Pancreatic Cancer

Pancreatic cancer is the third most common cause of cancer death in the United States, with a low 5-year survival rate due to its typically late stage at the time of diagnosis (Surveillance, Epidemiology, and End Results program [SEER]). Fine needle aspiration (FNA) via endoscopic ultrasound (EUS) is the initial diagnostic procedure of choice. Genetic testing for individuals with suspected familial pancreatic cancer may include germline analysis of ATM, BRCA1/BRCA2, and CKDN2A, among others.

Diagnosis

Indications for Testing

  • Patient presenting with jaundice and pancreatic mass
  • Monitoring for tumor recurrence after treatment (neoadjuvant therapy, surgical resection, chemotherapy)
  • Evaluation of cystic pancreatic masses for malignancy

Laboratory Testing

  • Initial testing
    • Bilirubin and alkaline phosphatase – elevation can indicate bile duct obstruction by pancreatic mass
    • Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) – may be elevated secondarily
  • Markers
    • Cancer antigen (CA) 19-9
      • Sensitivity depends on stage of cancer (50-75% sensitivity, 80-85% specificity)
      • May be elevated in benign obstructive jaundice, tissue inflammation (as in 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
      • Carcinoembryonic antigen (CEA) and CA 125
        • May be elevated, but testing is not necessarily recommended 
        • Potentially useful for patients who have Lewis-negative blood group phenotype (and, therefore, may have undetectable CA 19-9)
      • S100 calcium-binding protein (S-100P)
        • High sensitivity (87%) and specificity (88%) for pancreatic cancer (National Comprehensive Cancer Network [NCCN], 2017)
      • TIMP1 and LRG1
        • May improve detection of early-stage cancer when used with CA 19-9 (NCCN, 2017); testing not offered at ARUP Laboratories
  • Aspirated cystic fluid testing – amylase, CEA, and CA 19-9 
  • Cytology – positive cytology from laparoscopy or laparotomy washings is diagnostic of distant metastatic disease (NCCN, 2017)
  • Molecular testing
    • KRAS gene mutation in ductal adenocarcinoma is common; testing may be useful for evaluation of cystic lesions with negative cytology and fluid analysis (Reid, 2014; Maker, 2015)
    • For other molecular testing options in familial syndromes, refer to Genetic Testing in Diagnosis

Histology

  • Definitive diagnosis requires biopsy with pathologist evaluation
    • Useful immunohistochemical stains may include cytokeratin 8,18 low molecular weight (CAM 5.2), epithelial membrane antigen (EMA), and synaptophysin
    • For detailed descriptions, including recommended tests, refer to ARUP’s ​Immunohistochemistry Stain Offerings

Genetic Testing

  • Individuals may be considered at risk for familial pancreatic cancer when any of the following are present (American College of Gastroenterology [ACG], 2015)
    • 2 relatives with pancreatic cancer, 1 of whom is a first-degree relative
    • ≥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

Imaging Studies

  • Computed tomography (CT) – typically, scan of abdomen and pelvis for initial diagnosis to determine presence of mass; 1 of the following may be used in addition
    • Endoscopic ultrasound (EUS) – preferred imaging; may be used with FNA
    • CT using 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) – used to outline extent of ductal involvement
    • Magnetic resonance imaging (MRI)/magnetic resonance cholangiopancreatography (MRCP)

Differential Diagnosis

Screening

  • Screening recommendations for high risk patients (refer to Diagnosis) (American College of Gastroenterology [ACG], 2015)
    • Screening should be performed in high volume centers
    • EUS and/or magnetic resonance imaging (MRI)
      • Annually starting at 50 years or 10 years younger than earliest pancreatic diagnosis in relative
      • Peutz-Jeghers syndrome – consider starting at 35 years
      • Refer to Genetics information in Risk Factors in Background

Monitoring

  • Cancer antigen (CA) 19-9 – serial monitoring recommended for follow-up assessment after potentially curative surgery or response to palliative chemotherapy
  • Carcinoembryonic antigen (CEA) – less useful than CA 19-9 for monitoring

Background

Epidemiology

  • Incidence – 12.5/100,000 
  • Death rate – 10.9/100,000
  • Age – peak incidence, 65-74 years
  • Sex – M>F (slight difference)
  • Ethnicity – 30-40% higher incidence in African Americans

Epidemiology information (SEER, 2017)

Risk Factors

  • Tobacco use
  • Helicobacter pylori infection
  • Chronic pancreatitis
  • Type 2 diabetes mellitus – ≥5 years
  • Increased body mass index – ≥30 kg/m2
  • Insulin and sulfonylureas, and possibly other diabetes medications, excluding metformin
  • Occupational exposures – dichlorodiphenyltrichloroethane (DDT), benzidine, dry cleaning agents, polychlorinated biphenyls, asbestos
  • Dietary factors – red meat consumption, low fruit and folate consumption, high alcohol intake
  • Genetics (American College of Gastroenterology [ACG], 2015)
    • Risk is increased for individuals with
      • 2 relatives with pancreatic adenocarcinoma (1 of whom is first-degree relative)
      • ≥3 relatives with pancreatic cancer
    • Familial syndromes associated with increased risk
    • Familial pancreatitis

Pathophysiology

Clinical Presentation

  • No specific early warning symptoms
  • Signs and symptoms are 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)

ARUP Lab Tests

Initial screening for hepatobiliary inflammation

Panel includes alkaline phosphatase; aspartate aminotransferase (AST); alanine aminotransferase (ALT); protein, total; albumin; and bilirubin, direct and total

Monitor pancreatic cancer

Sensitivity/specificity: vary depending on cancer stage

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

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

Results obtained with different methods cannot be used interchangeably

May aid diagnosis and monitoring of pancreatic cancer

For information on body fluid reference ranges and/or interpretive guidance, visit http://aruplab.com/bodyfluids/

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

Possible tumor marker for pancreatic cancer

Assist with differentiating malignant pancreatic cysts from benign

For information on body fluid reference ranges and/or interpretive guidance, visit http://aruplab.com/bodyfluids/

Evaluate and monitor ovarian cancer, usually epithelial subtype

Not a stand-alone test for ovarian cancer screening or diagnosis

​Not recommended for breast cancer or germ cell tumors

Useful as a biomarker of various central nervous system (CNS) pathologies and as a tumor marker for malignant melanoma

Assist with evaluation of pancreatic cysts

For more information on body fluid reference ranges and/or interpretive guidance, visit http://aruplab.com/bodyfluids

Predict response to anti-EGFR and MAPK pathway therapies in a variety of malignancies (eg, colorectal and lung cancer)

Detect aneuploidy for chromosomes 3, 7, and 17

Use in conjunction with current standard diagnostic procedures as an aid for diagnosis of pancreatobiliary carcinoma

Related Tests

Stained and returned to client pathologist; consultation available if needed

Aid histologic diagnosis of pancreatic cancer

Stained and returned to client pathologist; consultation available if needed

Medical Experts

Contributor

Chadwick

Barbara Chadwick, MD
Associate Professor of Anatomic Pathology, University of Utah
Medical Director, Anatomic Pathology and Cytopathology, ARUP Laboratories
Contributor

Genzen

Jonathan R. Genzen, MD, PhD
Associate Professor of Clinical Pathology, University of Utah
Chief Operations Officer, Medical Director of Automated Core Laboratory and Farmington Health Center Clinical Laboratory, ARUP Laboratories
Contributor

References

Additional Resources
  • 25394175

    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. Reaffirmed with Addendum: Genetics in Medicine (2019) 21:2844.

    PubMed
  • Resources from the ARUP Institute for Clinical and Experimental Pathology®