EP53 – BRAF Mutation in Patients with Bethesda Cytological Indeterminate Thyroid Nodules: After reclassification of a variant thyroid carcinoma


    Maneeprasopchoke. P.1; Pongsapich, W.1; Poungvarin, N.2; Amornpichetkul, K.3, Metheetrairut, C.1; Piyawattayakorn, N.1; Vejvisithsakul, P.2; Chongkolwatana, C.1

    1 Department of Otorhinolaryngology, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand
    2 Department of Clinical Pathology, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand
    3 Department of Pathology, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand


    Background: Fine needle aspiration biopsy (FNAB) is widely accepted as a tool for thyroid cancer risk stratification. Atypia of undetermined significant (AUS) and suspicious for malignant cell (SMC) have significant risk for papillary thyroid carcinoma. After the reclassification of a variant thyroid carcinoma, the term “Noninvasive follicular thyroid neoplasm with papillary-like nuclear features” (NIFTP)1 has recently been introduced.

    To investigate clinical utility of BRAF mutation in Bethesda cytological indeterminate (AUS and SMC) thyroid nodules.

    A Cross-sectional study was conducted in 76 Thai patients with indeterminate nodules from July 2014 to October 2016. Pre-incisional FNAB was performed and sent for BRAFV600 analysis. Mutational status was studied by  direct sequencing and real time PCR techniques. The results were blinded to a pathologist who reviewed the final diagnosis.

    BRAFV600 mutation was positive in 13/76 (17.1%) patients with 48.1% sensitivity and 100% specificity for cancer. The malignancy rate was 18.64% in AUS (11/59) with 8 papillary carcinoma, 2 NIFTP, and 1 follicular carcinoma, and 94.2% in SMC (16/17) with 14 papillary thyroid carcinoma and 2 papillary microcarcinoma.
    No BRAF mutation was noted in the NIFTP pathological report, which the patients were treated as papillary microcarcinoma.

    Malignancy rate in indeterminate nodule is high. With 100% specificity, BRAF mutation from FNAB has acceptable accuracy that can be part of surgical decision. Following the introduced reclassification, molecular diagnosis could likely be useful for nature of NIFTP.

    1. Nikiforov YE, Seethala RR, Tallini G, Baloch ZW, Basolo F, Thompson LD, et al. Nomenclature Revision for Encapsulated Follicular Variant of Papillary Thyroid Carcinoma: A Paradigm Shift to Reduce Overtreatment of Indolent Tumors. JAMA oncology. 2016


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