Leptomeningeal metastases

Leptomeningeal metastases, also known as carcinomatous meningitis and meningeal carcinomatosis, refers to the spread of malignant cells through the CSF space. These cells can originate from primary CNS tumors (e.g. in the form of drop metastases), as well as from distant tumors that have metastasized via hematogenous spread.

This article has a focus on subarachnoid space involvement. Refer to intradural extramedullary metastases for a discussion of leptomeningeal metastases in the spine. For other intracranial metastatic locations, please refer to the main article on intracranial metastases. 

Epidemiology

The demographics follow those of the underlying malignancy. Meningeal metastases were found in 8% of patients with systemic cancer in cadaveric studies ²².

Clinical presentation

Clinical presentation is varied, but most commonly includes a headache, spine or radicular limb pain or sensory abnormalities, nausea and vomiting, and focal neurological deficits ³. Meningism is only present in a minority of patients (13% ³).

Pathology

The primary intracranial malignancies that may cause metastases to the subarachnoid space are:

• glioblastoma (GBM) and anaplastic astrocytoma
• medulloblastoma
• sPNET
• ependymoma
• germinoma
• choroid plexus carcinoma
• pineoblastoma/pineocytoma ⁵

The vast majority of leptomeningeal metastases occur in the context of widespread metastatic disease, likely by hematogenous spread. Over 50% of cases have concurrent brain (parenchymal) metastases ¹³.  The most common primary sites are: 

• breast cancer (particularly infiltrating lobular carcinoma)
• lung cancer
• melanoma 
• gastrointestinal (gastric carcinoma ^4,5, colorectal cancer ⁸)
• hematological: lymphoma/leukemia: may be called leptomeningeal lymphomatosis

Less common reported primary sites include:

• pancreatic carcinoma ⁶
• ovarian cancer ⁷
• renal cell cancer ⁹
• carcinoma of the uterine cervix ¹⁰
• adrenal cortical carcinoma ¹¹
• esophageal cancer ¹²
• urinary bladder adenocarcinoma ¹⁴
• prostate cancer ¹⁵
• malignant pleural mesothelioma ¹⁶
• testicular cancer ¹⁷
• intradural malignant peripheral nerve sheath tumor (MPNST) ¹⁸
• anaplastic thyroid carcinoma ¹⁹
• transitional cell carcinoma of the bladder ²⁰
• cholangiocarcinoma (extremely rare) ²¹

Radiographic features

MRI

• T1: usually normal
• T1 C+ (Gd): leptomeningeal enhancement is the primary mode of diagnosis, often scattered over the brain in a 'sugar coated' manner
• T2: usually normal; may show hyperintensity 
• FLAIR
  • abnormally elevated signal within sulci ²
  • can be performed both non-contrast and post-contrast but is slightly less specific if performed post-contrast ¹

Treatment and prognosis

Leptomeningeal metastases have a poor prognosis with patients usually succumbing within a few months (median overall survival 2.4 months ¹³).  Treatment may extend survival to 6-10 months ^2,3. Treatment can consist of ³:

• intrathecal chemotherapy
• radiotherapy

Resection is usually inappropriate due to the presence of widespread metastases at the time of diagnosis.

Differential diagnosis

• leptomeningeal inflammation: leptomeningitis
• slow flow in vessels
• propofol, high oxygen tension, and subarachnoid blood (hemorrhage) can all elevate sulcal FLAIR signal