Med. 2015; 17(1): 70-87. PubMed

Locker GY, Hamilton S, Harris J, Jessup JM, Kemeny N, Macdonald JS, Somerfield MR, Hayes DF, Bast RC, ASCO. ASCO 2006 update of recommendations for the use of tumor markers in gastrointestinal cancer. J Clin Oncol. 2006; 24(33): 5313-27. PubMed

NCCN Clinical Practice Guidelines in Oncology, Breast and Ovarian Cancer Genetic/Familial High-Risk Assessment: Breast and Ovarian . National Comprehensive Cancer Network. Fort Washington, PA [Accessed: Apr 2016]

NCCN Clinical Practice Guidelines in Oncology, Neuroendocrine Tumors. National Comprehensive Cancer Network. Fort Washington, PA [Accessed: Mar 2016]

NCCN Clinical Practice Guidelines in Oncology, Pancreatic Adenocarcinoma. National Comprehensive Cancer Network. Fort Washington, PA [Accessed: Jun 2015]

Pitman MB, Layfield LJ. Guidelines for pancreaticobiliary cytology from the Papanicolaou Society of Cytopathology: A review. Cancer Cytopathol. 2014; 122(6): 399-411. PubMed

Protocol for the Examination of Specimens from Patients with Carcinoma of the Pancreas. Based on AJCC/UICC TNM, 7th ed. Protocol web posting date: Jan 2016. College of American Pathologists (CAP). Northfield, IL [Accessed: Jun 2015]

Syngal S, Brand RE, Church JM, Giardiello FM, Hampel HL, Burt RW, American College of Gastroenterology. ACG clinical guideline: Genetic testing and management of hereditary gastrointestinal cancer syndromes. Am J Gastroenterol. 2015; 110(2): 223-62; quiz 263. PubMed

Vege SSwaroop, Ziring B, Jain R, Moayyedi P, Clinical Guidelines Committee, American Gastroenterology Association. American gastroenterological association institute guideline on the diagnosis and management of asymptomatic neoplastic pancreatic cysts. Gastroenterology. 2015; 148(4): 819-22; quize12-3. PubMed

General References

De La Cruz MSyl D, Young AP, Ruffin MT. Diagnosis and management of pancreatic cancer. Am Fam Physician. 2014; 89(8): 626-32. PubMed

Fukushima N, Zamboni G. Mucinous cystic neoplasms of the pancreas: update on the surgical pathology and molecular genetics. Semin Diagn Pathol. 2014; 31(6): 467-74. PubMed

Galli C, Basso D, Plebani M. CA 19-9: handle with care. Clin Chem Lab Med. 2013; 51(7): 1369-83. PubMed

Hutchins G, Draganov PV. Diagnostic evaluation of pancreatic cystic malignancies. Surg Clin North Am. 2010; 90(2): 399-410. PubMed

Klimstra DS, Pitman MB, Hruban RH. An algorithmic approach to the diagnosis of pancreatic neoplasms. Arch Pathol Lab Med. 2009; 133(3): 454-64. PubMed

Maker AV, Carrara S, Jamieson NB, Pelaez-Luna M, Lennon AMarie, Dal Molin M, Scarpa A, Frulloni L, Brugge WR. Cyst fluid biomarkers for intraductal papillary mucinous neoplasms of the pancreas: a critical review from the international expert meeting on pancreatic branch-duct-intraductal papillary mucinous neoplasms. J Am Coll Surg. 2015; 220(2): 243-53. PubMed

McIntyre CA, Winter JM. Diagnostic evaluation and staging of pancreatic ductal adenocarcinoma. Semin Oncol. 2015; 42(1): 19-27. PubMed

Muniraj T, Jamidar PA, Aslanian HR. Pancreatic cancer: a comprehensive review and update. Dis Mon. 2013; 59(11): 368-402. PubMed

Reid MD, Saka B, Balci S, Goldblum AS, Adsay V. Molecular genetics of pancreatic neoplasms and their morphologic correlates: an update on recent advances and potential diagnostic applications. Am J Clin Pathol. 2014; 141(2): 168-80. PubMed

Rishi A, Goggins M, Wood LD, Hruban RH. Pathological and molecular evaluation of pancreatic neoplasms. Semin Oncol. 2015; 42(1): 28-39. PubMed

Ryan DP, Hong TS, Bardeesy N. Pancreatic adenocarcinoma. N Engl J Med. 2014; 371(11): 1039-49. PubMed

Singh P, Srinivasan R, Wig JDev. Major molecular markers in pancreatic ductal adenocarcinoma and their roles in screening, diagnosis, prognosis, and treatment. Pancreas. 2011; 40(5): 644-52. PubMed

Vincent A, Herman J, Schulick R, Hruban RH, Goggins M. Pancreatic cancer. Lancet. 2011; 378(9791): 607-20. PubMed

Xu X, Strimpakos AS, Saif MWasif. Biomarkers and pharmacogenetics in pancreatic cancer. Highlights from the "2011 ASCO Annual Meeting". Chicago, IL, USA; June 3-7, 2011. JOP. 2011; 12(4): 325-9. PubMed

References from the ARUP Institute for Clinical and Experimental Pathology®

Awadallah NS, Shroyer KR, Langer DA, Torkko KC, Chen YK, Bentz JS, Papkoff J, Liu W, Nash R, Shah RJ. Detection of B7-H4 and p53 in pancreatic cancer: potential role as a cytological diagnostic adjunct. Pancreas. 2008; 36(2): 200-6. PubMed

Chadwick B, Willmore-Payne C, Tripp S, Layfield LJ, Hirschowitz S, Holden J. Histologic, immunohistochemical, and molecular classification of 52 IPMNs of the pancreas. Appl Immunohistochem Mol Morphol. 2009; 17(1): 31-9. PubMed

Chadwick BE. Beyond cytomorphology: expanding the diagnostic potential for biliary cytology. Diagn Cytopathol. 2012; 40(6): 536-41. PubMed

Chen R, Pan S, Ottenhof NA, de Wilde RF, Wolfgang CL, Lane Z, Post J, Bronner MP, Willmann JK, Maitra A, Brentnall TA. Stromal galectin-1 expression is associated with long-term survival in resectable pancreatic ductal adenocarcinoma. Cancer Biol Ther. 2012; 13(10): 899-907. PubMed

Crnogorac-Jurcevic T, Chelala C, Barry S, Harada T, Bhakta V, Lattimore S, Jurcevic S, Bronner M, Lemoine NR, Brentnall TA. Molecular analysis of precursor lesions in familial pancreatic cancer. PLoS One. 2013; 8(1): e54830. PubMed

La'ulu SL, Roberts WL. Performance characteristics of five automated CA 19-9 assays. Am J Clin Pathol. 2007; 127(3): 436-40. PubMed

Layfield LJ, Bentz J. Giant-cell containing neoplasms of the pancreas: an aspiration cytology study. Diagn Cytopathol. 2008; 36(4): 238-44. PubMed

Layfield LJ, Hirschowitz SL, Adler DG. Metastatic disease to the pancreas documented by endoscopic ultrasound guided fine-needle aspiration: a seven-year experience. Diagn Cytopathol. 2012; 40(3): 228-33. PubMed

Layfield LJ, Jarboe EA. Cytopathology of the pancreas: neoplastic and nonneoplastic entities. Ann Diagn Pathol. 2010; 14(2): 140-51. PubMed

Moore JC, Hilden K, Bentz JS, Pearson RK, Adler DG. Osteoclastic and pleomorphic giant cell tumors of the pancreas diagnosed via EUS-guided FNA: unique clinical, endoscopic, and pathologic findings in a series of 5 patients. Gastrointest Endosc. 2009; 69(1): 162-6. PubMed

Schmidt RL, Witt BL, Matynia AP, Barraza G, Layfield LJ, Adler DG. Rapid on-site evaluation increases endoscopic ultrasound-guided fine-needle aspiration adequacy for pancreatic lesions. Dig Dis Sci. 2013; 58(3): 872-82. PubMed

Willmore-Payne C, Volmar KE, Huening MA, Holden JA, Layfield LJ. Molecular diagnostic testing as an adjunct to morphologic evaluation of pancreatic ductal system brushings: potential augmentation for diagnostic sensitivity. Diagn Cytopathol. 2007; 35(4): 218-24. PubMed

Medical Reviewers

Last Update: March 2016