Clinical Impact of KRAS and GNAS Analysis Added to CEA and Cytology in Pancreatic Cystic Fluid Obtained by EUS-FNA

Pancreatic cysts are common incidental findings with malignant potential, raising diagnostic and treatment dilemmas.

To determine the added value of KRAS and GNAS mutation analysis on cyst classification and decision making.

We analyzed 52 frozen samples of pancreatic cystic fluid obtained by EUS-FNA between 2008 and 2014. In addition to cytology and CEA, mutations of GNAS (exons 8 and 9) and KRAS (exons 2 and 3) genes were analyzed using Sanger sequencing.

There were 52 patients, 67% females, with a mean age of 59 ± 15 years (29–91). Cysts were classified as mucinous in 21 patients (40%) (14 low-risk, seven malignant) and non-mucinous in 31 patients (60%). After EUS-FNA, 11 patients had surgery, six had chemotherapy or palliation, one had endoscopic drainage, and 34 are on follow-up after a mean of 57 months. KRAS mutation was detected in nine and GNAS in two samples. Patients harboring cysts with KRAS mutations were older (p = 0.01), cysts were more commonly mucinous (p = 0.001) and malignant (p = 0.01). KRAS mutations were present in both low-risk and malignant mucinous lesions. For identifying mucinous lesions, CEA > 192 ng/mL performed better (AUC ROC = 93%), whereas for malignant/high-risk mucinous lesions, EUS imaging had the best accuracy (AUC ROC = 88%). After molecular analysis, a modification in cyst classification occurred in ten patients, but was correct in only two, a pseudocyst re-classified as IPMN and a malignant cyst as a non-mucinous cyst.