<p>BRAF mutation in cytologically indeterminate thyroid nodules: after reclassification of a variant thyroid carcinoma</p>

Abstract

Purpose Fine-needle aspiration biopsy (FNAB) is regarded by the Bethesda system as the gold-standard investigation for stratifying the risk of malignancy of a thyroid nodule. However, some limitations affect the adequacy of the obtained materials, resulting in 30% of the cytological results remaining in the indeterminate category. We aimed to investigate the diagnostic value of the BRAF mutation in cytologically indeterminate thyroid nodules after the reclassification of a variant thyroid carcinoma. Patients and methods In this prospective diagnostic study, 76 patients with FNAB findings of atypia of undetermined significance (AUS) and suspicious for malignancy (SUS) were included. The BRAF V600 mutation from FNAB was confirmed by a PCR-based method (Sanger sequencing combined with allele-specific real-time PCR techniques) and immunohistochemistry (IHC). Pathological specimens and features, including noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP), were reviewed and compared to the FNAB results. Results Using the PCR-based method, the BRAF mutation was positive in 13/76 cases (17.1%), with the diagnostic values of 16.7% sensitivity, 100% specificity, 100% positive predictive value (PPV), and 82.8% negative predictive value (NPV) in the AUS compared to 73.3% sensitivity, 100% specificity, 100% PPV, and 20% NPV in the SUS. For the IHC technique, only 20 of the 76 cytological specimens were qualified for testing. The BRAF mutation was positive in 13/20 cases, with the diagnostic values of 100% sensitivity, 63.6% specificity, 42.9% PPV, and 100% NPV in the AUS compared to 100% sensitivity and PPV in the SUS. The BRAF mutation was not found in the pathological reports for NIFTP. Conclusion The malignancy rate is high in our data, with specific and acceptable accuracy rates for the BRAF mutation from FNAB found by using the PCR-based method. NIFTP has been introduced after the pathological reclassification. Molecular diagnosis might be useful to establish the nature of the disease.

Correlation of ThyroSeq Results with Surgical Histopathology in Cytologically Indeterminate Thyroid Nodules

“…However, when found in combination with BRAF or RAS mutations, TERT/TP53 nodules have high rates of malignancy and are associated with clinically aggressive cancer phenotypes [13,21]. Similarly, previous literature has established that BRAF-like mutated nodules have a high risk of malignancy and are associated with classic or aggressive variants of papillary thyroid carcinoma [22,23]. Our findings support prior reports, as all nodules with either TERT/TP53 combination or BRAF-like mutations were malignant.…”

Diagnostic and prognostic significance of detecting mutations in the <i>BRAF, TERT, RAS, RET/PTC, PAX8/PPARG</i> in the material of fine needle aspiration biopsy thyroid nodules in the IV cytological group (Bethesda, 2017)

“…Распространенность мутации V600E в гене BRAF при папиллярной карциноме составила 33,3 %, при фолликулярном варианте данной патологии -4,2 %. Схожие результаты для этих гистологических типов были продемонстрированы в ряде европейских исследований [15]. Примечание.…”

Risk assessment of cytologically indeterminate thyroid nodules with integrated molecular testing and repeat biopsy: a surgical decision-oriented tool

“…Some studies have shown that a single method, such as molecular testing or repeat FNAB, can help determine the prevalence of malignancy in ITNs. (7,(28)(29)(30)(31)(32)(33)(34)(35)(36)(37)(38) In recent years, two kinds of gene tests have appeared on the market, the A rma Gene Expression Classi er and ThyroSeq genomic classi er. A randomized clinical trial including 346 patients with indeterminate nodules indicated that both products have high speci city and can help 49% of patients with ITNs avoid diagnostic surgery.…”