**2. Epidemiology and pathogenesis**

ATC accounts for 1–2% of all thyroid malignancies. It usually affects patients in their 6th to 7th decade with a female predominance (male/female ratio: 1.5:2) [1–3]. However, it contributes up to 14–50% of the annual mortality associated with thyroid cancer [1]. The age-adjusted annual incidence is one to two per million people [4, 5].

Based on different tumor registries, the frequency of ATC is variable in different countries; however, there has been a drastic reduction in its incidence owing to better dietary iodine intake as well as timely diagnosis and treatment of DTC and MNG [1].

ATC usually originates in the background of a long-standing goiter. Dedifferentiation of differentiated thyroid cancer cells is considered the most common cause of ATC. Dedifferentiation arises due to multiple chromosomal aberrations, alteration in signal transduction pathways, and cell-cycle derangement.

BRAF, RAS oncogene, PIK3CA, PTEN, and TP53 mutations are the most commonly associated genetic alterations in ATC [6, 7]. Reduced levels of E-cadherin and beta-catenin are also associated with ATC [8].

Around 20–30% of patients have coexisting differentiated thyroid cancer with papillary being the most common (20%) [9, 10]. Serial biopsies of the thyroid gland also predispose to ATC [11]. Commonly seen mutations and their expression are listed in **Table 1**.
