Histopathologic Characteristics of Choroidal Melanoma in Eyes Enucleated After Iodine 125 Brachytherapy in the Collaborative Ocular Melanoma Study

Abstract

To describe the histopathologic findings in eyes with uveal melanoma that had secondary enucleation after failed brachytherapy plaque treatment. Methods: Histopathologic findings in eyes that had secondary enucleation after plaque radiation therapy in the Collaborative Ocular Melanoma Study (COMS) were reported on a standardized data form. The findings were compared with eyes that had primary enucleation for uveal melanoma. Results: Seventy-five eyes that had secondary enucleation were studied. Compared with primary enucleations, tumors in the irradiated eyes had lower mitotic activity, a smaller proportion of histologically intact tumor, more inflammation, more fibrosis, and more vascular damage within the tumor. In addition, compared with primary enucleations, eyes previously irradiated had a higher frequency of retinal invasion by the tumor and greater damage to the retinal vasculature, consistent with radiation retinopathy; neovascularization of the iris; and vitreous hemorrhage. Tumor growth or extrascleral extension was confirmed histopathologically in 25 of 42 eyes (60%) enucleated because of a reported failure of local control. Conclusions: Eyes with secondary enucleation after brachytherapy differ histopathologically from eyes with primary enucleation for uveal melanoma. These histopathologic differences may be due to the effects of radiation, tissue conditions related to plaque failure, and, in some cases, tumor growth. In 40% of eyes enucleated because of suspected failure of local control, increased tumor size could not be histologically confirmed.

Expression of neurotrophin receptors by retinoinvasive uveal melanoma

“…Retinoinvasive melanomas were described in nonirradiated eyes with primary ciliary body melanomas and in untreated small choroidal melanomas, also supporting the conclusion that factors other than irradiation drive the pathogenesis of this unusual tumor variant [1][2][3]5,6,17,18].…”

Extrascleral Tumor Extension Associated with Localized Scleral Melt following Plaque Brachytherapy for Uveal Melanoma: Clinical and Histologic Findings

“…In studies in which histopathologic analyses were performed on post-enucleation specimens without scleral melt, less mitotic activity was found in post-plaque-brachytherapy eyes compared to those primarily enucleated, even though the authors note that whether this represents a direct cytotoxicity/radiation effect or slower-growing tumors at baseline is difficult to determine [12,13,14]. Histologic examinations and in vitro studies of melanoma cell growth after pre-enucleation external beam radiation have found decreased mitotic and Ki-67 activity, and decreased cell adhesion, growth, and viability in cell culture, attributable to the radiation effect [15,16,17].…”

Cavernous Hemangiomalike Changes in a Choroidal Melanoma After Brachytherapy

“…Eyes studied histologically after brachytherapy exhibit prominent tumor vessels with signs of vascular damage when compared with choroidal melanomas treated with primary enucleation. [6][7][8] The dilated vascular channels in this melanoma most likely represent an extreme example of postradiation telangiectasia. The absence of smooth muscle in these vascular walls and lack of surrounding collagen support predisposed them to mechanical stress, probably made worse by the 12-o'clock position that this tumor occupied at the equator of the eye.…”