眼附属器淋巴组织增生性病变的临床病理和分子遗传学特征及其意义

目的 分析眼附属器淋巴组织增生性病变的临床病理特点,探讨其分子遗传学特征及其意义.方法 收集1995-2007年37例眼附属器淋巴组织增生性病变石蜡组织标本(其中5例为反应性增生性病变,32例为淋巴瘤),依据2001年WHO肿瘤分类标准对32例淋巴瘤标本重新诊断分类.采用IgH、MALT1、bcl-6、c-Mye、bcl-2、CCND1、bcl-10、FOXP1双色分离重排探针、IgH/bcl-2双色融合易位探针和18号染色体着丝粒探针,利用间期荧光原位杂交(FISH)的方法 检测眼附属器淋巴组织增生性病变的分子遗传学特点.结果 32例淋巴瘤均为非霍奇金B细胞淋巴瘤.其中,黏膜相关淋巴组织结外边缘区B细胞淋巴瘤(MALT)淋巴瘤28例(87.5%),滤泡性淋巴瘤2例,弥漫性大B细胞淋巴瘤2例.60.7%(17/28)的眼附属器MALT淋巴瘤携带分子遗传学异常.其中,IgH基因断裂1例,但未找到与其发生相互易位的伙伴基因;基因3拷贝者16例,其中MALT1基因、bcl-6基因和c-Myc基因3拷贝的发生率分别为25%(7/28)、43%(12/28)和7%(2/28).16例基因3拷贝病例中,两种基因3拷贝合并存在者5例,其中bcl-6基因合并MALT1基因3拷贝者4例,bcl-6基因合并c-Myc基因3拷贝者1例.进一步研究显示,MALT1基因3拷贝者均存在18号染色体三体.2例滤泡性淋巴瘤都携带t(14;18)(q32;q21)/IgH-bcl-2.2例弥漫性大B细胞淋巴瘤均存在遗传学异常,1例表现为bcl-6基因3拷贝合并18号染色体三体,另1例表现为bcl-6基因3拷贝合并IgH和c-Myc基因双断裂.5例反应性淋巴组织增牛性标本均未见分子遗传学异常.结论 MALT淋巴瘤是眼附属器最常见的淋巴瘤类型;间期FISH有助于淋巴组织增生性病变的良恶性鉴别及淋巴瘤的分类;MALTI基因3拷贝者由18号染色体三体所致;18号染色体三体和bcl-6基因3拷贝(可能为3号染色体三体所致)是眼附属器MALT淋巴瘤常见的分子遗传学异常.

Primary ocular adnexal lymphoproliferative lesions: clinicopathologic features and genetic alterations

Objective To investigate clinicopathological and genetic characteristics of primary ocular adnexal lymphoproliferative lesions.Methods Clinical,morphological and immunohistochemical features of 37 archival cases of primary ocular adnexal lymphoproliferative lesions were studied including 5 cases of reactive lymphoid hyperplasia and 32 lymphomns retrospectively.Classification of the lymphomas were made according to the WHO classification of tumors of haematopeietic and lymphoid tissues.All cases were studied by interphase fluorescence in situ hybridization (FISH) using dual color break apart probes of IgH,MALT1,bcl-6,c-Myc,bcl-2,CCND1,bcl-10,and FOXP1 for detection of chromosomal aberrations involving IgH,MALT1,bcl-6,c-Myc,bcl-2,cyclinD1,bcl-10 and FOXP1 genes,respectively.FISH with IgH / bcl-2 dual color dual fusion probe was used for detection of t(14;18)(q32;q21)/IgH-bcl-2.CEP18 spectrum orange probe was used for detection of aneuploidy of the chromosome 18.Results Among 32 cases of lymphomas,28 cases (87.5%) were extranodal marginal zone B-cell lymphomas of mucesa associated lymphoid tissue (MALT lymphoma),2 cases were follicular lymphoma (FL) and 2 cases diffuse large B cell lymphoma (DLBCL).Among the 28 cases of MALT lymphoma,chromosomal aberrations were found in 60.7% (17/28) by interphase FISH analysis.One case showed positive lgH break-apart signal with unknown partner.16 cases showed three copies of different genes,of which,three copies of MALT1,bcl-6,and c-Myc were identified in 7 cases (25%),12 cases (43%),and 2 cases (8%) of MALT lymphomas,respectively.In addition,5 cases showed two genes including three copies of bcl-6 and MALT1 in 4 cases,and three copies of bcl-6 together with c-Myc in one ease.Furthermore,all cases with three copies of MALTI had trisomy 18.t(14;18) (q32;q21) was detected in beth follicular lymphomas.Of the 2 DLBCL cases,one showed three copies of bcl-6 together with trisomy 18 and the other one showed three copies of bcl-6 together with IgH and c-Myc rearrangements.Chromosomal aberration was not found in all 5 cases of reactive lymphoid hyperplasia.Conclusions The most common entity of primary ocular adnexal lymphomas is MALT lymphoma and FISH is helpful for their differential diagnosis and claasification.Trisomy 18 and three copies of bel-6 are common chromosomal aberrations in primary ocular adnexal MALT lymphomas.