Which mutation is most characteristic of a solid pseudopapillary neoplasm?

• A. KRAS mutation
• B. CTNNB1 mutation
• C. GNAS mutation
• D. MEN1 mutation

Answer: (B)

Solid pseudopapillary neoplasm is driven by activating mutations in CTNNB1, which encodes beta-catenin. This change disrupts the regulation of the Wnt signaling pathway, leading to stabilization and accumulation of beta-catenin in the nucleus. The result is ongoing transcriptional activation that promotes the unique growth pattern of SPN. Immunohistochemically, nuclear beta-catenin staining is a hallmark feature, helping distinguish SPN from other pancreatic tumors. By contrast, KRAS mutations are typical of pancreatic ductal adenocarcinoma, GNAS mutations are associated with intraductal papillary mucinous neoplasms, and MEN1 mutations are linked to multiple endocrine neoplasia and pancreatic neuroendocrine tumors. Hence, CTNNB1 mutation is the most characteristic change in solid pseudopapillary neoplasm.