What is the cyst marker profile for a solid pseudopapillary neoplasm (SPN)?

• A. KRAS mutation, high amylase, high CEA
• B. GNAS mutation, low amylase, high CEA
• C. CTNNB1 mutation, low amylase, low CEA
• D. No mutation, high amylase, low CEA

Answer: (C)

SPN is driven by activating mutations in CTNNB1, which activate the Wnt/beta-catenin pathway and lead to nuclear localization of beta-catenin in tumor cells. This molecular profile helps distinguish SPN from other pancreatic tumors. In cyst fluid, SPN typically shows low amylase because it does not closely communicate with the pancreatic ductal system, and it also shows low CEA because it is not a mucinous cyst. Thus the cyst marker profile of CTNNB1 mutation with low amylase and low CEA aligns with solid pseudopapillary neoplasm.

Other pancreatic cystic neoplasms are driven by different mutations (KRAS with pancreatic ductal adenocarcinoma; GNAS with IPMN), and they usually have different cyst fluid signatures such as higher amylase (from duct communication) or higher CEA (mucinous content). The combination described—CTNNB1 mutation plus low amylase and low CEA—best fits SPN.