pancreatoblastoma

Definition: Pancreatoblastoma (PB), or infantile pancreatic carcinoma, is an extremely rare pancreatic tumor in childhood, comprising 0.5% of pancreatic non-endocrine tumors. Although PB mainly presents during childhood but can also occur in adults.

Localization

The majority of these tumors arise in the head of the pancreas.

Clinical synopsis

Children with PB usually present late with upper abdominal pain and many have a palpable mass in the epigastrium. Mechanical obstruction of the upper duodenum and gastric outlet by tumor in the head of the pancreas.

 vomiting
 jaundice
 gastrointestinal bleeding

Microscopical synopsis

 distinct acinar and squamoid cell differentiation.

Molecular biology

PB has been associated with alterations in the Wnt signaling pathway and chromosome 11p loss of heterozygosity (LOH).

Tumoral predisposition

 Beckwith-Wiedemann syndrome (BWS)
 familial adenomatous polyposis (FAP)

Diagnosis

Alpha-fetoprotein may be elevated in up to 68% of patients with PB. Ultrasound and CT scan may be useful but preoperative diagnosis is often quite difficult.

Treatment

The treatment of choice is complete resection, that may often be curative. The role of adjuvant chemotherapy or radiotherapy is still under discussion due to small number of patients treated as yet.

Chemotherapy regimens consisting of cyclophosphamide, etoposide, doxorubicin, and cisplatin have been used in neoadjuvant setting with anecdotal benefit.

Prognosis

Prognosis of this rare tumor is good, when resected completely. Prognosis is poorer, when there is metastasis or when it is inoperable.

On the whole, PB is regarded to be a curable tumor; hence the clinical diagnosis should be made early.

PB tend to be less aggressive in infants and children compared to adults.

Cytogenetics: 7889500

 add(1)(q42)
 t(13;22)(q10;q10) (7889500)
 t(13;13)(q10;q10), i(6p)(p10), and del(1) (7889500)

CGH

 11p loss
  8q gain (15721631)

Molecular biology

 11p LOH (86%) (12116082, 11696422)
 IGF2 overexpression (12116082)

 activating mutations of the beta-catenin gene CTNNB1 (67%) (11696422)

 germline truncating mutation combined with loss of the wild-type allele in familial adenomatous polyposis-associated pancreatoblastoma (11696422)

Predisposition

 Beckwith-Wiedemann syndrome
 familial adenomatous polyposis (FAP)

Links

 Pancreatoblastoma at JOP

References

 Saif MW. Pancreatoblastoma. JOP. 2007 Jan 9;8(1):55-63. PMID: 17228135

 Barenboim-Stapleton L, Yang X, Tsokos M, Wigginton JM, Padilla-Nash H, Ried T, Thiele CJ. Pediatric pancreatoblastoma: histopathologic and cytogenetic characterization of tumor and derived cell line. Cancer Genet Cytogenet. 2005 Mar;157(2):109-17. PMID: 15721631

 Kerr NJ, Chun YH, Yun K, Heathcott RW, Reeve AE, Sullivan MJ. Pancreatoblastoma is associated with chromosome 11p loss of heterozygosity and IGF2 overexpression. Med Pediatr Oncol. 2002 Jul;39(1):52-4. PMID: 12116082

 Abraham SC, Wu TT, Hruban RH, Lee JH, Yeo CJ, Conlon K, Brennan M, Cameron JL, Klimstra DS. Genetic and immunohistochemical analysis of pancreatic acinar cell carcinoma: frequent allelic loss on chromosome 11p and alterations in the APC/beta-catenin pathway. Am J Pathol. 2002 Mar;160(3):953-62. PMID: 11891193

 Abraham SC, Wu TT, Klimstra DS, Finn LS, Lee JH, Yeo CJ, Cameron JL, Hruban RH. Distinctive molecular genetic alterations in sporadic and familial adenomatous polyposis-associated pancreatoblastomas : frequent alterations in the APC/beta-catenin pathway and chromosome 11p. Am J Pathol. 2001 Nov;159(5):1619-27. PMID: 11696422

 Nagashima Y, Misugi K, Tanaka Y, Ijiri R, Nishihira H, Nishi T, Kigasawa H, Kato K. Pancreatoblastoma: a second report on cytogenetic findings. Cancer Genet Cytogenet. 1999 Mar;109(2):178-9. PMID: 10087957

 Wiley J, Posekany K, Riley R, Holbrook T, Silverman J, Joshi V, Bowyer S. Cytogenetic and flow cytometric analysis of a pancreatoblastoma. Cancer Genet Cytogenet. 1995 Feb;79(2):115-8. PMID: 7889500

 Klimstra DS, Wenig BM, Adair CF, Heffess CS. Pancreatoblastoma. A clinicopathologic study and review of the literature. Am J Surg Pathol. 1995 Dec;19(12):1371-89. PMID: 7503360