Histological features of BRAF V600E-mutant anaplastic thyroid carcinoma

Aims Treatment with a BRAF inhibitor, alone or in combination with a MEK inhibitor, may be considered forBRAF-mutant anaplastic thyroid carcinoma (ATC). The purpose of this study was to characterise the histology ofBRAFV600E-mutant ATC. Methods and results We identified 28 ATC that were consecutively resected between 2003 and 2019. All tumour slides for each case were evaluated for the presence of a precursor tumour and for ATC morphology (sarcomatoid, pleomorphic giant cell, epithelioid or squamous).BRAFV600E mutation status was determined by BRAF V600E IHC or molecular analysis (OncoPanel NGS). Eighteen (64%) ATC had an associated well-differentiated precursor, including 10 (36%) with associated papillary thyroid carcinoma (PTC) and eight (29%) with associated follicular thyroid carcinoma (FTC) or Hurthle cell carcinoma (HCC). Most ATC (19 cases, 68%) demonstrated a mixed anaplastic morphology. Squamous morphology was present in four cases. Ten (36%) ATC had aBRAFV600E mutation. All ATC that had a PTC precursor had aBRAFV600E mutation (and all ATC with aBRAFV600E mutation had a PTC precursor), whereas no ATC with an FTC or HCC precursor had aBRAFV600E mutation. All four cases of ATC with a squamous morphology had a PTC precursor and aBRAFV600E mutation. Conclusion In our cohort, the presence of a PTC precursor predicted the presence of theBRAFV600E mutation, whereas ATC with an FTC or HCC precursor lacked aBRAFV600E mutation. A squamous morphology was associated with the presence of a PTC precursor and aBRAFV600E mutation.