Pilot of BRAF mutation analysis in indeterminate, suspicious and malignant thyroid FNA cytology

Abstract

BRAF mutational analysis by melt curve analysis is feasible in routine thyroid cytology, and in our series had a 100% specificity for PTC in subsequent histology. The application of BRAF analysis could be useful for indeterminate cytology, but we suggest that it would be most appropriate and cost-effective for Thy4/suspicious cases, for which it could enable one-stage therapeutic surgery in the context of multidisciplinary discussion. In contrast, the sensitivity is low and there is no role for avoiding diagnostic thyroid surgery if wild-type BRAF is found.

Evaluation of Indeterminate Thyroid Cytology by Second-Opinion Diagnosis or Repeat Fine-Needle Aspiration: Which Is the Best Approach?

“…Potentially, these tumors would be managed as malignant (total thyroidectomy), avoiding the costs and risks related to a secondary neck surgery (completion thyroidectomy). Johnson et al [42] showed that BRAF analysis was feasible on the majority (90.2%) of their thyroid FNAs and the frequency of BRAF mutation was 5.2 and 26.7% for the indeterminate and suspicious diagnostic categories, respectively. On histological follow-up, all BRAF -positive cases proved to be papillary thyroid carcinomas.…”

BRAF mutation analysis in thyroid nodules with indeterminate cytology: our experience on surgical management of patients with thyroid nodules from an area of borderline iodine deficiency

“…In the clinical setting, especially in case of FNA showing follicular neoplasia, markers would be helpful to discriminate in particular between follicular carcinoma and follicular adenoma. An ideal development would be a marker (or a panel of markers) that could be applied to indeterminate thyroid FNA cytology to predict the benignity or malignancy of the nodule to avoid diagnostic surgery and to allow therapeutic surgery to be performed at one operation [31]. TSH receptor genetic analysis, the miRInform™ Thyroid (Asuragen) and Veracyte® (Afirma) commercial methods [32,33], and the noncommercial use of BRAF, RAS, RET/PTC and PAX8/PPARγ testing have promising roles in the diagnosis and treatment of patients with nodular thyroid disease and thyroid cancer.…”

“…However, at this time, experience with these molecular methods remains limited, no test has perfect sensitivity and specificity and no evidence-based recommendation for or against the use of these methods can be made [34]. Nevertheless, among several immunocytochemical and molecular markers that were proposed, only BRAF V600E mutation has almost 100 % specificity for PTC and represents a potentially accurate marker for the reassignment of indeterminate thyroid FNA cytology to diagnostic cytology [31]. The detection of V600E BRAF in FNA cells also can improve the pre-operative diagnosis in thyroid papillary microcarcinoma, being the presence of the mutation independent from the size of the tumor [35].…”

“…Therefore, the presence of V600E BRAF may confirm the diagnosis of PTC, but is of low importance in TIR3B nodules which have anyway an elevated cancer risk. In recent years, it has been demonstrated that BRAF genetic testing is feasible in selected archival histology and routine cytology cases [31,36]. Molecular analysis of thyroid FNA smears can be easily performed after FNA and permit later analysis of samples having indeterminate cytology features.…”

Cytomorphologic features in thyroid nodules read as “suspicious for malignancy” on cytology may predict thyroid cancers with the BRAF mutation

“…For one-stage treatment of a nodule read as "suspicious for malignancy", several studies have reported the additional diagnostic role of the BRAF V600E mutation [2,10,11]. The BRAF V600E mutation is a common finding in papillary thyroid cancer (PTC), as confirmed by its 29%-83% prevalence [12,13].…”