Leptomeningeal metastases (carcinomatous meningitis) are a rare but frequently devastating complication of advanced cancer. Patients can present with a broad range of signs and symptoms due to involvement of multiple areas of the craniospinal axis. Diagnosis often requires a high index of suspicion and is confirmed by neuroimaging and cerebrospinal fluid analysis.
The pathophysiology, clinical manifestations, and diagnosis of leptomeningeal metastases (LM) from solid tumors will be reviewed here. The treatment of LM and leptomeningeal involvement in hematologic malignancies, especially large cell lymphomas and acute leukemias, is discussed separately. (See "Treatment of leptomeningeal metastases (carcinomatous meningitis)" and "Clinical presentation and diagnosis of secondary central nervous system lymphoma", section on 'Leptomeningeal metastasis' and "Involvement of the central nervous system with acute myeloid leukemia".)
Leptomeningeal metastases (LM) are diagnosed in approximately 5 percent of patients with metastatic cancer [1-3], but undiagnosed or asymptomatic involvement is more common [4-10]. At autopsy, the frequency of LM averages 20 percent and is much higher with some tumor types [2,11,12]. Co-existing brain metastases are present in 50 to 80 percent of patients in modern series [13-17].
The most common solid tumors giving rise to LM are breast cancer (12 to 35 percent), lung cancer (10 to 26 percent), melanoma (5 to 25 percent), gastrointestinal malignancies (4 to 14 percent), and cancers of unknown primary (1 to 7 percent) [1-3,13]. In women with breast cancer, infiltrating lobular carcinoma has a particular predilection to metastasize to the leptomeninges [18-20]. Primary brain tumors, including low- and high-grade astrocytomas, medulloblastomas, ependymomas, pineoblastomas, and oligodendrogliomas, can infiltrate the leptomeninges or disseminate along cerebrospinal fluid (CSF) pathways [21,22].
The development of LM may also be influenced by treatment: