Primary central nervous system lymphoma (PCNSL) has been known by many other names, including reticulum cell sarcoma, diffuse histiocytic lymphoma, and microglioma. The proliferation of names reflects initial uncertainty about the cell of origin.
PCNSL is now known to be a form of extranodal, high-grade non-Hodgkin B-cell neoplasm, usually large cell or immunoblastic type. It originates in the brain, leptomeninges, spinal cord, or eyes; typically remains confined to the CNS; and rarely spreads outside the nervous system. Therefore, it can be classified as stage 2 disease.
Previously a rare tumor accounting for less than 2% of cerebral neoplasms, PCNSL is being seen with increasing frequency in immunocompetent patients.
Although the cells of origin are lymphocytes, PCNSL should be considered a brain tumor, because its therapeutic challenges resemble those of other brain tumors. In particular, drug delivery is impaired by the blood-brain barrier, and cerebral toxicity limits the use of available treatment modalities.
Most PCNSLs (about 90%) are diffuse large B-cell lymphomas (DLBCLs); the remaining 10% are poorly characterized low-grade lymphomas, Burkitt lymphomas, and T-cell lymphomas. 
Primary symptoms may result from local mass effect due to raised intracranial pressure, from ocular involvement, or from focal deposits on cranial or spinal nerve roots.
Also see Non-Hodgkin Lymphoma.
Since the clinical and neuroimaging presentation of PCNSL can be varied and the differential diagnostic possibilities are therefore large, no patient should be treated for PCNSL without definitive cytologic proof of diagnosis, either by vitrectomy, positive CSF cytology, or brain biopsy.
Patients with acquired immunodeficiency syndrome (AIDS) may have coexisting infections; any change in neurologic examination findings or neuroimaging studies should be accordingly investigated broadly for the possibility of a diagnosis besides PCNSL.
The predilection of PCNSL for certain cerebral sites gives rise to its characteristic appearance on neuroimaging studies. Seventy-five percent of immunocompetent patients with these tumors have solitary lesions. The dense cellularity of the tumor accounts for its isodense or hyperdense appearance on nonenhanced CT scan and hypointense appearance on long TR-weighted MRI. 
Following administration of either iodinated contrast for CT or gadolinium for MRI, almost all PCNSLs enhance homogeneously. PCNSLs are assumed to be diffusely infiltrative at the time of presentation. The areas of disease are not visible on neuroimaging studies because they are behind a relatively intact blood-brain barrier.
The DLBCL type of PCNSL is composed of immunoblasts or centroblasts that have a predilection for blood vessels. Lymphoid clustering around small cerebral vessels is typically seen. Reactive T-cell infiltrates can also be present in varying degrees.
Evidence from a study by Sugita et al supported the concept that PCNSLs originate from a later germinal center to an early postgerminal center, and they may be capable of further maturation steps.  The study involved 32 PCNSL cases, with expression of proteins found at different stages in lymphocyte development; tumor specimens were immunophenotyped for antigens associated with germinal centers (CD10, Bcl-6) and with nongerminal center stages (SHP-1, CD138). In 30 of 32 cases, tumors were positive for SHP-1 but negative for CD138.
However, current evidence argues against the possibility that malignant lymphocytes perform further maturational steps. [4, 5] The tumor likely arises in an extraneural environment with subsequent localization to the CNS, possibly by virtue of a specific neurotropism.
Risk factors in immunocompetent patients
No clear risk factors for PCNSL in immunocompetent patients are known.
The disease is more common in men (the male-to-female ratio is 2:1) and in elderly persons. 
Risk factors in immunocompromised patients
The nature, intensity, and duration of immune suppression are factors in determining the risk of developing PCNSL. 
Prolonged glucocorticoid use usually is required (>6 mo).
Patients with AIDS who have low CD4+ counts are at the greatest risk for PCNSL. Patients with AIDS generally have CD4+ counts of fewer than 30 cells/µL.
Virtually all PCNSLs in patients with AIDS express an Epstein-Barr virus (EBV)-related genome. PCNSL is less frequently associated with EBV in patients without AIDS.
The overwhelmingly common risk factor for PCNSL related to human immunodeficiency virus (HIV) infection is intravenous (IV) drug abuse.
Corboy et al reported that 56% of a group of immunocompetent and immunocompromised patients had human herpes virus 8 (HHV-8) in their tumors. This is the same herpes virus that is associated with Kaposi sarcoma and with primary effusion (ie, body-cavity-based lymphomas); however, a direct causal relationship of this herpes virus to any PCNSL has not yet been established.  (HHV-8 has been detected in PCNSLs by PCR at low copy number, suggesting that HHV-8 is present in a cell compartment other than the malignant one.)
Gomez-Brouchet et al studied 35 patients (17 with and 18 without AIDS) with PCNSL for the presence of HHV-8 in tumor cells. The antibody LN53, which reacts with the latent nuclear antigen 1 (LNA1) of HHV-8, was used on tissue sections from these patients and in addition, DNA was available for PCR. They found none of the 35 cases contained either DNA sequences or LNA1-positive cells in the tumor cells of PCNSL. 
Incidence in the United States
PCNSL incidence has risen steadily since the end of the 20th century. Incidence in immunocompetent patients is approximately 51 cases per 10,000,000 per year.
PCNSL has been reported in 6-20% of patients infected with HIV, and the incidence is expected to rise as patients with low CD4+ counts survive longer.
Similar trends toward rising frequency of diagnosis of PCNSL are reported.
Among immunocompetent patients with PCNSL, males outnumber females by approximately 2:1.
Almost 95% of HIV-infected patients with PCNSL are males.
The median age of immunocompetent patients with PCNSL is 55 years.
The median age of HIV-infected patients with PCNSL is 35 years.
The most typical presentation of PCNSL in an immunocompetent patient is progressive focal symptoms indicative of a mass lesion. Seizures may occur. Sometimes, nonspecific mental status change leads to the diagnosis. Several variant presentations of PCNSL are discussed in this section.
Patients with AIDS are more likely to present with an encephalopathy than other patients with PCNSL. This correlates with the more often multifocal, diffuse enhancement pattern seen on magnetic resonance imaging (MRI) scans. A history of concurrent infections is quite common, and the median CD4+ count is 20 cells/µL.
Much of the history taking should be devoted to establishing whether the patient may have immune deficiency. A careful sexual and drug abuse history is necessary. If the patient is a transplant recipient, the nature and duration of immune suppression must be clarified.
The diagnosis of PCNSL in immunocompetent and immunocompromised patients is particularly difficult if they present with one of the variant syndromes outlined here.
Isolated, ocular, or meningeal tumor may occur in the absence of any focal abnormalities on MRI. Such patients give a history of (1) blurred vision, (2) headache, (3) isolated cranial nerve dysfunction (eg, diplopia, dizziness, dysphagia, facial numbness, monocular visual loss), or (4) spinal nerve root symptoms (eg, pain, dysfunction localized to 1 dermatome, bowel or bladder problems).
Relapsing, remitting lesions may disappear for periods of as long as several months to a year or more. Administration of corticosteroids may cause prolonged remission of clinical and radiographic signs and symptoms, but remission also occurs spontaneously.
Progressive dementia or stupor with no focal signs and with little or no enhancement on MRI may be more common in patients with AIDS who have PCNSL.
Intravascular malignant lymphomatosis (previously called neoplastic angioendotheliosis) is a series of strokelike focal events, and the MRI may look like multiple large- and small-vessel ischemic strokes and at times single or multiple focal intracerebral hemorrhage. Parasitosis, malignant lymphoma, or metastatic brain tumor often enter the differential diagnosis. Diagnosis often moves away from stroke by the steady progressive clinical course and is often confirmed by brain biopsy and histology and immunochemical staining of the biopsy specimen.
Neurolymphomatosis is the only PCNSL syndrome that involves both the central and peripheral nervous systems at presentation. Cerebral lymphoma with focal mass lesions, as well as infiltration of peripheral nerves, is seen.
Levin et al report 100 cases of PCNS lymphoma over a period of 10 years, of which 5% were primary meningeal lymphoma.  These 5 patients presented with leptomeningeal involvement as the sole manifestation and 4 of them presented with neuronal lymphomatosis affecting cranial and peripheral nerves. These manifestations can mimic other neurologic conditions such as pseudotumor cerebri or vasculitis. Meningeal or nerve biopsies were required for conclusive diagnosis.
Lenarz et al report a case of primary CNS lymphoma involving both internal auditory canals that presented with sudden deafness and disequilibrium accompanied by facial and abducens nerve palsy. 
Khong et al reported a rare case of neurolymphomatosis manifesting as acute cauda equina syndrome in a 16-year-old patient. 
The goal of the general physical examination is to detect possible extraneural sources of lymphoma. Examine for lymphadenopathy, abdominal masses, and skin lesions (sarcoidosis may mimic PCNSL on neuroimaging studies, or cutaneous lymphoma may be present).
Neurologic examination should be directed toward determining which compartments of the nervous system are involved, as follows:
Examination for focal deficits
Examination of peripheral nerves for evidence of neuropathy (suggestive of systemic process or neurolymphomatosis)
Eye examination for vitreous involvement
The eye examination will require ophthalmologic consultation and slit-lamp examination and is a necessary part of the workup in all patients with PCNSL who have raised intracranial pressure. Papilledema may be present.
Differential diagnosis of a patient with suspected PCNSL depends on the patient's immune status and the radiographic appearance of the lesions. For example, the major differential diagnostic possibilities raised in an immunocompetent patient with a solitary lesion (besides PCNSL) are high-grade primary brain tumor, such as glioblastoma, and isolated metastasis.
In patients with AIDS, multifocal, ring-enhancing lesions raise the question of toxoplasmosis or another opportunistic infection. More diffuse cognitive and MRI abnormalities suggest the possibility of some infectious encephalitic process, such as herpes zoster, cytomegalovirus encephalitis, cryptococcal meningitis, or AIDS/dementia complex.
Differentials to consider in PCNSL include the following:
Abducens nerve (cranial nerve VI) palsy
Acute disseminated encephalomyelitis
Cauda equina and conus medullaris syndromes
Epilepsy in children with mental retardation
Granulomatous angiitis of the CNS
HIV-1 associated opportunistic infections: PML
The following should be ordered in an immunocompetent patient whose computed tomography (CT)/MRI scan suggests PCNSL:
Withhold corticosteroids, as their use may complicate diagnosis
Chest radiograph to rule out metastatic disease
Complete blood count (CBC)
Slit-lamp examination for vitreous lymphoma
Lumbar puncture for cells, glucose, protein, and cytology in the cerebrospinal fluid (CSF)
The following should be ordered in an HIV-infected or otherwise immunocompromised patient whose CT/MRI scan suggests PCNL:
Toxoplasma gondii serology
Slit-lamp examination for vitreous lymphoma
Lumbar puncture for cells, glucose, protein, cytology, syphilis testing, and cryptococcal antigen
Fischer et al presented the first prospective comparison of the diagnostic value of cerebrospinal fluid (CSF) cytomorphology, polymerase chain reaction (PCR) assay of the rearranged immunoglobulin heavy-chain (IgH) genes, and MRI in conjunction with cell count and protein concentration for the detection of meningeal dissemination in patients with PCNSL treated in a large multicenter study. They found a low rate of meningeal dissemination in primary CNS lymphoma in this large prospective study. The rate of discordant PCR and cytomorphologic results was high. Thus, they feel that these methods should be regarded as complementary. CSF pleocytosis had predictive value for meningeal dissemination detection. 
MRI of the brain shows a hypointense lesion or lesions on long TR-weighted images, which enhance densely and homogeneously after contrast administration. Lesions are multifocal in 50% of patients with AIDS, whereas only 25% of immunocompetent patients have multifocal disease at presentation. MRI also gives information about leptomeningeal enhancement, hydrocephalus, and concurrent alternative diagnoses, such as infections in patients with AIDS.
Patients with focal spinal, root, or cord symptoms should undergo MRI of the spine with and without contrast to localize the deposits of lymphoma. These lesions, when found, may be amenable to radiation therapy.
Chest and abdominal CT scans should be performed, because a small minority of immunocompetent patients has an extraneural source for their cerebral lymphoma. Common sites are abdomen and breast. Therefore, after the establishment of a definitive diagnosis of PCNSL, these staging procedures should be performed. Staging of extent of extraneural lymphoma has a higher yield in patients with AIDS.
Thallium-201 single-photon emission computed tomography (SPECT) scanning is appropriate in patients with AIDS to help distinguish between infectious processes and PCNSL. Patients with AIDS may have a cystic, ring-enhancing lesion with PCNSL instead of the homogeneously enhancing abnormalities seen in immunocompetent patients. The presence of single or multiple ring-enhancing lesions in patients with AIDS raises suspicion of toxoplasmosis, Nocardia asteroides infection, or neurosyphilis.
Liver function tests
Because the mainstay of treatment for many patients is high-dose methotrexate, hepatic function must be evaluated. Tests should include serum bilirubin (total/direct), aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase.
Twenty-four-hour urine collection for creatinine clearance
Patients being considered for methotrexate chemotherapy must have a glomerular filtration rate (GFR) of greater than 100 mL/min, because inadequate renal clearance enhances methotrexate toxicity.
Slit-lamp examination and possible vitrectomy
Although fewer than 10% have vitreous involvement at initial presentation, all patients should undergo slit-lamp examination. Vitrectomy may establish the diagnosis, sparing brain biopsy in these patients.
Stereotactic brain biopsy is the most appropriate method for the diagnosis of PCNSL. However, open brain biopsy may be necessary in those patients who have lesions located in areas of the brain that are difficult to access (eg, brainstem). If possible, the procedure should be performed before corticosteroids have been administered.
PCNSL is a densely cellular, aggressive non-Hodgkin B-cell lymphoma. Immunocompetent patients usually have a small, noncleaved cell or immunoblastic subtype. Perivascular clusters of lymphocytes and T-lymphocyte infiltrates are common in immunocompetent patients. T-lymphocyte infiltrates are not found in patients with AIDS.
The goal of treatment is eradication of contrast-enhancing mass lesions and microscopic infiltration of brain, spine, leptomeninges, and vitreous. Successful therapy in immunocompetent patients leads to a median survival duration as long as 44 months. Treatment must be designed to maximize efficacy and minimize toxicity to cerebral white matter.
The optimal treatment for PCNSL has not been established. Standard systemic chemotherapy regimens such as CHOP (ie, cyclophosphamide, doxorubicin, vincristine, prednisone) are ineffective, which presumably reflects the difficulty of penetration of the blood-brain barrier by chemotherapeutic drugs.
Methotrexate is the single most effective chemotherapeutic agent for PCNSL.
Initial chemotherapy without radiation therapy results in excellent initial tumor response rates and avoids the toxicity associated with combined modality therapy (ie, radiation and chemotherapy).
The following recommendations are based on an ongoing protocol at the author's and several other institutions, and on observation that radiation therapy alone, while initially effective, produces a median survival duration of only 18 months. Combination chemotherapy and radiation therapy more than doubled survival time, but such success was achieved at the price of a greater than 50% incidence of dementia in patients who survived more than 18 months on these regimens.
The decision to offer chemotherapy as the sole initial treatment modality, therefore, must be made while keeping in mind that optimal dose and timing are still under investigation. Current active protocols for the treatment of PCNSL have been described by Hoang-Xuan and Delattre.
Methotrexate-based chemotherapy regimens have been the most successful treatment strategies to date. Methotrexate is a folate analogue that interferes with DNA synthesis and repair. For treatment of PCNSL, patients receive high-dose systemic methotrexate. This is because when the drug is administered in high doses systemically, it achieves therapeutic levels in brain parenchyma and obviates intrathecal therapy as an initial treatment for PCNSL.
Close monitoring and adjustment of IV fluids and calcium leucovorin rescue necessitates inpatient administration of this drug.
Corticosteroids are avoided during the initial workup, because their administration may have a direct antitumor effect on B-cell lymphoma (B lymphocytes have glucocorticoid receptors on their surfaces) and cause dramatic reduction in MRI abnormalities, making biopsy and histologic confirmation more difficult.
Similarly, corticosteroids should be avoided, if possible, during chemotherapy, because repair of the blood-brain barrier may decrease the delivery of methotrexate into the brain parenchyma. However, the use of corticosteroids may improve quality of life by minimizing symptoms due to vasogenic edema or tumor mass effect; the smallest effective dose should be prescribed.
Other chemotherapeutic drugs
Voloschin et al reported that topotecan, as a salvage therapy in patients with relapsed or refractory PCNSL, is associated with an overall response proportion of 40% and should be considered in patients who have failed prior methotrexate-based chemotherapy and/or whole brain irradiation. However, progression was frequent and early, and most patients required growth factor support due to myelotoxicity. 
In a retrospective study of 221 patients with brain and ocular lymphoma, Grimm et al found that dedicated ocular therapy improved disease control but did not affect overall survival. The patients in the study were HIV-negative and immunocompetent, and none had systemic lymphoma. 
In phakic intraocular lenses (PIOL), vitrectomy improves vision by eliminating opacities formed by cellular clumps and debris in the vitreous cavity. Because of the high incidence of bilateral disease, ocular external-beam radiotherapy is recommended for both eyes. The trend is now toward using systemic chemotherapy for PIOL. If refractory or recurrent intraocular disease is encountered, additional systemic/intrathecal chemotherapy with adjunctive intravitreal methotrexate is administered. PIOL remains an aggressive disease with an overall 5-year survival rate of less than 25%.
Prophylactic use of antiepileptic drugs (AEDs) should be avoided and their use should be confined to patients who experience seizures. Any of the first-line AEDs (eg, phenytoin, carbamazepine, valproic acid) would be appropriate for patients with PCNSL, although leukopenia and liver function abnormalities from any of these drugs potentially could be confused with chemotherapy-related toxic effects. New-generation antiepileptic drugs, such as levetiracetam (Keppra), have high efficacy and fewer side effects.
Antiemetics are useful in the treatment of nausea associated with chemotherapy and radiation therapy.
Long-term sequelae of radiation therapy and chemotherapy in PCNSL are significant. Although median survival duration has been extended with combined chemotherapy and radiation therapy, the percentage of survivors with late cerebral white-matter toxicity resulting in cognitive dysfunction approaches 50%.
Serious leukoencephalopathy also is seen in patients receiving methotrexate chemotherapy alone, but the incidence appears to be lower than that of the cerebral white-matter toxicity seen with combination therapy.
Aggressive debulking has no role in the treatment of PCNSL lesions.
Placement of an Ommaya reservoir sometimes is needed for repetitive instillation of intrathecal chemotherapy in patients with leptomeningeal lymphoma; however, it is not a routine procedure for patients with PCNSL of the brain parenchyma.
Ophthalmologic consultation is required as part of the initial workup and staging of PCNSL, in order to exclude vitreous involvement. Vitrectomy may be performed to establish diagnosis for patients with abnormal findings on slit-lamp examination.
Medical oncologic consultation is appropriate for any patient with suspected PCNSL who has an abnormal chest or abdominal CT scan; patients with CBC abnormalities may need bone marrow biopsy. Before beginning treatment for PCNSL, systemic disease that would alter the planned chemotherapy drug regimen must be ruled out.
Diet and Activity
During chemotherapy with high-dose methotrexate, patients must be hydrated adequately. They must take sodium bicarbonate (3 g q4h) during the 24 hours prior to and during the methotrexate therapy. They should avoid fruit juices that might acidify the urine. Drugs to be avoided during methotrexate therapy include salicylates, nonsteroidal anti-inflammatory drugs, and sulfonamides.
No major activity restrictions apply to patients with PCNSL, although vigorous physical activity is discouraged for 3 weeks following brain biopsy.
In-Hospital Care Considerations
After biopsy, some patients may require inpatient care because of neurologic deficits related to the primary site of the tumor.
The use of corticosteroids to control symptoms may be unavoidable, but administration of dexamethasone or its equivalent, in doses greater than 8 mg/day for more than 2 weeks, raises the risk of steroid myopathy. Patients with muscle weakness due to steroids may require inpatient rehabilitation.
High-dose systemic methotrexate must be administered in the hospital.
Recurrence or Failure of First-Line Chemotherapy
Patients are monitored with monthly MRI scans after initiation of methotrexate chemotherapy. Those with primary leptomeningeal disease should undergo lumbar puncture with cytologic sampling of CSF at monthly intervals.
The management of progressive (ie, methotrexate failure) or recurrent PCNSL is not yet well established. The age and performance status of the patient must be considered. In general, a greater than 25% enlargement of previous areas of gadolinium-contrast enhancement, the appearance of new contrast-enhancing lesions, or the appearance of malignant cells in the CSF, vitreous or, rarely, elsewhere in the body, constitutes treatment failure. Treatment options include the following:
Return from monthly (maintenance) to biweekly methotrexate therapy
Consider IV cytarabine
Radiation therapy is probably the best second-line anti-PCNSL treatment
Chemotherapy failure indicates that combined therapy is necessary, accepting that the risk of neurotoxicity from radiation and chemotherapy is considerable
Until the efficacy of repeat intensive methotrexate therapy is established in relapsed disease or until other chemotherapeutic agents are tested more extensively, whole-brain radiation therapy with 4000 cGy in 20-25 daily treatments is recommended.
Deterrence and Prevention of PCNSL
Because the reasons for the development of PCNSL in immunocompetent patients are unknown, whether deterrent or preventive maneuvers can be undertaken also is unknown.
Patients receiving immunosuppressive therapy after organ transplantation should receive the smallest effective doses compatible with the viability of the transplant. Corticosteroid-sparing therapy is advised, and lowering of the intensity of immunosuppression, if feasible, is advised for transplant recipients who develop PCNSL.
Patients with AIDS who have low CD4+ counts are at the greatest risk for PCNSL. The extent to which highly effective antiretroviral therapy will affect the incidence and prognosis of PCNSL in AIDS is not yet known.
Roth et al found, in a large cohort of 526 PCNSL patients, about 126 who were ≥70 years old. The success with high-dose methotrexate-based chemotherapy was 44% in the elderly versus 57% in the younger patients. The risk of severe leukopenia was greater in the older patients, and the risk of death while on chemotherapy was also greater in this cohort. Progression-free survival rate was 4.0 months in the elderly compared to 7.7 months in the younger group. Overall survival was shorter, 12.5 months in the elderly group, contrasting with 26.5 months in younger patients. Lastly, older patients were less likely to undergo salvage therapy with whole brain radiation or cytarabine chemotherapy.
Based on their observations, the authors postulate that PCNSL in older patients is a biologically different tumor that is typically more resistant to treatment. The authors discuss possible treatment strategies to be developed in older patients who achieved a complete remission initially.
The awareness of a different prognosis in different age groups is a significant contribution. The possible benefit of newly developed agents may also identify better treatments for the older PCNSL patient. 
The initial response to radiation therapy is excellent, often resulting in complete resolution of radiographic abnormalities. Nevertheless, the duration of response is short, and median survival duration with radiation therapy alone averages only 18 months. Relapse in patients with parenchymal disease is usually within the brain, although leptomeningeal, vitreous and, rarely, systemic recurrences are reported.
Methotrexate-based chemotherapy as the sole treatment modality results in median survival duration approaching 48 months.
Patients with AIDS
Patients with AIDS have only a 4-month median survival duration with radiation therapy. Untreated, such patients often die within 2.5 months, sometimes because of coexisting infections.
Extended survival in subgroups of HIV-infected patients with CD4+ counts greater than 200 cells/µL and no concurrent opportunistic infections have been reported. With a regimen of intrathecal methotrexate, concurrent systemic procarbazine, cyclohexylchloroethylnitrosourea (CCNU), vincristine, and whole-brain radiotherapy, this small subset of patients with AIDS had median survival durations ranging from 10-18 months.
The prognostic value of serum markers in PCNSL was reported in a prospective study of 45 PCNSLs.  Disease status, radiographic appearance, and length of survival correlated with serum levels of YKL-40 and MMP-9. The authors’ main objective was to identify disease severity markers as a treatment guide. YKL-40 is a tissue marker of inflammation related to carcinogenesis, and MMP-9 tissue controls remodeling permeability. YKL-40 and MMP-9 levels were associated with “active disease,” particularly if a longitudinal, steady serum level increment was noted. Consistently low serum levels, on the other hand, were found with “absence of tumor.”
In another study, overexpression of BCL-6 was associated with improved survival (median, 101 months) over that of patients whose tumors that did not express BCL-6 (median, 14.7 months).  The search is on for additional prognostic markers.
Patients receiving high-dose IV methotrexate must be educated carefully about the drugs to be avoided in the week prior to chemotherapy and about the fluid and intensive monitoring requirements of their inpatient stay.
Patients who have left the hospital should be educated about the possibility of seizures and should be encouraged to pursue physical therapy to maximize motor function.
Patients with AIDS should continue to follow the antiretroviral regimen recommended by their physician.
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- Physical Examination
- Differential Diagnosis
- Diagnostic Overview
- CT Scanning
- SPECT Scanning
- Other Tests
- Histologic Findings
- Medical Care
- Surgical Care
- Diet and Activity
- In-Hospital Care Considerations
- Recurrence or Failure of First-Line Chemotherapy
- Deterrence and Prevention of PCNSL
- Patient Education
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