Acinar Cell Carcinoma of the Pancreas

Acinar cell carcinoma of the pancreas is a rare malignant epithelial tumour with differentiation toward pancreatic acinar cells. It has a better outcome than ductal adenocarcinoma but is still aggressive.

It makes up 1% to 2% of adult exocrine pancreatic tumours and about 15% in children. The mean age is 60 years and men are more affected. Tumours are often large (mean 6 to 10 cm) and well circumscribed, and about half have metastases at diagnosis. Median survival is about 18 to 36 months, longer after resection.

A lipase hypersecretion syndrome (subcutaneous fat necrosis, polyarthralgia and eosinophilia) occurs in about 10% to 15%.

Pathophysiology.

Tumour cells produce digestive enzymes (trypsin, chymotrypsin, lipase). Genomic changes include RAF family fusions and about a quarter with defects in DNA repair (BRCA2, PALB2, microsatellite instability), which has treatment implications.

Abdominal pain, weight loss, nausea, vomiting, diarrhoea, a palpable mass and, less often than with ductal carcinoma, jaundice. Fat necrosis, joint pains and eosinophilia indicate the lipase syndrome.

Red flags.

• Jaundice or cholangitis.
• Gastric outlet obstruction.
• Weight loss with liver metastases.
• Painful skin nodules with arthritis.

CT or magnetic resonance imaging shows a large, well defined, heterogeneous exophytic mass with enhancement lower than normal pancreas. Endoscopic ultrasound with biopsy and immunostaining (trypsin, BCL10, chymotrypsin) confirms the diagnosis. Serum lipase may be very high, while CA 19-9 is often normal. Stage with chest CT. Test for BRCA1, BRCA2, PALB2 and microsatellite instability.

Differential diagnosis.

• Pancreatic ductal adenocarcinoma.
• Pancreatic neuroendocrine tumour.
• Solid pseudopapillary neoplasm.
• Pancreatoblastoma.
• Pancreatic lymphoma.

Surgical resection with negative margins is the treatment for localised disease, and is often feasible because tumours rarely encase vessels. Add adjuvant chemotherapy, and use systemic therapy for advanced disease.

• Modified FOLFIRINOX (adjuvant or metastatic): oxaliplatin 85 mg/m2 IV, irinotecan 150 mg/m2 IV, leucovorin 400 mg/m2 IV and fluorouracil 2,400 mg/m2 IV over 46 hours on day 1 of a 14-day cycle; 12 cycles adjuvant, or until progression in advanced disease; maximum fluorouracil 2,400 mg/m2 each cycle; monitor blood counts, liver and renal function, neuropathy and diarrhoea; check dihydropyrimidine dehydrogenase status first; reduce irinotecan for UGT1A1 deficiency and bilirubin over 17 micromol/L, and omit oxaliplatin if creatinine clearance is under 30 mL/min.
• Platinum containing regimens and PARP inhibitors are considered when DNA repair defects are found, and immunotherapy for microsatellite instability, by specialist decision.
• Pancreatic enzyme replacement (pancrelipase) when steatorrhoea occurs: 25,000 to 50,000 lipase units with each main meal and 10,000 to 25,000 with snacks; maximum 10,000 lipase units/kg daily; monitor weight and stool; reduce if over 10,000 units/kg.

Resect or ablate liver metastases in selected patients.

Monitoring. Imaging every 3 months for 2 years after resection, then every 6 months; lipase as a tumour marker if raised at diagnosis.

Referral and escalation. Pancreatic multidisciplinary team, oncology and genetics.