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共聚焦显微镜诊断眼表鳞状上皮肿瘤的组织病理学表现及影像学特征

[Histopathology manifestation and imaging characteristics of confocal microscopy for diagnosis of ocular surface squamous neoplasia].

作者信息

Liang Q F, Huang J J, Cao K, Su G Y, Wang Z Q, Zhang Y, Li B

机构信息

Beijing Institute of Ophthalmology, Beijing Tongren Eye Center, Beijing Tongren Hospital, Capital Medical University, Beijing Ophthalmology & Visual Sciences Key Lab., Beijing 100005, China.

出版信息

Zhonghua Yan Ke Za Zhi. 2018 Sep 11;54(9):652-660. doi: 10.3760/cma.j.issn.0412-4081.2018.09.004.

Abstract

To study the histopathology manifestation and imaging characteristics of confocal microscopy (IVCM) for diagnosis of ocular surface squamous neoplasia (OSSN) and analyze the reliability of IVCM in differential diagnosis from OSSN cases. A prospective study. Twenty-three patients (23 eyes) with OSSN were collected from September 2015 to November 2017 in Beijing Tongren Eye center. They were underwent the examinations sequentially as follows: visual examination; slit-lamp microscope examination and ocular surface photography; color fundus image; anterior segment optical coherence tomography examination; IVCM examination and histopathology examination after surgery. With histopathology diagnosis, all subjects were divided into two groups: conjunctival intraepithelial neoplasm (CIN) and squamous cell carcinoma (SCC). Compared with histopathological findings, the IVCM results (cell morphology, cytoplasm and nucleus) of OSSN were analyzed. The difference analysis between the count data of two groups was carried out by the chi square test or Fisher's exact test. Receiver operating characteristic curve and area under the curve (AUC) were used to describe the accuracy of each parameter to differentiate SCC from OSSN. There were 12 males and 11 females among the 23 patients aged (62±15) years. With the histopathological diagnosis, there were 15 cases (15 eyes) in the CIN group and 8 cases (8 eyes) in the SCC group. Eye redness, pain, foreign body sensation and tears were the symptoms of OSSN. There was no significant difference in clinical symptoms between the CIN and SCC groups. The size of tumors and the incidence of trophoblastic vessels in the SCC group were greater than those in the CIN group [8.5(6.5-15.5) mm . 5.8(4.0-8.5)mm, 4.702,0.029; 7/8 . 5/15, χ=6.135, 0.013). In histopathology, multilayered epithelia with cellular polymorphism, varied cytoplasm staining, and slightly thicker nuclei were observed in the CIN group. The corneal epithelial cells of SCC patients were markedly heterogeneous, and the intercellular bridge structure can be detected. Proliferative cells appeared with spindle shaped cells, nuclear mitotic figures and syncytial cells in the SCC group. The IVCM examination in the CIN group and SCC group showed that the cytoplasm was high and the ratio of nuclear plasma increased. There was no significant difference between the two groups in the size of epithelial cells, cytoplasm reflectivity, and nuclear cytoplasm ratio (0.053, 0.108, 0.067). The proportions of nuclear mitotic figures, spindle or chimeric cells, nests of whirlpool cells and the abnormal cells of the superficial stroma layer (8/8, 8/8, 8/8 and 8/8) in the SCC group was higher than those (2/15, 1/15, 4/15 and 0/15) in the CIN group, and the difference was statistically significant (0.001, 0.001, 0.003; <0.001). Among these IVCM parameters, the abnormal cells of the superficial stroma layer had the highest diagnostic ability with the AUC value of 1.000, and the following AUC values were 0.933 for mitotic or double nuclei, 0.901 for spindle or chimeric cells, and 0.867 for the nests of whirlpool cells. The IVCM characteristics of OSSN are the dysplastic cells, hyper-reflective cytoplasm and increased nuclear plasma ratio in the corneal epithelium. Dysplastic cells appearing in the superficial stroma layer, nuclear mitotic figures and nests of vortex cells are the main IVCM parameters to support the malignant change of OSSN lesions. .

摘要

研究共焦显微镜(IVCM)诊断眼表鳞状上皮肿瘤(OSSN)的组织病理学表现及影像学特征,并分析IVCM在OSSN病例鉴别诊断中的可靠性。一项前瞻性研究。2015年9月至2017年11月在北京同仁眼科中心收集23例(23只眼)OSSN患者。他们依次接受以下检查:视力检查;裂隙灯显微镜检查及眼表照相;彩色眼底图像;眼前节光学相干断层扫描检查;IVCM检查及术后组织病理学检查。根据组织病理学诊断,将所有受试者分为两组:结膜上皮内瘤变(CIN)和鳞状细胞癌(SCC)。将OSSN的IVCM结果(细胞形态、细胞质和细胞核)与组织病理学结果进行比较分析。两组计数资料的差异分析采用卡方检验或Fisher确切概率法。采用受试者操作特征曲线及曲线下面积(AUC)描述各参数鉴别SCC与OSSN的准确性。23例患者中男性12例,女性11例,年龄(62±15)岁。根据组织病理学诊断,CIN组15例(15只眼),SCC组8例(8只眼)。眼红、疼痛、异物感和流泪是OSSN的症状。CIN组和SCC组临床症状无显著差异。SCC组肿瘤大小及滋养血管发生率均大于CIN组[8.5(6.5 - 15.5)mm. 5.8(4.0 - 8.5)mm,4.702,0.029;7/8. 5/15,χ=6.135,0.013]。组织病理学上,CIN组可见多层上皮细胞,细胞多形性,细胞质染色多样,细胞核稍增厚。SCC患者角膜上皮细胞明显异质性,可检测到细胞间桥结构。SCC组增殖细胞呈梭形细胞、核分裂象及合体细胞。CIN组和SCC组的IVCM检查显示细胞质高,核浆比增加。两组上皮细胞大小、细胞质反射率及核质比无显著差异(0.053,0.108,0.067)。SCC组核分裂象、梭形或嵌合细胞、漩涡状细胞巢及浅层基质层异常细胞的比例(8/8,8/8,8/8和8/8)高于CIN组(2/15,1/15,4/15和0/15),差异有统计学意义(0.001,0.001,0.003;<0.001)。在这些IVCM参数中,浅层基质层异常细胞诊断能力最高,AUC值为1.000,其次有丝分裂或双核的AUC值为0.933,梭形或嵌合细胞为0.901,漩涡状细胞巢为0.867。OSSN的IVCM特征为角膜上皮细胞发育异常、细胞质高反射及核浆比增加。浅层基质层出现发育异常细胞、核分裂象及漩涡状细胞巢是支持OSSN病变恶变的主要IVCM参数。

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