Primary central nervous system lymphoma

Primary central nervous system lymphoma (PCNSL) is a rare variant of non-Hodgkin’s lymphoma that is increasing in incidence. Methotrexate-based chemotherapy in combination with whole-brain radiotherapy (WBRT) has dramatically improved the outcome of patients. However, treatmentrelated neurotoxicity is a significant complication, especially after radiotherapy in the elderly. Despite advances in therapy, several important questions remain regarding optimal methotrexate dose, dosing frequency, adjunct chemotherapy, and the impact of deferring WBRT. Advances in biologic therapy and strategies to intensify the delivery of chemotherapy may help to limit the use of radiotherapy, thus lessening potential neurotoxicity. Studies looking at oncogenic proteins as potential prognostic markers for PCNSL may help us to develop risk-adapted therapies.     

Primary central nervous system lymphoma

Primary central nervous system lymphoma (PCNSL) is a rare form of non-Hodgkin lymphoma (NHL) that is restricted entirely to the brain, leptomeninges, eyes, and rarely the spinal cord. It typically presents with focal neurologic symptoms and is characterized by diffuse infiltration of the brain. Corticosteroids are useful for symptomatic treatment but can interfere with definitive pathological diagnosis. PCNSL is radiosensitive and responds to whole-brain radiotherapy. The use of preirradiation high-dose methotrexate-based regimens has significantly improved response rates and patient survival. Longer survival, however, is often marred by devastating neurotoxicity to which the elderly are particularly susceptible. Newer regimens aim to minimize such toxicity while maintaining the survival benefit of combined modality treatment.     

Primary central nervous system lymphoma: essential points in diagnosis and management

Primary central nervous system lymphoma (PCNSL) is an extra-nodal non-Hodgkin lymphoma. PCNSL is defined as lymphoma involving the brain, leptomeninges, eyes, or spinal cord without evidence of lymphoma outside the CNS. Treatment includes induction with chemotherapy and consolidation with whole-brain radiotherapy or high-dose chemotherapy supported by autologous stem cell transplantation. High-dose methotrexate is the most important drug in cases with PCNSL, and this drug will be used in combination with small molecules, BTK inhibitors, new monoclonal antibodies, and checkpoint blockers.     

Primary central nervous system lymphoma

Primary central nervous system lymphoma is an aggressive lymphoma with a molecular biology and genetic profile that appears to be distinct from other types of diffuse large B-cell lymphoma. The median survival after whole brain radiotherapy alone is poor, but is significantly improved after high-dose methotrexate-based combination chemotherapy. The rarity of primary central nervous system lymphoma means that randomised studies have proved challenging, particularly as many patients are elderly and more susceptible to the toxic effects associated with these treatments. Promising treatment strategies are emerging and, wherever possible, patients should be treated within clinical trials. Quality of life and neurocognitive data should be collected prospectively to assess the effect of the disease and treatment.     

Primary lymphoma of the central nervous system

Primary lymphoma of the central nervous system (CNS) represents a pathology that is no longer considered rare, also in the light of its high correlation with the human immunodeficiency virus (HIV) syndrome reported recently. Often the correct diagnosis of the disease is difficult to reach, owing to the wide spectrum of non-lymphoma pathologies from which it should be differentiated and the invasiveness of some diagnostic techniques. The biologic aggressiveness of the neoplasm often makes a combined radio-chemotherapeutic approach necessary. In contrast, surgical resection does not seem to provide any significant benefit. The clinical experience reported here, together with a review of the most recent literature, lead the authors to suggest the opportunity of treating primary lymphoma of the CNS with the most active and modern chemotherapeutic protocols in association with traditional treatments to obtain an improvement in overall survival.     

Primary central nervous system lymphoma: A curable disease

Primary central nervous system lymphoma is a rare subtype of non‐Hodgkin lymphoma that is confined to the brain, leptomeninges, or the eye and is associated with a relatively poor prognosis compared to other extranodal diffuse large B‐cell lymphomas. However, methotrexate‐based induction chemotherapy followed by consolidative chemotherapy or high‐dose therapy and autologous stem cell transplantation is associated with improved survival and reduced neurotoxicity. Aberrant activation of B‐cell receptor signaling and activation of nuclear factor kappa beta is a frequent genetic alteration and offers opportunities for targeted therapies in this lymphoma subtype.     

Primary central nervous system lymphoma with testicular relapse

We report the case of a 54-year-old man with primary central nervous system lymphoma (PCNSL) who achieved a radiological complete response to high-dose methotrexate and 6 months later had a simultaneous local and testicular relapse.     

Primary malignant lymphoma of the central nervous system

Between 1960 and 1983, 19 patients with primary malignant lymphoma of the central nervous system (CNS) were seen at McGill University Hospitals. The diagnosis was made at autopsy in 3 patients, and by biopsy in 16. Results of treatment were poor. All four patient who underwent surgery alone died within 2 months of diagnosis. Of 12 patients who underwent surgery and postoperative radiotherapy, 11 died between 2 and 56 months (median, 12 months) following diagnosis, and one is alive with disease at 47 months. Patterns of involvement at first recurrence and/or at autopsy were analyzed for 13 patients. Failure at the original site of involvement was unusual after treatment consisting of surgery and radiotherapy. In contrast, failure in the brain at sites other than those originally involved was common in spite of the use of whole brain irradiation. Local leptomeningeal involvement was seen in one patient whose diagnosis was made at autopsy, and cerebral spinal fluid seeding was seen in two additional patients, one within 1 month of diagnosis and one at relapse at 6 months after diagnosis. No patient developed disease outside the CNS. The limitations of current therapy for this disease are discussed, and certain suggestions made regarding the management of future patients with this diagnosis.     

Primary large-cell lymphoma of the central nervous system

Primary non-Hodgkin's lymphoma of the central nervous system (CNS) is a rare disease. Seven patients were seen and treated at the University of Michigan Medical Center between January 1969 and December 1983. All patients had histologically proven diagnoses of large cell lymphoma with clinical and radiologic evidence of involvement limited to the CNS. Five of seven patients received postoperative radiation therapy, two of whom have had apparent local control at 1- and 2-year follow-up. The two patients without postoperative radiation died of local recurrence 2 and 3 months following subtotal resection. These poor results suggest that adjuvant therapy may be required for improved control of this type of extranodal lymphoma.     

Primary central nervous system lymphoma imitates multiple sclerosis

Primary central nervous system lymphoma (PCNSL) can be confused with multiple sclerosis (MS) in patients who present with neurological dysfunction, a non-enhancing periventricular lesion, and CSF pleocytosis. Administration of corticosteroid causes clinical improvement and regression of PCNSL in some patients which may be interpreted as a steroid-induced remission from an exacerbation of MS. Sustained clinical dependance upon corticosteroid is unusual in MS, and should lead to consideration of PCNSL. Repeat CSF examination and gadolinium-enhanced MRI scan obtained off corticosteroid should differentiate between the two diagnostic possibilities.     

Primary central nervous system lymphoma in Japan: a nationwide survey

PURPOSE: To analyze clinical features, treatment results, and prognostic factors of primary central nervous system lymphoma (PCNSL) in Japan, we conducted a nationwide survey. METHODS AND MATERIALS: We analyzed 466 patients with histologically proven PCNSL treated between 1985 and 1994 at 62 institutions, including 56 medical schools. RESULTS: Patient and tumor characteristics of the 466 patients were not greatly different from those reported previously, except for the relatively high proportion of T-cell lymphoma (8.5%). The median survival time of the 466 patients was 18 months, and the 5- and 10-year survival rates were 15.2% and 8.2%, respectively. Complete response was observed in 63% of evaluable patients, but 64% of the complete responders developed recurrence (77% within the irradiated volume). Among patient- or tumor-related factors, higher age, worse performance status, presence of B symptom, multiple lesions, presence of meningeal dissemination, and elevated lactate dehydrogenase (LDH) level were associated with poorer survival, whereas no significant difference was observed in prognosis with respect to sex, T/B phenotype, or histological subclassification. In 410 patients receiving at least 40 Gy to the tumor, there was no difference in survival with respect to total radiation dose or field. Patients receiving 2 or more cycles of systemic chemotherapy had a slightly longer median survival time (22 months) and higher 5-year survival rate (20%) than those receiving radiotherapy alone (18 months and 17%, respectively), but the difference was not significant (p = 0.13). No chemotherapy protocol appeared to be better than any other. CONCLUSIONS: In addition to age and performance status, which are well-known prognostic factors, B symptom, tumor number, presence of meningeal dissemination, and serum LDH level also seemed to influence survival. Higher radiation dose was not associated with better prognosis. The role of chemotherapy could not be clarified because of the use of various protocols, but it seemed that the influence of various prognostic factors is greater than the effect of chemotherapy.     

Diagnosis and management of primary central nervous system lymphoma

Primary central nervous system lymphoma (PCNSL) is a rare and aggressive extranodal non‐Hodgkin lymphoma (NHL) that is confined to the brain, eyes, spinal cord, or leptomeninges without systemic involvement. The overall prognosis, diagnosis, and management of PCNSL differ from those for other types of NHL. Prompt diagnosis and initiation of treatment are vital for improving clinical outcomes. PCNSL is responsive to radiation therapy; however, whole‐brain radiotherapy (WBRT) inadequately controls the disease when it is used alone, and its delayed neurotoxicity causes neurocognitive impairment, especially in elderly patients. High‐dose methotrexate (HD‐MTX)–based induction chemotherapy with or without autologous stem cell transplantation (ASCT) or reduced‐dose WBRT leads to durable disease control and less neurotoxicity. The optimal treatment has yet to be defined; however, HD‐MTX–based induction chemotherapy is considered standard for newly diagnosed PCNSL. Ongoing randomized trials are addressing the roles of rituximab and consolidative treatment with ASCT or reduced‐dose WBRT. Despite high tumor response rates with the initial treatment, many patients relapse with a very poor prognosis. The optimal treatment for refractory or relapsed PCNSL is poorly defined. The choice of salvage treatment depends on a patient's age, previous treatment and response, performance status, and comorbidities at the time of relapse. This review provides an overview of the clinical features, diagnosis, pathology, and management of PCNSL in immunocompetent patients, and it focuses on recent advances in treatment. Cancer 2017;123:4314‐24 . © 2017 American Cancer Society.     

Primary central nervous system lymphoma presenting as autonomic dysfunction

Summary We describe a patient with primary central nervous system lymphoma (PCNSL) who presented with symptoms of subacute onset of dysautonomia. Autonomic testing indicated a peripheral autonomie neuropathy while magnetic resonance imaging revealed brainstem involvement. We propose that this patient's autonomie dysfunction could be the result of a paraneoplastic syndrome and PCNSL should be considered in the differential diagnosis of dysautonomia.     

Primary central nervous system lymphoma as a secondary malignancy

Primary central nervous system lymphoma (PCNSL) is a rare neoplasm, but it is occurring with increased frequency even among apparently immunocompetent patients. Although secondary malignancies frequently involve the lymphoreticular system, PCNSL has been reported as a second neoplasm only once previously. Seven patients are discussed who developed PCNSL after successful treatment for a prior neoplasm. The original cancer was colon (one), breast (one), thyroid (one), Hodgkin's disease (two), and non-Hodgkin's lymphoma (two). Patients with systemic non-Hodgkin's lymphoma were thought to have a separate cerebral lymphoma on the basis of a prolonged disease-free interval from their systemic lymphoma, and the absence of systemic disease, when PCNSL was diagnosed and through subsequent follow-up. The PCNSL developed a median of 10 years after the diagnosis of the first tumor and 6 years after the last evidence of systemic disease. The diagnosis of PCNSL was often delayed because of confusion with brain metastases, and initial shrinkage or disappearance of the lesion after corticosteroids. Formation of PCNSL may be a consequence of treatment for the first malignancy, reflect an unidentified inherent predisposition to neoplastic transformation, or result from the changing epidemiology of PCNSL in the general population. These mechanisms are not mutually exclusive, and a single hypothesis cannot account for all these cases.     

Primary lymphoma of the central nervous system: A clinicopathologic study

We performed clinicopathologic examinations of 27 cases of primary lymphoma of the central nervous system not related to acquired immune deficiency syndrome. We considered age and change of performance status (PS) to be especially important in clinical examination. We also conducted pathological studies of these tumors and the characteristics of their cells, in order to characterize pathological subtypes, cell kinetics, and involvement of viruses. PS of patients more than 70 years old decreased markedly before treatment and did not show the improvement after treatment that was exhibited by those under 70 years of age. Low PS (60% or less) after initial treatment, high MIB-1 positivity (over 44.0%), and high counts of AgNOR (over 4.56/cell) were significantly associated with lower survival rates. Patients with immunoblastic lymphoma and high MIB-1 positivity are likely to die from general debilitation, without evidence of recurrence from imaging. Preoperative steroid therapy was significantly associated with higher apoptotic positivity.     

Primary central nervous system lymphoma: a role for adjuvant chemotherapy

Summary Sixteen immunocompetent patients, 10 of whom were previously reported, with primary non-Hodgkins lymphoma of the central nervous system (PCNSL) were treated and followed longitudinally by the Neurooncology Service at the University of California, San Francisco (UCSF) and the University of California, San Diego (UCSD). After undergoing surgery (biopsy or resection), these patients received radiation therapy (RT) with hydroxyurea (HU) followed by adjuvant chemotherapy with the combination of procarbazine, CCNU, and vincristine (PCV) as previously reported. All patients ultimately died of progressive recurrent PCNSL. Toxicity using the HU + RT followed by PCV schedule was tolerable. Median and quartile survival data (41 and 65 months, respectively) suggest efficacy for this chemotherapy schedule and further emphasizes a role for adjuvant chemotherapy in the primary treatment of PCNSL.     

原发性中枢神经系统淋巴瘤28例临床分析

目的　探讨原发性中枢神经系统淋巴瘤 (PCNSL)的合理治疗方式及影响预后的因素。方法　回顾性分析 2 8例PCNSL的临床特征、治疗结果及预后因素 ,运用SPSS 10 .0软件包进行统计分析。结果　 2 8例PCNSL患者中 ,男性 18例 ,女性 10例 ,中位年龄 5 2岁。全组中位生存期 (MST) 2年 ,5年生存率 2 1.4 % ;单病灶 19例 ,多病灶 9例。病理检查为B细胞来源者占 78.6 % (2 2 / 2 8) ,病理类型以弥漫性大细胞淋巴瘤为主。依国际工作分类 (WF) ,中度恶性占 5 7.7% (15 / 2 8)。多因素分析结果显示 ,病灶的单发或多发是影响预后的独立因素 (P =0 .0 4 17)。对B细胞来源、WF高度恶性及多病灶的PCNSL患者 ,合并化疗的综合治疗效果较好 ,其中合并非常规化疗的疗效优于常规化疗疗效(P =0 .0 191)。结论　PCNSL较一般的NHL具有独特的预后因素 ;化疗在PCNSL的综合治疗中极为重要 ,临床应尽可能采用非常规的易透过血脑屏障的药物或给药方式     

Primary nervous system lymphoma

Opinion statement Primary nervous system lymphoma (PNSL) is a rare type of non-Hodgkin’s lymphoma confined to the nervous system. Although significant progress has been made in the treatment of PNSL over the past decade, patients with this disease are rarely cured. Until recently, whole brain radiation therapy has been the standard treatment for PNSL. However, whole brain radiation therapy is associated with a high relapse rate and late neurotoxicity after chemotherapy, especially in patients older than 60 years of age. Methotrexate-based chemotherapy has become the standard approach to treat patients with newly diagnosed PNSL. Ongoing research efforts are focused on identifying chemotherapeutic agents with good antilymphoma activity that penetrate the blood-brain barrier. The roles of intrathecal chemotherapy and blood-brain barrier disruption are not fully defined. Given the rarity of this tumor, patients with PNSL should be referred to tertiary cancer centers where ongoing clinical trials are underway to identify the optimal treatment of PNSL.