The Diagnosis of Endometrial Carcinomas With Clear Cells by Gynecologic Pathologists: An Assessment of Interobserver Variability and Associated Morphologic Features
The Diagnosis of Endometrial Carcinomas With Clear Cells by Gynecologic Pathologists: An Assessment of Interobserver Variability and Associated Morphologic Features
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DOI：
10.1097/pas.0b013e31825dd4b3
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发表时间：
2012-08-01
影响因子：
5.6
通讯作者：
Hecht, Jonathan L.
中科院分区：
文献类型：
--
作者：
Fadare, Oluwole;Parkash, Vinita;Hecht, Jonathan L.
本研究的目的是评估观察者间变异水平的诊断子宫内膜癌透明细胞的妇科病理学家纯粹基于他们的形态学特征，并比较描述的情况下，假定透明细胞癌（CCC）的观察者之间的差异和不显着。来自11个北美机构的11名妇科病理学家（中位经验：10年）共审查了35例子宫内膜癌（每例1张切片）。这些病例是根据至少存在局灶性透明细胞从3个机构的档案中选择的，并且先前在这些机构中被分类为各种组织型。诊断以盲态方式进行，没有预先确定的诊断标准或类别。任何一对观察者之间的kappa值范围为0.18至0.69（合并为0.46），这表明该组观察者间的一致性处于“中等”水平。比较“确诊CCC”亚组[11名观察者中至少有8名（73%）诊断为CCC的病例，n = 14]和“可能CCC”亚组（>= 1名但< 8名观察者诊断为CCC的病例，n = 13）的各种半定量形态学特征。通过结合在单变量分析中显示两组之间存在统计学显著差异的选定形态学特征，证实CCC组出现以下近似形态学特征：>= 33%的病变中有乳头状突起伴透明化核心，>= 33%的病变中有透明细胞，>= 33%的病变中有染色过度，在乳头上> 3个细胞中没有核假分层，在>= 33%的病变中腺体中没有核假分层，没有弥漫性3级核，在>= 33%的病变中没有细长的乳头，腺体和乳头由立方到扁平的非柱状细胞排列。在后向逐步logistic回归分析中，预测CCC组的特征包括：（1）3级核弥漫性片层缺失或极少[P = 0.025; 95%置信区间（CI），0.0266-0.363];（2）腺体和乳头核分层缺失或极少（P = 0.040; 95%CI，-0.228至-0.0054）;（3）腺体和乳头内衬立方至扁平、非柱状细胞（P = 0.008; 95%CI，0.0911-0.566）。两组在各种特征方面表现出明显的重叠，没有一个病例表现出完整的潜在诊断特征。与观察者间变异性水平非常高的病例（定义为≥ 4种不同诊断的病例，n = 9）相关的形态学模式包括透明细胞（3/9）和腺体/乳头状增生（其唯一的CCC样特征是透明细胞的存在）（2/9）的近排他性或排他性实性模式。总之，妇科病理学家对透明细胞型子宫内膜癌的诊断与观察者间中等程度的变异性相关。然而，有一个形态学特征的情况下，妇科病理学家更统一地分类为CCC，这些功能的存在是支持CCC诊断的子宫内膜癌与透明细胞。显示与上述特征有广泛和显著定性偏差的病例应考虑CCC以外的诊断。
The purposes of this study are to assess the level of interobserver variability in the diagnosis of endometrial carcinomas with clear cells by gynecologic pathologists based purely on their morphologic features and to comparatively describe the cases of putative clear cell carcinoma (CCC) with and without significant interobserver variability. A total of 35 endometrial carcinomas (1 slide per case) were reviewed by 11 gynecologic pathologists (median experience: 10 y) from 11 North American institutions. The cases were selected from the files of 3 institutions on the basis of the presence of at least focal clear cells and had previously been classified as a variety of histotypes at these institutions. Diagnoses were rendered in a blinded manner and without predetermined diagnostic criteria or categories. The kappa values between any pair of observers ranged from 0.18 to 0.69 (combined 0.46), which was indicative of a "moderate" level of interobserver agreement for the group. Subgroups of "confirmed CCC" [cases diagnosed as such by at least 8 (73%) of the 11 observers, n = 14] and "possible CCC" (cases diagnosed as CCC by >= 1 but < 8 observers, n = 13) were compared with regard to a variety of semiquantified morphologic features. By combining selected morphologic features that displayed statistically significant differences between the 2 groups on univariate analyses, the following approximate morphologic profile emerged for the confirmed CCC group: papillae with hyalinized cores in >= 33% of the lesion, clear cells in >= 33% of the lesion, hyperchromasia in >= 33% of the lesion, the absence of nuclear pseudostratification in > 3 cells on the papillae, the absence of nuclear pseudostratification in glands in >= 33% of the lesion, the absence of diffuse grade 3 nuclei, the absence of long and slender papillae in >= 33% of the lesion, and glands and papillae lined by cuboidal to flat, noncolumnar cells. In a backward stepwise logistic regression analysis, features from the profile that predicted the confirmed CCC group included: (1) absence or minimality of diffuse sheets of grade 3 nuclei [P = 0.025; 95% confidence interval (CI), 0.0266-0.363]; (2) absence or minimality of nuclear stratification in glands and papillae (P = 0.040; 95% CI, -0.228 to -0.0054); and (3) glands and papillae lined by cuboidal to flat, noncolumnar cells (P = 0.008; 95% CI, 0.0911-0.566). The 2 groups displayed significant overlap regarding a wide variety of features, and no single case displayed a full complement of potentially diagnostic features. Morphologic patterns associated with cases with very high levels of interobserver variability (defined as cases with >= 4 different diagnoses rendered for them, n = 9) included the near-exclusive or exclusively solid pattern of clear cells (3/9) and glandular/papillary proliferations whose only CCC-like feature was the presence of clear cells (2/9). In conclusion, the diagnosis of endometrial carcinomas with clear cells by gynecologic pathologists is associated with a moderate level of interobserver variability. However, there is a morphologic profile that characterizes cases that gynecologic pathologists more uniformly classify as CCC, and the presence of these features is supportive of a CCC diagnosis in an endometrial carcinoma with clear cells. Cases that display broad and significant qualitative deviations from the aforementioned profile should prompt the consideration of a diagnosis other than CCC.