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Kaltrina Zahiti, Kirsten H. Eibl, Alexander Muacevic, Anselm Kampik, Elisabeth M. Messmer; Ocular Pathology after Irradiation with Ruthenium, Gammaknife and Cyberknife for Uveal Melanoma. Invest. Ophthalmol. Vis. Sci. 2012;53(14):3416.
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© ARVO (1962-2015); The Authors (2016-present)
To describe the (immuno-) histological findings in eyes enucleated after different types of irradiation for uveal melanoma
Seventy eyes irradiated with ruthenium (42.9%), gammaknife (GN; 40.0%), or cyberknife (CK; 17.1%) for uveal melanoma were examined (immuno-) histologically with H&E, PAS, PTAH stains, melanocytic markers (S-100, HMB45, Melan-A, MITF), inflammatory markers (CD3, CD20, CD68), and the proliferation marker Ki 67.
Eyes were mainly enucleated for tumor recurrence (54.7%) or secondary glaucoma (39.1%). Mean time between irradiation and enucleation was 39.1 months (1-193 months). Mean age at the time of enucleation was 62 years. The tumor involved the iris (3.3%), the ciliary body (17.1%), ora serrata to equator (38.6%), and equator to optic disc (85.7%). Mean histological tumor base and height were 13.4 +/- 5.3mm and 6.6 +/- 3.4mm, respectively. Whereas tumor height did not differ between the three groups, tumor base was significantly larger in the GK cohort (p=0.007). Uveal melanomas were mainly heavily pigmented (45.7%), with intact tumor > 50% present in 60%, and tumor necrosis > 50% being a feature in 15.7% of specimens. Spindle cell morphology was prominent (55.7%). 32.7% of melanomas showed a focal/diffuse tumor hemorrhage, 24.3% were associated with vitreous hemorrhage. Tumors stained positive for HMB 45 (83.3%), Melan A (84.8%), and MITF (72.7%). Ki67 was negative in 43.9%. Inflammation in the tumor was moderate to severe for CD-3+ T-lymphocytes (66.6%) and CD68+ macrophages (83.3%). Cell type, pigmentation, necrosis, inflammation, and Ki67 proliferation were similar in all tumors. Infiltration into the optic disc was observed in 3 eyes after GK irradiation and was significantly associated with mixed/epitheloid cell type (p=0.04). Extrascleral invasion of the tumor occurred significantly more often in eyes after GK treatment (14.3%) compared to ruthenium irradiation (0%, p=0.048) and CK (8.3%). Histological rubeosis iridis (p=0.021), clinically manifest glaucoma (p=0.018), and enucleation due to glaucoma (p=0.004) were significantly more common after GK and CK treatment.
Tumor necrosis and inflammation did not differ between treatment groups indicating that tumor destruction may follow the same mechanisms. Extrascleral invasion and optic nerve infiltration of uveal melanomas were significantly associated with GK irradiation. However, these tumors had a larger tumor base and mixed/epitheloid cell type known to be more aggressive. Neovascular glaucoma is a major risk after GK and CK irradiation compared to ruthenium treatment, and may be responsible for enucleation despite tumor control.
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