Zimpfer Annette, Schneider Bjoern, Blanck Oliver, Riedel Katrin, Zhivov Andrey, Jonigk Danny, Erbersdobler Andreas, Jünemann Anselm, Andratschke Nicolaus, Hildebrandt Guido, Guthoff Rudolf F, Kakkassery Vinodh
Institute of Pathology, University Medical Center Rostock, Strempelstr. 14, 18057, Rostock, Germany.
Department for Radiation Oncology, University Medical Center Schleswig-Holstein, Arnold-Heller-Str. 3, 24105, Kiel, Germany.
Pathol Oncol Res. 2019 Apr;25(2):731-740. doi: 10.1007/s12253-018-00565-1. Epub 2019 Jan 7.
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.
评估立体定向射波刀放射外科治疗后5例患者标本中葡萄膜黑色素瘤细胞的活性和病理特征。本研究纳入了5例接受分三次治疗的射波刀放射外科治疗的患者标本。由于3例患者持续性视网膜脱离，在射波刀放射外科治疗后4、7和10个月进行了肿瘤内切除。在治疗后9个月和12个月，2例患者因继发性肿瘤出血和消退不佳而进行了眼球摘除术。在进行组织形态学分析并测定Ki67增殖指数后，进行了DNA细胞光度测定、3号染色体缺失的荧光原位杂交评估、GNA11和GNAQ突变分析。本研究纳入的5个肿瘤中有4个显示出不同程度的辐射诱导形态学变化，表现为细胞和细胞核增大、细胞质空泡化和核碎裂。大部分肿瘤细胞的DNA含量为亚二倍体。另一方面，单个显著深染的黑色素瘤细胞显示出明显的非整倍体。3例内切除肿瘤的增殖分数非常低（<1%），但在眼球摘除病例中升高。在2例内切除病例中检测到3号染色体单体，但在眼球摘除病例中均未检测到。所有患者均未出现局部肿瘤复发，但有2例患者发生了肝转移。在射波刀放射外科治疗后的前6个月内，许多黑色素瘤细胞似乎仍然存活，但明显的辐射诱导形态学变化，包括肿瘤坏死、亚二倍体DNA含量加上低Ki-67指数，可能表明细胞受到亚致死性损伤。
