What is the likely diagnosis and management for an elderly male with masses in the adrenal, pancreatic, and lung tissues, elevated Carcinoembryonic Antigen (CEA), Cancer Antigen 19-9 (CA 19-9), and cortisol levels, and normal gastroscopy and colonoscopy results?

Likely Diagnosis: Metastatic Pancreatic Adenocarcinoma with Adrenal and Lung Metastases

This clinical presentation—pancreatic mass with elevated CA 19-9 and CEA, plus adrenal and lung masses—most strongly suggests metastatic pancreatic adenocarcinoma (Stage IV disease). The elevated cortisol likely represents adrenal metastasis rather than a functional tumor, given the multifocal disease pattern 1, 2.

Diagnostic Reasoning

Tumor Marker Interpretation

The combination of elevated CA 19-9 and CEA in the setting of a pancreatic mass is highly specific for pancreatic adenocarcinoma.

• CA 19-9 is elevated in up to 85% of pancreatic cancer patients and serves as the most validated serum marker for this malignancy 1, 3
• When CA 19-9 exceeds 100 U/mL, it suggests advanced disease with greater likelihood of metastases and increased probability of positive findings on staging laparoscopy 1, 2
• The dual elevation of both CEA and CA 19-9 carries particularly poor prognosis—patients with both markers elevated show dramatically shorter 5-year survival (23%) compared to single marker elevation or neither elevated 4
• Critical pitfall: Approximately 5-10% of the population is Lewis antigen-negative and cannot produce CA 19-9, making the test ineffective in these individuals 2, 3

Adrenal Mass Evaluation

The adrenal mass in this context is most likely metastatic disease rather than a primary adrenal tumor, despite the elevated cortisol.

• Unilateral adrenal masses in NSCLC patients are more likely metastatic when associated with large intrathoracic tumors or other extrathoracic metastases 1
• The presence of pancreatic and lung masses makes metastatic spread to the adrenal gland highly probable
• While benign adrenal adenomas can produce cortisol and occasionally CEA (as documented in rare case reports 5), the multifocal disease pattern argues strongly against this
• PET scanning performs exceptionally well for distinguishing adrenal metastases from adenomas, with accuracy as high as 100% in some series 1

Lung Mass Significance

The lung mass represents either:

• Metastatic disease from pancreatic primary (most likely given elevated pancreatic cancer markers)
• Synchronous primary lung cancer (less likely but possible)
• The normal gastroscopy and colonoscopy effectively exclude primary gastrointestinal sources 1

Diagnostic Algorithm

Immediate Next Steps

1. Obtain high-quality cross-sectional imaging with pancreatic protocol CT of chest/abdomen/pelvis to assess:

   • Pancreatic mass size, location, and vascular involvement
   • Number and size of lung and adrenal lesions
   • Presence of liver metastases or peritoneal disease 1

2. Perform PET-CT scan to:

   • Distinguish adrenal metastasis from adenoma (accuracy up to 100%) 1
   • Identify additional occult metastatic sites
   • Assess metabolic activity of all lesions 1, 2

3. Obtain tissue diagnosis via EUS-guided FNA of the pancreatic mass as the preferred approach:

   • Provides histologic confirmation
   • Allows molecular profiling for treatment planning
   • EUS is superior to ERCP for diagnostic purposes when biliary decompression is not immediately needed 1

4. If adrenal lesion remains indeterminate after PET-CT, perform percutaneous adrenal biopsy:

   • This is safe and effective for definitive diagnosis
   • Critical when histology will dictate management
   • May be nondiagnostic due to anatomic constraints 1

Staging Considerations

If pancreatic adenocarcinoma is confirmed and appears potentially resectable on imaging (unlikely given apparent metastases), strongly consider staging laparoscopy:

• CA 19-9 >100 U/mL is associated with increased probability of occult peritoneal metastases 1
• Laparoscopy can identify peritoneal implants missed even on high-quality CT (12% yield for pancreatic adenocarcinoma) 1
• Positive peritoneal cytology is equivalent to M1 disease 1

Important Caveats

Biliary obstruction can cause false-positive CA 19-9 elevation:

• If jaundice or elevated bilirubin is present, perform biliary decompression first
• Recheck CA 19-9 after decompression is complete
• Persistent elevation after decompression strongly suggests malignancy 1, 2

Do not rely solely on tumor markers for diagnosis:

• CA 19-9 is not tumor-specific and can be elevated in cholangitis, choledocholithiasis, pancreatitis, and severe hepatic injury 1, 2
• Diagnosis must be confirmed with imaging and tissue biopsy 1

Management Approach

If Metastatic Disease Confirmed (Most Likely Scenario)

Systemic chemotherapy is the primary treatment modality for metastatic pancreatic adenocarcinoma:

• Refer urgently to medical oncology for consideration of combination chemotherapy (gemcitabine plus nab-paclitaxel or FOLFIRINOX regimens)
• Measure baseline CA 19-9 and monitor every 1-3 months during active treatment 1
• Serial CA 19-9 elevation may indicate progressive disease and should prompt confirmatory imaging 1
• Consider palliative biliary stenting if obstruction develops 1

If Oligometastatic Disease (Adrenal Lesion Only)

In rare cases of isolated adrenal metastasis with controlled pancreatic primary, multimodal therapy including adrenalectomy may be considered:

• Case reports document complete pathologic response with chemoradiotherapy followed by adrenalectomy 6
• This approach requires multidisciplinary tumor board discussion
• Not standard of care but may be considered in highly selected patients 6

Monitoring Strategy

• Restaging with high-quality abdominal and chest imaging after each treatment modality 1
• Serial CA 19-9 measurements to track treatment response (though not sufficient alone) 1
• Different CA 19-9 testing methods are not interchangeable—use consistent methodology 2

The prognosis is poor with metastatic pancreatic cancer, but early initiation of systemic therapy and supportive care can improve quality of life and potentially extend survival.