Samenvatting

Introduction: Uveal melanoma (UM) is a common tumor in the eye. The uvea is with 82% the most frequent site of origin of ocular melanomas in the western world and has an incidence of 4 to 5 per million in the Netherlands. Uveal melanoma arises from melanocytes located in the uveal tract of the eye. The tumor can be classified into three categories: namely consisting of spindle cells, epithelioid cells and mixed cell type. The tumor can occur in the iris (5%), ciliary body (23%) or the choroid (72%).
The eye is mainly devoid of lymphatic vessels, except for the conjunctiva and the limbus of the cornea. The lymphatic vessels in the conjunctiva contribute to the ocular homeostasis and play an important role in ocular disorders. Generally there will be no lymphatic vessels inside both the eyes and in uveal melanomas, but a recent study described that lymphatic vessels may be present in uveal melanomas, especially in the choroid surrounding the tumor. The phenomenon that lymphatic vessels are absent in healthy eyes and uveal melanomas has therefore become a point of discussion and further research is important to explain the presence, origin, and development of any lymphatic vessels in the eye.
Purpose: The main aim of this study is to show whether lymphatic vessels are absent or present in uveal melanomas with extraocular extension. In addition, it will be examined which cells or ocular structures are stained for the lymphatic markers which also have been used in previous studies.
Methods: This study consisted of 14 patients with uveal melanomas with extraocular extension. The FFPE material from all 14 patients was retrieved from the archives of the department of pathology of the Erasmus MC. Sections of 4µm were cut and stained using immunohistochemistry. After the optimization, consecutive sections were stained for Lyve-1, Prox-1, D2-40, CD31 and CD34. The three lymphatic markers Lyve-1, Prox-1 and D2-40 were compared with the endothelial markers CD31 and CD34 to determine the presence or absence of lymphatic vessels in uveal melanomas.
Results: In all uveal melanomas with extraocular extension, 14/14 (100%), no lymphatic vessels are observed in both the tumor and in the choroid with the lymphatic markers Prox-1 and D2-40. Some macrophages are Lyve-1, Prox-1 and D2-40 positive in the choroid, ciliary body and sclera, but all vascular structures were negative for Prox-1 and D2-40. Lyve-1 positive vascular structures were detected in 3 of 14 (21%) malignant melanomas of the choroid with extraocular extension. One Lyve-1 positive vascular structure was found anterior in the eye. By contrast, the Lyve-1 positive vascular structures were negative with Prox-1 and D2-40, but positive with CD31 and CD34. There was no co-expression of Lyve-1, Prox-1 and D2-40 as would be expected in lymphatic vessels.
Conclusions: This study has shown that there are no lymphatic vessels present in uveal melanomas with extraocular extension. Future studies to investigate lymphatics with both multiple and proliferation markers and possibly molecular research may help to study lymphatics in uveal melanomas.