间变性淋巴瘤激酶阳性的间变性大细胞淋巴瘤研究进展

Stein于1985年首先报道间变性大细胞淋巴瘤(anaplas-tic large cell lymphoma,ALCL)是非霍奇金淋巴瘤(NHL)的一种独立类型[1]。最新的WHO分类中ALCL被归类于外周T细胞淋巴瘤,占同期NHL的2%~7%[2]。研究发现,约有半数患者产生致癌性的异常间变性淋巴瘤激酶(anaplasticlymphoma k     

间变性淋巴瘤激酶阳性弥漫大B细胞淋巴瘤的研究进展

摘 要：间变性淋巴瘤激酶阳性弥漫大B细胞淋巴瘤（anaplastic lymphoma kinase-positive diffuse large B-cell lymphoma,ALK+DLBCL）是弥漫大B细胞淋巴瘤(DLBCL)的一种罕见的亚型,具有特征性形态学、免疫表型和细胞遗传学特点。其临床过程具侵袭性,预后不良,明确认识该疾病是诊断的关键。选择性ALK抑制剂可能是ALK+DLBCL患者潜在的治疗选择。     

ALK阳性间变性大细胞淋巴瘤合并噬血细胞综合征1例

噬血细胞综合征(hemophagocytic syndrome,HPS),又称噬血细胞性淋巴组织细胞增多症(hemophagocyt ic lympho-histiocytosis,HLH),是一组罕见的、致命的以细胞因子风暴为特征的临床综合征,常以发热、脾大、血细胞减少、铁蛋白升高和肝功能受损等为主要特征[1] . ...     

系统型间变性大细胞淋巴瘤30例临床分析

 目的　探讨系统型间变性大细胞淋巴瘤（S-ALCL）的临床特征和预后相关因素。方法　回顾性分析30例S-ALCL患者的临床资料。30例患者均以联合化疗为主,配合局部病灶野放疗8例。化疗方案主要为 CHOP、EPOCH、Hyper-CVAD,以CHOP方案为主。结果　30例S-ALCL患者中位年龄36岁,男女比例为1.5∶1,有B症状、Ⅲ～Ⅳ期和结外侵犯者分别占60.0 %（18／30）、73.3 %（22／30）和60.0 %（18／30）;乳酸脱氢酶（LDH）升高者占46.7 %（14／30）;间变性大细胞淋巴瘤激酶（ALK）+ 18例（60.0 %）,其发病年龄小于ALK- 者（u＝3.92,P＝0.001）。单因素分析显示ALK-及LDH升高是重要的预后不良因素。结论　S-ALCL患者发病年龄较轻,预后较好。但ALK-、LDH升高者预后不良。治疗以联合化疗为主,对于有不良预后因素的患者,大剂量治疗可能获益。     

系统性间变性大细胞淋巴瘤病理诊断新进展

阐述了系统性间变性大细胞淋巴瘤的临床特点、形态学特征、免疫组化特征、分子遗传学特征、鉴别诊断生物学行为及预后、病因学等。     

间变性大细胞淋巴瘤中ALK与clusterin的表达及其临床病理意义

背景与目的：间变性淋巴瘤激酶（ALK）是系统性间变性大细胞淋巴瘤（ALCL）较为特异的标志,近来研究发现一种新的蛋白clusterin在ALCL中也有较高的表达率,其可能在ALCL的发展中起作用,并对诊断和治疗具有潜在价值.本研究探讨ALCL中ALK及clusterin蛋白表达特点、相互关系及临床病理意义.方法：应用免疫组织化学EnVision法检测90例淋巴瘤组织中ALK及clusterin蛋白表达,其中包括47例ALCL及对照组周围T细胞淋巴瘤非特殊型（PTCL-u）22例,经典型霍奇金淋巴瘤（CHL）21例.结果：ALK在ALCL、PTCL和CHL中的阳性率分别为60%（28/47）、0和0;clusterin在三者中的阳性率分别81%（38/47）、27%（6/22）和14%（3/21）,ALK和clusterin在ALCL的阳性率均显著高于PTCL和CHL的阳性率（P＜0.05）,clusterin在ALK阴性的ALCL中的阳性率为68%（13/19）,也显著高于PTCL和CHL的阳性率（P＜0.05）.ALK阳性的ALCL中位年龄20岁（3～70岁）,显著低于ALK阴性者（P＜0.05）,阴性中位年龄48岁（4～71岁）,ALK阳性与否与发生部位、性别无关（P＞0.05）.clusterin的表达与否与年龄、部位和性别均无关（P＞0.05）.结论：ALK在ALCL中的特异性表达对其诊断、鉴别诊断并可能对临床预后判断具有重要价值.clusterin作为一新的分子标志物,在ALCL中的相对特异性高表达对ALCL的诊断、特别是对ALK阴性的ALCL与PTCL和CHL的鉴别诊断将具有重要意义.     

间变性大细胞淋巴瘤

198 5年Stein等[1] 首次描述间变性大细胞淋巴瘤(anaplasticlargecelllymphoma ,ALCL) ,并确认为一种新的淋巴瘤类型。ALCL具有下列特征 :肿瘤细胞呈间变性 ,生长具黏结成团倾向 ,侵犯淋巴结窦 ,间变细胞CD30 (Ki 1)强阳性。ALCL也称之为Ki 1阳性大细胞淋巴瘤。虽然ALCL具有上述共同特征 ,但病理形态、基因表型和临床表现有广泛的异质性 (表 1)。B细胞来源ALCL在REAL和WHO分类中归于弥漫性大B细胞淋巴瘤[2 ,3 ] 。文中如未提到细胞来源 ,则特指T/null细胞ALCL。　　一、病理ALCL诊断性病理特点为淋巴结结构部分消失 ,肿瘤…     

间变性淋巴瘤激酶阳性和阴性间变性大细胞淋巴瘤分子遗传学研究

目的：研究间变性大细胞淋巴瘤（ALCL）的遗传学特征,探讨其发病机制,寻找有助于ALCL诊断、分类及预后评估的新分子靶标。方法收集ALCL病例石蜡包埋组织10例,其中4例间变性淋巴瘤激酶（ALK）阳性,6例ALK阴性。采用免疫组织化学染色及荧光原位杂交技术分别检测表型及2p23重排,利用OncoScan芯片在全基因组水平上扫描分析10例ALCL的拷贝数变异。结果10例ALCL均存在拷贝数变异,拷贝数获得者多于拷贝数缺失者。拷贝数获得主要累及17q11.2、Xp22.3、Xq28,拷贝数缺失主要累及3q26.1、14q11.2、22q11.23。 ALK阴性者拷贝数变异比ALK阳性者更为复杂：ALK阴性者拷贝数获得主要累及9q24.3-24.1、14q32.33,拷贝数缺失主要累及2p11.2、16p13.3,而ALK阳性者并无此变异。结论 ALCL存在复杂的遗传学不平衡,染色体片段获得多于缺失,ALK阴性ALCL遗传学不平衡更为复杂。 ALCL是异质性明显的一类肿瘤。     

间变性大细胞淋巴瘤的ALK和c-myc基因研究

 目的　探讨间变性大细胞淋巴瘤（ALCL）中间变性淋巴瘤激酶（ALK）基因与c-myc基因的分子遗传学改变。方法　收集原发系统性ALCL石蜡包埋组织标本72例,利用间期荧光原位杂交（FISH）技术检测ALCL肿瘤组织中ALK和c-myc基因结构与数目的变化。结果　72例ALCL中,ALK阳性者42例,40例存在涉及ALK基因的染色体易位,其中17例同时伴有ALK基因的多拷贝;ALK阴性的30例均未发现ALK基因的易位,但其中14例存在ALK基因的多拷贝。ALK基因多拷贝的发生率在ALK阳性与 阴性组中的差异无统计学意义（P＞0.05）。72例病例中,均未发现涉及c-myc基因的染色体易位,但其中24例存在c-myc基因的多拷贝。结论　大部分ALCL伴有ALK基因的异常（75.0 %）。以涉及ALK基因的染色体易位最为多见（55.6 %）,ALK基因多拷贝也是ALCL较为常见的遗传学改变（43.1 %）。前者只出现于ALK阳性ALCL中,后者既可出现在ALK阳性也可出现在ALK阴性的ALCL中。ALCL中不见或罕见涉及c-myc基因的染色体易位,但c-myc基因多拷贝的现象较为常见（33.3 %）。     

间变性大细胞淋巴瘤

间变性大细胞淋巴瘤（ＡＬＣＬ）是形态学和免疫学上一种独特类型的非霍奇金淋巴瘤（ＮＨＬ）,它的发生与ｔ（２;５）（ｐ２３;ｑ３５）梁色体易位形成ＡＬＫ－ＮＰＭ融全基因有关。本文综述了ＡＬＣＬ在形态学、免疫学、遗传学和临床方面的特点及其诊断、治疗、预后。     

Research progresses in the pathogenesis of anaplastic large cell lymphoma

Anaplastic large cell lymphoma(ALCL) is a distinct subset of T-cell non-Hodgkin's lymphoma.As a consequence of its low incidence,general pathogenic consideration of ALCL is lacking.In this review,we summarize the pathogenesis,epidemiology,clinical manifestations,and treatment of ALCL,so as to better understand key stages of the development of this disease and provide valuable information for future treatment.     

Targeting autophagy enhances the anti-tumoral action of crizotinib in ALK-positive anaplastic large cell lymphoma

Anaplastic Lymphoma Kinase-positive Anaplastic Large Cell Lymphomas (ALK+ ALCL) occur predominantly in children and young adults. Their treatment, based on aggressive chemotherapy, is not optimal since ALCL patients can still expect a 30% 2-year relapse rate. Tumor relapses are very aggressive and their underlying mechanisms are unknown. Crizotinib is the most advanced ALK tyrosine kinase inhibitor and is already used in clinics to treat ALK-associated cancers. However, crizotinib escape mechanisms have emerged, thus preventing its use in frontline ALCL therapy. The process of autophagy has been proposed as the next target for elimination of the resistance to tyrosine kinase inhibitors. In this study, we investigated whether autophagy is activated in ALCL cells submitted to ALK inactivation (using crizotinib or ALK-targeting siRNA). Classical autophagy read-outs such as autophagosome visualization/quantification by electron microscopy and LC3-B marker turn-over assays were used to demonstrate autophagy induction and flux activation upon ALK inactivation. This was demonstrated to have a cytoprotective role on cell viability and clonogenic assays following combined ALK and autophagy inhibition. Altogether, our results suggest that co-treatment with crizotinib and chloroquine (two drugs already used in clinics) could be beneficial for ALK-positive ALCL patients.     

Long-term remission of primary refractory ALK-positive anaplastic large cell lymphoma after allogeneic hematopoietic stem cell transplantation

ALK-positive anaplastic large cell lymphoma (ALK+ ALCL) has a favorable prognosis in general; however, some cases are resistant to chemotherapy, which leads to a poor clinical outcome. We herein report the case of a 32-year-old male with aggressive ALK+ ALCL who presented with hemorrhage from a large tumor in the duodenum and multiple tumors in the lungs, mediastinum, and peritoneal cavity. Although induction chemotherapy resulted in a marked reduction of the tumor lesions, premature progression with massive pulmonary infiltration and central nervous system invasion occurred immediately after the completion of chemotherapy. The patient was then promptly treated with brentuximab vedotin (BV) and high-dose methotrexate, which resulted in complete remission. Subsequently, he successfully underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT) from an unrelated donor and has been healthy and did not relapse for more than 3 years after transplantation without any additional therapy. Allo-HSCT may be a promising treatment option for ALK+ ALCL due to its graft-versus-lymphoma effect. In addition, molecular targeting agents, such as BV, may be promising as a bridging therapy before allo-HSCT to achieve disease remission.     

Cytomorphologic examination of anaplastic large cell lymphoma by fine‐needle aspiration cytology

BACKGROUND.

The cytomorphology of anaplastic large cell lymphoma (ALCL) is distinctive yet variable. To the authors' knowledge, to date only small case series have described the cytologic findings noted in patients with ALCL. The current series is the largest case series presented to date to retrospectively review the cytomorpholgic findings noted in patients with ALCL, with specific attention paid to those with anaplastic lymphoma kinase (ALK)‐negative ALCL.

METHODS.

Over a 13‐year period, the available Diff‐Quik cytology smears and surgical excision specimens taken from patients with ALCL were evaluated. Different clinical and morphologic parameters were evaluated, including ALK status.

RESULTS.

A total of 37 cases were retrieved and evaluated, 19 of which had both cytology and surgical pathology specimens available for review. ALK‐negative ALCL cytology smears were found to have a high number of anaplastic cells compared with ALK‐positive cases. The hallmark cells in the ALK‐negative cases were not classic.

CONCLUSIONS.

ALCL can be diagnosed accurately by fine‐needle aspiration cytology (FNAC) alone when aided by immunocytochemistry in ALK‐positive cases. Ancillary studies should be anticipated such that material for cell block preparation and molecular studies is taken at the time of FNAC. The results of the current study demonstrate the varied FNAC morphology of ALCL. The presence of severe pleomorphism and anaplasia was found to correlate with ALK‐negative status. Cancer (Cancer Cytopathol( 2007. © 2007 American Cancer Society.     

间变性大细胞淋巴瘤的临床病理与免疫组化研究(附3例报告及文献复习)

目的　研究间变性大细胞淋巴瘤 (ALCL)的临床病理和免疫组化特征。方法　应用免疫组化染色 (SP法 )对 3例ALCL进行免疫表型标记 ,采用了一种新的间变性大细胞淋巴瘤的特异性抗体ALKp80 (间变性淋巴瘤激酶 )。 结果　 3例ALCL的ALKp80均呈强阳性 ,2例CD30 阳性 ,2例LCA阳性 ,2例EMA阳性 ,1例CD685 0 %以上细胞阳性。 3例T、B细胞标记均不表达 ,CD15均呈阴性。结论　ALKp80不仅是ALCL的一个特异性标记物 ,而且对判断ALCL的预后有重要的意义。     

Breast implant-associated anaplastic large cell lymphoma: A comprehensive review

Breast implant-associated anaplastic large cell lymphoma (BIA-ALCL) is a recently recognized non-Hodgkin lymphoma of T-cell origin. Despite the low incidence of this new disease, the increasing use of breast implants for cosmetic or post-mastectomy reconstruction purposes places BIA-ALC as an emerging and compelling medical challenge. The real BIA-ALCL pathogenesis has not been fully uncovered so far, while different putative causal factors have been proposed. Breast implants with textured surfaces seem to be associated with nearly all cases of BIA-ALCL, while the real the risk of disease development has not been well estimated so far. Late onset, persistent seroma around breast implant represents the classical clinical presentation. Most of the BIA-ALCL patients presents with localized disease, which confers an excellent prognosis. Unlike other non-Hodgkin lymphomas, surgical excision of the mass has a key role in the treatment. For patients with advanced and disseminated diseases, the treatment did not differ from other types of T-cell lymphoma. For these reasons, BIA-ALCL represents an emerging disease which requires multidisciplinary team approach to well define diagnostic workup and treatment for each patient. This review article aims to summarize available data on BIA-ALCL. First, we will outline available data on BIA-ALCL epidemiology, pathogenesis, diagnostic work-up, and treatment. Second, we will point out the potential psychological implications as well as the risk of perception distortion for women with breast implants, especially for those with previous breast cancer. Lastly, we will summarize the current national recommendations regarding textured breast implants and discuss the diagnostic-therapeutic algorithm for BIA-ALCL management.     

原发皮肤型间变大细胞淋巴瘤研究进展

原发皮肤型间变大细胞淋巴瘤(PC-ALCL)是一种发生于皮肤的T细胞淋巴瘤,由间变性、多形性或免疫母细胞样大淋巴细胞组成,多数肿瘤细胞(>75%)表达CD30.现就近年来流行病学、生物学特征、临床表现、诊断和鉴别诊断以及治疗、预后等方面的研究进展进行综述.     

42例初治原发系统性间变大细胞淋巴瘤临床特点分析

目的:分析42例初治原发系统性间变大细胞淋巴瘤（ALCL）临床特点。方法:回顾性分析2012年1月至2016年12月河南省肿瘤医院淋巴瘤病区42例初治原发系统性ALCL住院病人的临床资料,根据是否表达间变性淋巴瘤激酶(anaplastic lymphoma kinase ALK)分为ALK＋组和ALK－组。根据临床特征数据的类型,分别采用秩和检验、卡方检验和Student's t检验比较各组临床特征的差异。结果:ALK＋组ALCL患者年龄低于ALK－组患者,差异有统计学意义（P＜0.05）;ALK＋组患者外周血PLT、Ann Arbor分期Ⅲ-Ⅳ比例和EMA表达比例高于ALK－组患者,差异有统计学意义（P均＜0.05）。结论:与ALK－ALCL患者相比,ALK＋ALCL患者年龄较小,有较高的外周血PLT,Ann Arbor分期多为Ⅲ-Ⅳ,有高的EMA表达。