51628121
Neuroradiological features of lymphomatosis cerebri: A systematic review of the English literature with a new case report
Lymphomatosis cerebri is a rare form of diffusely infiltrating primary central nervous system (CNS) lymphoma (PCNSL). The neuroradiological findings of lymphomatosis cerebri have not been adequately characterized, as the relevant literature consists only of case reports and small case series. The present study describes an unusual presentation of lymphomatosis cerebri in a 56-year-old immunocompetent woman who presented with diffusely infiltrating lesions with perivascular curvilinear enhancement on initial magnetic resonance imaging (MRI) and multiple nodules on the later follow-up computed tomography (CT) scan. A systematic review of the literature is also performed searching PubMed between January 1996 and December 2016 to collect all pertinent case reports and series written in the English language with pathologically confirmed lymphomatosis cerebri and diffuse infiltrative PCNSL without cohesive masses on initial MRI. A total of 45 cases were identified from 39 articles and the present case report. The patient ages ranged from 28 to 85 years (mean, 57.3 years). Only 3 patients (6.7%) were immunosuppressed (acquired immune deficiency syndrome patients). The most common clinical presentation was cognitive changes or dementia (46.7%). Cerebrospinal fluid analysis in all cases was non-specific. Diffuse and asymmetric abnormal T2-hyperintensity in deep and subcortical white matter was observed in all cases. Gray matter involvement (17.8%), spreading along the corticospinal tract (35.6%) and a slight mass effect (51.1%) also were observed. Contrast-enhanced patterns on MRI could be divided into three forms of non-enhancement (64.4%) and non-mass-like enhancement (35.6%) on initial MRI, as well as nodular or mass-like enhancement on the later follow-up MRI (15.6%). There were non-specific findings on magnetic resonance spectroscopy for 4 patients, on positron emission tomography/CT for 12 patients and on single-photon emission CT for 1 patient. Diagnosis was established by brain biopsy in 35 cases (77.8%) and autopsy in 9 cases (20%), involving B-cell lymphoma in 40 cases (88.9%) and T-cell lymphoma in 4 cases (8.9%). In conclusion, lymphomatosis cerebri, namely diffuse PCNSL or diffuse lymphoma of the CNS, is characterized by rapidly progressive dementia in the elderly, diffusely infiltrated CNS white matter along the corticospinal tract, possible involvement of the gray matter, a slight mass effect and varied contrast-enhancement patterns on MRI. Non-enhancement or non-mass-like enhancement on MRI may be a special form of diffuse PCNL during disease development and progression.
26656068
Diagnosis and treatment of primary CNS lymphoma in immunocompetent patients: guidelines from the European Association for Neuro-Oncology.
The management of primary CNS lymphoma is one of the most controversial topics in neuro-oncology because of the complexity of the disease and the very few controlled studies available. In 2013, the European Association of Neuro-Oncology created a multidisciplinary task force to establish evidence-based guidelines for immunocompetent adults with primary CNS lymphoma. In this Review, we present these guidelines, which provide consensus considerations and recommendations for diagnosis, assessment, staging, and treatment of primary CNS lymphoma. Specifically, we address aspects of care related to surgery, systemic and intrathecal chemotherapy, intensive chemotherapy with autologous stem-cell transplantation, radiotherapy, intraocular manifestations, and management of elderly patients. The guidelines should aid clinicians in their daily practice and decision making, and serve as a basis for future investigations in neuro-oncology.
57958380
Lymphomatous Involvement of the Central Nervous System
Involvement of the nervous system by lymphoma can become manifest in a variety of ways. Direct effects may include parenchymal mass lesions, infiltration of the leptomeninges, extradural compression of the spinal cord and/or brain, and infiltration or compression of cranial and peripheral nerves. In addition, the lymphomas may be associated with such disorders as neuromuscular paraneoplastic syndromes, multifocal leukoencephalopathy, Herpes zoster or opportunistic infections of the nervous system. Toxic side effects of treatment may also affect the nervous system, as seen with vincristine-induced peripheral neuropathy, methotrexate leukoencephalopathy and radiation myelitis. In the following manuscript three direct effects of lymphomatous involvement of the central nervous system will be examined: primary malignant lymphoma of the brain, spinal cord compression by epidural lymphoma, and lymphomatous meningitis.
1926301
Preferred Reporting Items for Systematic Review and Meta-Analyses of individual participant data: the PRISMA-IPD Statement.
IMPORTANCE
Systematic reviews and meta-analyses of individual participant data (IPD) aim to collect, check, and reanalyze individual-level data from all studies addressing a particular research question and are therefore considered a gold standard approach to evidence synthesis. They are likely to be used with increasing frequency as current initiatives to share clinical trial data gain momentum and may be particularly important in reviewing controversial therapeutic areas.


OBJECTIVE
To develop PRISMA-IPD as a stand-alone extension to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) Statement, tailored to the specific requirements of reporting systematic reviews and meta-analyses of IPD. Although developed primarily for reviews of randomized trials, many items will apply in other contexts, including reviews of diagnosis and prognosis.


DESIGN
Development of PRISMA-IPD followed the EQUATOR Network framework guidance and used the existing standard PRISMA Statement as a starting point to draft additional relevant material. A web-based survey informed discussion at an international workshop that included researchers, clinicians, methodologists experienced in conducting systematic reviews and meta-analyses of IPD, and journal editors. The statement was drafted and iterative refinements were made by the project, advisory, and development groups. The PRISMA-IPD Development Group reached agreement on the PRISMA-IPD checklist and flow diagram by consensus.


FINDINGS
Compared with standard PRISMA, the PRISMA-IPD checklist includes 3 new items that address (1) methods of checking the integrity of the IPD (such as pattern of randomization, data consistency, baseline imbalance, and missing data), (2) reporting any important issues that emerge, and (3) exploring variation (such as whether certain types of individual benefit more from the intervention than others). A further additional item was created by reorganization of standard PRISMA items relating to interpreting results. Wording was modified in 23 items to reflect the IPD approach.


CONCLUSIONS AND RELEVANCE
PRISMA-IPD provides guidelines for reporting systematic reviews and meta-analyses of IPD.
26452154
Nonenhancing primary central nervous system lymphoma
Primary central nervous system lymphoma (PCNSL) is rare, although its frequency has increased in recent years. Radiographically, almost all PCNSL enhance on CT and/or MRI, and nonenhancing PCNSL has been thought to be extremely rare. We present PCNSL showing multiple nonenhancing lesions on MRI in an immunocompetent patient.
30510907
Rapidly progressive dementia caused by nonenhancing primary lymphoma of the central nervous system.
A 76-year-old woman had rapidly progressive dementia over 4 months. Proton density- and T2-weighted MR images of the head showed increased signal in the periventricular and subcortical white matter of both cerebral hemispheres and the brain stem. Enhancement was not seen after administration of contrast material. Because of the rapid progression of the dementia and increasing signal abnormalities within the cerebral white matter, the patient underwent a craniotomy with biopsies of the right frontal lobe. Pathologic specimens were positive for malignant large-cell lymphoma, B-cell phenotype. The MR appearance is atypical for primary lymphoma of the central nervous system.
26019490
Non‐HTLV‐I associated pleomorphic T‐cell lymphoma of the brain mimicking post‐vaccinal acute inflammatory demyelination
Two weeks after vaccination against tick‐borne encephalitis (TBE), a 57‐year‐old female suddenly developed mental confusion and hemiparesis of the left side. Cranial MRI demonstrated extensive bilateral lesions in the fronto‐parietal white matter of both hemispheres, suggesting an acute inflammatory demyelinating disease following vaccination. Despite administration of high‐dose corticosteroids, the patient died 3 weeks after onset of neurological symptoms. Autopsy revealed diffuse infiltrates of a primary cerebral pleomorphic T‐cell lymphoma of medium and large cell type. PCR on brain tissue for HTLV‐I and serology for anti‐HTLV‐I antibodies in CSF and serum were negative; immunocytochemistry on brain tissue did not detect EBV‐related antigen. This is the first recorded observation of a diffusely infiltrating primary central nervous system T‐cell lymphoma, clinically and radiologically mimicking a fatal acute inflammatory demyelinating complication after vaccination.
30149450
Lymphomatosis cerebri Presenting as a Rapidly Progressive Dementia: Clinical, Neuroimaging and Pathologic Findings
Primary central nervous system lymphoma (PCNSL) usually presents with clinical and neuroimaging findings consistent with single or multiple intracranial mass lesions. On cranial magnetic resonance imaging (MRI), such lesions are nearly always contrast enhancing, reflecting disruption of the blood-brain barrier at the site of tumor nodules. We describe 2 cases from the UCLA Medical Center who developed a rapidly progressive dementia due to extensive gray and white matter cerebral lesions involving much of the brain. In the patient who came to autopsy, widely infiltrating, focally necrotic B-cell plasmacytoid lymphoma was noted throughout the cerebral neuraxis. MRI findings in case 2 were consistent with diffuse lymphomatous brain infiltration without mass lesions, which was biopsy proven. We conclude that PCNSL may occur in a diffusely infiltrating form which may occur without MRI evidence of mass lesions or blood-brain barrier compromise. We refer to this entity as ‘lymphomatosis cerebri’ and add it to the differential diagnosis of a rapidly progressive dementia.
6563148
Primary central nervous system lymphoma in AIDS: a wider spectrum of CT and MRI findings
Abstract Diagnosis of primary central nervous system lymphoma (PCNSL) in patients with AIDS based on radiological findings is still a challenging problem. Our purpose was to review the CT and MRI findings in PCNSL in our patients with AIDS and compare them with those reported in the literature. CT and MRI of 28 patients with AIDS and pathologically confirmed PCNSL were analysed retrospectively for the number of lesions, their site, size, density, signal intensity, contrast enhancement, oedema and mass effect. We found 82 lesions. On CT 45 lesions were found in 22 patients, whereas MRI revealed 66 in 20 patients. The lymphoma was solitary in 20 patients (29 %) and multiple in 20 (71 %). Spontaneous haemorrhage was seen in 7 patients. Contrast-enhanced MRI showed no enhancement in 27.3 % (18/66) of the lesions. In one patient diffuse signal abnormalities in the white matter were seen on T2-weighted images. Our findings suggest that the previously described spectrum imaging characteristics of PCNSL has widened. Neuroradiologists should be aware of the variable appearance in patients with AIDS. Spontaneous haemorrhage, a nonenhancing lesion, or diffuse white matter changes do not exclude lymphoma in an immunocompromised patient.
7986048
Cerebral lymphoma presenting as a leukoencephalopathy.
Cerebral lymphoma is infrequent in immunocompetent patients. This tumour usually appears on CT and MRI as a single lesion or as multiple lesions with mass effect and homogeneous enhancement after contrast administration. A patient is described with a cerebral lymphoma, confirmed by histopathological examination, who presented as a progressive leukoencephalopathy.
13058626
Lymphomatosis cerebri as a cause of white matter dementia.
Primary central nervous system lymphoma most often presents as a solitary, isolated lesion in immunocompetent patients. Rarely, the disease presents as a diffuse, infiltrating condition without formation of a cohesive mass, a pattern called lymphomatosis cerebri. We present 3 immunocompetent individuals who developed rapidly progressive dementia. Magnetic resonance imaging features mimicked other disorders of white matter and prompted preoperative diagnoses of Binswanger's disease (subcortical ischemic vascular dementia), unknown leukoencephalopathy, viral infection, or infiltrating glioma. Neuropathologic examination at biopsy (Poon T, Matoso I, Tchertkoff V, Weitzner I Jr, Gade M. CT features of primary cerebral lymphoma in AIDS and non-AIDS patients. J Comput Assist Tomogr . 1989;13:6-9) and autopsy (Schwaighofer BW, Hesselink JR, Press GA, Wolf RL, Healy ME, Berthoty DP. Primary intracranial CNS lymphoma: MR manifestations. Am J Neuroradiol . 1993;10:725-9) demonstrated nonnecrotic, diffusely infiltrating, large-cell B-cell lymphoma of white matter, with relative sparing of gray matter, and without significant leptomeningeal involvement or bulky periventricular disease at autopsy. Microglial and astrocytic reactions, but only subtle myelin pallor, were evident as individual tumor cells permeated the entire brain and spinal cord, albeit with considerable variation in cell density. Individual tumor cells could be identified from the optic nerve to spinal cord, documenting the "whole-brain" nature of the disease. CD20 immunostaining was necessary to fully appreciate the extent of individual lymphoma cell percolation through the white matter. The neurobehavioral deficits manifested by these patients demonstrate that lymphomatosis cerebri is an additional neoplastic cause of white matter dementia and can be added to the growing list of disorders responsible for this syndrome.
10243878
Dementia and leukoencephalopathy due to lymphomatosis cerebri
Lymphomatosis cerebri (LC) is a rare variant of primary central nervous system lymphoma (PCNSL). Clinically, the disease typically presents with a rapidly progressive dementia and unsteadiness of gait. Its presentation on cerebral MRI, which is characterised by diffuse leukoencephalopathy without contrast enhancement, often causes diagnostic confusion1 with suspected diagnoses ranging from Binswanger’s disease to leukoencephalopathy or encephalomyelitis.

Here we report a patient with subacute dementia and diffuse bilateral white matter changes in the cerebral hemispheres and additional involvement of the brainstem, basal ganglia and thalamus on MRI. Initially, she was considered to suffer from an autoimmune encephalitis, transiently responded to immunosuppression but then developed multiple solid appearing cerebral lymphomas.

This 65-year-old woman had a history of insidious personality changes and forgetfulness of several months. Shortly before admission she developed double vision. Neurological examination revealed bilateral sixth nerve palsy. Neuropsychological examination showed mild dementia. CSF examination showed an increased protein level (931 mg/l; normal 150–400) and cell count (18/μl; normal <4). On cytology, many activated lymphocytes but no malignant cells were found. There was IgM synthesis and positive oligoclonal bands in the CSF. Serum levels of β2-microglobulin were normal (2.0 mg/l) and CSF levels were increased to 3.37 mg/l (normal <3). Antinuclear antibody titres (1:320; normal <1:80) and circulating …
17801861
A case of ‘lymphomatosis cerebri’ diagnosed in an early phase and treated by whole brain radiation: case report and literature review
Abstract‘Lymphomatosis cerebri’ (LC) is a term indicating a diffusely infiltrating form of primary central nervous system lymphoma (PCNSL) without evidence of a mass lesion. Not infrequently, diagnostic confusion is caused by its presentation on cranial magnetic resonance images (MRI), which is characterized by diffuse leukoencephalopathy without contrast enhancement. In this report, we describe a 53-year-old, immunocompetent man who had an insidiously progressive dementia and right weakness. On serial MRI in 4 months duration, diffuse white matter lesions without contrast enhancement gradually progressed, which was clinically consistent with his worsening condition. Biopsy specimen demonstrated nondestructive, diffusely infiltrating, large B-cell lymphoma, diagnosing LC. After the biopsy, corticosteroids were initiated, which dramatically alleviated his symptoms. Afterwards, he was treated by whole brain irradiation (total 36Gy) and discharged without noticeable deficits. Diagnosis of LC requires additional examinations generally not performed in the other white matter disorders. In suspected cases, biopsy should be performed to avoid deferring adequate cytostatic treatment.
11761374
Diffusion tensor images and magnetic resonance spectroscopy in primary central nervous system T-cell lymphoma: a case report.
PURPOSE
Primary central nervous system lymphoma (PCNSL) is rare and usually B cell in origin. T-cell lymphoma constitutes only 1.8% to 4.6% of the PCNSL, and may present as solitary or multiple homogeneous enhanced lesions. There have been few reports showing unusual leukoencephalopathy in PCNSL, which may be confused with other white matter diseases including multiple sclerosis and acute disseminated encephalomyelitis.


CASE REPORT
We reported a patient with T-cell PCNSL who presented a progressive dull response and extrapyramidal symptoms. Brain magnetic resonance imaging showed multiple focal leukoencephalopathy. Diffusion weighted imaging demonstrated hyper-intensity lesions and apparent diffusion coefficient images showed hypo-intensity lesions. Diffuse tensor images showed decreased fractional anisotropy. Pathology examination finally confirmed T-cell lymphoma.


CONCLUSION
Although recent development of neuro-imaging studies, the diagnosis of PCNSL still await further pathological confirmation in some occasions.
15748384
Lymphomatosis cerebri Presenting as a Recurrent Leukoencephalopathy
A 29-year-old immunocompetent woman was admitted in 2006 with ataxia, limb weakness, generalized dystonia, and vertical diplopia that developed after a febrile episode. Brain magnetic resonance imaging (MRI) revealed the presence of extensive periventricular white matter lesions that did not enhance after gadolinium injection. As low titers of cytomegalovirus-IgM antibodies were found in the serum, a presumed diagnosis of postviral acute disseminated encephalomyelitis (ADEM) was made, and the patient received a 5-day course of 1 g methylprednisolone. The clinical and radiological outcome was very rapidly favorable, and subsequent brain MRIs in 2007 and 2008 were normal. In March 2011, the patient was readmitted with the complaints of abnormal fatigue, imbalance, and speech disorder. The neurological examination showed fluctuating spatiotemporal disorientation with dyscalculia, verbal deafness, gait ataxia, right hemianopia, and pyramidal signs in the four limbs. The brain MRI demonstrated extensive T2 hyperintense white matter lesions predominating in the left temporal and parieto-occipital lobes, with a pseudotumoral aspect enhancing with gadolinium contrast. A clinical improvement was transiently noted after pulse steroid therapy, but after relapse and radiological worsening, the diagnosis of recurrent ADEM was challenged. The brain biopsy confirmed the presence of primary central nervous system lymphoma (PCNSL) under the variant form of lymphomatosis cerebri. Despite a partial response to chemotherapy, the patient died 8 months after the diagnosis. We discuss the role of sentinel lesions that may precede PCNSL for several years and insist on the importance to consider early brain biopsy in the presence of extensive, non-enhancing white matter lesions, even in a young and immunocompetent patient.
19354340
Lymphomatosis cerebri: clinical characteristics, neuroimaging, and pathological findings
Lymphomatosis cerebri is a rare variant of primary central nervous system lymphoma. We present a case involving a 56-year-old immunocompetent woman who complained of rapid deterioration of her higher brain function over a 4-month period. Magnetic resonance imaging showed extensive white-matter lesions. During brain biopsy, a diffusely infiltrating lymphoma with distinctive immunohistochemical features was detected. Awareness of this unique presentation and early tissue diagnosis provide the best hope for instituting appropriate treatments.
22975217
Primary central nervous system anaplastic large-cell lymphoma mimicking lymphomatosis cerebri
Primary central nervous system lymphoma (PCNSL) is usually diffuse large B-cell lymphoma. Anaplastic large-cell lymphoma (ALCL) rarely occurs in the central nervous system. PCNSL always presents as single or multiple nodular contrast-enhancing mass lesions within T2-hyperintense areas on magnetic resonance imaging (MRI). Infrequently, diffuse infiltrating change with little contrast enhancement called lymphomatosis cerebri can be seen in PCNSL. In this report, we describe a 75-year-old immunocompetent man who had progressive dementia. On MRI, diffuse white matter lesions with little contrast enhancement were observed to gradually progress, which was clinically consistent with his worsening condition. A biopsy specimen revealed non-destructive, diffusely infiltrating, anaplastic large CD30-positive lymphoma, indicating a diagnosis of ALCL. After the biopsy, he was treated by whole brain irradiation (total 46 Gy) and focal boost irradiation (total 14 Gy). However, his performance status worsened and there was no symptom improvement. The patient died 8 months after symptom onset. The clinical course, diagnostic workup, pathologic correlates, and treatment outcomes are described herein.
9535881
Lymphomatosis Cerebri
Lymphomatosis cerebri is considered a diffuse form of primary central nervous system lymphoma and very rare. It is not well recognized and may be misdiagnosed with infiltrating tumors, degenerative disorders, ischemic diseases, and infectious diseases developed in the brain. Awareness of the possibility of this rare disease and early biopsy are required for differential diagnosis and preventing poor clinical outcomes. We report a case with lymphomatosis cerebri who presented with rapid neurological deteriorations and review the relevant literatures.
6879879
CNS lymphoma: a practical diagnostic approach.
The concept and understanding of central nervous system (CNS) lymphoma have greatly evolved in the past few years. Better characterization of a number of lymphoproliferative neoplasms through clinical, immunophenotyping, and molecular studies is reflected in a much more complex WHO Classification of Tumours of Hematopoietic and Lymphoid Tissue. The term "primary CNS lymphoma" is now restricted to primary diffuse large B-cell lymphoma confined to the CNS (and/or to the eye) that occurs in immunocompetent patients. Many other lymphoma subtypes, some of which are primary or exclusive to the CNS, such as lymphomas of the dura and immunodeficiency-associated lymphomas, are excluded from this definition. We describe the clinical and morphologic features of a diverse group of lymphomas occurring in the CNS, including primary CNS lymphoma, primary vitreoretinal lymphoma, lymphomatosis cerebri, Epstein-Barr virus-associated lymphoproliferative disorders, low-grade B-cell lymphoma, T-cell lymphoma, anaplastic large cell lymphoma, intravascular large B-cell lymphoma, and Hodgkin lymphoma. The purpose of this review is to provide a practical approach to the diagnosis of an often-challenging entity, focusing on how to maximize the use of small tissue biopsies and prevent diagnostic traps, which we have encountered with similar cases. Clinical, radiologic, and histologic examples are presented.
1022359
Lymphomatosis cerebri: a treatable cause of rapidly progressive dementia
Lymphomatosis cerebri (LC) is a rare variant of primary central nervous system lymphoma (PCNSL) pathologically characterised by diffuse cerebral infiltration of a non-cohesive mass of malignant lymphoid cells. We describe a case of rapidly progressive dementia where MRI demonstrated a diffuse leukoencephalopathy. After a series of normal investigations, brain biopsy was undertaken with histology consistent with LC. Our patient was successfully treated with chemoradiotherapy and neurorehabilitation. This case underlines the importance of timely brain biopsy in rapidly progressive cognitive decline to allow earlier therapy for potentially curable pathology.

A 50-year-old previously fit and well lady with no vascular risk factors presented to her general practitioner with personality change and emotional lability, against a background of subacutely progressive amnestic syndrome over 3 weeks. She next developed severe anxiety and insomnia and was commenced on citalopram and temazepam. Neurological examination demonstrated universally brisk reflexes with no clonus and downgoing plantar responses. There was marked language difficulty with both expressive and receptive components and ideational and ideomotor apraxia. Formal neuropsychometric testing showed marked impairment in memory, naming, literacy skills and information processing speed (all <5th centile) with relative preservation of executive functioning (phonemic fluency 25th–50th centile). Testing was consistent with marked and pervasive cognitive dysfunction affecting mainly posterior, cortical and subcortical regions.

Full blood count, C-reactive protein, ESR, renal and liver function tests were normal. EEG showed left temporal irregular slowing with occasional low-voltage sharp waves suggestive of epileptiform activity. MRI examination (figure 1A–C) demonstrated extensive confluent areas of T2-weighted hyperintensity diffusely throughout the cerebrum and brainstem. There was no perceptible mass effect, …
7043906
Diffuse leukoencephalopathy due to lymphomatosis cerebri: a clinicopathological report
Lymphomatosis cerebri (LC) is a rare variant of primary central nervous system lymphoma (PCNSL), characterized by diffuse infiltration of brain tissue by neoplastic cells without formation of discrete mass lesions [1, 2]. MRI appearance is usually consistent with a diffuse nonenhancing leukoencephalopathy [3]. A 57-year-old man came to our observation in May 2010 because of head trauma with transient loss of consciousness. Cranial CT evidenced a diffuse hypodensity of hemispheric white matter. Since the recent history of anorexia, confusion, and falls, the patient entered our neurologic ward. Neurologic examination disclosed mental slowness, bradykinesia, and mild ataxia. His previous medical history was unremarkable. Brain MRI confirmed a diffuse leukoencephalopathy involving cerebral hemispheres, hippocampi, corpus callosum, basal ganglia region, and midbrain (Fig. 1a–c). No contrast enhancement was present. Laboratory data, in particular hematograms and inflammatory profiles were unremarkable. Cerebrospinal fluid analysis evidenced raised protein concentration (75 mg/dl) with rare lymphocytes (1–2 elements/ll). Cytology was negative for malignant cells. Cytofluorometry ruled out clonal restriction. A discrete alteration of blood–brain barrier with no intrathecal IgG synthesis or oligoclonal bands was present. Microbiologic and virologic markers (including HIV testing) were all negative. A total body CT ruled out occult neoplasms or lymphoadenopathies. Moreover, no hypermetabolic areas were present on FDG-PET scans. An empiric treatment with high-dose systemic steroids (methylprednisolone 1 g/die per 10 days) was decided. The clinical picture significantly improved and the patient was discharged at home almost asymptomatic. In the following days (July 2010), the patient’s neurologic status gradually deteriorated. The patient was conducted again into our emergency department because of severe dyspnea and fever. Blood gas analysis evidenced marked hypoxia with hypocapnia. The suspect of pulmonary thromboembolism was confirmed by CT angiography. He was intubated and transferred to the intensive care unit. Anticoagulation was started. Brain MRI showed progression of white matter abnormalities and a punctiform area of contrast enhancement in left frontal lobe white matter (Fig. 1d). One week later, the patient expired because of a multiorgan failure syndrome. On autopsy, there was no macroscopic and histological evidence of systemic lymphoproliferative diseases or neoplasms. Brain gross appearance was unremarkable. Microscopy examination highlighted a diffuse infiltration of atypical cells, immunopositive for the CD20 antigen (Fig. 2a, b). Ki-67 positive cells were numerous (Fig. 2c). Neoplasm cells were evident in all sampled areas (cerebral cortex, hippocampi, white matter, basal ganglia, midbrain, and pons). Rare interspersed reactive CD3-positive T lymphocytes and moderate reactive gliosis were present, too. D. Imperiale (&) S. Taraglio C. Atzori R. Testi Centro Regionale Diagnosi ed Osservazione Malattie Prioniche DOMP, ASL To2, Via Cibrario72, 10144 Turin, Italy e-mail: daniele.imperiale@aslto2.piemonte.it
73388625
P11.06LYMPHOMATOSIS CEREBRI: A RARE FORM OF PRIMARY CENTRAL NERVOUS SYSTEM LYMPHOMA
INTRODUCTION: Primary central nervous system lymphomas (PCNSL) are a unusual form of non-Hodgkin lymphoma, restricted to the neuroaxis and eyes.In most cases magnetic resonance imaging (MRI) disclose single or multiples lesions with mass effect and contrast enhancement. Rarely,PCNSL may occur as a diffuse non enhanced infiltrative lesion, a variant called Lymphomatosis Cerebri (LC).LC can present with a progressive course and diffuse white matter abnormalities on MRI what includes a wide differential diagnosis, becoming a diagnostic challenge. OBJECTIVE: To present the detailed characteristics of 4 patients who were diagnosed of LC at our centers and analyze the results of a systematic review of this entity. MATERIAL AND METHODS: A systematic literature search was carried out using Pubmed an ISI Web of knowledge to 1 February 2014.The search also included reference lists of papers identified. Demographic, clinical, histological, cerebrospinal fluid (CSF), MRI and therapeutic data were extracted. Patients with nodular enhancement at first MRI or concurrent systemic lymphoma were excluded. RESULTS: 28 patients from literature and 4 new patients were included. The median age was 58.5 years old (29-80).53.1% of patients were women. Only 1 was not inmunocompetent.62.5% out of patients presented with a Karnofsky Performance Status (KPS) <70. Most common presenting symptoms were cognition impairment (59.4%) and behavioral changes (50%).18.8% developed seizures. First MRI showed patchy enhancement in 33.3% of patients. Nearly half of patients (48.6%) had infratentorial and supratentorial infiltration. Both hemispheres were infiltrated in 96.8% of cases. Spinal cord was affected in 2 patients. CSF results were normal in 18.8% of patients. The median time to diagnosis was 150 days (30-900). Diagnosis was postmortem in 35.5% of patients. Treatments administered included: only corticoids (34.4%), chemotherapy and/or radiotherapy (46.9%). Median overall survival was 248 days (80-1890). According treatment, median survival was 3, 6.9, 44.3 months in no treated, only receiving corticoids and treated with chemotherapy/radiotherapy patients, respectively. One third of all patients were alive 1 year after the onset of the illness. Univariate analysis revealed that age ≥ 59 years (p = 0.029), KPS < 70 (p = 0.01), hypoglycorrhachia (p < 0.001) and lack of chemotherapy and/or radiotherapy treatment (p = 0.02) were associated with worst prognosis.The multivariate analysis demonstrated that KPS was the only independent prognostic factor for survival (HR: 0.65; ( CI95%:0.004-0.946); p = 0.045). CONCLUSION: LC is frequently misdiagnosed and associated with a considerable diagnostic delay that could explain the low performance status of patients at diagnosis. Despite to the fact that some patients can respond to the oncologic treatment, KPS is the only independent prognostic factor identified.
1864864
A case of lymphomatosis cerebri mimicking inflammatory diseases
BackgroundLymphomatosis cerebri (LC) is a rare subtype of primary central nervous system malignant lymphoma. The typical features of this disease exhibited on magnetic resonance imaging (MRI) without contrast enhancement are similar to those observed with diffuse leukoencephalopathy, mimicking white matter disorders such as encephalitis. Clinical features and examination findings that are suggestive of inflammatory diseases may indeed confound the diagnosis of LC.Case presentationA 66-year-old woman with continuous fever over a two-month period developed left hemiparesis despite presenting in an alert state with normal cognitive function. Sampling tests showed autoantibodies in the serum and inflammatory changes in the cerebrospinal fluid. The results from an MRI demonstrated multiple non-enhanced brain lesions in the splenium of the corpus callosum and deep white matter. Single photon emission computed tomography revealed increases in blood flow in the basal ganglia, thalamus and brainstem. No systemic malignancies were found. The patient was suspected of having a diagnosis of nonvasculitic autoimmune inflammatory meningoencephalitis and treated with intravenous methylprednisolone pulse therapy. Her fever transiently dropped to within the normal range. However, she had a sudden seizure and a second MRI exhibited infiltrative lesions gradually extending throughout the whole brain. We performed a brain biopsy, and LC was histologically diagnosed. The patient received whole-brain radiation therapy, which diminished the fever and seizures. The patient died one year after the initial onset of fever.ConclusionsThe present case yields an important consideration that brain neoplasms, especially LC, cannot be ruled out, even in cases with clinical characteristics and examinations consistent with inflammatory diseases. Careful follow-up and histological study are vital for the correct diagnosis of LC.
42720713
Primary central nervous system lymphoma masquerading as herpes encephalitis: clinical, magnetic resonance imaging, and pathologic findings.
An 84-year-old man presented with acute confusion, global aphasia, and fever. Magnetic resonance imaging (MRI) showed hyperintense lesions on T2-weighted and fluid-attenuated inversion recovery (FLAIR) images predominantly affecting the cortical gray matter of the left mesial temporal and inferior frontal lobes, and insula. Acyclovir was prescribed for presumed viral encephalitis. Clinical and MRI worsening prompted a left temporal lobe biopsy that revealed primary central nervous system lymphoma (PCNSL). This case adds to the MRI spectrum of PCNSL and illustrates that it may mimic the clinical and MRI presentation of herpes simplex encephalitis.
6481166
Primary brain T-cell lymphoma of the lymphoblastic type presenting as altered mental status
The authors present a case of a 56-year-old man with altered mental status. Magnetic resonance imaging (MRI) of the brain revealed non-enhancing abnormalities on T2 and FLAIR imaging in the brainstem, cerebellum, and cerebrum. Immunohistochemisty demonstrated precursor T-cell lymphoblastic lymphoma. After treatment with methotrexate, he improved clinically without focal sensorimotor deficits and with improving orientation. MRI showed almost complete resolution of brainstem and cerebral lesions. To the authors’ knowledge, there are only five previous reports of primary central nervous system T-cell lymphoblastic lymphoma. Since treatable, it deserves consideration in patients with altered mental status and imaging abnormalities that include diffuse, non-enhancing changes with increased signal on T2-weighted images.
6705459
Development of primary central nervous system lymphoma associated with human immunodeficiency virus and JC virus infection.
We report here a case of a 37-year-old man with human immunodeficiency virus (HIV) infection followed by JC virus (JCV) infection and primary central nervous system lymphoma (PCNSL). The patient had been infected with HIV type 1 due to blood products for hemophilia A during infancy. He had progression of nervous symptoms and was diagnosed with progressive multifocal leukoencephalopathy (PML) clinically at the age of 36, when his CD4-positive lymphocyte counts ranged between 350 and 450/μl. Oral mefloquine, intravenous methylprednisolone pulse therapy, and intravenous immunoglobulin were not effective for the PML, and the patient entered a vegetative state. Brain biopsy revealed JCV infection without pathological findings of PML. Eight months after the clinical diagnosis of PML, he developed respiratory failure and brain magnetic resonance imaging revealed a mass lesion in the brain stem. The patient died 19 months after the diagnosis of PML. Autopsy findings were compatible with PCNSL. EBV-encoded small RNA-1-positive cells were not detected. We present a case of JCV-positive PCNSL with HIV infection complicated with clinical PML.
6561139
A case of primary central nervous system lymphoma presenting diffuse infiltrative leukoencephalopathy.
A 58-year-old immunocompetent man gradually developed loss of appetite, cognitive decline, gait disturbances, and personality changes over 4 months. Brain magnetic resonance imaging (MRI) revealed bilateral diffuse leukoencephalopathy without mass formation on admission. His condition progressively deteriorated, and we treated him with intravenous high-dose steroids. His symptoms improved rapidly, but exacerbated when therapy was withdrawn. A brain biopsy was performed, and the diagnosis of primary central nervous system lymphoma (PCNSL) was confirmed. He was successfully treated with high-dose methotrexate therapy. Although it is difficult to diagnose PCNSL without mass formation in the early stages, steroid responsiveness is important and brain biopsy is essential for the correct diagnosis of PCNSL.
43662765
MRI Findings in Lymphomatosis Cerebri: Description of a Case and Revision of the Literature
Lymphomatosis cerebri (LC) is a rare form of primary central nervous system lymphoma; we report a case of LC mainly involving the brainstem and cerebellum. This diagnosis should be considered in patients presenting with diffuse white matter disease, and a subacute clinical history of cognitive deficits, ataxic gait, and personality changes. We present our findings along with a review of the neuroradiological literature.
3489682
A rare case of nonenhancing primary central nervous system lymphoma mimic multiple sclerosis
Primary central nervous system lymphoma (PCNSL) is reported to have increased in the last decades. Early diagnosis is crucial for proper management of this tumor. We report a case of a 48-year-old man who was initially diagnosed with multiple sclerosis. Magnetic resonance imaging of the brain revealed multiple lesions with hypersignals in the bilateral basal ganglia and brain stem in T2-weighted image and non-enhancement, while positron emission tomography showed a low uptake of 18F-fluorodeoxyglucose in the affected brain, indicative of demyelination. However, this individual was correctly diagnosed with PCNSL after biopsy and further histological analysis. Primary central nervous system lymphoma must be considered even when nonenhancing, diffuse lesions are seen on MRI. A visible tumor on imaging is essential to ensure an early brain biopsy and histological diagnosis.
39378622
Usefulness of [18F]FDG-PET kinetic analysis in non-enhancing primary central nervous system lymphoma: Case report
A 62-year-old woman experienced headache and rapidly progressive left hemiparesis over 2 weeks. Diffusion-weighted and fluid-attenuated inversion recovery MR images of the head showed increased signal intensity in the right basal ganglia, periventricular white matter and the brain stem. Enhancement was not observed on a T1-weighted spin-echo MR image after the administration of a contrast material. An18F-fluorodeoxyglucose positron emission tomography ([18F]FDG-PET) study with kinetic analysis showed decreased FDG transport and increased hexokinase activity in the lesions compared with the contralateral hemisphere. The diagnosis was made by biopsy of the right caudate head and pathologic specimens were positive for malignant large-cell lymphoma, B-cell phenotype. The patient received high-dose methotrexate with CHOP chemotherapy, and an [18F]FDG-PET study with kinetic analysis showed decreased hexokinase activity after the first chemotherapy. Kinetic [18F]FDG-PET analysis may be useful to diagnose and monitor the treatment effect in non-enhancing primary central nervous system lymphoma.
4566250
Lymphomatosis cerebri with intramedullary spinal cord involvement.
Lymphomatosis cerebri (LC) is a rare form of primary central nervous system lymphoma (PCNSL). Little is known about cases of LC with spinal cord involvement. Among the 11 PCNSL patients treated in our hospital during a four-year period, we identified two cases of LC with spinal cord lesions. One showed a spinal cord lesion followed by leukoencephalopathy. The other showed a spinal cord lesion after LC. In both cases, the histopathology was diffuse large B-cell lymphoma. It is possible that LC may affect the entire central nerve system, and tumor infiltration to the brain and spinal cord in LC may occur more frequently than has been previously considered.
30830237
Primary central nervous system lymphoma mimicking Bickerstaff’s encephalitis
Primary central nervous system (CNS) lymphomas are malignant, predominantly B cell, lymphomas arising within the CNS, which account for 1–2 % of malignant lymphomas. Although there has been a steady increase in the incidence of primary CNS lymphomas over the last two decades, their primary presentation in the brainstem is still rare, which often leads to their misdiagnosis [1]. A highintensity signal on diffusion-weighted magnetic resonance imaging (MRI) of the brain usually provides the best delineation for a primary CNS lymphoma. However, the diagnosis of a primary CNS lymphoma still depends greatly on biopsy. A good response to corticosteroids does not aid in the differential diagnosis of a primary CNS lymphoma; under these circumstances, the diagnosis of a malignant lymphoma is a great challenge for clinicians. Here, we report an autopsy case of a primary CNS diffuse large B cell lymphoma of the brainstem mimicking Bickerstaff’s encephalitis (BE). A 62-year-old immunocompetent male presented with a 2-week history of gait ataxia, tetraparesis, and dyspnea, and was admitted to a general hospital. On the day of hospitalization, he became intubated and bedridden due to the deterioration of his dyspnea and tetraparesis. He was then transferred to our hospital for further treatment. 2 weeks before presentation, he had had a mild upper respiratory tract infection. On examination, he was somnolent and found to have ptosis and almost complete external ophthalmoplegia with slight spontaneous nystagmus. Tendon reflexes were all reduced. A routine nerve conduction study (NCS) revealed the absence of F waves in the extremities without any prolongation of distal latency or a conduction block. A cerebrospinal fluid (CSF) examination showed a normal cell count, but a slight elevation of protein (52 mg/ dL) was observed. The patient’s serum was screened for anti-ganglioside antibody with an enzyme-linked immunosorbent assay (ELIZA) as reported previously [2]. Only anti-GT1a IgG antibody was weekly positive, not GQ1b. Serum soluble interleukin-2 receptor, which often increases in systemic malignant lymphoma or intravascular large B cell lymphoma, beta2 microglobulin in the CSF, other autoantibodies, and viral PCR examinations were all negative. T2 fluid-attenuated inversion recovery MRI of the brain demonstrated a confluent high-signal lesion extending from the posterior region of the medulla oblongata to the left thalamus with slight contrast enhancement (Fig. 1a–d). Iso-signal intensity was observed in the same lesion on diffusion-weighted imaging (DWI). We diagnosed atypical BE due to the acute development of ataxia, tetraparesis, impaired consciousness, and external ophthalmoplegia with an absence of F waves on NCS. After the administration of intravenous immunoglobulin (0.4 g/kg for 5 days) with steroid pulse therapy (1,000 mg methylpredonine for 3 days), he became alert and able to breathe and walk without aid. The extent of the lesion in the brainstem also shrank on MRI in accordance with his symptomatic improvement. However, at 1 month after immunotherapy, he complained of difficulty in expectorating and mild Y. Miki (&) M. Tomiyama M. Baba Department of Neurology, Aomori Prefectural Central Hospital, Higashitsukurimichi 2-1-1, Aomori 030-8553, Japan e-mail: yasuomiki@hotmail.com
24827003
Interleukin 10 Level in the Cerebrospinal Fluid as a Possible Biomarker for Lymphomatosis Cerebri.
A 71-year-old immunocompetent man developed cognitive decline and gait disturbance. Brain magnetic resonance imaging (MRI) revealed bilateral diffuse leukoencephalopathy without a mass lesion. An analysis of the cerebrospinal fluid (CSF) showed elevated levels of interleukin (IL)-10. The condition of the patient progressively deteriorated, and intravenous high-dose steroids proved ineffective. Detection of non-destructive, diffusely infiltrating, large B-cell lymphoma in biopsy and autopsy specimens led to a diagnosis of lymphomatosis cerebri (LC). On serial MRI, the basal ganglia and white matter lesions increased in parallel with the levels of IL-10. These findings suggest that the IL-10 level in the CSF may represent a potentially useful biomarker for the early diagnosis and monitoring of the disease progression in LC.
13572357
Lymphomas-Part 2.
There are 2 types of central nervous system lymphoma: primary and secondary. Both have variable imaging features making them diagnostic challenges. Furthermore, a patient's immune status significantly alters the imaging findings. Familiarity with typical appearances, variations, and common mimics aids radiologists in appropriately considering lymphoma in the differential diagnosis. Moreover, special types of lymphoma, such as lymphomatosis cerebri, intravascular lymphoma, and lymphomatoid granulomatosis, also are found. This article discusses uncommon types of lymphoma and the differential diagnosis for focal, multifocal, meningeal, and infiltrative lymphomas.
22714929
Lymphomatosis cerebri presenting as a rapidly progressive dementia with a high methylmalonic acid
We report a case of a patient with a rapidly progressive dementing illness and gait disturbance, in whom initial screening demonstrated a high methylmalonic acid level only, suggestive of a functional vitamin B12 deficiency. Despite B12 replacement therapy, he continued to decline. Further investigations demonstrated extensive signal change on magnetic resonance imaging involving grey and white matter within the corpus callosum, deep grey matter, brainstem and cerebellar peduncles, and patchy post-contrast enhancement. Laboratory testing revealed a raised erythrocyte sedimentation rate, raised anti-nuclear, intrinsic factor and lupus anticoagulant antibody titres, and a IgG kappa paraprotein. Cerebrospinal fluid was unremarkable. Bone marrow trephine biopsy showed monoclonal gammopathy of unknown significance. The patient initially responded to steroids, and underwent a brain biopsy, which was uninformative. However, 3 weeks following admission, he died due to an aspiration pneumonia. Autopsy findings were consistent with a diffuse primary central nervous system small cell B-cell lymphoma. This has been rarely reported in the medical literature, but our case exhibits typical clinical features, although patchy enhancement on imaging and the high methylmalonic acid have not been previously described. We hypothesise that his functional B12 deficiency may have resulted from rapid cell turnover, perhaps in conjunction with the presence of intrinsic factor antibodies.
9909844
Primary central nervous system lymphoma presenting as diffuse cerebral infiltration.
We report a case of primary central nervous system lymphoma presenting as diffuse cerebral infiltration. On T2-weighted spin echo MR imaging using a 1.0 Tesla unit, high signal intensity lesions were presented mainly in the bilateral pyramidal tracts and also diffusely extended to white matter with brain swelling. No enhancing lesion was demonstrated after the intravenous injection of Gadolinium-DTPA, during the course of her disease. Radiological diagnosis of gliomatosis cerebri was made because of the characteristic MR appearance. Stereotactic biopsy was performed, and diffusely scattered lymphocytes, probably neoplastic, in the cerebral white matter were demonstrated histopathologically. Oral corticosteroids, radiation therapy, and chemotherapy were applied soon after her admission. The patient's condition improved dramatically. MR imaging using a 1.5 Tesla unit after the treatments showed marked regression and reduction of high intensity lesions on T2-weighted images and improvement of brain swelling. It should be emphasized that brain biopsy is important method for correct diagnosis in case of diffuse non-enhancing brain lesions like our case.
23180660
A rare case of Primary Central Nervous System Lymphoma initially diagnosed as demyelinating encephalopathy.
We report a case of histopathologically-confirmed primary central nervous system lymphoma who was initially diagnosed as demyelinating encephalopathy. A 58-year-old woman was admitted with confusion and left hemiparesis. Head MR showed abnormal flaky hypointense T1 and hyperintense T2 signals at right thalamus, splenium of corpus callosum, bilateral cerebral peduncle, pons, medulla oblongata, basal ganglia and right corona radiata. Her mental status improved a little and she was discharged from hospital after neuroprotective treatment. 10 days after her discharge, her confusion appeared again with hallucination and unsteady walking. Pathological examination revealed non-Hodgkin's lymphoma (WHO classification: DLBCL). The patient continued to deteriorate after the surgery and died 10 days later.
27691635
A 64‐YEAR‐OLD WOMAN WITH PROGRESSIVE DEMENTIA AND LEUKOENCEPHALOPATHY
In a 64-year-old woman presenting with rapidly progressive dementia, brain magnetic resonance imaging revealed a diffuse leukoencephalopathy without gadolinium enhancement, and the 14.3.3 protein was found to be positive in the cerebrospinal fluid. An electroencephalogram showed diffused slow waves and epileptic seizures without periodic paroxysmal activity. The patient died 3 months after onset of symptoms, and an autopsy restricted to the brain was performed. Gross examination was not informative, and only microscopic examination permitted identification of scattered lymphomatous cells on all sections from the brain hemispheres, brain stems and cerebellum. Immunopositivity of these tumor cells for CD20 attested their B phenotype. This observation illustrates "lymphomatosis cerebri," a recently described entity, which has to be considered in the differential diagnosis of rapidly progressive dementia in adults.
43602711
Primary central nervous system lymphoma initially mimicking lymphomatosis cerebri: An autopsy case report
A 59‐year‐old immunocompetent man was admitted to our hospital because of progressive dementia with concomitant bilateral uveitis. The first brain MRI revealed diffuse hyperintense lesions in the cerebral white matter of both hemispheres on a T2‐weighted image and fluid‐attenuated inversion recovery image. However, another MRI taken more than 1 month later revealed enhanced cohesive mass lesions in the bilateral thalami, in addition to the white matter lesions. The white matter lesions were slightly hyperintense on a diffusion‐weighted image and apparent diffusion coefficient map image, suggesting vasogenic edema. One year after the onset of uveitis, he died of respiratory failure. Pathological diagnosis was diffuse large B‐cell lymphoma with perivascular proliferation and diffuse scattered infiltration in the cerebrum and brainstem. Microscopically, cohesive mass lesions in the bilateral thalami were a massive cluster of lymphoma cells. This is a case of primary CNS lymphoma (PCNSL) mimicking ‘lymphomatosis cerebri (LC)’ at first but later exhibiting typical mass lesions, giving rise to the possibility that cases of LC might unmask features of regular lymphomas in their later course more often than believed thus far.
19405787
Lymphomatosis cerebri presenting with orthostatic hypotension, anorexia, and paraparesis
To increase awareness about lymphomatosis cerebri by describing a patient with a unique presentation Case report a 58 year old woman presented with progressive lower extremity weakness, postural hypotension, and 90 pound weight loss over 3 months a brain magnetic resonance image revealed multiple non-enhancing foci of T2 hyperintensity in the periventricular white matter despite treatment with corticosteroids, she expired autopsy demonstrated normal gross appearance of the brain and spinal cord microscopic inspection revealed diffuse infiltration of the central nervous system (CNS) parenchyma and white matter by large atypical B cells, consistent with a diagnosis of lymphomatosis cerebri lymphomatosis cerebri is a primary CNS lymphoma variant that is poorly recognized and often misdiagnosed it commonly presents as a rapidly progressive dementia, although patients may present with neurologic dysfunction without dementia diagnosis requires a pathological examination treatment with intravenous high–dose methotrexate based chemotherapy should be considered in appropriate patients.
12017499
The clinical diagnosis and treatment of microgliomatosis: report of a case.
Microgliomatosis (Russell, Marshall, and Smith, 1948) or primary reticulosis of the brain (Miller and Ramsden, 1963) is usually considered a pathological curiosity and the diagnosis has almost invariably been made on necropsy material. Yet the structure of the tumour suggests that it may be radiosensitive and every effort should therefore be made to reach a diagnosis during life. In reporting a case in which the condition has been treated by radiotherapy with some success we wish to discuss the diagnostic criteria and the therapeutic measures adopted.
7820645
Computed Tomography in Primary Malignant Lymphoma of the Brain
Primary malignant lymphoma of the brain is a rare lesion characterized clinically by varied nonspecific neurologic deficits and usually a rapid fulminant deterioration and death. This course may be altered by radiotherapy, and early diagnosis assumes major importance. Laboratory tests. EEG. radionuclide scans, angiography, and pneumoencephalography may not show definite abnormality in the early stages. This report concerns four cases in which good correlation between the location of the brain lesion and the abnormality on computed tomography scan was demonstrated.
9037237
Onset of primary brain T-lymphoma simulating a progressive leukoencephalopathy
We describe the clinical, CT and MRI evolution of a patient with a primary T-lymphoma of the brain showing features similar to those of leukoencephalopathy. We report the findings that led to the cerebral biopsy performed and we discuss the striking features of this case in the light of previous reports in the literature.SommarioViene descritta l'evoluzione clinica, TC ed MRI di un paziente affetto da linfoma T primitivo dell'encefalo con caratteristiche simili a quelle di una leucoencefalopatia.Sono esposti i reperti che hanno motivato l'indagine bioptica e discussi gli aspetti salienti del caso in relazione alle descrizioni della letteratura.
46505092
Primary brain tumors in adults.
Primary malignant brain tumors account for 2 percent of all cancers in U.S. adults. The most common malignant brain tumor is glioblastoma multiforme, and patients with this type of tumor have a poor prognosis. Previous exposure to high-dose ionizing radiation is the only proven environmental risk factor for a brain tumor. Primary brain tumors are classified based on their cellular origin and histologic appearance. Typical symptoms include persistent headache, seizures, nausea, vomiting, neurocognitive symptoms, and personality changes. A tumor can be identified using brain imaging, and the diagnosis is confirmed with histopathology. Any patient with chronic, persistent headache in association with protracted nausea, vomiting, seizures, change in headache pattern, neurologic symptoms, or positional worsening should be evaluated for a brain tumor. Magnetic resonance imaging is the preferred initial imaging study. A comprehensive neurosurgical evaluation is necessary to obtain tissue for diagnosis and for possible resection of the tumor. Primary brain tumors rarely metastasize outside the central nervous system, and there is no standard staging method. Surgical resection of the tumor is the mainstay of therapy. Postoperative radiation and chemotherapy have improved survival in patients with high-grade brain tumors. Recent developments in targeted chemotherapy provide novel treatment options for patients with tumor recurrence. Primary care physicians play an important role in the perioperative and supportive treatment of patients with primary brain tumors, including palliative care and symptom control.
39360052
White Matter Diseases with Radiologic-Pathologic Correlation.
White matter diseases include a wide spectrum of disorders that have in common impairment of normal myelination, either by secondary destruction of previously myelinated structures (demyelinating processes) or by primary abnormalities of myelin formation (dysmyelinating processes). The pathogenesis of many white matter diseases remains poorly understood. Demyelinating disorders are the object of this review and will be further divided into autoimmune, infectious, vascular, and toxic-metabolic processes. Autoimmune processes include multiple sclerosis and related diseases: tumefactive demyelinating lesions, Balo concentric sclerosis, Marburg and Schilder variants, neuromyelitis optica (Devic disease), acute disseminated encephalomyelitis, and acute hemorrhagic leukoencephalopathy (Hurst disease). Infectious processes include Lyme disease (neuroborreliosis), progressive multifocal leukoencephalopathy, and human immunodeficiency virus (HIV) encephalopathy. Vascular processes include different types of small-vessel disease: arteriolosclerosis, cerebral amyloid angiopathy, cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), primary angiitis of the central nervous system, Susac syndrome, and neurolupus. Toxic-metabolic processes include osmotic myelinolysis, methotrexate leukoencephalopathy, and posterior reversible encephalopathy syndrome. The imaging spectrum can vary widely from small multifocal white matter lesions to confluent or extensive white matter involvement. Understanding the pathologic substrate is fundamental for understanding the radiologic manifestations, and a systematic approach to the radiologic findings, in correlation with clinical and laboratory data, is crucial for narrowing the differential diagnosis. (©)RSNA, 2016.
34161349
Diffusely infiltrating central nervous system lymphoma involving the brainstem in an immune-competent patient.
A 49-year-old right-handed woman presented with a 3-week history of progressive ataxia, dysarthria, right hemiparesis, cognitive decline, and headache. Infectious, inflammatory, neoplastic, and paraneoplastic workup results were unremarkable. The ophthalmologic evaluation findings were unremarkable for inflammatory or neoplastic involvement. Repeated lumbar puncture findings revealed mild lymphocytic pleocytosis with mildly elevated proteins. Cerebrospinal fluid cytology and flow cytometry results were negative. Magnetic resonance imaging of the brain showed a diffusely enhancing lesion typical for CLIPPERS (chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids). 1 Biopsy was felt to be risky given the deep location of the lesion, hence the patient was treated with steroids. The patient showed moderate clinical improvement initially and there was significant reduction in edema on magnetic resonance imaging but persistent perivascular curvilinear enhancement (Figure 1 and Figure 2). With subsequent clinical progression while the patient was taking steroids, a cerebellar biopsy was performed and revealed primary large B-cell non-Hodgkin lymphoma (Figure 3). The patient underwent 4 cycles of high-dose methotrexate, rituximab, and temozolomide. Following the first 2 cycles, she had a complete resolution of her speech symptoms and significant improvement of her rightsided weakness. Unfortunately, her treatment was complicated by steroid-induced diabetes mellitus, bilateral avascular necrosis of the hips and right shoulder, and septic right hip arthritis, which resulted in deconditioning and generalized weakness. Magnetic reso
36047611
Recurrent primary central nervous system lymphoma mimicking neurodegenerative disease--an autopsy case report.
A 42-year-old female presented with recurrent primary central nervous system lymphoma mimicking the roentgenographic appearance of diffuse brain degeneration. Betamethazone was administered, but her condition worsened. Biopsy of a swollen neck lymph node demonstrated lymphoma cells. Computed tomography and magnetic resonance (MR) imaging showed no contrast-enhanced lesions. T2-weighted MR imaging revealed diffuse, high intensity areas in the white matter of the bilateral cerebrum, basal ganglia, and brainstem. Despite chemotherapy for systemic lymphoma, she died of respiratory arrest. Histological examination of autopsy specimens showed diffuse infiltration of lymphoma cells in the perivascular space of the cerebral cortex, but little neovascularization. The absence of contrast enhancement may have been due to preservation of the blood-brain barrier. Histological confirmation of roentgenographic findings of brain degeneration is important in patients treated for primary central nervous system lymphoma.
6804229
Case report of unusual leukoencephalopathy preceding primary CNS lymphoma
A previously healthy 35 year old woman presented with bilateral uveitus associated with multiple, evolving, non-enhancing white matter lesions consistent with a progressive leukoencephalopathy such as multiple sclerosis. Thirty months after her initial presentation, she was diagnosed with primary CNS lymphoma and died 14 months later. The unusual clinical course preceding the diagnosis suggests that a demyelinating disease may have preceded, and possibly heralded, the development of primary CNS lymphoma. Cases of “sentinel lesions” heralding the diagnosis of primary CNS lymphoma have been reported, and this case further corroborates such instances and raises further issues regarding possible neoplastic transformation occurring in inflammatory diseases such as multiple sclerosis.
40465718
Patterns of contrast enhancement in the brain and meninges.
Contrast material enhancement for cross-sectional imaging has been used since the mid 1970s for computed tomography and the mid 1980s for magnetic resonance imaging. Knowledge of the patterns and mechanisms of contrast enhancement facilitate radiologic differential diagnosis. Brain and spinal cord enhancement is related to both intravascular and extravascular contrast material. Extraaxial enhancing lesions include primary neoplasms (meningioma), granulomatous disease (sarcoid), and metastases (which often manifest as mass lesions). Linear pachymeningeal (dura-arachnoid) enhancement occurs after surgery and with spontaneous intracranial hypotension. Leptomeningeal (pia-arachnoid) enhancement is present in meningitis and meningoencephalitis. Superficial gyral enhancement is seen after reperfusion in cerebral ischemia, during the healing phase of cerebral infarction, and with encephalitis. Nodular subcortical lesions are typical for hematogenous dissemination and may be neoplastic (metastases) or infectious (septic emboli). Deeper lesions may form rings or affect the ventricular margins. Ring enhancement that is smooth and thin is typical of an organizing abscess, whereas thick irregular rings suggest a necrotic neoplasm. Some low-grade neoplasms are "fluid-secreting," and they may form heterogeneously enhancing lesions with an incomplete ring sign as well as the classic "cyst-with-nodule" morphology. Demyelinating lesions, including both classic multiple sclerosis and tumefactive demyelination, may also create an open ring or incomplete ring sign. Thick and irregular periventricular enhancement is typical for primary central nervous system lymphoma. Thin enhancement of the ventricular margin occurs with infectious ependymitis. Understanding the classic patterns of lesion enhancement--and the radiologic-pathologic mechanisms that produce them--can improve image assessment and differential diagnosis.
560688
Punctate and curvilinear gadolinium enhancing lesions in the brain: a practical approach
IntroductionCerebral punctate and curvilinear gadolinium enhancements (PCGE) correspond to opacification of small vessel lumen or its perivascular areas in case of blood-brain barrier (BBB) disruption. We will discuss the possible causes of intra-parenchymal central nervous system PCGE.MethodsOur review is based on French database including patients presenting with central nervous system PCGE and literature search using PubMed database with the following keywords: punctate enhancement, linear enhancement, and curvilinear enhancement. Disorders which displayed linear leptomeningeal or periventricular enhancements without intra-parenchymal PCGE are excluded of this review.ResultsAmong our 39 patients with PCGE, 16 different diagnoses were established. After combining our PCGE causes with those described in the literature, we propose a practical approach. Besides physiologic post-contrast enhancement of small vessels, three pathologic conditions may exhibit PCGE: (1) small collateral artery network seen in Moyamoya syndrome, (2) small veins congestions related to developmental or acquired venous outflow disturbance, and (3) disorders causing small vessels BBB disruption indicated by T2 and FLAIR hyperintensities in the corresponding areas of PCGE. Disruption of the BBB could be caused by a direct injury of the endothelial cell, as in posterior reversible encephalopathy syndrome, Susac syndrome, and radiochemotherapy-induced injuries, or by an angiocentric cellular infiltrate, as in inflammatory disorders, demyelinating diseases, host immune responses fighting against infections, prelymphoma states, lymphoma, and in CLIPPERS.ConclusionPCGE may conceal several causes, including physiological and pathological conditions. Nevertheless, a practical approach could improve its management and limit the indications of brain biopsy to very specific situations.
14035778
Modern techniques of magnetic resonance in the evaluation of primary central nervous system lymphoma: contributions to the diagnosis and differential diagnosis
In addition to findings from conventional magnetic resonance imaging, modern magnetic resonance imaging techniques have provided important information about tumor metabolism, in vivo metabolite formation, water molecule diffusion, microvascular density, and blood-brain barrier permeability, all of which have improved the in vivo diagnostic accuracy of this method in the evaluation of primary central nervous system lymphoma. These nonconventional magnetic resonance techniques are useful in the clinical practice because they enhance conventional magnetic resonance imaging by reinforcing the possibility of a diagnosis and by allowing the early detection of disease recurrence. This report is a review of the most relevant contributions of nonconventional magnetic resonance techniques to the imaging diagnosis of primary central nervous system lymphoma, the differential diagnosis of this disease, and the prognosis of patients. This paper aims to describe a wide range of presentations of primary central nervous system lymphoma, their appearance in imaging, and the differential diagnoses of this disease.
33135830
Advances in Primary Central Nervous System Lymphoma
Primary central nervous system lymphoma (PCNSL) is a rare form of non-Hodgkin lymphoma that is limited to the CNS. Although novel imaging techniques aid in discriminating lymphoma from other brain tumors, definitive diagnosis requires brain biopsy, vitreoretinal biopsy, or cerebrospinal fluid analysis. Survival rates in clinical studies have improved over the past 20 years due to the addition of high-dose methotrexate-based chemotherapy regimens to whole-brain radiotherapy. Long-term survival, however, is complicated by clinically devastating delayed neurotoxicity. Newer regimens are attempting to reduce or eliminate radiotherapy from first-line treatment with chemotherapy dose intensification. Significant advances have also been made in the fields of pathobiology and treatment, with more targeted treatments on the horizon. The rarity of the disease makes conducting of prospective clinical trials challenging, requiring collaborative efforts between institutions. This review highlights recent advances in the biology, detection, and treatment of PCNSL in immunocompetent patients.
6050213
Can morphological MRI differentiate between primary central nervous system lymphoma and glioblastoma?
BackgroundPrimary central nervous system lymphoma (PCNSL) is a rare, aggressive brain neoplasm that accounts for roughly 2-6% of primary brain tumors. In contrast, glioblastoma (GBM) is the most frequent and severe glioma subtype, accounting for approximately 50% of diffuse gliomas. The aim of the present study was to evaluate morphological MRI characteristics in histologically-proven PCNSL and GBM at the time of their initial presentation.MethodsWe retrospectively evaluated standard diagnostic MRI examinations in 54 immunocompetent patients (26 female, 28 male; age 62.6 ± 11.5 years) with histologically-proven PCNSL and 54 GBM subjects (21 female, 33 male; age 59 ± 14 years).ResultsSeveral significant differences between both infiltrative brain tumors were found. PCNSL lesions enhanced homogenously in 64.8% of cases, while nonhomogeneous enhancement was observed in 98.1% of GBM cases. Necrosis was present in 88.9% of GBM lesions and only 5.6% of PCNSL lesions. PCNSL presented as multiple lesions in 51.9% cases and in 35.2% of GBM cases; however, diffuse infiltrative type of brain involvement was observed only in PCNSL (24.1%). Optic pathways were infiltrated more commonly in PCNSL than in GBM (42.6% vs. 5.6%, respectively, p <0.001). Other cranial nerves were affected in 5.6% of PCNSL, and in none of GBM. Signs of bleeding were rare in PCNSL (5.6%) and common in GBM (44.4%); p < 0.001. Both supratentorial and infratentorial localization was present only in PCNSL (27.7%). Involvement of the basal ganglia was more common in PCNSL (55.6%) than in GBM (18.5%); (p < 0.001). Cerebral cortex was affected significantly more often in GBM (83.3%) than in PCNSL (51.9%); mostly by both enhancing and non-enhancing infiltration.ConclusionRoutine morphological MRI is capable of differentiating between GBM and PCNSL lesions in many cases at time of initial presentation. A solitary infiltrative supratentorial lesion with nonhomogeneous enhancement and necrosis was typical for GBM. PCNSL presented with multiple lesions that enhanced homogenously or as diffuse infiltrative type of brain involvement, often with basal ganglia and optic pathways affection.
24198633
Use of PET in the diagnosis of primary CNS lymphoma in patients with atypical MR findings
ObjectiveThe diagnosis of primary central nervous system lymphoma (PCNSL) in immunocompetent patients with atypical magnetic resonance (MR) findings such as disseminated lesions or no (non-enhancing) lesion is sometimes difficult because of mimicking other tumorous and non-tumorous diseases. Positron emission tomography (PET) with 18F-fluorodeoxyglucose (FDG) and 11C-methionine (MET) can measure the glucose and amino acid metabolism in the lesions and may provide useful information for diagnosing PCNSL in patients with such subtle MR findings.MethodsWe performed PET studies with FDG and MET in 17 histologically proven PCNSL and compared the uptake of FDG and MET qualitatively and quantitatively in the tumors between 12 typical and 5 atypical MR findings.ResultsAll typical PCNSL showed strong uptake of FDG and MET; however, visual analysis of FDG and MET uptake in atypical PCNSL was not very useful for finding lesions in the brain. Semiquantitative FDG and MET uptake values (SUVmax) and quantitative FDG influx rate constant (Ki) in the tumors are significantly lower in atypical PCNSL compared with those in typical PCNSL. These values obtained in the lesions with atypical MR findings were also not useful for differentiating PCNSL from other tumorous and non-tumorous diseases. The k3 values evaluated by FDG kinetic analysis in atypical PCNSL were similar to those obtained in typical PCNSL.ConclusionsVisual analysis of FDG and MET uptake in atypical PCNSL was not useful for finding the lesions in the brain. Semiquantitative and quantitative values obtained in the lesions with atypical MR findings were also not useful for differentiating PCNSL from other tumorous and non-tumorous diseases. The k3 values evaluated by FDG kinetic analysis in atypical PCNSL may provide valuable information in the diagnosis of PCNSL.