Background: When US characteristics and the diameter of a thyroid nodule (TN) justify further evaluation to rule out or to establish the diagnosis of thyroid cancer (TC), fine needle aspiration (FNA) biopsy for cytology (FNAC) is indicated. A major limitation of FNAC is the high rate of indeterminate significance (~30%) results, which require further evaluation. Although recently introduced molecular testing contributed to the ability to differentiate benign from malignant TNs, these approaches are costly, and not available worldwide. Punctate calcifications detected within a TN by neck US are considered a high-risk feature for TC. We hypothesized that the small amount of material that remains in the syringe at the end of the FNA procedure contains microscopic calcifications (MCs), that may differentiate benign from malignant TNs, by chemical analysis for composition and morphology.
Aim: To assess the diagnostic potential of MCs within TNs obtained during routine FNAC procedure.
Methods: In this single-center proof-of-concept study, samples were collected between 11/2020 and 12/2022 during FNAC procedures, conducted as clinically indicated. Clinical decisions were made according to the accepted guidelines based on thyroid US and cytological findings. Comparisons between the final diagnosis of a TN as benign or malignant and the results of the thorough compositional and morphological MCs analyses were conducted retrospectively.
Results: Samples from 124 patients were collected and sent for chemical analysis in parallel with the routine cytological evaluation. Samples from 26 patients were used for protocol development, and 35 patients were still under clinical evaluation. The remaining 63 patients underwent full clinical evaluation, and FNA samples from these patients were subject to the MCs isolation protocol. In 52/63 patients (82.5%), FNA MCs were identified. Interestingly, all 11 patients without identifiable MCs were diagnosed with benign TNs. The final study cohort included 30 patients with benign TNs (median age: 54 years [range: 26-76 years], 83.3% females), and 22 patients with TC (median age: 42 years [range: 18-80 years], 63.6% females). Morphologically, while MCs from patients with TC were spherical, MCs from benign TNs were crystals with sharp edges. Regarding elemental composition, zinc was present in 91% and 7% of MCs obtained from patients with final diagnosis of TC and benign TN, respectively.
Conclusion: The presence of zinc in MCs isolated from samples collected during routine FNAC can offer value as a biomarker for TC.
13 May 2023 - 16 May 2023