Wide and cystic brain metastases reveal RET-rearranged non–small-cell lung cancers

CONTEXT Key Objective Morphologic features characterize brain metastases from EGFR- and ALK-positive non–small-cell lung cancer (NSCLC). No evidence is available concerning RET-rearranged NSCLC, an entity of emerging interest given the current development of selective RET inhibitors, also active against CNS disease. Knowledge Generated Here we report the similar clinical histories of two patients with RET-positive NSCLC, whose diagnoses were obtained on pathologic and molecular analyses performed on wide, cystic, and symptomatic brain metastases with a peculiar neuroradiologic presentation. Relevance A characteristic behavior of CNS lesions from RET-rearranged NSCLC was recognized. The current or upcoming availability of selective, CNS-active RET inhibitors strongly reinforces the importance of wide molecular screening of CNS lung metastases, even more so in the presence of the reported neuroradiologic and pathologic features of brain lesions.