You are in: eMedicine Specialties > Radiology > BRAIN/SPINE Brain, LymphomaArticle Last Updated: Sep 9, 2008AUTHOR AND EDITOR INFORMATIONSection 1 of 13
  Author: Djamil Fertikh, MD Attending Physician, Division of Radiology, Association of Alexandria Radiologists Djamil Fertikh is a member of the following medical societies: American College of Radiology, American Medical Association, and Radiological Society of North America Coauthor(s): Christian E Artman, MD, Staff Physician, Department of Diagnostic Radiology, Mercy Catholic Medical Center; Michael L Brooks, MD, JD, FCLM, Clinical Associate Professor of Radiology, Philadelphia College of Osteopathic Medicine; Director of Neuroradiology, Mercy Diagnostic Imaging, Department of Radiology, Mercy Fitzgerald Hospital Editors: Hugh J F Robertson, MD, DMR, FRCPC, FRCR, FACR, Professor Emeritus of Radiology, Professor of Clinical Radiology, Louisiana State University Health Sciences Center, New Orleans; Clinical Professor of Radiology, Tulane University School of Medicine; Active Staff, Department of Radiology, University Hospital; Bernard D Coombs, MB, ChB, PhD, Consulting Staff, Department of Specialist Rehabilitation Services, Hutt Valley District Health Board, New Zealand; Robert M Krasny, MD, Consulting Staff, Department of Radiology, The Angeles Clinic and Research Institute; James G Smirniotopoulos, MD, Professor of Radiology, Neurology, and Biomedical Informatics, Chairman, Department of Radiology and Radiological Sciences, Uniformed Services University of the Health Sciences Author and Editor Disclosure Synonyms and related 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 INTRODUCTIONSection 2 of 13
  BackgroundBefore 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. PathophysiologyAlmost 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. FrequencyUnited StatesPrimary 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/MorbidityFor 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 RaceNo racial predilection is known for CNS lymphoma. SexThe male-to-female ratio for CNS lymphoma is estimated to be 3:2 in immunocompetent patients and 9:1 in persons with AIDS.14 AgeCNS lymphoma affects persons of all ages; the peak incidence occurs in those aged 40-60 years.
Clinical DetailsThe 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 ExaminationMRI 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. Limitations of TechniquesAlthough sensitive, MRI characteristics are not specific for CNS lymphoma; however, MRI findings may be suggestive of lymphoma in the proper clinical setting. DIFFERENTIALSSection 3 of 13
Astrocytoma, Brain Cryptococcosis, CNS Meningioma, Brain Meningioma, Spine Toxoplasmosis, CNS Tuberculosis, CNS Other Problems To Be ConsideredMetastatic neoplasm
RADIOGRAPHSection 4 of 13
FindingsPlain radiographic examinations have no role in the evaluation of CNS lymphoma. CT SCANSection 5 of 13
FindingsNonenhanced CT images typically show focal nodular areas of high attenuation, representing high tumor cellularity, with ill-defined margins and little surrounding vasogenic edema (see Image 1). Corresponding contrast-enhanced CT images usually demonstrate marked and diffuse enhancement of the lesions (see Image 2).16, 17 In patients with AIDS-related immunocompromise, lymphomas often appear as ring-enhancing lesions (see Image 3) because of central areas of necrosis. The enhancing ring typically appears thick and nodular. Calcifications do not occur in lymphoma, except rarely in patients who have undergone prior radiation therapy. Hemorrhage in lymphoma is rare. Contrast-enhancing, thickened ependyma may be seen. Degree of ConfidenceIn patients with immunodeficiency or immunosuppression, other lesions, such as toxoplasmosis, cryptococcosis, metastasis, and pyogenic abscess, may have the same ring-enhancing appearance as that of CNS lymphoma. Clinical correlation is necessary in diagnosis. False Positives/NegativesAlthough in the proper clinical setting, radiographic findings may suggest CNS lymphoma, such findings are often not pathognomonic. Other lesions, such as toxoplasmosis, abscesses, cryptococcoma, glioma, and metastases, may have a similar appearance. MRISection 6 of 13
FindingsThe classic appearance of CNS lymphoma on nonenhanced T1-weighted MRIs is that of an isointense to isointense-to-hypointense nodule or mass. On T2-weighted MRIs, the appearance is that of an isointense-to-hyperintense mass. On postgadolinium-enhanced T1-weighted MRIs, lymphoma tends to enhance intensely and diffusely. In patients with AIDS-related immunosuppression, a ringlike enhancing pattern is seen most often (see Images 4-5). Often, little or no surrounding vasogenic edema is demonstrated.18 Tumor lesions may cross the midline and may appear as a butterfly tumor involving both cerebral hemispheres. In 30% of patients, leptomeningeal involvement is encountered, usually in secondary systemic lymphoma; in such cases, meningeal involvement is typical. Involvement of the perivascular spaces with contrast enhancement is strongly suggestive of CNS lymphoma (in such cases, lymphoma must be differentiated from sarcoidosis and CNS tuberculosis); involvement of the corpus callosum is also strongly suggestive of CNS lymphoma (in such cases, lymphoma must be differentiated from glioma and metastatic neoplasm). Contrast-enhancing, thickened ependyma may be seen (cytomegalovirus ependymitis in AIDS or metastatic neoplasm such as carcinoma of lung or breast, and ependymal spread of anaplastic glioma must be differentiated). Degree of ConfidenceLeptomeningeal extension is depicted better on enhanced MRIs than on CT scans. False Positives/NegativesCare should be taken, especially in cases involving ring-enhancing lesions, to differentiate lymphoma from other disorders, such toxoplasmosis, cryptococcosis, gliomas, and metastasis; on MRI, the appearance of these disorders may be similar to that of lymphoma. Involvement of the corpus callosum is highly suggestive of CNS lymphoma, but such involvement also occasionally occurs with anaplastic glioma and metastatic neoplasm. ULTRASOUNDSection 7 of 13
FindingsUltrasonography has no role in imaging CNS lymphoma. Sonograms may show enlarged intra-abdominal lymph nodes or involvement of abdominal organs in patients with associated systemic disease. NUCLEAR MEDICINESection 8 of 13
FindingsThallium-201 single-photon emission computed tomography may demonstrate intense uptake of the radiotracer within tumor tissue. Carbon-11 methionine or 18-fluorodeoxyglucose positron emission tomography may show increased uptake within the tumor tissue.19, 20 ANGIOGRAPHYSection 9 of 13
FindingsOn cerebral angiograms, lymphomas may simulate meningioma, with diffuse vascular staining in the late arterial or early venous phase, as well as meningeal enhancement. Arterial encasement and dilation of the deep medullary veins may be seen. Degree of ConfidenceAngiographic findings are nonspecific for CNS lymphoma. INTERVENTIONSection 10 of 13
Radiation therapy and chemotherapy are used to treat patients with CNS lymphomas. High doses of intravenous methotrexate, cyclophosphamide, hydroxydaunomycin-doxorubicin, vincristine, and prednisone are used in chemotherapy. Steroid therapy, radiation therapy, or both may result in rapid shrinkage of the tumors. Recurrence is frequent, and long-term survival is poor.21, 22 Medical/Legal Pitfalls
FURTHER READINGSection 11 of 13
Neurologic complications in HIV-infected children and adolescents. MULTIMEDIASection 12 of 13
REFERENCESSection 13 of 13
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