Raman-based cytopathology: an approach to improve diagnostic accuracy in medullary thyroid carcinoma

Raman-based cytopathology: an approach to improve diagnostic accuracy in medullary thyroid carcinoma
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DOI:
10.1364/boe.410359
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发表时间:
2020-12-01
影响因子:
3.4
通讯作者:
Chan, James W.
Chan, James W.
中科院分区:
医学2区
文献类型:
--
作者:
de Oliveira, Marcos A. Soares;Campbell, Michael;Chan, James W.

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甲状腺髓样癌(MTC)是一种罕见的甲状腺恶性肿瘤,在细针吸取细胞学(FNA)的诊断上具有挑战性。辅助测试,如升高的血清或免疫组织化学阳性降钙素,是有帮助的,但它们偶尔也会提供假阳性结果。为了寻找一种提高诊断准确率(DA)的替代方法,我们应用高光谱拉曼光谱来表征MTC单个细胞的生化成分,并将它们的光谱信息与其他类型的甲状腺结节细胞进行比较。用线扫描高光谱拉曼显微镜对117例消化组织中的单个MTC细胞进行了高光谱拉曼成像,并与127例良性和121例经典型变异型乳头状甲状腺癌(CVPTC)细胞进行了比较。用主成分分析和线性判别分析对光谱数据进行分类,可将MTC细胞与良性细胞和CVPTC细胞区分开来,DA分别为97%和99%。此外,MTC细胞在1003 cm(-1)处有一个显著的拉曼峰,其强度分别比良性细胞和CVPTC细胞高84%和226%。当仅使用该峰作为光谱标记时,MTC细胞与良性细胞和CVPTC细胞分别具有87%和95%的DA。由于该峰与苯丙氨酸有关,苯丙氨酸已知与甲状腺滤泡旁细胞中降钙素的释放有关,这一增强的强度进一步表明该拉曼峰可能成为MTC的一个新的诊断标志。此外,从模拟FNA程序分离的MTC细胞(n=21)的初步数据与来自消化的单个细胞相比提供了类似的拉曼信号。这些结果表明,“基于拉曼的细胞病理学”可以作为一种辅助技术,在单细胞水平上提高FNA细胞病理学的诊断准确率。(C)OSA开放获取出版协议条款下的2020年美国光学学会
Medullary thyroid carcinoma (MTC) is a rare form of thyroid malignancy that can be diagnostically challenging on fine needle aspiration (FNA) cytology. Ancillary tests such as elevated serum or immunohistochemical positive calcitonin have been helpful, yet they can occasionally provide false positive results. In search for an alternative method to improve diagnostic accuracy (DA), we applied hyperspectral Raman spectroscopy to characterize the biochemical composition of single cells from MTC and compared their spectral information to cells from other types of thyroid nodules. Hyperspectral Raman images of 117 MTC single cells from digested tissue were obtained with a line-scan hyperspectral Raman microscope and compared to 127 benign and 121 classic variant of papillary thyroid carcinoma (CVPTC) cells. When principal component analysis and linear discriminant analysis were used to classify the spectral data, MTC cells were differentiated from benign and CVPTC cells with 97% and 99% DA, respectively. In addition, MTC cells exhibited a prominent Raman peak at 1003 cm(-1), whose intensity is 84% and 226% greater on average than that observed in benign and CVPTC cells, respectively. When specifically utilizing only this peak as a spectral marker, MTC cells were separated from benign and CVPTC cells with 87% and 95% DA, respectively. As this peak is linked to phenylalanine, which is known to be associated with calcitonin release in thyroid parafollicular cells, the increased intensity further suggests that this Raman peak could potentially be a new diagnostic marker for MTC. Furthermore, preliminary data from MTC cells (n=21) isolated from a simulated FNA procedure provided similar Raman signatures when compared to single cells from digestion. These results suggest that "Raman-based cytopathology" can be used as an adjunct technique to improve the diagnostic accuracy of FNA cytopathology at a single cell level. (c) 2020 Optical Society of America under the terms of the OSA Open Access Publishing Agreement