BRAF V600E-mutant squamous cell carcinoma of the lung in patients with a history of papillary thyroid carcinoma: A three-case series.

There is limited data on BRAF V600E-mutant squamous cell carcinoma (SCC). We report three cases of SCC of the lung with a history of resected papillary thyroid carcinoma (PTC), showing p40 positivity, TTF-1 negativity, and PAX8 expression. While treated as lung SCC, metastatic thyroid carcinoma was unconfirmed due to absence of PTC recurrence, clinicopathologic features consistent with primary lung origin, and unavailable archival PTC pathology. BRAF inhibitors yielded only transient responses, and outcomes were poor. These cases underscore the diagnostic and therapeutic value of multigene testing in SCC, highlighting the need to integrate detailed clinical history into precision oncology strategies.