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Pancreatic Cyst Fluid Tests

Pancreatic cystic lesions have been detected in 2.4% to 19.6% of the general population during CT or MRI imaging for unrelated medical reasons. Pancreatic cysts can be mucinous or nonmucinous lesions. Mucinous cysts include intraductal papillary mucinous neoplasm (IPMN) and mucinous cystic neoplasm (MCN). Nonmucinous cysts include pseudocyst and serous cystadenoma. Mucinous cysts need to be distinguished from nonmucinous cysts because they have a higher risk of malignancy.

The accuracy of imaging in distinguishing benign from malignant cysts is approximately 50%. Since imaging is not definitive, endoscopic ultrasound guided fine needle aspiration (EUS FNA) is performed to collect cystic fluid for cytology and measurement of biochemical markers.

Cytology identifies malignant cells, mucin-containing cells, or glycogen-containing cells. Cytologic sensitivity is limited by the paucicellular nature of cystic fluid samples and the presence of blood and epithelial cells from gastric or duodenal mucosa.

The most commonly ordered biomarkers include CEA, amylase, and glucose. CEA is helpful in distinguishing mucinous (IPMN and MCN) from nonmucinous cysts. CEA values are generally undetectable or low (<5 ng/mL) in aspirates from pseudocysts and serous cystadenomas. CEA levels are high in IPMN and MCN cysts due to their mucinous lining. CEA levels of 192 ng/mL or higher are suggestive of mucinous pancreatic cysts. In general, the higher the CEA value, the more likely the cyst is a mucinous cyst. A CEA cutoff of 192 ng/mL has a sensitivity of 73% and specificity of 89% for detection of mucinous cysts.

Amylase may be helpful in differentiating pseudocyst from serous cystadenoma. Amylase is almost always elevated in pseudocysts, but low in serous cystadenoma. Pseudocyst amylase values often exceed 1000 U/mL because they communicate with the pancreatic duct. Amylase levels are also often high in IPMN because they communicate with the pancreatic duct. MCN have variable amylase levels because they less often communicate with the pancreatic duct.

Pancreatic cyst glucose levels can also distinguish between mucinous and nonmucinous cysts. Mucinous cysts have a mean glucose level of 15.9 +/- 6.2 mg/dL, while nonmucinous cysts have a mean level of 94.0 +/-12.2 mg/dL. A glucose cutoff of 50 mg/dL or less has a sensitivity of 88% and specificity of 78% for detection of mucinous cysts.

Molecular testing for KRAS mutation may also by helpful in specific circumstances. The presence of KRAS mutation with allelic loss is associated with mucinous cystic tumors. The combination of KRAS mutation with CEA elevation appears to be more sensitive for detection of malignancy than either test alone.

References

McCarty TR et al. Pancreatic cyst fluid glucose in differentiating mucinous from nonmucinous pancreatic cysts: a systematic review and meta-analysis. Gastrointestinal Endoscopy 2021;94:698-712.

Lopes CV. Cyst fluid glucose: An alternative to carcinoembryonic antigen for pancreatic mucinous cysts. World J Gastroenterol 2019;25:2271-2278.

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