Primary Central Nervous System Lymphoma

doi:10.1016/S0025-6196(12)61228-2

Mayo Clinic Proceedings

Volume 64, Issue 8, August 1989, Pages 1005-1020

https://doi.org/10.1016/S0025-6196(12)61228-2 Get rights and content

Primary central nervous system lymphomas constitute less than 2% of primary brain tumors. Although their cause is unknown, they are in some way related to immunosuppression. The typical patient is a middle-aged man who displays the syndrome of a subacute mass lesion. These tumors most commonly occur as a single, bulky mass in the hemispheric white matter or the deep gray matter, but multiple tumors occur in approximately a fourth of the patients. The findings on computed tomography are distinctive and nearly pathognomonic. The majority of these tumors are B-cell lymphomas with aggressive histologic changes. Surgical intervention should be reserved for tissue diagnosis because surgical removal does not seem to influence the outcome. Conventional therapy consists of whole-brain irradiation with or without chemotherapy. The prognosis for patients with such tumors is grim, the median duration of survival being less than 2 years with conventional therapy and the 5-year survival being less than 5%.

Section snippets

PATHOLOGIC FEATURES

The tumor currently called PCNSL was first described by Bailey¹³ as a “perithelial small cell sarcoma.” Various morphologic criteria have been used to categorize the cell of origin of this tumor; thus, PCNSL has previously been referred to as reticulum cell sarcoma,¹⁴ microglioma,¹⁵ and immunoblastic sarcoma.¹⁶ The neoplastic cells of PCNSL, however, are identical to those that constitute extracranial lymphomas. On the basis of morphologic, ultrastructural, and immunologic studies, they are

ETIOLOGIC FACTORS

Although the cause of PCNSL is unknown, interesting advances in the knowledge about etiologic mechanisms have been made from patients with AIDS and with tropical spastic paraparesis.33, 34 What may be accepted as true today, however, may change dramatically as new data emerge. Other useful reviews have been published about the pathogenesis of lymphomas.28, 35

PCNSL are more likely to occur in certain clinical situations and within certain identifiable groups. An increased risk of developing

CLINICAL FINDINGS

The typical patient with PCNSL is a middle-aged man with a recent appearance of nonfocal neurologic symptoms. Most frequently, involvement occurs in patients from 40 to 60 years old, and in most series, a 2-to-1 male-to-female distribution has been reported.12, 22, 31, 58, 59 The duration of symptoms from onset to diagnosis is approximately 3 months. A survey by Hobson and associates³¹ found nonfocal and nonspecific symptoms in more than 50% of the patients. At the time of initial examination,

CEREBROSPINAL FLUID

In most studies, cerebrospinal fluid examinations were limited to those patients with PCNSL in whom increased intracranial pressure was not a concern and in whom a lumbar puncture could be performed safely. In a review by Murray and associates,²² cerebrospinal fluid studies were performed in 92 of 267 patients (34%), and of these 92, only 9 (10%) had evidence of lymphoma cells. Hobson and colleagues,³¹ who reviewed five other articles and their own experience, concluded that more than 80% of

RADIOGRAPHIC CHARACTERISTICS

No computed tomographic appearance is absolutely diagnostic of PCNSL (Table 6); however, a homogeneously enhancing lesion (or lesions) located in the central gray matter or corpus callosum should be considered highly suggestive of PCNSL because few other lesions have this type of appearance. In most series, at least 60% of cases have been denser than adjacent normal brain tissue, and less than 10% have been hypodense.31, 58 In our experience, however, most PCNSL (67%) were isodense relative to

SURGICAL TREATMENT

There is ample evidence, and almost unanimous belief, that aggressive surgical decompression with partial or gross total removal of a PCNSL is of no benefit to the patient.²⁷ This outcome is partly attributable to the characteristics of the tumor (large mass, subacute course) and of the patients (elderly) and partly attributable to the multifocal diffuse nature of the neoplasm. Murray and associates²² reviewed the results in 85 patients with PCNSL who underwent only surgical treatment. The

RADIATION THERAPY

Radiation therapy significantly improves survival of patients with PCNSL over that of no treatment or surgical treatment only.22, 27, 72, 73, 74, 75 Investigators, however, do not agree about what the total dose of irradiation should be and whether the dose is best delivered to the whole brain or locally. Also, controversy surrounds the issue of irradiation of the spinal axis for prevention of relapse.

Dose-response information suggests that an improved survival time is associated with

CHEMOTHERAPY

Drugs effective in systemic non-Hodgkin's lymphomas, such as bleomycin, cyclophosphamide, doxorubicin, and vincristine, have poor penetration of the blood-brain barrier. Although many studies have demonstrated alteration of the blood-brain barrier in patients with intracranial neoplasms, Neuwelt and co-workers⁸⁰ suggested that only a partial permeability of the blood-brain barrier is present in patients with PCNSL. To counter this, they administered hyperosmolar concentrations of mannitol

PROGNOSIS

Among the various reports of prognosis of patients with PCNSL (Table 7), Jellinger and associates³² estimated that patients who receive no treatment have a median survival of 1.8 months. The combination of surgical treatment, irradiation, and chemotherapy extended the duration of survival to 17.2 months in a group in which most patients had what were considered “good prognosis” histologic findings. Henry and colleagues²⁷ reported a mean survival of 3.3 months for patients with PCNSL who

CONCLUSION

PCNSL is a rare tumor, constituting less than 2% of primary brain tumors and 1% of all non-Hodgkin's lymphomas. Its clinical manifestation is typically that of a subacute mass lesion. No clear predilection for focal versus general findings has been noted. Rather, increased intracranial pressure, headache, nausea, vomiting, changes in mental status, and dementia are the most common clinical manifestations. Results of cerebrospinal fluid examination are often nonspecifically abnormal (increased

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Cited by (148)

Extranodal Marginal Zone Lymphoma of the Central Nervous System
2018, Clinical Lymphoma, Myeloma and Leukemia
Citation Excerpt :
A multicenter study of 1378 cases of NHL revealed that MZBL accounts for 5% to 17% of all NHLs.2 Primary NHLs of the central nervous system (CNS), which account for less than 1% of all NHL cases, are usually aggressive lymphomas and have a poor prognosis.3 They usually present as masses in hemispheric white or deep gray matter and very rarely occur as isolated meningeal lesions.
Extranodal marginal zone lymphoma of the central nervous system (CNS EMZBL) is a rare disease. We present a review of the literature and describe its presentation, differential diagnosis, treatment options, and outcomes. Systematic search of PubMed, Medline, and Embase databases via the Ovid engine for primary articles and case reports yielded 37 unduplicated peer-reviewed articles of CNS EMZBL. We identified 69 cases in these articles and 1 unreported case at our institution, which were included for this review's analysis. Median age at diagnosis was 55 years (range, 18-78 years), with a female preponderance of 77% (n = 54). Most common presenting symptoms were headache in 43% (n = 30), seizures in 31% (n = 22), and visual defects in 27% (n = 19). The most common treatment modalities were localized therapies, which were provided to 67% (n = 47) of cases. These included radiotherapy in 27% (n = 19), radiotherapy with surgery in 24% (n = 17), and surgery alone in 16% (n = 11). Ninety percent (n = 63) of patients had a median follow-up of 23 months. Complete remission was experienced by 77% (n = 49) patients, and 22% (n = 14) were alive with disease. Three patients had evidence of relapse, and one patient died. CNS EMZBL is an indolent, low-grade, radiosensitive lymphoma with good treatment outcomes and prognosis. It is an important differential to consider in extra-axial dural-based masses. Individualized management plans, with preference given to localized treatment options, should be considered after factoring in the site and extent of disease, its resectability, and the expected adverse effects of systemic therapy.
Neuroimagen del linfoma primario del sistema nervioso central en pacientes inmunodeprimidos
2014, Revista Argentina de Radiologia
El linfoma primario del sistema nervioso central (LPSNC) es una entidad rara con un pronóstico fatal. Dado el aumento en el número de casos con inmunosupresión adquirida, nuestros objetivos son estudiar las características epidemiológicas y neurorradiológicas de aquellos pacientes inmunodeprimidos con diagnóstico de LPSNC con afectación cerebral e investigar si existen diferencias entre los pacientes con el virus de la inmunodeficiencia humana (VIH) positivo y negativo.
Se realizó un estudio descriptivo y retrospectivo de los pacientes inmunodeprimidos con afectación cerebral por LPSNC, diagnosticados durante los últimos 13 años en 2 hospitales de referencia. Se evaluaron múltiples variables. El nivel de significación estadística utilizado fue p < 0,05.
El grupo VIH-positivo tenía una media de edad de 36,82 ± 5,4 años, frente a los 55,60 ± 21,43 años de los pacientes VIH-negativo (p < 0,022). Los pacientes VIH-positivo tuvieron una media de 1,27 ± 0,65 lesiones por paciente, mientras que en el grupo VIH-negativo fue de 2,60 ± 1,78 (p < 0,039). El 18,2% (n = 2) del grupo VIH-positivo y el 80% (n = 8) del grupo VIH-negativo presentaron lesiones homogéneas (p < 0,005). Ningún paciente VIH-positivo tuvo afectación del cuerpo calloso, pero el grupo VIH-negativo presentó un 50% (n = 5) de afectación (p < 0,012).
El LPSNC en pacientes inmunodeprimidos puede presentar múltiples características en las imágenes. Existen diferencias entre los pacientes VIH positivo y negativo, por lo que es importante reconocerlas para establecer un manejo y tratamiento diferente entre ambos grupos.
Primary central nervous system lymphoma (PCNSL) is a rare tumour with poor prognosis. Due to the increased number of patients with acquired immunodeficiency, our purposes are to describe epidemiological and imaging findings in immunodeficient patients with PCNSL of the brain and to study the differences between HIV-positive and HIV-negative patients with PCNSL.
A retrospective, descriptive study was performed with immunodeficient patients diagnosed of PCNSL of the brain during the last 13 years in two reference hospitals. Twenty-one patients fulfilled the inclusion criteria. Multiple variables were evaluated. Significance was defined as p<0.05.
HIV-positive group was a mean age of 36,82 ± 5,4 years and the mean age in HIV-negative group was 55,60 ± 21,43 years (p < 0,022). The mean number of lesions was 1,27 ± 0,65 in HIV-positive group and 2,60 ± 1,78 in HIV-negative group (p < 0,039). The lesions were homogeneous in 18,2% (n = 2) HIV-positive group and 80% (n = 8) in HIV-negative group (p < 0,005). No HIV-positive patient and 50% (n = 5) of HIV-negative patients showed corpus callosum involvement (p < 0,012).
PCNSL in immunodeficient patients is associated with a large spectrum of radiological findings. There were differences between HIV-positive and HIV-negative patients, is important recognize these differences as the therapeutic management of these two groups vary.
Neoplasms of the brain
2014, A Comprehensive Guide to Geriatric Rehabilitation, Third Edition
Primary central nervous system lymphoma
2012, Handbook of Clinical Neurology
Citation Excerpt :
When PCNSL is suspected, diagnostic biopsy is the recommended surgical intervention. Attempts at surgical removal do not improve survival and, because of the deep-seated nature of these lesions, may result in undue neurological injury (O'Neill and Illig, 1989; DeAngelis, 1995). Lumbar puncture, which can be performed safely in the majority of patients, is used to detect CSF dissemination of tumor, and if diagnostic may also preclude the need for brain biopsy (Table 34.1).
Primary central nervous system lymphoma (PCNSL) is a rare non-Hodgkin lymphoma restricted to the nervous system, affecting the brain, cerebrospinal fluid, eyes, or spinal cord. It occurs with increased frequency in immunocompromised patients, particularly those with human immunodeficiency virus infection. Diagnosis is usually established by stereotactic biopsy as resection is not an essential component of therapy. Initial treatment should include chemotherapy, particularly regimens containing high-dose methotrexate, which is the single most important drug for the treatment of PCNSL. Complete response rates can approach 80% but, even with vigorous therapy, relapse is common. Median survival is approximately 3–4 years with high-dose methotrexate-based regimens with or without cranial irradiation. Combined modality treatment is associated with a high rate of neurotoxicity, with older age and long follow-up as the primary risk factors. Current approaches have focused on reducing relapse rates and improving disease control while minimizing neurotoxicity. These include: (1) reducing the dose of cranial irradiation in patients who have achieved a complete response to chemotherapy; (2) intensifying chemotherapy using autologous stem cell rescue regimens; and (3) intensifying standard chemotherapy alone.
Brainstem tumors
2012, Handbook of Clinical Neurology
Citation Excerpt :
Other tumors may also rarely involve the brainstem. About 3% of primary CNS lymphomas (PCNSLs) are located primarily in the brainstem, and mostly consists of T-cell lymphomas (Murray et al., 1986; O'Neill and Illig, 1989; Shams et al., 2002). The clinical picture usually points to a brainstem lesion but atypical presentations have been reported, such as central neurogenic hyperventilation (Shams et al., 2002).
Diffuse brainstem glioma is the most common subtype of brainstem tumor and remains a devastating malignancy, particularly in children. Recent advances in radiological diagnostic techniques may improve the classification of these heterogeneous tumors and contribute to differential diagnosis. However, biopsy remains indicated in many contrast-enhancing brainstem masses in adults because of the great variety of differential diagnoses. New magnetic resonance imaging techniques can also help neurosurgeons in removing resectable brainstem tumors. Conventional radiotherapy is the standard of care. Classical chemotherapy drugs have been disappointing to date, suggesting that a better understanding of the biology of this tumor may be the key to more targeted therapy. Improvement in the pattern of care of brainstem gliomas is strongly needed.
Follicular dural lymphoma. Case report
2009, Neurochirurgie
A case of a meningeal B-cell lymphoma is described. A 48-year-old man presented with an episode of grand mal seizure following a brain injury. An initial diagnosis of extradural hematoma was made based on the results of the cerebral computerized tomography scan. Magnetic resonance images demonstrated an enhanced mass with a dural tail attached to the meningeal layer of the temporal bone, suggesting a meningioma “en plaque”. The mass was surgically excised. Tumoral removal was subcomplete (Simpson 2). Operative inspection also suggested a meningioma, but histological analysis and electron microscopy revealed a grade IV follicular B-cell lymphoma. Biological studies were normal. An extensive workup found an external iliac adenopathy with several osseous locations on PET. The patient underwent chemotherapy and radiotherapy. Three years after the first symptoms appeared, the patient is alive and free of symptoms. The clinicopathological features and treatments were discussed.
Nous rapportons le cas d’un lymphome méningé à cellules B. Il s’agissait d’un homme de 48 ans présentant une crise d’épilepsie généralisée dans les suites d’un traumatisme crânien. Le scanner cérébral d’entrée posait le diagnostic d’hématome extradural. L’imagerie par résonance magnétique montrait une lésion se rehaussant après gadolinium avec une queue de comète le long de la méninge temporale faisant évoquer un méningiome en plaque. Le patient était opéré. L’exérèse tumorale était subcomplète Simpson 2. L’aspect macroscopique peropératoire suggérait un méningiome mais l’analyse histopathologique concluait à un lymphome folliculaire à cellules B de grade IV. Les examens biologiques étaient normaux. Le bilan d’extension révélait une adénopathie iliaque externe ainsi que plusieurs localisations au TEP-scan. Une chimiothérapie puis radiothérapie étaient réalisées. Trois ans plus tard, le patient reste toujours asymptomatique. Les caractéristiques clinicopathologiques et les thérapeutiques des lymphomes qu’ils soient primitifs ou secondaires étaient discutées.

View all citing articles on Scopus

^*: Current address: William Beaumont Army Medical Center, El Paso, Texas.

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Primary Central Nervous System Lymphoma

Section snippets

PATHOLOGIC FEATURES

ETIOLOGIC FACTORS

CLINICAL FINDINGS

CEREBROSPINAL FLUID

RADIOGRAPHIC CHARACTERISTICS

SURGICAL TREATMENT

RADIATION THERAPY

CHEMOTHERAPY

PROGNOSIS

CONCLUSION

Blood

Am J Med

Am J Med

Am J Ophthalmol

Clin Radiol

Int J Radiat Oncol Biol Phys

The non-Hodgkin's lymphomas

CA

Neurological complications of malignant lymphoma

Involvement of the central nervous system by non-Hodgkin's lymphoma in adults: a review of 36 cases

Q J Med

Central nervous system involvement in non-Hodgkin's lymphoma: an analysis of 105 cases

Cancer

CNS involvement in the non-Hodgkin's lymphomas

Cancer

Meningeal involvement in non-Hodgkin's lymphoma: symptoms, incidence, risk factors and treatment

Scand J Haematol

Secondary involvement of the central nervous system in malignant non-Hodgkin's lymphoma

Oncology

Occurrence and prognosis of extranodal lymphomas

Cancer

Primary lymphomas of the brain: a clinco-pathologic review of 37 cases

Tumori

Increasing incidence of primary brain lymphoma in the US

Cancer

Primary lymphoma of the central nervous system: clinicopathological study of experience at Stanford

J Neurosurg

Intracranial sarcomatous tumors of leptomeningeal origin

Arch Surg

Reticulum cell sarcoma of the brain

Arch Neurol Psychiatry

Microgliomatosis: a form of reticulosis affecting the brain

Brain

Neoplasms of the reticuloendothelial system of the brain

Cancer

Primary reticulum cell sarcoma (microglioma) of brain: an electron microscopic study

Arch Pathol

Immunoblastic sarcoma (histiocytic lymphoma) of the brain with B cell markers

J Neurosurg

Primary malignant lymphomas of the central nervous system: a histological and immunohistological study of 12 cases

Histopathology

Primary malignant lymphoma of the brain: an immunohistochemical study of eight cases using a panel of monoclonal and heterologous antibodies

Acta Neuropathol (Berl)

National Cancer Institute sponsored study of classifications of non-Hodgkin's lymphomas: summary and description of a working formulation for clinical usage

Cancer

Primary malignant lymphoma of the central nervous system: results of treatment of 11 cases and review of the literature

J Neurosurg

Central nervous system lymphoma: histologic types and CT appearance

Radiology

Computer-assisted stereotaxic biopsy for the diagnosis of primary central nervous system lymphoma

Neurology

Astrocytomas: old and newly recognized variants, their spectrum of morphology and antigen expression

Can J Neurol Sci

Primary malignant lymphomas of the central nervous system

Cancer

Hodgkin's disease and the non-Hodgkin's lymphomas

Tumors of the hematopoietic system

Atlas of Tumor Pathology. Section III, Fascicle 8

Primary cerebral lymphoma: a histologic and immunohistochemical study of six cases

Arch Pathol Lab Med

Primary lymphoma of the central nervous system: Manitoba experience and literature review

Can J Neurol Sci

Primary malignant lymphomas of the central nervous system in man

Acta Neuropathol [Suppl] (Berl)

Lymphomas in men at high risk for acquired immune deficiency syndrome (AIDS): a study of 21 cases

Cancer

Chronic progressive myelopathy associated with elevated antibodies to human T-lymphotropic virus type I and adult T-cell leukemialike cells

Ann Neurol