Key Points
Question Can an artificial intelligence–assisted approach integrated into the routine molecular profiling workflow differentiate lung squamous cell carcinoma (SCC) from metastases of other origins?
Findings In this cross-sectional study of 3958 cases submitted as lung SCC for molecular profiling, 123 (3.1%) were confirmed as metastases of other origins, including cutaneous SCC, urothelial carcinoma, head and neck SCC, and thymic carcinoma.
Meaning These findings suggest the importance of an artificial intelligence–assisted approach to distinguishing tissues of origin in patients with presumed primary lung SCC, thus avoiding misdiagnosis and associated impacts on prognosis and therapy selection.