Insights into the Clinical Prognosis of High-grade Appendiceal Mucinous Neoplasms

High-grade appendiceal mucinous neoplasm (HAMN) is used to describe a rare epithelial neoplasm of the appendix characterized by pushing-type invasion and high-grade cytologic atypia. Its implications regarding lymph node spread and the necessity of right colectomy are currently debate. The objective of the present study was to assess the clinicopathologic characteristics, the risk of lymph node and peritoneal metastasis, and long-term outcomes of patients diagnosed as HAMN in comparison to low-grade appendiceal mucinous neoplasm (LAMN) and appendiceal adenocarcinoma, treated by right hemicolectomy. A total of 443 patients diagnosed with LAMN (n=246), HAMN (n=34), or appendiceal adenocarcinoma (n=163) and who underwent right colectomy with lymph node dissection in all cases within 32 institutions of the French Network for Rare Peritoneal Malignancies (RENAPE) were included. The median age was 56.5 years (range: 21 to 91), and the majority were female (n=250, 56.4%) without difference between groups ( P =0.604). Lymph node metastases were identified in 17.8% of appendiceal adenocarcinoma cases (29/163); none were found among LAMN or HAMN cases. A higher number of lymph nodes were analyzed in those treated for appendiceal adenocarcinoma than LAMN ( P <0.001) and HAMN ( P =0.035). Regarding peritoneal metastasis, a higher proportion of cases were classified as high-grade with/without signet cells in patients treated for HAMN ( P <0.001) and appendiceal adenocarcinoma ( P <0.001) than those treated for LAMN. Among patients with perforation of the appendix, those treated for LAMN had longer overall survival (OS; P <0.001) and progression-free survival (PFS; P <0.0001) than those treated for appendiceal adenocarcinoma or those treated for HAMN; among patients without perforation, those treated for LAMN and HAMN had longer OS ( P =0.042) and PFS ( P =0.012) than those treated for appendiceal adenocarcinoma. No lymph node metastases were observed in patients treated for HAMN, and those without appendix perforation had a similar prognosis to LAMN. This study supports staging HAMN using the same system as LAMN and treating it with appendectomy alone in the absence of appendix perforation.