Primary CNS Lymphoma in AIDS

Introduction:

Primary central nervous system lymphoma (PCNSL) is a rare cerebral mass lesion in acquired immunodeficiency syndrome (AIDS). It is a type of non-Hodgkin's lymphoma that is diffuse, aggressively confined to the nervous system, and has more than 95 % B-cell origin. Two to 13 percent of AIDS patients eventually develop PCNSL.

What Is Lymphoma?

Lymphoma is a blood cancer that arises from lymphocytes, which cause the proliferation of T-cells, B- cells, and natural killer (NK) cells, subsets of lymphocytes. Lymphocytes are a type of white blood cell that is made in the bone marrow and is found in the blood and lymph tissue (part of the immune system that protects the body from foreign invasion); lymphocytes are of two types t-cell (help kill tumor cells and control immune responses) and b-cell (produces antibodies). Lymphoma is broadly classified into two types, Hodgkin lymphoma, and non-Hodgkin lymphoma. If a characteristic Reed-Sternberg cell (a cancer cell that is large and has multiple nuclei) is present microscopically, it is called Hodgkin lymphoma; if it is not, it is called non-Hodgkin lymphoma.

What Is AIDS?

AIDS is caused by a virus called human immunodeficiency virus (HIV). This virus weakens the immune system of the body; eventually, the patient will develop severe infections and cancers, and this weakness is called acquired immunodeficiency syndrome. The virus stays in the body for life.

What Is the Pathogenesis of Primary CNS Lymphoma in AIDS?

An important etiologic factor for Primary CNS Lymphoma in AIDS is Epstein-Barr virus (EBV) infection, identified in all PCNSL tumors. EBV mRNA identified in PCNSL specimens can discriminate PCNSL from other central nervous system processes. A person with acute Epstein-Barr virus infection has infected B-cells that persist, and T-cells maintain control over these immortalized B-cells by keeping their number small. When HIV-1 destroys T-cells, it will lose T-cell control over B-cell growth. Therefore, in an AIDS person who is immunocompromised, this uncontrolled growth of B cells may acquire features of malignancy. In addition, the EBV genome in infected cells causes malignant transformation by expressing oncogenic activity to latent membrane activity proteins (LMP-1 and 2), EBV nuclear antigen, and small EBV-encoded nuclear RNA (EBERs); in immunocompromised patients, these proliferate into malignant lymphomas.

What Are the Clinical Manifestations of Primary CNS Lymphoma?

The clinical manifestations include:

• It often presents multiple supratentorial lesions (upper part of the brain), although a single lesion can also occur.

• Headache, nausea, and visual loss or double vision due to increased intracranial pressure.

• Hearing loss.

• Seizures.

• Arm or leg weakness.

• Impaired cognitive functions like confusion, lethargy, and memory loss.

• Focal neurologic deficits include hemiparesis (loss of strength on one side of the body), speech and language disorders, and cranial nerve palsies.

What Are the Diagnostic Approaches for Primary CNS Lymphoma in AIDS?

Definitive diagnosis depends on histopathological findings, but brain biopsies have a risk of severe intracranial hemorrhage. Therefore, other diagnostic procedures are done.

• Ophthalmic evaluation should include examining vitreoretinal lymphoma (intraocular lymphoma).

• A cerebrospinal fluid (CSF) examination for lymphomas should be done.

• Flow cytometric immunophenotyping of lymphocytes in the CSF.

• Magnetic resonance imaging (MRI) shows multiple or single lesions with mild to moderate edema, and with contrast material, ring enhancement is seen. Lesions spread to the periventricular and subependymal areas.

• Thallium single-photon emission computed tomography (SPECT) scans show increased accumulation of thallium by lymphoma cells.

• A polymerase chain reaction can detect Epstein Barr virus DNA in cerebrospinal fluid, which is a minimally invasive technique.

• F-18 fluorodeoxyglucose positron emission tomography (PET) imaging shows higher fluorodeoxyglucose uptake by lymphomas.

What Is the Differential Diagnosis of Primary CNS Lymphoma in AIDS?

The differential diagnosis includes:

• Cerebral toxoplasmosis (an infection caused by an intracellular protozoan parasite that causes cerebral abscess).

• Progressive multifocal leukoencephalopathy (a viral infection that targets the brain's white matter, which contains nerve fibers).

• Tuberculoma (firm, spherical masses without blood supply in the brain, which is a manifestation of tuberculosis).

• Cryptococcal abscess, Nocardia, or Candida abscess (fungal brain abscess).

• Syphilitic gummas (it's a rare manifestation of tertiary syphilis).

• Primary or metastatic central nervous system tumors.

• Cerebral vascular disease.

What Is the Treatment of Primary CNS Lymphoma in AIDS?

Treatment includes:

• Radiotherapy: In this therapy, high-energy X-rays are given to kill cancer cells. It is given as whole-brain radiotherapy (WBRT) rather than focal irradiation because of the infiltrative nature of the disease. This is an effective therapy showing clinical improvement and tumor regression, but it can cause damage to healthy brain tissues, affecting memory, learning, problem-solving, and speech abilities. However, the survival rate is only two to five months.

• Chemotherapy: Drugs are used to kill or stop the growth of cancer cells. High-dose methotrexate (HD-MTX)-based chemotherapy is combined with cART therapy. Systemic chemotherapy (drugs are given through mouth or are injected and reach the cancer cells through the bloodstream), intrathecal chemotherapy (drugs are administered into the cerebrospinal fluid), or intraventricular chemotherapy (drugs are placed into the ventricles [fluid-filled cavities] of the brain) can be given.

• Antiviral Therapy: Includes treatment with cART (combined antiretroviral) agents in which at least two drugs from two different classes of drugs are used, such as high-dose zidovudine or ganciclovir. It should be combined with high-dose methotrexate chemotherapy or whole-brain radiotherapy for maximum effect.

What Is the Prognosis of Primary CNS Lymphoma in AIDS?

The prognosis of patients with PCNSL is poor compared to immunocompetent patients. The overall survival rate of these patients is four months, and it is 14 months in immunocompetent patients. After combining the treatments (cART with chemotherapy), there was an improvement in survival, which was similar to that of immunocompetent patients.

Conclusion:

Primary CNS is a common complication of AIDS with poor clinical prognosis; it presents late in the process of disease, and even after treatment, the survival rates are low.