流式细胞仪在蕈样肉芽肿和Sézary综合征中的应用

流式细胞仪具有快速、定量,同时分析多种细胞属性的优势,已越来越广泛应用于皮肤T细胞淋巴瘤.流式细胞仪可通过T细胞表面抗原相应抗体和T细胞受体Vβ抗体分别检测肿瘤性T细胞的异常免疫表型及单克隆性,成为蕈样肉芽肿和Sézary综合征辅助诊断和治疗监测的重要工具,其在伴外周血受累的蕈样肉芽肿和Sézary综合征诊断和治疗监测乃至发病机制研究中的应用将会有更加广阔的前景.     

皮肤T细胞淋巴瘤分子生物学研究进展

皮肤T细胞淋巴瘤的经典类型是蕈样肉芽肿和Sézary综合征。近年来,其发病率有逐渐增高的趋势。目前国内外从不同角度对该病的分子生物学进行了较多研究。本文就皮肤T细胞淋巴瘤的肿瘤形成,皮肤浸润,以及预后指标等分子生物学研究进展作了综述。     

长链非编码RNA在T细胞相关性皮肤病中的作用

长链非编码RNA(lncRNA)是长度＞200个核苷酸且不能编码蛋白的RNA.研究发现lncRNA可以调节T细胞的增殖、分化、凋亡等过程.T细胞在某些皮肤疾病的发病机制中具有重要作用,良性疾病如银屑病、特应性皮炎、白癜风和扁平苔藓,恶性疾病如蕈样肉芽肿、Sézary综合征和间变性大细胞淋巴瘤.本文就lncRNA在T细胞...     

皮肤T细胞淋巴瘤的治疗选择

皮肤T细胞淋巴瘤是一种少见的淋巴细胞增生性疾病,依据疾病的分类及分期不同,治疗选择有很大差异性。多数的皮肤T细胞淋巴瘤病程进展缓慢,诸如早期的蕈样肉芽肿和淋巴瘤样丘疹病,只需要选择皮肤局部治疗的方案。侵袭性或顽固性如Sézary综合征、复发性CTCL等,则需系统治疗,包括化疗。本文对国内现有药物及最新治疗方法进行综述。     

西达本胺联合干扰素α对人皮肤T细胞淋巴瘤细胞系Hut78的协同作用及其分子机制的研究

目的 研究西达本胺联合干扰素α(IFN-α)对蕈样肉芽肿及Sézary综合征相关的人皮肤T细胞淋巴瘤细胞系Hut78的协同作用及可能的分子机制,进而为治疗蕈样肉芽肿及Sézary综合征提供一种更有效的治疗方案.方法 用不同浓度的西达本胺和不同浓度的干扰素(IFN)-α以及西达本胺联合IFN-α分别作用Hut78细胞系2...     

TCR基因重排在皮肤T细胞淋巴瘤中的应用

T细胞在成熟过程中通过T细胞表面受体基因重排,从而具有特异性识别抗原的能力,在这一过程中的任何失调都会导致疾病。皮肤T细胞淋巴瘤是由于单个淋巴细胞的恶性增殖所导致的,病变组织表现出T细胞受体基因重排克隆性。蕈样肉样肿和Sézary综合征为最常见的皮肤T细胞淋巴瘤。T细胞受体基因重排的检测在皮肤T细胞淋巴瘤的发病机制研究、分类、诊断、判断预后上有重要的作用。     

皮肤T细胞淋巴瘤

皮肤T细胞淋巴瘤(Cutaneous T Cell Lymphoma CTCL)包括蕈样肉芽肿、Sézary综合征、真皮T细胞淋巴瘤等。它们均具有两个共同的特点:第一,是一个T细胞克隆的恶性增生,此T细胞克隆可以源自从骨髓中的原始细胞到辅助性T细胞发生过程中的某个阶段;第二,这种恶性的增生发生在     

皮肤淋巴瘤第六讲非MF/SS皮肤恶性淋巴瘤及其治疗原则

阐述非蕈样肉芽肿/Sézary综合征皮肤恶性淋巴瘤包括原发性皮肤淋巴增殖性疾病(淋巴瘤样丘疹病、原发性皮肤CD30阳性大T细胞淋巴瘤)、CD30阴性皮肤大T细胞淋巴瘤、多形小/中等大T细胞淋巴瘤、皮下脂膜炎样T细胞淋巴瘤、鼻和鼻型自然杀伤/T细胞淋巴瘤以及原发性皮肤滤泡中心细胞性淋巴瘤、原发性皮肤边缘区淋巴瘤和小腿大B细胞淋巴瘤、富于T细胞的B细胞淋巴瘤与血管内大B细胞淋巴瘤的治疗。     

第一讲向表皮性皮肤T细胞淋巴瘤的分期和预后

向表皮性皮肤T细胞淋巴瘤(epidermotropic cutaneous T-cell lymphomas,ECTCL)系恶性辅助T细胞疾病,常开始于皮肤而后累及骨髓、血中淋巴细胞、淋巴结和内脏器官[1],包括具有独特和重叠临床表现的蕈样肉芽肿(mycosis fungoides,MF)和Sézary综合征(Sézary's syndrome,SS).近应用聚合酶链反应扩增T-细胞受体γ链基因重排,证明MF在早期即示克隆性T细胞成分系统性侵犯[2],SS患者血中恶性T细胞成分明显扩增[3].ECTCL的分期与预后有关.兹阐述ECTCL的分期和预后如下:     

皮肤T细胞淋巴瘤的免疫治疗相关进展

皮肤T细胞淋巴瘤(CTCL)是一组异质性明显的非霍奇金淋巴瘤,最常见的是蕈样肉芽肿(MF)和Sézary综合征。CTCL早期病变进展缓慢,晚期则可累及多系统,预后较差,目前尚无有效的治疗方案。肿瘤的免疫疗法是指通过修复、增强宿主的免疫功能从而控制、清除肿瘤的一种治疗方法,治疗反应比传统疗法更为持久,目前已经在多种实体肿瘤中得到验证。本文就免疫治疗在CTCL中的研究进展作一综述。     

Mycosis fungoides and Sézary syndrome: Role of chemokines and chemokine receptors

Mycosis fungoides is the most common form of cutaneous T-cell lymphoma (CTCL), and is characterized by a clonal expansion of malignant CD4⁺ T lymphocytes with skin-homing properties. Clinically and pathologically, mycosis fungoides can be categorized into patch, plaque and tumor stages. The clinical course of mycosis fungoides is usually chronic and indolent, but a proportion of patients may develop progressive disease with peripheral blood, lymph node and visceral organ involvement. Sézary syndrome is an aggressive leukemic form of CTCL characterized by a clonal population of malignant T cells in the peripheral blood. Various forms of skin-directed and systemic treatments are available for mycosis fungoides and Sézary syndrome. However, current treatments are generally not curative, and can only control the disease. Currently, the etiology and pathogenesis of mycosis fungoides and Sézary syndrome are not well defined. Proposed mechanisms include chronic antigenic stimulation by infectious agents, expression of specific adhesion molecules, altered cytokine production, mutations of oncogenes and tumor suppressor genes, and avoidance of apoptosis. In recent years, a number of chemokine receptors and their corresponding chemokine ligands have been found to contribute to the migration and survival of lymphoma cells in mycosis fungoides and Sézary syndrome, including CC chemokine receptor 4 (CCR4), CCR10, C-X-C chemokine receptor type 4 (CXCR4), CCR7, CCR3 and CXCR3. Since chemokines and chemokine receptors have been found to play important roles in the pathophysiology of mycosis fungoides and Sézary syndrome, they may be potentially useful targets for the development of new treatments for these diseases in the future.     

Cutaneous T cell lymphoma in children.

Cutaneous T cell lymphoma (CTCL) is a term used to describe a heterogeneous group of lymphoproliferative disorders that involve the skin. Mycosis fungoides and Sézary syndrome are two forms of CTCL that arise in adults and are uncommon in children. Dermatologists frequently employ the term CTCL as a synonym for mycosis fungoides and Sézary syndrome. There has been increased recognition that the mycosis fungoides and Sézary syndrome forms of CTCL may arise in children and adolescents. Moreover, younger adults with these types of CTCL report onset of symptoms during adolescence. The literature regarding CTCL in childhood is limited. The purpose of this article is the review the literature regarding CTCL arising in children. The clinical presentation including morphologic variants, diagnosis, prognosis, and management are summarized.     

A modified staging classification for cutaneous T-cell lymphoma

BACKGROUND: Despite refinements in the diagnosis of cutaneous T-cell lymphoma (CTCL), since 1979 there have been no changes to the staging of CTCL used to classify mycosis fungoides and Sézary syndrome. OBJECTIVE: We reviewed the current staging of CTCL and examined the usefulness of a new staging scheme for mycosis fungoides and Sézary syndrome. METHODS: We determined overall survival of 450 patients with mycosis fungoides and Sézary syndrome using the current and modified staging classifications. RESULTS: There were no significant differences between survival of patients with stage IB (patches/plaques involving greater than 10% body surface area) and IIA (peripheral adenopathy) disease and of patients with stage IIB (tumor) and III (erythroderma) disease. There was a significant difference in survival between patients with extensive patch versus extensive plaque stage disease. Modification of the current classification by splitting T2 into patch versus plaque stage disease and incorporating tumors and erythroderma into stage III proved superior to the current scheme in predicting overall survival. CONCLUSION: Modification of the current staging classification for CTCL yields subgroups useful in the prognostic assessment of CTCL.     

CD25+ folliculotropic Sézary syndrome with CD30+ large cell transformation

Folliculotropic Sézary syndrome is a rare and unique variant of cutaneous T‐cell lymphoma (CTCL) characterised by both follicular and leukaemic involvement of mycosis fungoides (MF). It is associated with a more aggressive clinical course and fatal outcomes. Large cell transformation (LCT) of mycosis fungoides/Sézary syndrome is also associated with an aggressive disease course and shortened survival, requiring an intensive therapeutic approach. This report describes a case of folliculotropic Sézary syndrome with CD30+ LCT. Most of the larger lymphocytes in the lesions were positive for CD25, the expression of which is associated with advanced CTCL. In addition, we review the literature on this unusual CTCL and provide evidence that this entity represents a distinct clinicopathological entity occasionally associated with extracutaneous involvement and LCT.     

Interleukin-15 expression in cutaneous T-cell lymphoma (mycosis fungoides and Sézary syndrome)

BACKGROUND: Cytokines are of potential importance in the pathogenesis of cutaneous T-cell mediated disorders, including cutaneous T-cell lymphoma (CTCL). OBJECTIVES: To compare interleukin (IL)-15 expression in certain inflammatory cutaneous diseases, with that in CTCL (mycosis fungoides and Sézary syndrome). METHODS: IL-15 mRNA and protein expression were examined by in situ hybridization and immunohistochemistry, respectively, on formalin-fixed, paraffin-embedded biopsies of normal human skin, atopic dermatitis, psoriasis, parapsoriasis and CTCL. RESULTS: Despite similar expression of IL-15 mRNA, we found differences in IL-15 protein expression between normal human skin, atopic dermatitis and psoriasis on the one hand, and parapsoriasis and CTCL on the other. IL-15 protein expression was not detected in normal human skin, atopic dermatitis or psoriasis, but was detected, mainly at low levels but in a few patients at higher levels, in epidermal keratinocytes in parapsoriasis, mycosis fungoides and Sézary syndrome. CONCLUSIONS: Induction of keratinocyte IL-15 expression appears to be a feature of CTCL. The factors stimulating such an expression remain unknown.     

Cutaneous T‐cell lymphoma and atopy: is there an association?

BACKGROUND: Case reports have suggested a relationship between atopic diatheses and Sézary syndrome, pre-Sézary syndrome or mycosis fungoides. However, Sézary and pre-Sézary syndromes are rare entities, and this association has never been analysed in greater detail for specific subtypes of cutaneous T-cell lymphoma (CTCL). OBJECTIVES: To evaluate the prevalence of atopy in subjects with Sézary syndrome, pre-Sézary syndrome or mycosis fungoides, and to compare the rates with the reported prevalence of atopy in the general population. METHODS: We retrospectively reviewed the records of 157 patients with the diagnosis of Sézary or pre-Sézary syndrome seen between 1965 and 2000, and 102 patients with the diagnosis of mycosis fungoides evaluated from 1994 to 2000 at Mayo Clinic. RESULTS: Of 157 subjects with Sézary or pre-Sézary syndrome and 102 subjects with mycosis fungoides, 18 and 12, respectively, were identified as having a history of atopic dermatitis, asthma or allergic rhinitis. The prevalence rates of atopy in Sézary or pre-Sézary syndrome and mycosis fungoides were 11.5% (95% confidence interval 6.9-17.5%) and 11.8% (6.2-19.7%), respectively. CONCLUSIONS: No significant difference exists in the prevalence of atopy in Sézary or pre-Sézary syndrome compared with that in mycosis fungoides (chi2-test, P = 1.00). Furthermore, the rates of atopy in Sézary or pre-Sézary syndrome and mycosis fungoides are not significantly different from the prevalence of atopy in the general population (17-40%). On the basis of these observations, no evidence currently implicates a causal association of CTCL with atopy.     

Decreased expression of Fas (APO-1/CD95) on peripheral blood CD4+ T lymphocytes in cutaneous T-cell lymphomas

BACKGROUND: The usually protracted and indolent course of cutaneous T-cell lymphoma (CTCL) is consistent with an accumulation of lymphocytes rather than being a true proliferative disorder, perhaps as the result of defective lymphocyte apoptosis. Fas (CD95) is the main signalling membrane molecule involved in postactivation T-lymphocyte apoptosis. OBJECTIVES: To evaluate expression of Fas on circulating CD4+ lymphocytes in patients with CTCL. METHODS: Fas expression on peripheral blood CD4+ T cells in 16 patients with mycosis fungoides (patch and infiltrated plaque stages) and in four patients with Sézary syndrome was compared with that in 25 matched patients with lymphocyte-mediated cutaneous benign inflammatory disorders and in 15 subjects without inflammatory cutaneous diseases. RESULTS: Fas expression on peripheral CD4+ lymphocytes was significantly lower in patients with CTCL compared with subjects with benign inflammatory cutaneous disorders and with healthy donors. CONCLUSIONS: This pattern supports the hypothesis that a defect in T-cell apoptosis may play a part in the pathophysiology of CTCL, perhaps through abnormalities of the Fas/Fas ligand system. Alternatively, this decrease could be the result of the presence of the soluble Fas ligand molecule in the sera of patients with CTCL.     

Erythrodermic cutaneous T cell lymphoma with hypereosinophilic syndrome: Treatment with interferon alfa and extracorporeal photopheresis

BACKGROUND: Hypereosinophilic syndrome (HES) is a heterogeneous group of disorders characterized by a sustained eosinophilia leading to end organ dysfunction. The lymphoproliferative variant of HES is thought to be mediated by an underlying hematologic process that drives eosinophil production through specific cytokines. Eosinophilia is also recognized as a poor prognostic factor in cutaneous T-cell lymphoma (CTCL) in which neoplastic T cells may produce eosinophilopoietic cytokines. OBJECTIVE: We report a case of HES with cardiac involvement that developed in the context of erythrodermic mycosis fungoides, discuss the possible relationship between these diseases, and speculate on the role that eosinophils might play as a prognostic factor in CTCL. METHODS: Case report and review of the literature. RESULTS: CTCL may be added to the group of lymphoproliferative disorders associated with HES. CONCLUSION: A patient with erythroderma and concomitant diagnosis of "idiopathic" HES may warrant further investigation for CTCL.