Prediction of the Aggressive Clinical Course of Papillary Thyroid Carcinoma Based on Fine Needle Aspiration Biopsy Molecular Testing.

Molecular genetic events are among the numerous factors affecting the clinical course of papillary thyroid carcinoma (PTC). Recent studies have demonstrated that aberrant expression of miRNA, as well as different thyroid-related genes, correlate with the aggressive clinical course of PTC and unfavorable treatment outcomes, which opens up new avenues for using them in the personalization of the treatment strategy for patients with PTC. In the present work, our goal was to assess the applicability of molecular markers in the preoperative diagnosis of aggressive variants of papillary thyroid cancer. The molecular genetic profile (expression levels of 34 different markers and BRAF mutations) was studied for 108 cytology specimens collected by fine-needle aspiration biopsy in patients with PTC having different clinical manifestations. Statistically significant differences with adjustment for multiple comparisons (p < 0.0015) for clinically aggressive variants of PTC were obtained for four markers: miRNA-146b, miRNA-221, fibronectin 1 (FN1), and cyclin-dependent kinase inhibitor 2A (CDKN2A) genes. A weak statistical correlation (0.0015 < p < 0.05) was observed for miRNA-31, -375, -551b, -148b, -125b, mtDNA, CITED1, TPO, HMGA2, CLU, NIS, SERPINA1, TFF3, and TMPRSS4. The recurrence risk of papillary thyroid carcinoma can be preoperatively predicted using miRNA-221, FN1, and CDKN2A genes.

New Opportunities for Preoperative Diagnosis of Medullary Thyroid Carcinoma.

The preoperative diagnostics of medullary thyroid carcinoma (MTC), including the measuring of the blood calcitonin level, has a number of limitations. Particular focus has recently been placed on the role of miRNAs in the development of various malignant tumors; a comparative analysis of accuracy of the existing methods for MTC diagnosis with a novel diagnosis method, evaluation of the miRNA-375 expression level, was performed in this study. The expression level of miRNA-375 in cytology samples from 555 patients with the known histological diagnosis, including 41 patients with confirmed postoperative diagnosis of MTC, was assessed. The diagnostic parameters of the basal calcitonin level, calcitonin in wash-out fluid from the FNAB needle, and miRNA-375 were compared. An assessment of the miRNA-375 expression level made it possible to detect all the MTC samples with a 100% accuracy among all the 555 cytology specimens, as well as in non-informative FNAB specimens, and specimens from the ipsilateral thyroid lobe. Parameters such as sensitivity, specificity, PPV, and NPV were 100%. The miRNA-375 level, unlike calcitonin, does not correlate with tumor volume, so it does not have the so-called "gray zone". An assessment of the miRNA-375 expression allows one to accurately distinguish MTC from other malignant and benign thyroid tumors.

Persistence of primary hyperparathyroidism: a single-center experience.

BACKGROUND: Parathyroidectomy is the only definitive treatment for primary hyperparathyroidism (PHPT). Precise localization of abnormal glands is a key to a successful surgery. Most patients are expected to be successfully treated with focused parathyroidectomy. However, this approach is associated with a risk of existing multiglandular disease which may lead to the postoperative persistence of PHPT. METHODS: Eight hundred ten patients who underwent an initial surgery for PHPT at SPBU Hospital in 2017-2018 were included in the study. Preoperative imaging results were evaluated. Multivariate logistic regressions were calculated to estimate predictive values of preoperative data for the risk of postoperative persistence and risk of MGD. RESULTS: Multiglandular disease was found to be a leading cause of persistent hyperparathyroidism. An anamnesis of thyroid surgery was found to be a significant risk factor for the persistence of hyperparathyroidism. The rate of persistence did not differ significantly between groups with bilateral neck exploration and focused parathyroidectomy. Age, sex, body mass index as well as negative results of preoperative US, MIBI, and 4D CT were not independently associated with a higher risk of MGD. All preoperative imaging modalities showed from low to moderate sensitivity for the detection of MGD. The frequency of cases of a missed second adenoma did not differ significantly between patients with concordant and discordant preoperative data. There were 7 cases with previously unsuspected second adenomas found solely due to bilateral neck exploration. CONCLUSIONS: None of the combination of preoperative visualization modalities was able to rule out the MGD and reliably identify patients for focused parathyroidectomy. Additional preoperative visualization failed to improve overall results. Bilateral neck exploration appeared to have a slight benefit for the patients with concordant preoperative imaging results.

Preoperative Typing of Thyroid and Parathyroid Tumors with a Combined Molecular Classifier.

In previous studies, we described a method for detecting and typing malignant tumors of the thyroid gland in fine-needle aspiration biopsy samples via analysis of a molecular marker panel (normalized HMGA2 mRNA level; normalized microRNA-146b, -221, and -375 levels; mitochondrial-to-nuclear DNA ratio; and BRAFV600E mutation) in cytological preparations by quantitative PCR. In the present study, we aimed to estimate the specificity of the typing of different thyroid tumors by the proposed method. Fine-needle aspiration cytological preparations from 278 patients were used. The histological diagnosis was known for each sample. The positive and negative predictive values of the method assessed in this study were, respectively, 100% and 98% for papillary thyroid carcinoma (n = 63), 100% and 100% for medullary thyroid carcinoma (n = 19), 43.5% and 98% for follicular carcinoma (n = 15), and 86% and 100% for Hürthle cell carcinoma (n = 6). Thus, we demonstrate that the diagnostic panel, including the analysis of microRNA expression, mRNA expression, the BRAFV600E mutation, and the mitochondrial-to-nuclear DNA ratio, allows the highly accurate identification of papillary thyroid carcinoma, medullary thyroid carcinoma, and Hürthle cell carcinoma but not malignant follicular tumors (positive predictive value was below 50%).