Clinicopathological predictors of radioiodine response in differentiated high-grade thyroid carcinoma

Differentiated high-grade thyroid carcinoma (DHGTC) is a recently recognized entity characterized by increased mitotic activity and/or tumor necrosis while retaining the morphological features of differentiated thyroid carcinoma. Data regarding clinicopathological predictors of radioactive iodine (RAI) response in DHGTC remain limited. This retrospective study included 39 patients diagnosed with DHGTC. Clinicopathological parameters including tumor size, multifocality, extrathyroidal extension (ETE), capsular invasion, lymph node metastasis (LNM), lymphovascular invasion (LVSI), and coexistent lymphocytic thyroiditis were evaluated. Response to therapy was assessed during follow-up and categorized as radioiodine-sensitive (RAI-S) or radioiodine-refractory (RAI-R). Associations between clinicopathological variables and RAI response were assessed using Fisher's exact test with univariate odds ratio analysis, followed by multivariable generalized linear modeling. Of the 24 evaluable patients, 15 were RAI-sensitive and 9 developed RAI-refractory disease. Univariate analysis demonstrated significant associations between RAI-refractory disease and tumor size ≥2 cm, ETE, LNM, LVSI, and capsular invasion (all p < 0.05), whereas multifocality and coexistent lymphocytic thyroiditis showed significant inverse associations. ETE exhibited the strongest association with RAI-refractory disease (OR = 24.18, 95% CI: 9.33-58.26; p < 0.0001). Exploratory multivariable analysis demonstrated that extrathyroidal extension remained significantly associated with radioiodine-refractory disease (p = 0.024). DHGTC demonstrates heterogeneous response to radioactive iodine therapy. Extrathyroidal extension showed the strongest association with radioiodine-refractory disease in the present cohort, suggesting its potential utility as a practical marker for risk stratification and follow-up planning. Larger multicentre studies are warranted to validate these findings.