B-cell Lymphoma Of Central Nervous System Research Articles

The Autologous Hematopoietic Stem Cells Transplantation Combination-Based Chimeric Antigen Receptor T-Cell Therapy Improves Outcomes of Relapsed/Refractory Central Nervous System B-Cell Lymphoma.

The objective is to explore the effectiveness and safety of CAR T-cell therapy in advanced relapsed/refractory central nervous system B-cell lymphoma and compare the impact of autologous stem cell transplantation (ASCT) plus CAR T-cell therapy versus sequential CART therapy on the survival of patients. The retrospective analysis was based on the data of 17 patients with advanced relapsed/refractory central nervous system B-cell lymphoma. Bridging chemotherapy was applied before CAR T-cell infusion to further reduce the tumor burden. For patients with autologous hematopoietic stem cell successful collection, CD19/20/22CAR T-cell immunotherapy following ASCT was performed with the thiotepa-containing conditioning regimen, while sequential CD19/CD20/CD22CAR T-cell therapy was applied. For lymphodepletion, patients received bendamustine or fludarabine monotherapy or fludarabine combined with cyclophosphamide pre-CART-cell infusion. Out of the 17 patients, 8 completed ASCT plus CART cell therapy, while 9 patients completed CART cell alone therapy. In efficacy assessment at 3 months after infusion, the objective response rate (ORR) was 12/17 (71%) and the complete response rate (CRR) was 11/17 (65%). The CRR of the ASCT group and non-ASCT was 100% and 44.4%, respectively (P < 0.01). The median progression-free survival was 16.3 (2.6-24.5) months, and the median overall survival was 19.3 (6-24.5) months. Patients who underwent ASCT plus CART cell therapy had significantly longer PFS (P < 0.01) and OS (P < 0.01). Grade 3 or higher immune effector cell-associated neurologic toxicity syndrome (≥grade 3 ICANS) and cytokine release syndrome (≥grade 3 CRS) events occurred in 29% and 41% of the patients, respectively. No treatment-related death occurred. The CAR T-cell therapy could augment its efficacy in the treatment of advanced relapsed/refractory CNS B-cell lymphoma, while ASCT in combination with CART can induce durable responses and OS with a manageable side effect.

Enhancement pattern of demyelination‐mimicking cerebral B‐cell lymphoma

Central nervous system (CNS) B-cell lymphoma-mimicking demyelinating diseases creates a diagnostic dilemma. This study aimed to determine the specific magnetic resonance imaging (MRI) features of CNS B-cell lymphoma to facilitate the early identification of the disease. We retrospectively reviewed the brain MRI of biopsy-confirmed CNS B-cell lymphoma patients. They were initially diagnosed with CNS demyelination, and these images were compared with those of actual patients with demyelinating diseases. A total of 20 patients with CNS B-cell lymphoma and 12 patients with demyelination were included in this study. Cohesive enhancement with satellite enhancing foci surrounded by prominent non-enhancing areas of oedema is the major contrast-enhancing pattern of lymphoma patients, accounting for 81% (13) of patients with primary diffuse large B-cell lymphoma (DLBCL). This imaging pattern revealed a sensitivity of 81% and a specificity of 75% for lymphoma in the differential diagnosis between primary DLBCL and demyelinating disease in our cohort. Among these lesions, most of the nodules were located deeply, which yielded a specificity of 100% and a sensitivity of 69% for primary DLBCL. Enhancement in a single pattern (mainly ring-like, patchy or punctate; 57%) and no enhancement (30%) were commonly observed in demyelinating lesions, distinct from primary DLBCL (p&lt;0.05). Lesions with cohesive enhancement and satellite foci on T1 contrast-enhanced imaging could be a specific hallmark of CNS B-cell lymphoma, suggesting the need to withdraw steroidal therapy and biopsy confirmation.

A tumefactive anti-MOG antibody associated disorder heralding central nervous system B-cell lymphoma: Case report on diagnostic challenge

We present the case of a 52-year-old woman with right hemiparesis due to a mass lesion in the left parietal white matter and corpus callosum. The lesion was hyperintense on diffusion weighted image and homogenously enhanced with gadolinium on magnetic resonance imaging, and was radiologically indistinguishable with lymphoma. Following progressive aggravation of symptoms, craniotomy for biopsy of the lesion was performed, and it was revealed that the patient had anti-myelin oligodendrocyte glycoprotein-associated disease by histopathological and serological diagnosis. Initial treatment with steroid dramatically improved the symptoms, but they exacerbated again. Then, through cerebrospinal fluid examination, it was revealed that the patient had B-cell lymphoma.

Blood Coagulation Factor Fibrinogen in Tumor Pathogenesis of Central Nervous System B-Cell Lymphoma

Central nervous system (CNS) lymphoma is an extranodal non-Hodgkin B-cell lymphoma characterized by malignant lymph tissue arising in the brain or spinal cord, associated with inflammation and blood-brain barrier (BBB) disruption. Although BBB disruption is known to occur in patients with CNS lymphoma, a direct link between these two has not been shown. Herein, abundant deposition of the blood coagulation protein fibrinogen around B-cell lymphoma was detected in CNS lymphoma patients and in the CNS parenchyma in an orthotopic mouse model. Functional enrichment analysis of unbiased cerebrospinal fluid proteomics of CNS B-cell lymphoma patients showed that coagulation protein networks were highly connected with tumor-associated biological signaling pathways. Invivo two-photon imaging demonstrated that lymphoma growth was associated with BBB disruption, and invitro experiments identified a role for fibrinogen in promoting lymphoma cell adhesion. Overall, these results identify perivascular lymphoma clustering at sites of fibrinogen deposition, and suggest that fibrinogen may be a target for pharmacologic intervention in metastatic B-cell lymphoma associated with BBB disruption.

Alteration of BAFF and APRIL in the cerebrospinal fluid based on the therapeutic response in primary central nervous system B-cell lymphoma

We evaluated the cerebrospinal fluid (CSF) levels of the B-cell activating factor of the tumor necrosis factor family (BAFF) and A proliferation-inducing ligand (APRIL) in two cases of primary central nervous system B-cell lymphoma (PCNSBL) before and after treatment. One patient achieved clinical remission, and demonstrated decrease in the CSF levels of both BAFF and APRIL after treatment. Meanwhile, the other patient with insufficient therapeutic response showed increase in the BAFF levels despite decrease in APRIL levels. This report suggests that the combination of BAFF and APRIL levels could be useful in estimating the therapeutic efficacy in treating PCNSBL as reliable CSF markers.

Oculomotor Nerve Palsy as a Rare Presentation of Large B-Cell Central Nervous System Lymphoma

Oculomotor Nerve Palsy as a Rare Presentation of Large B-Cell Central Nervous System Lymphoma

CXCR4-Targeted PET Imaging of Central Nervous System B-Cell Lymphoma.

C-X-C chemokine receptor 4 (CXCR4) is a transmembrane chemokine receptor involved in growth, survival, and dissemination of cancer, including aggressive B-cell lymphoma. MRI is the standard imaging technology for central nervous system (CNS) involvement of B-cell lymphoma and provides high sensitivity but moderate specificity. Therefore, novel molecular and functional imaging strategies are urgently required. Methods: In this proof-of-concept study, 11 patients with lymphoma of the CNS (8 primary and 3 secondary involvement) were imaged with the CXCR4-directed PET tracer 68Ga-pentixafor. To evaluate the predictive value of this imaging modality, treatment response, as determined by MRI, was correlated with quantification of CXCR4 expression by 68Ga-pentixafor PET in vivo before initiation of treatment in 7 of 11 patients. Results:68Ga-pentixafor PET showed excellent contrast with the surrounding brain parenchyma in all patients with active disease. Furthermore, initial CXCR4 uptake determined by PET correlated with subsequent treatment response as assessed by MRI. Conclusion:68Ga-pentixafor PET represents a novel diagnostic tool for CNS lymphoma with potential implications for theranostic approaches as well as response and risk assessment.

CXCR4-Targeted Positron Emission Tomography Imaging of Central Nervous System B-Cell Lymphoma

Introduction Central nervous system lymphoma (CNSL) is a rare neoplasia and arises as primary (PCNSL) or secondary CNSL (SCNSL) and most commonly occurs as diffuse large B-cell lymphoma. Although prognosis of this disease has significantly improved due to advantages in diagnostic procedures and intensification of treatment over the last decade there remain major challenges in the clinical management. Magnetic resonance imaging (MRI) - as the standard imaging modality - has difficulties to discriminate CNSL from other brain-derived tumors or metastasis. Moreover, prognostic scores in CNSL lack the ability to reliable define patients with high relapse risk 1. Therefore, novel strategies to facilitate diagnosis and to select patients that profit from intense treatment protocols are urgently needed. The C-X-C chemokine receptor 4 (CXCR4) is a transmembrane chemokine receptor with pivotal roles in cell homing and is often overexpressed in hematologic malignancies. CXCR4-directed positron emission tomography (PET) imaging with the tracer [68Ga]Pentixafor has been proven to be a suitable in vivo imaging modality for CXCR4 expression in lymphoid malignancies 2. To evaluate the feasibility of CXCR4-directed PET and the prognostic value of this imaging modality this retrospective proof-of-concept study evaluated [68Ga]Pentixafor PET imaging in patients with CNSL. Methods 11 patients with lymphoma of the CNS (n=8 PCNSL, n=3 SCNSL) were imaged with the CXCR4-directed PET tracer [68Ga]Pentixafor in this retrospective proof-of-concept study after signing inform consent. Lymphoma tissue was assessed for CXCR4 expression ex vivo by immunohistochemistry. The prognostic value of CXCR4-directed PET imaging was evaluated in a computed analysis in 7 patients with follow-up MRI. Treatment response calculated as treatment efficiency η by sequential MRI was correlated with [68Ga]Pentixafor PET derived parameters at diagnosis such as volume of PET positive lymphoma lesion V(PET), maximal PET uptake value within the lesion max(PET) or integrated uptake values over the lymphoma lesion ∫(PET). Analysis was performed in a lesion- and patient-based manner. Results [68Ga]Pentixafor PET imaging was positive in all patients with active disease (10/11 patients) with excellent contrast characteristics to the surrounding brain parenchyma. PET positive lesions correlated well with lymphoma lesions in MRI-T1c sequences. The surrounding edema depicted in MRI-FLAIR sequences was evaluated as PET negative (Figure 1). Semi-quantitative analysis revealed maximum standard uptake values of [68Ga]Pentixafor-derived PET from 4.2 to 23.3 within the lesions with a high tumor-to-background-ratio ranging from 13.2 to 83.0. The computed analysis revealed that CXCR4-directed PET parameters at diagnosis given by max(PET) and ∫(PET) significantly correlated with treatment response in the lesion-based as well as in the patient-based analysis. Specifically, ∫(PET) was the most significant prognostic factor in the present study (Figure 2 C, D, F). On the other hand tumor volume at diagnosis measured either by MRI or by [68Ga]Pentixafor PET did not denote a predictive marker for treatment response (Figure 2 A, B, E). Conclusion/Outlook CXCR4-directed PET imaging represents a novel imaging modality for CNSL. Due to its excellent contrast properties it might help to facilitate diagnosis and refine response assessment. Moreover, owing the predictive value for treatment response, CXCR4-directed PET could serve as a biomarker for the selection of patients profiting from intense treatment protocols. Furthermore, the feasibility of endoradiotherapeutic approaches targeting CXCR4 with Pentixather - the therapeutic twin of the imaging peptide Pentixafor - has been shown in hematologic malignancies and could be incorporated in the treatment of CNSL.

Technical and anatomical aspects of endoscopically assisted septostomy in unilateral ventriculoperitoneal shunt placement for the management of isolated lateral ventricles

Abstract Background Isolated lateral ventricle is a specific form of non-communicating hydrocephalus that is caused by an obstruction of the foramen of Monro. The condition was previously treated with bilateral shunt placement. However, the emergence of endoscopic surgery has provided more options in the management of this condition. Case description 46-year-old female presented with obstructive hydrocephalus caused by a right thalamic primary central nervous system B-cell lymphoma. Endoscopic septostomy with unilateral shunt placement was performed because of bilateral foramen of Monro obstruction. Conclusion Endoscopic septostomy can be used as a tool to avoid bilateral shunt placement in certain cases of bilateral isolated lateral ventricles.

Incidence and survival patterns of primary central nervous system (CNS), systemic and concurrent diffuse large B-cell lymphoma (DLBCL).

e13512Background: Concurrent CNS and systemic involvement with DLBCL is a rare presentation. To our knowledge there is no study looking at the incidence and survival patterns of concurrent CNS and ...

P11.08 * CENTRAL NERVOUS SYSTEM LYMPHOMA IN A PATIENT WITH MYCOSIS FUNGOIDES

Mycosis fungoides (MF), the most common malignant T-cell lymphoma of the skin with an annual incidence of 4.2 cases per million in the United States, usually evolves slowly over many years. Extracutaneous manifestations of MF are observed in 50-75% of cases, typically occurring in patients with advanced infiltration of other organs. The incidence of central nervous system (CNS) involvement in MF was reported to be 14% in autopsy series and less than 1.6% in clinical cohorts particularly in patients with large-cell transformation of MF. A 67-year-old woman was diagnosed with plaque stage MF in 1990 after having developed disseminated, well demarcated, erythematous macules and plaques on the trunk. The patient reported that psoriasiform skin lesions had been present over the past 35 years. Treatment consisted of topical corticosteroids, systemic psoralen plus ultraviolet A, acitretin and interferon, resulting in a complete remission since 2007, without further treatment. In April 2013, the patient presented with a 2-month history of cognitive deficits and bifrontal headache, followed by rapidly decreasing visual acuity with central and peripheral visual field defects. Magnetic resonance imaging (MRI) showed thickening of the optic chiasm and both optic nerves with homogeneous contrast medium enhancement and space-occupying effect on the hypothalamus. Cerebrospinal fluid (CSF) analysis revealed lymphocytic pleocytosis of 107 cells/µl, no lymphoma cells were detected, CSF protein was elevated (116 mg/dl), glucose and lactate were normal. A subsequent brain biopsy confirmed the diagnosis of a diffuse large-cell lymphoma of the B-cell type. Despite preoperatively started dexamethasone treatment the patient experienced severe visual loss. Following 4 cycles of chemotherapy containing high-dose methotrexate and cytarabine according to the IELSG protocol and 2 cycles of methotrexate monotherapy from May until October 2013, clinical examination showed marked visual improvement, consistent with almost complete resolution of the MRI abnormalities. Due to pituitary gland insufficiency the patient needs further hormone replacement therapy. This case illustrates the importance of considering CNS lymphoma in the context of MF, even after long-term remission of the disease limited to the skin. To the best of our knowledge, this is the first description of a primary CNS B-cell lymphoma secondary to MF.

Primary B-cell central nervous system lymphoma involving fourth ventricle: A rare case report with review of literature

Primary B-cell central nervous system lymphoma involving fourth ventricle: A rare case report with review of literature

A case of oculo‐cerebral B‐cell lymphoma in a cat

To describe a case of a cat with primary B-cell lymphoma affecting the eye and brain and which shared features similar to oculo-cerebral lymphoma in humans. A 13-year-old castrated male Persian cat presented with clinical signs of anterior uveitis and increased intraocular pressure (IOP) in the left eye (OS). A complete diagnostic work-up was declined, and left-eye enucleation was performed. The globe was submitted for histopathology. One week after surgery, the cat became inappetent, hypothermic, and aggressive. Euthanasia was requested by the owner, and a necropsy was permitted. Histopathology of the enucleated globe revealed an extensive neoplastic infiltration consistent with large-cell lymphoma, affecting the anterior uvea, neuroretina and optic nerve. At necropsy, all organs were unremarkable except for the brain, where there was a neoplastic cell population consistent with that described in the left eye, infiltrated and expanded meninges, and perivascular spaces. Immunohistochemically, the neoplastic cells were positive for B-cell marker (CD20) and negative for T-cell marker (CD3). Histology and immunophenotyping suggested a diagnosis of primary central nervous system and ocular large B-cell lymphoma. The lymphoma in this cat resembled oculo-cerebral lymphoma in humans, sharing similar clinical features and histopathological findings, including the perivascular pattern of neoplastic cell infiltration. To the best of the authors' knowledge, this is the first description of a primary oculo-cerebral B-cell lymphoma in a cat.

Isolated leptomeningeal infiltration of a primary CNS B-cell lymphoma diagnosed by flow cytometry and confirmed by necropsy

The diagnosis of the isolated leptomeningeal involvement of a primary central nervous system B-cell lymphoma without parenchyma lesions may be difficult. Patients with leptomeningeal meningeosis lymphomatosa can present with various neurologic deficits. To demonstrate the impact of cerebrospinal fluid (CSF) flow cytometry in the diagnosis of an isolated leptomeningeal manifestation of B-cell lymphoma by presenting an interesting case report. Flow cytometric analysis of B-cell monoclonality of the CSF was performed as complementary diagnostic procedure in addition to CSF cytology. Final diagnosis was confirmed by necropsy. We suspected isolated leptomeningeal manifestation of B-cell lymphoma with palsy of the VI and VII cranial nerves in a 79-year-old male, because of mononuclear pleocytosis in CSF. Interestingly, the decisive diagnostic hint was given by implementation of flow cytometry of the CSF. Diagnosis was confirmed by postmortem autopsy. Our case shows that flow cytometry of the CSF in addition to conventional CSF cytology has the potential to accelerate diagnosis of lymphomeningeal infiltration of B-cell lymphoma.

A Collision Tumor: Primary Central Nervous System B-Cell Lymphoma and Anaplastic Astrocytoma

A collision tumor in the central nervous system (CNS) is a rare entity. We report a case of a collision tumor with primary CNS lymphoma and astrocytoma in an otherwise healthy young male and the diagnostic challenge associated with it. The tumor showed 2 histologic patterns. The predominant component consisted of anaplastic astrocytoma with gemistocytic appearance, and the lymphoma cells were kappa restricted B cells with variable cell sizes and some plasmacytoid differentiation. In situ hybridization demonstrated that the lymphoma cells were Epstein-Barr virus (EBV) positive. The patient was neurologically asymptomatic for 2 and half years following surgery, chemotherapy, and radiation.

The Development of Primary Central Nervous System B-Cell Lymphoma in Multiple Sclerosis

When coupled with classical clinical signs and symptoms, magnetic resonance imaging can significantly aid in the diagnosis of multiple sclerosis (MS). However, the differential diagnosis of multiple sclerosis is large and, in the absence of pathognomonic clinical features, can be challenging to diagnose initially. Some conditions, such as primary central nervous system lymphoma (PCNSL) and progressive multifocal leukoencephalopathy (PML), can mimic clinically some of the symptoms prominent in multiple sclerosis. Early treatment with corticosteroids can dramatically improve patient symptoms in MS and PCNSL. We report a case of a man diagnosed with histologically confirmed relapsing remitting multiple sclerosis who subsequently developed histologically confirmed primary central nervous system lymphoma. Immunosuppressant therapy in the treatment of multiple sclerosis may be a potential catalyst in the development of central nervous system lymphoma. The course of his disease and treatment are presented and the current literature reviewed.

Meningioma interdigitated with primary central nervous system B-cell lymphoma: A case report and literature review

Background:Simultaneous presentation of multiple primary central nervous system (CNS) malignancies is extremely rare. There have been only eight cases of meningiomas co-existing with primary cerebral lymphoma, reported in the literature.Case Description:We present a case of a patient who underwent surgical resection of an olfactory grove meningioma that was interdigitated with a primary CNS B-cell lymphoma. Following surgery, the patient was treated with high-dose methotrexate, and has no evidence of recurrence after 18 months.Conclusion:Because of the early recognition of these two distinct pathologies, the patient received directed adjuvant therapies, and has exceeded the survival of all other cases reported in the literature.

Primary diffuse large B-cell central nervous system lymphoma presenting as an acute space-occupying subdural mass

Primary dural lymphomas are very rare tumors--usually low-grade B-cell lymphomas of mucosa-associated lymphoid tissue type or marginal zone B-cell lymphomas. Primary dural involvement by diffuse large B-cell lymphoma is extremely rare, with only a few cases reported in the literature. The authors present an unusual case of primary dural involvement by a high-grade diffuse large B-cell lymphoma that presented as an acute subdural space-occupying mass and required emergency neurosurgical intervention.

Low levels of monoclonal small B cells in the bone marrow of patients with diffuse large B-cell lymphoma of activated B-cell type but not of germinal center B-cell type

Multiparameter flow cytometry allows the detection of minor monoclonal B-cell populations. Using this technique combined with morphology, we were struck by the presence of minor populations of small monoclonal B cells in bone marrows of patients with diffuse large B-cell lymphoma in routine diagnostic samples and performed a systematic retrospective study. Bone marrows of 165 patients with primary diffuse large B-cell lymphoma without histological evidence of concurrent non-Hodgkin's lymphoma were studied by routine microscopy of trephines and smears, immunohistochemistry and multiparameter flow cytometry. Diffuse large B-cell lymphoma infiltration in marrows was documented in 11 of 165 patients. Morphological examination consistently revealed a higher tumor load than evidenced by flow cytometry. Of interest, only 3 of 119 patients with diffuse large B-cell lymphoma not otherwise specified, the largest subtype, showed marrow infiltration. By contrast, flow cytometry revealed a minor monoclonal B-cell population in 24 of 165 patients, none of whom showed diffuse large B-cell lymphoma infiltration by morphology. Of interest, morphological examination revealed the presence of small B cells in the marrows of those patients. Moreover, 11 of 39 (28.2%) of patients with diffuse large B-cell lymphoma not otherwise specified of ABC subtype and only 3 of 80 (3.7%) with the GCB subtype showed these monoclonal small B cells (P=0.0002). In addition 4 of 8 (50%), 4 of 15 (26.7%) and 2 of 3 (66.7%) patients with primary testicular, primary central nervous system and leg-type diffuse large B-cell lymphoma, respectively, showed monoclonal small B cells. Bone marrow infiltration with diffuse large B-cell lymphoma in patients with diffuse large B-cell lymphoma not otherwise specified is rare at diagnosis. By contrast, a high number of diffuse large B-cell lymphoma not otherwise specified of the ABC subtype but not of GCB subtype is associated with monoclonal small B cells in the marrow. Whether these monoclonal small B cells are precursors of diffuse large B-cell lymphoma of the ABC type or arise in a common background that favors clonal B-cell expansion remains to be demonstrated.

Central nervous system b-cell lymphoma in multiple sclerosis

The differential diagnosis of multiple sclerosis is extensive and it can be challenging to diagnose initially in the absence of pathognomonic clinical features. Furthermore, these patients can also develop other diseases during their course of treatment, which usually lasts for many years. Some conditions, such as primary central nervous system lymphoma, can mimic clinically some of the symptoms prominent in multiple sclerosis. Early treatment with corticosteroids can also dramatically improve patient symptoms in both conditions. We report a case of a man diagnosed with histologically confirmed relapsing remitting multiple sclerosis who subsequently developed histologically confirmed primary central nervous system lymphoma. The course of his disease and treatment are presented and the current literature reviewed.