Direct extension from primary tumour to nodes: Can molecular profiling solve the dilemma?

• Extranodal extension determines the prognosis and post-operative treatment of head and neck cancer patients. • Direct tumour invasion to nodes, metastasis with extranodal extension, & capsular invasion can present similar histology. • Molecular profiling, particularly the analysis of tumour heterogeneity, hold a great promise in solving the dilemma. • Combining molecular analysis with clinical & histological data could enhance diagnostic accuracy of these three scenarios.