间变性大细胞淋巴瘤的p80蛋白表达及其临床意义

目的 研究染色体易位ｔ（２;５）所形成的嵌合基因ＮＰＭ－ＡＬＫ的蛋白产物－－Ｐ８０蛋白在间变性大细胞淋巴瘤（ＡＬＣＬ）中的表达及与其亚型和预后的关系。方法 对已进行临床、病理和免疫学分析胼有随访资料的１９例ＡＬＣＬ用免疫组织化学ＡＢＣ法标记Ｐ８０蛋白。结果 Ｐ８０蛋白在１９例中有９例呈强阳性,组织学亚型为普通型和小细胞型,无１例为霍金样型（Ｐ〈０．０５）。Ｐ８０蛋白阳性病例的免疫学表型为Ｔ细胞性产     

间变性淋巴瘤激酶阴性的间变性大细胞淋巴瘤中C-MYC和PD-L1基因及蛋白表达的研究

目的:探讨C-MYC和PD-L1基因和蛋白在间变性淋巴瘤激酶阴性的间变性大细胞淋巴瘤（ALK －ALCL）患者中的表达,探讨两者在ALK －ALCL发病机制中的作用以及与临床病理特征的关系。 方法:收集福建省立医院病理科2003年1月至2017年1月ALK －ALCL患者3...     

表达间变性淋巴瘤激酶蛋白的弥漫性大B细胞淋巴瘤的临床病理和免疫表型观察

目的探讨表达间变性淋巴瘤激酶（ALK）蛋白的弥漫性大B细胞淋巴瘤（DLBCL）的临床病理特点。方法根据2001年版WHO淋巴造血组织肿瘤分类收集945例DLBCL,以LSAB法作ALK-11染色。对阳性病例再用EnVision法作ALK-11染色,仅EnVision法阳性病例为最终纳入病例。对纳入病例标本用LSAB法加做CD20、CD3、CD30、上皮细胞膜抗原（EMA）、粒酶B、T细胞胞质内抗原（TIA）-1和浆细胞（PC）抗体等免疫表型检测,进行IgH基因重排检测并收集随访资料。结果945例弥漫性大B细胞淋巴瘤中仅5例表达ALK蛋白。4例男性,1例女性,年龄34—72岁,全部原发于淋巴结。临床分期Ⅰ期1例、Ⅱ期2例、Ⅲ期2例。5例随访最长32个月,最短4个月。随访截止时死亡4例,死亡病例最长存活时间32个月。表达ALK蛋白的DLBCL包括中心母细胞性2例、免疫母细胞性1例、间变性1例、浆母细胞性1例;2例中心母细胞性、1例免疫母细胞性和1例间变性均表达CD20。浆母细胞性表达K轻链而不表达CD20。5例均检测到IgH基因重排。ALK蛋白表达：在CD20阳性4例中,1例免疫母细胞性为胞膜和胞质阳性,2例中心母细胞性和1例间变性为胞质颗粒状阳性;1例浆母细胞性为胞核和胞质弥漫阳性。结论ALK蛋白阳性表达DLBLC是一种罕见的,临床过程具侵袭性且预后较差的淋巴瘤,可见于浆母细胞性、中心母细胞性、免疫母细胞性和间变性的大B细胞淋巴瘤。发现1例ALK蛋白表达于胞膜和胞质。     

小儿间变性大细胞性淋巴瘤

目的 :探讨小儿间变性大细胞性淋巴瘤的临床、病理及预后。方法 :对 17例外检和尸检小儿间变性大细胞性淋巴瘤的临床资料、病理切片和随访结果进行分析。结果 :间变性大细胞性淋巴瘤占小儿非霍奇金淋巴瘤的 12 8% ;临床表现主要是外周淋巴结肿大及皮肤损害 ,长期反复发热常见 ;病理特征为淋巴结部分受累 ,成片异形大细胞侵犯淋巴窦及副皮质区 ,免疫组化CD30强阳性 ;预后相对较好。结论 :小儿间变性大细胞性淋巴瘤并不少见 ,需与恶性组织细胞增生症、T区或多形T淋巴瘤、霍奇金淋巴瘤、蕈样霉菌病和转移性癌等鉴别。CD30、CD15、LCA和EMA免疫酶标检查对诊断及鉴别诊断十分有用。     

间变性大细胞性淋巴瘤--浆细胞样小细胞变型

1　临床资料患者男 ,2 7岁。临床表现为左腹股沟包块伴皮肤破溃 ,查体发现 1 2ｃｍ× 0 8ｃｍ× 0 5ｃｍ的包块 ,在当地医院体检未发现明显异常 ,切除包块并送病检。标本经常规 10 %福尔马林液固定 ,石蜡包埋 ,切片 ,分别进行ＨＥ染色及免疫组织化学染色。病理诊断 :“高度疑为淋巴浆细胞性淋巴瘤” ,后来我院病理科会诊。2　病理检查2 .1　镜检　低倍镜下表现为淋巴结结构不清、完全破坏 ,瘤细胞侵犯淋巴结周围组织 ,瘤细胞呈弥漫性、浸润性、破坏性生长 ,局部区域出现大片坏死。高倍镜下见大部分瘤细胞排列疏松。细胞间缺乏粘附 ,局部区…     

间变性大细胞淋巴瘤形态学及免疫表型观察

目的：探讨间变性大细胞淋巴瘤（ALCL）的形态学和免疫表型特征。方法：对6例ALCL和2例弥温性大B细胞淋巴瘤（DLBCL）进行形态学和免疫组织化学染色（ABC法）观察。结果：6例ALCL中，普通型2例、淋巴组织细胞型2例、ALK－变型2例，均可见单型性或多形性的标志性大细胞。普通型和ALK－变型大细胞沿淋巴窦内生长，而淋巴组织细胞型大细胞则呈散在分布；2例DLBCL形态上颇似ALCL；6例ALCL均为T细胞，CD30＋，儿童患者共同表达ALK＋和EMA＋，年长者则ALK－和EMA－。2例DLBCL均为B细胞，ALK＋、CD30－和EMA－。结论：不论何型ALCL，均可见CD30＋的标志性大细胞，淋巴窦内生长多见于普通型和ALK－变型。ALCK均为T细胞，儿童常有ALK和EMA共同表达，年长者则ALK和EMA－。DLBCL的免疫表型不同于ALCL。     

间变性大细胞淋巴瘤临床病理分析

目的：研究间变性大细胞淋巴瘤（ALCL）的临床病理特点。方法；在光镜下对ALCL分型，用免疫组化ABC法研究ALCL的免疫表型特点，使用的抗体有CD45、CD3、CD45RO、CD20、CD79、CD30、CD15、EMA、ALK1、CD68、S－100蛋白、CK、HMB45。结果：28例ALCL均强烈表达CD30，除5例为B细胞性外，18例为T细胞性，5例为裸细胞性。其中多形性7例，单形必7例（包括原发皮肤ALCL2例），淋巴组织细胞性4例，富于粒细胞性5例。结论：ALCL具有较广的细胞学范围，免疫组化在诊断与鉴别诊断中有重要作用。     

非霍奇金淋巴瘤与p53蛋白表达的关系

目的 :探讨非霍奇金淋巴瘤 (NHL)与 p5 3蛋白表达的关系。 方法 :用免疫组化S P法检测 10 2例 (低度恶性 2 3例 ,中度恶性 36例 ,高度恶性 4 3例 )NHLp5 3蛋白表达 ,根据 p5 3蛋白阳性细胞百分率将其表达水平分为 4级 :0级 (阴性 ) ,1级 (1%～ 2 5 % ) ,2级 (2 6 %～ 5 0 % ) ,3级 (>5 0 % )。结果 :低度恶性组 2 0 / 2 3(87% )p5 3表达为 0级 ,中度恶性组 31/ 36 (86 1% )表达为 1级 ,高度恶性组 33/ 4 3(76 7% )表达为 2～ 3级。 2 5例随访 7～ 6 8个月 ,p5 30～ 1级NHL完全缓解率 (CRR ,11/ 14 )高于p5 32～ 3级NHLCRR (1/ 11,P <0 0 1) ,前者生存率 (13/ 14 )高于后者 (3/ 11,P <0 0 1)。NHLp5 3蛋白表达水平与其恶性度密切相关 (P <0 0 1)。结论 :p5 3蛋白表达阳性细胞百分率是判断NHL恶性度、疗效及预后较可靠的参数。肿瘤性p5 3蛋白表达检测对中高度恶性NHL的诊断有参考价值     

间变性大细胞淋巴瘤的临床病理和免疫组织化学分析

目的 了解间变性大细胞淋巴瘤的临床病理特点,免疫表型和生物学行为。方法 对８例ＡＬＣＬ进行临床病理和免疫组织化学ＡＢＣ法观察及随访６－２５个月。结果 ８例ＡＬＣＬ占同期淋巴瘤的４．１％。平均年龄４０岁,男性和女性各４例。皮肤型２例,全身型６例。临床分为Ⅰ期２例,Ⅱ期１例,Ⅲ期５例。     

Caspase-4在霍奇金及间变性大细胞淋巴瘤中的表达

目的:在利用基因芯片技术研究霍奇金氏淋巴瘤(HL)及间变性大细胞淋巴瘤(ALCL)细胞株凋亡相关基因的表达时发现caspase-4 在两者的mRNA表达水平存在明显差异的基础上,我们拟检测caspase-4在HL 及ALCL肿瘤组织中蛋白质水平的表达及试图探讨它们的表达与此两种淋巴瘤的发生机制的关系。方法:选取临床手术切除、石蜡包埋的标本HL 18例、ALCL 15例,4 μm厚连续切片,HE染色及CD30(Ber-H2)、CD15(C3D-1)、CD20(L26)、CD45RO(UCHL1) 等免疫组织化学染色,通过形态学和免疫分型进行严格的病例筛选,确定诊断。切片经微波抗原修复,抗caspase-4抗体(SP法)染片,DAB显色,光学显微镜高倍镜下计数阳性细胞。结果:在ALCL组,15/15例(100%)均高表达caspase-4;而在HL病例组16例(88.8%)不表达、2例(11.2%)弱表达caspase-4,两者表达差异显著(P<0.01)。结论:①Caspase-4在两种淋巴瘤中的表达存在明显差异,即在ALCL的表达明显高于在HL的表达。Caspase-4在HL和ALCL中表达的显著差异,提示两种肿瘤在发生发展的过程中存在不同的病理机制以及细胞凋亡信号转导途径受损部位不同。②Caspase-4的表达特点有助于HL及ALCL的鉴别诊断。     

Expression of p63 in anaplastic large cell lymphoma but not in classical Hodgkin's lymphoma

Immunohistochemical determination of p63 protein is frequently used in the pathologic diagnosis of nonhematological solid tumors. In malignant hematological disease, p63 expression has been reported in 22% of follicular lymphoma, about 35% of diffuse large B-cell lymphoma, 23% of chronic lymphocytic leukemia, and in some cases of blast crisis of chronic myelogenous leukemia. Anaplastic large cell lymphoma is a rare disease that accounts for less than 5% of all cases of non-Hodgkin's lymphoma. There is little information concerning p63 expression in this specific type of lymphoma. In some cases, the morphological and phenotypic features between anaplastic large cell lymphoma and classical Hodgkin's lymphoma are similar, making this differential diagnosis challenging. We studied p63 expression using a tissue microarray approach in 154 cases of anaplastic large cell lymphoma, including 38% anaplastic large cell kinase positive and 62% anaplastic large cell kinase negative, and 58 Hodgkin's lymphoma cases. Sixty-eight cases of anaplastic large cell lymphoma (44%) showed p63 nuclear positivity (41% of anaplastic large cell kinase positive and 47% of anaplastic large cell kinase negative). Of 130 cases of systemic-anaplastic large cell lymphoma, 42% showed p63 positivity. The neoplastic cells expressed p63 in 38% of the cases of CD45-negative/anaplastic large cell kinase-negative null cell-type anaplastic large cell lymphoma, a subgroup that offers the most difficulties in the differential diagnosis with classical Hodgkin's lymphoma. In contrast, none of the cases of classical Hodgkin's lymphoma demonstrated any p63 expression. These results demonstrate that p63 protein expression is frequently expressed in a subset of anaplastic large cell lymphoma cases and may be used as a potential tool in the differential diagnosis between anaplastic large cell lymphoma and classical Hodgkin's lymphoma.     

间变性淋巴瘤激酶在神经母细胞瘤的表达及其意义

目的探讨间变性淋巴瘤激酶(anaplastic lymphoma kinase,ALK)在神经母细胞瘤(neuroblastoma,NB)中的表达及与预后的关系。方法应用免疫组化EnVision法检测NB内ALK的表达情况,应用国际NB病理分类及分期系统进行病理分类及分期,结合随访资料分析ALK的表达程度与预后之间的关系。结果 80例NB中ALK阳性70例,阳性率为87.5%,阳性表达定位于肿瘤细胞胞质及神经毡内,Schwannian纤维及间质中血管、淋巴细胞均阴性。ALK的表达程度在肿瘤的不同临床分期之间差异明显;患者的平均生存时间与ALK表达程度有关。结论 ALK在NB中异常表达,且其表达水平和NB的侵袭性及预后之间存在联系,即高表达间变性淋巴瘤激酶的肿瘤,更具有侵袭性,预后较差。     

Oncogenic anaplastic lymphoma kinase (ALK) mutation in neuroblastomas and other pediatric tumors

Neuroblastoma (NB) is one of the most common malignant pediatric tumors that show aggressive behavior. Most advanced-stage NBs have proven refractory to many treatment modalities, and a fundamental alternative therapy, such as inhibition of biological pathways, is now being explored. Anaplastic lymphoma kinase (ALK) has recently been identified as an activation mutation in familial or high-risk sporadic NBs. We examined the prevalence of the ALK mutation in 54 NB cases (23 pre-treatment cases and 31 cases for which specimens were available before and after treatment) and the presence of the ALK mutation in various pediatric tumors. We detected the ALK mutation (F1174C and R1275Q) in 2 (3.7%) of the 54 NB specimens. Both cases showed poorly differentiated and advanced-stage NBs. No ALK mutations were detected in other pediatric tumors. The frequency of the ALK mutation was somewhat lower than that expected in Korean patients with NBs. The mutation detected in the present study was one of the hotspot mutations, including positions of F1174 and R1275 reported previously. The results of the present study suggest the possibility of potential roles of ALK inhibitors in the therapeutics of a small population of neuroblastoma carrying mutated ALK kinases.     

Anaplastic lymphoma kinase-positive anaplastic large cell lymphoma presenting as retroperitoneal fibrosis

Retroperitoneal fibrosis is a rare fibroinflammatory condition involving the abdominal aorta, iliac vessels, and ureters that carries an association with several other autoimmune conditions. Most cases of retroperitoneal fibrosis are thought to be idiopathic. The disorder can affect all age groups but is most common in persons between the ages of 50 and 70 years. A subset of cases is associated with an underlying immunohematologic abnormality including lymphoma. We describe in this case report a highly unusual presentation of a young woman who died with a diagnosis of "idiopathic retroperitoneal fibrosis" based on multiple biopsy procedures. Postmortem examination, however, revealed disseminated anaplastic lymphoma kinase-positive anaplastic large cell lymphoma. The clinical and histopathologic importance of this very unusual presentation of anaplastic lymphoma kinase-positive anaplastic large cell lymphoma with retroperitoneal fibrosis is discussed.     

ALK-negative anaplastic large cell lymphoma primarily involving the bronchus: a case report and literature review

Anaplastic large cell lymphoma (ALCL) is a mature T cell lymphoma with characteristic morphologic, immunophenotypic and cytogenetic features. Current WHO classification includes anaplastic lymphoma kinase (ALK)-positive and ALK-negative variants. ALCL rarely presents with obstructive symptoms of the main airway. In addition to reporting a HIV-associated bronchial ALK-negative ALCL in a 44 year-old female, our literature review identified eight cases of bronchial ALCL with several interesting clinicopathological features, including: 1) a female predominance (67%); 2) two thirds of patients younger than 18 years old; 3) uniformly presented with respiratory symptoms and progressed to respiratory failure; 4) the tumor involving the main airways; 5) often with localized disease at the initial presentation. This unusual presentation of ALCL may pose as a diagnostic pitfall and delay the treatment.     

Intrinsic apoptotic pathway in anaplastic large cell lymphoma

Anaplastic large cell lymphoma (ALCL) includes a subset of tumors that has abnormalities of chromosome 2p23, resulting in overexpression of anaplastic lymphoma kinase (ALK). Previous studies have reported differences in apoptotic rate and expression levels of apoptosis regulatory proteins between ALK+ and ALK- ALCL. In this study, we assessed for expression of the intrinsic apoptotic pathway proteins cytochrome c, apoptosis protease-activating factor 1, and procaspase 9 in 2 ALK+ ALCL cell lines and 42 ALCL tumors (17 ALK+, 25 ALK-). We used the Karpas 299 and SU-DHL-1 cell lines, and the inhibitors Z-LEHD-FMK (specific for caspase 9) and Boc-D-FMK (general caspase inhibitor) to investigate the role of caspase 9 activation in chemotherapy-induced apoptotic cell death. Caspase 9 activity was significantly increased in Karpas-299 and SU-DHL-1 cells after chemotherapy treatment, but remained as low as control levels with addition of either caspase inhibitor. Both caspase inhibitors rescued a substantial fraction of Karpas 299 and SU-DHL-1 cells from drug-induced cell death. In ALCL tumors, expression of cytochrome c, apoptosis protease-activating factor 1, and procaspase 9 was also assessed and correlated with apoptotic rate and activated caspase 3 levels. Cytochrome c was expressed in all 13 (100%) ALK+ and 18 (95%) of 19 ALK- ALCL tumors. Apoptosis protease-activating factor 1 was detected in 14 (88%) of 16 ALK+ and 19 (79%) of 24 ALK- ALCL tumors. Procaspase 9 was expressed in 5 (30%) of 17 ALK+ and 2 (8%) of 25 ALK- ALCL tumors (P = .09). In the entire study group (ALK+ and ALK- ALCL), procaspase 9 expression levels significantly correlated with apoptotic rate (P = .02) and activated caspase 3 levels (P = .05). This correlation could not be shown in the ALK+ or ALK- ALCL subgroups, presumably because of the small sample size. In conclusion, chemotherapy-induced cell death in ALK+ ALCL cells involves the intrinsic apoptotic pathway, and apoptosome function may be an important determinant of apoptosis in ALCL tumors.     

Primary systemic anaplastic large cell lymphoma in Korean adults: 11 years' experience at Asan Medical Center

PURPOSE: Anaplastic large cell lymphoma (ALCL), a CD30+ T-cell non-Hodgkin's lymphoma, represents only 2-8% of lymphoma overall. Information on the clinical findings of primary systemic ALCL in Korea is limited. Our aims were to report the clinical features and outcomes of primary systemic ALCL. PATIENTS AND METHODS: We retrospectively reviewed the medical records of 36 adult patients diagnosed with primary systemic ALCL at Asan Medical Center from February 1995 through June 2006. RESULTS: Of 36 patients, 29 were male. The median age was 39 years (range, 17-67 years), and 26 (72%) presented with Ann Arbor stages III and IV. The most commonly involved extranodal sites were bone (n = 7) and soft tissue (n = 6). Thirty-two of all patients (89%) were treated with an anthracycline-based regimen including cyclophosphamide/doxorubicin/vincristine/prednisone (CHOP) as induction chemotherapy; 16 (50%) achieved complete remission (CR), and 13 (41%) achieved partial remission (PR). Median overall survival (OS) and event-free survival (EFS) were 49 and 17 months, respectively. Univariate analysis showed that performance status (p = 0.035), international prognostic index (IPI) (p = 0.025), and age-adjusted IPI (p = 0.034) were significant prognostic factors for OS, whereas anaplastic lymphoma kinase (ALK) expression did not affect OS (p = 0.483). CONCLUSION: Our retrospective analysis of Korean primary systemic ALCL patients showed that median OS was 49 months and overall response to CHOP was 91%. Performance, IPI, and age-adjusted IPI were predictors of OS, whereas ALK expression did not have prognostic significance.     

荧光原位杂交检测石蜡包埋间变性大细胞淋巴瘤病例中ALK基因转位及其意义

目的　比较荧光原位杂交 (fluorescence in situ hybridization,FISH)和免疫组织化学在检测间变性大细胞淋巴瘤 (anaplastic large cell lymphoma,AL CL )中间变性淋巴瘤激酶 (anaplastic lymphomakinase,AL K)基因转位及其融合蛋白中的作用 ,并探讨 FISH在石蜡包埋组织中的应用。方法　采用双色FISH和免疫组织化学检测 2 2例石蜡包埋 AL CL病例中 AL K基因转位及其融合蛋白。结果　通过调整组织切片的酶消化时间等优化措施 ,成功地在石蜡切片上进行了双色 FISH实验 ;FISH和免疫组织化学均在 6 0 % (12 /2 0 )系统性 AL CL中检测到 AL K基因转位或融合蛋白 ,在 2例皮肤原发 AL CL中未检测到基因转位或融合蛋白 ,两种方法的符合率为 10 0 %。结论　 (1)在检测 AL CL中有无 AL K基因转位时 ,AL K蛋白免疫组化由于其简单、快捷、价廉成为一般情况下的首选方法 ;在具备 FISH条件时 ,也可以将 FISH作为首选 ;(2 )通过优化实验条件 ,可以在石蜡包埋组织上成功地进行 FISH实验。