Expression of neurotrophin receptors by retinoinvasive uveal melanoma

Abstract

Retinoinvasive uveal melanoma demonstrates prominent diffuse retinal and optic nerve invasion, with little or no involvement of the adjacent choroid. Prior studies have advanced hypotheses on the potential role of molecular and cellular interactions in the pathogenesis of retinoinvasiveness and neuroinvasiveness, but the precise molecular events are not known. Here, we investigate the role of neutrotrophic factors in the pathogenesis of retinoinvasive uveal melanoma. The records of three ophthalmic pathology departments (The New York Eye and Ear Infirmary, Wills Eye Institute, and University of California San Francisco) were searched to identify all cases of retinoinvasive uveal melanoma, yielding four eyes (all previously irradiated). Eight eyes with nonretinoinvasive melanomas (four irradiated and four nonirradiated) were randomly selected as controls. All enucleated eyes were examined histopathologically and immunohistochemically for the expression of neurotrophic factor receptors [Pan-Trk, p75 neurotrophin receptor (p75(NTR) and ciliary neurotrophic factor receptor-α]. Histopathologic features were similar in both retinoinvasive and control melanomas with regard to choroidal tumor location and size, neovascular glaucoma, and cell type. The eyes with retinoinvasive melanoma showed diffuse retinal invasion beyond the choroidal tumor (n=4) and prelaminar (n=1) and retrolaminar (n=2) optic nerve invasion. The control melanomas showed focal retinal invasion over the tumor apices (n=6) and prelaminar optic nerve invasion (n=1). Nonirradiated melanomas demonstrated no trace immunoreactivity for neurotrophic factor receptors, whereas irradiated melanomas showed more prominent (trace to moderate) immunoreactivity. When controlled for irradiation, no difference in immunoreactivity for neurotrophin receptors nor tumor duration was observed between retinoinvasive and nonretinoinvasive melanomas. This study failed to demonstrate a direct causation between the expression of neurotrophin receptors and a retinoinvasive uveal melanoma growth pattern.

Multifocal Intraretinal Tumour Deposits following Treatment of an Ipsilateral Choroidal Melanoma

“…Finally, these lesions may suggest the presence of a retinoinvasive melanoma. This is a rare subtype of uveal melanoma, which was described by Kivelä and Summanen [14] in 1997, and has been further reported in a small number of limited case series [15, 16]. It is characterised by transvitreal melanoma invasion of the retina at a site non-contiguous with the uveal tumour.…”

Vitreous Seeding of Choroidal Melanoma

“…1. Mechanism: The possible routes by which the melanoma cells can reach the vitreous include 1) retinal invasion, 1 2) ciliary body melanoma with direct access to vitreous, 8,9 and 3) a rare metastasis of malignant cutaneous melanoma cells through the retinal vessels into the vitreous cavity. 10 We limited our review to all the cases of vitreous seeding from primary choroidal melanoma.…”

Retinoinvasive Uveal Melanoma: Report of 2 Cases and Review of the Literature

“…There have been 8 previously reported cases [1,2,4,5,6]. The age range of these patients is 53-79 years, and men and women are equally affected.…”

“…This subtype is thought to be a late presentation of uveal melanomas. A retrospective review of pathology records from 3 tertiary referral centers showed invasion of the inner retina from a site distinct from the primary tumor in only 0.4% of eyes enucleated for uveal melanoma [2]. …”

“…This melanoma rarely involves the choroid and may exhibit optic nerve invasion [1]. This unusual variant occurs in approximately 0.4% of all eyes enucleated with uveal melanoma [2]. We recently evaluated 2 eyes with retinoinvasive melanoma; one eye from a patient with known iris/ciliary body melanoma had been enucleated; the other eye was eviscerated from a patient with a clinical diagnosis of iridocorneal endothelial (ICE) syndrome.…”