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International Journal of Clinical... Aug 2018Leptomeningeal metastasis is an uncommon but devastating complication. The incidence of non-Hodgkin's lymphoma has been increasing in recent decades, due to the poor...
BACKGROUND
Leptomeningeal metastasis is an uncommon but devastating complication. The incidence of non-Hodgkin's lymphoma has been increasing in recent decades, due to the poor central nervous system penetration of drugs and the prolonged overall survival of patients, leptomeningeal metastases has gradually increased over time. Patients with leptomeningeal metastases have short survival durations and poor quality of life; there are few studies about non-Hodgkin's lymphoma with leptomeningeal metastases. We investigated characteristics and outcomes of non-Hodgkin's lymphoma patients with leptomeningeal metastases.
METHODS
This study included 27 non-Hodgkin's lymphoma patients with leptomeningeal metastases diagnosed at Tianjin Medical University Cancer Institute and Hospital between 2013 and 2016. Statistical analysis was performed to investigate the overall survival of non-Hodgkin's lymphoma with leptomeningeal metastases.
RESULTS
Diffuse large B cell lymphoma was the most common cancer subtype (21/27, 78%), and more than half of the patients showed extranodal involvement (18/27, 67%). Survival analysis has shown extranodal involvement (P = 0.0205), International Prognostic Index (P = 0.0112), performance status (P < 0.0001), parenchymal involvement (P = 0.0330) and received radiotherapy (P = 0.0056) were predictive factors of prognosis for these patients with leptomeningeal metastases. Cox regression analysis has shown patients with concurrent parenchymal involvement and received radiotherapy are correlated with good prognosis.
CONCLUSIONS
Given the small number of patients who were included, this study exhibited limitations with respect to analytical power and the random selection of patients. Nevertheless, this investigation revealed characteristics of non-Hodgkin's lymphoma patients with leptomeningeal metastases and suggested that such patients could benefit from multimodal therapy.
Topics: Adolescent; Adult; Combined Modality Therapy; Female; Humans; Lymphoma, Large B-Cell, Diffuse; Male; Meningeal Carcinomatosis; Middle Aged; Prognosis; Quality of Life; Retrospective Studies; Survival Rate; Young Adult
PubMed: 29558001
DOI: 10.1007/s10147-018-1268-5 -
Oncotarget Jan 2016There is limited data on the impact of specific patient characteristics, tumor subtypes or treatment interventions on survival in breast cancer LM. (Review)
Review
BACKGROUND
There is limited data on the impact of specific patient characteristics, tumor subtypes or treatment interventions on survival in breast cancer LM.
METHODS
A systematic review was conducted to assess the impact of hormone receptor and HER-2 status on survival in breast cancer LM. A search for clinical studies published between 1/1/2007 and 7/1/2012 and all randomized-controlled trials was performed. Survival data from all studies are reported by study design (prospective trials, retrospective cohort studies, case studies).
RESULTS
A total of 36 studies with 851 LM breast cancer subjects were identified. The majority (87%) were treated with intrathecal chemotherapy. Pooled median overall survival ranged from 14.9-18.1 weeks depending on study type. Breast cancer LM survival (15 weeks) was longer than other solid tumor LM 8.3 weeks and lung cancer LM 8.7 weeks, but shorter than LM lymphoma (15.4 versus 24.2 weeks). The impact of hormone receptor and HER-2 status on survival could not be determined.
CONCLUSIONS
A median overall survival of 15 weeks in prospective studies of breast cancer LM provides a historical comparison for future LM breast cancer trials. Other outcomes including the impact of molecular status on survival could not be determined based on available studies.
Topics: Breast Neoplasms; Female; Humans; Meningeal Neoplasms
PubMed: 26543235
DOI: 10.18632/oncotarget.5911 -
Cancer Jun 2020Clinical experience is limited for primary central nervous system (CNS) lymphoma that arises from the dura mater, which is denoted with the term primary dural lymphoma...
BACKGROUND
Clinical experience is limited for primary central nervous system (CNS) lymphoma that arises from the dura mater, which is denoted with the term primary dural lymphoma (PDL). This study was aimed at determining the relative incidence, presentation, and outcomes of PDL.
METHODS
The institutional databases of the Divisions of Neuro-Oncology at the Massachusetts General Hospital and the Yale School of Medicine were retrospectively searched for patients with primary CNS lymphoma. Patients with pathologically confirmed dural lymphoma and no evidence of primary cerebral or systemic involvement were identified. Clinical data, diagnostic findings, treatments, and outcomes were recorded.
RESULTS
A total of 20 patients with PDL were identified, and they represented 6.3% of the individuals with primary CNS lymphomas (20 of 316). Histopathological examination of PDL revealed the following underlying subtypes: diffuse large B-cell lymphoma (10 of 20 patients), marginal zone lymphoma (6 of 20), follicular lymphoma (2 of 20), undefined B-cell non-Hodgkin lymphoma (1 of 20), and T-cell non-Hodgkin lymphoma (1 of 20). On imaging, all tumors appeared as extra-axial masses with avid contrast enhancement and mostly mimicked meningioma. The median apparent diffusion coefficient value was 667 ± 26 mm /s. Cerebrospinal fluid analyses and symptoms were nonspecific, and the diagnosis rested on tissue analysis. Therapeutic approaches included surgery, radiotherapy, and chemotherapy. The median overall survival was not reached after 5 years. Three patients were deceased at database closure because of tumor progression. The extent of tumor resection correlated positively with overall survival (P = .044).
CONCLUSIONS
PDL is a rare variant of primary CNS lymphoma that can be radiographically mistaken for meningioma. The outcome is excellent with multimodality treatment, and aggressive surgery may convey a survival advantage in select cases.
Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Central Nervous System Neoplasms; Cerebrospinal Fluid Proteins; Dura Mater; Female; Humans; Kaplan-Meier Estimate; Lymphoma; Magnetic Resonance Imaging; Male; Middle Aged; Neuroimaging; Prognosis; Radiosurgery; Treatment Outcome
PubMed: 32176324
DOI: 10.1002/cncr.32834 -
Neurotherapeutics : the Journal of the... Jul 2009Primary central nervous system lymphoma (PCNSL) is a rare variant of extranodal non-Hodgkin lymphoma that is restricted in distribution to the brain, leptomeninges,... (Review)
Review
Primary central nervous system lymphoma (PCNSL) is a rare variant of extranodal non-Hodgkin lymphoma that is restricted in distribution to the brain, leptomeninges, spinal cord, and intraocular compartments. Although PCNSL shares overlapping features with systemic lymphoma, recent studies also reveal a unique pattern of gene and protein expression in PCNSL. These findings have yielded new insights into the pathophysiology of the disease, as well as the identification of novel prognostic biomarkers. Immune system compromise, such as is seen in acquired immune deficiency syndrome (AIDS), is the best established known risk factor for PCNSL. Like other lesions of the brain, meninges, and eye, the presenting symptoms associated with PCNSL typically include focal neurological deficits related to the site of disease or more global consequences of increased intracranial pressure. Diagnosis of PCNSL typically includes gadolinium-enhanced MRI and pathologic tissue analysis, as well as additional studies aimed at excluding concurrent systemic disease. PCNSL typically has a worse overall prognosis than systemic lymphoma. High-dose chemotherapy, particularly with methotrexate-based regimens, is the backbone of therapy for most patients, and chemotherapy is associated with much lower rates of treatment-related morbidity and mortality than whole-brain irradiation. Autologous stem cell transplantation is an emerging treatment modality, particularly in younger patients with relapsed disease, but high rates of treatment-related mortality are observed in older patients. Immunotherapy, including treatment with intrathecal rituximab, is another area of active research that may have promise in refractory or relapsed disease. Treatment options for intraocular lymphoma parallel those for PCNSL elsewhere in the brain: systemic chemotherapy, radiation, and local delivery of cytotoxic and immunologically active agents such as anti-CD20 antibody.
Topics: Biomarkers; Brain Neoplasms; Diagnosis, Differential; Drug Therapy; Eye Neoplasms; Humans; Immunologic Deficiency Syndromes; Immunotherapy; Lymphoma; Radiotherapy; Risk Factors; Salvage Therapy; Stem Cell Transplantation
PubMed: 19560747
DOI: 10.1016/j.nurt.2009.04.013 -
Brain Pathology (Zurich, Switzerland) Oct 2001Herpesviruses cause various acute, subacute, and chronic disorders of the central (CNS) and peripheral (PNS) nervous systems in adults and children. Both immunocompetent... (Review)
Review
Herpesviruses cause various acute, subacute, and chronic disorders of the central (CNS) and peripheral (PNS) nervous systems in adults and children. Both immunocompetent and immunocompromised individuals may be affected. Zoster (shingles), a result of reactivation of varicella zoster virus (VZV), is the most frequent neurologic complication. Other neurological complications include encephalitis produced by type I herpes simplex virus (HSV-1), and less frequently HSV-2, as well as by VZV and cytomegalovirus (CMV). Acute meningitis is seen with VZV and HSV-2, and benign recurrent meningitis with HSV-2. Combinations of meningitis/ encephalitis and myelitis/radiculitis are associated with Epstein Barr Virus (EBV); myelitis with VZV, CMV, EBV, and HSV-2; and ventriculitis/encephalitis with VZV and CMV. Brainstem encephalitis due to HSV and VZV, and polymyeloradiculitis due to CMV are well documented. HHV-6 produces childhood exanthem subitum (roseola) and febrile convulsions. Immunocompetent and immunocompromised hosts manifest different incidences and patterns of herpesvirus infections. For example, stroke due to VZV-mediated large vessel disease (herpes zoster ophthalmicus) occurs predominantly in immunocompetent hosts, while small vessel disease (leukoencephalitis) and ventriculitis develop almost exclusively in immunocompromised patients. EBV-associated primary CNS lymphomas also are restricted to immunosuppressed individuals. Recent large CSF PCR studies have shown that VZV, EBV, and CMV more frequently produce meningitis, encephalitis, or encephalopathy in immunocompetent hosts than was formerly realized. We review herpesvirus infections of the nervous system and illustrate the expanding spectrum of disease by including examples of a 75-year-old male on steroid treatment for chronic lung disease with fatal HSV-2 meningitis and an 81-year-old male with myasthenia gravis, long-term azathioprine use, and an EBV-associated primary CNS lymphoma.
Topics: Adolescent; Adult; Aged; Child; Child, Preschool; Cytomegalovirus; Female; Herpesviridae Infections; Herpesvirus 1, Human; Herpesvirus 2, Human; Herpesvirus 3, Human; Herpesvirus 4, Human; Herpesvirus 6, Human; Humans; Infant; Infant, Newborn; Male; Middle Aged; Nervous System
PubMed: 11556690
DOI: 10.1111/j.1750-3639.2001.tb00413.x -
British Journal of Haematology Nov 2019
Topics: Humans; Lymphoma, B-Cell; Magnetic Resonance Imaging; Male; Meningeal Neoplasms; Middle Aged
PubMed: 31423572
DOI: 10.1111/bjh.16163 -
Haematologica Jul 2014The benefit of intrathecal therapy and systemic rituximab on the outcome of diffuse large B-cell lymphoma at risk of central nervous system disease is controversial....
The benefit of intrathecal therapy and systemic rituximab on the outcome of diffuse large B-cell lymphoma at risk of central nervous system disease is controversial. Furthermore, the effect of intrathecal treatment and rituximab in diffuse large B-cell and Burkitt lymphoma with occult leptomeningeal disease detected by flow cytometry at diagnosis is unknown. Untreated diffuse large B-cell (n=246) and Burkitt (n=80) lymphoma at clinical risk of central nervous system disease and having had pre-treatment cerebrospinal fluid were analyzed by flow cytometry and cytology. Spinal fluid involvement was detected by flow cytometry alone (occult) in 33 (13%) diffuse large B-cell and 9 (11%) Burkitt lymphoma patients, and detected by cytology in 11 (4.5%) and 5 (6%) patients, respectively. Diffuse large B-cell lymphoma with occult spinal fluid involvement had poorer survival (P=0.0001) and freedom from central nervous system relapse (P<0.0001) compared to negative cases. Burkitt lymphoma with occult spinal fluid involvement had an inferior freedom from central nervous system relapse (P=0.026) but not survival. The amount of intrathecal chemotherapy was quantitatively associated with survival in diffuse large B-cell lymphoma with (P=0.02) and without (P=0.001) occult spinal fluid involvement. However, progression of systemic disease and not control of central nervous system disease was the principal cause of treatment failure. In diffuse large B-cell lymphoma, systemic rituximab was associated with improved freedom from central nervous system relapse (P=0.003) but not with survival. Our results suggest that patients at risk of central nervous system disease should be evaluated by flow cytometry and that intrathecal prophylaxis/therapy is beneficial.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Antibodies, Monoclonal, Murine-Derived; Antineoplastic Agents; Burkitt Lymphoma; Cerebrospinal Fluid; Child; Female; Flow Cytometry; Humans; Injections, Spinal; Lymphoma, Large B-Cell, Diffuse; Male; Meningeal Neoplasms; Middle Aged; Neoplasm Staging; Risk Factors; Rituximab; Treatment Outcome; Young Adult
PubMed: 24727817
DOI: 10.3324/haematol.2013.101741 -
Neurology(R) Neuroimmunology &... Nov 2023Persistent impaired immunity is possible even years after B-cell depleting therapies. This may favor the occurrence of infections, including infectious meningitis and...
OBJECTIVES
Persistent impaired immunity is possible even years after B-cell depleting therapies. This may favor the occurrence of infections, including infectious meningitis and encephalitis. In this study, we report a case of chronic enterovirus meningoencephalitis in prolonged B-cell depletion years after rituximab therapy.
METHODS
This is a case report from a German academic hospital. In addition to repeated clinical examinations, repeated brain MRI and extended CSF and laboratory diagnostics were performed. We used the CARE checklist when writing our report.
RESULTS
A 38-year-old man presented with high fever (>40°C), severe headache, and progressive neurologic and cognitive deficits. As result of previous lymphoma therapy with rituximab years ago, prolonged B-cell aplasia was detected. To restore humoral immunity, the patient received repeated infusions of immunoglobulins. In the end, a complete restitution of the physical and mental condition was achieved with the established therapy.
DISCUSSION
This case report should emphasize the importance of assessing humoral immunity even years after B-cell depletion therapy, especially in case of opportunistic infections.
Topics: Male; Humans; Adult; Rituximab; Enterovirus; Enterovirus Infections; Meningoencephalitis; B-Lymphocytes
PubMed: 37813597
DOI: 10.1212/NXI.0000000000200171 -
Journal of Hematology Apr 2023Primary central nervous system lymphoma (PCNSL) is an aggressive form of extranodal non-Hodgkin lymphoma that arises in the brain parenchyma, eyes, meninges, or spinal...
Primary central nervous system lymphoma (PCNSL) is an aggressive form of extranodal non-Hodgkin lymphoma that arises in the brain parenchyma, eyes, meninges, or spinal cord in the absence of systemic disease. Primary dural lymphoma (PDL), in contrast, arises from the dura mater of the brain. PDL is usually a low-grade B-cell marginal zone lymphoma (MZL), whereas other types of PCNSL are usually high-grade large B-cell lymphoma. This specific pathological subtype has important therapeutic and prognostic implications, making PDL a distinct subtype of PCNSL. Herein, we report a case of PDL in an African American patient, in her late thirties, who presented to our emergency room with chronic headaches. An emergent magnetic resonance imaging (MRI) of the brain showed a dural-based homogeneously enhancing extra-axial mass along the left hemisphere, which was contained within the anterior and parietal dural mater. A surgical specimen was collected after an emergency debulking procedure. The flow cytometry, done on the surgical specimen obtained, was positive for CD19, CD20, and CD22, but negative for CD5 and CD10. These findings were consistent with a clonal B-lymphoproliferative disorder. The surgical pathology specimen immunohistochemistry was positive for CD20 and CD45, but negative for Bcl-6Cyclin D1 and CD56. The Ki67 was 10-20%. These findings were consistent with extranodal MZL. Given the location and pathology, the patient was diagnosed with PDL. Due to MZL's indolent nature, location outside the blood-brain barrier, and known efficacy to bendamustine-rituximab (BR), we decided to treat our patient with BR. She completed six cycles without major complications, and her post-therapy brain MRI showed complete remission (CR). Our case adds to the sparse literature about PDL and highlights the efficacy of BR systemic chemotherapy on MZLs.
PubMed: 37187500
DOI: 10.14740/jh1113 -
Neuropsychiatric Disease and Treatment 2018Secondary central nervous system lymphoma (SCNSL) is a rare and aggressive disease, which is defined as secondary central nervous system (CNS) involvement in patients...
BACKGROUND
Secondary central nervous system lymphoma (SCNSL) is a rare and aggressive disease, which is defined as secondary central nervous system (CNS) involvement in patients with systemic lymphoma. According to previous reports, SCNSL presents mostly with leptomeningeal spread; however, our experience differs. In the present study, we demonstrate the diversity of magnetic resonance imaging (MRI) patterns in SCNSL.
PATIENTS AND METHODS
Initial morphological MRI findings in 21 patients (10 women and 11 men with mean age 62.3±16.2 years) with SCNSL were retrospectively evaluated. All patients suffered from neurological symptoms and underwent MRI, and all cases were histologically verified. Twelve patients were treated by corticosteroids at the time of the initial MRI.
RESULTS
Parenchymal lesions were present in 18 of 21 cases (85.7%), solitary meningeal infiltration was present in 1 patient (4.8%), leptomeningeal infiltration in combination with hypophyseal involvement in 1 patient (4.8%), and solitary involvement of the sixth cranial nerve (CN) was found in 1 patient (4.8%). Multiple lesions were present in 11 of 21 cases (52.4%). Diffusion restriction in all or part of the lesion was detected in 14 of 18 cases (77.8%). All parenchymal lesions had an infiltrative appearance and most enhanced homogenously (11 of 17 cases; 64.7%). A combination of parenchymal and meningeal involvement was found in 10 of 21 cases (47.6%). Infiltration of the CNs, basal ganglia, corpus callosum, and ependyma was present in 8 of 21 cases (38.1%) for each of the abovementioned structures; hypothalamic-hypophyseal axis was affected in 7 of 21 cases (33.3%).
CONCLUSION
In contrast to previous reports, SCNSL presented as parenchymal disease. MRI is not sufficient for differentiation between primary and secondary CNS lymphoma.
PubMed: 29559780
DOI: 10.2147/NDT.S157959