皮下脂膜炎样T细胞淋巴瘤六例临床及病理特点分析

目的 皮下脂膜炎样T细胞淋巴瘤(subcutaneous pannieulitis-like T cell lymphoma,SPTCL)是一类非常罕见的皮肤T细胞恶性淋巴瘤,相关报道较少且易误诊.本研究旨在分析SPTCL患者的临床及病理特征.方法 回顾性分析2010-01-01-2015-12-31天津医科大学肿瘤医院收治的6例SPTCL患者的临床治疗、预后及病理特征.结果 6例SPTCL患者中,男3例,女3例.6例患者的年龄2～53岁,平均诊断年龄为29岁,其中4例的患者＜30岁.起病部位主要为四肢,5例患者表现为皮下的硬结肿物,1例患者表现为皮肤溃疡和渗出.皮肤损害出现的中位时间为13个月(1～60个月).6例患者中无伴发嗜血细胞综合症(hemophagocytic syndrome,HPS)者.6例患者镜下共同特征是小或中等大小的不典型肿瘤细胞围绕脂肪细胞生长.免疫组化特征为CD3+(100％)、CD4+ (100％)、CD8+(100％)、CD20-(100％)、CD56-(83％)、TCRβF-1+ (100％)、TIA-1+ (100％)、GrB+ (100％)、穿孔素阳性(100％).6例SPTCL患者均接受了以CHOP或CHOP样方案为主的多药联合化疗,化疗后3例患者获得CR,2例患者PR,1例患者SD.CR的3例患者中有2例患者出现复发,其中1例患者经自体造血干细胞移植后获得CR,1例在间断化疗状态下维持SD.获得PR的1例患者经自体造血干细胞移植后获得CR.中位随访时间为47个月(7～73个月),1例失访,3例患者无病生存,2例患者带瘤生存.结论 本研究SPTCL患者呈惰性进展且预后较好,常用的化疗方案为CHOP或CHOP样方案,早期复发或化疗效果欠佳的患者采取自体造血干细胞移植可能获益.     

Clinical outcome of patients with subcutaneous panniculitis-like T-cell lymphoma

Subcutaneous panniculitis-like T-cell lymphoma (SPTCL) is a rare form of cytotoxic T-cell lymphoma. The objective of this study was to characterize the clinical presentation, treatment, and prognosis of patients with SPTCL. Twenty-one patients with SPTCL were seen at Mayo Clinic (Rochester, Minnesota, USA) between July 1973 and June 2004. The median age at diagnosis was 42 years (range 23 - 80 years) and 15 (71%) were women. Constitutional symptoms occurred in 14 (67%) patients, including fever, serositis, arthralgias and myalgias. The Eastern Cooperative Oncology Group performance score was poor (3 - 4) in 3 (15%) patients. Liver enzymes (at least 2 enzymes, Aspartate aminotransferase (AST), alkaline phosphatase and/or lactate dehydrogenase) were elevated in 11 (52%) patients. Therapy consisted of chemotherapy in 13 (62%) patients, or other therapeutic interventions in 8 (38%) patients, including surgical excision, corticosteroids alone or in combination with either plaquenil, colchicine, hydroxychoroquine, or azathioprine. Bone marrow transplantation was performed in 5 (24%) patients, 3 autologous and 2 allogeneic. The median overall survival from diagnosis was 15 months (range 0.1 - 104 months). Two groups of patients were identified and categorized as having a favorable or unfavorable disease course. The factors associated with an unfavorable disease course were a low white blood cell count or elevated lactate dehydrogenase. Patients treated aggressively with stem cell transplantation appeared to have an improved overall survival.     

皮下脂膜炎样T细胞淋巴瘤与皮肤的结外鼻型NK/T细胞淋巴瘤的对比研究

目的:通过对20例皮下脂膜炎样T细胞淋巴瘤(subcutaneous panniculitis-like T-cell lymphoma,SPTL)和19例皮肤的结外鼻型NK/T细胞淋巴瘤的对比研究,加深对2者的认识.方法:从临床病理、免疫标记、EB病毒(Epstein-Barr virus,EBV)感染和T细胞受体(T-cell receptor, TCR)基因重排等多个方面对2者进行比较.结果: 临床表现上2者不易鉴别,但皮肤NK/T细胞淋巴瘤常伴皮肤外播散、预后差;组织学上,SPTL常严格局限于皮下脂肪组织,而皮肤NK/T细胞淋巴瘤以真皮为中心形成弥漫性浸润,常累及皮下脂肪层,更易于见到大片凝固性坏死、血管中心性浸润和亲表皮现象;免疫表型上,SPTL常表达βF1、膜型CD3、CD8,不表达CD4、CD56,而大部分皮肤NK/T细胞淋巴瘤则表达CD56和细胞质CD3ε,仅少数表达膜型CD3、CD8.CD56、CD3、CD8和βF1的表达差异有统计学意义(P<0.05).SPTL患者中检出 EBER1/2原位杂交阳性,而皮肤NK/T细胞淋巴瘤100%病例为阳性,2者比较差异有统计学意义(P<0.05).SPTL患者中检出TCR-γ基因克隆性重排,而皮肤NK/T细胞淋巴瘤患者仅有4/18例(22.2%)检出重排,2者之间差异有统计学意义(P<0.05).结论:有无皮肤外播散,组织学上有无大片凝固性坏死、血管中心性浸润和亲表皮现象,是否表达免疫组织化学标记CD56、CD3、CD3ε、CD8和βF1,EB病毒原位杂交阳性与否,以及TCR-γ克隆性重排检出与否,均可作为SPTL和皮肤NK/T细胞淋巴瘤的鉴别要点.准确鉴别2者需综合临床、组织病理学、免疫表型、EB病毒感染和基因重排等结果进行全面分析.     

皮下脂膜炎样T细胞淋巴瘤的诊断及文献复习

目的 :观察皮下脂膜炎样T细胞淋巴瘤 (SPTCL)的临床表现并分析SPTCL的病理组织学形态、诊断及鉴别诊断。方法 :报道 3例发生在四肢、躯干的多发性病灶的病例 ,从临床病理组织学及免疫组化、临床表现等方面进行了观察。结合文献 ,探讨SPTCL的发病学、临床表现、实验室检查、治疗及转归。结果 :SPTCL主要表现四肢、躯干皮肤水疱、皮下结节、多发溃疡。 2例合并噬血细胞综合征 ,临床进展迅速 ,于发病后 4个月及 8个月内死亡。组织病变均呈脂膜炎样改变 ,瘤细胞主要浸润皮肤真皮及皮下组织 ,瘤组织可见明显大片状坏死 ,肿瘤细胞浸润血管壁并见血管壁的凝固性坏死。免疫组化肿瘤细胞LCA、CD4 5R0阳性 ,证实瘤细胞为T细胞型。结论 :SPTCL是一种特殊类型的皮肤原发性恶性肿瘤 ,具有特殊生物学行为 ,预后差     

Transimmunization for cutaneous T cell lymphoma: a Phase I study

Extracorporeal photochemotherapy (ECP) is a widely used immunotherapy for cutaneous T cell lymphoma (CTCL). It involves four sequential steps: conversion of blood monocytes into dendritic antigen presenting cells (DC) by repetitive adherence and disadherence to plastic surface; reinfusion of the new DC; presumed in vivo loading of the new DC with apoptotic malignant leukocytes; and expansion of the anti-tumor CD8 T cell pool. To assess the safety of a methodology designed to increase ex vivo contact between the apoptotic malignant cells and new DC prior to reinfusion, a single-center, open-label Phase I clinical study of a revised procedure—referred to as “Transimmunization”—was conducted in CTCL patients. Twenty-seven subjects were treated monthly for 3 to 5 months, alone or in combination with electron beam therapy. For those receiving Transimmunization alone, there was an overall diminution in infiltrative lesions in eleven (55%) of twenty patients. In the twelve leukemic CTCL patients, there was a significant mean reduction of 50.1% in the circulating malignant cells, as determined with family-specific anti-T cell receptor Vβ monoclonal antibodies (P ≤ 0.021). Because this therapy permits the synchronous induction and tumor loading of DC, with minimal toxicity, Transimmunization may merit further investigation in CTCL and other malignancies.     

血管内T细胞淋巴瘤一例报道并文献复习

目的提高对血管内淋巴瘤（IVL）的认识。方法报道一例IVL的临床表现和诊治经过,并进行文献复习。结果以发热、皮疹和嗜血细胞综合征为表现的IVL少见,该例患者经过积极化疗效果不显著,最后死于肝衰竭和消化道出血。结论IVL少见,患者生前诊断困难,病情进展快,预后差。     

Defining the toxicity of current regimens for extranodal NK/T cell lymphoma: a systematic review and metaproportion

Objectives: The aim of this study is to compare the toxicity profiles of SMILE versus less intense L-asparaginase-containing regimens, CCRT or “sandwich” RT+CT regimens.

Methods: PRISMA protocol was used to search Pubmed and Embase for studies of treatment regimens for extranodal NK/T-cell lymphoma, nasal type (ENKTL) in English published before March 2018. Pooled data were grouped into five categories: A) CHOP-like regimens; B) Gemcitabine-based regimens; C) SMILE-like regimens; D) Concurrent and “sandwich” RT + CT; and E) Methotrexate-based combinations. We pooled prevalence of selected adverse events from each study to calculate the weighted overall prevalence using meta-proportion in Stata.

Results: Group C was the most toxic with the pooled neutropenia 72% (95 CI 64;80) and thrombocytopenia 48% (95% CI 40;55) prevalence. The use of Group D treatment regimens was associated with the lowest anemia (10% (95% CI 1;19)) prevalence. Group E was the least toxic with regard to thrombocytopenia (6% (95% CI 1;11).

Conclusion: Our analysis confirms that SMILE regimen, which is current standard to treat advanced-stage ENKTL may be associated with more severe hematological toxicity compared to other L-asparaginase combinations, including methotrexate-based (AspaMetDex, MESA and MEDA) or gemcitabine-based (GELOX, PGEMOX, DDGP, GDL, GOLD, GLIDE) or CCRT-based regimens.     

皮肤T细胞淋巴瘤的免疫治疗

阐述免疫治疗包括细胞因子[白介素—2(IL—2)、白介素-12(IL—12)]、免疫核素(^131I—T101)、免疫毒素IL—2—融合毒素(DAB389-IL2)]、单克隆抗体抗CD5(T101)和某些新的局部免疫调节剂(如CTLA4—1g、LFA-tip、BCX—34)、维甲酸类药物如targretin、panretin与光效应药物如hypercin或δ—ALA试治皮肤T细胞淋巴瘤。     

Cutaneous T cell lymphoma with multiple oral lesions

Cutaneous T cell lymphoma is a type of non Hodgkins lymphoma occurring rarely (two-three percentage of NHL) and that with an ENT manifestation is much more rare. We present here a case of cutaneous T cell lymphoma presenting with multiple skin lesions and oral and oropharyngeal ulcerations.     

家族性噬血细胞综合征继发皮下脂膜炎样T细胞淋巴瘤一例并文献复习

目的:探讨家族性噬血细胞综合征（FHL）继发皮下脂膜炎样T细胞淋巴瘤（SPTCL）的临床特点及基因突变情况。方法:选取2012年6月河南省儿童医院收治的1例FHL继发SPTCL患儿为研究对象,回顾性分析其临床特征、疾病演变过程、基因突变及遗传学特点,并复习相关文献。结果:患儿有UNC13D纯合突变伴STXBP2杂合突变,父母及兄长UNC13D为杂合突变。给予HLH-2004方案规律化疗,4年后疾病复发,二次化疗缓解1年后继发SPTCL,给予SMILE方案化疗后行异基因造血干细胞移植,至截稿前无病生存。结论:对儿童噬血细胞综合征应及时完善相关基因检测,以明确原发病诊断。FHL可继发SPTCL,化疗联合异基因造血干细胞移植可能是目前唯一的治愈途径。     

鼻腔NK/T细胞淋巴瘤的临床特征和治疗现状

鼻NK／T细胞淋巴瘤属恶性淋巴瘤的一种少见的特殊类型，其诊断和治疗尚存在争议。本文综述了该病的流行病学、病因和发病机制、临床表现、分期、病理特征、诊断、治疗现状及预后，为提高认识、规范治疗提供线索。     

Hydrochlorothiazide and cutaneous T cell lymphoma

BACKGROUND:

Mycosis fungoides (MF) and leukemic Sézary syndrome (SS) are the most common cutaneous T cell lymphomas (CTCL), but their etiology remains unknown. After patients were observed with hydrochlorothiazide (HCTZ)‐associated CTCL, HCTZ was examined as a putative chronic antigen in a cohort of prospectively staged patients.

METHODS:

Demographic and drug exposure data was examined from 1443 confirmed MF and SS patients. Hypertensive CTCL patients were divided into HCTZ users or nonusers for statistical analysis by chi‐square and t tests. Causality in a case series was rated by the Naranjo Adverse Drug Reaction Probability Scale.

RESULTS:

A total of 815 of 1443 MF and SS patients (56.5%) were hypertensive; 205 (25.2%) were taking HCTZ at initial staging. Comparing stage of patients who were using or not using HCTZ, the most significant difference was between stage I and stage IV (odds ratio of 0.45; 95% confidence interval of 0.25‐0.78, P = .003), demonstrating reduced likelihood of being stage IV in patients who were on HCTZ. Seventy‐seven percent of the MF patients on HCTZ were stage I. A total of 125 patients of 196 (63.8%) started HCTZ prior to developing CTCL lesions, and 35 of 121 (28.0%) started within 1 year of first skin rash. Thirty‐six of 125 patients (28.8%) experienced complete or partial remissions after discontinuing HCTZ. A monoclonal T cell receptor rearrangement was detected more frequently in the hypertensive stage I patients not taking HCTZ as compared with those who were (55.3% vs 69.1%, P = .032). Three patients were rechallenged and developed MF lesions that resolved or improved with discontinuation.

CONCLUSIONS:

HCTZ is commonly prescribed and may be a putative antigen in a small subset of early MF patients. Careful drug histories and a trial off medication are warranted. Cancer 2013. © 2012 American Cancer Society.     

Angioimmunoblastic T cell lymphoma: treatment experience with cyclosporine

Angioimmunoblastic T cell lymphoma is a distinct entity for which there is no standard therapy. On the basis of the rationale that CsA may represent a novel drug for AITL, a disease with considerable immune dysregulation, and encouraging case reports, the authors have treated 12 patients with this agent. Ten had failed prior steroids and/or chemotherapy and two had no prior therapy. CsA was administered at a dose of 3 - 5 mg/kg PO bid for 6 - 8 weeks and gradually tapered by 50 mg every 1 - 3 weeks. Responding patients received a maintenance dose of 50 - 100 mg, with a gradual taper after a maximal response was achieved as tolerated. Doses were titrated for renal dysfunction or hypertension. CsA levels were not monitored. Eight of 12 patients responded (three complete and five partial remissions). Dose reductions were required in six patients; renal insufficiency (n = 3), fatigue (n = 2), and hypertension (n = 1). Two patients developed acute infections and one patient died shortly after active treatment. These results suggest that CsA deserves further testing as a novel therapy for AITL. By interrupting T-cell activation, CsA may alter the immune dysregulation that characterizes AILT. The efficacy of CsA is being explored in patients with recurrent AILT in a prospective trial (ECOG 2402).     

CD20阳性血管免疫母细胞性 T 细胞淋巴瘤1例及文献复习

目的:探讨CD20阳性血管免疫母细胞性T细胞淋巴瘤（angioimmunoblastic T cell lymphoma,AITL）的临床特征及预后。方法:回顾分析我院1例CD20阳性AITL患者的临床病理特征、治疗转归并复习相关文献。结果:患者男性,69岁,以水肿及腹腔积液为首发表现,CT提示全身淋巴结肿大。免疫表型:CD20阳性、CD3(+)、CD5(+)、Ki-67(+,85%),其它B细胞标记阴性,EBER原位杂交阳性,TCR基因重排及IGH单克隆性重排阳性,多种治疗方案均无效。结论:CD20阳性AITL患者的临床病理特征易与B细胞淋巴瘤混淆,病理形态学、免疫组织化学及TCR基因重排检测等可减少误诊。利妥昔单抗及其他靶向药物的应用可能提高治愈率,改善患者预后。     

自体外周血干细胞移植治疗Ｔ细胞淋巴瘤的临床研究

【摘　要】　目的：探讨自体外周血干细胞移植（ＡＰＢＳＣＴ）治疗Ｔ细胞淋巴瘤的临床疗效和安全性。方法：２０００年７月～２００８年４月,行ＡＰＢＳＣＴ的Ｔ细胞淋巴瘤患者共１７例,包括Ｔ淋巴母细胞淋巴瘤１０例,鼻型ＮＫ／Ｔ淋巴瘤４例,外周细胞Ｔ淋巴瘤２例,间变大细胞淋巴瘤１例。按照ＡｎｎＡｒｂｏｒ标准和ＩＰＩ分期评分。８例患者的采集物采用ＣＤ３４＋细胞纯化。所有患者均采用ＣＴＸ＋ＶＰ １６＋ＴＢＩ预处理方案。结果：（１）所有患者移植后造血功能均顺利重建,中性粒细胞恢复至０５×１０９／Ｌ为移植后（１２１８±２６３）天,血小板恢复至２０×１０９／Ｌ为移植后（１４５０±４０２）天。（２）中位随访７个月（１～９４个月）,２年预期的无疾病生存率为６２８９％,总生存率为７１８７％。（３）随访２年以上未复发的６例患者,均无病存活,中位随访５４个月（２４～９４个月）。（４）死亡均发生在移植后半年内,移植前未缓解的２例患者移植后均死亡,移植前处于复发状态的患者移植后３个月时再次出现复发,带病生存。（５）至随访截止时间,获完全缓解患者行或未行ＣＤ３４＋细胞分选移植的疗效无明显差别。结论：ＡＰＢＳＣＴ对移植前完全缓解和部分缓解的Ｔ细胞淋巴瘤患者疗效较好,造血重建顺利,且安全性好,但复发和原发难治的患者疗效相对差,应考虑选择异基因造血干细胞移植治疗。     

血管免疫母细胞性T细胞淋巴瘤14例临床分析

目的探讨血管免疫母细胞性T细胞淋巴瘤(AITL)的临床病理特征及治疗。方法分析1997年2月至2004年7月收治的14例AITL。结果14例就诊的AITL患者主要症状为全身淋巴结肿大,9例伴有发热等全身症状,3例并发自身免疫性溶血性贫血。病理组织学呈淋巴结结构破坏,免疫母细胞增生,树枝状血管增生的特点,免疫表型全部为T细胞性。14例均用ProMACE-CytaBOM方案化疗,CR3例,PR5例,总有效率57%。2年生存率为60%,全组中位生存25个月,3例缓解的患者已无瘤生存超过5年。结论AITL临床过程呈侵袭性,进展快,中位生存期短,预后差,应探索更为有效的治疗策略。     

NK/T细胞淋巴瘤细胞凋亡和细胞增殖特征及意义

Objective:The aim was to study the features and clinical significance of cell apoptosis and proliferation of NK/T cell lymphoma.Methods:TdT-mediated dUTP nick end labeling and immunohistochemical Streptavidin-peroxidase method were used to study cell apoptosis and the expression of proliferation cell nuclear antigen in 25 NK/T cell lymphoma and 10 reactive lymphoid tissues.Results:Apoptotic index(AI) and proliferative index(PI) averaged(1.92%±0.86%) and(41.48%±5.10%) respectively in the 25 NK/T cell lymphom...     

塞来昔布对T细胞淋巴瘤细胞增殖及侵袭功能的影响

目的：研究塞来昔布对T细胞淋巴瘤细胞增殖、化疗敏感性及侵袭能力的影响,并探讨其作用机制。方法：分别用不同浓度（0、20、40及80μmol/L）塞来昔布处理T细胞淋巴瘤Jurkat和Hut78细胞系24、48和72 h后,采用MTT法检测Jurkat和Hut78细胞的增殖活性。再用40μmol/L塞来昔布处理Jurkat和Hut78细胞48 h后,采用MTT法检测其对化疗药物敏感性的影响;流式细胞术检测塞来昔布对Jurkat和Hut78细胞凋亡水平的影响;Transwell小室检测塞来昔布致Jurkat和Hut78细胞侵袭能力的变化;实时荧光定量PCR （qPCR）及Western blot技术分别从mRNA及蛋白水平检测塞来昔布对Jurkat和Hut78细胞系P38、P65、Bcl-2、Bax、MDR1、MMP2及MMP9表达水平的影响。结果：与对照组比较,20～80μmol/L塞来昔布作用于Jurkat和Hut78细胞不同时间后,细胞增殖活性均受到明显抑制（P<0.05）。40μmol/L塞来昔布对化疗药物的敏感性明显增强（P<0.05）,且凋亡水平明显增加（P<0.01）;与40μmol/L塞来昔布共培养的Jurkat和Hut78细胞,其穿透Transwell小室的能力明显下降（P<0.01）,且P38及Bax蛋白的表达水平均明显增加（P均<0.01）,而P65、MDR1、Bcl-2、MMP2及MMP9表达水平均明显降低（P均<0.01）。结论：塞来昔布对T表型淋巴瘤细胞增殖和侵袭能力具有明显抑制作用,提示其在T细胞淋巴瘤的临床治疗中具有应用前景。     

NK／T细胞淋巴瘤治疗和预后研究进展

NK／T细胞淋巴瘤发病率低,占恶性淋巴瘤2％-10％,其临床病理特征和预后仍不明确,本文就2001年至2009年关于NK／T细胞淋巴瘤临床病理特征、治疗策略和预后因素方面的研究进展作一综述。     

Restriction of T cell receptor variable region in lymph nodes of adult T cell leukemia/lymphoma

Adult T cell leukemia/lymphoma (ATLL) is a mature T cell malignancy, especially derived from the CD4 positive T cell. To characterize the T cell, we examined the representation of T cell antigen receptor variable region, using the monoclonal antibodies [β V 5 (a), β V 5 (b), β V 6 (a), β V 8 (a), β V 12 (a), α V 2 (a), α-β V (a)]. Clinicopathologically we classified the lymph nodes of patients with ATLL into three states (1) human T cell leukemia virus type I (HTLV-I) associated lymphadenitis, reactive state; (2) incipient ATLL, early or pre-neoplastic state; and (3) ATLL, neoplastic state. The lymph nodes of all three states were composed of unvarying CD4 positive T cells. Most of the lymph nodes with ATLL consistently presented α V 2 antigen, but no others. In HTLV-I associated lymphadenitis, only a few cells reacted for α V 2, as in non-specific lymphadenitis without ATLL features. One of three cases with incipient ATLL presented α V 2. The selective expression of T cell antigen receptor V region might be associated with the presence of HTLV-I encoded superantigen, similar to human immunodeficiency virus (HIV).