Issues in Assigning the T Category in the Staging of Low-Grade Appendiceal Mucinous Neoplasm and High-Grade Appendiceal Mucinous Neoplasm

To the Editor.—We read with interest the article by Gonzalez et al,¹  “High-Grade Appendiceal Mucinous Neoplasm: Clinicopathologic Findings in 35 Cases” published in the December 2022 issue of the Archives of Pathology & Laboratory Medicine. This is an excellent study that shows that the outcome of high-grade appendiceal mucinous neoplasm (HAMN) is similar to that of low-grade appendiceal mucinous neoplasm (LAMN) when these tumors are confined to the appendix. When the appendix staging was revised in the American Joint Committee on Cancer (AJCC) 8th edition,²  there were insufficient data on HAMN, and it was included with invasive adenocarcinoma for staging. The results of this study,¹  as well as 2 earlier series including outcome as well as molecular data,^3,4  support that HAMN should be staged using the same system as LAMN. We draw attention to 2 important points in this regard.

First, the authors appear to use the term “perforation” synonymously with involvement of serosal surface by tumor (cellular or acellular mucin). It would be preferable to use “involvement of serosal surface” and reserve the term “perforation” for destruction of the appendiceal wall, typically accompanied by a prominent neutrophilic response. When defined this way, perforation may or may not be associated with tumor, and the presence of perforation without associated tumor will not impact the T category but may have prognostic implications. It has been suggested that perforation may pose a risk for recurrence even with localized pTis (in situ) disease. In one series,⁵  recurrence was observed in 7 of 217 patients (3.2%) with LAMN associated with perforation and localized to the appendix. One of these patients had no extra-appendiceal mucin or epithelium at the time of appendectomy. Given the limited data on the role of perforation in the outcome of appendiceal mucinous neoplasms, it is a good practice to report the presence of perforation and the distance of tumor from the perforation site, as this information may be factored into patient management and follow-up.

Second, the study by Gonzalez et al¹  shows that HAMN confined to the appendix (pT3 or lower) was not associated with recurrence, which is similar to most of the outcome data reported for LAMN.⁶  However, it is important to note that peritoneal recurrence has been reported in LAMN confined to the muscularis propria (pTis) in rare instances after microscopic examination of the entire appendix. It is likely that similar HAMN cases will come to light as additional series are published. Such cases pose a question of whether the pTis category needs to be revisited in the AJCC staging scheme.