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Raman-based cytopathology: an approach to improve diagnostic accuracy in medullary thyroid carcinoma
Biomedical Optics Express ( IF 3.4 ) Pub Date : 2020-11-06 , DOI: 10.1364/boe.410359
Marcos A. Soares de Oliveira , Michael Campbell , Alaa M. Afify , Eric C. Huang , James W. Chan

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.

中文翻译:

基于拉曼的细胞病理学:提高甲状腺髓样癌诊断准确性的方法

甲状腺髓样癌(MTC)是一种罕见的甲状腺恶性肿瘤,对细针穿刺(FNA)细胞学检查可能具有诊断挑战。辅助检查,如血清升高或降钙素阳性或免疫组化阳性也有帮助,但有时可提供假阳性结果。为了寻找提高诊断准确性(DA)的替代方法,我们应用了高光谱拉曼光谱来表征来自MTC的单个细胞的生化成分,并将它们的光谱信息与来自其他类型甲状腺结节的细胞进行比较。使用线扫描高光谱拉曼显微镜获得了来自消化组织的117个MTC单细胞的高光谱拉曼图像,并将其与127例良性和121个乳头状甲状腺癌(CVPTC)经典变体进行了比较。当使用主成分分析和线性判别分析对光谱数据进行分类时,MTC细胞与良性和CVPTC细胞分别具有97%和99%DA的区别。此外,MTC细胞在1003 cm处表现出突出的拉曼峰-1,其强度分别比良性和CVPTC电池分别高84%和226%。当仅将这个峰专门用作光谱标记时,MTC细胞与良性和CVPTC细胞分离,DA分别为87%和95%。由于该峰与苯丙氨酸有关,而苯丙氨酸与降钙素在甲状腺滤泡旁细胞中的释放有关,因此强度增加进一步表明,该拉曼峰可能是MTC的新诊断标志。此外,与来自消化的单个细胞相比,从模拟FNA程序中分离的MTC细胞(n = 21)的初步数据提供了相似的拉曼信号。这些结果表明,“基于拉曼的细胞病理学”可以用作辅助技术,以在单个细胞水平上提高FNA细胞病理学的诊断准确性。
更新日期:2020-12-01
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