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

Abstract

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.

Keywords: high-grade appendiceal mucinous neoplasms; lymph nodes; metastasis; pseudomyxoma.

FIGURE 1

Examples of neoplasia of appendix. A, LAMN exhibited subepithelial fibrosis and a broad pushing margin. B, The neoplastic epithelium displayed low-grade features. C, HAMN shared similar histologic characteristics, but (D) the neoplastic epithelium demonstrated unequivocal high-grade features. E, Appendiceal adenocarcinoma was identified by its infiltrative invasion into the chorion. F, Tumor proliferation was characterized by crowded, expansile mucin pools containing detached strips, glands, and clusters of atypical neoplastic cells.

FIGURE 2

Proportion of lymph node metastases according to histologic type of appendix. No patients treated for LAMN and HAMN had lymph node metastases in comparison with appendiceal adenocarcinoma (17.8%, 29/163).

FIGURE 3

Examples of peritoneal metastases. Peritoneal metastases were graded according to the latest WHO classification as either (A) low (grade 1), including acellular, and (B) hypocellular mucinous deposits, high grade, (C) without signet-ring cells (grade 2), and (D) with signet-ring cells (grade 3).

FIGURE 4

Distribution of grade of peritoneal metastasis in the cohort-based histologic type of appendix. A higher proportion of cases were classified significantly as high grade with/without signet cells (Grade 2/3) in HAMN and appendiceal adenocarcinoma in comparison with LAMN (P<0.001).

FIGURE 5

Overall survival stratified on histologic type. A, Among patients presenting appendiceal perforation, those treated for LAMN had a longer survival than those treated for HAMN or appendiceal adenocarcinoma (P<0.001). B, Among patients without appendiceal perforation, patients treated for LAMN and HAMN had a longer survival than those treated for appendiceal adenocarcinoma (P=0.042).

FIGURE 6

Progression survival stratified on histologic type. A, Among patients presenting appendiceal perforation, those treated for LAMN had a longer survival than those treated for HAMN and appendiceal adenocarcinoma (P<0.0001). B, Among patients without appendiceal perforation, patients treated for LAMN and HAMN had a longer survival than those treated for appendiceal adenocarcinoma (P=0.012).