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 treatment (neo-adjuvant, resection, chemotherapy)
  • Evaluation of cystic pancreatic masses for malignancy

Laboratory Testing

  • Initial testing
    • Elevated bilirubin and alkaline phosphatase – can be indicative of pancreatic mass obstructing the bile duct
    • AST and ALT – may be elevated secondarily
  • Markers
    • CA 19-9 – sensitivity depends on stage of cancer (50-75% sensitivity and 80-85% specificity)
      • May be elevated in benign obstructive jaundice, tissue inflammation (eg, chronic pancreatitis, emphysema), or other cancers
      • Should be used in conjunction with imaging studies to diagnose pancreatic cancer
      • Limited use as early screening tool
      • Levels may be predictive of outcome
    • Possible additional tumor markers
      • CA15-3 (also called MUC-1), carcinoembryonic antigen (CEA), and CA 125 may be elevated, but testing not necessarily recommended 
      • CEA and CA 125 – potentially useful for patients who do not express Lewis antigen-1 (and, therefore, do not express CA 19-9)
  • Aspirated cystic fluid testing
    • Amylase, CEA, and CA 19-9 
  • 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 and may be useful for evaluation of cystic lesions with negative cytology and fluid analysis
    • For other molecular testing options in familial syndromes (refer to Genetic Testing in Diagnosis section)

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 (refer to 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

  • Individuals may be considered at-risk for familial pancreatic cancer when any of the following are present (ACG, 2015)
    • Two relatives with pancreatic cancer, where one is a first-degree relative of patient
    • ≥3 relatives with pancreatic cancer
    • Individuals with a history of hereditary pancreatitis
  • Genetic testing for individuals with suspected familial pancreatic cancer may include germline analysis of the following (ARUP Additional Technical Information documents linked where available for full testing criteria and indications)​

Imaging Studies

  • CT scan – usually CT scan of abdomen and pelvis for initial diagnosis to determine presence of mass; may be followed by one of the following
    • EUS – preferred imaging and may be used with FNA
    • 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
    • Endoscopic retrograde cholangiopancreatography (ERCP) – outline extent of ductal involvement
    • MRI/magnetic resonance cholangiopancreatography (MRCP) – also used but less sensitive

Differential Diagnosis

  • Screening recommendations for high risk patients (refer to Diagnosis section) (ACG, 2015)
    • Screening should be performed in high volume centers
    • Endoscopic ultrasound (EUS) and/or MRI (refer to Genetics in Background section)
    • EUS and/or MRI
      • Annually starting at 50 years or 10 years younger than the earliest pancreatic diagnosis in relative
      • Peutz-Jeghers syndrome – 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 is the fourth most common cause of cancer deaths in the United States, on its way to becoming third, with a low 5-year survival rate due to the typically late stage of cancer at time of diagnosis.

Epidemiology

  • Incidence – 12.4/100,000 (Siegel, 2016)
  • Death rate – 10.9/100,000
  • Age – peak incidence in 60s
  • Sex – M>F
  • Ethnicity – 30-40% higher incidence in African Americans

Risk Factors

  • Tobacco use
  • Chronic pancreatitis
  • Diabetes mellitus – type II ≥5 years
  • Increased body mass index – ≥30kg/m2
  • Insulin and sulfonylureas, possibly other diabetes medications, excluding metformin
  • Occupational exposures
    • DDT, benzidine, dry cleaning agents, polychlorinated biphenyls, asbestos
  • Genetics ( ACG, 2015 )
    • Two relatives with pancreatic adenocarcinoma (1 relative is first degree)
    • Three or more relatives with pancreatic cancer
    • Familial syndromes associated with increased risk
    • Familial pancreatitis

Pathophysiology

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

KRAS Mutation Detection 0040248
Method: Polymerase Chain Reaction/Pyrosequencing

Carcinoembryonic Antigen 0080080
Method: Quantitative Electrochemiluminescent Immunoassay

Cancer Antigen 125 0080462
Method: Quantitative Electrochemiluminescent Immunoassay

Carcinoembryonic Antigen, Fluid 0020742
Method: Quantitative Electrochemiluminescent Immunoassay

Muc-1 by Immunohistochemistry 2004002
Method: Immunohistochemistry

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: Dec 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: Dec 2016]

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 [Revised Aug 2016; Accessed: Dec 2016]

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 SS, 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 MS, 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

Hanada K, Okazaki A, Hirano N, Izumi Y, Minami T, Ikemoto J, Kanemitsu K, Hino F. Effective screening for early diagnosis of pancreatic cancer. Best Pract Res Clin Gastroenterol. 2015; 29(6): 929-39. PubMed

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

Kamisawa T, Wood LD, Itoi T, Takaori K. Pancreatic cancer. Lancet. 2016; 388(10039): 73-85. 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 AM, 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

Siegel RL, Miller KD, Jemal A. Cancer statistics, 2016. CA Cancer J Clin. 2016; 66(1): 7-30. PubMed

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

Stark A, Donahue TR, Reber HA, Hines J. Pancreatic Cyst Disease: A Review. JAMA. 2016; 315(17): 1882-93. PubMed

Xu X, Strimpakos AS, Saif MW. 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

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Last Update: February 2017