Intraocular lymphangiogenesis in malignant melanomas of the ciliary body with extraocular extension.
OBJECTIVE
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.
Heindl
Ludwig M
LM
Department of Ophthalmology and Eye Hospital, Ophthalmic Pathology Laboratory, Friedrich-Alexander University Erlangen-Nürnberg, Erlangen, Germany. ludwig.heindl@uk-erlangen.de
Hofmann
Tanja N
TN
Knorr
Harald L J
HL
Rummelt
Carmen
C
Schrödl
Falk
F
Schlötzer-Schrehardt
Ursula
U
Holbach
Leonard M
LM
Naumann
Gottfried O H
GO
Kruse
Friedrich E
FE
Cursiefen
Claus
C
D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism; D016022:Case-Control Studies; D002924:Ciliary Body / Q000378:metabolism / Q000473:pathology*; D018572:Disease-Free Survival; D004729:Endothelium, Lymphatic / Q000378:metabolism; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D042583:Lymphangiogenesis; D008207:Lymphatic Metastasis; D042601:Lymphatic Vessels / Q000473:pathology*; D008297:Male; D008545:Melanoma / Q000378:metabolism / Q000401:mortality / Q000556:secondary*; D008562:Membrane Glycoproteins / Q000378:metabolism; D018613:Microscopy, Confocal; D008875:Middle Aged; D015996:Survival Rate; D014604:Uveal Neoplasms / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D033921:Vesicular Transport Proteins / Q000378:metabolism; D000098853:Podoplanin
D014408:Biomarkers, Tumor; D008562:Membrane Glycoproteins; D033921:Vesicular Transport Proteins; C119248:LYVE1 protein, human; C117468:PDPN protein, human; D000098853:Podoplanin