The Long Journey towards Personalized Targeted Therapy in Poorly Differentiated Thyroid Carcinoma (PDTC): A Case Report and Systematic Review

Background: Poorly differentiated thyroid carcinoma (PDTC) has an intermediate prognosis between indolent well-differentiated thyroid carcinoma (TC) and anaplastic carcinoma. Herein, we present a case report with a PDTC component, along with a systematic review of the literature. Case Report: We report a case of a 45-year-old man diagnosed with a PDTC component, along with hobnail and tall-cell variant features positive for BRAFV600E mutation, after a total thyroidectomy and neck dissection. Radioactive iodine (RAI)-131 therapy was applied, but an early recurrence led to complementary surgeries. The anti-Tg rise, the presence of new lymph nodes, and the negative whole-bodyradioiodine scan were suggestive of a radioiodine-resistant tumor. Lenvatinib, sorafenib, dabrafenib/trametinib, cabozantinib and radiotherapy were all administered, controlling the tumor for a period of time before the patient ultimately died post-COVID infection. Systematic Review: We searched PubMed, Scopus, and WebofScience to identify studies reporting clinicopathological characteristics, molecular marker expression, and management of non-anaplastic TC with any proportion of PDTC in adult patients. Of the 2007 records retrieved, 82were included in our review (PROSPERO-ID545847). Conclusions: Our case, together with the systematic review, imply that a combination of molecular-targetedtreatments may be safe and effective in patients with RAI-resistantBRAF-mutated advanced PDTC when surgery has failed to control tumor progression.