Intraocular Lymphatics in Ciliary Body Melanomas With Extraocular Extension

Abstract

To assess the functional significance of intraocular tumor-associated lymphatic vessels in ciliary body melanomas with extraocular extension. Methods: Twelve consecutive patients enucleated for a malignant melanoma of the ciliary body with extraocular extension and immunohistochemical presence of intraocular LYVE-1-positive and podoplanin-positive lymphatic vessels were examined for proliferation status and tumor invasion into tumor-associated lymphatics. Proliferating lymphatic vessels were identified using LYVE-1 and podoplanin as specific lymphatic endothelial markers and Ki-67 as the proliferation marker. Tumor invasion into lymphatic vessels was assessed using Melan-A as the melanoma marker. Kaplan-Meier analyses of survival and metastasis were performed. Results: Intraocular proliferating lymphatic vessels were detected in all 12 ciliary body melanomas with extra

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.…”

“…1,12,15,19,20,24 Furthermore, malignant melanomas of the ciliary body can attract extraocular lymphatics into the physiologically alymphatic eye when extraocular tumor extension provides routes of entry through the sclera, which otherwise seems to be a natural barrier against the invasion of lymphatic vessels. [16][17][18] Our data suggested that in a similar manner, preexisting conjunctival and/or limbal lymphatic vessels can outgrow and proliferate into the eye if the eye wall is opened by trauma. The hypothesis that the intraocular lymphatics that we detected actually are invading rather than displaced preexisting conjunctival lymphatic vessels is supported by the following observations.…”

“…In conclusion, secondary invasion of lymphatic vessels into the physiologically alymphatic intraocular space can be found not only in intraocular malignant tumors with extraocular extension, [16][17][18] but also in traumatically injured eyes with opening of the eye wall. Intraocular lymphatic vessels after open globe injury could be important for wound healing, immunologic defense against intruding microorganisms, and autoimmune reactions against intraocular antigens.…”

“…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.…”

“…In case of malignant tumors, lymphatic vessels are relevant for the dissemination of tumor cells. 17,18 Furthermore, they take an important part in mediating immunologic responses. In the context of corneal injury or corneal transplantation, invading lymphatic vessels can serve as the ''afferent arm of the immune reflex arc'' by facilitating the passage of antigen-presenting cells with foreign antigens from the cornea or corneal graft to the regional lymph node.…”