Cytologic artifacts and pitfalls of thyroid fine-needle aspiration using ThinPrep® The brand names ThinPrep® Cytyc®, Cytolyt®, and PreserveCyt® used throughout this article are registered trademarks of the Cytyc Corporation, Boxborough, MA.

BACKGROUND The ThinPrep® Processor has gained popularity as a collection and preparation technique for fine-needle aspiration biopsy (FNAB). Specific cytologic criteria to evaluate ThinPrep preparation (TP) may differ from those of conventional preparation (CP). The authors retrospectively reviewed the quality, cytologic features, and pitfalls of TP versus CP in thyroid FNABs and addressed the cytomorphologic criteria used to evaluate TP specimens. METHODS Thyroid FNABs received between January 1996–July 1999 were identified from the computer files of the Department of Pathology, University of Michigan (Ann Arbor, MI). Histologic correlation and clinical follow-up were reviewed. The cytology slides were reevaluated for cellularity, cellular preservation, artifacts, background material, architectural integrity, cytoplasmic details, and nuclear details by two observers. RESULTS Of the 209 thyroid FNABs performed during the study period, TP and CP prepared 127 and 82 cases respectively. Histologic correlation was available in 68 (33%) cases (32 TP and 36 CP). Overall sensitivity was 80% and specificity was 98%. The sensitivity of CP versus TP was 87% and 70%, respectively. Thyroid FNABs prepared by TP, as compared with CP, were characterized by the following: The TP slide 1) allowed assessment of the overall specimen cellularity but not individual passes of an FNAB, 2) contained only “hard” colloid that appeared dense, markedly fragmented, or in droplets, 3) showed crowded, tight, tissue clusters with loss of cellular preservation, especially in the larger aggregates, 4) demonstrated more cell shrinkage, 5) showed increased disruption of the cytoplasm and numerous naked nuclei, 6) occasionally gave nucleoli a more prominent appearance, and 7) was less likely to show nuclear grooves and “pseudoinclusions” in papillary carcinoma. CONCLUSIONS This study concluded that cytologic features used to evaluate thyroid FNABs prepared by CP may need to be modified when using TP. Awareness of the above-described findings and further studies to evaluate TP are essential to avoid potential diagnostic pitfalls. Cancer (Cancer Cytopathol) 2001;93:179–186. © 2001 American Cancer Society.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/34358/1/9027_ftp.pd

Hyperspectral Raman microscopy can accurately differentiate single cells of different human thyroid nodules.

We report on the use of line-scan hyperspectral Raman microscopy in combination with multivariate statistical analyses for identifying and classifying single cells isolated from clinical samples of human thyroid nodules based on their intrinsic Raman spectral signatures. A total of 248 hyperspectral Raman images of single cells from benign thyroid (n = 127) and classic variant of papillary carcinoma (n = 121) nodules were collected. Spectral differences attributed to phenylalanine, tryptophan, proteins, lipids, and nucleic acids were identified for benign and papillary carcinoma cells. Using principal component analysis and linear discriminant analysis, cells were identified with 97% diagnostic accuracy. In addition, preliminary data of cells from follicular adenoma (n = 20), follicular carcinoma (n = 25), and follicular variant of papillary carcinoma (n = 18) nodules suggest the feasibility of further discrimination of subtypes. Our findings indicate that hyperspectral Raman microscopy can potentially be developed into an objective approach for analyzing single cells from fine needle aspiration (FNA) biopsies to enable the minimally invasive diagnosis of "indeterminate" thyroid nodules and other challenging cases

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

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

Simulated fine-needle aspiration diagnosis of follicular thyroid nodules by hyperspectral Raman microscopy and chemometric analysis

SignificanceFollicular thyroid carcinoma carries a substantially poor prognosis due to its unique biological behavior and less favorable outcomes. In particular, fine-needle aspiration (FNA) biopsies, which play a key role in screening thyroid nodules, cannot differentiate benign from malignant follicular neoplasm.AimWe report on the use of hyperspectral Raman microscopy in combination with chemometric analysis for identifying and classifying single cells obtained from clinical samples of human follicular thyroid neoplasms.ApproachWe used a method intended to simulate the FNA procedure to obtain single cells from thyroid nodules. A total of 392 hyperspectral Raman images of single cells from follicular thyroid neoplasms were collected.ResultsMalignant cells were identified based on their intrinsic Raman spectral signatures with an overall diagnostic accuracy of up to 83.7%.ConclusionsOur findings indicate that hyperspectral Raman microscopy can potentially be developed into an ancillary test for analyzing single cells from thyroid FNA biopsies to better stratify "indeterminate" nodules and other cytologically challenging cases

SARS-CoV-2 vaccination modelling for safe surgery to save lives: data from an international prospective cohort study

Background: Preoperative SARS-CoV-2 vaccination could support safer elective surgery. Vaccine numbers are limited so this study aimed to inform their prioritization by modelling. Methods: The primary outcome was the number needed to vaccinate (NNV) to prevent one COVID-19-related death in 1 year. NNVs were based on postoperative SARS-CoV-2 rates and mortality in an international cohort study (surgical patients), and community SARS-CoV-2 incidence and case fatality data (general population). NNV estimates were stratified by age (18-49, 50-69, 70 or more years) and type of surgery. Best- and worst-case scenarios were used to describe uncertainty. Results: NNVs were more favourable in surgical patients than the general population. The most favourable NNVs were in patients aged 70 years or more needing cancer surgery (351; best case 196, worst case 816) or non-cancer surgery (733; best case 407, worst case 1664). Both exceeded the NNV in the general population (1840; best case 1196, worst case 3066). NNVs for surgical patients remained favourable at a range of SARS-CoV-2 incidence rates in sensitivity analysis modelling. Globally, prioritizing preoperative vaccination of patients needing elective surgery ahead of the general population could prevent an additional 58 687 (best case 115 007, worst case 20 177) COVID-19-related deaths in 1 year. Conclusion: As global roll out of SARS-CoV-2 vaccination proceeds, patients needing elective surgery should be prioritized ahead of the general population