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BRAF POSITIVE INTRADUCTAL PAPILLARY MUCINOUS NEOPLASMS (IPMN) HAVE VARIABLE PRESENTING SYMPTOMS, MORPHOLOGIC FEATURES, CYST FLUID ANALYTE, AND SOMATIC MUTATION PROFILES, WHEN COMPARED WITH BRAF NEGATIVE: A MULTICENTER PROSPECTIVE COHORT STUDY

Date
May 21, 2024

Background
Clinical presentation, imaging, and endoscopic ultrasound (EUS) findings, as well as fluid analysis possess prognostic features for intraductal papillary mucinous neoplasms (IPMN); however, classification of IPMN-risk remains challenging1,2. As a means for further distinguishing high-risk IPMNs, next-generation sequencing (NGS) allows for validation of cyst subtype and prognostic mutation analysis3.
The KRAS and GNAS pathways are often present in IPMNs when compared with non-mucinous cysts. Other changes, such as SMAD4 and TP53, portend higher-risk IPMN. However, the BRAF mutation, a Raf isoform involved in the Ras oncogene signaling, is a lesser-known entity in IPMNs4,5. In this study, we evaluated features of BRAF positive (BRAF+) when compared to BRAF negative (BRAF-) IPMNs. We predicted BRAF+ IPMNs would possess variable features compared to BRAF- IPMNs.
Methods
A multicenter prospective cohort study at two tertiary care centers in the United States in which subject data was gathered into a data repository. Initial demographics, radiologic parameters, location, and high-risk features were obtained. All subjects underwent EUS-guided aspiration or biopsy (EUS-FNA/FNB) for cyst fluid analysis, NGS, and cytology.
Subject data was separated by BRAF+ v. BRAF- mutations, and continuous variables were analyzed using student's t-test, categorical variables, a one-tailed Fischer’s exact testing using SPSS software.
Results
From 2018-2023, 134 IPMNs, were identified (24 BRAF+, 110 BRAF-). The mean age of the BRAF+ group was 71.3 years, and 45.5% were women, no different than the BRAF- group. The baseline size of the BRAF+ was no different than the BRAF- [22.8 millimeters (mm) by 14.4 mm versus (v.) 24.3 mm by 18.1 mm], nor was the distribution of cyst location (Table 1).
Morphologically, there was a higher proportion of IPMNs with septae in the BRAF- v. BRAF+ group (47.3% v. 16.7%, p=0.008) and wall enhancement (26.4% v. 4.2%, p=0.02). More BRAF- subjects had pancreatic ductal (PD) dilation compared to BRAF+ patients (28.2% v. 8.3%, p=0.03). The BRAF- group was also more likely to present with weight loss (17.3%, p=0.02), worsening glycemic control (30.9%, p=0.007), and pain (38.2%, p=0.02), v. BRAF+ subjects. There was a difference in mean amylase levels detected within cyst fluid (p=0.03) and glucose (p=0.0001), but not CEA levels. There was no significant difference seen in high-grade IPMN or cancer in the BRAF- v. BRAF+ groups. GNAS was seen more often in BRAF+ subjects (p=0.02), KRAS less often (p=0.01)(Table 2).
Conclusions
BRAF+ IPMNs possess a lower proportion of symptoms, including weight loss, worsening glycemic control, and pain. Morphologically, BRAF+ IPMNs have lower proportions of septae, wall enhancement, and PD dilation, with lower amylase levels and KRAS+; however, the significance of these findings requires further investigation.

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