Pancreatoblastoma
Incidence and Risk Factors
Pancreatoblastoma accounts for 10% to 20% of all pancreatic tumors during childhood. It is the most common pancreatic tumor of young children and typically presents in the first decade of life, with a median age at diagnosis of 5 years.[1,2]
Patients with Beckwith-Wiedemann syndrome have an increased risk of developing pancreatoblastoma. This syndrome is identified in up to 60% of cases of pancreatoblastoma developing during early infancy and in 5% of children developing pancreatoblastoma later in life.[3] Pancreatoblastoma has also been associated with familial adenomatous polyposis syndromes.[4]
Histology and Molecular Features
Pancreatoblastoma is thought to arise from the persistence of the fetal analogue of pancreatic acinar cells. Pathology shows an epithelial neoplasm with an arrangement of acinar, trabecular, or solid formations separated by dense stromal bands.[1] These tumors will often have activation of Wnt signaling (most commonly caused by somatic variants in CTNNB1). IGF2 gene alterations have also been frequently observed in individuals with pancreatoblastoma. These findings suggest that pancreatoblastoma might result from the disruption of normal pancreas differentiation.[5,6]
Clinical Presentation
Although approximately one-half of pancreatoblastoma cases originate in the head of the pancreas, jaundice is uncommon. Close to 80% of the tumors secrete alpha-fetoprotein, which can be used to measure response to therapy and monitor for recurrence.[2] In some cases, the tumor may secrete adrenocorticotropic hormone or antidiuretic hormone, and patients may present with Cushing syndrome and the syndrome of inappropriate antidiuretic hormone secretion.[3] Metastases are present in 30% to 40% of patients, usually involving liver, lungs, and lymph nodes.[2]
Outcome
Using a multimodality approach, close to 80% of patients can be cured.[2]
Treatment of Pancreatoblastoma
Treatment options for pancreatoblastoma include the following:
- Surgery.
- Chemotherapy.
The European Cooperative Study Group for Pediatric Rare Tumors within the PARTNER project (Paediatric Rare Tumours Network - European Registry) has published consensus guidelines for the diagnosis and treatment of childhood pancreatoblastoma.[7] Surgery is the mainstay treatment, and a complete surgical resection is required for cure. Because of the common origin in the head of the pancreas, a Whipple procedure is usually required.[8,9]
For large, unresectable, or metastatic tumors, preoperative chemotherapy is indicated. Pancreatoblastoma commonly responds to chemotherapy. A cisplatin-based regimen is usually recommended and the PLADO regimen, which includes cisplatin and doxorubicin, is most commonly used. Treatment is modeled after the management of hepatoblastoma, with two to three cycles of preoperative therapy, followed by resection and adjuvant chemotherapy.[2,4,10,11]
Although radiation therapy has been used for unresectable tumors and relapsed cases, its role in the treatment of microscopic disease after surgery has not been defined.[4]
Response has been seen for patients with relapsed or persistent pancreatoblastoma treated with gemcitabine in one case [12] and vinorelbine and oral cyclophosphamide in two cases.[13]
High-dose chemotherapy with autologous hematopoietic stem cell rescue has been reported to be effective in selected cases.[10,14]
References:
- Chung EM, Travis MD, Conran RM: Pancreatic tumors in children: radiologic-pathologic correlation. Radiographics 26 (4): 1211-38, 2006 Jul-Aug.
- Bien E, Godzinski J, Dall'igna P, et al.: Pancreatoblastoma: a report from the European cooperative study group for paediatric rare tumours (EXPeRT). Eur J Cancer 47 (15): 2347-52, 2011.
- Chisholm KM, Hsu CH, Kim MJ, et al.: Congenital pancreatoblastoma: report of an atypical case and review of the literature. J Pediatr Hematol Oncol 34 (4): 310-5, 2012.
- Glick RD, Pashankar FD, Pappo A, et al.: Management of pancreatoblastoma in children and young adults. J Pediatr Hematol Oncol 34 (Suppl 2): S47-50, 2012.
- Honda S, Okada T, Miyagi H, et al.: Spontaneous rupture of an advanced pancreatoblastoma: aberrant RASSF1A methylation and CTNNB1 mutation as molecular genetic markers. J Pediatr Surg 48 (4): e29-32, 2013.
- Isobe T, Seki M, Yoshida K, et al.: Integrated Molecular Characterization of the Lethal Pediatric Cancer Pancreatoblastoma. Cancer Res 78 (4): 865-876, 2018.
- Bien E, Roganovic J, Krawczyk MA, et al.: Pancreatoblastoma in children: EXPeRT/PARTNER diagnostic and therapeutic recommendations. Pediatr Blood Cancer 68 (Suppl 4): e29112, 2021.
- Vasudevan SA, Ha TN, Zhu H, et al.: Pancreaticoduodenectomy for the treatment of pancreatic neoplasms in children: A Pediatric Surgical Oncology Research Collaborative study. Pediatr Blood Cancer 67 (9): e28425, 2020.
- Lindholm EB, Alkattan AK, Abramson SJ, et al.: Pancreaticoduodenectomy for pediatric and adolescent pancreatic malignancy: A single-center retrospective analysis. J Pediatr Surg 52 (2): 299-303, 2017.
- Dall'igna P, Cecchetto G, Bisogno G, et al.: Pancreatic tumors in children and adolescents: the Italian TREP project experience. Pediatr Blood Cancer 54 (5): 675-80, 2010.
- Défachelles AS, Martin De Lassalle E, Boutard P, et al.: Pancreatoblastoma in childhood: clinical course and therapeutic management of seven patients. Med Pediatr Oncol 37 (1): 47-52, 2001.
- Belletrutti MJ, Bigam D, Bhargava R, et al.: Use of gemcitabine with multi-stage surgical resection as successful second-line treatment of metastatic pancreatoblastoma. J Pediatr Hematol Oncol 35 (1): e7-10, 2013.
- Dhamne C, Herzog CE: Response of Relapsed Pancreatoblastoma to a Combination of Vinorelbine and Oral Cyclophosphamide. J Pediatr Hematol Oncol 37 (6): e378-80, 2015.
- Hamidieh AA, Jalili M, Khojasteh O, et al.: Autologous stem cell transplantation as treatment modality in a patient with relapsed pancreatoblastoma. Pediatr Blood Cancer 55 (3): 573-6, 2010.