Poorly differentiated thyroid carcinoma: molecular, clinico-pathological hallmarks and therapeutic perspectives.

Poorly differentiated thyroid carcinoma (PDTC) is a rare and extremely aggressive tumor, accounting for about 2-15% of all thyroid cancer. PDTC has a distinct biological behavior compared to well-differentiated and anaplastic thyroid carcinoma and, in last years, it has been classified as a separate entity from both anatomopathological and clinical points of view. Nevertheless, there is still a lack of consensus among clinicians regarding inclusion criteria and definition of PDTC that affects its diagnosis and clinical management. Due to its rarity and difficulty in classification compared to other tumors, very few studies are available to date and series often include different histotypes in addition to PDTC. This review focuses on main studies concerning PDTC summarizing the evolution in the definition of its diagnosis criteria, clinicopathological features, management, and outcome. The data available confirm that the pathological evaluation and classification of PDTC are crucial and should therefore be standardized. Since the clinical presentation and prognosis of PDTC may vary widely depending on the different stage of the disease at diagnosis, the patient's management may differ in treatment and should be tailored to each patient. Finally, this review discusses advances in molecular insights of PDTC that, together with the implementation of both in vitro and in vivo models, will provide valuable insights into biological mechanisms of progression, metastasis, and invasion of this aggressive thyroid carcinoma. Further studies on larger, carefully selected series are needed to better assess the peculiar features of PDTC and to better define its management by focusing on the best diagnostic and therapeutic approaches.