Pathologic Features of Tumor Activity and Stability in Uveal Melanoma Specimens after Fractionated CyberKnife Radiosurgery
- 34 Downloads
To evaluate uveal melanoma cell activity and pathologic features after stereotactic CyberKnife radiosurgery in specimens from five patients. Specimens from five patients treated by CyberKnife radiosurgery in three fractions were included in this study. Because of persistent retinal detachment in 3 patients, tumour endoresection was performed at four, seven and ten month after CyberKnife radiosurgery. At nine and twelve months after treatment, enucleation of the eye globe was performed in 2 patients because of secondary tumour bleeding and missing regression. After histomorphological analysis and determination of Ki67-proliferation index, DNA cytophotometry, fluorescence in-situ hybridization evaluation for chromosome 3 loss, GNA11and GNAQ mutation analysis were performed. Four of the five tumours included in this study showed variable radiation-induced morphologic changes in the form of enlargement of cells and nuclei, cytoplasmic vacuolisation and nuclear fragmentation. The DNA content of a large fraction of tumour cells was hypoploid. On the other hand, single strikingly hyperchromatic melanoma cells showed marked aneuploidy. The proliferation fraction in the three endoresected tumours was very low (<1%), but it was elevated in the enucleation cases. Monosomy 3 was detected in two of the endoresection cases, but none of the enucleation cases. None of the patients experienced a local tumour recurrence, but two of the patients developed liver metastasis. Many melanoma cells seemed to be vital within the first 6 months after CyberKnife radiosurgery, but obvious radiation-induced morphologic changes, including tumour necrosis, hypoploid DNA content plus low Ki-67 index could indicate sublethal cell damage.
KeywordsUveal melanoma CyberKnife Stereotactic radiosurgery Proliferation index DNA image cytometry
We thank Mrs. Koelbel, Mrs. Westphal, Mrs. Stegemann and Mrs. Schmidtgen for their excellent technical assistance.
- 1.Eagle CR (2011) Eye pathology. An atlas and text. Lippincott Williams & Wilkins, Philadelphia, pp 177–206Google Scholar
- 2.Font RL, Croxatto JO, Rao NA (2006) AFIP atlas of tumor pathology. Tumors of the eye and ocular adnexa. Armed Forces Institute of Pathology, Washington DCGoogle Scholar
- 4.Bergman L, Seregard S, Nilsson B, Lundell G, Ringborg U, Ragnarsson-Olding B (2002) Incidence of uveal melanoma in Sweden from 1960 to 1998. Invest Ophthalmol Vis Sci 43:2579–2583Google Scholar
- 6.Damato B (2012) Progress in the management of patients with uveal melanoma. The 2012 Ashton lecture. Eye (Lond) 2012 Sep; 26(9):1157-72. https://doi.org/10.1038/eye.2012.126
- 21.Avery RB, Diener-West M, Reynolds SM, Grossniklaus HE, Green WR, Albert DM (2008) Histopathologic characteristics of choroidal melanoma in eyes enucleated after iodine 125 brachytherapy in the collaborative ocular melanoma study. Arch Ophthalmol 126:207–212. https://doi.org/10.1001/archopthalmol.2007.50 CrossRefGoogle Scholar
- 23.Brierley JD, Gospodarowicz MK, Wittekind C (eds) (2017) 8th edition of the Union for International Cancer Control / American Joint Committee on Cancer TNM classification. Wiley, OxfordGoogle Scholar
- 25.Gouvêa AF, Santos Silva AR, Speight PM, Hunter K, Carlos R, Vargas PA, de Almeida OP, Lopes MA (2013) High incidence of DNA ploidy abnormalities and increased Mcm2 expression may predict malignant change in oral proliferative verrucous leukoplakia. Histopathology 62:551–562. https://doi.org/10.1111/his.12036 CrossRefGoogle Scholar
- 26.Schilling H, Sehu KW, Lee WR (1997) A histologic study (including DNA quantification and Ki-67 labeling index) in uveal melanomas after brachytherapy with ruthenium plaques. Invest Ophthalmol Vis Sci 38:2081–2092Google Scholar
- 27.Van den Bosch T, van Beek JG, Vaarwater J, Verdijk RM, Naus NC, Paridaens D, de Klein A, Kiliç E (2012) Higher percentage of FISH-determined monosomy 3 and 8q amplification in uveal melanoma cells relate to poor patient prognosis. Invest Ophthalmol Vis Sci 53:2668–2674. https://doi.org/10.1167/iovs.11-8697 CrossRefGoogle Scholar
- 28.Schneider B, Riedel K, Zhivov A, Huehns M, Zettl H, Guthoff RF, Jünemann A, Erbersdobler A, Zimpfer A (2017) Frequent and Yet Unreported GNAQ and GNA11 Mutations are found in Uveal Melanomas. Pathol Oncol Res. https://doi.org/10.1007/s12253-017-0371-7
- 34.Fernandes BF, Weisbrod D, Yücel YH, Follwell M, Krema H, Heydarian M, Xu W, Payne D, McGowan H, Simpson ER, Laperriere N, Sahgal A (2011) Neovascular glaucoma after stereotactic radiotherapy for juxtapapillary choroidal melanoma: histopathologic and dosimetric findings. Int J Radiat Oncol Biol Phys 80:377–384. https://doi.org/10.1016/j.ijrobp.2010.04.073 CrossRefGoogle Scholar