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Improving the AJCC/TNM staging for adenocarcinomas of the appendix: The prognostic impact of histologic grade.

402 Background: Though histological grade is known to have a major prognostic impact in metastatic mucinous appendiceal adenocarcinomas; the prognostic impact of grade in localized disease, and the validity of the AJCC Cancer Staging Manual 7th edition decision to combine moderately and poorly differentiated mucinous adenocarcinomas into a single mucinous high-grade category, is not known.


METHODS
Patients with adenocarcinoma of the appendix diagnosed between 1988-2007 were identified from the SEER database. Cancer-specific survival (CSS) stratified by histological subtype, stage and grade were calculated; and Cox proportional hazards regression analyses were performed.


RESULTS
We analyzed a total of 2,469 appendiceal adenocarcinomas, of which 1,375 had mucinous histology, 860 had non-mucinous histology, and 234 had signet-ring cell histology. Though overall CSS was similar for mucinous and non-mucinous subtypes, differences in stage distribution and stage-stratified CSS were seen. Female gender (57% vs.45%, P<0.01), stage IV disease (48% vs. 25%, P<0.01), and well differentiated histology (31% vs. 14%, P<0.01) were more common in mucinous as compared to non-mucinous adenocarcinomas. While histological grade for stage I-III cases was not statistically significant, it had strong prognostic impact for stage IV disease. The adjusted hazard ratios for stage IV well, moderately and poorly differentiated histological grade were 1 (reference), 1.63 (95%CI: 1.14-2.34) and 4.94 (95%CI: 3.32-7.35) for mucinous, in comparison to 1 (reference), 1.44 (95%CI: 0.82-2.52) and 1.90 (95%CI: 0.95-3.80) for non-mucinous histological subtypes, respectively.


CONCLUSIONS
The strong prognostic impact of histological grade for mucinous adenocarcinomas is primarily restricted to stage IV disease. Stage IV moderately and poorly differentiated mucinous adenocarcinomas have distinctly different CSS and this data does not support the combination of these two histological grades in the recent AJCC 7th edition.