Histopathology manifestation and imaging characteristics of in vivo confocal microscopy for diagnosis of ocular surface squamous neoplasia

Abstract

Objective: To study the histopathology manifestation and imaging characteristics of in vivo confocal microscopy (IVCM) for diagnosis of ocular surface squamous neoplasia (OSSN) and analyze the reliability of IVCM in differential diagnosis from OSSN cases. Methods: 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. Results: 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 vs. 5.8(4.0-8.5)mm, Z=4.702,P=0.029; 7/8 vs. 5/15, χ2=6.135, P=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 (P=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 (P=0.001, 0.001, 0.003; P<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. Conclusions: 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. (Chin J Ophthalmol, 2018, 54: 652-660).