Tall cell Papillary Thyroid Carcinoma: new diagnostic criteria and mutations in BRAF and TERT

Matthias S Dettmer, Anja Maria Schmitt, Hans Steinert, David Capper, Holger Moch, Paul Komminoth, Aurel Perren
2015
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
more » ... ost 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). CONCLU-SION: 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. 23 24 Article word count: 3703; Abstract word count: 250; number of tables: 3; number of supplementary 25 tables: 3; number of figures: 3; number of supplementary figures: 1; number of References: 40. 26 27 Abstract 41 The tall cell variant of papillary thyroid carcinoma (PTC) has an unfavorable prognosis. The 42 diagnostic criteria remain inconsistent and the role of a minor tall cell (TC) component is unclear. 43 Molecular diagnostic markers are not available; however, there are two potential candidates: BRAF 44 V600E and TERT promoter mutations. Using a novel approach, we enriched a collective with PTC 45 harboring an adverse outcome, overcoming the limited statistical power of most studies. This 46 enabled us to review 125 PTC patients, 57 of them with an adverse outcome. The proportion of TC 47 56 the search for tall cells. TERT promoter mutations are a strong predictor of tumor relapse but their role 57 as a surrogate marker for TC is limited. 58 59 60 61
doi:10.5167/uzh-110616 fatcat:63jdparvzffitaabos7bsdet7q