Contemporary Thyroid Nodule Evaluation and Management

Grani, Giorgio; Sponziello, Marialuisa; Pecce, Valeria; Ramundo, Valeria; Durante, Cosimo

doi:10.1210/clinem/dgaa322

Cited by 143 publications

(128 citation statements)

References 115 publications

(125 reference statements)

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“…Overall, different guidelines consider hypo-echogenicity of lesions, irregular or lobulated margins, intranodular vascularity, and the presence of microcalcification as features of a high-risk nodule [ 67 , 68 ]. The hypothesis that the different compositions can affect the nature of the lesion and have possible implications on a differential diagnosis, cuts a path to more detailed studies.…”

Section: Microcalcifications In Thyroid Lesionsmentioning

confidence: 99%

Molecular Aspects and Prognostic Significance of Microcalcifications in Human Pathology: A Narrative Review

Bonfiglio

Granaglia

Giocondo

et al. 2020

IJMS

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The presence of calcium deposits in human lesions is largely used as imaging biomarkers of human diseases such as breast cancer. Indeed, the presence of micro- or macrocalcifications is frequently associated with the development of both benign and malignant lesions. Nevertheless, the molecular mechanisms involved in the formation of these calcium deposits, as well as the prognostic significance of their presence in human tissues, have not been completely elucidated. Therefore, a better characterization of the biological process related to the formation of calcifications in different tissues and organs, as well as the understanding of the prognostic significance of the presence of these calcium deposits into human tissues could significantly improve the management of patients characterized by microcalcifications associated lesions. Starting from these considerations, this narrative review highlights the most recent histopathological and molecular data concerning the formation of calcifications in breast, thyroid, lung, and ovarian diseases. Evidence reported here could deeply change the current point of view concerning the role of ectopic calcifications in the progression of human diseases and also in the patients’ management. In fact, the presence of calcifications can suggest an unfavorable prognosis due to dysregulation of normal tissues homeostasis.

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Section: Microcalcifications In Thyroid Lesionsmentioning

confidence: 99%

Molecular Aspects and Prognostic Significance of Microcalcifications in Human Pathology: A Narrative Review

Bonfiglio

Granaglia

Giocondo

et al. 2020

IJMS

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“…Molecular testing has emerged as an option to reduce the need for diagnostic surgery in indeterminate thyroid nodules, 8 recommended by the American Thyroid Association (ATA) 11 and National Comprehensive Cancer Network (NCCN) 12 guidelines. We have recently reported the development and validation of a new microRNA-based thyroid molecular classifier test for a precision endocrinology (mir-THYpe) with high sensitivity and specificity, which could be performed directly from readily available cytological smear slides at a significantly lower cost without the need for a new dedicated FNA.…”

Section: And the Six-tier Bethesda System For Reportingmentioning

confidence: 99%

Real-world, Prospective, and Multicenter Validation of a microRNA-based Thyroid Molecular Classifier

Santos

Rodrigues

Shizukuda

et al. 2020

Preprint

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Background The diagnosis of cancer in thyroid nodules with indeterminate cytology (Bethesda III/IV) is challenging as fine-needle aspiration (FNA), the gold standard method, has limitations, and these cases usually require diagnostic surgery. As approximately 77% of these nodules are not malignant, a diagnostic test accurately identifying benign thyroid nodules can reduce surgery rates. We have previously reported the development and validation of a microRNA-based thyroid molecular classifier for precision endocrinology (mir-THYpe) with high sensitivity and specificity, which could be performed directly from readily available cytological smear slides without the need for a new dedicated FNA. We sought to evaluate whether the use of this test in real-world clinical routine can reduce the rates of surgeries for Bethesda III/IV thyroid nodules and analyze the test performance. Methods We designed a real-world, prospective, multicenter cohort study. Molecular tests were performed in a real-world clinical routine with samples (FNA smear slides) prepared at 128 cytopathology laboratories. Patients were followed-up from March 2018 until surgery or until March 2020 (for those patients not recommended for surgery). The final diagnosis of thyroid tissue samples was retrieved from postsurgical anatomopathological reports. Results After applying the exclusion criteria, 435 patients (440 nodules) classified as Bethesda III/IV were followed-up. The rate of avoided surgeries was 52.5% for all surgeries and 74.6% for potentially unnecessary surgeries. After the statistical treatment of non-resected test-negative samples, the test achieved 89.3% sensitivity (95% CI 82-94.3), 81.65% specificity (95% CI 76.6-86), 66.2% positive predictive value (95% CI 60.3-71.7), and 95% negative predictive value (95% CI 91.7-97) at 28.7% (95% CI 24.3-33.5) cancer prevalence. The test influenced 92.3% of clinical decisions. Conclusions The reported data demonstrate that the use of the microRNA-based classifier in the real-world can reduce the rate of thyroid surgery with robust performance and significantly influence clinical decision-making.

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“…More recent studies suggest that repeating US risk stratification can be useful in predicting malignancy in the indeterminate nodules ( 15 – 17 ). However, in indeterminate thyroid nodules at high risk of malignancy, the utility of this approach may be limited ( 18 ).…”

Section: Introductionmentioning

confidence: 99%

The Combination of Sonographic Features and the Seven-Gene Panel May be Useful in the Management of Thyroid Nodules With Indeterminate Cytology

et al. 2021

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IntroductionThe management of patients with indeterminate thyroid nodules, which account for 10–25% of thyroid fine needle aspiration biopsies (FNABs), is still very challenging.AimTo verify the utility of the seven-gene panel in combination with ultrasound features in the clinical management of indeterminate thyroid nodules.ResultsThe study group included 188 indeterminate thyroid nodules, divided into TIR3A (56.4%) and TIR3B (43.6%). A significant correlation between US categories and both cytological and molecular results was observed. In detail, TIR3B cytology was more frequent in EU-TIRADS 4 and 5 nodules (54.7 and 50%, respectively) than in EU-TIRADS 2 and 3 nodules (31%, p = 0.04). Similarly, the rate of a nodule with a mutation increased with the increase of US risk class (6.0% in EU-TIRADS 2 and 3, 9.3% in EUTIRADS-4 and 27.8% in EUTIRAD-5, p = 0.01). Among thyroid nodules submitted to surgery, final histology was benign in 61.4% nodules, while malignancy was diagnosed in 38.6% nodules. Using US score as tool for decision-making in TIR3A subgroup, we correctly classified 64.5% of thyroid nodules. The second tool (seven-gene panel test) was used in the subgroup of US high-risk nodules. By multiple tests with a series approach (US in all cases and US plus seven-gene panel in US high risk nodules) 84% of cases were correctly classified. In TIR3B nodules, using only seven-gene panel as tool for decision making, we correctly classified 61.9% of indeterminate nodules. By multiple tests with series approach (seven-gene panel in all cases and seven-gene panel plus US score in non-mutated nodules) only a slight improvement of thyroid nodule classification (66.6%) was observed.ConclusionsUS score seems able to correctly discriminate between TIR3A nodules in which a conservative approach may be used, and those in which additional test, such as molecular test, may be indicated. On the contrary, in TIR3B nodules both US risk stratification and seven-gene panel seem to be of little use, because the risk of thyroid cancer remains high regardless of US score and mutational status.

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Contemporary Thyroid Nodule Evaluation and Management

Cited by 143 publications

References 115 publications

Molecular Aspects and Prognostic Significance of Microcalcifications in Human Pathology: A Narrative Review

Molecular Aspects and Prognostic Significance of Microcalcifications in Human Pathology: A Narrative Review

Real-world, Prospective, and Multicenter Validation of a microRNA-based Thyroid Molecular Classifier

The Combination of Sonographic Features and the Seven-Gene Panel May be Useful in the Management of Thyroid Nodules With Indeterminate Cytology

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