Background:Anaplastic thyroid cancer (ATC) is a rare, highly aggressive malignancy associated with rapid progression and poor survival.Emerging evidence supports neoadjuvant BRAF and MEK inhibition as an effective strategy in selected patients with BRAF V600E-mutated ATC, improving resectability and short-term outcomes. Case Presentation:A 63-year-old man with prior papillary thyroid carcinoma presented with a rapidly enlarging, initially unresectable 15-cm anaplastic thyroid mass causing airway compromise.Initial BRAF V600E immunohistochemistry was negative, and empiric cytotoxic chemotherapy and immunotherapy were initiated while awaiting molecular testing.Subsequent next-generation sequencing identified a BRAF V600E mutation, prompting transition to neoadjuvant dabrafenib J o u r n a l P r e -p r o o f and trametinib.After five months of therapy, the tumor demonstrated significant radiographic regression to 5 cm, enabling successful thyroidectomy with lymph node dissection.The clinical course was complicated by treatment-related cardiomyopathy, subsequent metastatic disease, and airway obstruction requiring tracheostomy.Discussion:This case illustrates real-world challenges in ATC management, including delays in molecular diagnosis, limitations of immunohistochemistry, complexities of treatment sequencing, and toxicities associated with highly effective targeted therapies.It underscores the importance of protocolized strategies for rapid assessment, molecular classification, and initiation of targeted therapy in suspected ATC. Conclusion:Neoadjuvant BRAF/MEK inhibition can convert unresectable ATC into surgically manageable disease.Given reported response rates of approximately 56% in BRAF V600E-mutated ATC, early comprehensive molecular testing, multidisciplinary coordination and close monitoring are critical to optimizing outcomes in this aggressive malignancy.
Kuruppu et al. (Sun,) studied this question.