Intraocular Lymphangiogenesis in Malignant Melanomas of the Ciliary Body with Extraocular Extension

Abstract

Malignant melanomas of the ciliary body with extraocular extension show intraocular lymphatic vessels. This first evidence of lymphangiogenesis into the normally alymphatic eye may explain the increased risk of lymphatic metastasis in ciliary body melanoma with extraocular extension.

Invasion of Lymphatic Vessels into the Eye after Open Globe Injuries

“…First, podoplanin þ /laminin À lymphatic vessels can be detected within the cornea, sclera, and intraocular space of globes enucleated after open globe injury. To our knowledge, following our studies on intraocular malignancies with extraocular extension, [16][17][18] this is the second evidence of secondary lymphangiogenesis into the physiologically alymphatic intraocular space. Secondly, the presence of these pathologic lymphatic vessels does not seem to be associated with the mechanism of trauma, anatomic site of the eye wall defect, and time interval between trauma and enucleation.…”

“…23 However, the absence of LYVE-1 þ /podoplanin þ lymphatic vessels with an erythrocytefree lumen in the ciliary body region of human control eyes devoid of ciliary body melanoma, and eyes with ciliary body melanoma without extraocular extension indicates that the normal eye is thought to be devoid physiologically of true lymphatic vessels. 16 It has been shown for pathologic conditions that preexisting lymphatic vessels of conjunctiva and limbus are able to grow secondarily into physiologically lymphatic-free ocular structures, such as cornea. 12 Secondary to several inflammatory diseases of the cornea, blood and lymphatic vessels can invade the normally avascular cornea.…”

“…1,12 Secondarily, malignant melanomas of the ciliary body with extraocular extension are capable of inducing secondary lymphangiogenesis into the intraocular space of the eye. [16][17][18] The primary role of lymphatic vessels is the transport of extravasated fluid, proteins, and cells. In case of malignant tumors, lymphatic vessels are relevant for the dissemination of tumor cells.…”

“…Blood vessels represent the ''efferent arm of the immune reflex arc'' by allowing invasion of immunologic effector cells into the cornea and, thus, enhancing an immune rejection, for example after corneal transplantation. 19,20 Based on our observation that lymphatic vessels can invade the eye walls as well as the intraocular space of the eye under pathologic conditions, such as malignant melanomas of the ciliary body with extraocular extension, 16 we were interested in analyzing whether lymphatic vessels can be found in human eyes after open globe injuries. Therefore, in our study 21 eyes enucleated after an open globe injury were analyzed by means of immunohistochemistry.…”

The Trojan Horse Tale Revisited: An Eye on Metastatic Spread of Carcinoma Cells

“…This finding of a single-cell suspension of a solid malignancy in the AH of the eye raised the question of how these tumor cells originally got there. The anterior chamber of the immune-privileged eye is devoid of lymphatic vessels (10), making the putative route of entry for Ber-EP4 þ carcinoma cells solely hematogenous. Ber-EP4 is expressed by epithelial and adenocarcinoma but not hematopoietic cells (4).…”