Molecular and clinicopathological features of appendiceal mucinous neoplasms

Appendiceal mucinous tumors (AMTs) include low-grade mucinous appendiceal neoplasms (LAMNs), high-grade mucinous appendiceal neoplasms (HAMNs), and mucinous adenocarcinomas (MACs). We collected 51 AMT samples (LAMN: 34, HAMN: 8, MAC: 9). Three of the eight HAMN cases contained LAMN components, and four out of nine MAC cases contained LAMN and/or HAMN components within the tumor. A next-generation sequencing (NGS) cancer hotspot panel was used to analyze 11 pure LAMN, 4 HAMN, and 3 MAC cases. The results revealedKRASandGNASas the most frequently mutated genes. Sanger sequencing was then performed to detectKRAS,GNAS, andTP53mutations in the remaining 31 cases andRNF43mutations in all cases.KRAS/GNASandTP53mutations occurred exclusively in pure LAMNs; however, five LAMN cases had mutations in bothKRASandGNAS.RNF43mutations almost exclusively occurred withKRAS/GNASmutations in pure LAMNs. In MAC and HAMN,KRAS/GNASmutation status was nearly preserved between lower-grade areas. Most of the detectedRNF43mutations was missense type.RNF43mutations were detected in both components of MAC with lower-grade area; however,RNF43mutations detected in these two lesions were entirely different.RNF43mutations were detected in only one of the eight HAMN patients, which was the sole case without pseudomyxoma peritonei (PMP). None of the four MAC patients withRNF43mutation showed PMP. These findings suggest thatRNF43mutations occur at a later stage of MAC development and do not associate with PMP. Furthermore, a gradual transition from LAMN to MAC via HAMN could be considered.