Which mutation is most characteristic of a solid pseudopapillary neoplasm?

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

Answer: (D)

Solid pseudopapillary neoplasms are driven by activation of the Wnt/β-catenin pathway due to mutations in CTNNB1, the gene encoding beta-catenin. This mutation prevents normal degradation of beta-catenin, so it accumulates in the nucleus and cytoplasm and alters gene transcription, promoting tumor growth. That nuclear/cytoplasmic beta-catenin pattern is a hallmark of SPN and underpins its characteristic biology.

Other mutations point to different pancreatic tumors. KRAS mutations are common in pancreatic ductal adenocarcinoma, not SPN. GNAS mutations appear in mucinous pancreatic neoplasms like IPMNs. MEN1 mutations are associated with pancreatic neuroendocrine tumors and MEN1 syndrome. Therefore, CTNNB1 mutation best fits the profile of solid pseudopapillary neoplasm.