Aggressive variants of papillary thyroid cancer: incidence, characteristics and predictors of survival among 43,738 patients.

BACKGROUND: The diffuse sclerosing (DSV) and tall cell (TCV) variants are considered aggressive subtypes of papillary thyroid cancer (PTC) for which data are limited.
METHODS: The Surveillance, Epidemiology, and End Results (SEER) database (1988-2008) was used to compare the incidence and clinical/pathologic characteristics of DSV and TCV with classic PTC. Prognostic factors associated with survival were analyzed by chi-square test, analysis of variance, log rank test, and Cox multivariate regression.
RESULTS: There were 261 DSV, 573 TCV, and 42,904 PTC patients. Compared to a 60.8% increase in classic PTC incidence, DSV and TCV incidence increased by 126% (P (trend) = 0.052) and 158% (P (trend) = 0.002), respectively. Aggressive variants were associated with higher rates of extrathyroidal extension, multifocality, and nodal and distant metastasis (all P < 0.001) compared to classic PTC. Nodal metastasis was more likely with DSV (72.2% vs. 66.8% TCV vs. 56.3% PTC, P < 0.001); distant metastasis was most common with TCV (11.1% vs. 7.3% DSV vs. 4.3% PTC, P < 0.001). After adjustment, DSV [hazard ratio (HR) 1.8, P = 0.007] and TCV (HR 1.9, P < 0.001) histologies were associated with significantly reduced survival (5-year overall: 87.5% DSV, 80.6% TCV vs. 93.5% PTC, P < 0.001). Tumor size independently predicted worse prognosis for TCV (HR 1.29, P < 0.001) but not DSV patients. Thyroid surgery and radioiodine improved survival of DSV and TCV patients (all P < 0.05). Patients with aggressive variants who received external-beam radiotherapy did not experience improved survival.
CONCLUSIONS: DSV and TCV are rare, increasing in incidence, and have a worse prognosis than classic PTC. Patients with these variants should be treated aggressively with thyroidectomy and radioiodine, regardless of tumor size.