Department of Pathology, University of Pittsburgh Medical Center, Pittsburgh, PA, USA.
Department of Surgery, Division of Surgical Oncology, University of Pittsburgh Medical Center, Pittsburgh, PA, USA.
Mod Pathol. 2014 Nov;27(11):1521-39. doi: 10.1038/modpathol.2014.37. Epub 2014 Mar 14.
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.
先前的研究表明，播散性黏液性阑尾肿瘤的预后高度依赖于肿瘤分级。反映这一点，美国癌症联合委员会（AJCC）第 7 版分期系统现在纳入了黏液性阑尾肿瘤的预后分期的三级分级系统。然而，分级标准描述得并不完善。为了解决这个问题，我们评估了 2004 年至 2012 年期间在我们机构治疗的 151 名广泛播散性阑尾黏液性肿瘤患者的 219 例病例的临床病理和分子特征。我们发现，在单因素分析中，与总生存较差相关的组织学特征有：破坏性浸润、高细胞分级、高肿瘤细胞密度、血管淋巴管浸润、神经周围浸润和印戒细胞成分（均 P<0.0001）。我们使用这些形态学特征将肿瘤分为三个等级：AJCC 分级 G1 缺乏所有不良组织学特征；AJCC 分级 G2 至少有一个不良组织学特征（除印戒细胞成分外）；AJCC 分级 G3 由印戒细胞成分的存在定义。AJCC 分级 G2 和 G3 腺癌患者的预后明显差于 AJCC 分级 G1（各 P<0.0001）。AJCC 分级 G3 腺癌患者的总生存趋势比 AJCC 分级 G2 腺癌患者更差（P=0.07）。我们的多变量分析发现，这种三级分级系统是预后的显著预测因素（P=0.008），独立于其他预后变量。在控制其他预后变量后，AJCC 分级 G2 与死亡风险增加 2.7 倍相关（95%置信区间（CI），1.2-6.2），AJCC 分级 G3 与死亡风险增加 5.1 倍相关（95%CI，1.7-14），与分级 G1 肿瘤相比。我们的结果表明，评估一组有限的不良组织学特征可以将阑尾来源的播散性黏液性肿瘤分为 AJCC 所倡导的三种形态定义和具有预后意义的等级。
