Leptomeningeal Carcinomatosis

Background: Leptomeningeal carcinomatosis (LC) is a serious complication of cancer that carries substantial rates of morbidity and mortality. It may occur at any stage in the neoplastic disease, either as the presenting sign or as a late complication, though it is associated frequently with relapse of cancer elsewhere in the body.

First recognized by Eberth in 1870, LC remains underdiagnosed even today. Nevertheless, it has been recognized more frequently in the last 3 decades than before because of improved diagnostic tools, therapy, and awareness.

LC occurs with invasion to and subsequent proliferation of neoplastic cells in the subarachnoid space. Malignancies of diverse origins may spread to this space, which is bound by the leptomeninges. Spread of hematologic cancers to this space and direct CSF seeding of intraparenchymal intraaxial CNS tumors are also well recognized.

The leptomeninges consist of the arachnoid and the pia mater; the space between the 2 contains the CSF. When tumor cells enter the CSF (either by direct extension, as in primary brain tumors, or by hematogenous dissemination, as in leukemia), they are transported throughout the nervous system by CSF flow, causing either multifocal or diffuse infiltration of the leptomeninges in a sheetlike fashion along the surface of the brain and spinal cord. This multifocal seeding of the leptomeninges by malignant cells is called LC if the primary is a solid tumor, and lymphomatous meningitis or leukemic meningitis if the primary is not a solid tumor.

Lymphomatous meningitis or leukemic meningitis is somewhat of a misnomer, as meningitis implies an inflammatory response that may or may not be present. It is not a single entity pathologically; it can occur concurrently with CNS invasion or wide dissemination in the intraventricular spaces, or in association with CNS metastases, with the clinical picture differing somewhat in each case.


Pathophysiology: Metastatic seeding of the leptomeninges may be explained by the following 5 postulated mechanisms: (1) hematogenous spread to choroid plexus and then to leptomeninges, (2) primary hematogenous metastases through the leptomeningeal vessels, (3) metastasis via the Batson venous plexus, (4) retrograde dissemination along perineural lymphatics and sheaths, and (5) centripetal extension along perivascular and perineural lymphatics from axial lymphatic nodes and vessels through the intervertebral and possibly form the cranial foramina to the leptomeninges.

Signs and symptoms usually are attributable to obstruction of CSF flow that leads to increased intracranial pressure (ICP) or hydrocephalus, local tumor infiltration in the brain or spinal cord that causes cranial-nerve palsies or radiculopathies, alterations in the metabolism of nervous tissue that causes seizures, and encephalopathy or focal deficits or occlusion of blood vessels as they cross the subarachnoid that lead to infarcts.



Mortality/Morbidity: The median survival is 7 months for patients with LCs from breast cancers, 4 months for patients with LCs from small-cell lung carcinomas, and 3.6 months for patients LCs from melanomas.



Lab Studies:

Imaging Studies:

Other Tests:


Histologic Findings: Leptomeningeal biopsy may be necessary if the patient has no evidence of a primary tumor. The findings can be diagnostic if results of all other tests are negative. Macroscopic pathology shows diffuse fibrotic thickening of the brain and spinal cord, as well as layering of the nerve roots with tumor tissue. Microscopic examination shows local fibrosis with tumor cells covering the blood vessels and nerves, either as a single layer or as aggregates.

Staging: Staging varies by primary cancer, but metastatic disease is stage IV by definition.

Medical Care: Treatment goals include improvement or stabilization of the patient's neurologic status and prolongation of survival. Patients most likely to benefit from therapy are those with indolent systemic cancers that are likely to respond to therapy and those with minimal or absent systemic disease and no fixed neurologic deficits. Some clinicians are hesitant to even treat LC, given the short duration of survival and risk of neurotoxicity, but a high index of suspicion and prompt treatment can prevent serious and irreversible neurologic damage.

Surgical Care: