Raman Spectroscopy as a Potential Adjunct of Thyroid Nodule Evaluation: A Systematic Review

The incidence of thyroid nodules (TNs) is estimated at 36.5% and 23% in females and males, respectively. A single thyroid nodule is usually detected during ultrasound assessment in patients with symptoms of thyroid dysfunction or neck mass. TNs are classified as benign tumours (non-malignant hyperplasia), benign neoplasms (e.g., adenoma, a non-invasive follicular tumour with papillary nuclear features) or malignant carcinomas (follicular cell-derived or C-cell derived). The differential diagnosis is based on fine-needle aspiration biopsies and cytological assessment (which is burdened with the bias of subjectivity). Raman spectroscopy (RS) is a laser-based, semiquantitative technique which shows for oscillations of many chemical groups in one label-free measurement. RS, through the assessment of chemical content, gives insight into tissue state which, in turn, allows for the differentiation of disease on the basis of spectral characteristics. The purpose of this study was to report if RS could be useful in the differential diagnosis of TN. The Web of Science, PubMed, and Scopus were searched from the beginning of the databases up to the end of June 2023. Two investigators independently screened key data using the terms "Raman spectroscopy" and "thyroid". From the 4046 records found initially, we identified 19 studies addressing the differential diagnosis of TNs applying the RS technique. The lasers used included 532, 633, 785, 830, and 1064 nm lines. The thyroid RS investigations were performed at the cellular and/or tissue level, as well as in serum samples. The accuracy of papillary thyroid carcinoma detection is approx. 90%. Furthermore, medullary, and follicular thyroid carcinoma can be detected with up to 100% accuracy. These results might be biased with low numbers of cases in some research and overfitting of models as well as the reference method. The main biochemical changes one can observe in malignancies are as follows: increase of protein, amino acids (like phenylalanine, tyrosine, and tryptophan), and nucleic acid content in comparison with non-malignant TNs. Herein, we present a review of the literature on the application of RS in the differential diagnosis of TNs. This technique seems to have powerful application potential in thyroid tumour diagnosis.