Pancreatoblastoma (ORPHA:677)
A rare neoplastic gastroenterologic disease most often found in children, which usually presents with the non-specific symptoms of a palpable mass, vomiting, abdominal pain, jaundice, and weight loss/failure to thrive. Histologically, this malignant epithelial pancreatic neoplasm of the exocrine cells is characterized by multiple lines of differentiation (acinar, ductal, mesenchymal, neuroendocrine) and the presence of squamoid nests.
Epidemiology
The incidence is less than 1/1,000,000 in Europe. Pancreatoblastoma accounts for 0.5% of all pancreatic exocrine tumors and occurs equally in females and males. It is the most common malignant pancreatic tumor in young children and has a mean age of diagnosis of 5 years.
Clinical description
Pancreatoblastoma most often presents in children under the age of 10 (mean of 5 years). Onset in adulthood (third/fourth decade) is extremely rare, and patients are more likely to develop metastases. Symptoms are often non-specific and include a large abdominal mass, abdominal distension/pain, failure to thrive, diarrhea, vomiting and jaundice. Tumors in the head of the pancreas can lead to mechanical obstruction of the upper duodenum and gastric outlet, as well as gastrointestinal bleeding. Local invasion and metastasis to the liver (most commonly), lungs and/or regional lymph nodes can often be discovered at diagnosis. Pancreatoblastoma can sometimes be associated with Beckwith-Wiedemann syndrome and familial adenomatous polyposis (FAP).
Etiology
The etiology is unknown but pancreatoblastoma can occur in any part of the pancreas. It is a malignant embryonal tumor that seems to recapitulate the embryogenesis of the pancreas, presumably because it originates from the pluripotent pancreatic stem cells during foregut development. Sporadic and FAP-associated pancreatoblastomas have frequent alterations in the adenomatous polyposis coli (APC)/beta-catenin pathway, and allelic loss in chromosome 11p.
Diagnostic methods
Diagnosis is based on histological characteristics. Pancreatoblastoma is usually a large (2 to 20 cm), encapsulated mass with a histological picture of multiple squamoid nests composed of whorls of spindle-shaped cells that are diagnostic of this tumor. It shows significant acinar cell differentiation but also ductal, mesenchymal and neuroendocrine differentiation. The tumor marker alpha-fetoprotein (AFP) is raised in 68% of cases, regardless of age. Full staging needs to be performed, including ultrasound and computed tomography (CT) or magnetic resonance imaging (MRI) scans of the primary tumor, as well as CT scans of the chest to detect any metastasis.
Differential diagnosis
Differential diagnoses include poorly differentiated adenocarcinomas, solid pseudopapillary tumors, pancreatic carcinoma, pancreatic neuroendocrine tumors and autoimmune pancreatitis.
Management and treatment
Treatment involves complete surgical resection of the tumor. Procedures include a distal pancreatectomy with or without splenectomy (for tumors in the body and tail of pancreas) and pancreaticoduodenectomy (for those in the head of the pancreas). Chemotherapy (usually cisplatin and doxorubicin) and radiotherapy are used in cases of unresectable, recurrent or metastatic tumors with variable results. In adults, 5-fluorouracil/doxorubicin/mitomycin and doxorubicin/carboplatin have been given as adjuvant therapy.
Prognosis
The prognosis for pediatric cases is usually good if the tumor is resectable, but recurrences still occur. If unresectable and in the presence of metastasis, pancreatoblastoma has an aggressive course and prognosis is poor. Adult cases usually have a poorer prognosis, with a median survival time of 15 months.

                            Last update: 
                            August 2019


                            - Expert reviewer(s): 
                            Pr Ewa BIEN  - Pr Bernadette BRENNAN