Selective central nervous system tropism of primary central nervous system lymphoma

Primary Central nervous system lymphoma (PCNSL) is most frequently a diffuse large B cell lymphoma (DLBCL), which is confined to the Central nervous system (CNS). We performed an experiment in which lymphoma cells from a PCNSL patient were implanted subcutaneously in an athymic mouse. The lymphoma cells were shown to home to the CNS with histologic evaluations of the brain showing multiple large B cells in blood vessels consistent with intravascular large B cell lymphoma (IVL). We did not find any evidence of lymphoma at the site of implantation or other locations. The findings are consistent with highly selective tropism of PCNSLforthe CNS and its vasculature.     

Primary central nervous system lymphoma

Primary central nervous system lymphoma (PCNSL) is an uncommon extranodal non-Hodgkin lymphoma. Its incidence has increased during the last 3 decades and has been reported in both immunocompromised and immunocompetent patients. Immunocompromised patients are affected at a younger age compared with immunocompetent patients. It presents with raised intracranial pressure and focal neurologic and neuropsychiatric symptoms. The lesions are typically solitary. The majority of the lesions are located in the periventricular area, whereas in a few cases they are located in the supratentorial area. Diffuse large B-cell lymphomas constitute most PCNSLs, whereas T-cell, low-grade, anaplastic, and Hodgkin lymphomas are rarely encountered. The morphology of PCNSL shows a characteristic angiocentric pattern and is positive for B-cell markers by immunohistochemistry. The differential diagnosis of PCNSL includes central nervous system gliomas, metastatic tumors, demyelinating disorders, subacute infarcts, and space-occupying lesions due to an infectious etiology. The understanding of the molecular mechanisms involved in the pathogenesis of PCNSL and the identification of molecular biomarkers have lagged behind that of systemic nodal lymphomas. Primary central nervous system lymphomas are treated with combined radiotherapies and chemotherapies. The prognosis for PCNSL is worse than for other extranodal lymphomas.     

Non-Hodgkin's lymphoma following Hodgkin's disease. A case report and immunohistochemical corroboration

Two non-Hodgkin's lymphomas, one a follicular mixed cell type and the other a diffuse large cell type (Working Formulation), appeared 7 and 12 years, respectively, after the initial histopathologic diagnosis of Hodgkin's disease (nodular sclerosis) in an elderly male. The clinicopathologic implications of non-Hodgkin's lymphoma complicating Hodgkin's disease as a second malignant neoplasm are discussed on the basis of immunohistochemical studies performed on the sequentially biopsied lymph nodes using various monoclonal antibodies, in particular, anti-Leu-M1, which is known as a valuable marker of the neoplastic cells of Hodgkin's disease.     

Primary T-cell lymphoma of the central nervous system

We describe a 64-year-old man who presented with a 9-month history of a progressive neurologic disturbance affecting principally his short-term memory, eye movements, and sense of balance. Computed tomography and magnetic resonance imaging showed a 3-cm mass in the left cerebellar hemisphere. This was removed at craniotomy and proved histologically to be a diffuse non-Hodgkin's lymphoma. Further investigation showed no evidence of lymphoma elsewhere in the body. Immunohistochemical studies with an extensive panel of monoclonal antibodies showed the tumor cells to be T cells staining with the markers UCHL1, MT1, OKT3, and OKT11. Cells of the helper phenotype predominated. A small admixed reactive population of polyclonal B cells and macrophages was also present. The proliferation count as judged with the antibody Ki67 was about 15%. Primary cerebral lymphoma is in itself a rare entity with most cases being of B-cell origin. Primary cerebral T-cell lymphoma is extremely rare and the few previously reported cases are reviewed.     

Primary infratentorial lymphoma of the central nervous system

An 39 year-old woman presented with neurotic and neurologic symptoms is described. Computerized tomography revealed contrast uptake in nodular form of oval centers and perilesional edema. Clinic characteristics and possible etiopathogeny are discussed. Post-mortem examination disclosed presence of a primary cerebral lymphoma type B, not involving other organs.     

Lymphoproliferative disease with features of lymphoma in the central nervous system of a horse

Lymphoma (malignant lymphoma, lymphosarcoma) is uncommon in horses in the United Kingdom. This report describes an unusual form of lymphoproliferative disease with features of lymphoma restricted to the central nervous system (CNS) and with no evidence of a primary lesion elsewhere. Immunohistochemical examination defined an overwhelming predominance of T lymphocytes with admixed B lymphocytes and activated macrophages. This case exemplifies the challenges associated with definitive diagnosis of lymphoproliferative disease of the equine CNS.     

Stereotaxic biopsy diagnosis of central nervous system lymphoma

Twelve cases of central nervous system lymphoma diagnosed by stereotaxic brain biopsy are reviewed to determine the most effective method to establish the diagnosis given the small amount of tissue obtained by this technique. The stereotaxic biopsy material was examined cytologically, histologically, and immunocytochemically. The diagnosis was established by a smear made at the time of biopsy in eight cases. Histologic sections were diagnostic of lymphoma in 11 of 12 cases. Accurate classification according to the Working Formulation was possible in six cases, with diagnosis of diffuse small non-cleaved non-Burkitt's in three, large cell immunoblastic in two, and mixed small and large cell type in one. Five additional cases were diagnosed as high-grade lymphoma but could not be further subclassified because of the small biopsy size or formalin fixation. Immunocytochemical stains for lymphoid markers on paraffin-embedded material confirmed the diagnosis in ten cases, and, in one of these, the demonstration of monoclonality on air-dried cytospins identified an atypical polymorphous lymphocytic population as neoplastic.     

Diffuse large B-cell lymphoma involving the central nervous system

Lymphomas involving the central nervous system are recognized increasingly in immunocompetent as well as immunosuppressed individuals, and the majority of the cases are diffuse large B-cell lymphoma (DLBCL). The aim of this study was to compare the immunophenotype, clinicopathological features, and association with Epstein-Barr virus (EBV) of DLBCL of the central nervous system (CNS) in 3 different clinical situations: primary, in immunocompetent patients; "primary," in immunosuppressed patients; and in patients with secondary involvement by systemic lymphoma. The authors reviewed the clinicopathological features, morphology, immunophenotype (according to germinal-center B-cell-like and nongerminal B-cell-like subtypes), and association with EBV in 36 cases of DLBCL of the CNS, including 25 primary cases, 5 associated with immunosuppression, and 6 cases with secondary involvement. Survival was evaluated in 15 cases of primary CNS lymphomas. Of the 36 patients, 19 were male and 18 female. Only 2 cases of lymphomas were EBV-positive; both occurred in immunosuppressed patients. Separation into germinal-center and non-germinal center subtypes by an immunohistochemistry panel showed that 68% of primary, 80% of secondary, and 83% of the cases associated with immunosuppression were of non-germinal-center subtype, respectively. Patients with non-germinal-center immunophenotype showed significantly worse survival than those with CNS lymphomas of the germinal-center subtype.     

肾移植后中枢神经系统并发症的临床诊疗

背景：目前国内外关于肾移植后中枢神经系统并发症的研究较少。 目的：探讨肾移植后中枢神经系统并发症的临床诊疗方案。 方法：对河南中医学院第一附属医院2008-01/2010-08收治的277例同种异体肾移植后出现中枢神经系统并发症的15例患者进行回顾性分析。 结果与结论：15例(5.41%)出现中枢神经系统并发症的患者中：弥漫性脑病7例(2.52%),脑血管意外4例(1.44%),癫痫发作3例(1.08%),中枢神经系统感染1例(0.36%)。提示肾移植后中枢神经系统原因较复杂,包括感染、缺氧、代谢、电解质紊乱、移植后排斥反应及免疫抑制剂(钙调蛋白抑制剂)等。     

Primary central nervous system lymphoma in immunocompetent patients

Primary central nervous system lymphoma has been traditionally described in patients with immunodeficiency syndromes; however, there is an increasing number of immunocompetent patients with this type of tumor that have been reported recently. In this paper we have retrospectively analyzed 22 immunocompetent patients with a confirmed diagnosis of primary lymphoma of the brain. The mean age in this group was 65 years with a similar male/female ratio. The time of evolution of the clinical course was 80.4 days and it was mainly characterized by headache and focal neurological deficit. In four patients multiple lesions were observed, while the remaining presented single lesions mainly located in the periventricular area of the cerebral hemispheres. All patients were initially administered steroids and a stereotactic biopsy was performed. The majority of tumors were histologically classified as diffuse large cells and all of them showed a positive reaction to B-cells antigens on immunohistochemistry. All patients were treated with radiotherapy and in 10 of them, chemotherapy with methotrexate was also indicated. The mean survival rate was II months among patients treated with radiotherapy alone and increased to 36 months when chemotherapy was added.     

Primary lymphoma of the central nervous system and HTLV-I infection

Only a few cases of AIDS-related primary lymphomas of the central nervous system (CNS) show a T-cell phenotype. We have recently studied two intravenous drug users with HIV infection who had primary CNS T-cell lymphomas. In both cases, the enzyme immunoassay (EIA) for HTLV gave a positive result. In the first case, study by western-blot (WB) and specific PCR confirmed the human T-cell lymphotropic virus type I (HTLV-I) infection and serological study by EIA for HTLV of his mother was negative. In the second case, analysis of ante-mortem serum samples by two different WBs showed an indeterminate pattern suggestive of HTLV-I infection, but adequate samples for PCR were not available. We speculate about the possibility that the horizontal transmission of HTLV-I infection could have facilitated the devepolment of a primary CNS T-cell lymphoma in these HIV patients, although they cannot be strictly considered as ATLL cases.     

Measles and central nervous system disease

This ia a summary and review of the Workshop, which points out that there is sufficient evidence to relate SSPE to a measles virus. This evidence is both direct-virus isolation- and indirect-immunological data. However the pathogenic process responsible for SSPE has not yet been elucidated. In the case of multiple sclerosis the evidence of the etiologic role of measles virus is only indirect and not as firm as in SSPE. Both diseases have stimulated investigations of the biology of the measles virus or provided ideas for studies in the future.     

Local cryoglobulin deposition in primary central nervous system lymphoma

Primary central nervous system lymphomas (PCNSLs) represent malignant non-Hodgkin's B-cell lymphomas confined to the central nervous system. Recent years have brought a dramatic increase in the frequency of PCNSL in the immunocompromised and immunocompetent populations. Cryoglobulins are cold-precipitable immunoglobulins associated with a number of infectious, autoimmune, and neoplastic disorders. Although it is known that patients with hematologic malignancies (eg, B-cell lymphomas, chronic lymphocytic leukemia, plasma cell dyscrasias) may have cryoglobulinemias and cryoglobulin deposition in several organs (eg, kidney, liver skin, blood vessels, peripheral nervous system), PCNSL associated with cryoglobulin deposition has not been previously described. This report demonstrates localized cryoglobulin deposition within the tumor bed in an immunocompetent patient with PCNSL.     

中枢神经系统原发性恶性淋巴瘤临床与病理分析

通过对１４例中枢神经系统原发性恶性淋巴瘤临床资料分析及光镜，电镜和免疫组化研究，结果表明：临床上以颅内压增高为主要症状，肿瘤可发生于中枢系统的任何部位。组织学特点，瘤细胞单一，异形，早期常围血管呈袖套样排列，中晚期呈弥漫性分布，无滤波形成。ＬＣＡ，Ｌ２６，ＵＣＨＬ１，ＧＦＡＰ，ＥＭＡ免疫组织化学染色及电镜检查提示肿瘤多数为Ｂ细胞起源。并对其病间，发病机理，诊断和鉴别诊断作了讨论     

Primary lymphoma of the central nervous system: a diagnostic problem

Primary lymphoma of the central nervous system (CNS) is difficult to diagnose because of the difficulty in differentiating it from multiple sclerosis, sarcoidosis, metastatic disease, chronic granulomatous disease, and cerebral cysticercosis. With the patient presented in this report, no abnormalities were found after performing laboratory tests, using radiographic modalities, and taking biopsies. Dexamethasone treatment was initiated, and patient''s symptoms improved.     

Primary anaplastic large cell lymphoma of the central nervous system.

Central nervous system (CNS) involvement is extremely rare in anaplastic large cell lymphoma (ALCL), and in children only isolated cases have been reported, mainly as secondary CNS involvement. A case of fatal primary ALCL of the brain in a 13-year-old white boy is reported. Magnetic resonance imaging of the brain showed decreased absorption in T1- and T2-weighted image showed a hyperintense signal in the right parietal lobe and 2 masses in the right frontal lobe. A frontal lobe biopsy showed a pleomorphic neoplasm diffusely infiltrating the brain parenchyma and composed of large cells with bizarre, often polylobated or horseshoe-shaped nuclei. Immunohistochemical stains showed diffuse strong positivity for CD30, anaplastic lymphoma kinase protein (ALK-1), p80, leucocyte common antigen, CD45RO (UCHL1), and focal staining for epithelial membrane antigen. Immunostainings for cytokeratins, monocyte-macrophage, and B-cell markers were negative. Epstein-Barr virus latent membrane protein was not detected. To the best of our knowledge, there is only 1 case of primary ALCL of the brain in childhood previously reported in the literature. Before the biopsy, both cases were clinically misdiagnosed as mycobacterial CNS infection. Therefore, primary ALCL should also be included in the differential diagnosis when a mycobacterial CNS infection is suspected in pediatric patients; a careful cytological evaluation of the cerebrospinal fluid or cerebral biopsy are essential for an accurate diagnosis.     

原发性中枢神经系统淋巴瘤临床病理及病因学分析

目的 探讨原发性中枢神经系统淋巴瘤(primary central nervous system lymphoma, PCNSL)的临床病理特征、预后指标及病因学.方法 复习39例PCNSL患者的临床资料,同时进行免疫组化、原位杂交检测EBER及PCR检测bcl-2/JH基因重排,并对临床资料、免疫标志物与预后的关系进行分析.结果 34例PCNSL患者的3年生存率为46.4%,5年生存率为27.1%,年龄≥60岁及病变部位深对预后不利(P=0.009和P=0.027),bcl-6阳性表达者的生存率高于阴性表达者(P=0.044),但多因素Cox回归分析显示,进入回归方程的为年龄因素.CD10/bcl-6/MUM-1/CD138分型和治疗方法对预后的判断无显著性差异(P＞0.05).39例患者EBER原位杂交均为阴性,bcl-2/JH基因重排5例阳性(12.8%),其中3例为CD10阳性病例.结论 PCNSL是一种少见的高侵袭性结外非霍奇金淋巴瘤,年龄因素是判断预后的独立性指标,CD10/bcl-6/MUM-1/CD138分型未发现有预后意义,但显示PCNSL的同质性较高,可能是弥漫性大B细胞淋巴瘤的一种亚型.EB病毒感染与PCNSL的病因无相关性.     

Thyroid diseases after treatment of Hodgkin's disease

BACKGROUND AND METHODS. Thyroid disease, especially hypothyroidism, is common in patients with Hodgkin's disease who have been treated with irradiation. We reviewed the records of 1787 patients (740 women and 1047 men) with Hodgkin's disease who were treated with radiation therapy alone (810 patients), radiation and chemotherapy (920 patients), or chemotherapy alone (57 patients) at Stanford University between 1961 and 1989. Among these patients, 1533 were alive at the last follow-up, and 254 had died of causes other than Hodgkin's disease. (Four other patients were excluded from the analysis because they had undergone thyroidectomy before treatment for Hodgkin's disease. The thyroid was irradiated in 1677 patients. Follow-up averaged 9.9 years. RESULTS. A total of 573 patients had clinical or biochemical evidence of thyroid disease. Among the 1677 patients whose thyroid was irradiated, the actuarial risk of thyroid disease 20 years after treatment was 52 percent, and it was 67 percent at 26 years. Hypothyroidism was found in 513 patients. A total of 486 patients received thyroxine therapy for elevated serum thyrotropin concentrations and either low free thyroxine (208 patients) or normal free thyroxine values (278 patients); 27 had transient elevations of the serum thyrotropin level that were not treated. Graves' hyperthyroidism developed in 30 patients (2 of whom had not undergone thyroid irradiation), and ophthalmopathy developed in 17 of these patients. Ophthalmopathy developed in four other patients with Graves' disease during a period of hypothyroidism (n = 3) or euthyroidism (n = 1). The risk of Graves' disease was 7.2 to 20.4 times that for normal subjects. Silent thyroiditis with thyrotoxicosis developed in six patients. Forty-four patients were found to have single or multiple thyroid nodules, 26 of whom underwent thyroidectomy. Six of the 44 had papillary or follicular cancers. Among the patients who did not undergo operation, 12 had small functioning nodules, 4 had cysts, and 2 had multinodular goiters. The actuarial risk of thyroid cancer was 1.7 percent. The risk of thyroid cancer was 15.6 times the expected risk. CONCLUSIONS. High risks of thyroid disease persist more than 25 years after patients have received radiation therapy for Hodgkin's disease, reinforcing the need for continued clinical and biochemical evaluation. Prolonged follow-up confirms an elevated risk of thyroid cancer and Graves' disease as well as hypothyroidism in these patients.