OBJECTIVE: The prevalence of thyroid cancer has increased significantly. Aggressive subtypes of papillary thyroid cancer (AG-PTC) and high-grade follicular cell-derived malignancies (HGFM) are malignancies that lie between well-differentiated and undifferentiated cancers, and their management needs to be clarified. The aim of our study is to describe the clinicopathological characteristics of AG-PTC and HGFM and to assess their prognostic value. METHODS: This was a retrospective chart review study at single center of patients with AG-PTC or HGFM. HGFM comprised of patients with poorly differentiated thyroid cancer (PDTC) and differentiated high-grade thyroid carcinoma. The clinical presentation, pathological characteristics, molecular markers, specific treatments, and clinical outcomes were compared between the groups. RESULTS: Of the 3244 thyroid cancer charts reviewed, 136 met the criteria for AG-PTC and HGFM. The mean age at diagnosis was 49 years, with a predominance of women. The median follow-up duration was 3 years. The rate of persistent or recurrent disease was 40.3% in the AG-PTC group and 29.3% in the HGFM group, 4.5% died in the AG-PTC group, and 1.8% died in the HGFM group. The presence of vascular, lymphovascular invasion and extrathyroidal extension were associated with a higher incidence of persistent or recurrent disease (Hazard ratio: 2.5, 3.8, and 4.2, respectively
p <
0.05). When the Ki-67 index was divided into five groups, the recurrence rate was higher in the ≥ 20% Ki-67 group. CONCLUSIONS: Possible prognostic markers for predicting worse prognosis include vascular/lymphovascular invasion, extrathyroidal extension, and the proliferative index Ki-67.