Introduction
Background
Before 1970, CNS lymphoma accounted for less than 1% of brain neoplasms. The incidence has increased several-fold since that time, mainly because of AIDS-related immunodeficiency and the use of immunosuppressive drugs with organ transplantation and cancer chemotherapy. Several rare congenital immunodeficiency syndromes may result in CNS lymphoma. These include Wiskott-Aldrich syndrome, X-linked immunodeficiency, immunoglobulin A deficiency, and severe immunodeficiency syndrome.1,2,3,4,5,6,7
Approximately 10-30% of patients with systemic lymphoma have secondary CNS involvement8,9 ; primary lymphomas represent approximately 70-90% of all CNS lymphomas. Secondary systemic and primary CNS lymphomas have similar imaging characteristics. Meningeal involvement occurs commonly in patients with secondary lymphoma; it occurs less frequently in patients with primary lymphoma. Of patients with primary lymphoma, 75-85% present with supratentorial tumor. As many as 50% of patients present with multiple tumor nodules.
For excellent patient education resources, visit eMedicine's Blood and Lymphatic System Center and Cancer and Tumors Center. Also, see eMedicine's patient education articles Lymphoma and Brain Cancer.
Related eMedicine topics:
HIV-1 Associated Opportunistic Neoplasms: CNS Lymphoma
Lymphoma, Non-Hodgkin
Human T-Cell Lymphotrophic Viruses
Related Medscape topics:
Specialty Link Radiology
Specialty Link Oncology
Resource Center Brain Cancer
Resource Center Non-Hodgkin's Lymphoma
CME Audiologic and Radiographic Response of NF2-related Vestibular Schwannoma to Erlotinib Therapy
Pathophysiology
Almost all CNS lymphomas are non-Hodgkin B-cell tumors. Rarely, patients with human T-cell lymphotropic virus type 1 (HTLV-1) disease develop Burkitt lymphoma or T-cell lymphoma. Typically, lymphoma is represented by histiocytic cells or large immunoblastic cells bearing B-cell surface markers.10,11
Tumor nodules typically develop in the subcortical and subependymal white matter and the corpus striatum. The corpus callosum is frequently involved with tumor extension; a butterfly tumor may thereby involve both cerebral hemispheres.
In cases of secondary lymphoma, spread of tumor occurs from the affected meninges via the perivascular spaces of Virchow-Robin; rarely, secondary involvement with Hodgkin disease occurs. Within the brain substance, the irregular tumor edge extends along perivascular spaces. The spinal cord is frequently affected by secondary lymphoma.
In cases associated with AIDS or other immunodeficiency disorders, lymphoma tumor nodules are often multiple. Infection with Epstein-Barr virus has been suggested as a causative factor in CNS lymphoma.
Frequency
United States
Primary CNS lymphoma now represents as many as 2% of all intracranial neoplasms, 7-15% of primary brain tumors, and less than 1% of non-Hodgkin lymphomas. Approximately 2% of patients with AIDS have CNS lymphoma.
Mortality/Morbidity
For immunocompromised and nonimmunocompromised patients with CNS lymphoma who remain untreated, the mean survival rate is 1-3 months. The mean survival rate for patients who are treated is better for patients without AIDS (18.9 mo) than for individuals with AIDS (2.6 mo).12,13
Race
No racial predilection is known for CNS lymphoma.
Sex
The male-to-female ratio for CNS lymphoma is estimated to be 3:2 in immunocompetent patients and 9:1 in persons with AIDS.14
Age
CNS lymphoma affects persons of all ages; the peak incidence occurs in those aged 40-60 years.
- Patients with inherited immunodeficiency, such as Wiskott-Aldrich syndrome, tend to develop CNS lymphoma in childhood.
- Patients with AIDS are likely to develop the tumor in early adulthood.
- Patients with AIDS-associated primary CNS lymphoma usually have advanced HIV infection, with CD4+ T cell counts of less than 50 cells per millimeter.
Presentation
The clinical presentation of patients with CNS lymphoma is nonspecific and depends on the location of the neoplasm. Patients with CNS lymphoma may present with focal neurologic impairment, cognitive changes, or seizure disorder.
Preferred Examination
MRI is the examination of choice for CNS lymphoma because of its high sensitivity and multiplanar capability. MRI images typically show a single or multiple poorly demarcated masses, more or less deeply located within the brain parenchyma. These masses demonstrate uniform intense gadolinium enhancement with little or no edema.15
Gadolinium-based contrast agents (gadopentetate dimeglumine [Magnevist], gadobenate dimeglumine [MultiHance], gadodiamide [Omniscan], gadoversetamide [OptiMARK], gadoteridol [ProHance]) have been linked to the development of nephrogenic systemic fibrosis (NSF) or nephrogenic fibrosing dermopathy (NFD). For more information, see the eMedicine topic Nephrogenic Fibrosing Dermopathy.
NSF/NFD has occurred in patients with moderate to end-stage renal disease after being given a gadolinium-based contrast agent to enhance MRI or MRA scans. NSF/NFD is a debilitating and sometimes fatal disease. Characteristics include red or dark patches on the skin; burning, itching, swelling, hardening, and tightening of the skin; yellow spots on the whites of the eyes; joint stiffness with trouble moving or straightening the arms, hands, legs, or feet; pain deep in the hip bones or ribs; and muscle weakness. For more information, see the FDA Public Health Advisory or Medscape.
Limitations of Techniques
Although sensitive, MRI characteristics are not specific for CNS lymphoma; however, MRI findings may be suggestive of lymphoma in the proper clinical setting.
Differential Diagnoses
Astrocytoma, Brain
Cryptococcosis, CNS
Meningioma, Brain
Meningioma, Spine
Toxoplasmosis, CNS
Tuberculosis, CNS
Other Problems to Be Considered
Metastatic neoplasm
Toxoplasmosis
Cryptococcosis
Glioma or gliomatosis cerebri
Pyogenic abscess
Meningioma
Sarcoidosis
Tuberculosis
Primitive neuroectodermal tumor
Progressive multifocal leukoencephalopathy
Encephalitis
More on Brain, Lymphoma |
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References
Greenberg JO. Cerebral lymphoma. In: Adams RD. Neuroimaging: A Companion to Adams and Victor's Principles of Neurology. McGraw-Hill;1995:418-9.
Lenhard RE Jr, Osteen RT, Gansler T. Cancer of the central nervous system and pituitary gland. Clin Oncol. 2001;680-1.
Paulus W, Jellinger K, Morgello S. Malignant lymphoma in WHO classification of tumors. Pathology and genetics. In: Kleihues and CaVenee, eds. Tumors of the Nervous System. Vol 1. Oxford: W.K. Press Lyon. Who & Oxford Univ Press;2000.
Sheikh B, Siqueira E. Primary lymphoma of the central nervous system. Br J Neurosurg. 1994;8(4):427-32. [Medline].
Gerstner E, Batchelor T. Primary CNS lymphoma. Expert Rev Anticancer Ther. May 2007;7(5):689-700. [Medline].
Hochberg FH, Baehring JM, Hochberg EP. Primary CNS lymphoma. Nat Clin Pract Neurol. Jan 2007;3(1):24-35. [Medline].
Batchelor T, Loeffler JS. Primary CNS lymphoma. J Clin Oncol. Mar 10 2006;24(8):1281-8. [Medline].
Barnard RO, Scott T. Patterns of proliferation in cerebral lymphoreticular tumors. Acta Neuropathol. 1977;Suppl vi.
Zee CS, Segall HD. Neuroradiology: A Study Guide. McGraw-Hill;1996:158-60.
Gerstner ER, Abrey LE, Schiff D, Ferreri AJ, Lister A, Montoto S, et al. CNS Hodgkin lymphoma. Blood. Sep 1 2008;112(5):1658-61. [Medline].
Mazhar D, Stebbing J, Bower M. Non-Hodgkin's lymphoma and the CNS: prophylaxis and therapy in immunocompetent and HIV-positive individuals. Expert Rev Anticancer Ther. Mar 2006;6(3):335-41. [Medline].
Fine HA, Mayer RJ. Primary central nervous system lymphoma. Ann Intern Med. Dec 1 1993;119(11):1093-104. [Medline].
Nasir S, DeAngelis LM. Update on the management of primary CNS lymphoma. Oncology (Huntingt). Feb 2000;14(2):228-34; discussion 237-42, 244. [Medline].
Miller DC, Hochberg FH, Harris NL. Pathology with clinical correlations of primary central nervous system non-Hodgkin''s lymphoma. The Massachusetts General Hospital experience 1958-1989. Cancer. Aug 15 1994;74(4):1383-97. [Medline].
Grossman RI, Yousem DM. Neuroradiology: The Requisites. St Louis: Mosby-Year Book;1994:186-7.
Watanabe M, Tanaka R, Takeda N, et al. Correlation of computed tomography with the histopathology of primary malignant lymphoma of the brain. Neuroradiology. 1992;34(1):36-42. [Medline].
Hongsakul K, Laothamatas J. Computer tomographic findings of the brain in HIV-patients at Ramathibodi Hospital. J Med Assoc Thai. Jun 2008;91(6):895-907. [Medline].
Cordoliani YS. Primary cerebral lymphoma in patients with AIDS: MR findings--17 cases. AJR Am J Roentgenol. 1992;159:841-7.
Kosaka N, Tsuchida T, Uematsu H, Kimura H, Okazawa H, Itoh H. 18F-FDG PET of common enhancing malignant brain tumors. AJR Am J Roentgenol. Jun 2008;190(6):W365-9. [Medline].
Huang Z, Zuo C, Guan Y, Zhang Z, Liu P, Xue F, et al. Misdiagnoses of 11C-choline combined with 18F-FDG PET imaging in brain tumours. Nucl Med Commun. Apr 2008;29(4):354-8. [Medline].
Macnealy MW, Newton HB, McGregor JM, Bell SD, Ray Chaudhury A, Slone HW, et al. Primary meningeal CNS lymphoma treated with intra-arterial chemotherapy and blood-brain barrier disruption. J Neurooncol. Aug 30 2008;[Medline].
Ekenel M, Iwamoto FM, Ben-Porat LS, Panageas KS, Yahalom J, Deangelis LM, et al. Primary central nervous system lymphoma: The role of consolidation treatment after a complete response to high-dose methotrexate-based chemotherapy. Cancer. Sep 1 2008;113(5):1025-31. [Medline].
Further Reading
Neurologic complications in HIV-infected children and adolescents.
New York State Department of Health. 2003 Mar. 19 pages. NGC:003047
Long-term follow-up guidelines for survivors of childhood, adolescent, and young adult cancers. Sections 6-37: chemotherapy.
Children's Oncology Group. 2003 Sep (revised 2006 Mar). 37 pages. NGC:005598
Long-term follow-up guidelines for survivors of childhood, adolescent, and young adult cancers. Sections 38-91: radiation.
Children's Oncology Group. 2003 Sep (revised 2006 Mar). 74 pages. NGC:005599
(1) Neoplastic complications of HIV infection. (2) July 2007 addendum.
New York State Department of Health. 2007 Jul. 19 pages. NGC:005840
Keywords
brain lymphoma, brain neoplasm, brain tumor, malignant lymphoma, reticulum cell sarcoma, histiocytic lymphoma, microglioma, Wiskott-Aldrich syndrome, x-linked immunodeficiency, immunoglobulin A deficiency, severe immunodeficiency syndrome, CNS lymphoma, central nervous system lymphoma, non-Hodgkin B-cell tumors, Burkitt lymphoma, T-cell lymphoma in human T-cell lymphotropic virus type 1 disease, HTLV-1
