Mucoepidermoid carcinoma - A clinicopathologic study of 80 patients with special reference to histological grading
Mucoepidermoid carcinoma - A clinicopathologic study of 80 patients with special reference to histological grading
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DOI：
10.1097/00000478-200107000-00001
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发表时间：
2001-07-01
影响因子：
5.6
通讯作者：
Mills, SE
中科院分区：
文献类型：
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作者：
Brandwein, MS;Ivanov, K;Mills, SE
我们试图回顾我们的经验，唾液粘液表皮样癌（MEC）超过20年，以确认组织学分级的有效性和可重复性，并探讨MIB-1指数作为一个衡量。80例病例确诊，48例患者进行了病历审查或患者联系，随访时间为5至240个月（中位36个月）。对一部分病例进行了MIB-1柠檬酸盐抗原修复免疫组化。根据我们提出的分级系统，生成每个分期、部位和分级的Kaplan-Meier生存曲线。为了解决分级再现性问题，在染料观察员之间分发了20张载玻片，事先未进行讨论;根据自己的“自己的”标准，然后根据Goode等人提出的AFIP标准，将载玻片分类为低、中或高级别。(10)获得加权Kappa（K）估计值以描述成对评级之间的一致程度。Wilcoxon符号秩检验或Friedman检验（视情况而定）检验了评级间的变化。性别不占主导地位，年龄范围广泛（15-86岁，中位数49岁）。最常见的两个部位是腮腺和腭。所有1级MEC均表现为I期肿瘤，该类别未观察到失败。75个月时2级和3级MEC的局部疾病失败率分别为30%和70%。肿瘤分级、分期和阴性切缘状态均与无病生存期（DFS）相关（分别为p = 0.0091、0.0002和0.048）。MIB指数不能预测等级。关于分级的再现性，病理学家使用他们自己的分级的观察者间差异，如由K值表示的，范围从良好的一致性（K = 0.79）到差（K = 0.27）（平均K = 0.49）。当病理学家使用标准化AFIP标准时，观察者间的重现性有所改善（平均K = 0.61，范围0.38-0.77）。这种更大的一致性也反映在Friedman检验（观察者内平等性的统计检验）中，该检验表明使用自己的分级系统（p = 0.0001）而不是应用AFIP“标准化”分级（p = 0.33）时存在显著差异。当将自己的评分与AFIP评分进行比较时，有100对评分“事件”，每100对中有46个分歧。对于98%的不一致，AFIP分级“降级”肿瘤。这使我们重新分析了一个子集的31例患者的DFS与等级，我们的分级方案与AFIP分级相比。尽管该子集未达到统计学显著性，但与Goode模式（p = 0.2493）相比，对数秩值显示了我们的分级（p = 0.0993）的趋势。该临床病理分析证实了肿瘤分期和三层组织学分级的预测价值。我们的分级练习证实，即使在经验丰富的耳鼻喉科/口腔病理学家中，MEG也存在显著的分级差异。当使用加权AFIP标准时获得的改进的再现性说明了对可接受且易于再现的系统的需求。然而，这些建议的标准有降低MEG的趋势。因此，增加其他标准（如血管浸润、肿瘤浸润模式[即，小岛和单个细胞vs粘性岛]）是必要的。我们提出了一个修改后的分级方案，提高了可预测性，并提供了急需的再现性。
We sought to review our experience with salivary mucoepidermoid carcinoma (MEC) over two decades to confirm the validity and reproducibility of histologic grading and to investigate MIB-1 index as a prognosticator. Diagnosis was confirmed on 80 cases, and chart review or patient contact was achieved for 48 patients, with follow-up from 5 to 240 months (median 36 months). Immunohistochemistry with citrate antigen retrieval for MIB-1 was performed on a subset of cases. Kaplan-Meier survival curves were generated for each stage, site, and grade according to our proposed grading system. To address the issue of grading reproducibility, 20 slides were circulated among dye observers, without prior discussion; slides were categorized as low-, intermediate-, or high-grade according to one's "own" criteria, and then according to the AFIP criteria proposed by Goode et al.(10) Weighted kappa (K) estimates were obtained to describe the extent of agreement between pairs of rating. The Wilcoxon signed rank test or the Friedman test as appropriate tested variation across ratings. There was no gender predominance and a wide age range (15-86 years, median 49 years). The two most common sites were parotid and palate. All grade 1 MECs presented as Stage I tumors, and no failures were seen for this category. The local disease failure rates at 75 months for grades 2 and 3 MEC were 30% and 70%, respectively. Tumor grade, stage, and negative margin status all correlated with disease-free survival (DFS) (p = 0.0091, 0.0002, and 0.048, respectively). The MIB index was not found to be predictive of grade. Regarding the reproducibility of grading, the interobserver variation for pathologists using their "own" grading, as expressed by the K value, ranged from good agreement (K = 0.79) to poor (K = 0.27) (average K = 0.49). A somewhat better interobserver reproducibility was achieved when the pathologists utilized the standardized AFIP criteria (average K = 0.61, range 0.38-0.77). This greater agreement was also reflected in the Friedman test (statistical testing of intraobserver equality), which indicated significant differences in using one's own grading systems (p = 0.0001) but not in applying the AFIP "standardized" grading (p = 0.33). When one's own grading was compared with the AFIP grading, there were 100 pairs of grading "events," with 46 disagreements/100 pairs. For 98% of disagreements, the AFIP grading "down-graded" tumors. This led us to reanalyze a subset of 31 patients for DFS versus grade, for our grading schema compared with the AFIP grading. Although statistical significance was not achieved for this subset, the log rank value revealed a trend for our grading (p = 0.0993) compared with the Goode schema (p = 0.2493). This clinicopathologic analysis confirms the predictive value of tumor staging and three-tiered histologic grading. Our grading exercise confirms that there is significant grading disparity for MEG, even among experienced ENT/oral pathologists. The improved reproducibility obtained when the weighted AFIP criteria were used speaks to the need for an accepted and easily reproducible system. However, these proposed criteria have a tendency to downgrade MEG. Therefore, the addition of other criteria (such as vascular invasion, pattern of tumor infiltration [i.e., small islands and individual cells vs cohesive islands]) is necessary. We propose a modified grading schema, which enhances predictability and provides much needed reproducibility.