TY - JOUR
T1 - Molecular markers for the classification of cytologically indeterminate thyroid nodules
AU - Muzza, M.
AU - Colombo, C.
AU - Pogliaghi, G.
AU - Karapanou, O.
AU - Fugazzola, L.
N1 - Funding Information:
This work was partially supported by the Ricerca Finalizzata program of Italian Ministry of Health, Rome (code: RF 2013-02354985) and by the Ministero dell’Istruzione, dell’Università e della Ricerca (MIUR, Investigator Grant 2015, PRIN 2017YTWKWH).
Publisher Copyright:
© 2019, Italian Society of Endocrinology (SIE).
Copyright:
Copyright 2020 Elsevier B.V., All rights reserved.
PY - 2020/6/1
Y1 - 2020/6/1
N2 - Background: The diagnosis of indeterminate lesions of the thyroid is a challenge in cytopathology practice. Indeed, up to 30% of cases lack the morphological features needed to provide definitive classification. Molecular tests have been developed to assist in the diagnosis of these indeterminate cases. The first studies dealing with the preoperative molecular evaluation of FNA samples focused on the analysis of BRAFV600E or on the combined evaluation of two or three genetic alterations. The sensitivity of molecular testing was then improved through the introduction of gene panels, which became available for clinical use in the late 2000s. Two different categories of molecular tests have been developed, the ‘rule-out’ methods, which aim to reduce the avoidable treatment of benign nodules, and the ‘rule-in’ tests that have the purpose to optimize surgical management. The genetic evaluation of indeterminate thyroid nodules is predicted to improve patient care, particularly if molecular tests are used appropriately and with the awareness of their advantages and weaknesses. The main disadvantage of these tests is the cost, which makes them rarely used in Europe. To overcome this limitation, customized panels have been set up, which are able to detect the most frequent genetic alterations of thyroid cancer. Conclusions: In the present review, the most recent available versions of commercial molecular tests and of custom, non-commercial panels are described. Their characteristics and accuracy in the differential diagnosis of indeterminate nodules, namely Bethesda classes III (Atypical follicular lesion of undetermined significance, AUS/FLUS) and IV (Suspicious for follicular neoplasm, FN/SFN) are fully analyzed and discussed.
AB - Background: The diagnosis of indeterminate lesions of the thyroid is a challenge in cytopathology practice. Indeed, up to 30% of cases lack the morphological features needed to provide definitive classification. Molecular tests have been developed to assist in the diagnosis of these indeterminate cases. The first studies dealing with the preoperative molecular evaluation of FNA samples focused on the analysis of BRAFV600E or on the combined evaluation of two or three genetic alterations. The sensitivity of molecular testing was then improved through the introduction of gene panels, which became available for clinical use in the late 2000s. Two different categories of molecular tests have been developed, the ‘rule-out’ methods, which aim to reduce the avoidable treatment of benign nodules, and the ‘rule-in’ tests that have the purpose to optimize surgical management. The genetic evaluation of indeterminate thyroid nodules is predicted to improve patient care, particularly if molecular tests are used appropriately and with the awareness of their advantages and weaknesses. The main disadvantage of these tests is the cost, which makes them rarely used in Europe. To overcome this limitation, customized panels have been set up, which are able to detect the most frequent genetic alterations of thyroid cancer. Conclusions: In the present review, the most recent available versions of commercial molecular tests and of custom, non-commercial panels are described. Their characteristics and accuracy in the differential diagnosis of indeterminate nodules, namely Bethesda classes III (Atypical follicular lesion of undetermined significance, AUS/FLUS) and IV (Suspicious for follicular neoplasm, FN/SFN) are fully analyzed and discussed.
KW - Afirma
KW - AUS/FLUS
KW - BRAF
KW - FN/SFN
KW - Indeterminate nodules
KW - Thyroseq
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U2 - 10.1007/s40618-019-01164-w
DO - 10.1007/s40618-019-01164-w
M3 - Review article
C2 - 31853887
AN - SCOPUS:85077045394
VL - 43
SP - 703
EP - 716
JO - Journal of Endocrinological Investigation
JF - Journal of Endocrinological Investigation
SN - 0391-4097
IS - 6
ER -