Diagnosis of leptomeningeal metastasis with concurrent tuberculous meningitis assisted by cerebrospinal fluid metagenomic next-generation sequencing combined with copy number variation analysis: a case report

Concurrent tuberculous meningitis (TBM) and leptomeningeal metastasis from lung adenocarcinoma (LUAD-LM) are exceptionally rare and pose significant diagnostic challenges. Overlapping clinical and neuroimaging features often lead to misdiagnosis or diagnostic delay. Here, we report a 69-year-old woman with a prior history of bilateral invasive lung adenocarcinoma lesions who had undergone surgical resection. Although genetic testing identified an epidermal growth factor receptor (EGFR) mutation, targeted therapy was not initiated at that time. Two weeks before admission, the patient developed progressive dizziness and headache, which rapidly evolved into cognitive impairment and intractable projectile vomiting. Contrast-enhanced magnetic resonance imaging (MRI) revealed hydrocephalus and diffuse leptomeningeal enhancement. Cerebrospinal fluid (CSF) cytology demonstrated atypical cells, initially suggesting LUAD-LM. However, metagenomic next-generation sequencing combined with copy number variation analysis (mNGS-CNV) of the CSF detected both multiple chromosomal copy number alterations and Mycobacterium tuberculosis. These findings supported the concurrent diagnoses of LUAD-LM and TBM. The patient was treated with EGFR-targeted therapy in combination with a four-drug anti-tuberculosis regimen. At one-year follow-up, her condition remained stable. This case highlights the potential value of CSF mNGS-CNV in recognizing concurrent infectious and neoplastic meningeal diseases from a single CSF specimen.