Early hint of mNGS and CNVs, an occult case of leptomeningeal metastasis with rapid cognitive decline

Abstract Background: EGFR-positive non-small cell lung cancer may develop leptomeningeal metastasis during the terminal stage, significantly shortening the survival time of patients. Therefore, early detection and treatment are critical for improving the prognosis of patients with leptomeningeal metastasis. However, heterogeneous clinical manifestations, non-specific imaging, and limited sensitivity of cerebrospinal fluid cytology posed challenges to identifying leptomeningeal metastasis in the early stage of cancer. Case presentation: Here we reported a case of lung adenocarcinoma with EGFR L858R mutation complained of rapid cognitive decline, whose magnetic resonance imaging showed interstitial brain edema. Under the circumstances of negative cerebrospinal fluid cytology, metagenome next-generation sequencing combined with Copy-number variations analysis was applied to analyze the cerebrospinal fluid for information on pathogenic microorganisms and chromosomes’ copy number, which indicated leptomeningeal metastasis and was confirmed in the subsequent cytology. Conclusion: MNGS and CNVs of cerebrospinal fluid should be conducted when cancer patients come with unexplained neurological symptoms. Physicians should promptly distinguish leptomeningeal metastasis and initiate anti-tumor therapy to reduce brain damage and prolong the patient's survival period.