Leptomeningeal metastases

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

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 intracerebral 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 a widespread metastatic disease, likely by haematogenous 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, but 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
• 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).  With treatment, that time may be extended up 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.

Differential diagnosis

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