Clinicopathologic and Molecular Characteristics of High-Grade Appendiceal Mucinous Neoplasms

Background: Although 2016 consensus guidelines defined high-grade appendiceal mucinous neoplasms (HAMNs) as a distinct histologic entity, their clinical course and optimal management remain poorly characterized. Comparative data with low-grade appendiceal mucinous neoplasms (LAMNs) are limited. This study aims to detail the clinical management and outcomes of patients with HAMN and those with LAMN. Methods: This retrospective cohort study was conducted at a large academic cancer center. An internal database was queried to identify patients with LAMN or HAMN who underwent appendectomy between 2016 and 2024. Kaplan–Meier survival analyses were used to assess the impact of primary tumor type and peritoneal disease (PD) on recurrence-free survival (RFS) and overall survival (OS). Results: Of the 375 patients, 276 (73.6%) had LAMN and 99 (26.4%) had HAMN. Localized disease was most common (187 patients [49.9%]). Acellular mucin, low-grade mucinous carcinoma peritonei (LGMCP), and high-grade mucinous carcinoma peritonei (HGMCP) were observed in 14.9, 25.3, and 9.9% of patients, respectively. HAMNs were associated with increased PD (69.7% vs 43.1%, P < 0.001) and HGMCP (19.2% vs 6.5%, P < 0.001). Patients with localized disease or acellular mucin experienced almost no recurrences (99.2%). Patients with HAMN trended towards worse 5 year RFS (80.7% vs 90.4%, P = 0.083). OS was similar (91.1% vs LAMN 93.4%, P = 0.23). Conclusions: This is the largest cohort of patients with HAMN characterized to date. HAMNs are associated with more frequent and higher-grade PD than are LAMNs. The presence and type of PD influence both RFS and OS for patients with AMN. Overall, there is a trend towards decreased RFS in patients with HAMN than with LAMN, but OS was similar.