Kimura Fumikazu, Kobayashi Takaki, Kanai Ryo, Kobayashi Yukihiro, Yuhi Ohtani, Ota Hiroyoshi, Yamaguchi Masahiro, Yokokawa Yoshiharu, Uehara Takeshi, Ishii Keiko
Department of Biomedical Laboratory Sciences, School of Health Sciences, Shinshu University.
Department of Laboratory Medicine, Shinshu University Hospital.
Diagn Cytopathol. 2019 Jun;47(6):553-563. doi: 10.1002/dc.24155. Epub 2019 Feb 13.
Lobular endocervical glandular hyperplasia (LEGH) was first described by Nucci et al. in 1999 and is believed to be a precancerous lesion of minimal deviation adenocarcinoma and gastric-type adenocarcinoma in the uterine cervix. LEGH lesions do not always exhibit apparent cellular and structural atypia, so are difficult to distinguish from normal endocervical cells (EC cells) with cytological examination. Therefore, we often struggle to make a definite diagnosis of LEGH.
We used microscopy images of cytological specimens that were diagnosed as EC cells and LEGH cells. Signal intensity in whole nuclear area and in heterochromatin and euchromatin regions, euchromatin area ratio, and nuclear morphological features were quantified in each cell nucleus of the cases. Statistical analyses were conducted to determine statistical significance. Finally, we performed linear support vector machine (LSVM) modeling as a discriminant analysis using the quantified features.
Signal intensity in whole nuclear area, and heterochromatin and euchromatin regions of EC cell nuclei were higher than that of the LEGH cell nuclei. Morphologically, EC cell nuclei were larger than LEGH cell nuclei, and nuclei of LEGH cells had irregular nuclear respectively membrane structure and an elongated shape. The LSVM accuracy of 10-fold cross validation and leave-one-case-out cross-validation (LOCOCV) using all measured features were 84.7% to 89.3% and 78.6% to 86.0%, respectively.
The LVSM analysis using features extracted from signal intensity and morphological analysis was useful for discrimination of EC cells vs LEGH cells. We therefore believe that this image analysis method could be used for early detection of LEGH.
宫颈小叶状腺性增生（LEGH）于1999年由努奇等人首次描述，被认为是子宫颈微小偏离腺癌和胃型腺癌的一种癌前病变。LEGH病变并不总是表现出明显的细胞和结构异型性，因此通过细胞学检查很难与正常宫颈细胞（EC细胞）区分开来。因此，我们常常难以对LEGH做出明确诊断。
我们使用了被诊断为EC细胞和LEGH细胞的细胞学标本的显微镜图像。对病例中每个细胞核的全核区域、异染色质和常染色质区域的信号强度、常染色质面积比以及核形态特征进行了量化。进行统计分析以确定统计学意义。最后，我们使用量化特征进行线性支持向量机（LSVM）建模作为判别分析。
EC细胞核的全核区域、异染色质和常染色质区域的信号强度高于LEGH细胞核。在形态上，EC细胞核大于LEGH细胞核，LEGH细胞的核分别具有不规则的核膜结构和细长的形状。使用所有测量特征进行10倍交叉验证和留一法交叉验证（LOCOCV）的LSVM准确率分别为84.7%至89.3%和78.6%至86.0%。
使用从信号强度和形态分析中提取的特征进行LVSM分析有助于区分EC细胞和LEGH细胞。因此，我们认为这种图像分析方法可用于LEGH的早期检测。
