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INTRACRANIAL NEOPLASMS AND PARANEOPLASTIC DISORDERS
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seems to be the most important factor, coupled with the age of the patient (most are under 5 years old) It has been speculated that radiation breaks down the blood-brain barrier, allowing methotrexate to injure myelin Lack of circulation in the necrotic zones prevents the usual liquefaction and eventual cavitation In this respect it resembles radiation necrosis Involvement of the Nervous System in Systemic Lymphoma Extradural compression of the spinal cord or cauda equina is the most common neurologic complication of all types of lymphoma, the result of extension from vertebrae or paravertebral lymph nodes Treatment is radiation or, if a tissue diagnosis is lacking, surgical decompression Systemic lymphoma rarely metastasizes to the brain In a review of more than 100 autopsies at the Mallory Institute of Pathology; our colleague R D Adams observed only a half-dozen instances where patients with lymphomas had deposits of tumor cells in the brain, and in none of these cases were they from multiple myeloma or plasmacytoma (Sparling et al) In the series of Levitt et al, comprising 592 patients with non-Hodgkin lymphoma, there were only 8 with intracerebral metastases Much more common is meningeal dissemination of non-Hodgkin lymphoma, the clinical and CSF pictures being similar to those of meningeal leukemia and carcinomatosis described above In the rare cases of meningeal involvement with Hodgkin lymphoma, there may be an eosinophilic pleocytosis Leptomeningeal dissemination occurs almost exclusively in small-cell, high-grade lymphomas with diffuse (rather than nodular) changes in the lymph nodes Cranial nerve palsies are common, with a predilection for the eighth nerve; the cauda equina is involved eventually in most cases The optimal treatment has not yet been ascertained Radiotherapy and systemic and intraventricular chemotherapy have all met with some degree of success Intravascular Lymphoma (Malignant Angioendotheliomatosis, Angiotropic or Angioblastic Lymphoma, and Lymphomatoid Granulomatosis) These related conditions are presented here with other forms of lymphoma, although their clinical behavior is more in keeping with a vasculitic process and the diagnosis is dif cult Although considered rare, we encounter a new case yearly on our services The nomenclature is confusing and the original term, lymphomatoid granulomatosis, is not universally accepted as equivalent to the more recently elucidated process of intravascular lymphoma; it is more accurate to consider it a prelymphomatous process As originally described by Liebow and colleagues, lymphomatoid granulomatosis is a systemic disease with prominent pulmonary, dermal, and lymph node changes and, in approximately 30 percent of cases, with involvement of the CNS In a small proportion of cases, the changes are con ned to the nervous system According to Katzenstein and associates, a systemic malignant lymphoma develops in about 12 percent of such patients, but others have noted this transformation in a considerably higher number The angioblastic or intravascular lymphoma, on the other hand, is regarded as a multifocal neoplasm of large anaplastic lymphocytes that in ltrate the walls of blood vessels and surrounding areas (Sheibani et al) or grow intravascularly and cause occlusion of small and moderate-sized vessels; hence the several alternative designations for the same pathologic process The disease can be distinguished from brain lymphoma, which is typically angiocentric, meaning centered around vessels, but brain lymphoma does not selectively invade and occlude vascular structures In the brain and spinal cord there are lesions of various sizes that represent the
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combined effects of occlusion of small vessels and concentric in ltration of the adjacent tissue by neoplastic cells In half of the cases, meningeal vessels are involved and the neoplastic cells have incited an in ammatory response that can be detected in the spinal uid, although malignant cells are not found in the uid In a few cases, the peripheral nerves, or more particularly the roots, have also been involved by the neoplasm, and we have seen two cases with a accid paraplegia on this basis Although the lymphoid origin of the anaplastic cells is now clear, not all of them are T cells, as was at one time believed; an equal number have the features of B cells Moreover, in some cases as in primary CNS lymphoma, portions of the genome of the Epstein-Barr virus (EBV) have been isolated from the malignant B cells within the pleocellular in ltrates For these reasons it has been proposed that the disorder represents an EBV-induced proliferation of B cells with a prominent in ammatory T-cell reaction (Guinee et al) Because of the inconsistent location and size of the nervous system lesions, there is no uniform syndrome, but the disease should be suspected in patients with a subacute encephalopathy and indications of focal brain and spinal cord or nerve root lesions Headache is a prominent early component in some cases One of our patients had intermittent seizures 3 months before confusion and progressive encephalopathy The variety of clinical presentations is emphasized in the reviews of 8 cases by Beristain and Azzarelli and the article by Glass and associates All had focal cerebral signs, 7 had dementia, 5 had seizures, and 2 had myelopathy Some of our own cases, as mentioned above, have also had a accid paraplegia due to in ltration of the cauda roots; this peripheral involvement has been commented on by other authors Only a few patients will have nodular or multiple in ltrative pulmonary lesions, skin lesions, or adenopathy; almost all of our cases were restricted to the brain and spinal cord, but other reports suggest systemic disease in a high proportion MRI shows multiple nodular or variegate abnormalities in T2weighted images throughout the white matter of the brain; most lesions are enhanced by gadolinium In one of the cases we studied there were numerous hemorrhagic lesions De nitive diagnosis is possible only through a biopsy of radiographically involved lung or nervous tissue that includes numerous intrinsic blood vessels A helpful diagnostic feature is the presence of antibodies to nuclear cytoplasmic antigens (c-ANCA), which are present in some cases, as they are in a number of other vasculitic and granulomatous processes A few of our own patients have also had adrenal or renal enlargement; presumably due to in ltration of the vessels of these organs by the neoplasm The spinal uid has a variable lymphocytic pleocytosis and protein elevation, but malignant cells are not found The sedimentation rate and serum LDH are said to be elevated in most patients, but this has not been so in our experience Like demyelinating and lymphomatous lesions, these abnormalities may recede temporarily in response to treatment with corticosteroids, and some clinical improvement occurs The course tends to be indolent and relapsing over months or years, although one of our patients died within weeks despite treatment In a few cases, whole-brain irradiation has been successful in prolonging survival, but the outlook in most instances is poor An uncertain number of these patients have AIDS (none in our group) The illness must be distinguished from multiple sclerosis, brain lymphoma, gliomatosis cerebri, and a process that simulates it closely, sarcoidosis (which produces brain and lung lesions) as well as from the cerebral vasculitides and Behcet disease,
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