间变性淋巴瘤激酶阳性和阴性系统性间变性大细胞淋巴瘤临床病理特征对比研究

目的 探讨间变性淋巴瘤激酶(ALK)阳性和阴性原发性系统性间变性大细胞淋巴瘤(ALCL)与临床病理学特征、免疫表型及分子遗传学之间的差异.方法 收集北京友谊医院病理科2003年lO月至2008年10月活检及会诊中83例ALCL.最后确诊为原发性系统性ALCL 74例,其中有8例未做ALK检测.通过分析临床资料、观察组织形态,采用免疫组织化学EliVision法检测肿瘤细胞表达CD30、ALK、上皮细胞膜抗原(EMA)、CD2、CD3、颗粒酶B/T细胞内抗原(TIA)-1的情况,采用原位杂交的方法检测EB病毒小mRNA,荧光原位杂交(FISH)方法检测染色体是否存在异常.结果 ALK~+ALCL 48例,ALK-ALCL 18例.ALK~+ALCL发病年龄明显较ALK~-ALCL年轻,中位年龄分别为18和36岁,差异有统计学意义(P＜0.05).ALK~+ALCL比ALK~-ALCL患者更多伴有发热症状(33∶4),常常是高热,并且总体存活率(80%∶71%)和中位生存时间(21个月∶12.5个月)更长,但差异均无统计学意义(P＞0.05).ALK~+ALCL更多原发于结内(81%∶56%).ALK~+ALCL和ALK~-ALCL在形态学上差异不明显,多数病例呈弥漫生长,少数表现为结节状生长;66例ALCL中均可以见到标志性细胞,8例有灶状坏死,偶见黏液基质.ALK~+ALCL主要亚型是普通型(35例),其次是淋巴组织细胞型(8例),小淋巴细胞型(3例)和肉瘤型(2例)少见;ALK~-ALCL绝大多数是普通型(17例),仅1例是淋巴组织细胞型.ALK~+ALCL总是同时表达ALK、CD30和EMA;ALK~+ALCL的EMA表达率更高(100%:72%,P＜0.05),ALK~+ALCL的T细胞标记(如CD2/CD3、CD43/CD45RO)的表达率较低,细胞毒性分子表达率较高(P＞0.05).ALCL未检测到EB病毒感染.FISH结果显示4例ALK~+ALCL中1例ALK基因正常,1例基因断裂伴多拷贝,2例仅有断裂;1例ALK~+ALCL中ALK基因正常.结论 ALK~+ALCL与ALK~-ALCL在形态学上没有显著性差异,但在临床特征和免疫表型和分子遗传学特点方面存在一定差异,这些有助于二者的鉴别诊断.     

间变性大细胞淋巴瘤组织间变性淋巴瘤激酶及survivin蛋白表达及其临床意义

目的研究间变性大细胞淋巴瘤（ALCL）中间变性淋巴瘤激酶（ALK）蛋白及survivin蛋白的表达特点及其临床意义。方法应用免疫组织化学LSAB法检测ALK蛋白及survivin蛋白的表达。结果ALK蛋白在81例ALCL中有51例（63％）阳性,30例（37％）阴性。ALK阳性患者预后优于阴性患者（P〈0．05）。survivin蛋白在77例ALCL中均有不同程度的表达,其中高表达33例（42．9％）,低表达44例（57．1％）。survivin的表达与ALK蛋白表达无关（P〉0．05）。预后：Survivin高表达患者较低表达者差（P〈0．05）。在ALK蛋白阳性病例中,survivin高表达患者较低表达者差（P〈0．05）;ALK阴性病例中,survivin的表达状况与预后无关（P〉0．05）。Cox比例风险回归分析表明ALK的表达、体质性症状及survivin的不同表达状况对存活的影响有统计学意义（P〈0．05）,其中ALK的表达对生存的影响最大,survivin表达的影响最小。结论survivin蛋白在ALCL中的表达与ALK蛋白的表达不相关,是一个独立的指标,可有助于判断ALK阳性ALCL病例的预后。     

Biochemical detection of novel anaplastic lymphoma kinase proteins in tissue sections of anaplastic large cell lymphoma.

The (2;5) translocation, found in many T-cell and null cell anaplastic large cell lymphomas (ALCLs), creates a hybrid gene encoding the 80-kd NPM-ALK protein. Typically neoplastic cells show labeling of both nucleus and cytoplasm for anaplastic lymphoma kinase (ALK) and for the N-terminus of nucleophosmin (NPM). However, 10-20% of cases exhibit cytoplasmic labeling only for ALK, indicating the probable presence of variants of the classical (2;5) translocation that do not involve the NPM gene. We report the detection (using Western blotting and an in vitro kinase assay) in seven such ALCL cases, of ALK proteins with molecular masses of 85 kd, 97 kd (one case exhibiting a (2;3)(p23;q21) translocation), 104 kd (one case carried a (1;2)(q21;p23) translocation), and 113 kd. Tyrosine kinase activity was detected in four of these proteins, but the N-terminal portion of NPM could not be detected. These results show how ALCL cases that express ALK proteins other than NPM-ALK can be detected by sensitive biochemical techniques using routine cryostat sections.     

Leukemic phase of mantle cell lymphoma, blastoid variant

Six patients with mantle cell lymphoma, blastoid variant, involving the blood are described. The circulating blast-like cells suggested the possibility of acute leukemias, chronic lymphoproliferative disorders or peripheralized lymphomas. The WBC counts ranged from 3,700 to 249,000/microL (3.7-249.0 x 10(9)/L) and the absolute lymphocyte counts from 1,000 to more than 200,000/microL (1.0 to > 200.0 x 10(9)/L). The peripheral blood smears showed a spectrum of cells, from small mature lymphocytes with irregular nuclei to medium-sized lymphocytes with blast-like chromatin. However, the morphologic features in a lymph node biopsy specimen and the immunophenotype confirmed a diagnosis of mantle cell lymphoma, blastoid variant. By flow cytometry the lymphoma cells expressed B-cell-associated antigens (CD19, CD20 and CD22), coexpressed CD5, lacked CD23, and expressed moderate intensity monoclonal surface immunoglobulin and CD20. Cytogenetic analysis showed the characteristic t(11;14) in 2 of 4 analyzed specimens. Mantle cell lymphoma, blastoid variant, is part of the differential diagnosis for blast-like cells.     

Twelve cases of Ki-1 positive anaplastic large cell lymphoma of skin.

In seven of 12 cases of Ber-H2 (Ki-1) positive anaplastic large cell non-Hodgkin's lymphoma (Ki-1 ALCL) disease remained localised to skin, and in five there was extracutaneous spread. Four patients had histological evidence of pre-existing or coexisting mycosis fungoides, and three patients had a long standing history of eczema or ichthyosis. In two cases the presence of a T phenotype was shown in frozen sections, and in a further six cases a T phenotype was firmly established in paraffin wax sections. Four patients died less than one year after presentation (two with disseminated lymphoma; two from other causes); one died at five years with widespread lymphoma and the remaining seven cases were alive one to 14 1/2 years after presentation. Three of the four patients with associated mycosis fungoides had prolonged survival, contrary to the findings of previous reports which suggest secondary Ki-1 ALCL behaves aggressively. The recognition of these tumours is important because of their relatively good prognosis. The diagnosis can be readily substantiated immunohistochemically, using a simple panel of antibodies.     

梭形细胞间变性大细胞淋巴瘤

1.病例简介:患者男,40岁.2个月前自觉右腹股沟区疼痛,行走时加剧,于2009年6月在外院行B超检查发现腹股沟区多枚淋巴结肿大,直径约4.0～5.0 cm,胰周、腹主动脉及髂血管旁多发低回声实性结节,最大直径为4.5 cm;行CT检查,提示腹膜后、肝门部多发肿大淋巴结.血常规检查:白细胞、中性粒细胞升高,淋巴细胞减少.2009年7月23日手术切除右腹股沟淋巴结.原单位病理诊断:考虑为指状突树突状细胞肿瘤.因多家医院诊断结果存在分歧,遂来我院会诊,详细询问病史,患者既往无其他脏器肿瘤病史.     

Ultrastructural study of 4 cases of Ki-1 positive large anaplastic cell malignant lymphoma

Summary The ultrastructural morphology of 4 cases of large anaplastic cell malignant lymphoma (Ana ML) is reported. Three cases were primary Ana ML and one pleomorphic large T cell lymphoma with some Ki-1 positive cells. All were confirmed by immunohistochemistry on frozen and paraffin sections. The Ki-1 and EMA positive tumour cells had an abundant cytoplasm, with no differentiation and large pale nuclei with multiple compact or dispersed nucleoli. The morphology is that of an activated cell engaged in protein synthesis and/or in the mitotic cycle. These tumour cells resemble to the Hodgkin's and monolobated Reed-Sternberg cells described in Hodgkin's disease.     

Peripheral eosinophilia camouflaging anaplastic large cell lymphoma

Eosinophilia is a nonspecific laboratory finding, often noted incidentally during routine blood analysis. When persistent, eosinophilia can herald an underlying parasitic infection, drug reaction or less commonly, a neoplastic process. Anaplastic large cell lymphoma (ALCL) and tissue eosinophilia has been described; however, such cases have not displayed marked leukocytosis with eosinophilia. This article reports a patient presenting with marked leukocytosis with profound peripheral eosinophilia initially thought to be related to a chronic myeloproliferative disorder, likely chronic eosinophilic leukemia. After further diagnostic evaluation, ALCL was noted in the bone marrow, masked by the myeloid hyperplasia and eosinophilia. This case emphasizes the importance of a full diagnostic workup for T-cell malignancies, including ALCL rather than focusing on the far less common eosinophilia-associated myeloid malignancies in the clinicopathologic setting of marked eosinophilia. Moreover, bone marrow involvement by ALCL is exceedingly rare and when noted, presents as one or more localized lytic lesions. This is the first reported case of ALCL primarily involving bone marrow without radiographic evidence of lytic bone lesions.     

The small cell variant of anaplastic large cell lymphoma

Anaplastic large cell lymphomas constitute a heterogeneous group of hematopoietic neoplasms that are characterized by immunopositivity for CD30 and the presence, in varying degrees, of large, pleomorphic "hallmark" cells. Primary systemic anaplastic lymphoma kinase-positive anaplastic large cell lymphomas are a subset of this group. Numerous heterogeneous histomorphologic patterns have been described in anaplastic lymphoma kinase-positive anaplastic large cell lymphomas, and all patterns tend to have a better prognosis than that found in anaplastic lymphoma kinase-negative cases. We provide a short review of the small cell variant of anaplastic large cell lymphoma to facilitate the diagnosis of this difficult-to-recognize entity, which may be confused with reactive processes, commonly presents with disseminated disease, and pursues an aggressive clinical course.