What are the next steps in diagnosis and treatment for a patient with immunohistochemistry (IHC) results suggesting adenocarcinoma of pancreatico-biliary origin?

Management of Adenocarcinoma of Pancreatico-Biliary Origin

Immediate Next Steps in Diagnosis

The first priority is completing staging with pancreatic protocol CT of chest, abdomen, and pelvis to determine resectability and detect metastatic disease, as this fundamentally determines whether curative surgery versus palliative chemotherapy is appropriate. 1

Complete Staging Workup

• Obtain pancreatic protocol CT with triphasic imaging (non-contrast, arterial, pancreatic parenchymal, and portal venous phases) using 3mm thin cuts to assess vascular involvement and detect metastases as small as 3-5mm 1
• Chest CT with contrast (preferred over chest x-ray) to exclude pulmonary metastases 1
• Baseline CA 19-9 measurement for prognostic information and future monitoring, though this is elevated in only 80% of cases and can be falsely elevated with cholestasis 2
• Consider staging laparoscopy before definitive surgery, especially for body/tail lesions, markedly elevated CA 19-9, large tumors, or borderline resectable disease to detect occult peritoneal metastases 1

Exclude Metastatic Disease from Other Primary Sites

The IHC pattern (CK7+, CK20-, MUC-1+, CA19-9+, CK19+, CDX2-) strongly favors pancreatico-biliary origin, but you must exclude metastatic adenocarcinoma from other sites 1:

• Pancreas: EUS or MRI if not already performed 1
• Stomach: Upper endoscopy if clinically indicated 1
• Lung: Already covered by chest CT 1
• Colon: The CDX2-negative result argues strongly against colonic origin 1
• Breast: Clinical examination; mammography only if breast mass present 1

Determining Resectability Classification

Based on imaging, classify the tumor as 1:

• Resectable: No arterial or venous involvement, no metastases
• Borderline resectable: Limited vascular involvement potentially amenable to resection
• Locally advanced unresectable: Extensive vascular involvement (celiac axis or SMA encasement) without distant metastases
• Metastatic (Stage IV): Any distant metastases present

Critical distinction: Stage IV disease with distant metastases remains unresectable regardless of treatment response because systemic disease persists, and surgery provides no survival benefit 3

Treatment Pathways Based on Stage

For Resectable Disease

• Refer to high-volume center performing 15-20+ pancreatic resections annually 1
• Multidisciplinary consultation involving diagnostic imaging, interventional endoscopy, medical oncology, radiation oncology, surgery, and pathology 1
• Tissue diagnosis is NOT required before surgical resection when clinical suspicion is high; non-diagnostic biopsy should not delay surgery 1
• If biopsy needed, EUS-guided FNA is preferable to CT-guided approach due to better yield, safety, and lower peritoneal seeding risk 1
• Avoid percutaneous biopsy in resectable disease due to tumor seeding risk 1
• Surgery within appropriate timeframe after staging completion 1
• Adjuvant chemotherapy should begin within 12 weeks post-operatively for patients who did not receive neoadjuvant therapy 1

For Borderline Resectable Disease

• Consider neoadjuvant chemotherapy if CA 19-9 >500 IU/ml, as this suggests higher risk and may improve resectability 2
• Induction chemotherapy (preferably 4-6 months) followed by reassessment 1
• Re-staging imaging after neoadjuvant therapy to assess response 1

For Locally Advanced Unresectable Disease (Stage III)

• First-line systemic chemotherapy as primary treatment 1
• Consider induction chemotherapy (4-6 months) followed by chemoradiation or SBRT in selected patients without systemic metastases 1
• Clinical trial participation is preferred when available 1

For Metastatic Disease (Stage IV)

Systemic chemotherapy is the treatment of choice; surgery has no role. 3, 4

• Gemcitabine-based chemotherapy is FDA-approved for metastatic (Stage IV) pancreatic adenocarcinoma 4
• FOLFIRINOX or gemcitabine/nab-paclitaxel for good performance status patients 1
• Molecular profiling should be performed: KRAS, BRCA, MSI status, NTRK fusions, FGFR alterations, IDH mutations 1, 2
• Genetic counseling for patients with family history or young age 1, 2

Management of Biliary Obstruction

If jaundice is present:

• Obtain imaging BEFORE biliary drainage to avoid artifacts 2
• Avoid preoperative biliary stenting in resectable disease, as it increases post-operative morbidity 1
• For unresectable disease with biliary obstruction: Endoscopic metal stents are preferred over plastic stents (lower complication rates: 46.7% vs 87.5%) 5
• Biliary complications reduce chemotherapy completion rates (47.6% vs 64.2%) and worsen survival 5

Surveillance After Resection

• Every 3-6 months for 2 years, then every 6-12 months 1
• History and physical for symptom assessment 1
• CA 19-9 levels if initially elevated 1
• Abdominal CT with contrast 1

Critical Pitfalls to Avoid

• Do not delay surgery for tissue diagnosis in clearly resectable disease with high clinical suspicion 1
• Do not perform percutaneous biopsy in potentially resectable tumors due to seeding risk 1
• Do not place biliary stents before surgical evaluation in resectable disease 1
• Do not pursue surgical resection in Stage IV disease—survival is only 15% at 1 year and 2% at 5 years regardless of surgery 3
• Do not assume resectability without proper pancreatic protocol imaging 1