Case report suggests second primary glioblastoma in ALK-positive lung adenocarcinoma patient treated with ensartinib and lorlatinib

In patients with a known diagnosis of lung cancer, a new intracranial space-occupying lesion is most frequently interpreted as a brain metastasis. However, distinguishing it from an independent double primary brain tumor is critical, as treatment strategies and prognoses differ substantially. We report a rare case of primary glioblastoma occurring approximately two years after surgery for anaplastic lymphoma kinase (ALK)-positive lung adenocarcinoma. A 63-year-old female underwent radical resection for stage IA lung adenocarcinoma (ALK-positive) and received adjuvant ensartinib. Two years postoperatively, brain magnetic resonance imaging (MRI) revealed a solitary lesion in the right centrum semiovale, which was clinically misdiagnosed as a brain metastasis. The patient was subsequently treated with lorlatinib combined with stereotactic radiotherapy. Despite these interventions, she developed progressive left-sided limb weakness, and imaging demonstrated continuous lesion progression. Subsequent surgical resection and pathological examination confirmed primary glioblastoma, strongly supporting a diagnosis of metachronous double primary cancers (DPCs). The patient died 10 months after the glioblastoma diagnosis. This case highlights that during long-term follow-up of patients with malignancies, a new intracranial lesions may warrant consideration of a second primary cancer (SPC), particularly when the treatment response is not consistent with the expected biology of the original tumor. Timely pathological confirmation and multidisciplinary review may help reduce diagnostic delay and improve treatment selection.