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

• Benign conditions
  • Chronic pancreatitis
  • Acute pancreatitis
  • Autoimmune pancreatitis
  • Acute cholecystitis
• Cystic lesions
  • Pseudocyst
• Autoimmune disease
  • Autoimmune hepatitis
  • Primary biliary cirrhosis
  • Primary sclerosing cholangitis

Screening

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

• Low socioeconomic status
• Male gender
• Tobacco use
• Increased body mass index
• Presence of chronic disease states
  • Chronic pancreatitis
  • Diabetes mellitus
  • Prior cholecystectomy
• Occupational exposures
  • DDT, benzidine, dry cleaning agents, polychlorinated biphenyls
• Genetics
  • Family history of pancreatic cancer
    • Familial pancreatic cancers account for up to 10% of cases
  • Familial syndromes
    • Ataxia-telangiectasia syndrome
    • Familial adenomatous polyposis
    • Familial atypical multiple mole melanoma syndrome
    • Familial breast-ovarian cancer (BRCA1 and BRCA2 mutations)
    • Familial pancreatic cancer (FPC) – first degree relatives with pancreatic cancer
    • Hereditary pancreatitis syndrome
    • Li-Fraumeni syndrome
    • Lynch syndrome (hereditary nonpolyposis colorectal cancer)
    • Peutz-Jeghers syndrome
    • von Hippel-Lindau syndrome

Pathophysiology

• Tumor is usually ductal adenocarcinoma
  • Accounts for >90% of pancreatic cancers
  • May also have mucinous cystadenocarcinomic variants
• Uncommon neuroendocrine tumors may also affect the pancreas
  • Insulinoma
  • Glucagonoma
  • Somatostatinoma
  • VIPoma
• 70-80% of tumors are located in head of pancreas
• Tumors may manifest solely as cysts

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