Incidence of potential glycosylation sites in immunoglobulin variable regions distinguishes between subsets of Burkitt's lymphoma and mucosa-associated lymphoid tissue lymphoma

Recently, a high incidence of novel N-glycosylation sites introduced by somatic mutation was observed in the immunoglobulin variable region genes of follicular lymphoma. As these are positively selected and are uncommon in normal B cells, they may have a role in tumour growth and behaviour. Sites are not characteristic of chronic lymphocytic leukaemia or myeloma, but are detectable in approximately 50% of diffuse large cell lymphomas. Another feature of the variable region genes of certain lymphomas is ongoing somatic mutation. To determine whether glycosylation is associated with this phenomenon, we analysed variable region gene sequences of Burkitt's lymphoma (BL) and mucosa-associated lymphoid tissue (MALT) lymphoma. Novel sites were common in endemic BL (82%) and in 4/5 patients with Iranian BL. However, sporadic BL had a lower incidence (43%). Patients with MALT lymphoma had a low frequency (9%) of novel sites, comparable to normal B cells. These findings distinguish glycosylation sites from ongoing mutation and may reflect different environmental influences on these tumours.     

A case of inflammatory demyelinating polyradiculoneuropathy associated with T-cell lymphoma

Malignant lymphoma may present prominent peripheral nervous system disorders with variable etiologies. We describe a patient who presented with chronic relapsing polyradiculoneuropathy accompanied by right facial nerve palsy. Gadolinium enhancement of the right facial nerve and cervical spinal roots was noted on magnetic resonance imaging (MRI). Sural nerve biopsy specimens showed mononuclear cell infiltration around the vessels in the epineurium. Histopathological and immunohistochemical investigations of sural nerve specimens revealed perivascular infiltration of lymphocytes with T-cell dominancy. No apparent direct invasion of lymphoma cells was seen. The results of nerve conduction studies, sural nerve biopsy and cerebrospinal fluid examination were suggestive of immune-mediated inflammatory demyelinating neuropathy. The chronic and relapsing fashion and unique radiological findings in our patient expand on the previously reported features of peripheral neuropathy associated with peripheral T-cell lymphoma.     

Treatment planning in cutaneous T-cell lymphoma

Effective long-term management of cutaneous T-cell lymphoma (CTCL) requires administration of skin-directed therapies such as topically applied nitrogen mustard or photochemotherapy to achieve a complete response in clinically early disease (patch and thin-plaque-phase mycosis fungoides, MF) and often the concomitant administration of well-tolerated drugs with systemic effects such as interferon alfa, bexarotene, methotrexate or extracorporeal photopheresis in more advanced, but not highly aggressive/nontransformed disease (thick plaque or tumor phase MF or erythrodermic CTCL). The author's approach is provided as a guide for dermatologists in private practice.     

恶性淋巴瘤mdr1和MRP mRNA及 P-gp表达水平与化疗疗效的相关研究

目的探讨恶性淋巴瘤mdr1、MRP mRNA和P-gp表达水平与化疗疗效的相关性.方法应用半定量逆转录多聚酶链反应(RT-PCR)技术和流式细胞术(FCM)方法,以8例人正常淋巴结为正常对照,对46例淋巴瘤患者[23例初治(HD1例,NHL22例)及23例复发(HD5例,NHL18例)]的mdr1 mRNA、MRP mRNA和P-gp表达水平与化疗疗效间的关系进行了前瞻性研究.结果复发患者mdr1基因和P-gp表达水平及阳性率均高于初治患者(P<0.001),而MRP基因表达水平及阳性率在复发与初治患者间差异无显著意义(P>0.05).mdr1基因及P-gp表达阳性患者的化疗有效(CR+PR)率(33.33%和26.67%)明显低于mdr1基因及P-gp表达阴性患者(85.71%和83.87%,P<0.001),而MRP基因表达阳性患者与阴性患者的化疗有效率差异无显著意义(P>0.05).相关分析显示,mdr1基因和P-gp表达水平之间有明显相关性(r=0.296 3,P<0.05),而mdr1和MRP之间、MRP与P-gp之间均无明显相关性(r=0.072 3,P>0.05;r=0.081 8,P>0.05).结论 mdr1基因及P-gp表达是恶性淋巴瘤患者多药耐药的主要机制,而MRP基因不是产生耐药的主要机制.mdr1基因及P-gp表达水平的高低与恶性淋巴瘤化疗疗效密切相关,而MRP基因的表达与化疗疗效未见相关.     

Ocular manifestation of primary nervous system lymphoma: what can be expected from imaging?

Primary ocular lymphoma, which affects the posterior parts of the eye, is an ocular manifestation of primary central nervous system lymphoma (PCNSL). It used to be the ocular disease with the shortest time of survival, even worse than ocular melanoma. Death ensues by CNS dissemination. Unfortunately, ocular lymphoma may be the initial manifestation of PCNSL and diagnosis is frequently difficult, even if vitreal biopsy is performed. Therefore, it should be determined whether cross sectional imaging may be helpful in detection and differential diagnosis of ocular lymphoma. MRI of seven patients (female = 6, male = 1, median age 62 years) with biopsy proven ocular lymphoma were retrieved from the files of our hospital and of a multicenter PCNSL study. In four patients, ocular lymphoma was the first manifestation of PCNSL, in three a cerebral lesion had occurred in the first place. Progression to cerebral lymphoma was seen in three of the four patients with initial eye manifestation. Imaging was performed using a dedicated thin section protocol in four patients. An intraocular abnormality was found in four cases, always in T1-weighted images after contrast injection. Differential diagnosis from uveitis or ocular melanoma was not possible by imaging alone. The examination was falsely negative in the remaining three patients. Hence, imaging has a low sensitivity for ocular lymphoma and does not facilitate differential diagnosis against uveitis or ocular melanoma. Received: 17 April 2002, Accepted: 9 July 2002 Correspondence to Dr. W. Küker     

Expression of basic fibroblast growth factor is associated with poor outcome in non-Hodgkin's lymphoma

It is now clear that angiogenesis and angiogenesis factors are important in the pathogenesis of haematological malignancies. High pretreatment levels of serum basic fibroblast growth factor have been shown to be associated with poor prognosis in patients with non-Hodgkin's lymphoma. The aim of this study was to evaluate whether non-Hodgkin's lymphoma cells express basic fibroblast growth factor and/or its receptor (fibroblast growth factor receptor-1) and whether basic fibroblast growth factor expression correlates with basic fibroblast growth factor serum levels, intratumoral microvessel density, and patient outcome. We measured basic fibroblast growth factor by enzyme-linked immunosorbent assay in sera taken from 58 patients with non-Hodgkin's lymphoma before treatment and in 19 of them also after treatment. Pathological specimens at diagnosis were evaluated by immunohistochemistry staining using polyoclonal antibody against factor-VIII-related antigen, basic fibroblast growth factor and fibroblast growth factor receptor-1 to determine the expression of the microvessel count and basic fibroblast growth factor and fibroblast growth factor receptor-1. The lymphoma specimens demonstrated positive staining for basic fibroblast growth factor (in 23%) and fibroblast growth factor receptor-1 (in 58.5%). The patients who expressed basic fibroblast growth factor had a significantly worse progression-free and overall survival than those who did not (P=0.003 and P=0.03 respectively), while patients expressing fibroblast growth factor receptor-1 were less likely to achieve complete remission than those lacking the receptor (33% vs 65%, P=0.047). There was no correlation of basic fibroblast growth factor staining with either serum basic fibroblast growth factor levels or microvessel count. Basic fibroblast growth factor serum levels did not change significantly after treatment These results suggest that non-Hodgkin's lymphoma specimens express basic fibroblast growth factor and its receptor (fibroblast growth factor receptor-1) and this expression is associated with poor patient outcome.     

SH2D1A expression in Burkitt lymphoma cells is restricted to EBV positive group I lines and is downregulated in parallel with immunoblastic transformation

The SH2 domain containing SH2D1A protein has been characterized in relation to the X-linked lymphoproliferative disease (XLP), a primary immunodeficiency that leads to serious clinical conditions after Epstein-Barr virus (EBV) infection. The SH2D1A gene is mutated in the majority of XLP patients. We previously detected SH2D1A in activated T and NK cells, but not in B lymphocytes. We have found SH2D1A protein in Burkitt lymphoma (BL) lines, but only in those that carried EBV and had a Group I (germinal center) phenotype. All the EBV-carrying Group III (immunoblastic) and the EBV-negative BL lines tested were SH2D1A-negative. Motivated by these differences, we studied the impact of EBV and the cellular phenotype on SH2D1A expression. We approached the former question with BL sublines after both the loss of the virus and subsequent reinfection. We also tested original EBV-negative BL lines carrying transfected EBV genes, such as EBNA1, EBNA2, EBNA6, EBER1, 2 and LMP1, respectively. In our experiments, no direct relationship could be seen between EBV and SH2D1A expression. We modified the phenotype of the Group I BL cells by LMP1 transfection or CD40 ligation. The phenotypic changes, indicated by expression of immunoblastic markers, e.g., SLAM, were accompanied by downregulation of SH2D1A. It seems, therefore, that the presence of EBV and the phenotype of the cell together regulate SH2D1A expression in the BL cells. It is possible that SH2D1A is expressed in a narrow window of B cell development represented by germinal center cells.