OBJECTIVE: The tall cell variant of papillary thyroid carcinoma (PTC) has an unfavorable prognosis. The diagnostic criteria remain inconsistent and the role of a minor tall cell (TC) component is unclear. Molecular diagnostic markers are not available; however, there are two potential candidates: BRAF V600E and TERT promoter mutations.
METHODS: Using a novel approach, we enriched a collective with PTC harboring an adverse outcome, overcoming the limited statistical power of most studies. This enabled us to review 125 PTC patients, 57 of them with an adverse outcome. The proportion of TC that constitute a poor prognosis was assessed. All tumors underwent sequencing for TERT promoter and BRAF V600E mutational status and were stained with an antibody detecting the BRAF V600E mutation.
RESULTS: A 10% cut off for TC was significantly associated with advanced tumor stage and lymph node metastasis. Multivariate analysis showed that tall cells above 10% were the only significant factor for overall, tumor-specific and relapse-free survival. 7% of cases had a TERT promoter mutation while 61% demonstrated a BRAF mutation. The presence of TC was significantly associated with TERT promoter and BRAF mutations. TERT predicted highly significant tumor relapse (p<0.001).
CONCLUSION: PTC comprising of at least 10% TC are associated with an adverse clinical outcome and should be reported accordingly. BRAF did not influence patient outcome. Nevertheless, a positive status should encourage the search for tall cells. TERT promoter mutations are a strong predictor of tumor relapse but their role as a surrogate marker for TC is limited.