primary central nervous system lymphoma
Introduction
Introduction to primary central nervous system lymphoma Primary central nervous system lymphoma (PCNSL) is a lymphoma that occurs only in the brain and spinal cord without infiltration of other lymph nodes or lymphoid tissues throughout the body. basic knowledge The proportion of illness: this disease is rare, the incidence rate is about 0.001%-0.002% Susceptible people: no special people Mode of infection: non-infectious Complications: central nervous system leukemia
Cause
The cause of primary central nervous system lymphoma
(1) Causes of the disease
The etiology of primary central nervous system lymphoma is still unclear, and the following four theories are more important:
Malignant lymphocytosis (25%):
The malignant clonal proliferation of orthostatic lymphocytes in the central nervous system is caused, but, so far, the study has not found that the tumor phenotypes of primary central nervous system lymphoma and secondary central nervous system lymphoma are different. Therefore, there is no exact basis for this theory.
Virus infection (35%):
In PCNSL patients with impaired immune system function, the theory of viral infection is more important, mainly EBV, and herpes virus. In many immunocompromised primary central nervous system lymphoma patients, higher EBV can be found. The DNA titer, EBV is currently thought to cause B lymphocyte proliferation, and in the investigation of epidemics, the occurrence of EBV has a great correlation with Burkitt lymphoma.
Tumor factors (20%):
Tumor cells are derived from lymphocytes in the systemic system, and such lymphocytes are centrally mediated by the expression of adhesion molecules on specific cell surfaces, resulting in this central nervous system, which is abnormally propagated in the central nervous system, most of which are central. The B cell activation markers of nervous system lymphoma cells such as B5, Blast2, and BB1 are negative, which is exactly opposite to systemic lymphoma cells, and, as mentioned above, primary and secondary central nervous system. The cell phenotype of lymphoma is not different, so this theory has been taken seriously, but it needs further confirmation.
Central System Asylum (20%):
All theories suggest that the primary central nervous system lymphoma is only present in the central nervous system, and no systemic metastasis is due to the "central system shelter" effect produced by the blood-cerebrospinal fluid barrier of the central nervous system. It is well known that blood-cerebrospinal fluid The barrier is formed by the tight, continuous attachment of capillary endothelial cells, which limits the entry and exit of macromolecular substances, and it also limits the contact of foreign antigens of the central nervous system with cellular and humoral immune systems.
(two) pathogenesis
In 1920, Murphy and Sturm experiments demonstrated that murine sarcoma can survive in the rat brain, while the autologous transplantation of the mouse spleen and the transplantation of murine sarcoma can inhibit the growth of murine sarcoma, indicating that the immune cells can be exposed to foreign antigens. That is, it can destroy allogeneic transplantation. At the same time, some lentiviruses can weaken the immune response after entering the central nervous system. This is also evidenced by some scholars that the blood-cerebrospinal fluid barrier can also restrict immune effector cells from entering the central nervous system. The nervous system works, although there are few studies in this area, but in some diseases, such as experimental allergic encephalitis and multiple sclerosis can be proved, so once the malignant lymphocytes enter After the central system, it can spread in the subarachnoid space without significantly affecting the entire immune system.
Some scholars have suggested that EBV infects certain B lymphocytes and causes clonal proliferation. In immunocompetent people, it will be restricted by immune mechanism, mainly due to the limitation of cellular immune system. Patients with impaired immune function have different degrees of T cells. Abnormalities (damaged or reduced in number), which causes EBV to cause B cells to proliferate indefinitely, and at the same time, impaired central nervous system function aggravates disease progression in immunodeficient PCNSL patients, in the study of the etiology and pathogenesis of PCNSL The EBV virus theory of patients with immune system defects has been more affirmed, and the various theories of patients with normal immune function have their imperfect aspects, which need further research and discussion.
Prevention
Primary central nervous system lymphoma prevention
1. Minimize infection and avoid exposure to radiation and other harmful substances, especially drugs that have an inhibitory effect on immune function.
2, appropriate exercise, enhance physical fitness, improve their disease resistance.
3, mainly for the prevention of various factors that may lead to primary central nervous system lymphoma. It is currently believed that the loss of normal immune surveillance function, the tumorigenic effect of immunosuppressants, the activity of latent viruses and the long-term application of certain physical (such as radiation), chemical (such as anti-epileptic drugs, adrenocortical hormone) substances, Lead to the proliferation of lymphatic network, and eventually the primary central nervous system lymphoma. Therefore, pay attention to personal and environmental hygiene, avoid drug abuse, and pay attention to personal protection when working in a harmful environment.
Complication
Primary central nervous system lymphoma complications Complications of central nervous system leukemia
This tumor can be associated with neurofibromatosis. Complications such as vision, visual field, olfactory or hearing impairment and limb dyskinesia can occur, so it is necessary to differentiate from intracranial infections and intracranial space-occupying diseases. In severe cases, vision loss can occur, which is related to the primary site of the tumor. Most of the symptoms of the optic canal appear early and severe. Once the disease is diagnosed, it needs active treatment.
Symptom
Primary central nervous system lymphoma symptoms Common symptoms Sensory disturbances, fatigue, drowsiness, forgetfulness, immunodeficiency, auditory hallucinations, increased intracranial pressure
The clinical manifestations of primary central nervous system lymphoma are very inconsistent, which is mainly related to the tumor growth site and extent. Most patients have symptoms and signs of intracerebral lesions, because 50% of PCNSL lesions are located in the frontal lobe and are involved. Multi-leaf, patients with multiple personality changes, headache, fatigue, lethargy, seizures than glioma, meningioma and intracerebral metastases, the incidence of this may be in the diagnosis of PCNSL, the lesions are less involved and prone to occur In addition to the cerebral cortex area of epilepsy, in addition, some patients manifested as hallucinations, hallucinations, auditory hallucinations and other mental symptoms, can also be expressed as forgetfulness, mental decline, the duration of symptoms for weeks to months, which is related to PCNSL Poor prognosis.
The clinical manifestations of immunodeficiency patients are different from those with normal immune function. For example, AIDS patients have more mental and intellectual changes, multiple systemic defects, and other diseases such as viral encephalitis and toxoplasmosis. Sexual multilobular white matter and so on.
It is currently believed that in many PCNSL patients diagnosed, PCNSL has spread in the central nervous system, and about 25% of patients with normal immune function and 50% of immunodeficient patients have been diagnosed with primary central lymphoma. Multi-leaf infiltration.
The multi-leaf dissemination of PCNSL is also manifested in the ocular infiltration of lymphoma. In systemic systemic lymphoma, the posterior sphere is the most common infiltrating area, while in PCNSL, the tumor cells often infiltrate the vitreous, retina, or Under choroidal and slit lamp examination, lymphocytes in the aqueous humor can be diagnosed. In the diagnosis of primary central nervous system lymphoma, the cause of infiltration of the eye is not clear. It has been reported to be as high as 20%, although some patients have Blurred vision, vitreous opacity, many patients have no ocular symptoms, so a comprehensive and detailed eye examination should be performed before treatment of PCNSL patients. PCNSL patients first appear non-specific in the eye lesions, unilateral Uveitis, this uveitis is not effective for conventional treatment, and develops into bilateral, 80% of patients with ocular lymphoma develop into primary central nervous system lymphoma, so for patients with ocular lymphoma should Brain CT or MRI was performed to determine the presence or absence of PCNSL.
Primary central nervous system lymphoma, which only occurs in the pia mater and spinal cord, is rare. The spinal cord PCNSL is clinically characterized by bilateral lower extremity muscle weakness, without back pain. As the disease progresses, the lower extremities gradually appear. Sensory disturbances and pain, however, cerebrospinal fluid is mostly normal, and pia mater PCNSL is often characterized by lymphatic meningitis, cerebral neuropathy, progressive lumbosacral syndrome, and symptoms and signs of elevated intracranial pressure, which is related to PCNSL. The general performance is different. Under normal circumstances, PCNSL does not manifest as pial symptoms (such as cerebral neuropathy, hydrocephalus, cervical and lumbosacral radiculopathy) unless the patient has a relatively high malignant cerebrospinal fluid lymphocytosis. The situation, therefore, this poses certain difficulties for diagnosis. This patient can present with malignant hydrocephalus without pathological changes of the brain, and the prognosis of pia mater PCNSL is extremely poor.
For clinically mental and neurological symptoms, intracranial hypertension and other intracranial lesions, CT or MRI examinations show that the brain has space-occupying lesions, should consider primary central nervous system lymphoma, especially AIDS, various immunity In patients with functional defects, low and disorder, the possibility of primary central nervous system lymphoma should be highly suspected. Before the diagnosis of PC-NSL, corticosteroids should be avoided (unless the patient has a risk of cerebral palsy) because of the cortex. Hormones have significant cytotoxicity in patients with primary central nervous system lymphoma, and about one-third of patients with PCNSL have curative effects on corticosteroids, which are manifested in imaging examinations, narrowing lesions, and even some patients. The lesion disappeared completely and was relieved. Even in patients with negative imaging findings, corticosteroids may affect the morphology of lymphocytes, causing difficulty in pathological diagnosis. If patients are in urgent need of corticosteroids, or if PCNSL diagnosis is not considered at the time, regular treatment is still needed. Check CT and MRI.
If the tumor shrinks or even disappears, the diagnosis of PSNSL should be considered. However, some non-neoplastic diseases, such as multiple sclerosis and sarcoma-like disease, also show high-density shadows on CT or MRI. Can be reduced, disappeared, so further pathological biopsy is needed to confirm the diagnosis. At present, the safest and simple method is directional biopsy. For an experienced neurosurgeon, it can be directed without risk in any part of the brain. Sexual biopsy, but the problem is that the tumor tissue obtained by directed biopsy is small, it is difficult to distinguish lymphoma cells and inflammatory cells, so it is necessary to use immune tissue markers and molecular level techniques (such as PCR technology) to assist diagnosis. If the directional biopsy fails, a cranial brain biopsy can be performed.
In addition, lumbar puncture should be performed for routine and biochemical examination of cerebrospinal fluid, such as cerebrospinal fluid lymphocyte count, PCR, etc., especially for patients with suspected pial and spinal cord PCNSL for spinal MRI because of the clinical manifestations of such patients. Atypical, and CT and MRI are negative in the brain. At the same time, this can also clarify the degree of dissemination of PCNSL in the central nervous system. Eye examination should also be performed to determine the extent of eye infiltration.
During the treatment of PCNSL, CT and MRI should be reviewed to guide treatment and to determine whether there is recurrence.
Examine
Examination of primary central nervous system lymphoma
1. Peripheral blood: generally no significant changes.
2. Cerebrospinal fluid examination: About one-third of PCNSL patients have cerebrospinal fluid showing malignant lymphocytosis. At the same time, immunohistochemical examination of and light chains and PCR examination of B cells can be performed to help diagnosis.
3. Imaging examination: The most valuable laboratory examination of primary central nervous system lymphoma is imaging examination, such as CT, MRI, PET, 99mT-SPECT (single-computed computed tomography), brain scanning, angiography, etc. .
(1) Angiography: Primary central nervous system lymphoma is mostly avascular, or less vascular.
(2) 99mT-labeled SPECT brain scan: Primary central nervous system lymphoma has an increased absorption of 99mT.
(3) CT: In plain CT, 90% of patients with PCNSL show lesions of equal density or high density, which are different from other tumors in the brain, such as glioma, meningioma, brain metastases, etc., CT Plain scans are mostly low-density lesions, which may be related to the large number of small lymphocytes based on PCNSL. At the same time, compared with other brain tumors, PCNSL causes less edema of brain tissue around the lesion. After injection of contrast agent, 90% PCNSL patients were enhanced on CT, 50% of the uniform density enhancement, mostly located in the convex and abdomen position of the cerebral cortex, accounting for about 75%.
(4) MRI: A strong signal appeared on the T1MRI. After the contrast agent was injected, the Ga-T1MRI showed a lesion larger than the CT range.
(5) FDG-PET: distinguishes between primary central nervous system lymphoma and infection-caused lesions.
Some patients do not increase after CT or MRI injection of contrast agents, which is difficult for diagnosis. Some people think that this is related to the hidden lesions under the intact blood-cerebrospinal fluid barrier.
There are also some differences in laboratory tests between patients with normal immune function and those with immunodeficiency. The most obvious is that the incidence of multilobal lesions in the brain of immunocompromised patients is much higher than that of normal immune function, about 2 times (50%: 25). In addition, in immunodeficient patients, a special type of cyclic enhancement (50%) is common on CT and MRI, but it is rare in those with normal immune function.
4. Double-eye slit lamp examination: lymphocytes increase in aqueous humor.
Diagnosis
Diagnosis and diagnosis of primary central nervous system lymphoma
diagnosis
1. Medical history: Ask whether there are symptoms of intracranial hypertension such as headache, nausea, vomiting, whether there are visual symptoms such as visual impairment, limb weakness, epilepsy, aphasia, dizziness, unstable walking, and whether there is mental retardation and abnormal behavior. You should also ask if you have an organ transplant, whether you are an AIDS patient or a congenital immunodeficiency.
2. Physical examination: Check the nervous system for clinical manifestations of intracranial hypertension and brain damage or spinal cord injury.
3. Cerebrospinal fluid examination: protein over 1.0 / L, lymphocytes in (0 ~ 400) × 10 6 / L, cerebrospinal fluid after centrifugation by immunocytochemistry can increase the positive detection rate.
4. CT and MRI scan: CT can find large regular mass shadows, high density or equal density, obvious enhancement effect, and enhanced around the ventricles when the subventricular membrane is infiltrated. MRI can show lymphoma in the brain parenchyma, and the enhancement effect is obvious, but it is not easy to show the subarachnoid and vitreous lesions. T2 weighting has a good diagnostic value for recurrent small lesions.
Differential diagnosis
Primary central nervous system lymphoma should be differentiated from secondary central lymphoma caused by systemic lymphoma, which has lymph node or lymphoid tissue lesions outside the central system, allowing for careful physical examination, blood examination, and chest X-ray and clear diagnosis, for more cryptic lesions, need to carry out gallium radionuclide scanning, chest and abdominal CT, bone marrow examination, lymph node biopsy to confirm the diagnosis, in addition, other brain tumors, such as glioma, brain toxoplasmosis , white matter disease, etc., CT and MRI lesions are mostly low-density can be identified, or biopsy to identify.
For patients with normal immune function and immunodeficiency patients, there are certain differences in the diagnostic procedures. In immunocompromised patients, the diagnosis of primary central nervous system lymphoma is more difficult. This patient is often associated with cerebral toxoplasmosis and multiple cases. The leukoencephalopathy, and the characteristic manifestations of Toxoplasma gondii, multiple, small ring lesions, is also one of the main manifestations of PCNSL. These patients have very poor prognosis and short survival time, which makes the diagnosis difficult. Therefore, for patients with immunodeficiency and suspected PCNSL, serum Toxoplasma antibody test, or other bacterial, fungal infection, embolism disease examination, if the test is negative, feasible pathological biopsy, if the test is positive, feasible anti-arch After treatment with worms, clindamycin and imipenem for 10 to 14 days, CT is reviewed. If there is improvement, treatment can be continued. If there is no change, pathological biopsy can be performed to confirm the diagnosis.
