What are the presentation, diagnostic evaluation, and management of pancreatoblastoma in pediatric patients?

Pancreatoblastoma in Pediatric Patients

Pancreatoblastoma is the most common malignant pancreatic tumor in children under 10 years of age, presenting typically with an abdominal mass and elevated AFP, requiring complete surgical resection combined with chemotherapy for optimal outcomes. 1

Clinical Presentation

Pancreatoblastoma occurs predominantly in early childhood with a median age of 4 years, showing a male predominance (approximately 2:1 ratio). 1 The most common presenting features include:

• Abdominal mass (most frequent symptom, occurring in approximately 50% of cases) 1
• Abdominal pain (present in nearly 50% of patients) 1, 2
• Diarrhea (less common but notable) 2
• Elevated serum alpha-fetoprotein (AFP) levels in nearly all cases (17/18 patients in one series), making it critical for both diagnosis and disease monitoring 1, 2

Unlike adult pancreatic adenocarcinoma which presents with jaundice in head lesions 3, pancreatoblastoma rarely causes obstructive symptoms initially. The tumor can occur anywhere in the pancreas, though there is some predilection for the pancreatic head. 4

Diagnostic Evaluation

Imaging Studies

The diagnostic workup should proceed systematically:

• Ultrasound (US) can identify a well-defined heterogeneous large mass in the pancreas or mesentery 2
• CT scan and/or MRI are essential for assessing tumor location, size, extent, and distant metastasis 1
• These imaging modalities typically reveal a well-defined heterogeneous mass, which is characteristic 2

Laboratory Markers

• Serum AFP is elevated in nearly all pediatric cases and serves as both a diagnostic marker and a tool for monitoring disease progression or recurrence 1, 2
• This contrasts sharply with adult pancreatic cancer where CA19.9 is used, though it has limited diagnostic value 3

Tissue Diagnosis

• Histopathological examination of resected specimen is required for definitive diagnosis 1
• Preoperative fine needle aspiration is unreliable due to cellular heterogeneity of the tumor 4
• Immunohistochemical staining typically shows:
  • Cytokeratin AE1/AE3 positive (all cases) 2
  • Carcinoembryonic antigen positive (all cases) 2
  • Variable positivity for epithelial membrane antigen, S-100, AFP, neurone-specific enolase, chromogranin A, synaptophysin 2

Management Strategy

Resectable Disease at Presentation

For tumors that are initially resectable, proceed directly to complete surgical resection followed by adjuvant chemotherapy. 1, 5

Surgical options include:

• Pancreaticoduodenectomy (Whipple procedure) for head lesions 1
• Pylorus-preserving pancreaticoduodenectomy 1
• Distal pancreatectomy (with or without splenectomy) for body/tail lesions 1
• Complete resection (R0 resection) is achieved in approximately 82% of cases and is associated with long-term survival 5

Unresectable Disease at Presentation

For tumors deemed unresectable at diagnosis (which occurs in the majority of cases), neoadjuvant chemotherapy is recommended to reduce tumor volume prior to surgical resection. 1

Effective chemotherapy regimens include:

• CDV (cyclophosphamide, doxorubicin, vincristine) 1
• OPEC (vincristine, cisplatin, etoposide, cyclophosphamide) 1
• PLADO (cisplatin, doxorubicin) 1
• IEV (ifosfamide, etoposide, vincristine) 1
• AVCP 1

In the second-line setting, combinations including etoposide, cyclophosphamide/ifosfamide, and cisplatin/carboplatin have shown evidence of response. 6

Treatment of Recurrent/Metastatic Disease

The outcome for recurrent pancreatoblastoma is not uniformly dismal, particularly when surgical resection remains possible. 6 Management options include:

• Surgical resection of recurrent disease when feasible (8 of 15 patients in one series) 6
• Second-line chemotherapy with various regimens showing response in approximately 50% of children 6
• High-dose chemotherapy with stem cell rescue in selected cases (5 of 6 patients alive in one analysis) 6
• Liver transplantation for isolated hepatic metastases (3 of 3 patients alive) 6
• Radiation therapy used selectively (only 3 of 15 patients in one series) 6

Prognosis and Follow-up

• Long-term survival is achievable with complete resection combined with chemotherapy, with 12 of 15 patients alive in one series and 10 with no evidence of disease 5
• In another series, 13 of 21 children were disease-free with median follow-up of 53 months (range 11-156 months) 1
• The risk of recurrence is high, particularly for pancreatoblastoma compared to other pediatric pancreatic tumors 5
• Liver metastases are the most frequent cause of treatment failure 6
• AFP monitoring is essential during follow-up to detect recurrence early 1

Critical Pitfalls to Avoid

• Do not delay imaging when pancreatoblastoma is suspected based on abdominal mass and elevated AFP 1
• Do not rely on fine needle aspiration for diagnosis due to tumor heterogeneity; proceed to surgical resection when feasible 4
• Do not withhold neoadjuvant chemotherapy in unresectable cases, as tumor volume reduction can enable subsequent complete resection 1
• Do not assume recurrent disease is uniformly fatal; aggressive multimodal therapy including repeat resection, high-dose chemotherapy, or liver transplantation can achieve long-term survival 6