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Mod Pathol. 2014 Nov;27(11):1521-39. doi: 10.1038/modpathol.2014.37. Epub 2014 Mar 14.

Clinicopathologic and molecular analysis of disseminated appendiceal mucinous neoplasms: identification of factors predicting survival and proposed criteria for a three-tiered assessment of tumor grade.

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1
Department of Pathology, University of Pittsburgh Medical Center, Pittsburgh, PA, USA.
2
Department of Surgery, Division of Surgical Oncology, University of Pittsburgh Medical Center, Pittsburgh, PA, USA.

Abstract

Previous studies have demonstrated that the prognosis of disseminated mucinous appendiceal neoplasms is highly dependent upon tumor grade. Reflecting this, the 7th edition of the American Joint Committee on Cancer (AJCC) staging system now incorporates a three-tier grading system for prognostic staging of mucinous appendiceal tumors. However, the grading criteria are not well described. In order to address this issue, we evaluated clinicopathologic and molecular features of 219 cases from 151 patients with widely disseminated appendiceal mucinous neoplasia treated at our institution between 2004 and 2012. We identified histologic features that were associated with worse overall survival on univariate analysis: destructive invasion, high cytologic grade, high tumor cellularity, angiolymphatic invasion, perineural invasion, and signet ring cell component (all with P<0.0001). We used these morphologic characteristics to classify neoplasms into three grades: AJCC grade G1 lacked all adverse histologic features; AJCC grade G2 had at least one adverse histologic feature (except a signet ring cell component); and AJCC grade G3 were defined by the presence of a signet ring cell component. Patients with AJCC grade G2 and grade G3 adenocarcinomas had a significantly worse prognosis compared with AJCC grade G1 (P<0.0001 for each). A trend toward worse overall survival was identified for patients with AJCC grade G3 adenocarcinomas compared with AJCC grade G2 adenocarcinomas (P=0.07). Our multivariate analysis found that this three-tier grading system was a significant predictor of outcome (P=0.008), independent of other prognostic variables. After controlling for other prognostic variables, AJCC grade G2 was associated with a 2.7-fold increased risk of death (95% confidence interval (CI), 1.2-6.2) and AJCC grade G3 was associated with a 5.1-fold increased risk of death (95% CI, 1.7-14) relative to grade G1 tumors. Our results indicate that evaluation of a limited set of adverse histologic features allows for the separation of disseminated mucinous neoplasms of appendiceal origin into three morphologically defined and prognostically relevant grades as advocated by the AJCC.

PMID:
24633196
DOI:
10.1038/modpathol.2014.37
[Indexed for MEDLINE]
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