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.

Clinicopathologic features of 66 cases of anaplastic lymphoma kinase positive and negative systemic anaplastic large cell lymphoma:a comparative study

Objective To study the clinicopathologie features of 66 cases of primary systemic anaplastic large cell lymphoma(ALCL),with emphasis on the differences between ALK-positive and ALK-negative cases.Methods The clinical data of 66 cases of ALCL was analyzed The histologic features were reviewed.Immunohistochemical study for CD30,ALK protein,epithelial membrane antigen,CD2,CD3,granzyme B and TIA-1 was carried out.In-situ hybridizationfor small mRNA of Epstein-Barr virus(EBER)was also performed.The chromosomal abnormalities were studied by fluorescence in-situ hybridization (FISH).The differences between ALK-positive and ALK-negative cases were statistically analyzed.Results There were 48 cases of ALK-positive ALCL and 18 cases of ALK-negative ALCL.The patients with ALK-positive ALCL were younger than those with ALK-negative ALCL(P＜0.05),with the median age being 18 years and 36 years,respectively.Fever,especially hyperpyrexia,was more commonly observed in ALK-positive ALCL patients than in ALK-negative ALCL patients(33 cases versus 4 eases,P＜0.05).The overall survival rate and median duration of survival in patients with ALK-positive ALCL were higher and longer than those in patients with ALK-negative ALCL(80%versus 71%;21 months versus 12.5 months,P＞0.05).There were however no significant differences in histology between ALK-positive ALCL and ALK-negative ALCL.Histologically,most cases showed diffuse growth pattern.Nodular pattern was demonstrated in a minority of cases."Hallmark" cells were seen in most of the ALCL cases.Focal necrosis and myxomatous stroma were identified in a few cases.Most ALK-positive cases belonged to the common variant(35 cases).A small number represented lymphohistiocytic variant(8 cases).Small cell variant and sarcomatoid subtype were found only in few cases(3 cases and 2 cases,respectively).On the other hand,common variant(17 cases)constituted the majority of ALK-negative ALCL.Lymphohistiocytic variant was seen in only 1 case.Immunohistochemical study showed that ALK-positive ALCL always expressed CD30 and epithelial membrane antigen.ALK-positive ALCL more often expressed epithelial membrane antigen(100%versus 72%;P＜0.05)but less so for T-cell markers(including CD2,CD3,CD43 and CD45RO).Cytotoxic molecules were more commonly expressed in ALK-positive ALCL(P＞0.05).EBER was negative in all cases studied.FISH showed that in ALK-positive ALCL,1 case had normal ALK gene,1 had deletion and multicopy and 2 had deletion.On the other hand,1 case of ALK-negative ALCL had normal ALK gene.Conclusions While there are no significant morphologic differences between ALK-positive ALCL and ALK-negative ALCL,the clinical features,immunophenotypes and genetic features of both groups vary.These differences are helpful in guiding the differential diagnosis.