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 revealed KRAS and GNAS as the most frequently mutated genes. Sanger sequencing was then performed to detect KRAS, GNAS, and TP53 mutations in the remaining 31 cases and RNF43 mutations in all cases. KRAS/GNAS and TP53 mutations occurred exclusively in pure LAMNs; however, five LAMN cases had mutations in both KRAS and GNAS. RNF43 mutations almost exclusively occurred with KRAS/GNAS mutations in pure LAMNs. In MAC and HAMN, KRAS/GNAS mutation status was nearly preserved between lower-grade areas. Most of the detected RNF43 mutations was missense type. RNF43 mutations were detected in both components of MAC with lower-grade area; however, RNF43 mutations detected in these two lesions were entirely different. RNF43 mutations 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 with RNF43 mutation showed PMP. These findings suggest that RNF43 mutations 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.

阑尾粘液性肿瘤（AMT）包括低度粘液性阑尾肿瘤（LAMN），高级别粘液性阑尾肿瘤（HAMN）和粘液性腺癌（MAC）。我们收集了51个AMT样本（LAMN：34，HAMN：8，MAC：9）。8例HAMN病例中有3例包含LAMN成分，而9例MAC病例中有4例包含LAMN和/或HAMN成分。下一代测序（NGS）癌症热点小组用于分析11例纯LAMN，4例HAMN和3例MAC病例。结果表明，KRAS和GNAS是最常见的突变基因。然后进行Sanger测序以检测其余31例病例和RNF43中的KRAS，GNAS和TP53突变在所有情况下都是突变。KRAS / GNAS和TP53突变仅发生在纯LAMN中；但是，有5例LAMN病例的KRAS和GNAS都有突变。RNF43突变几乎只与纯LAMN中的KRAS / GNAS突变一起发生。在MAC和HAMN中，低等级区域之间的KRAS / GNAS突变状态几乎得以保留。大多数检测到的RNF43突变是错义型。在具有较低品位区域的MAC的两个组件中均检测到RNF43突变；但是，RNF43在这两个病变中检测到的突变完全不同。仅在8例HAMN患者中检出了RNF43突变，这是唯一的无腹膜假性粘液瘤（PMP）的病例。4名具有RNF43突变的MAC患者均未显示PMP。这些发现表明RNF43突变发生在MAC发展的后期，并且与PMP不相关。此外，可以考虑通过HAMN从LAMN逐渐过渡到MAC。