Updated staging and patient outcomes in low-grade appendiceal mucinous neoplasms

Low-grade appendiceal mucinous neoplasms (LAMNs) exhibit drastically different clinical course and prognosis depending on tumor stage, particularly as it relates to the extent and cellularity of peritoneal involvement. In this context, recent changes in staging guidelines have sought to clarify criteria for pT and pM categories. This study's aim was to identify clinicopathological features associated with patient outcomes, especially as they pertain to updated stage groups. We reviewed LAMNs from 192 patients (mean age: 56.9 years, 119 (62.0%) women). The tumors consisted of 66 (34.4%) pTisM0, 16 (8.3%) pT3M0, 16 (8.3%) pT4aM0, 27 (14.1%) pTxM1a, and 67 (34.9%) pTxM1b cases. In multivariate analysis, only gross perforation was significantly associated with higher TNM group stage (p = 0.001; OR 3.3, 95% CI: 1.7-6.4). Of 165 (85.9%) patients with clinical follow-up, 51 (30.9%) had disease progression (over a mean 33.7 months, range: 4.7-121.7), whereas over significantly longer follow-up (mean 48.7 months, range: 3.1-143.9; p = 0.004), 114 (69.1%) patients did not. In multivariate analysis, higher TNM stage was significantly associated with disease progression (p = 0.029; OR 18.3, 95% CI: 1.4-246.0). In Kaplan-Meier analysis, none of 74 patients with disease limited to the appendix (pM0), 6 of 27 (22.2%) cases with peritoneal involvement by acellular mucin only (pM1a), and 45 of 64 (70.3%) tumors with intraperitoneal deposits containing neoplastic cells (pM1b) showed disease progression (p < 0.001). These differences in progression-free survival among TNM groups persisted when limiting the analysis to patients who had undergone successful cytoreductive surgery (p = 0.050). Finally, in four patients (all with pM1b disease) death was attributed to disease progression whereas there was no disease-specific mortality in the pM0 and pM1a groups (p = 0.020). These data support the designation of LAMNs with acellular peritoneal mucin as having an intermediate prognosis between cases limited to the appendix and those with intraperitoneal deposits containing neoplastic epithelium.