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。     

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.     

ALK阳性大B细胞淋巴瘤3例临床病理及分子遗传学分析

目的探讨间变性淋巴瘤激酶(anaplastic lymphoma kinase,ALK)阳性的弥漫性大B细胞淋巴瘤(diffuse large B-cell lym-phoma,DLBCL)的临床病理及分子遗传学特点。方法对3例ALK(+)DLBCL进行光镜观察、免疫组化及荧光原位杂交检测,并复习相关文献。结果镜下观察淋巴结结构破坏,可见淋巴窦侵犯,肿瘤细胞大,呈免疫母细胞样,免疫组化示肿瘤细胞ALK、Bob-1、CD4、CD10、CD45、CD56、CD138、EMA、MUM1、Oct-2均(+),CD20、CD79a、PAX-5、CD3和CD30均(-),3例荧光原位杂交均检测到ALK基因易位。结论 ALK(+)DLBCL是一种DLBCL的少见独立亚型,具有特征性免疫表型、形态学及分子遗传学特点。     

Clinicopathologic and genetic features of anaplastic lymphoma kinase (ALK)-positive diffuse large B-cell lymphoma:report of 3 cases

目的 探讨间变性淋巴瘤激酶(anaplastic lymphoma kinase,ALK)阳性的弥漫性大B细胞淋巴瘤(diffuse large B-cell lymphoma,DLBCL)的临床病理及分子遗传学特点.方法 对3例ALK(+) DLBCL进行光镜观察、免疫组化及荧光原位杂交检测,并复习相关文献.结果 镜下观察淋巴结结构破坏,可见淋巴窦侵犯,肿瘤细胞大,呈免疫母细胞样,免疫组化示肿瘤细胞ALK、Bob-1、CD4、CD10、CD45、CD56、CD138、EMA、MUM1、Oct-2均(+),CD20、CD79a、PAX-5、CD3和CD30均(-),3例荧光原位杂交均检测到ALK基因易位.结论 ALK(+) DLBCL是一种DLBCL的少见独立亚型,具有特征性免疫表型、形态学及分子遗传学特点.     

原发系统性间变性大细胞淋巴瘤分子分型的病理学研究

目的探讨间变性大细胞淋巴瘤(anaplastic large cell lymphoma,ALCL)分子分型及免疫表型特点,为ALCL的分型、诊断、治疗和预后提供依据。方法采用免疫组化EnVision法对40例原发系统性ALCL进行分子分型,以是否表达间变性淋巴瘤激酶(anaplastic lymphoma kinase,ALK)免疫标记分为ALK+组和ALK-组,分析其临床病理特征及CD30、ALK、T细胞标记、细胞毒相关抗原、EMA、Galectin-3的表达特点。结果 ALCL患者以男性多见,ALK+病例明显多于ALK-,青少年患者多为ALK+,ALK-常见于中老年患者。形态学上ALK+和ALK-较难鉴别,瘤细胞均强表达CD30,两组CD45RO、Galectin-3、CD43、细胞毒相关抗原表达无差异,多为(+)。ALK+者多表达EMA,瘤细胞大部分表达T细胞抗原CD2、CD4、CD45RO,CD5、CD7(-),CD8、CD3常(-);ALK-瘤细胞大部分表达T细胞抗原CD3、CD2、CD4、CD5,少数表达CD8、EMA;EBV+的ALK+组和ALK-组各1例,两者Ki-67增殖指数均>70%,差异无显著性。结论形态学相同的ALCL,通过免疫组化检测ALK蛋白可将其分为ALK+和ALK-两个独立的分子亚型,二者具有不同的临床特点、免疫表型及预后。     

结肠原发性CD3O阳性间变性大细胞淋巴瘤1例报道及文献复习

目的 探讨结肠原发问变性大细胞淋巴瘤(ALCL)的组织学特点及免疫组化特征。方法 运用组织形态学、免疫组化方法研究1例发生在结肠的间变性大细胞淋巴瘤并结合文献进行讨论。结果 间变性大细胞淋巴瘤其形态学表现为多样性，免疫组化显示CD30 ，另外CD45、CD45RO、CD3和EMA也可 。结论 间变性大细胞淋巴瘤发生在结肠非常罕见，其形态学和免疫组化表型有一定的特殊性，并且预后良好，有必要与其它类型淋巴瘤、霍奇金淋巴瘤、恶性组织细胞增生症、恶性黑色素瘤、低分化腺癌等进行鉴别。     

乳腺原发性ALK阴性的间变性大细胞淋巴瘤1例并文献复习

目的 探讨乳腺原发性间变性大细胞激酶(anaplastic large-cell kinase,ALK)阴性的间变性大细胞淋巴瘤(anaplastic large cell lymphoma,ALCL)的临床病理特征、免疫表型及其与乳腺植入物的关联.方法 采用HE及免疫组化EnVision两步法观察1例乳腺原发性ALK阴性的ALCL,并结合文献探讨.结果 肿瘤组织瘤细胞呈弥散分布,形态多样,胞质丰富,略呈嗜碱性,核形态多样,可见切迹,核仁较清晰.免疫表型:肿瘤细胞表达CD30、CD3、CD43、EMA,Ki-67增殖指数约80%,不表达ALK、CD20、CD10、CD56、PAX-5、TIA及MPO.结论 ALK阴性的ALCL是一种罕见的外周T细胞淋巴瘤,结合组织学特征及免疫组化染色有助于诊断与鉴别诊断.     

ALK阳性大B细胞淋巴瘤2例并文献复习

目的探讨间变性淋巴瘤激酶(anaplastic lymphoma kinase,ALK)阳性大B细胞淋巴瘤(large B cell lymphoma,LBCL)的临床病理学特征。方法采用免疫组化En Vision法和FISH法检测2例ALK+LBCL,分析患者的临床资料、组织学特征、免疫表型,并结合文献进行复习。结果镜下见淋巴结结构破坏,肿瘤细胞沿淋巴窦性生长或弥漫性生长,呈片、巢状分布,肿瘤细胞中等偏大,核仁较圆,胞质丰富,嗜碱性或嗜双色性,可见明显嗜双色核,呈免疫母细胞样和(或)浆母细胞样特点。免疫表型:ALK、CD138、CD4、CD45、EMA、Κappa、MUM1、Oct-2、Bob-1均阳性; CD3、CD5、CD20、CD79a、Pax-5、CD56均阴性。FISH检测2例患者均为ALK基因断裂,并发现ALK-EML4基因融合。结论 LBCL是弥漫大B细胞淋巴瘤的罕见类型,具有特征性的形态学、免疫表型和分子遗传学特点。     

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。     

原发性肾上腺淋巴瘤8例临床病理分析

目的探讨原发性肾上腺淋巴瘤(primary adrenal lymphoma, PAL)的临床病理学特征。方法回顾性分析8例PAL的临床病理学特征、免疫表型及EBER、荧光原位杂交结果,并复习相关文献。结果 8例中男性7例,女性1例。6例弥漫大B细胞淋巴瘤(diffuse large B cell lymphoma, DLBCL)中2例呈中心母细胞型、3例免疫母细胞型、1例间变型;1例中心母细胞型肿瘤细胞伴浆样分化。免疫表型:6例DLBCL均表达PAX-5及CD20,GCB型2例,non-GCB型4例;1例肿瘤细胞共表达CD5及MYC/BCL-6/BCL-2,1例表达ALK;6例DLBCL均示高增殖指数,Ki-67增殖指数70%～90%。2例为结外鼻型NK/T细胞淋巴瘤(NK/T cell lymphoma, NK/TCL),表达CD3、GrB、CD56,均不表达CD5,Ki-67增殖指数均为80%,EBER原位杂交结果均阳性。4例诊断为DLBCL,非特指型,1例CD5阳性三表达DLBCL,1例ALK阳性DLBCL;2例结外鼻型NK/TCL。结论 PAL以恶性度较高的病理类型多见,临床易与其他肾上腺肿瘤混淆,确诊依赖术后病理检查,且需结合免疫组化、FISH等结果。     

Bone marrow involvement in NPM-ALK-positive lymphoma: report of two cases.

Two cases of NPM-ALK-positive anaplastic large cell lymphoma (ALCL) with bone marrow involvement are reported. These cases were recognized within a group of NPM-ALK-positive ALCLs (n = 6) by using immunohistochemistry with the ALK1 monoclonal antibody. In case 1, the bone marrow showed diffuse infiltration of round to spindle-shaped lymphoma cells with moderate fibrosis. In case 2, lymphoma cells intermingling with hematopoietic cells could only be identified by immunohistochemical staining. In contrast to the four NPM-ALK-positive ALCL cases, which showed a cohesive growth pattern in the lymph nodes, the two cases reported here displayed lymphoma cells of smaller size, and they were classified as lymphohistiocytic variants histologically. ALK1 stained small-sized components more clearly than did CD30 (HRS-4). These results suggest that bone marrow involvement of NPM-ALK-positive ALCL may be frequently associated with a histological variant showing a small-sized cell component, and that ALK1 immunostaining is a useful tool to investigate lymphomas for bone marrow involvement.     

MUC1 (EMA) is preferentially expressed by ALK positive anaplastic large cell lymphoma, in the normally glycosylated or only partly hypoglycosylated form.

AIMS: To investigate whether MUC1 mucin, a high molecular weight transmembrane glycoprotein, also known as epithelial membrane antigen (EMA), differs in its expression and degree of glycosylation between anaplastic large cell lymphoma (ALCL) and classic Hodgkin's disease (HD), and whether MUC1 immunostaining can be used to differentiate between CD30 positive large cell lymphomas. METHODS/RESULTS: Using five different monoclonal antibodies (E29/anti-EMA, DF3, 139H2, VU-4H5, and SM3) that distinguish between various MUC1 glycoforms, high MUC1 expression (50-95% of tumour cells positive) was found in 13 of 17 anaplastic lymphoma kinase (ALK) positive systemic nodal ALCLs, and in one of 20 cases of classic HD. Scattered or focal staining (< 25% of tumour cells) was seen in two additional ALK positive systemic ALCLs, two additional classic HD cases, and in three of 20 cases of ALK negative systemic nodal ALCL. Primary cutaneous ALCL showed no staining with the anti-MUC1 antibodies. Antibodies detecting hypoglycosylated MUC1 were found to be absent in all lymphomas (SM3) or present in only six of 15 ALK positive ALCLs (VU-4H5). CONCLUSIONS: MUC1 is preferentially expressed by a subtype of systemic nodal ALCL, characterised by ALK expression, but is found in only a few cases of classic HD and ALK negative ALCL. Therefore, although MUC1 could be used in a panel of markers for CD30 positive lymphomas, it is probably not a valuable tool to differentiate between ALK negative CD30 positive large cell lymphomas. Finally, the degree of MUC1 glycosylation in lymphomas is relatively high, compared with the aberrant hypoglycosylation found in adenocarcinomas.     

Anaplastic large cell lymphoma: the shifting sands of diagnostic hematopathology.

Anaplastic large cell lymphoma (ALCL) is a paradigm for the process used to define new disease entities, and provides a model that is applicable to all areas of pathology. ALCL was first recognized based on characteristic histologic features (sinusoidal invasion) and a distinctive immunophenotype (CD30+). However, neither sinusoidal invasion nor CD30-positivity proved to be entirely specific. Subsequently, a characteristic cytogenetic abnormality was identified, the t(2;5), that led to identification of the genes involved in the translocation (NPM/ALK) and insights into the pathogenesis. Generation of monoclonal antibodies to the aberrantly expressed anaplastic large cell lymphoma kinase (ALK) such as ALK-1 can be used diagnostically, and have led to improved definition of the diagnostic entity with important clinical and prognostic implications. These studies also have clarified the relationship of ALCL to Hodgkin's disease, another lymphoid malignancy associated with CD30 expression. We have learned that the ultimate histologic spectrum of ALCL is both narrower and broader than originally believed. The small cell and lymphohistiocytic variants of ALCL are ALK-positive, and are an accepted part of the disease entity, although the neoplastic cells may appear neither large nor anaplastic. Conversely, most cases of Hodgkin's-like ALCL have proved to be more closely related to true Hodgkin's disease, and are unrelated to ALCL.     

Primary anaplastic large cell lymphoma in the dura of the brain: case report and prediction of a favorable prognosis

Anaplastic large cell lymphoma (ALCL) is a rare T-cell lymphoma composed of CD30-positive lymphoid cells. ALCL arising in the dura matter of the brain is even more infrequent, in which only one case has been reported worldwide so far. We report a case of a 30-year-old immunocompetent male with a dura-based mass, radiographically consistent with meningioma. However, the excised mass via a left parieto-occipital craniotomy was composed of large, pleomorphic lymphoid cells to be immunopositive for CD3, CD30, anaplastic lymphoma kinase protein-1 (ALK-1) and epithelial membrane antigen (EMA), and immunonegative for CD20, CD15 and CD68. Multiple ALK gene fusion signals in the ALK locus were detected by fluorescence in situ hybridization (FISH) analysis. The patient was treated with CHOP chemotherapy and intrathecal methotrexate along with brain radiation therapy, which resulted in a complete remission. In an analysis of 25 previously reported primary CNS ALCLs, ALK-1 positivity was shown to be prevalent in younger age, as ALCL occurs outside the brain. Patient less than 23 years, ALK-1 positivity and unifocal tumor may be associated with a better prognosis. However, sex, dural or leptomeningeal involvement, immune status, and tumor necrosis do not appear to have any influence on survival.