Intracranial dural based marginal zone MALT-type B-cell lymphoma: a case - Based update and literature review.

OBJECTIVES: Dural based Marginal Zone MALT-type B-Cell Lymphoma (MZBCL) is an intracranial tumor that can mimicking meningioma both from a clinical and a radiological point of view. A standard treatment protocol is still lacking. Aim of the present work is to provide an update of the present literature regarding this rare neoplasia. PATIENTS AND METHODS: We report the case of a patient with a dural-based lesion mimicking a meningioma of the tentorium. After surgical treatment, the diagnosis was of MZBCL. A literature review is performed to highlight the typical characteristics of this rare intracranial lesion and to define the best therapeutic approach. RESULTS: Literature review included 38 articles describing 126 cases of intracranial dural-based MZBCL. No clinical trial has been found. Clinical and histopathological features are properly collected to provide a guide for future cases. Different treatment options have been attempted. Combination of surgery with adjuvant radiation therapy is the most used option. CONCLUSIONS: MZBCL should be considered in differential diagnosis for dural-based intracranial lesion. Surgery followed by radiation therapy is the most reported treatment. As a consequence of the rarity of this disease, of its indolent progression and of the lack of adequate follow-up, it is not possible to define it is the best treatment option.

Epileptic seizures in patients with primary central nervous system lymphoma: A systematic review.

BACKGROUND: Primary central nervous system lymphoma (PCNSL) accounts for less than 5% of primary brain tumors. Epileptic seizures are a common manifestation of brain tumors; however, literature on the prevalence, characteristics, and oncological implications of seizures in patients with PCNSL is limited, and the management of antiepileptic drugs (AEDs) is unclear. This review aimed to summarize the existing knowledge on seizures in PCNSL, their potential association with surgery, oncological treatment, survival rates, and management of AEDs. METHODS: A systematic review was performed according to the PRISMA recommendations and included articles published between 1953 and 2023 describing seizures in patients with PCNSL. RESULTS: The search identified 282 studies, of which 21 were included. Up to 33% of patients with PCNSL developed seizures, mostly at the initial presentation. Little information was found on changes in seizure incidence through the course of the disease, and no details were found on seizure frequency, the percentage of treatment-resistant patients, or the evolution of seizures at remission. Younger age, cortical location, and immunodeficiency have been identified as potential risk factors for seizures, but evidence is very limited. The growing use of vigorous treatments including intensive chemotherapy with autologous stem cell transplantation and immunotherapy with CAR-T cells is associated with a higher incidence of seizures. The association between seizure development and patient mortality in PCNSL remains unknown. There are no data on AED prophylaxis or the use of specific AEDs in PCNSL. CONCLUSIONS: Further studies are needed to investigate seizures in larger cohorts of PCNSL, to clarify their prevalence, better characterize them, identify risk factors, analyze survival rates, and make recommendations on AED management. We recommend following general practice guidelines for seizures symptomatic of brain tumors and not to prescribe AED prophylaxis in PCNSL.

Neuro-oncological patients admitted in intensive-care unit: predictive factors and functional outcome.

The prognosis of oncology patients admitted to the intensive care unit (ICU) is considered poor. Our objective was to analyze the characteristics and predictive factors of death in the ICU and functional outcome following ICU treatment for neuro-oncology patients. A retrospective study was conducted on all patients with primary brain tumor admitted to our institutional ICU for medical indications. Predictive impact on the risk of death in the ICU was analyzed as well as the functional status was evaluated prior and following ICU discharge. Seventy-one patients were admitted to the ICU. ICU admission indications were refractory seizures (41 %) and septic shock (17 %). On admission, 16 % had multi-organ failure. Ventilation was necessary for 41 % and catecholamines for 13 %. Twenty-two percent of patients died in the ICU. By multivariate analysis, predictive factors associated with an increased risk of ICU death were: non-neurological cause of admission [p = 0.045; odds ratio (OR) 5.405], multiple organ failure (p = 0.021; OR 8.027), respiratory failure (p = 0.006; OR 9.615), and hemodynamic failure (p = 0.008; OR 10.111). In contrast, tumor type (p = 0.678) and disease control status (p = 0.380) were not associated with an increased risk of ICU death. Among the 35 evaluable patients, 77 % presented with a stable or improved Karnofsky performance status following ICU hospitalization compared with the ongoing status before discharge. In patients with primary brain tumor admitted to the ICU, predictive factors of death appear to be similar to those described in non-oncology patients. ICU hospitalization is generally not associated with a subsequent decrease in the functional status.

Safety and efficacy of primary central nervous system lymphoma treatment in elderly population.

Elderly patients represent an important subgroup in primary central nervous system lymphoma (PCNSL) that accounts for approximately half the cases. Furthermore age represents one of the heaviest prognostic factors and in some cases it has more effect on survival than therapies. We performed a retrospective analysis to assess the toxicity and the efficacy of high-dose methotrexate (HDMTX) chemotherapy in a PCNSL population older than 70 years. Seventeen consecutive immunocompetent patients older than 70 years, with histologically confirmed PCNSL, without systemic involvement, treated with HDMTX at our institution between May 2005 and April 2013, were retrospectively evaluated. Main outcome measures were acute toxicity and tumour response. No evidence of haematological toxicity was recorded in 47 % of patients and no deaths related to toxicity grade were reported. Patients achieved a partial response after 3 cycles of chemotherapy in 53 % of cases. The median overall survival (m-OS) from diagnosis was 20.9 months (range 5.2-34 months), with OS-12 of 58.8 % and an OS-24 of 45.4 %. Since there is no standard of care in the treatment of PCNSL in elderly population, it should be taken into account that elderly patients not always can be considered "fragile" and the general tendency to less treat to avoid severe toxicity should not be the rule.

Glofitamab-Associated Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS) Presenting as Serial Seizures and Responding Positively to Antiseizure Drugs and Anakinra: A Case Report.

Immune effector cell-associated neurotoxicity syndrome (ICANS) is a well-known side effect of chimeric antigen receptor (CAR) T-cell therapy but has occasionally been described with immune checkpoint inhibitors as well. Glofitamab-associated ICANS with a bispecific monoclonal antibody has rarely been reported. The patient is a 63-year-old male with a history of mantle cell lymphoma, diagnosed at age 37, and aggressive large-cell B-cell lymphoma, diagnosed at age 50. Despite adequate chemotherapy, immunotherapy, autologous stem cell transplantation, and CAR T-cell therapy, there were several relapses, including meningeal carcinomatosis at age 61 and intracerebral lymphoma at age 62. For this reason, glofitamab was started. One week after the ninth cycle, the patient developed drowsiness, behavioral changes, word-finding difficulties, aphasia, focal to bilateral tonic-clonic seizures, and focal onset seizures, which resolved after 16 days with levetiracetam, valproic acid, lorazepam, and midazolam. Since there was no infectious disease, electrolyte disturbance, metabolic disorder, cardiovascular disease, or relapse of lymphoma, glofitamab-associated ICANS was suspected, and anakinra was administered. The case shows that ICANS with drowsiness, behavioral changes, aphasia, and seizures can develop with glofitamab and that patients with structural brain abnormalities may be prone to this.

Prognostic Impact of Quality and Distribution of Adipose Tissue in Patients With Primary Central Nervous System Lymphoma.

BACKGROUND/AIM: Body composition assessment has shown promising results as a prognostic biomarker as depicted by cross-sectional imaging of several tumor entities including lymphomas. The present study sought to elucidate the prognostic relevance of subcutaneous and visceral fat tissue (SAT and VAT) in patients with primary central nervous system lymphoma (PCNSL). PATIENTS AND METHODS: Overall, 74 patients (36 female patients, 46.7%) with a mean age of 64.2±12.8 years (range=23-81 years) were identified in the database with sufficient clinical and imaging data and included into this retrospective study. Fat area assessment was performed on one axial slide on L3-height derived from staging computed tomography (CT) images. Subcutaneous, visceral, and intramuscular adipose tissues (SAT, VAT, IMAT) were estimated. Also, density of SAT, VAT, and IMAT were estimated. Finally, the ratio VAT/SAT (VSR) was calculated. Overall and progression-free survival (OS and PFS) were used as study end points. RESULTS: In the observation period, overall, 47 patients (63.5%) died. Mean OS was 33.8±45.4 months and mean PFS was 26.6±42.7 months. The mean VAT value was 162±99.5 cm2, the mean SAT was 202.4±103.3 cm2, the mean VSR was 0.92±0.69. The hazard ratios (HRs) for overall survival were 0.87 for high VAT, 1.52 for SAT, and 0.73 for VSR in univariable analysis. For PFS it was 0.24 for VAT, 1.11 for SAT, and 1.07 for VSR. No values achieved statistical significance. Similar results were shown in Kaplan-Meier analysis for OS and PFS, respectively. CONCLUSION: Parameters of adipose tissue are not associated with OS and PFS in patients with PCNSL.

Non-Hodgkin's lymphoma revealed by a cerebral vascular stroke: A case report.

Hemorrhagic lesions in CNS lymphoma are extremely rare. We report the case of a 75-year-old patient admitted to the emergency room following a classic hemorrhagic stroke. The CT scan showed a hyperdense tumor-like process with perilesional edema, the diagnosis reinforced by (MRI). The patient underwent macroscopically total surgical excision and the anatomo pathological examination concluded a diffuse non-Hodgkin's B large cell lymphoma. The follow up was marked by a clear clinical improvement. Primary cerebral lymphomas can be polymorphic, so this diagnosis should always be kept in mind during stroke manifestations. This case illustrates the diagnostic difficulty of this rare and poor prognosis condition.

[Hematological pathologies: the most successful model of de-escalation in radiotherapy]. / Pathologie hématologique : le modèle le plus abouti de désescalade en radiothérapie.

The proportion of patients irradiated in the context of malignant hematological pathologies decreased over the last decades. The main causes are the late side effects of the historical series and the new therapeutic strategies aiming to relay radiotherapy to the rank of option. At the same time, radiotherapy has been modernised, target volumes and total doses have been drastically reduced. Hodgkin's lymphomas, indolent follicular lymphomas and primary cerebral lymphomas are the main witnesses of this therapeutic deflation.

Primary cerebral lymphoma' characteristics, incidence, survival, and causes of death in the United States.

PURPOSE: This study aimed to provide an updated overview of primary central lymphoma (PCL) using a large cohort of 33 years. That being said, we attempted to examine the patient demographics, management plans and their outcome, causes of death and the time trends in overall incidence and mortality rates of these patients. METHODS: We conducted a retrospective cohort study using the Surveillance, Epidemiology, and End Results (SEER) database between 1983 and 2016. We calculated the frequencies and the average annual age-adjusted rate (AAR) of PCL patients. Uni- and multivariable accelerated failure time regression were used to identify possible prognostic factors affecting the patients' survival. Furthermore, detailed causes of death were extracted and joint point regression analysis was done to examine incidence and mortality trends. RESULTS: We identified 2925 PCL cases. The AAR was 0.148 per 100,000. An increase in age was significantly associated with shorter survival (HR: 1.01, 95%CI = 1.01-1.01, P < .001), while a recent year of diagnosis after 1993-2002 and 2002 was associated with improved survival (HR: 0.76, CI = 0.65-0.89, P = .001), and (HR: 0.48, CI = 0.41-0.56, P < .001), respectively. Overall, the trend of mortality rates in PCL patients has declined over the past years (-1.38% per year). CONCLUSION: Our results support the previous evidence by showing an increase in patients' survival over time. While most PCL-related deaths occur within the first year, subsequent slow progression was observed after the first few years of survival. More attention should be given to the other possible non-PCL causes of death, especially beyond ten years of survival.

Accuracy of apparent diffusion coefficients and enhancement ratios on magnetic resonance imaging in differentiating primary cerebral lymphomas from glioblastoma.

BACKGROUND AND PURPOSE: This study aimed to determine the accuracy of apparent diffusion coefficient (ADC) and enhancement ratio (ER) in discriminating primary cerebral lymphomas (PCL) and glioblastomas. MATERIALS AND METHODS: Circular regions of interest were randomly placed centrally within the largest solid-enhancing area of all lymphomas and glioblastomas on both post-contrast T1-weighted images and corresponding ADC maps. Regions of interest were also drawn in the contralateral hemisphere to obtain enhancement and ADC values of normal-appearing white matter. This helped us to calculate the ER and ADC ratio. RESULTS: Mean enhancement and ADC (mm2/s) values for PCL were 2220.56 ± 2948.30 and 712.00 ± 137.87, respectively. Mean enhancement and ADC values for glioblastoma were 1537.07 ± 1668.33 and 1037.93 ± 280.52, respectively. Differences in ADC values, ratios and ERs were all statistically significant between the two groups (p < 0.05). ADC values correctly predicted 71.4% of the lesions as glioblastoma and 83.3% as PCL (area under the curve (AUC) = 0.86 on receiver operating characteristic curve analysis). ADC ratios correctly predicted 85.7% of the lesions as glioblastoma and 100% as PCL (AUC = 0.93). ERs correctly predicted 71.4% of the lesions as glioblastoma and 88.9% as PCL (AUC = 0.92). The combination of ADC ratio and ER correctly predicted 100% tumour type in both patient subgroups. CONCLUSIONS: ADC values, ADC ratios and ERs may serve as useful variables to distinguish PCL from glioblastoma. The combination of ADC ratio and ER yielded the best results in identification of both patient subgroups.

Differentiating enhancing multiple sclerosis lesions, glioblastoma, and lymphoma with dynamic texture parameters analysis (DTPA): A feasibility study.

PURPOSE: MR-imaging hallmarks of glioblastoma (GB), cerebral lymphoma (CL), and demyelinating lesions are gadolinium (Gd) uptake due to blood-brain barrier disruption. Thus, initial diagnosis may be difficult based on conventional Gd-enhanced MRI alone. Here, the added value of a dynamic texture parameter analysis (DTPA) in the differentiation between these three entities is examined. DTPA is an in-house software tool that incorporates the analysis of quantitative texture parameters extracted from dynamic susceptibility contrast-enhanced (DSCE) images. METHODS: Twelve patients with multiple sclerosis (MS), 15 patients with GB, and five patients with CL were included. The image analysis method focuses on the DSCE image time series during bolus passage. Three time intervals were examined: inflow, outflow, and reperfusion time interval. Texture maps were computed. From the DSCE image series, mean, difference, standard deviation, and variance texture parameters were calculated and statistically analyzed and compared between the pathologies. RESULTS: The texture parameters of the original DSCE image series for mean, standard deviation, and variance showed the most significant differences (P-value between <0.00 and 0.05) between pathologies. Further, the texture parameters related to the standard deviation or variance (both associated with tissue heterogeneity) revealed the strongest discriminations between the pathologies. CONCLUSION: We conclude that dynamic perfusion texture parameters as assessed by the DTPA method allow discriminating MS, GB, and CL lesions during the first passage of contrast. DTPA used in combination with classification algorithms has the potential to find the most likely diagnosis given a postulated differential diagnosis.

ESHAP chemotherapy is efficient in refractory/relapsed primary central nervous system lymphoma: report of four cases.

Primary central nervous system non-Hodgkin's lymphoma is a rare presentation, almost always of diffuse large B-cell type. Although there is no consensus regarding therapy for this condition, induction regimens are based on high-dose methotrexate and consolidation whole-brain radiotherapy, or, more preferred recently, blood-brain barrier penetrating drugs such as etoposide, cytarabine, and alkylating agents like temozolomide, ifosfamide, and lomustine. We present here four cases of relapsed/refractory primary central nervous system lymphoma treated with ESHAP (etoposide, solumedrol, high-dose cytarabine, and platinum) chemotherapy to complete remission, with the eligible patients proceeding to autologous transplantation. We want to draw attention to this interesting, relatively well tolerated, underused therapeutic option, in a setting where treatment options are scarce and evidence-based recommendations are lacking.

Linfoma primario del sistema nervioso central en un paciente inmunocompetente / Primary central nervous system lymphoma in an immunocompetent patient

El linfoma primario del sistema nervioso central (LPSNC) constituye el 2% de los linfomas extranodales y entre 0,3% y 1,5% de todas las neoplasias intracraneales en pacientes inmunocompetentes, siendo más frecuente a partir de los 60 años. Reportamos el caso de un paciente varón de 76 años, sin antecedentes médicos de importancia, que inició su enfermedad con inestabilidad en la marcha, dificultad para mover el hemicuerpo izquierdo, a predominio braquial, cefalea holocraneal y mareos. Ingresó a emergencia despierto, parcialmente desorientado, Glasgow 14 y ptosis palpebral derecha; además, hemiparesia e hipoestesia izquierda, a predominio crural. Por tomografía computarizada cerebral se evidenció imagen captadora de contraste en región frontoparietal derecha, intra y extra craneal, edema cerebral y desplazamiento de la línea media. Se realizó craneotomía y biopsia del tumor, diagnosticándose linfoma difuso de células grandes B del sistema nervioso central. Fue VIH negativo. Se descartó otro tumor primario y metástasis. Recibió esquema CHOD/BVAM y radioterapia. Evolucionó favorablemente. Según resonancia magnética cerebral postratamiento, desapareció el tumor.

Primary central nervous system lymphoma (PCNSL) constitutes 2% of extranodal lymphomas and 0,3%-1,5% of all intracranial neoplasms in immunocompetent patients, being more frequent after the sixth decade of life. We report a case of a 76 year-old man with no antecedents who started his disease with march instability, difficulty to move left side of his body with brachial predominance, holocraneal headache and dizziness. He arrived at emergency with Glasgow 14 and right eyelid ptosis. He had left sided hemiparesis and hypoesthesia with crural predominance and occasional disorientation. Brain computed tomography (CT) showed a contrast-enhanced image in the right frontoparietal region with both extra- and intra-cranial components, cerebral edema and middle line deviation. Craniotomy and biopsy of the tumor resulted in diffuse large B cell lymphoma of the central nervous system. The patient was HIV negative. Other primary tumor and metastasis were discarded. He was treated with ‘CHOD/BVAM’ regimen and radiotherapy. He evolved favorably. No tumor was found in the post treatment brain MRI.

A common dementia in a rare disease.

The patient described was a 68-year-old man presenting with a severe, subacute depressive state with rapid decline in memory, psychomotor retardation and refusal to eat, who was referred by the medical team for ECT. His memory impairment could not be explained within the context of his depressed mood and he was eventually found to have a primary cerebral lymphoma of the non-Hodgkin's type. He died 10 weeks after initial psychiatric assessment.