Pancreatic acinar cell carcinoma

Acinar cell carcinoma arises from the exocrine cells that make digestive enzymes. Tumours are typically large, well circumscribed and soft, more often in the head, and are diagnosed by biopsy with immunohistochemistry for trypsin, chymotrypsin and BCL10; a minority are mixed acinar-neuroendocrine carcinomas. About one in ten patients has the lipase hypersecretion syndrome of subcutaneous fat necrosis, polyarthralgia and eosinophilia, and serum lipase and alpha-fetoprotein can serve as tumour markers. Metastases at diagnosis are common, most often to the liver.

The genetics differ sharply from ductal adenocarcinoma: KRAS mutations are rare, and instead sequencing finds recurrent BRAF or RAF1 fusions (SND1-BRAF and others) in roughly a fifth to a quarter of cases, alterations in homologous recombination genes including germline BRCA2 and PALB2 in a substantial minority, mismatch repair deficiency in a few, and APC or CTNNB1 changes in the Wnt pathway. Every patient should therefore have germline and tumour sequencing, and germline testing has consequences for relatives.

Surgery is the only curative treatment and is offered even for large tumours and selected metastatic disease, because outcomes after resection are better than for ductal adenocarcinoma. There is no randomised evidence for systemic treatment; retrospective series show that fluoropyrimidine and oxaliplatin regimens (FOLFOX, FOLFIRINOX) produce more responses than gemcitabine-based treatment, which is why guidelines favour them. Tumours with BRAF fusions respond to MEK inhibitors in case reports, homologous recombination-deficient tumours to platinum and PARP inhibitors, and mismatch repair deficient tumours to pembrolizumab. Mixed acinar-neuroendocrine tumours are treated as acinar cell carcinoma.