Background/Aims: Our study aims to better characterize the clinical and histopathologic features of eyes with extrascleral uveal melanoma associated with scleral melt following brachytherapy. Methods: A retrospective review was performed on patients who had undergone 125I (iodine-125) brachytherapy for uveal melanoma at our institution between 1992 and 2015. Patients with postradiation scleral necrosis who required enucleation were identified, and an analysis including a review of histopathology results was performed on those cases. Results: A total of 301 patients underwent plaque brachytherapy for uveal melanoma, of whom 31 required eventual enucleation. The histologic analysis showed extraocular extension through full-thickness scleral discontinuities in 6 cases. All but 1 (5 of 6) of these eyes exhibited either mitotic figures or Ki-67 positivity. Mitotic figures were noted in 4 specimens, including 3 eyes exhibiting mitoses within or adjacent to the extrascleral portion of the tumor. Two eyes exhibiting mitoses, as well as the case with Ki-67 positivity, also had clinical evidence of tumor regrowth. Conclusion: We found evidence of mitotic activity at the area of scleral discontinuity in some eyes with and in some without clinical evidence of tumor regrowth. Protruding pigmented material in areas of scleral necrosis after plaque brachytherapy may represent actively proliferating tumors even without internal evidence of tumor regrowth.

1.
Conway RM, Poothullil AM, Daftari IK, Weinberg V, Chung JE, O'Brien JM: Estimates of ocular and visual retention following treatment of extra-large uveal melanomas by proton beam radiotherapy. Arch Ophthalmol 2006;124:838-843.
2.
Gündüz K, Shields CL, Shields JA, Cater J, Freire JE, Brady LW: Plaque radiotherapy of uveal melanoma with predominant ciliary body involvement. Arch Ophthalmol 1999;117:170-177.
3.
Shields CL, Naseripour M, Cater J, Shields JA, Demirci H, Youseff A, Freire J: Plaque radiotherapy for large posterior uveal melanomas (> or = 8-mm thick) in 354 consecutive patients. Ophthalmology 2002;109:1838-1849.
4.
Radin PP, Lumbroso-Le Rouic L, Levy-Gabriel C, Dendale R, Sastre X, Desjardins L: Scleral necrosis after radiation therapy for uveal melanomas: report of 23 cases. Graefes Arch Clin Exp Ophthalmol 2008;246:1731-1736.
5.
Kaliki S, Shields CL, Rojanaporn D, Badal J, Devisetty L, Emrich J, Komarnicky L, Shields JA: Scleral necrosis after plaque radiotherapy of uveal melanoma: a case-control study. Ophthalmology 2013;120:1004-1011.
6.
Corréa ZM, Augsburger JJ, Freire J, Eagle RC Jr: Early-onset scleral necrosis after iodine I 125 plaque radiotherapy for ciliochoroidal melanoma. Arch Ophthalmol 1999;117:259-261.
7.
Jones IS, Reese AB: Focal scleral necrosis; a late sequel of irradiation. AMA Arch Ophthalmol 1953;49:633-636.
8.
Macfaul PA, Bedford MA: Ocular complications after therapeutic irradiation. Br J Ophthalmol 1970;54:237-247.
9.
Harbour JW, Char DH, Kroll S, Quivey JM, Castro J: Metastatic risk for distinct patterns of postirradiation local recurrence of posterior uveal melanoma. Ophthalmology 1997;104:1785-1792; discussion 1792-1793.
10.
Shields CL, Kaliki S, Furuta M, Fulco E, Alarcon C, Shields JA: American Joint Committee on Cancer classification of posterior uveal melanoma (tumor size category) predicts prognosis in 7,731 patients. Ophthalmology 2013;120:2066-2071.
11.
Gallie BL, Simpson ER, Saakyan S, Amiryan A, Valskiy V, Finger PT, Chin KJ, Semenova E, Seregard S, Fili M, Wilson M, Haik B, Caminal JM, Català J, Gutierrez C, Pelayes DE, Folgar AM, Jager MJ, Dogrusöz M, Luyten GP, Singh A, Schachat AP, Suzuki S, Aihara Y: Local recurrence significantly increases the risk of metastatic uveal melanoma. Ophthalmology 2016;123:86-91.
12.
Albert DM, Diener-West M, Robinson NL, Grossniklaus HE, Green WR, Vine AK, et al: Histopathologic characteristics of uveal melanomas in eyes enucleated from the Collaborative Ocular Melanoma Study. COMS report No. 6. Am J Ophthalmol 1998;125:745-766.
13.
Crawford JB, Char DH: Histopathology of uveal melanomas treated with charged particle radiation. Ophthalmology 1987;94:639-643.
14.
Avery RB, Diener-West M, Reynolds SM, Grossniklaus HE, Green WR, Albert DM: Histopathologic characteristics of choroidal melanoma in eyes enucleated after iodine 125 brachytherapy in the collaborative ocular melanoma study. Arch Ophthalmol 2008;126:207-212.
15.
Mooy CM, de Jong PT, Van der Kwast TH, Mulder PG, Jager MJ, Ruiter DJ: Ki-67 immunostaining in uveal melanoma. The effect of pre-enucleation radiotherapy. Ophthalmology 1990;97:1275-1280.
16.
Kenneally CZ, Farber MG, Smith ME, Devineni R: In vitro melanoma cell growth after preenucleation radiation therapy. Arch Ophthalmol 1988;106:223-224.
17.
Augsburger JJ, Eagle RC Jr, Chiu M, Shields JA: The effect of pre-enucleation radiotherapy on mitotic activity of choroidal and ciliary body melanomas. Ophthalmology 1987;94:1627-1630.
18.
Brantley MA Jr, Worley L, Harbour JW: Altered expression of Rb and p53 in uveal melanomas following plaque radiotherapy. Am J Ophthalmol 2002;133:242-248.
19.
Shields CL, Shields JA, Karlsson U, Menduke H, Brady LW: Enucleation after plaque radiotherapy for posterior uveal melanoma. Histopathologic findings. Ophthalmology 1990;97:1665-1670.
20.
Gerdes J, Schwab U, Lemke H, Stein H: Production of a mouse monoclonal antibody reactive with a human nuclear antigen associated with cell proliferation. Int J Cancer 1983;31:13-20.
21.
Onken MD, Worley LA, Ehlers JP, Harbour JW: Gene expression profiling in uveal melanoma reveals two molecular classes and predicts metastatic death. Cancer Res 2004;64:7205-7209.
22.
Gill HS, Char DH: Uveal melanoma prognostication: from lesion size and cell type to molecular class. Can J Ophthalmol 2012;47:246-253.
23.
Chappell MC, Char DH, Cole TB, Harbour JW, Mishra K, Weinberg VK, Phillips TL: Uveal melanoma: molecular pattern, clinical features, and radiation response. Am J Ophthalmol 2012;154:227-232.e2.
24.
Edge SB, Compton CC, Byrd DR (eds): American Joint Committee on Cancer Staging Manual, ed 7. Chicago, Springer, 2010, pp 549-552.
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