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Originally published In Press as doi:10.1167/iovs.08-2935 on January 17, 2009
 (Investigative Ophthalmology and Visual Science. 2009;50:1988-1995.)
© 2009 by The Association for Research in Vision and Ophthalmology, Inc.
doi:10.1167/iovs.08-2935
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Intraocular Lymphangiogenesis in Malignant Melanomas of the Ciliary Body with Extraocular Extension

Ludwig M. Heindl,1 Tanja N. Hofmann,1 Harald L. J. Knorr,1 Carmen Rummelt,1 Falk Schrödl,2 Ursula Schlötzer-Schrehardt,1 Leonard M. Holbach,1 Gottfried O. H. Naumann,1 Friedrich E. Kruse,1 and Claus Cursiefen1

1From the Department of Ophthalmology and Eye Hospital, Ophthalmic Pathology Laboratory, and the 2Department of Anatomy I, Friedrich-Alexander University Erlangen-Nürnberg, Erlangen, Germany.

PURPOSE. To analyze whether lymphatic vessels can invade the normally alymphatic eye (lymphangiogenesis) in patients with malignant melanoma of the ciliary body with extraocular extension and to correlate these findings with metastasis-free survival.

METHODS. Ten enucleated globes with the histopathologically and immunohistochemically (S-100, HMB-45, PNL-2, and Melan-A) confirmed diagnosis of malignant melanoma of the ciliary body with extraocular extension were matched with 10 globes with a ciliary body melanoma without extraocular extension regarding tumor size, cell type, melanin content, mitotic count, vascular networks, and patients’ age. In all 20 cases, immunohistochemistry was performed to identify lymphatic vessels by using LYVE-1 and podoplanin as specific markers for lymphatic vascular endothelium.

RESULTS. Intraocular LYVE-1+ and podoplanin+ lymphatic vessels were detected in 7 of 10 malignant melanomas of the ciliary body with extraocular extension (two of these developed a regional lymph node metastasis). Lymphatic vessels were found only at the tumor periphery directly adjacent to the sclera within the eye, more often in tumors of the epithelioid type (P = 0.017, Mann-Whitney test). Ciliary body melanomas without extrascleral extension revealed no intraocular LYVE-1+ and podoplanin+ lymphatic vessels. The presence of intraocular LYVE-1+/podoplanin+ lymphatic vessels was significantly associated with lower metastasis-free survival rates (P = 0.038, log-rank test).

CONCLUSIONS. 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.






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