CNS lymphoma is a rare neoplasm affecting the tissues of the brain and spinal cord, the back wall of the eye. The clinical picture depends on the localization of the process, includes general cerebral symptoms, paresis, coordination disorders, visual disorders. Diagnosis is carried out using neuroimaging methods, analysis of cerebrospinal fluid, histological examination of the biopsy. Chemotherapy, brain irradiation and their combination are actively used in the treatment. With a single tumor, neurosurgical intervention is possible.
ICD 10
C81 C82 C83
General information
CNS lymphoma was first isolated into a separate nosology in 1974 . It refers to malignant neoplasms, accounts for about 4% of tumors of the central organs of the nervous system. According to statistics, the prevalence of pathology is at the level of 0.5-0.75 cases per 100 thousand patients. Recently, there has been an increase in morbidity associated with an increase in immunosuppressive conditions. The risk of CNS lymphoma in AIDS patients is 4-6%, with congenital immunodeficiency — 4%. The average age of patients among immunocompetent individuals is 62 years. The median age in patients with congenital immunodeficiency is 10 years. Gender predisposition is not observed.
Causes
The etiology of lymphomas arising in the central nervous system has not been determined. In immunocompromised patients, traces of Epstein-Barr virus and herpes type VI, also characteristic of lymphoid tumors of other localization, are detected. However, the role of these viruses in the occurrence of the disease has not been proven. A further search is underway for triggers that cause the appearance of pathological, actively dividing lymphocytes. Among the established risk factors , the following immunosuppressive conditions are distinguished:
- Hereditary immunodeficiency: Louis-Bar syndrome, Wiskott–Aldrich syndrome, selective Ig A deficiency and others.
- HIV infection: the T-cell component of immunity is affected in patients.
- Autoimmune pathology: systemic lupus erythematosus, rheumatoid arthritis.
- Conditions after transplantation: immunosuppression is created medicinally to prevent the transplant rejection reaction.
Pathogenesis
Most CNS lymphomas are extranodular, primarily developing in cerebral tissues without prior formation in the lymph node. In order to explain their occurrence in nervous tissue that does not have lymphoid formations, 2 hypotheses were put forward. The first involves the penetration of lymphocytes into brain structures under the influence of certain triggers, which can serve as viral infections. Getting into the nervous structures, lymphocytes change their properties and give rise to a pathological cell clone. The second hypothesis assumes the formation of a tumor lymphocytic clone in the distance, with subsequent migration to the central nervous system.
90% of CNS lymphomas consist of transformed B-lymphocytes. In most cases, the precursors of tumor cells are B-lymphocytes of the germinogenic center, less often — post-germinogenic activated lymphocytes. In some cases, pathological lymphocytes permeate the walls of cerebral vessels, giving a picture of vasculitis.
Classification
A unified classification of CNS lymphomas has not been developed. In modern clinical neuro-oncology, neoplasms are divided morphologically, according to the nature of their distribution and location.
According to the immunophenotype, the vast majority of formations are non-Hodgkin’s lymphomas. Hodgkin’s lymphoma, lymphoblastic and T-cell lymphomas are observed much less frequently.
According to the prevalence of the process in the central nervous system, formations can be single, infiltrative and multiple.
Cerebral and spinal lymphomas are distinguished by localization. The former make up the vast majority and are classified into hemispheric, leptomeningeal, and corpus callosum lymphomas. Spinal cord lesions are less than 1%.
Symptoms
The clinical manifestations are nonspecific cerebral and focal symptoms. In most patients, the disease manifests signs of central nervous system damage in the form of headaches, neuropsychiatric changes, drowsiness and disorders of consciousness. Possible cognitive impairment, discoordination. Episyndrome occurs in 10% of cases. A third of patients have symptoms of intracranial hypertension: intense cephalgia, nausea, a feeling of “heaviness” in the eyes. The location of foci in the posterior parts of the eyeball is accompanied by visual dysfunction, exophthalmos, ophthalmoplegia.
The cerebrospinal form is manifested by muscle weakness, loss of motor function, followed by the addition of sensory disturbances and pain syndrome. Leptomeningeal lesion occurs with sensorimotor disorders of the facial region, radicular syndrome with localization in the lumbosacral region. There is lower paraparesis, urination disorder, hydrocephalus. Typical for lymphomas of other localization, body temperature rises, sweating, and weight loss are not observed.
Complications
Being a volumetric formation, CNS lymphoma, as it grows, leads to a mass effect with an increase in liquor pressure and hydrocephalus. The latter is dangerous by dislocation of the brain with infringement of its tissues. Localized along the course of the cerebral vessels and sprouting them, the tumor can lead to a violation of the integrity of the vascular wall and hemorrhagic stroke. Possible dissemination of tumor cells with the formation of secondary foci in the central nervous system.
Diagnostics
The identification of general cerebral symptoms and focal prolapses in the neurological status allows the neurologist to suspect a neoplasm of the central nervous system and its presumed localization. Confirmation of the diagnosis is possible based on the results of neuroimaging examinations, morphological examination is required to verify the tumor. The list of necessary examinations for suspected lymphoma includes:
- Neuroimaging. Cerebral CT or MRI allows you to assess the size and location of the neoplasm, the degree of dislocation of the median structures. In favor of CNS lymphoma, the multifocality of the process, ring-shaped contrast, significant perifocal edema speaks.
- Ophthalmological examination. It is necessary for patients with visual disorders. It detects exophthalmos, increased intraocular pressure, congestion during ophthalmoscopy.
- CT of the whole body. It is necessary to search for a primary focus located outside the central nervous system. Its detection indicates the secondary nature of cerebral lymphoma.
- Examination of cerebrospinal fluid. The material is taken by spinal puncture. In half of the cases, an increase in protein, pleocytosis with a large number of reactive lymphocytes, and the presence of tumor cell elements are detected in the cerebrospinal fluid.
- Histological examination. Tumor tissue sampling is preferably performed by stereotactic biopsy, which minimizes the risk of dissemination. Under microscopy, a typical cytological picture is represented by a cluster of pathologically transformed lymphoid cells with light nuclei surrounded by mature lymphocytes. Immunophenotyping of CNS lymphoma makes it possible to establish its histological type, the degree of cell maturity, and predict the development of the disease.
Differential diagnosis
It is necessary to differentiate CNS lymphoma with other volumetric formations:
- glioblastoma;
- abscess;
- cerebral metastases.
Differentiation is carried out according to the characteristic features of MRI. For glioblastoma, necrotic foci of central localization are typical, absent in lymphoma. In order to exclude the metastatic nature of the neoplasm, the primary tumor of extraneural localization is searched. A cerebral abscess is characterized by a clear contour. CNS lymphoma should also be distinguished from neurosarcoidosis, leukoencephalopathy, demyelinating diseases, in favor of which the diffuse-multi-focal nature of the lesion will testify.
Treatment
Conservative therapy
Lymphomas are sensitive to chemotherapy and radiation. Current treatment recommendations are based on several prospective studies, however, due to the rare occurrence of tumors, the latter have a small sample size. Therapy is carried out individually in accordance with the nature of the lesion, the age of the patient, the premorbid background. The most popular methods include:
- Monotherapy with cytostatics. It is carried out with one cytostatic drug. It leads to complete remission in 30-40% of patients. Side effects are renal, hepatic insufficiency, hematological disorders, pneumonitis.
- Combined chemotherapy. The use of a combination of two cytostatics capable of penetrating the blood-brain barrier gives the best response to therapy. The disadvantages of the method include its high toxicity.
- Radiation therapy. Fractional irradiation of the brain in most patients leads to rapid remission. However, the early occurrence of relapses is characteristic. The average life expectancy of patients is 1-1.5 years.
- Combination therapy. Treatment includes chemo and radiotherapy. This combination makes it possible to prolong the patient’s life, but has high neurotoxicity, leading to leukoencephalopathy with cortical atrophy. In such cases, severe cognitive impairment, gait disorders, urinary incontinence are observed, and there is a need for patient care.
Surgical treatment
Resection can improve progression-free survival in patients with single lesions. Diffuse germination of CNS lymphoma into surrounding tissues, its localization in deep cerebral structures makes neurosurgical treatment ineffective. Surgical intervention can contribute to the spread of tumor lymphocytes with the occurrence of multiple relapses. The median survival of such patients after surgical treatment without the use of other methods does not exceed 4 months.
Experimental treatment
It is possible to use immunotherapy with checkpoint inhibitors. In modern neuro-oncology, the use of drugs that interfere with the transmission of B-cell receptor signals and thus affect the proliferation of lymphoma cells is considered, Drugs of the first group have been associated with significant toxicity in some patients. The means that replaced them are less toxic, but also less active. Currently, a search is underway for ways to increase their activity.
Prognosis and prevention
CNS lymphoma is a highly malignant neoplasm with an average survival rate of weeks to months if treatment is only symptomatic. With antitumor therapy, the 5-year survival rate is 31%. Elderly age, poor clinical condition, elevated protein levels in the cerebrospinal fluid, involvement of deep cerebral divisions, spinal lesion are associated with a more unfavorable prognosis. Prevention is reduced to the prevention and timely treatment of diseases leading to immunodeficiency.
