Primary CNS lymphoma …

Karan S Dixit MD

Neuro-Oncology

Updated 02.23.2026
Released 02.14.1994
Expires For CME 02.23.2029

Primary CNS lymphoma

Author: Karan S Dixit MD

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Editor: Rimas V Lukas MD

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Primary CNS lymphoma

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Introduction

Overview

Diffuse large B-cell lymphoma of the CNS (per WHO 2022 World Health Organization Classification of Haematolymphoid Tumours), or more commonly known as primary central nervous system lymphoma (PCNSL) throughout this article, is an extranodal non-Hodgkin lymphoma that arises within and is confined to the nervous system, including the brain, spinal cord, leptomeninges, and eyes. In this article, the author discusses developments in managing primary central nervous system lymphoma.

Key points

	• Diffuse large B-cell lymphoma of the CNS is a non-Hodgkin lymphoma that arises within and generally remains confined to the nervous system.
	• Staging work-up differentiates primary CNS lymphoma from extra-CNS lymphoma with CNS involvement.
	• In the immunocompromised setting, the disease is often associated with the Epstein-Barr virus.
	• Treatment options include systemic chemotherapy, intra-CSF chemotherapy, radiotherapy, and targeted therapies. High-dose methotrexate forms the backbone of many treatment protocols.

Historical note and terminology

Primary central nervous system lymphoma was first described in 1929 by Bailey (06). Over the following 2 to 3 decades, cerebral lymphoma was recognized as a discrete entity but described under a variety of names, including reticulum cell sarcoma, histiocytic sarcoma, and microglioma, highlighting the debate regarding the malignant cell of origin; however, modern immunohistochemical studies definitively established the lymphocytic nature of this tumor. Since 2022, the WHO has updated the nomenclature to primary diffuse large B-cell lymphoma (DLBCL) of the central nervous system (CNS), and is classified within the large B-cell lymphomas of immune-privileged sites category.

Clinical manifestations

Presentation and course

Primary central nervous system lymphoma usually occurs in the brain as an intracranial mass (masses) but may also involve the spinal cord parenchyma, leptomeninges, and eyes. Most commonly, these other disease sites occur along with brain lesions, but occasionally they may be the only site of lymphoma or the presenting location of disease. The peak incidence occurs in the sixth and seventh decades of life in immunocompetent patients and may be increasing in incidence (60).

Because primary central nervous system lymphoma can be a rapidly growing neoplasm, most patients have symptoms for only a few weeks before coming to medical attention. Neurologic dysfunction can progress rapidly over a few days; however, some patients may have a more indolent course, with symptoms gradually evolving over months. This is particularly true of patients whose disease begins within the eye, and ocular symptoms may wax and wane for years before a definitive diagnosis is established. Rarely, patients have spontaneous remissions of symptoms and even mass lesions identified on imaging; more commonly, remission is precipitated by corticosteroid administration (04; 59; 47).

The overwhelming majority of patients present with symptoms and signs suggestive of a brain tumor. These can be categorized as either localizable or nonlocalizable. The localizable symptoms correlate with involved neuroanatomy. Approximately 50% to 70% of patients present with focal neurologic deficits (08). Because the frontal lobes are commonly affected, cognitive changes and an altered level of alertness occur in one half to two thirds of patients. As a presenting complaint, seizures are seen in only 10% of patients, compared to 25% to 75% of those with other primary or metastatic brain tumors (17). Nonlocalizable symptoms are typically due to increased intracranial pressure and include symptoms such as headaches, which are often worse when first awakening in the morning or may wake patients from sleep.

Ocular lymphoma involves the vitreous, uvea, or retina (72; 94). Symptoms are often subtle and consist of floaters or visual blurring. These symptoms are nonspecific, and patients are often initially diagnosed with uveitis or vitreitis of unknown etiology. The symptoms and inflammatory cells seen in the vitreous on slit-lamp examination may persist for years, eventually causing visual loss, although visual loss is rare in the early stages. The absence of a durable clinical response to the usual therapy, topical steroids, should suggest the diagnosis of ocular lymphoma. Most patients with ocular involvement also have nonocular CNS involvement (36). Ocular involvement of primary CNS lymphoma is estimated to occur in 15% of cases at initial diagnosis (43). Approximately 37% to 50% of patients with primary vitreoretinal lymphoma have concurrent CNS involvement (55). Furthermore, patients with primary vitreoretinal lymphoma are at risk of developing CNS disease during their disease, estimated at over 30% to 80% by 50 months, which necessitates close radiographic and oncologic surveillance (76).

Leptomeningeal lymphoma presents with confusion, cranial neuropathies, radiculopathies that may be painful, symptoms of increased intracranial pressure (headache, nausea, and vomiting), or a combination of these symptoms. Tumor cells can gain access to the CSF by virtue of the periventricular location of lymphoma lesions, and leptomeningeal involvement can be documented in up to 40% of patients. Leptomeningeal lymphoma is more frequently a manifestation of CNS involvement in patients with extra-CNS lymphoma.

Spinal lymphoma often presents as a painless myelopathy with symptoms localizable to the cord level. Primary spinal cord lymphoma is exceedingly rare, accounting for only 1% of primary CNS lymphoma (95).

Prognosis and complications

There are two widely used prognostication systems. The first is the International Extranodal Lymphoma Study Group (IELSG) prognostication system. In this system, points are allotted for age, performance status, serum LDH, CSF protein, and deep-seated lesions. These points can be utilized to calculate a prognostic score (27). The second system is the Memorial Sloan-Kettering Cancer Center (MSKCC) prognostic system. This system relies only on age and performance status to estimate survival (01). In both systems increasing age and worsening performance status are associated with shorter survival. The inferior outcomes with increasing age are also reflected in epidemiologic studies (71). On analysis of a contemporary population of primary CNS lymphoma patients, 2-year survival is approximately 50%, and 5-year survival is 38% with aggressive therapy (43).

In elderly patients, the presence of Epstein-Barr virus in tumor tissue suggests a worse prognosis with a shorter survival from primary CNS lymphoma (90). This may merely reflect a confluence of two potential negative prognostic factors, age and immunosuppression (which is often associated with Epstein-Barr virus positivity). Numerous other prognostic biomarkers have been investigated, at times with conflicting results.

Clinical vignette

A 54-year-old man with a history of depression gradually developed memory disturbances, poor concentration, apathy, and fatigue. His symptoms were initially attributed to depression, but then he noted that his left foot was dragging. An MRI with contrast demonstrated an irregularly enhancing lesion in the right frontal lobe with surrounding T2 hyperintensity and mild mass effect. HIV testing was negative. He was placed on steroids before undergoing brain biopsy. Unfortunately, the biopsy was nondiagnostic. His symptoms resolved on steroids, and he was subsequently tapered off. A few weeks later, he developed slurred speech, confusion, and gait instability. A repeat brain MRI with contrast demonstrated a new, enhancing right cerebellar lesion as well as faint enhancement within the right frontal lobe. Steroids were not restarted, and he underwent biopsy of the right cerebellar lesion. Pathology demonstrated a diffuse large B cell lymphoma. To complete lymphoma staging, he underwent ophthalmologic examination, including slit lamp examination and body PET scans. There was no evidence of systemic or ocular lymphoma. He was started on a high-dose methotrexate (HD-MTX) containing regimen and achieved a complete response before moving forward with consolidation therapy.

This clinical vignette demonstrates the importance of withholding steroids in suspected cases of CNS lymphoma. Corticosteroids work as a lymphotoxic agent and may result in a marked decrease or complete disappearance of brain lymphoma lesions (59; 47). When the residual lesions are biopsied, they are frequently necrotic, or nondiagnostic tissue is obtained, and no definitive diagnosis is made. In this case, pathologic confirmation of primary central nervous system lymphoma was delayed due to corticosteroid administration. Hyperosmotic agents such as mannitol of hypertonic saline, in place of steroids, can be considered a means to decrease cerebral edema if necessary.

Biological basis

Etiology and pathogenesis

The etiology of cerebral lymphoma in immunocompetent patients is incompletely understood.

Immunophenotyping studies suggest that the malignant B cells are derived from highly mutated late germinal center or postgerminal center B cells (64; 88).

In immunosuppressed patients, particularly those with AIDS or transplant recipients, the Epstein-Barr virus appears to have an important etiologic role (61; 20). Most adults have had acute Epstein-Barr virus infection in childhood, and a small population of B lymphocytes becomes immortalized by the virus. Proliferation of this latently infected population is controlled by circulating T-cells and rarely leads to malignancy; however, when the host immune system is no longer capable of suppressing this latently infected lymphocyte population, uncontrolled cell growth leads to tumor formation. These Epstein-Barr virus-driven lymphomas tend to develop in the nervous system because the brain is an immunologically privileged site offering further protection from immune surveillance (58).

Most primary central nervous system lymphomas are classified as nongerminal cell B-cell-like (non-GCB) immunophenotypes according to the Hans classification system.

There is increasing understanding of the biological basis of lymphoid malignancies, including primary CNS lymphoma. Mutations in MYD88 L265P are frequently seen in systemic diffuse large B-cell lymphomas as well as primary CNS lymphoma. The MYD88 gene codes for a B-cell signal adaptor protein with mutations leading to constitutive activation for the NF-kappaB pathway (73).

In addition to MYD88, other mutations frequently seen are CD79B and CARD11, which are involved in the Toll-like and B-cell receptor signaling pathways (13). The primary CNS lymphoma mutational profile is most similar to the “MCD/C5” subtype for systemic lymphoma (15). There are several biologic cornerstones that have been described for primary central nervous system lymphoma: (1) chronic active BCR signaling through activating mutations of MYD88 (L265P) and CD79B which form the MYD88-TLR9-BCR) complex; (2) immune escape through inactivating mutations of class 1 and 2 HLA expression; (3) unregulated cell cycle activation through loss of CDKN2A; and (4) ongoing proliferation through inactivating mutations in transcription factors such as PRDM1 and TBL1XR1 (77).

Differential diagnosis

Patients with primary central nervous system lymphoma usually present with cerebral symptoms that prompt the physician to obtain CNS imaging. Although no absolute radiographic appearance exists that permits a definitive diagnosis, there are characteristic features that should strongly suggest the diagnosis and differentiate it from other space-occupying brain lesions such as demyelinating diseases, gliomas, meningiomas, metastasis, sarcoidosis, and toxoplasmosis. In immunocompetent patients, primary central nervous system lymphoma is usually isodense or hyperdense on CT scan before contrast administration and isointense or hyperintense on precontrast T1-weighted MR images.

Multifocal primary central nervous system lymphoma (MRI)

(Contributed by Dr. Lisa DeAngelis.)

On CT or MRI scan, cerebral lymphoma typically has a dense and uniform enhancement pattern after contrast administration. Ring enhancement, which is usually seen with infections, brain metastases, and malignant gliomas, is distinctly uncommon in cerebral lymphoma. Lymphomatous lesions are frequently periventricular and have indistinct borders. Thirty-five percent of patients have more than one lesion. Intraparenchymal lesions may be located in the hemispheres (38%), thalamus/basal ganglia (16%), corpus callosum (14%), ventricular areas (12%), and cerebellum (9%) (52). Cerebral metastases, which can have a similar appearance to primary central nervous system lymphoma on MRI, are usually located at the cortical gray-white junction and watershed zones. The amount of edema associated with lymphoma masses may be highly variable. Some patients do have extensive peritumoral edema as seen with other brain tumors; however, many patients have little or no edema surrounding their lesions, a rare finding in other primary or metastatic brain tumors. On MRI, diffusion-weighted imaging often demonstrates restricted diffusion throughout the lesions (62). Calcifications frequently seen in oligodendrogliomas and low-grade astrocytomas are usually absent in primary central nervous system lymphoma.

These radiographic features, which are present in most patients, should lead to diagnostic consideration of primary central nervous system lymphoma, even before histologic confirmation is obtained. This consideration should affect the preoperative management of patients and help to avoid several pitfalls that complicate establishing the pathologic diagnosis.

Confusing conditions

When intracranial mass lesions are identified on CT or MR scan, the initial reaction is often to begin corticosteroid therapy to reduce perilesional swelling and improve the patient's neurologic status. Although this may be the proper approach for patients with metastases or malignant gliomas, it frequently destroys the opportunity to establish the diagnosis of cerebral lymphoma. Corticosteroids work as a chemotherapeutic agent against systemic and central nervous system lymphomas; they are cytotoxic and will produce cell lysis of malignant lymphocytes. At least 40% of patients have a marked decrease or complete disappearance of their brain lymphoma lesions, often within days of corticosteroid administration (41; 59; 47; 07). When the neurosurgeon biopsies residual lesions, frequently necrotic or nondiagnostic tissue, often demonstrating a T cell infiltrate, is obtained, and no definitive diagnosis is made, compromising subsequent treatment. Some consider resolution of an intracranial mass diagnostic of cerebral lymphoma; however, other lesions are known that contrast-enhance and resolve with steroid administration, such as multiple sclerosis and sarcoidosis, neither of which would require treatment with an HD-MTX regimen. Therefore, steroids should be withheld from patients whose cranial MRI or CT images suggest primary central nervous system lymphoma unless the patient is in imminent clinical danger of cerebral herniation, an extremely rare situation. Even in those circumstances, acute management plans can often utilize mannitol or hypertonic saline in place of steroids.

In HIV-positive patients, the radiographic appearance of primary central nervous system lymphoma is more variable and less distinctive. The lesions are hypodense (CT scan) or hypointense (MRI scan) before contrast and usually ring-enhancing, reflecting the high incidence of central necrosis seen in AIDS-related cerebral lymphoma (12; 46).

Ring-enhancing lesion in suspected CNS lymphoma (MRI)

Axial brain MRI (T1 with contrast) shows a 7 mm ring-enhancing periventricular lesion in the right frontal lobe abutting the frontal horn of the right lateral ventricle and corpus callosum in a HIV-positive patient. Differential d...

Diffuse enhancement is rarely seen in immunocompromised patients, and the lesions are more frequently cortical in location than in immunocompetent patients. No characteristic radiographic features of brain lymphoma exist in immunocompromised patients, and the lesions can be indistinguishable from toxoplasmosis or other infectious or neoplastic processes (58; 35). Positron emission tomographic scans or SPECT scans are reported to accurately differentiate cerebral lymphoma from infection in AIDS patients and may assist in early diagnosis. Particularly when combined with the detection of Epstein-Barr virus DNA in the CSF, these techniques can help facilitate a noninvasive diagnosis in many patients (05; 84). However, in most cases in the contemporary era, obtainment of a tissue diagnosis is necessary to move forward with confidence with the treatment via a high-dose chemotherapy regimen.

Associated or underlying disorders

Patients with single lesions are most often confused with patients harboring other malignant primary brain tumors such as gliomas. The extent of tumor resection may favorably influence survival of patients with gliomas, and complete radiographic resection is often the surgical goal. In primary central nervous system lymphoma, there is longstanding evidence to support worse outcomes with surgical resection. However, this is being debated by some (93; 96; 75).

Patients with chronic immunosuppression, such as those after organ transplant, are at higher risk of developing post-transplant lymphoproliferative disease. A minority of these cases, up to 15%, can present only the CNS (25).

Diagnostic workup

Brain MRI scan with gadolinium is the single most important imaging study for the evaluation of a patient with primary central nervous system lymphoma. It will define the areas of tumor and may demonstrate leptomeningeal involvement in an occasional patient. CT scan can be used when MR scanning is not available, but it is inferior. Stereotactic biopsy is indicated for pathologic confirmation. At this time there is no definitive serum or CSF diagnostic biomarker that can be utilized in all patients in place of biopsy.

Once the diagnosis of primary central nervous system lymphoma is established, all patients should undergo an ophthalmologic examination, including slit-lamp, to exclude ocular involvement. Patients with spinal symptoms should have a spinal MRI with contrast. This is not typically indicated for patients without symptoms localizable to the spine. Lumbar puncture to look for leptomeningeal spread of tumor with CSF cytology, CSF protein, flow cytometry, and IgH gene rearrangement PCR studies may be performed. It is unclear whether it adds any diagnostic value. In patients with positive CSF, the CSF should be followed to assess treatment response. Molecular biomarkers are not widely used for diagnosis of primary CNS lymphoma; however, there is increasing evidence that MYD88 L265P mutations and elevated levels of interleukin-10 (IL-10) may be reliable CSF biomarkers but require additional validation (28). Liquid biopsy assays, such as with cell free DNA, may be effective ways to diagnose primary central nervous system lymphoma without tissue sampling but need to be validated in prospective studies (39; 54).

Systemic staging of 128 patients with cerebral lymphoma revealed that only five (3.9%) had evidence of occult systemic disease (70). All HIV-positive patients should undergo systemic staging because they have a high incidence of extranodal lymphomas with secondary central nervous system involvement. In both immunocompetent and immunocompromised scenarios, many contemporary clinicians and investigators would favor PET scan of the body to evaluate for occult extra-CNS disease. Bone marrow biopsy may be included as a component of the extra-CNS staging. It is unclear how much this adds to the staging yield. Testicular ultrasound may be considered as well in men to exclude an occult testicular lymphoma metastatic to brain, although it is unclear if this adds additional sensitivity to the staging (70). Furthermore, all patients should have an HIV-1 serology because HIV positivity may influence management.

Management

Contemporary primary central nervous system lymphoma treatment is often divided into induction chemotherapy (when the goal is to achieve a complete radiographic response) and consolidation chemotherapy (when additional therapy is administered to treat any microscopic disease that remains). Conventional therapy for primary central nervous system lymphoma in the past had been whole-brain radiotherapy, which almost always causes tumor regression; however, tumors recur and lead to death within 12 to 18 months for most patients. Gross total resection or surgical debulking offers little or no survival benefit compared to biopsy. However, this view has been challenged by the subset analysis of a large phase III study (93) and subsequent additional investigations (96; 75). The addition of chemotherapy to cranial radiotherapy or the use of chemotherapy alone prolongs life and disease-free survival. The chemotherapy regimens are built around a high-dose methotrexate (HD-MTX) backbone (18; 02; 19; 29; 09; 79).

Survival is enhanced only when the chemotherapeutic drugs employed or the drug delivery method is capable of penetrating the blood-brain barrier. HD-MTX is the single most active agent against cerebral lymphoma. Its optimal dosing is still unclear, with doses up to 8 gm/m2 being utilized routinely. The combination of HD-MTX and whole-brain radiation is associated with an overall 2-year survival of 43% to 73% (26). When combined with chemotherapy, cranial irradiation initially treated the whole brain to a total dose of approximately 4500 centigray; however, more recent studies demonstrate potential benefit from lower doses (34) or from omitting it completely (51). Higher total doses or boosts to areas with bulky disease do not improve local control but does increase toxicity. Focused radiotherapy or stereotactic radiosurgery is associated with high rates of in-field and out-of-field recurrence (83); in turn, it is not often utilized. The neurotoxicity from brain radiation is more pronounced in elderly patients (over the age of 60). Therefore, it is reasonable to defer radiotherapy in this age group, particularly if a complete response is achieved with chemotherapy alone (87). The trend in newer clinical trials and contemporary off-trial management to use more aggressive, multiagent chemotherapy regimens that permit dose reductions or elimination of radiotherapy as initial treatment.

Some combination chemotherapy regimens used for systemic lymphomas are not efficacious in the treatment of primary CNS lymphoma because the most active agents (eg, cyclophosphamide, doxorubicin) cannot penetrate an intact blood-brain barrier (81; 63). High-dose cytarabine, procarbazine, thiotepa, and temozolomide are examples of active agents that can penetrate the blood-brain barrier. It is less clear whether other agents, such as the monoclonal antibody rituximab, provide adequate blood-brain barrier penetration (82; 53; 31; 45; 79).

High-dose chemotherapy with autologous stem cell transplant, a successful regimen used in systemic lymphomas, has also been attempted in primary CNS lymphoma, both in the newly diagnosed (03; 49; 50; 21) and recurrent setting (86; 85). Kasenda and colleagues reported a 5-year overall survival of 82% (median survival 104 months) in 34 patients with newly diagnosed primary CNS lymphoma (age < 67 yrs) who were able to undergo ASCT with tolerable toxicity. In the study reported by Alimohamed and colleagues, all treatment-related mortality occurred in patients over the age of 60 with poor performance status (03). The randomized phase 2 cooperative group study, Alliance 51101, is evaluating the role of ASCT as a consolidation regimen. It has completed accrual, and its final results are eagerly awaited. Preliminary results demonstrate that a substantial proportion of patients could not move forward with consolidation (11). Subsequent results demonstrated that myeloablative consolidation with ASCT was associated with superior 2-year progression-free survival but not 2-year overall survival. Data suggest that stem cell transplantation is feasible even in an elderly population who were previously considered not good candidates for aggressive therapy (80).

The necessity of intrathecal chemotherapy is unknown; the use of high-dose methotrexate achieves therapeutic CSF levels and produces similar results as the combination of systemic and intrathecal therapy. There has been a strong trend away from including intrathecal therapy to treat newly diagnosed primary central nervous system lymphoma at many centers (48).

The optimal treatment for ocular lymphoma is also unknown but should eradicate disease and prevent relapses in the central nervous system. Options include systemic chemotherapy, intravitreal chemotherapy, and/or radiotherapy. Ocular lymphoma may be treated with ocular radiotherapy to a total of 3600 to 4000 cGy; however, this form of local therapy does not prevent or treat primary central nervous system lymphoma. High-dose cytarabine and high-dose methotrexate can reach the vitreous humor and may be useful in treating ocular lymphoma (91; 10). Intraocular injection of methotrexate has also been effective for ocular lymphoma.

Diagnosis of primary brain lymphoma in HIV-positive patients is usually more expeditious now and does not require failure of empiric antitoxoplasmosis therapy that can take weeks, leaving the patient neurologically compromised. The treatment choice is usually determined by the patient’s overall condition and CD4 count. Cranial radiotherapy is used in debilitated patients with very low CD4 counts to achieve rapid palliation. High-dose methotrexate is employed in patients with a good performance status, and it is usually well tolerated (30; 44). Immune reconstitution with antiretroviral therapies plays an important role in the treatment of cerebral lymphoma in HIV-positive patients (79). Regardless of specific therapy, patients may not have the predicted clinical improvement because cerebral infectious processes may coexist with brain lymphoma.

The management of elderly patients with primary central nervous system lymphoma is often made on a case-by-case basis and is influenced, at least in part, by medical comorbidities and their perceived influence on the tolerability of specific treatment regimens. In the sole phase 3 clinical trial (G-PCNSL-SG-1), elderly patients (over 70) appeared to experience decreased benefit and increased toxicity from aggressive chemotherapy (78). These age-related findings have not been seen across all therapeutic trials (79). Although the degree of benefit varies between populations, chemotherapy should be considered the preferred initial treatment for all patients with cerebral lymphoma and should be given before radiation therapy for those patients perceived to be able to tolerate the chemotherapy regimens.

Promising new agents are being investigated in treating primary central nervous system lymphoma. The targeted therapy ibrutinib (a Bruton tyrosine kinase inhibitor, BTKi), which has proven successful in extra-central nervous system lymphomas, has appeared tolerable in primary central nervous system lymphoma. Early results are promising, and further study results are eagerly awaited (23; 56; 57; 16).

Increasing understanding of the molecular basis of primary CNS lymphoma, especially dysregulation of Toll-like receptor and B-cell receptor signaling, which induce constitutive NFκB activation, has led to the evaluation of multiple signaling pathways that can be exploited therapeutically. Inhibitors of Bruton tyrosine kinase, such as ibrutinib, and mucosa-associated lymphoid tissue lymphoma translocation protein 1 (MALT1), such as lenalidomide or pomalidomide, have been studied and have shown evidence of activity in recurrent primary CNS lymphoma (37; 38; 74).

Several studies have demonstrated the benefit of BTKi in patients with recurrent/refractory primary central nervous system lymphoma, either monotherapy or in combination with other agents (Houillier at al 2021; 65; 92). Additional molecular targets such as immunomodulators class drugs, including lenalidomide and pomalidomide, are also showing some benefit (89; 32). Immunotherapy with checkpoint inhibitors and CAR-T are also being studied with signal of activity (66).

Outcomes

Immunocompetent patients treated with cranial irradiation alone have a median survival of 12 to 18 months and a 5-year survival of only 3% to 4%. When high-dose methotrexate-based chemotherapy is combined with radiation, the median survival increases to 40 to 60 months (18; 02; 19) with a 5-year survival of 23%. Of note, many therapeutic trials have not reported outcomes out to the 5-year landmark.

Even though immune recovery induced by highly active antiretroviral therapy leads to improved survival of patients with AIDS-associated cerebral lymphoma, overall prognosis remains poor (67; 40). This may, however, change in the contemporary era (48). Treatment of HIV-related primary central nervous system lymphoma leads to a median survival of only 2 to 5 months after cranial irradiation, although a few patients have prolonged survival when chemotherapy is added to radiotherapy (12; 30). Treatment with radiation therapy, completion of radiation therapy, receipt of a total dose of 30 Gray, ongoing therapy with two or more antiretroviral drugs, less than 1e AIDS-defining illnesses, and the absence of nonfocal CNS symptoms (such as confusion, cognitive decline, and memory loss) are associated with prolonged survival (67).

Complications may arise from treatment of primary nervous system tumors. Cranial irradiation combined with chemotherapy is associated with delayed leukoencephalopathy, leading to progressive dementia, ataxia, and urinary incontinence. Symptoms typically occur a median of 1 year after diagnosis and primarily affect patients 60 and older. Leukoencephalopathy can be diagnosed only in the absence of a tumor. Chemotherapy alone has a much-reduced risk of delayed neurotoxicity and is the recommended treatment for patients older than 60. Young age and a good performance status are important prognostic factors for response and survival, regardless of treatment. HD-MTX can crystalize in the renal tubules, leading to renal failure and, in turn, slowing excretion of MTX. The risk of this is decreased with the administration of alkalinized intravenous fluids and oral bicarbonate.

References

01: Abrey LE, Ben-Porat L, Panageas KS, et al. Primary central nervous system lymphoma: the Memorial Sloan-Kettering Cancer Center prognostic model. J Clin Oncol 2006;24(36):5711-5. PMID 17116938
02: Abrey LE, Yahalom J, DeAngelis LM. Treatment for primary CNS lymphoma: the next step. J Clin Oncol 2000;18:3144-50. PMID 10963643
03: Alimohamed N, Daly A, Owen C, Duggan P, Stewart DA. Upfront thiotepa, busulfan, cyclophosphamide, and autologous stem cell transplantation for primary CNS lymphoma: a single centre experience. Leuk Lymphoma 2012;53(5):862-7. PMID 22023529
04: Al-Yamany M, Lozano A, Nag S, Laperriere N, Bernstein M. Spontaneous remission of primary central nervous system lymphoma: report of 3 cases and discussion of pathophysiology. J Neurooncol 1999;42:151-9. PMID 10421073
05: Antinori A, DeRossi G, Ammassari A, et al. Value of combined approach with thallium-201 single-photon emission computed tomography and Epstein-Barr virus DNA polymerase chain reaction in CSF for the diagnosis of AIDS-related primary CNS lymphoma. J Clin Oncol 1999;17:554-60. PMID 10080599
06: Bailey P. Intracranial sarcomatous tumors of leptomeningeal origin. Arch Surg 1929;18:1359-402.
07: Baskaran AB, Dixit KS, Sonabend AW, Horbinski CM, Abutalib SA, Lukas RV. From the ER to the OR: initial evaluation of primary central nervous system lymphoma. Neurologist 2023;28(3):135-42. PMID 37027168
08: Bataille B, Delwail V, Menet E, et al. Primary intracerebral malignant lymphoma: report of 248 cases. J Neurosurg 2000;92(2):261-6. PMID 10659013
09: Batchelor T, Carson K, O’Neill A, et al. Treatment of primary CNS lymphoma with methotrexate and deferred radiotherapy: a report of NABTT 96-07. J Clin Oncol 2003a;21:1044-9. PMID 12637469
10: Batchelor T, Kolak G, Ciordia R, et al. High-dose methotrexate for intraocular lymphoma. Clin Cancer Res 2003b;9:711-5. PMID 12576439
11: Batchelor W, Patel K, Hurt J, et al. Incidence, prognosis and predictors of major vascular complications and percutaneous closure device failure following contemporary percutaneous transfemoral transcatheter aortic valve replacement. Cardiovasc Revasc Med 2020;21(9):1065-73. PMID 31974033
12: Baumgartner JE, Rachlin JR, Beckstead JH, et al. Primary central nervous system lymphomas: natural history and response to radiation therapy in 55 patients with acquired immunodeficiency syndrome. J Neurosurg 1990;73:206-11. PMID 2366078
13: Bodor C, Alpár D, Marosvári D, et al. Molecular subtypes and genomic profile of primary central nervous system lymphoma. J Neuropathol Exp Neurol 2020;79(2):176-83. PMID 31886867
14: Burnette BL, Jentoft MA, Porrata LF, Boyce TG, Witzig TE. Single-agent rituximab for primary CNS lymphoma during pregnancy as a bridge to definitive management. J Clin Oncol 2014;32(7):e14-7. PMID 24395859
15: Chapuy B, Stewart C, Dunford AJ, et al. Molecular subtypes of diffuse large B cell lymphoma are associated with distinct pathogenic mechanisms and outcomes. Nat Med 2018;24(5):679-90. PMID 29713087
16: Chen F, Pang D, Guo H, et al. Clinical outcomes of newly diagnosed primary CNS lymphoma treated with ibrutinib-based combination therapy: a real-world experience of off-label ibrutinib use. Cancer Med 2020;9(22):8676-84. PMID 33068336
17: Chen H, Judkins J, Thomas C, et al. Mutant IDH1 and seizures in patients with glioma. Neurology 2017;88(19):1805-13. PMID 28404805
18: Dahlborg SA, Henner WD, Crossen JR, et al. Non-AIDS primary CNS lymphoma: the first example of a durable response in a primary brain tumor using enhanced chemotherapy delivery without cognitive loss and without radiotherapy. Cancer J Sci Am 1996;2:166-74. PMID 9166517
19: DeAngelis LM, Seiferfeld W, Schold SC, et al. Combination chemotherapy and radiotherapy for primary central nervous system lymphoma: Radiation Therapy Oncology Group study 93-10. J Clin Oncol 2002;20:4643-8. PMID 12488408
20: DeAngelis LM, Wong E, Rosenblum M, Furneaux H. Epstein-Barr Virus in acquired immune deficiency syndrome (AIDS) and non-AIDS primary central nervous system lymphoma. Cancer 1992;70:1607-11. PMID 1325277
21: DeFillip Z, Li S, El-Jawahri A, et al. High-dose chemotherapy with thiotepa, busulfan, and cyclophosphamide and autologous stem cell transplantation for patients with primary central nervous system lymphoma in first complete remission. Cancer 2017;123(16):3073-9. PMID 28369839
22: Devesa SS, Fears T. Non-Hodgkin's lymphoma time trends: United States and international data. Cancer Res 1992;52(Suppl):5432s-40s. PMID 1394149
23: Dunleavy K, Lai CE, Roschewski M, et al. Phase I study of dose-adjusted-Teddi-R with ibrutinib in untreated and relapsed/refractory primary CNS lymphoma. Blood 2015;126;abstract 472.
24: Eby NL, Grufferman S, Flannelly CM, et al. Increasing incidence of primary brain lymphoma in the U.S. Cancer 1998;62:2461-5. PMID 3179963
25: Evens AM, Choquet S, Kroll-Desrosiers AR, et al. Primary CNS posttransplant lymphoproliferative disease (PTLD): an international report of 84 cases in the modern era. Am J Transplant 2013;13(6):1512-22. PMID 23721553
26: Ferreri AJ, Abrey LE, Blay JY, et al. Management of primary central nervous system lymphoma: A summary statement from the 8th International Conference on Malignant Lymphoma. J Clin Oncol 2003a;21:2407-14.
27: Ferreri AJ, Blay JY, Reni M, et al. Prognostic scoring system for primary CNS lymphomas: the International Extranodal Lymphoma Study Group experience. J Clin Oncol 2003b;21:266-72. PMID 12525518
28: Ferreri AJM, Calimeri T, Lopedote P, et al. MYD88 L265P mutation and interleukin-10 detection in cerebrospinal fluid are highly specific discriminating markers in patients with primary central nervous system lymphoma: results from a prospective study. Br J Haematol 2021;193(3):497-505. PMID 33620087
29: Ferreri AJ, Reni M, Pasini F, et al. A multicenter study of treatment of primary CNS lymphoma. Neurology 2002;58:1513-20. PMID 12034789
30: Forsyth PA, Yahalom J, DeAngelis LM. Combined modality therapy in the treatment of primary central nervous system lymphoma in AIDS. Neurology 1994;44:1473-9. PMID 8058152
31: Fritsch K, Kasenda B, Hader C, et al. Immunochemotherapy with rituximab, methotrexate, procarbazine, and lomustine for primary CNS lymphoma (PCNSL) in the elderly. Ann Oncol 2011;22(9):2080-5. PMID 21303800
32: Ghesquieres H, Chevrier M, Laadhari M, et al. Lenalidomide in combination with intravenous rituximab (REVRI) in relapsed/refractory primary CNS lymphoma or primary intraocular lymphoma: a multicenter prospective 'proof of concept' phase II study of the French Oculo-Cerebral lymphoma (LOC) Network and the Lymphoma Study Association (LYSA)†. Ann Oncol 2019;30(4):621-8. PMID 30698644
33: Gittleman HR, Ostrom QT, Rouse CD, et al. Trends in central nervous system tumor incidence relative to other common cancers in adults, adolescents, and children in the United States, 2000 to 2010. Cancer 2015;21(1):102-12. PMID 25155924
34: Glass J, Won M, Schultz CJ, et al. Phase I and II study of induction chemotherapy with methotrexate rituximab, and temozolomide, followed by whole-brain radiotherapy and post-irradiation temozolomide for primary CNS lymphoma: NRG Oncology RTOG 0227. J Clin Oncol 2016;34(14):1620-5. PMID 27022122
35: Grebenciucova E, Collins JM, Lukas RV. Neurologic manifestations of human immunodeficiency virus infection and acquired immunodeficiency syndrome. 8th edition. Youmans and Winn Neurological Surgery, 2022.
36: Grimm SA, McCannel CA, Omuro AM, et al. Primary CNS lymphoma with intraocular involvement: International PCNSL Collaborative Group Report. Neurology 2008;71(17):1355-60. PMID 18936428
37: Grommes C, Pastore A, Palaskas N, et al. Ibrutinib unmasks critical role of bruton tyrosine kinase in primary CNS lymphoma. Cancer Discov 2017;7(9):1018-29. PMID 28619981
38: Grommes C, Nayak L, Tun HW, Batchelor TT. Introduction of novel agents in the treatment of primary CNS lymphoma. Neuro Oncol 2019;21(3):306-13. PMID 30423172
39: Gupta M, Bradley JD, Massaad E, et al. Rapid tumor DNA analysis of cerebrospinal fluid accelerates treatment of central nervous system lymphoma. Blood 2024;144(10):1093-100. PMID 38776489
40: Gupta NK, Nolan A, Omuro A, et al. Long-term survival in AIDS-related primary central nervous system lymphoma. Neuro Oncol 2017;19(1):99-108. PMID 27576871
41: Hochberg FH, Miller DC. Primary central nervous system lymphoma. J Neurosurg 1988;68:835-53. PMID 3286832
42: Houillier C, Chabrot CM, Moles-Moreau MP, et al. Rituximab-lenalidomide-ibrutinib combination for relapsed/refractory primary CNS lymphoma: A case series of the LOC Network. Neurology 2021;97(13):628-31. PMID 34580183
43: Houillier C, Soussain C, Ghesquières H, et al. Management and outcome of primary CNS lymphoma in the modern era: An LOC network study. Neurology 2020;94(10):e1027-39. PMID 31907289
44: Jacomet C, Girard PM, Lebrette MG, et al. Intravenous methotrexate for primary central nervous system non-Hodgkin’s lymphoma in AIDS. AIDS 1997;11:1725-30. PMID 9386807
45: Jiang X, Reardon DA, Desjardins A, et al. O6-methylguanine-DNA methyltransferase (MGMT) immunohistochemistry as a predictor of resistance to temozolomide in primary CNS lymphoma. J Neurooncol 2013;114(1):135-40. PMID 23686298
46: Johnson BA, Fram EK, Johnson PC, Jacobowitz R. The variable MR appearance of primary lymphoma of the central nervous system: comparison with histopathologic features. Am J Neuroradiol 1997;18:563-72. PMID 9090424
47: Kam KL, Brooker SM, Mao Q, et al. Newly diagnosed enhancing lesions: steroid initiation may impede diagnosis of lymphoma involving the central nervous system. J Clin Neurosci 2020;81:61-4. PMID 33222970
48: Karmali R, Nabhan C, Petrich AM, et al. Impact of treatment variability on survival in immune-competent and immune-compromised patients with primary central nervous lymphoma. Br J Haematol 2017;177(1):72-9. PMID 28211579
49: Kasenda B, Schorb E, Fritsch K, Finke J, Illerhaus G. Prognosis after high-dose chemotherapy followed by autologous stem-cell transplantation as first-line treatment in primary CNS lymphoma--a long-term follow-up study. Ann Oncol 2012;23(10):2670-5. PMID 22473593
50: Kiefer T, Hirt C, Späth C, et al. Long-term follow-up of high-dose chemotherapy with autologous stem-cell transplantation and response-adapted whole-brain radiotherapy for newly diagnosed primary CNS lymphoma: results of the multicenter Ostdeutsche Studiengruppe Hamatologie und Onkologie OSHO-53 phase II study. Ann Oncol 2012;23(7):1809-12. PMID 22115927
51: Korfel A, Thiel E, Martus P, et al. Randomized phase III study of whole-brain radiotherapy for primary CNS lymphoma. Neurology 2015;84(12):1242-8. PMID 25716362
52: Kuker W, Nagele T, Korfel A, et al. Primary central nervous system lymphomas (PCNSL): MRI features at presentation in 100 patients. J Neurooncol 2005;72:169-77. PMID 15925998
53: Kurzwelly D, Glas M, Roth P, et al. Primary CNS lymphoma in the elderly: temozolomide therapy and MGMT status. J Neurooncol 2010;97(3):389-92. PMID 19841864
54: Larson A, Udhane V, Adams JN, et al. Demonstrating the impact of the Belay Cerebrospinal Fluid Liquid Biopsy Tests Summit™ and Vantage™ to inform diagnosis and management of central nervous system lymphoma. Lymphatics 2026;4(1):9.
55: Levasseur SD, Wittenberg LA, White VA. Vitreoretinal lymphoma: a 20-year review of incidence, clinical and cytologic features, treatment, and outcomes. JAMA Ophthalmol 2013;131(1):50-5. PMID 23307208
56: Lionakis MS, Dunleavy K, Roschewski M, et al. Inhibition of B cell receptor signaling by ibrutinib in primary CNS lymphoma. Cancer Cell 2017;31(6):833-43. PMID 28552327
57: Low JT, Peters KB. Ibrutinib in primary central nervous system diffuse large B-cell lymphoma. CNS Oncol 2020;9(1):CNS51. PMID 32141313
58: Lukas RV, Collins J, Nicholas MK. AIDS. In: Winn HR, editor. Youmans and Winn neurological surgery, 7th edition. Elsevier, 2016.
59: Lukas RV, Riedell P, Horowitz PM, Pytel P, Kamson DO. Diagnostic evaluation in primary CNS lymphoma. Neurologist 2018;23(2):53-4. PMID 29494436
60: Lv C, Wang J, Zhou M, Xu JY, Chen B, Wan Y. Primary central nervous system lymphoma in the United States, 1975-2017. Ther Adv Hematol 2022;13:20406207211066166. PMID 35096360
61: MacMahon EM, Glass JD, Hayward SD, et al. Epstein-Barr virus in AIDS-related primary central nervous system lymphoma. Lancet 1991;338:969-73. PMID 1681341
62: Mansour A, Qandeel M, Abdel-Razeq H, Abu Ali HA. MR imaging features of intracranial primary CNS lymphoma in immune competent patients. Cancer Imaging 2014;14:22. PMID 25608570
63: Mead GM, Bleehen NM, Gregor A, et al. A medical research council randomized trial in patients with primary cerebral non-Hodgkin’s lymphoma: cerebral radiotherapy with and without cyclophosphamide, doxorubicin, vincristine and prednisone chemotherapy. Cancer 2000;89:1359-70. PMID 11002232
64: Montesinos-Rongen M, Kuppers R, Schluter D, et al. Primary central nervous system lymphomas are derived from germinal-center B cells and show a preferential usage of V4-34 gene segment. Am J Pathol 1999;155:2077-86. PMID 10595937
65: Narita Y, Nagane M, Mishima K, et al. Phase I/II study of tirabrutinib, a second-generation Bruton's tyrosine kinase inhibitor, in relapsed/refractory primary central nervous system lymphoma. Neuro Oncol 2021;23(1):122-33. PMID 32583848
66: Nayak L, Iwamoto FM, LaCasce A, et al. PD-1 blockade with nivolumab in relapsed/refractory primary central nervous system and testicular lymphoma. Blood 2017;129(23):3071-3. PMID 28356247
67: Newell ME, Hoy JF, Cooper SG, et al. Human immunodeficiency virus-related primary central nervous system lymphoma. Cancer 2004;100:2627-36 PMID 15197806
68: Olson JE, Janney CA, Rao RD, et al. The continuing increase in the incidence of primary central nervous system non-Hodgkin lymphoma: a surveillance, epidemiology and end results analysis. Cancer 2002:95:1504-10. PMID 12237919
69: O’Mahony D, Abdul Razal AR, Brett F, et al. Primary central nervous system lymphoma (PCNSL) occurring in pregnancy. J Neurol 2005;252:1133-4. PMID 16003500
70: O’Neill BP, Dinapoli RP, Kurtin PJ, Habermann TM. Occult systemic non-Hodgkin's lymphoma (NHL) in patients initially diagnosed as primary central nervous system lymphoma (PCNSL): how much staging is enough. J Neurooncol 1995;25:67-71. PMID 8523091
71: Ostrom QT, Gittleman H, Liao P, et al. CBTRUS statistical report: primary brain and central nervous system tumors diagnosed in the United States in 2010-2014. Neuro Oncol 2017;19(suppl_5):v1-v88. PMID 29117289
72: Peterson K, Gordon KB, Heinemann MH, DeAngelis LM. The clinical spectrum of ocular lymphoma. Cancer 1993;72:843-9. PMID 8334638
73: Poulain S, Boyle EM, Tricot S, et al. Absence of CXCR4 mutations but high incidence of double mutant in CD79A/B and MYD88 in primary central nervous system lymphoma. Br J Haematol 2015;170(2):285-7. PMID 25643939
74: Radke J, Ishaque N, Koll R, et al. The genomic and transcriptional landscape of primary central nervous system lymphoma. Nat Commun 2022;13(1):2558. PMID 35538064
75: Rae AI, Mehta A, Cloney M, et al. Craniotomy and survival for primary central nervous system lymphoma. Neurosurgery 2019;84(4):935-44. PMID 29660011
76: Riemens A, Bromberg J, Touitou V, et al. Treatment strategies in primary vitreoretinal lymphoma: a 17-center European collaborative study. JAMA Ophthalmol 2015;133(2):191-7. PMID 25412269
77: Roschewski M, Phelan JD, Jaffe ES. Primary large B-cell lymphomas of immune-privileged sites. Blood 2024;144(25):2593-603. PMID 38635786
78: Roth P, Martus P, Kiewe P, et al. Outcome of elderly patients with primary CNS lymphoma in the G-PCNSL-SG-1 trial. Neurology 2012;79(9):890-6. PMID 22895585
79: Rubenstein JL, His ED, Johnson JL, et al. Intensive chemotherapy and immunotherapy in patients with newly diagnosed primary CNS lymphoma: CALGB 50202 (Alliance 50202). J Clin Oncol 2013;31(25):3061-8. PMID 23569323
80: Schorb E, Kasenda B, Ihorst G, et al. High-dose chemotherapy and autologous stem cell transplant in elderly patients with primary CNS lymphoma: a pilot study. Blood Adv. 2020;4(14):3378-81. PMID 32722778
81: Schultz C, Scott C, Sherman W, et al. Preirradiation chemotherapy with cyclophosphamide, doxorubicin, vincristine, and dexamethasone for primary CNS lymphomas: initial report of Radiation Therapy Oncology Group protocol 88-06. J Clin Oncol 1996;14:556-64. PMID 8636771
82: Shah GD, Yahalom J, Correa DD, et al. Combined immunochemotherapy with reduced whole-brain radiotherapy for newly diagnosed primary CNS lymphoma. J Clin Oncol 2007;25(30):4730-5. PMID 17947720
83: Shibamoto Y, Hayabuchi N, Hiratsuka J, et al. Is whole brain irradiation necessary for primary central nervous system lymphoma. Patterns of recurrence after partial brain irradiation. Cancer 2003:128-33. PMID 12491514
84: Skiest DJ, Erdmann W, Chang WE, et al. SPECT thallium-201 combined with Toxoplasma serology for the presumptive diagnosis of focal central nervous system mass lesions in patients with AIDS. J Infect 2000;40:274-81. PMID 10908023
85: Soussain C, Choquet S, Fourme E, et al. Intensive chemotherapy with thiotepa, busulfan and cyclophosphamide and hematopoietic stem cell rescue in relapsed or refractory primary central nervous system lymphoma and intraocular lymphoma: a retrospective study of 79 cases. Haematologica 2012;97(11):1751-6. PMID 22581000
86: Soussain C, Hoang-Xuan K, Taillandier L, et al. Intensive chemotherapy followed by hematopoietic stem-cell rescue for refractory and recurrent primary CNS and intraocular lymphoma: Societe Francaise de Greffe de Moelle Osseuse-Therapie Cellulaire. J Clin Oncol 2008;26(15):2512-8. PMID 18413641
87: Swinnen LJ. Primary central nervous system lymphoma: recent progress, many remaining questions. Curr Opin Oncol 2009;21(5):393-6. PMID 19593137
88: Thompsett AR, Ellison DW, Stevenson FK, Zhu D. V(H) gene sequences from primary central nervous system lymphomas indicate derivation from highly mutated germinal center B cells with ongoing mutational activity. Blood 1999;94:1738-46. PMID 10477699
89: Tun HW, Johnston PB, DeAngelis LM, et al. Phase 1 study of pomalidomide and dexamethasone for relapsed/refractory primary CNS or vitreoretinal lymphoma. Blood 2018;132(21):2240-8. PMID 30262659
90: Utsuki S, Oka H, Miyajima Y, Kijima C, Yasui Y, Fujii K. Epstein-Barr virus (EBV)-associated primary central nervous system lymphoma: is incidence of EBV expression associated with median survival time. Brain Tumor Pathol 2011;28(2):145-9. PMID 21327439
91: Valluri S, Moorthy RS, Kahn A, Rao NA. Combination treatment of intraocular lymphoma. Retina 1995;15:125-9. PMID 7624599
92: Wang N, Chen FL, Pan L, et al. Clinical outcomes of newly diagnosed primary central nervous system lymphoma treated with zanubrutinib-based combination therapy. World J Clin Oncol 2023;14(12):606-19. PMID 38179402
93: Weller M, Martus P, Roth P, Thiel E, Korfel A; German PCNSL Study Group. Surgery for primary CNS lymphoma. Challenging a paradigm. Neuro Oncol 2012;14(12):1481-4. PMID 22984018
94: Whitcup SM, deSmet MD, Rubin BI, et al. Intraocular lymphoma clinical and histopathologic diagnosis. Ophthalmology 1993;100:1399-406. PMID 8371930
95: Yang W, Garzon-Muvdi T, Braileanu M, et al. Primary intramedullary spinal cord lymphoma: a population-based study. Neuro Oncol 2017;19(3):414-21. PMID 28011925
96: Yun J, Iwamoto FM, Sonabend AM. Primary central nervous system lymphoma: a critical review of the role of surgery for resection. Arch Cancer Res 2016;4(2). PMID 28239600

Contributors

All contributors' financial relationships have been reviewed and mitigated to ensure that this and every other article is free from commercial bias.

Author

Karan S Dixit MD

Dr. Dixit of Northwestern University Feinberg School of Medicine has no relevant financial relationships to disclose.
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Editor

Rimas V Lukas MD

Dr. Lukas of Northwestern University Feinberg School of Medicine received honorariums from Jazz Therapeutics, Novocure, and Servier for speaking engagements, honorariums from Cardinal Health, Catalyx, Merck, and Novocure for advisory board membership, research support from BMS as principal investigator, and an honorarium from GT Medical Technologies for DSMB membership.
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Former Authors

Lisa M DeAngelis MD
Lauren E Abrey MD
Eudocia Quant Lee MD MPH
Santosh Kesari MD PhD
Jai Grewal MD
Harpreet K Grewal MD
Rimas V Lukas MD

Patient Profile

Age range of presentation: 2 to 65+ years
Sex preponderance: male>female, >1:1
Heredity: none
Population groups selectively affected: immunosuppressed patients
Occupation groups selectively affected: none selectively affected

ICD & OMIM codes

ICD-10: Malignant neoplasm of nervous system, unspecified: C72.9
ICD-11: Primary diffuse large B-cell lymphoma of CNS: XH2MP0

Malignant neoplasm metastasis in spinal cord, cranial nerves or remaining parts of central nervous system: 2D52
ICD-O: Malignant lymphoma, non-Hodgkin's, NOS: M-9591/3

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Primary CNS lymphoma

Associated Disorders

AIDS lymphoma
Leptomeningeal lymphoma
Ocular lymphoma
Spinal lymphoma

Differential Diagnosis

brain metastases
malignant primary brain tumors

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