Pathological and molecular genetic characteristics in patients with extrabulbar growth of uveal melanoma

Abstract

to analyze the association of extrabulbar tumor growth with pathological and molecular genetic changes in patients with uveal melanoma (UM). A total of 134 UM patients aged 22 to 84 years were examined and treated. The mean height of the tumor was 9.2±2.9 mm; the diameter of its base was 15.3±3.5 mm. Enucleation of the affected eye was performed in 97.8% of cases. Spindle-cell (n=61 (45.6%)), mixed cell (n=46 (34.3%)), and epithelioid cell (n=27 (20.1%)) tumors were identified according to their histological structure. Polymerase chain reaction-restriction fragment length polymorphism analysis was used to determine full and partial monosomy of chromosome 3, deletion of the short arm of chromosome 1, and RASSF1A gene methylation (n=134). The patients were divided into two groups: 1) those with extrabulbar growth (EG) (n=12) and 2) those without EG (n=122). There was a topographic association between the tumor invasion zone and the largest area of exit of the scleral vessels, along which the tumor invaded: the anterior and posterior segments of the eyeball. The specific features of the invasion pattern of UM were shown: there was its broader invasion in the posterior segment and thinner growing tissue interlayers in the anterior segment. Two UM types stopping the process of UM invasion through the scleral fibrous tunic of the eye were established: 1) that with nodule formation and 2) that with tumor cell dissemination within the episclera. The cellular composition of growing tumor tissue in the episclera was ascertained to differ from the main UM focus in the choroid towards its more atypization. The rate was shown to be significantly lower (20% versus 47.9% for the relatively favorable spindle cell type of UM) in the EG group. The frequency of full or partial chromosome 3 monosomy was significantly higher in the extrabulbar tumor growth group (80% versus 50.4%). The morphological features of the EG of UM were defined. The use of a statistically significant sample of patients with UM confirmed the favorable course of the tumor in its spindle cell type and the negative role of chromosome 3 monosomy, as well as the relationship to extrabulbar tumor growth.