What is the recommended workup for a patient presenting with a pancreatic mass, considering potential risk factors such as smoking, obesity, and family history of pancreatic cancer?

Workup for Pancreatic Mass

Proceed directly to pancreatic protocol CT (contrast-enhanced multi-detector CT with late arterial and portal venous phases) as the first-line imaging study for any patient with a suspected pancreatic mass. 1

Initial Imaging Strategy

• Obtain pancreatic protocol CT immediately as the standard first-line diagnostic test, which provides the best overall assessment of pancreatic masses and is often the only imaging required 1, 2
• Complete all imaging within 4 weeks before initiating any treatment 1
• Perform imaging before any biliary drainage or stenting if jaundice is present, as stenting obscures imaging findings and compromises diagnostic accuracy 1
• If CT cannot be performed or is inconclusive, substitute abdominal MRI (which has 90-100% accuracy for detection and staging), though chest CT remains mandatory 3, 4
• MRI provides very high soft-tissue contrast resolution and can be a helpful adjunct to CT for detecting extrapancreatic disease in high-risk patients 3, 4

Laboratory Evaluation

• Obtain serum CA 19-9 to measure disease burden and guide treatment decisions 1
• CA 19-9 is elevated in approximately 80% of patients with advanced pancreatic cancer and serves as a prognostic marker 1
• Preoperative CA 19-9 ≥500 IU/ml indicates worse prognosis and should prompt caution regarding immediate surgery 1
• Note that CA 19-9 is undetectable in patients with Lewis antigen-negative phenotypes (approximately 10% of population) 1
• Obtain fasting blood glucose and/or HbA1c, as new-onset diabetes in older adults can indicate underlying pancreatic cancer 3, 5

Tissue Diagnosis Requirements

• Obtain cytology or biopsy proof before initiating chemotherapy for localized disease, preferably by EUS-guided fine needle aspiration 1
• EUS-guided biopsy is the preferred method for tissue diagnosis and has approximately 98% sensitivity for detecting pancreatic lesions 1, 4
• Perform EUS-FNA for solid lesions ≥5 mm, cystic lesions with worrisome features, or asymptomatic main pancreatic duct strictures 3
• Failure to obtain histological confirmation does not exclude malignancy and should not delay definitive management if clinical and radiological features are highly suspicious 1

Role of Endoscopic Ultrasound (EUS)

• Use EUS as a complementary tool to CT when no lesion is visible on CT or when there is questionable involvement of blood vessels or lymph nodes 3
• EUS has high accuracy in assessing involvement of certain veins (portal vein) but is less accurate for imaging tumor invasion of the superior mesenteric artery 3
• EUS can evaluate periampullary masses, separating invasive from noninvasive lesions, and better characterize cystic pancreatic lesions 3
• If no mass is apparent on CT, perform diagnostic ERCP or EUS/MRCP as clinically indicated 3, 2

Advanced Staging for Potentially Resectable Disease

• Obtain hepatic MRI before surgery to confirm absence of small liver metastases 1
• Consider chest imaging to evaluate for pulmonary metastases as part of the preoperative workup for patients with no evidence of abdominal metastases on CT 3
• PET-CT is not recommended for diagnosis of primary tumors but may be useful for staging localized tumors when distant metastases are uncertain (doubtful imaging or high CA 19-9) 1
• Consider laparoscopy when unresectability appears likely and cannot be confirmed in less invasive ways, as it can identify peritoneal, capsular, or serosal implants missed on imaging 3, 2
• EUS and/or laparoscopy with laparoscopic ultrasonography may be appropriate in selected cases for additional staging information 1

Multidisciplinary Review and Resectability Assessment

• All patients with localized disease must have imaging reviewed at a multidisciplinary tumor board with experts in pancreas imaging, pancreas surgery, and oncology 1
• This review determines resectability classification: resectable, borderline resectable, or unresectable 1
• Restage with high-quality abdominal and chest imaging after surgery for resectable disease and before initiation of adjuvant therapy 3

Genetic and Molecular Testing

• Refer patients with family history or high-risk features for genetic counseling 1
• KRAS and BRCA testing are generally recommended 1
• For KRAS wild-type tumors, assess MSI status, NTRK fusion status, and other rare fusions 1
• Consider screening for patients with hereditary pancreatitis, familial pancreatic cancer, BRCA1/BRCA2/PALB2/ATM mutations, Lynch syndrome, or Peutz-Jeghers syndrome 3

Risk Factors to Assess

• Tobacco use (present in 20% of patients) is the strongest aetiological association 3
• Family history of pancreatic cancer (two or more first-degree relatives reported in 10% of patients) 3
• Chronic pancreatitis, diabetes, obesity, and hereditary pancreatitis 3
• Adult-onset diabetes of less than two years' duration 3

Red Flag Clinical Features Indicating Advanced Disease

• Persistent back pain, marked and rapid weight loss, palpable abdominal mass, ascites, and supraclavicular lymphadenopathy typically indicate incurable disease 3, 1
• These features usually preclude surgical resection and indicate stage III or IV disease 3

Common Pitfalls to Avoid

• Do not delay imaging for initial ultrasound—proceed directly to pancreatic protocol CT in patients with high clinical suspicion 1
• Do not perform biliary stenting before obtaining definitive imaging, as this compromises diagnostic accuracy 1
• Do not rely solely on CA 19-9 for diagnosis, as it lacks sensitivity and specificity for early disease 1
• Recognize that proper identification of variants of ductal carcinomas and other malignant pancreatic tumors requires specialist pathological expertise 3
• Be aware that 80-85% of patients present with advanced disease without the option of surgical resection due to the insidious nature of pancreatic cancer 3