Pancreatoblastoma

Pancreatoblastoma is an embryonal tumour that recapitulates fetal pancreatic development, with acinar, ductal and neuroendocrine differentiation and the squamoid nests that define it under the microscope. It presents in preschool children as a large, painless abdominal mass, sometimes with weight loss, vomiting or jaundice, and serum alpha-fetoprotein is raised in most. Alterations in the Wnt pathway (CTNNB1 mutations or APC loss) and loss of heterozygosity at 11p, the Beckwith-Wiedemann locus, are the recurrent genetic findings, and the tumour occurs in children with Beckwith-Wiedemann syndrome and in families with familial adenomatous polyposis. Adult cases occur and behave more aggressively.

Because the disease is so rare, treatment follows consensus from the European Cooperative Study Group for Paediatric Rare Tumours (EXPeRT) and national rare-tumour registries rather than trials. Complete surgical resection is the cornerstone, usually a pancreatoduodenectomy or distal pancreatectomy; for the large tumours that cannot be removed at diagnosis, neoadjuvant chemotherapy with cisplatin and doxorubicin (the PLADO regimen used in hepatoblastoma) shrinks the tumour and makes surgery possible, and alpha-fetoprotein is followed as a response marker. Adjuvant chemotherapy is given after incomplete resection or for metastatic disease, and radiotherapy is reserved for residual disease. Metastases, most often to the liver, occur in a minority at diagnosis and are treated with chemotherapy and resection where possible.

Children with localised, completely resected disease usually do well; outcomes are worse with metastases at diagnosis and in adults. Late effects of platinum and anthracycline chemotherapy and of pancreatic surgery, including diabetes and exocrine insufficiency, need lifelong follow-up. International registries are pooling cases to learn about relapse treatment and the role of Wnt-directed therapy.