Tall Cell Variant Histology Predicts Poorer Disease-Free Survival in Papillary Thyroid Carcinoma: A Propensity-Matched Cohort Study.

Abstract

The tall cell variant of papillary thyroid carcinoma (TCV-PTC) is recognized as an aggressive subtype, yet its prognostic value independent of clinicopathological and molecular factors remains controversial, particularly in non-Western populations. We aimed to evaluate the impact of TCV histology on disease-free survival (DFS) in a large Middle Eastern cohort of patients with PTC undergoing standard surgical treatment and adjuvant radioactive iodine. This retrospective study included 1065 patients with TCV-PTC (n = 174) or classical variant PTC (CV-PTC; n = 891) treated at a single tertiary center. A 1:3 propensity score matching (PSM) was performed to balance age, sex, tumor stage, lymph node status, and extrathyroidal extension. Logistic regression was used to assess independent predictors of persistent or recurrent disease. Kaplan-Meier analysis evaluated disease-free survival (DFS). After PSM, 174 TCV-PTC cases were compared with 522 matched CV-PTC cases. TCV-PTC was associated with a higher rate of persistent/recurrent disease (42.0% vs. 31.4%; p = 0.0119) and shorter 5-year DFS (48.5% vs. 73.1%; p < 0.0001). On multivariate analysis, TCV histology remained an independent predictor of recurrence (OR = 2.09; 95% CI, 1.28-3.40; p = 0.0031), along with age ≥ 55, extrathyroidal extension, nodal metastases, advanced T stage, and TERT promoter mutations. TCV-PTC is independently associated with increased risk of disease persistence or recurrence following surgery. These findings support histological subtyping as a critical component of risk stratification and long-term surveillance planning in patients with PTC.