Annals of Surgical Oncology

, Volume 19, Issue 6, pp 1874–1880

Aggressive Variants of Papillary Thyroid Cancer: Incidence, Characteristics and Predictors of Survival among 43,738 Patients


  • Hadiza S. Kazaure
    • Department of SurgeryYale University School of Medicine
  • Sanziana A. Roman
    • Department of SurgeryYale University School of Medicine
    • Department of SurgeryYale University School of Medicine
Endocrine Tumors

DOI: 10.1245/s10434-011-2129-x

Cite this article as:
Kazaure, H.S., Roman, S.A. & Sosa, J.A. Ann Surg Oncol (2012) 19: 1874. doi:10.1245/s10434-011-2129-x



The diffuse sclerosing (DSV) and tall cell (TCV) variants are considered aggressive subtypes of papillary thyroid cancer (PTC) for which data are limited.


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.


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% (Ptrend = 0.052) and 158% (Ptrend = 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.


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.

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© Society of Surgical Oncology 2011