Leptomeningeal Carcinomatosis

Updated: Nov 27, 2017
  • Author: Michael J Schneck, MD, MBA; Chief Editor: Stephen A Berman, MD, PhD, MBA  more...
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Practice Essentials

Leptomeningeal carcinomatosis (LC) is a rare complication of cancer in which the disease spreads to the membranes (meninges) surrounding the brain and spinal cord. LC occurs in approximately 5% of people with cancer and is usually terminal. If left untreated, median survival is 4-6 weeks; if treated, median survival is 2-3 months. [28]

Signs and symptoms

Meningeal symptoms are the first manifestations in some patients (pain and seizures are the most common presenting complaints) and can include the following:

  • Headaches (usually associated with nausea, vomiting, light-headedness)

  • Gait difficulties from weakness or ataxia

  • Memory problems

  • Incontinence

  • Sensory abnormalities

CNS symptoms are divided into the following 3 anatomic groups:

  • Cerebral involvement: Headache, lethargy, papilledema, behavioral changes, and gait disturbance.

  • Cranial-nerve involvement: Impaired vision, diplopia, hearing loss, and sensory deficits, including vertigo; cranial-nerve palsies commonly involve CN III, IV, VI, VII, and VIII

  • Spinal-root involvement: Nuchal rigidity and neck and back pain, or invasion of the spinal roots.

See Clinical Presentation for more detail.


Diagnosis of LC is made with positive CSF cytologic results, subarachnoid metastases identified on radiologic studies, or a history and physical examination suggestive of LC along with abnormal CSF findings.

Lumbar puncture

  • The standard diagnostic procedure

  • Positive CSF cytology is found on the initial lumbar puncture in 50-70% and in nearly all cases after 3 attempts

  • Increased CSF pressure and elevated CSF protein are also commonly found.

Imaging studies

  • Gadolinium-enhanced multiplanar MRI is the preferred imaging modality over CT because of its sensitivity and specificity

  • MRI findings considered diagnostic of LC include leptomeningeal enhancement of the brain, spinal cord, cauda equina, or subependymal areas, which extend into the sulci of the cerebrum or folia of the cerebellum

  • MRI of the spinal cord can show nerve-root thickening, cord enlargement, intraparenchymal and subarachnoid nodules, or epidural compression

See Workup for more detail.


Leptomeningeal carcinomatosis is incurable and difficult to treat. Treatment goals include improvement or stabilization of the patient's neurologic status, prolongation of survival, and palliation. Most patients require a combination of surgery, radiation, and/or chemotherapy.

The standard therapies are (1) radiation therapy to symptomatic sites and regions where imaging has demonstrated bulk disease and (2) intrathecal chemotherapy. Systemic chemotherapy to further treat the underlying cancer may also be helpful.

Radiation palliates local symptoms, relieves CSF flow obstruction, and treats areas such as nerve-root sleeves, Virchow-Robin spaces, and the interior of bulky lesions that chemotherapy does not reach.

Intrathecal chemotherapy treats subclinical leptomeningeal deposits and tumor cells floating in the CSF, preventing further seeding. [2] Cytarabine (Ara-C), methotrexate (MTX), and thiotepa are 3 agents routinely administered.

Supportive care for patients includes analgesia with opioids, anticonvulsants for seizures, antidepressants, and anxiolytics. Attention problems and somnolence from whole-brain radiation can be treated with psychostimulants or modafinil.

See Treatment and Medication for more detail.



Leptomeningeal carcinomatosis (LC), also termed neoplastic meningitis, 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.

LC occurs with invasion to and subsequent proliferation of neoplastic cells in the subarachnoid space. Intra-axial CNS tumors of diverse origins and hematologic cancers may spread to this space, which is bound by the leptomeninges. Infiltration of the meningeal space may thus occur from drop metastases via spread of the extra-axial space, hematogenous seeding, or local perinueral invasion; perinueral invasion is not infrequently seen in the context of gastric cancer or head and neck cancers.

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 leptomeningeal carcinomatosis if the primary is a solid tumor, and lymphomatous meningitis or leukemic meningitis if the primary is not a solid tumor.

Lymphomatous or leukemic meningitis is somewhat of a misnomer, as meningitis implies an inflammatory response that may or may not be present. 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. 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.



Metastatic seeding of the leptomeninges may be explained by the following 6 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, (5) centripetal extension along perivascular and perineural lymphatics from axial lymphatic nodes and vessels through the intervertebral and possibly from the cranial foramina to the leptomeninges, and (6) direct extension from contiguous tumor deposits. CSF flow then seeds the tumor cells widely, with infiltration greatest at the basilar cisterns and dorsal surface of the spinal cord, particularly the cauda equina.

Signs and symptoms are usually attributable to obstruction of CSF flow by tumor adhesions that leads to one of the following:

  • 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 cause seizures, encephalopathy, or focal deficits

  • Occlusion of blood vessels as they cross the subarachnoid, leading to infarcts




United States

Approximately 1-8% of patients with cancer are diagnosed with LC, and it is present in 19% of those with cancer and neurologic signs and symptoms on autopsy, usually in those with disseminated systemic disease. LC is present in 1-5% of patients with solid tumors, 5-15% of patients with leukemia, and 1-2% of patients with primary brain tumors. LC can be the presenting symptom 5-10% of the time; however, the exact incidence is difficult to determine. Gross inspection at autopsy may miss LC, and microscopic pathologic examination findings may be normal if the seeding is multifocal or if an unaffected area of the CNS is examined.

Adenocarcinomas are the most common tumors to metastasize to the leptomeninges, although any systemic cancer can do so. Small-cell lung cancers spread to the leptomeninges in 9-25% of cases; melanomas, in 23%; and breast cancers, in 5%. However, because of the different relative frequencies of these cancers, most patients with LC have breast cancer. [3]  Lung cancer is the second most common tumor associated with LC.

Uncommon neoplasms, such as embryonal rhabdomyosarcoma and retinoblastoma, also tend to spread to leptomeninges, but sarcomas rarely do. Medulloblastomas are among those tumors that spread to the CSF, as do ependymomas and glioblastomas on occasion. Squamous cell carcinomas of head and neck can spread to the meninges along cranial-nerve paths. Although LC is uncommon in children, it can be seen in those with acute lymphocytic leukemia (ALL) and primary brain tumors, particularly ependymomas, medulloblastomas, and germ-cell tumors.

The incidence of LC increases the longer a patient has the primary cancer; LC is accompanied by other intracranial metastases in 98% of patients with a nonleukemic primary cancer. [4]  LC is becoming more common with increasing survival from systemic cancers. [28]

The central nervous system may be a particular repository for certain cancer subtypes. For example, anaplastic lymphoma kinase (ALK) gene rearrangements represent a NSLC subtype responsive to crizotinib, but the brain is a frequent site of relapse in patients treated with this agent.


The reported median survival is 7 months for patients with LC from breast cancers, 4 months for patients with LC from small-cell lung carcinomas, and 3.6 months for patients with LC from melanomas. However, with new chemotherapeutic regimens longer survival rates have been reported.

Without therapy, most patients survive 4-6 weeks, with death occurring because of progressive neurologic dysfunction.

With therapy, most patients die from the systemic complications of their cancer rather than the neurologic complications of LC.

Fixed focal neurologic deficits (eg, cranial-nerve palsies) generally do not improve, but encephalopathies can improve dramatically with treatment.

Race-, sex-, and age-related demographics

There is no evidence that races are differentially affected.

Men and women are equally affected.

The incidence of most forms of cancer that lead to LC increases with age.