细胞核直径在鉴别诊断肺炎症性病变和肺腺癌中的研究

The Value of Nuclear Diameter in the Differential Diagnosis of Pulmonary Lesions and Lung Adenocarcinoma

摘要: 背景：肺癌是世界范围内发病率最高的肿瘤，其中肺腺癌为主要的组织学类型，病理学表现多样，是全球肿瘤相关疾病死亡的主要原因。肺的炎症性病变和肺腺癌有时在病理组织和形态学上存在相似之处，给鉴别诊断带来了困难。病理学上常用细胞核形态异常程度来区分疾病的良恶性，但目前尚无统一诊断标准。因此，本文以肺结节的细胞核为研究对象，对其直径进行测量并统计分析，为鉴别诊断肺炎症性病变、原位腺癌和浸润性腺癌提供了一个新的思路。方法：收集济宁医学院附属医院的肺泡上皮增生、原位腺癌及浸润性腺癌病例各30例，病灶组织切片进行苏木精-伊红(hematoxylin-eosin, HE)染色和TTF-1免疫组化染色(Immunohistochemistry, IHC)。使用iViewer极速数字切片浏览器软件在每个切片病变最显著处随机寻找3个肺泡结构，测量细胞核直径，并统计每个肺泡中最大细胞核与最小细胞核(largest nuclear/smallest nuclear, L/S)比值。结果：3种疾病的HE染色与TTF-1的免疫组化染色所统计出的比值结果差异均无统计学意义(浸润性腺癌组P = 0.21，原位腺癌组P = 0.06，肺泡上皮增生组P = 0.21)。3种疾病每两组之间的L/S比值分布差异均有统计学意义(P < 0.001)。浸润性腺癌的L/S比值最大，其中位数95%的置信区间(confidence intervals, CI)范围为4.26~4.44，其次是原位腺癌，中位数95%CI为2.27~2.39，肺泡上皮增生的L/S比值最小，同上为1.58~1.64。结论：肺炎症性病变、原位腺癌与浸润性腺癌的细胞核最大直径与最小直径的比值的差异有统计学意义(P < 0.05)，可以作为鉴别这三种疾病的参考。

Abstract: Background: Lung cancer is the most prevalent tumor in the world, with lung adenocarcinoma being the main histological type. It has diverse pathological manifestations and is the leading cause of cancer-related death worldwide. Inflammatory lesions of the lung and lung adenocarcinoma sometimes have histopathological and morphologic similarities, which make differential diagnosis difficult. In pathology, the degree of nuclear abnormality is often used to distinguish benign and malignant diseases. Therefore, this study takes the nucleus of pulmonary nodules as the research object and measures their diameters, which provides a new idea for the differential diagnosis of pneumonia lesions, adenocarcinoma in situ and invasive adenocarcinoma. Methods: Thirty cases of alveolar epithelial hyperplasia, 30 cases of adenocarcinoma in situ and 30 cases of invasive adenocarcinoma were collected from the Affiliated Hospital of Jining Medical University. The lesion tissue sections of were stained for hematoxylin-eosin (HE) staining and TTF-1 immunohistochemical (IHC) staining. The iViewer digital slice software was used to randomly find 3 alveolar structures in each slice, measure the nuclear diameter, and calculate the ratio of the largest and smallest nuclear nuclei (L/S) in each alveolar. Results: There was no significant difference in the ratio between HE staining and TTF-1 immunohistochemical staining for each disease (P = 0.21 for invasive adenocarcinoma, P = 0.06 for in-situ adenocarcinoma, and P = 0.21 for alveolar epithelial hyperplasia). The differences in ratio distribution between each two groups of the three diseases were statistically distinct (P < 0.001). The ratio of L/S in invasive adenocarcinoma was the largest, with a median 95% confidence interval of 4.26~4.44, followed by adenocarcinoma in situ, with a median 95% confidence interval of 2.27~2.39, and the ratio of alveolar epithelial hyperplasia was the smallest, with a median 95% confidence interval of 1.58~1.64. The differences in the ratio distribution between each two groups of the three diseases were statistically significant (P < 0.001). Conclusions: The ratio of maximum to minimum nuclear diameter among Inflammatory lesions of the lung, adenocarcinoma in situ and invasive adenocarcinoma were statistically significant (P < 0.05), which could be used as a reference for differentiating these three diseases.