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Latest revision as of 04:16, 2 January 2020

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]Associate Editor(s)-in-Chief: Marjan Khan M.B.B.S.[2]

Overview

Primary CNS lymphoma is an intracranial tumor usually present in those with severe immunosuppression. It represents around 20% of all cases of lymphomas in HIV infection (other types being Burkitt's lymphoma and immunoblastic lymphoma). Primary central nervous system lymphoma may originate from a germinal center to an early postgerminal center in a secondary lymphoid organ, which may be capable of further maturation steps. EBV is almost always associated with primary CNS lymphoma in immunodeficient individuals, and latent EBV infection of B-cells leads to it's immortalization and to CNS tropism. In immunocompetent individuals, the B-cells infected with EBV are held in check by T-cells, and with the severity of immunosuppression, T cells gradually fall, leading to the B-cell proliferation and dissemination. . Primary central nervous system lymphoma constitutes approximately 3%-4% of all primary brain tumors and 1%-2% of all lymphomas. Primary central nervous system lymphoma has been diagnosed in at least 2% of individuals infected with human immunodeficiency virus, and in 9–14% of acquired immunodeficiency syndrome (AIDS)-autopsies. Primary CNS lymphoma is, after toxoplasmosis, the most common cause of focal brain lesions in AIDS patients. The overall incidence of primary central nervous system lymphoma is 0.4 per 100,000 individuals per year. The median age of occurrence of primary central nervous system lymphoma in immunocompetent and immunocompromised patients are 53-57 years and 31-35 years, respectively. The peak incidence is between 60 and 70 years old for immunocompetent patients. Significant increment of incidence rate over time is associated with increased incidence of AIDS and advanced age. Males are more commonly affected with primary central nervous system lymphoma than females.

Classification

Primary central nervous system lymphoma may be classified according to the site of involvement of the central nervous system into 3 groups:

Parenchymal
Intravascular lymphoma
Primary leptomeningeal lymphoma.

Primary CNS lymphomas are extranodal, malignant non-Hodgkin lymphomas of the diffuse large B-cell type that are confined to the brain, eyes, leptomeninges, or spinal cord, in the absence of systemic lymphoma. Primary CNS lymphomas are estimated to account for up to 1% of all lymphomas, 4–6% of all extranodal lymphomas, and about 3% of all CNS tumours. After a continuous rise in the incidence of primary CNS lymphoma during the 1980s and 1990s, epidemiological data in high-income countries show a decrease in incidence, particularly among young patients with AIDS.

Pathophysiology

Primary central nervous system lymphoma may originate from a germinal center to an early postgerminal center in a secondary lymphoid organ, which may be capable of further maturation steps.
EBV is almost always associated with primary CNS lymphoma in immunodeficient individuals, and latent EBV infection of B-cells leads to it's immortalization and to CNS tropism. In immunocompetent individuals, the B-cells infected with EBV are held in check by T-cells, and with the severity of immunosuppression, T cells gradually fall, leading to the B-cell proliferation and dissemination.
Genes involved in the pathogenesis of primary central nervous system lymphoma include IG, BCL6, CD95, PAX5, and PIM1.
Primary central nervous system lymphoma is highly associated with Epstein-Barr virus (EBV) infection (> 90%) in immunodeficient patients (such as those with AIDS and iatrogenically immunosuppressed).
Primary central nervous system lymphoma presents as a solitary or multiple, well circumscribed, greater than 2 cm in diameter, well-defined or infiltrating mass lesion/s that can arise in the cortex, white matter, or deep grey matter (more common in low-grade lesions). On gross pathology, the lesions could be brownish, gray-tan, or yellow, firm, homogenous, centrally necrotic with areas of hemorrhage.
On microscopic histopathological analysis, primary central nervous system lymphoma is characterized by accumulation of large atypical mononuclear cells around small calibre vascular channels with invasion of the walls of some vessels. The atypical cells have large round, oval and angulated hyperchromatic and vesicular nuclei, and a narrow rim of pale cytoplasm. An occasional mitotic figure is noted.
Primary central nervous system lymphoma is demonstrated by positivity to tumor markers, including B lymphocyte markers, such as CD19, CD20, CD79a, Ki-67, GFAP, BCL-2, and BCL-6.
Primary central nervous system lymphoma presents as a solitary or multiple, well circumscribed, greater than 2 cm in diameter, well-defined or infiltrating mass lesion/s that can arise in the cortex, white matter, or deep grey matter (more common in low-grade lesions).[5][2] On gross pathology, the lesions could be brownish, gray-tan, or yellow, firm, homogenous, centrally necrotic with areas of hemorrhage.[2] On microscopic histopathological analysis, primary central nervous system lymphoma is characterized by accumulation of large atypical mononuclear cells around small calibre vascular channels with invasion of the walls of some vessels.

Causes

There are no known direct causes for primary central nervous system lymphoma. To view a comprehensive list of risk factors that increase the risk of primary nervous system lymphoma, click here.

Differentiating Primary Central Nervous System Lymphoma from other Diseases

Primary central nervous system lymphoma must be differentiated from secondary CNS lymphoma, cerebral toxoplasmosis, glioblastoma multiforme, cerebral abscess, and tuberculoma.

Epidemiology and Demographics

Primary central nervous system lymphoma constitutes approximately 3%-4% of all primary brain tumors and 1%-2% of all lymphomas. Primary central nervous system lymphoma has been diagnosed in at least 2% of individuals infected with human immunodeficiency virus, and in 9–14% of acquired immunodeficiency syndrome (AIDS)-autopsies. Primary CNS lymphoma is, after toxoplasmosis, the most common cause of focal brain lesions in AIDS patients. The overall incidence of primary central nervous system lymphoma is 0.4 per 100,000 individuals per year. The median age of occurrence of primary central nervous system lymphoma in immunocompetent and immunocompromised patients are 53-57 years and 31-35 years, respectively. The peak incidence is between 60 and 70 years old for immunocompetent patients. Significant increment of incidence rate over time is associated with increased incidence of AIDS and advanced age. Males are more commonly affected with primary central nervous system lymphoma than females. The male to female ratio is approximately 1.2 to 1 in immunocompetent patients and approximately 7.38 to 1 in AIDS-associated primary central nervous system lymphoma.

Risk Factors

The most potent risk factor in the development of primary central nervous system lymphoma is a weakened or suppressed immune system in individuals who have acquired immunodeficiency syndrome (AIDS), received an organ transplant and are on immunosuppressants, inherited immunosuppressive disorders (IgA deficiency, Wiskott-Aldrich syndrome, ataxia telangiectasia), and autoimmune disorders (systemic lupus erythematosus, rheumatoid arthritis, myasthenia gravis).

Screening

There is insufficient evidence to recommend routine screening for primary central nervous system lymphoma.

Natural History, Complications and Prognosis

If left untreated, primary central nervous system lymphoma may progress to develop elevated intracranial pressure, ocular symptoms, focal neurological deficits, and neuropsychiatric problems. Common complications of primary central nervous system lymphoma include relapse, extracranial or subcutaneous metastasis, neuropsychiatric problems, and neurological toxicity. The prognosis of primary central nervous system lymphoma is generally poor.

Diagnosis

Staging

There is no established system for the staging of primary central nervous system lymphoma.

Symptoms

Symptoms of primary central nervous system lymphoma are identical to the other types of brain tumors and depend on the area of the brain that is affected. Primary central nervous system lymphoma is multifocal. Symptoms of primary nervous system lymphoma include headache, nausea, vomiting, difficulty swallowing, monocular vision loss, Muscle weakness or paralysis, memory loss, facial hypoesthesia, seizures, fever, night sweats, and weight loss.

Physical Examination

Common physical examination findings of primary central nervous system lymphoma include vision loss, papilledema, altered mental status, apathy, depression, aphasia, cranioneuropathies, ataxia, and hemiparesis.

Laboratory Findings

Laboratory tests performed in a case suspected of primary central nervous system lymphoma include complete blood count, complete metabolic panel, lactate dehydrogenase, serological testing for HIV, and CSF analysis. Laboratory findings consistent with the diagnosis of primary central nervous system lymphoma include elevated protein and decreased glucose on CSF analysis. Positive EBV DNA in CSF-PCR is helpful for diagnosis of primary central nervous system lymphoma, particularly in HIV/AIDS patients.

CT

Head CT scan may be helpful in the diagnosis of primary central nervous system lymphoma. Findings on CT scan suggestive of primary central nervous system lymphoma include supratentorial hyperattenuating, enhancing, hemorrhaging mass with subependymal extension crossing the corpus callosum. Chest, abdomen, and pelvic CT scans may be used to exclude any occult systemic disease from the spread of primary central nervous system lymphoma.

MRI

Contrast-enhanced MRI is the imaging modality of choice for primary central nervous system lymphoma. Findings on MRI suggestive of primary central nervous system lymphoma include solitary to multiple, 3-5 cm ring-enhancing lesions in almost any location, but usually deep in the white matter, which are typically hypointense on T1-weighted images and iso- to hypointense on T2-weighted images.

Other Imaging Findings

There are no other imaging findings associated with primary central nervous system lymphoma.

Other Diagnostic Studies

Other diagnostic studies for primary central nervous system lymphoma include magnetic resonance spectroscopy, magnetic resonance perfusion, scintigraphy, stereotactic biopsy, and polymerase chain reaction.

Treatment

Medical Therapy

The treatment of primary central nervous system lymphoma depends on the patient’s age, performance status, stage and location of the lymphoma, and whether or not the individual is immunosuppressed. Chemotherapy is the mainstay of treatment for primary central nervous system lymphoma. Corticosteroids are often used to destroy lymphoma cells and relieve cerebral edema. Radiation therapy may be given on its own or along with chemotherapy. The treatment of primary central nervous system lymphoma depends on the patient’s age, performance status, stage and location of the lymphoma, and whether or not the individual is immunosuppressed.

Surgery

Surgical intervention is not recommended for the management of primary central nervous system lymphoma, because the tumors are often deeply seated and spread throughout the brain.

Prevention

There are no primary or secondary preventive measures available for seminoma.

References

Template:WikiDoc Sources

@@ Line 1: / Line 1: @@
 __NOTOC__
 {{Primary central nervous system lymphoma}}
-{{CMG}}
+{{CMG}}{{AE}}{{Marjan}}
 ==Overview==
-'''Primary CNS lymphoma''' is a [[brain tumor|primary intracranial tumor]] usually present in those with severe immunosuppression --- commonly in those with [[AIDS]] --- and represents around 20% of all cases of lymphomas in HIV infection (other types being [[Burkitt's lymphoma]] and immunoblastic lymphoma). Primary CNS lymphoma (PCNSL) is highly associated with [[Epstein-Barr virus]] infection (> 90%) in immunodeficient patients<ref>Fine HA, Mayer RJ. Primary central nervous system lymphoma. ''Ann Intern Med'' 1993; 119(11):1093-1104</ref> (such as those with AIDS and those iatrogenically immunosupressed) and does not have predilections for any age group. Mean [[CD4]]+ count at time of diagnosis is ~50/uL. Because of the severity of immunosuppression at the time of diagnosis, it is to no surprise that prognosis is usually poor.  In immunocompetent patients (that is, patients that do not have AIDS or some other immunodeficiency) there is rarely an association with EBV infection or other infectious DNAs.  In the immunocompetent population, PCNSL typically affects older patients in their 50's and 60's.  Importantly, the incidence of PCNSL in the immunocompetent population has been reported to have increased more than 10-fold from 2.5 cases to 30 cases per 10 million population<ref>Eby NL, Grufferman S, Flannelly CM, Schold SC, Jr., Vogel FS, Burger PC. Increasing incidence of primary brain lymphoma in the US. ''Cancer'' 1988;62(11):2461-2465</ref><ref>Corn BW, Marcus SM, Topham A, Hauck W, Curran WJ, Jr. Will primary central nervous system lymphoma be the most frequent brain tumor diagnosed in the year 2000? ''Cancer'' 1997;79(12):2409-2413</ref>.  The cause for the increase in incidence of this disease in the immunocompetent population is unknown.
+Primary [[CNS]] [[lymphoma]] is an intracranial tumor usually present in those with severe [[immunosuppression]]. It represents around 20% of all cases of lymphomas in HIV infection (other types being Burkitt's lymphoma and immunoblastic lymphoma). Primary central nervous system lymphoma may originate from a germinal center to an early postgerminal center in a secondary lymphoid organ, which may be capable of further maturation steps. EBV is almost always associated with primary CNS lymphoma in immunodeficient individuals, and latent EBV infection of B-cells leads to it's immortalization and to CNS tropism. In immunocompetent individuals, the B-cells infected with EBV are held in check by T-cells, and with the severity of immunosuppression, T cells gradually fall, leading to the B-cell proliferation and dissemination. . Primary central nervous system lymphoma constitutes approximately 3%-4% of all primary brain tumors and 1%-2% of all lymphomas. Primary central nervous system lymphoma has been diagnosed in at least 2% of individuals infected with human immunodeficiency virus, and in 9–14% of acquired immunodeficiency syndrome (AIDS)-autopsies. Primary CNS lymphoma is, after toxoplasmosis, the most common cause of focal brain lesions in AIDS patients. The overall incidence of primary central nervous system lymphoma is 0.4 per 100,000 individuals per year. The median age of occurrence of primary central nervous system lymphoma in immunocompetent and immunocompromised patients are 53-57 years and 31-35 years, respectively. The peak incidence is between 60 and 70 years old for immunocompetent patients. Significant increment of incidence rate over time is associated with increased incidence of AIDS and advanced age. Males are more commonly affected with primary central nervous system lymphoma than females.
+==Classification==
+Primary central nervous system lymphoma may be classified according to the site of involvement of the central nervous system into 3 groups:
+# Parenchymal
+# Intravascular lymphoma
+# Primary leptomeningeal lymphoma.
+Primary CNS lymphomas are extranodal, malignant non-Hodgkin lymphomas of the diffuse large B-cell type that are confined to the brain, eyes, leptomeninges, or spinal cord, in the absence of systemic lymphoma. Primary CNS lymphomas are estimated to account for up to 1% of all lymphomas, 4–6% of all extranodal lymphomas, and about 3% of all CNS tumours. After a continuous rise in the incidence of primary CNS lymphoma during the 1980s and 1990s, epidemiological data in high-income countries show a decrease in incidence, particularly among young patients with AIDS.
+==Pathophysiology==
+* Primary central nervous system lymphoma may originate from a germinal center to an early postgerminal center in a secondary lymphoid organ, which may be capable of further maturation steps.
+* [[EBV]] is almost always associated with primary CNS lymphoma in immunodeficient individuals, and latent EBV infection of B-cells leads to it's immortalization and to CNS tropism. In immunocompetent individuals, the B-cells infected with EBV are held in check by T-cells, and with the severity of immunosuppression, T cells gradually fall, leading to the B-cell proliferation and dissemination.
+* Genes involved in the pathogenesis of primary central nervous system lymphoma include ''IG'', ''BCL6'', ''CD95'', ''[[PAX5]]'', and ''[[PIM1]]''.
+* Primary central nervous system lymphoma is highly associated with [[Epstein-Barr virus|Epstein-Barr virus (EBV) infection]] (> 90%) in immunodeficient patients (such as those with [[AIDS]] and iatrogenically immunosuppressed).
+* Primary central nervous system lymphoma presents as a solitary or multiple, well circumscribed, greater than 2 cm in diameter, well-defined or infiltrating mass lesion/s that can arise in the [[cerebral cortex|cortex]], white matter, or deep grey matter (more common in low-grade lesions). On gross pathology, the lesions could be brownish, gray-tan, or yellow, firm, homogenous, [[necrosis|centrally necrotic]] with areas of [[hemorrhage]].
+* On microscopic histopathological analysis, primary central nervous system lymphoma is characterized by accumulation of large atypical mononuclear cells around small calibre vascular channels with invasion of the walls of some vessels. The atypical cells have large round, oval and angulated hyperchromatic and vesicular nuclei, and a narrow rim of pale cytoplasm. An occasional mitotic figure is noted.
+* Primary central nervous system lymphoma is demonstrated by positivity to tumor markers, including B lymphocyte markers, such as [[CD19]], [[CD20]], [[CD79a]], [[Ki-67 (Biology)|Ki-67]], [[GFAP]], [[BCL-2]], and BCL-6.
+*Primary central nervous system lymphoma presents as a solitary or multiple, well circumscribed, greater than 2 cm in diameter, well-defined or infiltrating mass lesion/s that can arise in the cortex, white matter, or deep grey matter (more common in low-grade lesions).[5][2] On gross pathology, the lesions could be brownish, gray-tan, or yellow, firm, homogenous, centrally necrotic with areas of hemorrhage.[2] On microscopic histopathological analysis, primary central nervous system lymphoma is characterized by accumulation of large atypical mononuclear cells around small calibre vascular channels with invasion of the walls of some vessels.
+==Causes==
+There are no known direct causes for primary central nervous system lymphoma. To view a comprehensive list of risk factors that increase the risk of primary nervous system lymphoma, click [[Primary central nervous system lymphoma risk factors|'''here''']].
+==Differentiating Primary Central Nervous System Lymphoma from other Diseases==
+Primary central nervous system lymphoma must be differentiated from secondary CNS lymphoma, [[toxoplasmosis|cerebral toxoplasmosis]], [[glioblastoma multiforme]], [[cerebral abscess]], and [[tuberculoma]].
+==Epidemiology and Demographics==
+Primary central nervous system lymphoma constitutes approximately 3%-4% of all primary brain tumors and 1%-2% of all [[lymphomas]]. Primary central nervous system lymphoma has been diagnosed in at least 2% of individuals infected with [[HIV|human immunodeficiency virus]], and in 9–14% of acquired immunodeficiency syndrome (AIDS)-autopsies. Primary CNS lymphoma is, after [[toxoplasmosis]], the most common cause of focal brain lesions in [[AIDS|AIDS patients]]. The overall incidence of primary central nervous system lymphoma is 0.4 per 100,000 individuals per year. The median age of occurrence of primary central nervous system lymphoma in immunocompetent and immunocompromised patients are 53-57 years and 31-35 years, respectively. The peak incidence is between 60 and 70 years old for immunocompetent patients. Significant increment of incidence rate over time is associated with increased incidence of [[AIDS]] and advanced age. Males are more commonly affected with primary central nervous system lymphoma than females. The male to female ratio is approximately 1.2 to 1 in immunocompetent patients and approximately 7.38 to 1 in AIDS-associated primary central nervous system lymphoma.
+==Risk Factors==
+The most potent risk factor in the development of primary central nervous system lymphoma is a weakened or suppressed immune system in individuals who have [[Acquired immunodeficiency syndrome|acquired immunodeficiency syndrome (AIDS)]], received an organ transplant and are on [[immunosuppressants]], inherited immunosuppressive disorders ([[IgA deficiency]], [[Wiskott-Aldrich syndrome]], [[ataxia telangiectasia]]), and [[autoimmune disorders]] ([[systemic lupus erythematosus]], [[rheumatoid arthritis]], [[myasthenia gravis]]).
+==Screening==
+There is insufficient evidence to recommend routine screening for primary central nervous system lymphoma.
+==Natural History, Complications and Prognosis==
+If left untreated, primary central nervous system lymphoma may progress to develop [[elevated intracranial pressure]], ocular symptoms, focal neurological deficits, and neuropsychiatric problems. Common complications of primary central nervous system lymphoma include [[relapse]], [[metastasis|extracranial or subcutaneous metastasis]], neuropsychiatric problems, and neurological toxicity. The prognosis of primary central nervous system lymphoma is generally poor.
+==Diagnosis==
+===Staging===
+There is no established system for the staging of primary central nervous system lymphoma.
+===Symptoms===
+Symptoms of primary central nervous system lymphoma are identical to the other types of brain tumors and depend on the area of the brain that is affected. Primary central nervous system lymphoma is multifocal.  Symptoms of primary nervous system lymphoma include [[headache]], [[nausea]], [[vomiting]], [[Dysphagia|difficulty swallowing]], [[vision loss|monocular vision loss]], [[Muscle weakness|Muscle weakness or paralysis]], [[memory loss]], [[hypoesthesia|facial hypoesthesia]], [[seizures]], [[fever]], [[night sweats]], and [[weight loss]].
+===Physical Examination===
+Common physical examination findings of primary central nervous system lymphoma include [[vision loss]], [[papilledema]], [[altered mental status]], [[apathy]], [[depression]], [[aphasia]], [[Nerve palsy|cranioneuropathies]], [[ataxia]], and [[hemiparesis]].
+===Laboratory Findings===
+Laboratory tests performed in a case suspected of primary central nervous system lymphoma include [[complete blood count]], [[complete metabolic panel]], [[lactate dehydrogenase]], serological testing for HIV, and [[CSF analysis]]. Laboratory findings consistent with the diagnosis of primary central nervous system lymphoma include [[protein|elevated protein]] and [[glucose|decreased glucose]] on [[CSF analysis]]. Positive [[EBV|EBV DNA]] in [[PCR|CSF-PCR]] is helpful for diagnosis of primary central nervous system lymphoma, particularly in [[HIV]]/[[AIDS]] patients.
+===CT===
+Head CT scan may be helpful in the diagnosis of primary central nervous system lymphoma. Findings on CT scan suggestive of primary central nervous system lymphoma include [[Supratentorial|supratentorial]] hyperattenuating, enhancing, hemorrhaging mass with subependymal extension crossing the [[corpus callosum]]. Chest, abdomen, and pelvic CT scans may be used to exclude any occult systemic disease from the spread of primary central nervous system lymphoma.
+===MRI===
+Contrast-enhanced MRI is the imaging modality of choice for primary central nervous system lymphoma. Findings on MRI suggestive of primary central nervous system lymphoma include solitary to multiple, 3-5 cm ring-enhancing lesions in almost any location, but usually deep in the [[white matter]], which are typically hypointense on T1-weighted images and iso- to hypointense on T2-weighted images.
+===Other Imaging Findings===
+There are no other imaging findings associated with primary central nervous system lymphoma.
+===Other Diagnostic Studies===
+Other diagnostic studies for primary central nervous system lymphoma include [[In vivo magnetic resonance spectroscopy|magnetic resonance spectroscopy]], [[Perfusion weighted imaging|magnetic resonance perfusion]], [[scintigraphy]], [[Stereotactic|stereotactic biopsy]], and [[PCR|polymerase chain reaction]].
+==Treatment==
+===Medical Therapy===
+The treatment of primary central nervous system lymphoma depends on the patient’s age, performance status, stage and location of the lymphoma, and whether or not the individual is immunosuppressed. [[Chemotherapy]] is the mainstay of treatment for primary central nervous system lymphoma. Corticosteroids are often used to destroy lymphoma cells and relieve cerebral edema. [[radiotherapy|Radiation therapy]] may be given on its own or along with chemotherapy. The treatment of primary central nervous system lymphoma depends on the patient’s age, performance status, stage and location of the lymphoma, and whether or not the individual is immunosuppressed.
+===Surgery===
+[[surgery|Surgical intervention]] is not recommended for the management of primary central nervous system lymphoma, because the tumors are often deeply seated and spread throughout the brain.
+===Prevention===
+There are no primary or secondary preventive measures available for seminoma.
 ==References==
 {{Reflist|2}}
 [[Category:Neurology]]
 [[Category:Neurosurgery]]
 [[Category:Types of cancer]]
 [[Category:Viral diseases]]
+[[Category:Disease]]
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