Primary central nervous system lymphoma overview
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]Associate Editor(s)-in-Chief: Sujit Routray, M.D. [2]
Overview
Primary CNS lymphoma is a 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 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.[1] 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.[2] Genes involved in the pathogenesis of primary central nervous system lymphoma include IG, BCL6, CD95, PAX5, and PIM1.[3] 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).[4] 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. 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.[4][5] 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.[6][7][8] Primary central nervous system lymphoma must be differentiated from secondary CNS lymphoma, cerebral toxoplasmosis, glioblastoma multiforme, cerebral abscess, and tuberculoma.[9][10] Primary central nervous system lymphoma constitutes approximately 3%-4% of all primary brain tumors and 1%-2% of all lymphomas.[7] 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.[11] Primary CNS lymphoma is, after toxoplasmosis, the most common cause of focal brain lesions in AIDS patients.[11] The overall incidence of primary central nervous system lymphoma is 0.4 per 100,000 individuals per year.[7] 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.[2] The peak incidence is between 60 and 70 years old for immunocompetent patients.[7] 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.[7] 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.[2] If left untreated, primary central nervous system lymphoma may progress to develop elevated intracranial pressure, ocular symptoms, focal neurological deficits, and neuropsychiatric problems.[12] Common complications of primary central nervous system lymphoma include relapse, extracranial or subcutaneous metastasis, neuropsychiatric problems, and neurological toxicity.[12][13][14] The prognosis of primary central nervous system lymphoma is generally poor.[13][15]
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, and primary leptomeningeal lymphoma.[16]
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.[1] 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.[2] Genes involved in the pathogenesis of primary central nervous system lymphoma include IG, BCL6, CD95, PAX5, and PIM1.[3] 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).[4] 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).[17][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. 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.[4][5] 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.[2][5][11][14]
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.[6][7][8]
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.[9][10]
Epidemiology and Demographics
Primary central nervous system lymphoma constitutes approximately 3%-4% of all primary brain tumors and 1%-2% of all lymphomas.[7] 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.[11] Primary CNS lymphoma is, after toxoplasmosis, the most common cause of focal brain lesions in AIDS patients.[11] The overall incidence of primary central nervous system lymphoma is 0.4 per 100,000 individuals per year.[7] 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.[2] The peak incidence is between 60 and 70 years old for immunocompetent patients.[7] 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.[7] 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.[2]
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).[6][7][8][2]
Screening
There is insufficient evidence to recommend routine screening for primary central nervous system lymphoma.[18]
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.[12] Common complications of primary central nervous system lymphoma include relapse, extracranial or subcutaneous metastasis, neuropsychiatric problems, and neurological toxicity.[12][13][14] The prognosis of primary central nervous system lymphoma is generally poor.[13][15]
Diagnosis
Staging
There is no established system for the staging of primary central nervous system lymphoma.[19]
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.[20] 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.[3][20][21]
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.[12][22]
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.[17] Positive EBV DNA in CSF-PCR is helpful for diagnosis of primary central nervous system lymphoma, particularly in HIV/AIDS patients.[17]
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.[23] Chest, abdomen, and pelvic CT scans may be used to exclude any occult systemic disease from the spread of primary central nervous system lymphoma.[24]
MRI
Contrast-enhanced MRI is the imaging modality of choice for primary central nervous system lymphoma.[25] 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.[26]
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.[23][27][24][11]
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.[28][29] Chemotherapy is the mainstay of treatment for primary central nervous system lymphoma.[28] Corticosteroids are often used to destroy lymphoma cells and relieve cerebral edema.[28] Radiation therapy may be given on its own or along with chemotherapy.[28]
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.[28]
Prevention
There are no primary or secondary preventive measures available for seminoma.
References
- ↑ 1.0 1.1 PRIMARY CENTRAL NERVOUS SYSTEM LYMPHOMAS IN THE NEUROLOGICAL PRACTICE. file:///C:/Users/Owner/Downloads/psyneur_2014_1_2_8.pdf. Accessed on February 19, 2016
- ↑ 2.00 2.01 2.02 2.03 2.04 2.05 2.06 2.07 2.08 2.09 2.10 Bhagavathi S, Wilson JD (2008). "Primary central nervous system lymphoma". Arch Pathol Lab Med. 132 (11): 1830–4. doi:10.1043/1543-2165-132.11.1830. PMID 18976024.
- ↑ 3.0 3.1 3.2 Ferreri, A. J. M. (2011). "How I treat primary CNS lymphoma". Blood. 118 (3): 510–522. doi:10.1182/blood-2011-03-321349. ISSN 0006-4971.
- ↑ 4.0 4.1 4.2 4.3 Primary central nervous system lymphoma. Wikipedia 2016. https://en.wikipedia.org/wiki/Primary_central_nervous_system_lymphoma. Accessed on February 18, 2016
- ↑ 5.0 5.1 5.2 CNS lymphoma (primary). A.Prof Frank Gaillard. Radioapaedia 2016. http://radiopaedia.org/cases/cns-lymphoma-primary. Accessed on February 23, 2016
- ↑ 6.0 6.1 6.2 Risks of primary central nervous lymphoma. Canadian cancer society 2016. http://www.cancer.ca/en/cancer-information/cancer-type/non-hodgkin-lymphoma/non-hodgkin-lymphoma/types-of-nhl/primary-cns-lymphoma/?region=on. Accessed on February 17, 2016
- ↑ 7.00 7.01 7.02 7.03 7.04 7.05 7.06 7.07 7.08 7.09 7.10 Manenti, G.; Di Giuliano, F.; Bindi, A.; Liberto, V.; Funel, V.; Garaci, F. G.; Floris, R.; Simonetti, G. (2013). "A Case of Primary T-Cell Central Nervous System Lymphoma: MR Imaging and MR Spectroscopy Assessment". Case Reports in Radiology. 2013: 1–5. doi:10.1155/2013/916348. ISSN 2090-6862.
- ↑ 8.0 8.1 8.2 Epidemiology of primary CNS lymphoma. Dr Amir Rezaee and A.Prof Frank Gaillard et al. Radiopaedia 2016. http://radiopaedia.org/articles/primary-cns-lymphoma. Accessed on February 18, 2016
- ↑ 9.0 9.1 Differential diagnosis of primary central nervous system lymphoma. Dr Amir Rezaee and A.Prof Frank Gaillard et al. Radiopaedia 2016. http://radiopaedia.org/articles/primary-cns-lymphoma. Accessed on February 17, 2016
- ↑ 10.0 10.1 Cerebral ring enhancing lesions. Dr Bruno Di Muzio and A.Prof Frank Gaillard et al. Radioapaedia 2016. http://radiopaedia.org/articles/cerebral-ring-enhancing-lesions. Accessed on February 17, 2016
- ↑ 11.0 11.1 11.2 11.3 11.4 11.5 Haldorsen, Ingfrid S; Kråkenes, Jostein; Goplen, Anne K; Dunlop, Oona; Mella, Olav; Espeland, Ansgar (2008). "AIDS-related primary central nervous system lymphoma: a Norwegian national survey 1989–2003". BMC Cancer. 8 (1): 225. doi:10.1186/1471-2407-8-225. ISSN 1471-2407.
- ↑ 12.0 12.1 12.2 12.3 12.4 Symptoms of primary CNS Lymphoma. Lymphomation 2016. http://www.lymphomation.org/type-cns.htm. Accessed on February 24, 2016
- ↑ 13.0 13.1 13.2 13.3 Ahmed, Zartaj; Ramanathan, Ramesh K.; Ram, Sunil; Newell, James; Halepota, Maqbool (2014). "Unusual Relapse of Primary Central Nervous System Lymphoma at Site of Lumbar Puncture". Case Reports in Hematology. 2014: 1–4. doi:10.1155/2014/161952. ISSN 2090-6560.
- ↑ 14.0 14.1 14.2 Yamanaka, Ryuya (2013). "Primary Central Nervous System Lymphoma − Recent Advance on Clinical Research". doi:10.5772/52757.
- ↑ 15.0 15.1 Prognosis of primary central nervous system lymphoma. Canadian cancer society 2016. http://www.cancer.ca/en/cancer-information/cancer-type/non-hodgkin-lymphoma/non-hodgkin-lymphoma/types-of-nhl/primary-cns-lymphoma/?region=on. Accessed on February 17, 2016
- ↑ CNS lymphoma. Dr Henry Knipe and Dr Yuranga Weerakkody et al. Radiopaedia 2016. http://radiopaedia.org/articles/cns-lymphoma-1. Accessed on February 17, 2016
- ↑ 17.0 17.1 17.2 Pathology of primary central system lymphoma. Dr Amir Rezaee and A.Prof Frank Gaillard et al. Radiopaedia 2016. http://radiopaedia.org/articles/primary-cns-lymphoma. Accessed on February 18, 2016
- ↑ Screening of primary central nervous system lymphoma. U.S. preventive services task force 2016. http://www.uspreventiveservicestaskforce.org/BrowseRec/Search?s=PRIMARY+CENTRAL+NERVOUS+SYSTEM+LYMPHOMA. Accessed on February 24, 2016
- ↑ Staging of Primary CNS Lymphoma. National Cancer Institute 2016. http://www.cancer.gov/types/lymphoma/patient/primary-cns-lymphoma-treatment-pdq#section/_18. Accessed on February 23, 2016
- ↑ 20.0 20.1 Signs and symptoms of primary central nervous system lymphoma. Canadian cancer society 2016. http://www.cancer.ca/en/cancer-information/cancer-type/non-hodgkin-lymphoma/non-hodgkin-lymphoma/types-of-nhl/primary-cns-lymphoma/?region=on. Accessed on February 17, 2016
- ↑ Signs and symptoms of primary central nervous system lymphoma. Wikipedia 2016. https://en.wikipedia.org/wiki/Primary_central_nervous_system_lymphoma. Accessed on February 18, 2016
- ↑ Madani-Civi, M (2006), Clinicopathological features of primary central nervous system lymphoma, Neurosciences Check date values in:
|accessdate=(help);|access-date=requires|url=(help) - ↑ 23.0 23.1 Radiographic features of primary CNS lymphoma. Dr Amir Rezaee and A.Prof Frank Gaillard et al. Radiopaedia 2016. http://radiopaedia.org/articles/primary-cns-lymphoma. Accessed on February 18, 2016
- ↑ 24.0 24.1 Diagnostics of primary CNS lymphoma. National cancer institute 2016. http://www.cancer.gov/types/lymphoma/hp/primary-cns-lymphoma-treatment-pdq. Accessed on February 19, 2016
- ↑ Haldorsen, I. S.; Espeland, A.; Larsson, E.- M. (2010). "Central Nervous System Lymphoma: Characteristic Findings on Traditional and Advanced Imaging". American Journal of Neuroradiology. 32 (6): 984–992. doi:10.3174/ajnr.A2171. ISSN 0195-6108.
- ↑ Radiographic features of primary CNS lymphoma. Dr Amir Rezaee and A.Prof Frank Gaillard et al. Radiopaedia 2016. http://radiopaedia.org/articles/primary-cns-lymphoma. Accessed on February 23, 2016
- ↑ Diagnosis of primary central nervous system lymphoma. Canadian cancer society 2016. http://www.cancer.ca/en/cancer-information/cancer-type/non-hodgkin-lymphoma/non-hodgkin-lymphoma/types-of-nhl/primary-cns-lymphoma/?region=on. Accessed on February 18, 2016
- ↑ 28.0 28.1 28.2 28.3 28.4 Treatment of primary central nervous system lymphoma. Canadian cancer society 2016. http://www.cancer.ca/en/cancer-information/cancer-type/non-hodgkin-lymphoma/non-hodgkin-lymphoma/types-of-nhl/primary-cns-lymphoma/?region=on. Accessed on February 17, 2016
- ↑ Certain factors affect prognosis (chance of recovery) and treatment options. National cancer institute 2016. http://www.cancer.gov/types/lymphoma/patient/primary-cns-lymphoma-treatment-pdq. Accessed on February 19, 2016