Abstract Pancreatoblastoma, a rare pancreatic tumor, exhibits diverse differentiation pathways, including acinar, ductal, and neuroendocrine lineages, often with distinct squamoid nests [3]. We present a notable case of pancreatoblastoma coexisting with large cell neuroendocrine carcinoma in a 10-year-old boy, presenting with abdominal discomfort, weight loss, and lesions in the pancreas, spleen, and liver visible on imaging. A liver biopsy revealed a poorly differentiated carcinoma with neuroendocrine features, while a splenic biopsy showed acinar cell differentiation, raising possible diagnoses of pancreatoblastoma or acinar cell carcinoma. Subsequent surgical resection after chemotherapy revealed diverse components within the pancreatoblastoma, including well-differentiated acinar and neuroendocrine cells, squamoid nests, and a high-grade neuroendocrine carcinoma. Genetic analysis detected pathogenic variants in TP53 and SMAD4, rarely found in pancreatoblastomas. This juxtaposition of large cell neuroendocrine carcinoma and pancreatoblastoma suggests a potential evolution from well-differentiated neuroendocrine tumors to poorly-differentiated carcinomas within pancreatoblastomas.
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