Disclosure
Background: Prior to 1970, CNS lymphoma accounted for less than 1% of brain neoplasms. The incidence has increased several-fold since that time, mainly due to 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. Approximately 10-30% of patients with systemic lymphoma may develop secondary CNS involvement (Barnard, 1977; Zee, 1996); 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 secondary lymphoma and less frequently in primary lymphoma. Primary lymphoma presents with supratentorial tumor in 75-85% of patients. Tumor nodules at presentation are multiple in as many as 50% of patients. 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. Pathophysiology: Almost all CNS lymphomas are non-Hodgkin B-cell tumors. Rarely, Burkitt lymphoma or T-cell lymphoma in human T-cell lymphotropic virus type 1 (HTLV-1) disease may occur. Typically, lymphoma is represented by histiocytic cells or large immunoblastic cells bearing B-cell surface markers. Tumor nodules typically develop in the subcortical and subependymal white matter and the corpus striatum. The corpus callosum is frequently involved in tumor extension, and a butterfly tumor may thereby involve both cerebral hemispheres. Spread of tumor occurs from the affected meninges via the perivascular spaces of Virchow-Robin in secondary lymphoma, including the rare secondary involvement by Hodgkin disease. Within the brain substance, the irregular tumor edge extends along perivascular spaces. The spinal cord is frequently affected in secondary lymphoma. Lymphoma tumor nodules are often multiple with central necrosis in AIDS and other immunodeficiency disorders. Infection with Epstein-Barr virus has been suggested as a causative factor in CNS lymphoma. Frequency:
Mortality/Morbidity: Immunocompromised and nonimmunocompromised patients have a 1- to 3-month mean survival rate without therapy. 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) (Fine, 1993; Nasir, 2000). Race: No racial predilection is known. Sex: The male-to-female ratio is estimated to be 3:2 in immunocompetent patients and 9:1 in persons with AIDS (Miller, 1994). Age: CNS lymphoma affects persons at all ages, with a peak incidence in those aged 40-60 years.
Clinical Details: The clinical presentation of CNS lymphoma is nonspecific and depends on the location of the neoplasm. Patients with CNS lymphoma can present with focal neurologic impairment, cognitive changes, or seizure disorder. Preferred Examination: MRI is the examination of choice because of its high sensitivity and multiplanar capability. MRI images typically show 1 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. Gadolinium-based contrast agents (gadopentetate dimeglumine [Magnevist], gadobenate dimeglumine [MultiHance], gadodiamide [Omniscan], gadoversetamide [OptiMARK], gadoteridol [ProHance]) have recently 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. The disease 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. As of late December 2006, the FDA had received reports of 90 such cases. Worldwide, over 200 cases have been reported, according to the FDA. 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; however, MRI findings can be suggestive of lymphoma in the proper clinical setting.
Astrocytoma, Brain
Metastatic neoplasm
Findings: Plain radiographic examinations have no role in the evaluation of CNS lymphoma. |
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Findings: Nonenhanced CT images typically show focal nodular areas of high attenuation secondary to 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). 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 Confidence: In patients with immunodeficiency or immunosuppression, other lesions, such as toxoplasmosis, cryptococcosis, metastasis, and pyogenic abscess, can have the same ring-enhancing appearance as that of CNS lymphoma. Clinical correlation is necessary in diagnosis. False Positives/Negatives: Although suggestive in the proper clinical setting, the radiologic appearance of CNS lymphoma is often not pathognomonic. Other lesions, such as toxoplasmosis, abscesses, cryptococcoma, glioma, and metastases, can have a similar appearance.
Findings: The classic appearance of CNS lymphoma is an isointense to isointense-to-hypointense nodule or mass on -nonenhanced T1-weighted MRIs and isointense-to-hyperintense on corresponding T2-weighted MRIs. On postgadolinium-enhanced T1-weighted MRIs, lymphoma tends to enhance intensely and diffusely. A ringlike enhancing pattern is seen most often in patients with AIDS-related immunosuppression (see Images 4-5). Often, little or no surrounding vasogenic edema is demonstrated. Tumor lesions can 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 which meningeal involvement is typical. Involvement of the perivascular spaces with contrast enhancement (sarcoidosis or CNS tuberculosis must be differentiated) or of the corpus callosum (glioma or metastatic neoplasm must be differentiated) is strongly suggestive of CNS lymphoma. 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 Confidence: Leptomeningeal extension is depicted better on enhanced MRIs than on CT scans. False Positives/Negatives: Care should be taken, especially with ring-enhancing lesions, to differentiate other entities because toxoplasmosis, cryptococcosis, gliomas, and metastasis can have a similar appearance. Involvement of the corpus callosum is highly suggestive of CNS lymphoma, but it also occasionally occurs with anaplastic glioma and metastatic neoplasm.
Findings: Ultrasonography 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.
Findings: Thallium Tl 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 can show increased uptake within the tumor tissue.
Findings: On cerebral angiograms, lymphomas can simulate meningioma, with diffuse vascular staining in the late arterial or early venous phase and meningeal enhancement. Arterial encasement and dilated deep medullary veins can be seen. Degree of Confidence: Angiographic findings are nonspecific.
Intervention: 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 and/or radiation therapy can result in rapid shrinkage of the tumors. Recurrence is frequent, and long-term survival is poor. Medical/Legal Pitfalls:
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