Tall cell papillary thyroid carcinoma: new diagnostic criteria and mutations in BRAF and TERT

Abstract

The tall cell (TC) variant of papillary thyroid carcinoma (PTC) has an unfavorable prognosis. The diagnostic criteria remain inconsistent, and the role of a minor TC component is unclear. Molecular diagnostic markers are not available; however, there are two potential candidates:BRAF V600Eand telomerase reverse transcriptase (TERT) promoter mutations. Using a novel approach, we enriched a collective with PTCs that harbored an adverse outcome, which overcame the limited statistical power of most studies. This enabled us to review 125 PTC patients, 57 of which had an adverse outcome. The proportion of TCs that constituted a poor prognosis was assessed. All of the tumors underwent sequencing forTERTpromoter andBRAFV600Emutational status and were stained with an antibody to detect theBRAFV600Emutation. A 10% cutoff for TCs was significantly associated with advanced tumor stage and lymph node metastasis. Multivariate analysis showed that TCs above 10% were the only significant factor for overall, tumor-specific, and relapse-free survival. Seven percent of the cases had aTERTpromoter mutation, whereas 61% demonstrated aBRAFmutation. The presence of TC was significantly associated withTERTpromoter andBRAFmutations.TERTpredicted highly significant tumor relapse (P<0.001). PTCs comprised of at least 10% TCs are associated with an adverse clinical outcome and should be reported accordingly.BRAFdid not influence patient outcome. Nevertheless, a positive status should encourage the search for TCs.TERTpromoter mutations are a strong predictor of tumor relapse, but their role as a surrogate marker for TCs is limited.