Pancreatic Cancer

Diagnosis

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 (70-90% sensitivity and 90% 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
  • Other potential markers include MUC-1 antigen (also called CA15-3 antigen) and carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1), although neither has been sufficiently validated for pancreatic cancer
  • Cystic lesions 
    • Aspirated cystic fluid testing – amylase, 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)
  • KRAS2 gene mutation in ductal adenocarcinoma is common
    • May also be useful for cystic lesions with negative cytology and fluid analysis

Histology

  • Biopsy of tumor with histologic evaluation
    • Fine needle aspiration (FNA) via endoscopic ultrasound (EUS) is initial procedure of choice for diagnosis
      • EUS-guided 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

Imaging Studies

  • CT scan – use pancreatic triphasic protocol
    • 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/MRCP

Differential Diagnosis

Screening

  • No studies demonstrating efficacy for population at large
  • Only viable in high-risk patients (consensus from Fourth International Symposium of Inherited Diseases of the Pancreas, 2003)
    • Screen patients with one or more the following conditions
      • ≥3 first-degree family members with pancreatic cancer
      • Familial atypical multiple mole melanoma syndrome, Peutz-Jeghers syndrome, or hereditary pancreatitis
      • BRCA2 mutations and ≥1 family member with pancreatic cancer
    • Age to begin screening
      • Familial pancreatic cancer – 40-45 years or 10-15 years younger than the youngest relative with pancreatic cancer
      • Peutz-Jeghers syndrome – 30 years
  • Best screening tool appears to be EUS
    • Usually followed up with ERCP

Monitoring

  • CA 19-9 – serial monitoring recommended to assess follow-up after potentially curative surgery or response to palliative chemotherapy
    • CEA – less useful than CA 19-9 for monitoring

Clinical Background

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 (minimal)
  • Ethnicity – 30-40% higher incidence in African Americans

Risk Factors

Pathophysiology

Clinical Presentation

  • No specific early warning symptoms
  • Usually abdominal pain and weight loss
  • 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)

Indications for Laboratory Testing

  • 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
Test Name and Number Recommended Use Limitations Follow Up
Hepatic Function Panel 0020416
Method: Quantitative Enzymatic/Quantitative Spectrophotometry

Initial screening test for obstruction and jaundice

Panel includes albumin, alkaline phosphatase, aspartate aminotransferase, alanine aminotransferase, bilirubin direct and total, protein total

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

Monitor pancreatic cancer

70-90% sensitivity and 90% specificity 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-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

May aid diagnosis and monitoring of pancreatic cancer

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 2002461
Method: Fluorescence in situ Hybridization/Computer Assisted Analysis/Microscopy

Detect aneuploidy for chromosomes 3, 7, and 17

Use in conjunction with current standard diagnostic procedures as an aid for initial diagnosis of pancreatic cancer

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

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

Amylase, Body Fluid 0020506
Method: Quantitative Enzymatic

Assist with evaluating pancreatic cysts as benign or malignant

   
Muc-1 by Immunohistochemistry 2004002
Method: Immunohistochemistry

Aid histologic diagnosis of pancreatic cancer

Stained and returned to client pathologist; consultation available if needed

   
Carcinoembryonic Antigen, Fluid 0020742
Method: Quantitative Electrochemiluminescent Immunoassay

Assist with evaluating pancreatic cysts as benign or malignant

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

Aid histologic diagnosis of pancreatic cancer

Stained and returned to client pathologist; consultation available if needed

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

Aid histologic diagnosis of pancreatic cancer

Stained and returned to client pathologist; consultation available if needed

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

Aid histologic diagnosis of pancreatic cancer

Stained and returned to client pathologist; consultation available if needed

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

Aid histologic diagnosis of pancreatic cancer

Stained and returned to client pathologist; consultation available if needed

   
Synaptophysin by Immunohistochemistry 2004139
Method: Immunohistochemistry

Aid histologic diagnosis of pancreatic cancer

Stained and returned to client pathologist; consultation available if needed

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

Aid histologic diagnosis of pancreatic cancer

Stained and returned to client pathologist; consultation available if needed