Solid Tumor Leptomeningeal Disease - Clinical Features, Diagnosis, and Treatment

Introduction:

Solid tumor leptomeningeal disease is the third most common metastatic cancer involving the brain and spinal cord. Leptomeningeal metastases are a rare cancer of the cerebrospinal fluid and the membrane protecting the brain and spinal cord. They are metastatic cancers from solid tumors like breast cancer, lung cancer, and melanoma. Patients with leptomeningeal disease show various signs and symptoms as it involves many areas in the craniospinal axis.

What Is a Solid Tumor?

A solid tumor is a tumor that does not contain cysts or liquid inside the tumors. It only contains an abnormal mass of tissues. Solid tumors can be both benign and malignant. Carcinomas, sarcomas, and lymphomas are solid tumors. A solid tumor can originate in bones, muscles, or any organs. Some examples of solid tumors are Ewing sarcoma, osteosarcoma, and adrenocortical carcinoma.

What Is Solid Tumor Leptomeningeal Disease?

Leptomeningeal disease, leptomeningeal metastasis, or carcinomatous meningitis involves cancer in the cerebrospinal fluid (CSF) and leptomeninges (inner two meninges covering the cerebrospinal fluid- arachnoid mater and pia mater) by the spread of cancer from different parts of the body. The leptomeningeal disease is seen in the membranes surrounding the brain and the spinal cord. It is a rare disease. The leptomeningeal disease is different from metastatic brain tumors. Metastatic brain tumors are those cancers that have spread from other organs to the brain tissue. In contrast, leptomeningeal disease is cancer that spreads directly to the cerebrospinal fluid (CSF) or the membrane surrounding the brain and spinal cord, that is, the leptomeninges.

What Are the Causes of Solid Tumor Leptomeningeal Diseases?

In adults, the cause of leptomeningeal disease is due to solid tumors that are metastasized from different cancer sites present in the body like from breast cancer (12 to 34 %), lung cancer (10 to 26 %), melanoma (17 to 25 %), gastrointestinal tract cancer (4 to 14 %), and adenocarcinoma (1 to 7 %).

What Are the Clinical Features of Solid Tumor Leptomeningeal Disease?

Most patients with leptomeningeal disease from a solid tumor from other body parts have a poor prognosis. Leptomeningeal diseases show a variety of signs and symptoms, which are mainly neurological. They include -

• Dizziness.

• Cervical discomfort.

• Cranial nerve paralysis results in hearing loss, tinnitus (ringing sound in the ear), blurred vision, or diplopia (double vision).

• Headache.

• Nausea and vomiting.

• Rapid weight loss.

• Speech disorder.

• Excessive sleeping.

• Personality and behavioral change.

• Euphoria.

• Memory loss.

• Dullness or weakness.

• Reduced response.

• Seizures.

• Facial numbness.

How Is Solid Tumor Leptomeningeal Disease Diagnosed?

The following diagnostic methods confirm the leptomeningeal disease -

• Lumbar Puncture - In a lumbar puncture, a needle is inserted into the lower back between two lumbar bones to aspirate a sample of cerebrospinal fluid (CSF). Then the CSF is cytologically examined. If CSF cytology shows a positive result, that is, there is a presence of elevated protein, it confirms the leptomeningeal disease. There will also be an increase in CSF pressure.

• Magnetic Resonance Imaging (MRI) - Using a large magnetic field, radiation, and computer technology, a three-dimensional image of the brain and entire spinal cord is produced to confirm the leptomeningeal disease. Gadolinium-enhanced multiplanar MRI is the diagnostic imaging technique over computed tomography (CT) because of its specificity and sensitivity. In gadolinium-enhanced multiplanar MRI, there will be a leptomeningeal enhancement which can show nerve root thickening, spinal cord enlargement, epidural compression, and presence of nodules in subarachnoid (area containing CSF and blood vessels) and intraparenchymal (area containing neurons and glial cells) spaces.

What Are the Differential Diagnosis of Solid Tumor Leptomeningeal Disease?

As leptomeningeal disease show various neurological symptoms, it can be confused with alternative diagnosis caused by any infectious diseases, autoimmune disorders, vascular disorder, due to traumatic etiologies, or due to side effect from chemotherapy and radiation therapy in cancer treatment. The differential diagnosis includes -

• Paraneoplastic syndromes (a group of disorders caused by the abnormal immune system due to cancer).

• Toxic metabolic encephalopathy (altered metabolic disturbances caused by acute cerebral dysfunction).

• Brain abscess.

• Brain metastasis.

• Spinal cord compression.

• Meningitis and encephalitis (inflammation of the brain).

• Meningitis is caused by intrathecal or CSF chemotherapy.

• Stroke.

• Steroid myopathy (a neuromuscular disorder that causes muscle weakness because of the prolonged use of a glucocorticoid, which is a corticosteroid).

• Sarcoidosis (collection of inflammatory cells or granulomas in any part of the body, commonly in lungs and lymph nodes).

What Is the Treatment for Solid Tumor Leptomeningeal Disease?

Most leptomeningeal metastasis has poor prognoses. If the leptomeningeal disease is diagnosed early, the treatment prognosis is better than the advanced stage of leptomeningeal metastasis. They cannot be cured entirely. Treatments are done to reduce the signs and symptoms and decrease the pain, improving the quality of life.

• Surgical Oncology - Surgical therapy is usually not performed in solid tumor leptomeningeal diseases as it cannot cure cancer in the leptomeninges. A ventriculoperitoneal shunt (surgery done to treat excess CSF in the cavities present in the brain) is used to reduce the symptoms, and intraventricular catheters (a catheter is inserted into the left ventricular cavity present in the brain where the CSF is present) is used to deliver intrathecal chemotherapy drugs.

• CSF Chemotherapy - It is also called intrathecal chemotherapy. In intrathecal chemotherapy, a high dosage of anti-cancer drugs is injected into the cerebrospinal space between the tissues that protect the brain and spinal cord.

• Systemic Chemotherapy - High dosages of chemotherapeutic drugs are administered directly into the veins for the quick action of the drug.

• Site-Specific Chemotherapy - The drug will be delivered in site-specific chemotherapy on a specific targeted site.

• Anti-Epidermal Growth Factor Receptor (EGFR) Tyrosine Kinase Inhibitors - Use of Erlotinib and Gefitinib for lung cancer metastases, Trastuzumab in breast cancer metastases, Ipilimumab and Vemurafenib in case of melanoma.

• Involved Field Radiation Therapy (IFRT) - In involved field radiation therapy, the radiation will be delivered to the area or field that is affected or involved with cancer. It can reduce the symptoms caused by cancer.

Conclusion:

Leptomeningeal diseases are often undiagnosed. Only five percent of cases of people with metastatic cancer are diagnosed. Treatment during the early stages of leptomeningeal disease has a better prognosis than the advanced stages. They are usually metastasized from solid tumors in the breast, lungs, gastrointestinal tract, or other unknown sites.