Abstract
Thyroid malignancy represents the most common type of endocrine cancer, with an increasing incidence all over the world, including an increasing rate of detection among younger adults, 90% to 95% of all cases being non-medullary types. Poorly differentiated thyroid cancer, accounting 1% to 5% of all thyroid malignancies, is a less understood neoplasm compared to the other more frequent and better described thyroid cancers, associating various histological patterns that might bring pitfalls of diagnosis in everyday practice. We aimed to provide an updated analysis in the field of poorly differentiated thyroid carcinoma, based on a multimodal approach, including emergent biomarkers. The current data offers a robust framework for elucidating the biology of poorly differenced thyroid malignancy and further on, it provides the basis for a multilayered therapeutic approach. Emergent biomarkers might be detected from cytological analysis based on fine-needle aspiration or blood assays as cell-free deoxyribonucleic acid (cfDNA), but the most important remains the identification of the molecular and genetic constellation in terms of analyzing RAS, telomerase reverse transcriptase (TERT), B-Raf proto-oncogene, serine∕threonine kinase (BRAF), tumor protein p53 (TP53), phosphatase and tensin homolog (PTEN), copy number alterations (CNA) and phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA) profile, which serve as prognostic markers and pointers of anti-cancer medical therapy. Overall, despite recent advances in multimodal management, the prognostic remains severe. The issue is ongoing, and we expect a massive expansion within the following years, across a guideline-based, as well as a personalized decision.