眼附属器黏膜相关淋巴组织型淋巴瘤和反应性淋巴组织增生的鉴别诊断研究

目的　探讨诊断和鉴别诊断眼附属器黏膜相关淋巴组织 (MALT)型淋巴瘤和淋巴组织反应性增生的方法。方法　对 2 9例眼附属器MALT淋巴瘤和 8例淋巴组织反应性增生进行临床、形态学、免疫组化和分子生物学的研究。结果　 2 9例眼附属器MALT淋巴瘤和 8例淋巴组织反应性增生的临床表现相似 ,差异无显著意义。在病理学的诊断中 ,2 9例眼附属器MALT淋巴瘤全部表达B细胞标记 ,不表达T细胞标记 ;免疫球蛋白轻链κ或λ限制 1 1例 ;PCR检测单克隆增生 1 5例 ,无特异表达 1 4例。 8例淋巴组织反应性增生中 ,7例同时表达B细胞标记和T细胞标记 ,且T细胞标记 >30 %;κ和λ阴性 ;PCR检测呈多克隆增生。结论　在眼附属器MALT型淋巴瘤和淋巴组织反应性增生的鉴别诊断中 ,免疫组化和分子生物学技术有助于进一步明确诊断。     

脂多糖诱导的肿瘤坏死因子-α基因在眼附属器非霍奇金淋巴瘤的表达及意义

目的 研究脂多糖诱导的肿瘤坏死因子-α(lipopolysaccharide-induced TNF-α factor,LITAF)基因在眼附属器非霍奇金淋巴瘤中的表达,并探讨其与临床病理参数间的关系.方法 采用免疫组织化学法对从青岛大学附属医院收集的50例眼附属器非霍奇金淋巴瘤标本和10例反应性淋巴组织增生病变组织标本中LITAF基因的表达进行检测,并分析其与眼附属器非霍奇金淋巴瘤患者临床病理参数间的关系.结果 眼附属器非霍奇金淋巴瘤中LITAF基因阳性表达率显著低于反应性淋巴组织增生病变(P＜0.05);LITAF基因的阳性表达率与性别、年龄、发病部位、肿瘤大小无关(均为P＞0.05),与非霍奇金淋巴瘤病理分级有关(P＜0.05).结论 LITAF基因可能发挥着抑制眼附属器非霍奇金淋巴瘤的功能.     

Skp2,p27在眼附属器黏膜相关淋巴组织结外边缘区B细胞淋巴瘤中的表达和意义

目的：探讨眼附属器黏膜相关淋巴组织结外边缘区B细胞淋巴瘤(mucosa-associated lymphoid tissue lymphoma of ocular adnexal,MALT lymphoma of ocular adnexal)中Skp2和p27的表达及联系。

方法：收集1995～2011年青岛大学附属医院眼科切除的眼附属器MALT淋巴瘤患者及眼部反应性淋巴组织增生患者的石蜡包埋标本,用免疫组化法分别检测两组标本中Skp2和p27的表达。

结果：眼附属器 MALT淋巴瘤中Skp2 表达率与眼部反应性淋巴组织增生相比显著增高(P<0.05)。p27表达率与反应性淋巴组织增生相比显著降低(P<0.05)。Skp2和p27的表达与患者Ann Arbor病理分级无关。在眼附属器MALT淋巴瘤中Skp2与p27成负相关(r=-0.129,χ²=15.39,P<0.05)。

结论：综合分析眼附属器MALT淋巴瘤中P27及SKP2的表达对本病的预后有一定意义。两者的表达彼此相关。     

免疫球蛋白重链基因重排检测对眼附属器淋巴增生性病变的诊断研究

目的 探讨多聚酶链反应(PCR)检测免疫球蛋白重链(IgH)基因重排在眼附属器淋巴增生性病变良恶性鉴别中的应用价值.设计 实验性研究.研究对象 32例眼附属器淋巴增生性病变存档蜡块标本.方法 应用PCR检测眼附属器淋巴增生性病变的IgH基因重排,结合常规HE染色和免疫组织化学染色结果进行分析.主要指标 组织病理形态,免疫表型特征及基因重排形式.结果 17例淋巴瘤中12例IgH基因呈单克隆性重排,阳性率为70.6%;10例反应性淋巴细胞增生中1例呈单克隆性重排,阳性率为10%.两者差异有统计学意义(P=O.004).5例不典型淋巴细胞增生中,3例基因呈单克隆性重排,支持恶性淋巴瘤的诊断;2例呈多克隆性重排,支持良性反应性增生的诊断.结论 依靠常规HE染色和免疫组织化学染色有时难以明确眼附属器淋巴增生性病变的良恶性,此时应用PCR检测病变的IgH基因重排,有助于鉴别其良恶性.(眼科,2008,17:33-36)     

Skp2，p27,PTEN在眼附属器B细胞非霍杰金淋巴瘤中的表达

目的:探讨眼附属器B细胞非霍杰金淋巴瘤(B-cell non-Hodgkin lymphoma, NHL)中Skp2,p27和PTEN的表达。方法:收集1995年到2011年青岛大学附属医院眼科石蜡包埋标本,用免疫组化法分别检测眼附属器B细胞NHL(n=30) 标本中Skp2,p27和PTEN的表达,以眼部反应性淋巴组织增生(n=10)作为对照组。以患者的年龄、性别、发病部位,病理类型作为眼附属器B细胞NHL的的分类标准。结果:Skp2,p27和PTEN的表达与患者的年龄、性别、发病部位无关,而与病例类型有关。眼附属器B细胞NHL Skp2表达率与眼部反应性淋巴组织增生相比显著增高。 p27,PTEN表达率与反应性淋巴组织增生相比显著降低。随眼附属器B细胞NHL病理分级的提高,Skp2的表达显著增高,p27和PTEN的表达显著降低。在黏膜相关淋巴组织结(mucosa-associated lymphoid tissue, MALT)外边缘区B细胞淋巴瘤（diffuse large B-cell lymphoma, DLBCL）中,Skp2分别与p27,PTEN成负相关,p27和PTEN成正相关。结论: Skp2的表达升高,p27,PTEN蛋白的缺失以及可能与眼附属器B细胞NHL的发生有关;其中在MALT外边缘区DLBCL中,三种蛋白存在相关性。联合三种蛋白的检测眼附属器B细胞NHL的不同病理类型有重要意义。     

眼附属器淋巴组织增生性病变增殖细胞核抗原的表达及其与组织学分型的关系

应用增殖细胞核抗原单克隆抗体（ＰＣ１０）对眼附属器淋巴组织增生性病变３４例（炎性假瘤５例，淋巴组织反应性增生９例，不典型淋巴组织增生９例，恶性淋巴瘤１１例）标本石腊切片进行免疫组化（ＡＢＣ法）染色。结果显示炎性假瘤与反应性淋巴组织增生ＰＣＮＡ计数相差不显著（Ｐ＞０．０５），反应性增生与后二者ＰＣＮＡ计数之间均有显著的差异（Ｐ＜０．０５，Ｐ＜０．００１），不典型淋巴组织增生与恶性淋巴瘤之间阳性细胞均值差异显著（Ｐ＜０．０５）。认为ＰＣＮＡ计数有助于区别眼附属器淋巴组织增生性病变的良、恶性，本技术用于研究眼附属器淋巴组织增生性病变尚未见报道。     

114例眼附属器淋巴增生性病变的病理分析

目的：探讨眼附属器淋巴增生性病变的组织病理学分类。方法：对114例患者局部切除的眼附属淋巴增生性病变标本进行回顾性分析。结果：反应性淋巴样增生27例,非典型性增生7例,恶性淋巴瘤80例。80例恶性淋巴瘤包括76例原发性肿瘤和6例继发性肿瘤。粘膜相关组织细胞来源的恶性淋巴瘤有66例（89.19％）。结论：眼附属器原发性恶性淋巴瘤多数为粘膜相关组织细胞来源的恶性淋巴瘤。     

眼眶及眼附属器黏膜相关B细胞淋巴瘤中BCL10表达和染色体易位的检测

目的 研究眼眶及眼附属器黏膜相关(OA-MALT)淋巴瘤中BCL10蛋白表达及染色体易位情况.方法 收集60例OA-MALT淋巴瘤患者的标本,采用免疫组织化学法检测BCL10蛋白的表达,用荧光素原位杂交(FISH)法分别检测AP12-MALT1融合基因、BCL10、MALT1及IgH基因的异常.采用交叉分组设计,对结果进行Fisher精确检验.结果 OA-MALT淋巴瘤中BCLI0蛋白表达的阳性率为85.0%(51/60),其中胞质阳性率为41.7%(25/60),胞核阳性率为43.3%(26/60).FISH结果显示除2例患者有API2.MALTI融合基因外,其余患者的BCL10基因和IgH基因均未发现异常.统计学分析显示OA-MALT淋巴瘤中BCL10蛋白核表达不依赖于染色体异常(P=0.184).结论 OA.MALT淋巴瘤中有较高的BCL10蛋白核表达率,对OA-MALT淋巴瘤的诊断有一定的辅助价值.在全身其他部位MALT淋巴瘤中报道的染色体易位,在OA-MALT淋巴瘤中并不常见.     

MTDH与β-catenin在眼附属器淋巴瘤中的表达及意义

目的:探讨眼附属器淋巴瘤中MTDH与β-catenin的表达情况及临床意义.方法:收集青岛大学附属医院眼科1995-06/2015-12手术切除并确诊为眼附属器B细胞非霍奇金淋巴瘤(non-Hodgkin lymphoma,NHL)的病理标本40例,以同期手术切除的眼部反应性淋巴组织增生组织20例作为对照组.采用PCR法检测淋巴瘤组与对照组中MTDH与β-catenin的mRNA表达情况;采用免疫组化法检测两组中MTDH与β-catenin的蛋白表达情况,并分析其与眼附属器淋巴瘤临床特征的关系.结果:与对照组相比,眼附属器淋巴瘤中MTDH与β-catenin的mRNA与蛋白表达均显著增加(P＜0.05).MTDH与β-catenin蛋白的阳性表达率与淋巴瘤的病理类型有关,随肿瘤恶性程度的增高,其表达增加(P＜0.05),而与发病年龄、性别及部位无关(P＞0.05).在眼附属器淋巴瘤中,MTDH与β-catenin的蛋白表达呈正相关(r=0.389,P＜0.05).结论:MTDH与β-catenin的高表达可能与眼附属器淋巴瘤的发生发展有关,且两者表现为正相关.     

眼科首诊的黏膜相关淋巴组织淋巴瘤一例

黏膜相关淋巴组织（mucosa associated lymphoid tissue,MALT）淋巴瘤是一种淋巴结外淋巴瘤,常见部位包括胃肠道、肺、甲状腺、涎腺、眼眶等,眼附属器MALT淋巴瘤是眼附属器最常见的淋巴瘤,     

BCL10 expression in ocular adnexal lymphomas

PURPOSE: To study BCL10 expression in ocular adnexal lymphoma in the US population and its association with clinical outcomes. DESIGN: Institutional, retrospective study. METHODS: Immunohistochemistry was performed with antibody against BCL10 on two tissue microarray blocks that were constructed with paraffin-embedded tissues from the same cohort of 48 patients with ocular adnexal lymphomas. The main outcomes that were measured include extraorbital involvement, recurrence rate, and time to recurrence. The median length of the follow-up period was 40 months. RESULTS: Aberrant BCL10 expression (nuclear [moderate intensity] and cytoplasmic [weak to moderate intensity] staining) was observed in 10 of 33 cases (30.3%) of mucosa-associated lymphoid tissue (MALT) lymphoma, in 4 of 10 cases (40%) of follicular lymphoma (grade 1, 9 cases; grade 2, 1 case), in 0 of 2 cases of diffused large B-cell lymphoma, in 0 of 1 case of chronic lymphocytic leukemia/small lymphocytic lymphoma and in 1 of 1 case (100%) of mantle cell lymphoma. There were no differences in clinical parameters at examination (ie, average age, gender, site of occurrence, laterality, extraorbital involvement at diagnosis), recurrence rate, and time to recurrence for patients (MALT lymphoma or follicular lymphoma) with or without aberrant nuclear BCL10 expression. CONCLUSION: Aberrant BCL10 expression can occur in other types of ocular adnexal lymphomas besides MALT lymphoma. Ocular adnexal MALT lymphoma may have slightly lower frequency of aberrant BCL10 expression than gastric/pulmonary MALT lymphomas that have been reported in the literature. Furthermore, aberrant BCL10 nuclear expression in ocular adnexal lymphoma does not seem to correlate with clinical outcome. Further studies that include a larger number of cases and longer follow-up period are needed to confirm our observation.     

112例眼附属器淋巴增生性病变临床组织病理学初步分析

目的初步探讨眼附属器淋巴增生性病变的发病情况、临床特征以及组织病理学特点和分型。方法收集112例经组织病理学诊断为眼附属器淋巴增生性病变患者的116份石蜡切片标本,分析归纳临床相关资料,进一步分析组织病理学特点,并根据2001年世界卫生组织淋巴及血液组织肿瘤分类方案进行重新分类诊断。结果患者年龄8～80岁,平均49岁。病程20d至22年,平均22个月。双眼患病者16例（14．3％）。临床常见表现为眼球突出、局限性肿块（69例,占61．6％）。组织病理学检查显示反应性淋巴细胞增生11例（9．8％）,非典型淋巴细胞增生10例（8．9％）,淋巴瘤91例（81．3％）。其中,黏膜相关组织型边缘带B细胞淋巴瘤74例（占淋巴瘤患者81．3％）。结论眼附属器淋巴增生性病变以黏膜相关组织边缘带B细胞淋巴瘤最为多见,好发于中老年人,临床表现为慢性迁延性病程,双眼发病并不少见。（中华眼科杂志,2005,41：871-876）     

The expressions of metadherin and LEF-1 in mucosa-associated lymphoid tissue lymphoma of ocular adnexal

AIM: To investigate the expressions of metadherin (astrocyte elevated gene-1, AEG-1) and lymphoid enhancer-binding factor-1 (LEF-1) in ocular adnexal mucosa-associated lymphoid tissue (MALT) lymphoma. METHODS: The expressions of AEG-1 and LEF-1 were detected on specimens harvested from patients suffering from MALT lymphoma and lymphadenosis of ocular adnexal in Ophthalmology Department, Affiliated Hospital of Qingdao University from 2000 to 2015 by immunohistochemical and polymerase chain reaction (PCR) analysis. RESULTS: AEG-1 and LEF-1 expressions in MALT lymphoma was respectively higher than that in lymphadenosis, both by immunohistochemical and PCR analysis (P<0.05). Diversity of AEG-1 and LEF-1 expressions in different Ann Arbor clinical stages showed a statistically significant result (P<0.05). A positive relevance between AEG-1 and LEF-1 was observed in MALT ocular adnexal lymphoma (r=0.435, P=0.016). CONCLUSION: The over expressions of AEG-1 and LEF-1 at the level of protein and mRNA participates in the tumorigenesis of ocular adnexal MALT lymphoma. They should act as a new biological marker for pathological diagnosis in the future.     

B-Cells in ocular adnexal lymphoproliferative lesions express B-cell attracting chemokine 1 (CXCL13)

PURPOSE: The homeostatic chemokine, B cell attracting chemokine 1 (CXCL13), has been implicated in the pathogenesis of lymphocyte-mediated diseases. We investigated the cellular expression of this chemokine in the spectrum of ocular adnexal lymphoproliferative lesions. DESIGN: Laboratory investigation. METHODS: CXCL13 expression in paraffin-embedded adnexal biopsy specimens was determined by indirect immunohistochemistry with antigen retrieval. RESULTS: In 15 of 16 biopsy specimens, including reactive lymphoid hyperplasia (n = 7), atypical lymphoid hyperplasia (n = 3), and B cell lymphoma (n = 6), CXCL13 was detected. CD20-positive B-cells, as well as dendritic cells and endothelial cells, expressed the chemokine. CONCLUSIONS: B-cells in ocular adnexal lymphoproliferative lesions demonstrate expression of CXCL13, a chemokine that may participate in tumor pathogenesis and is a potential target for novel therapies.     

Ocular adnexal lymphoma-comparison of MALT lymphoma with other histological types.

AIMS: To correlate histological features of ocular adnexal lymphoma using the revised European American lymphoma classification (REAL), with stage of disease at presentation, treatment modalities, and patient outcome. MALT lymphoma defines an extranodal marginal zone B cell lymphoma as outlined in the REAL classification. Comparison groups of patients included those with primary ocular adnexal MALT lymphoma versus primary ocular adnexal lymphomas of other types, MALT lymphoma versus non-MALT lymphomas (primary and secondary), and primary ocular adnexal lymphoma (MALT lymphomas and other types) versus secondary ocular adnexal lymphomas. METHODS: A retrospective review of the National Ophthalmic Pathology Laboratory records identified 20 cases of ocular adnexal lymphoma over a 10 year period which were reclassified using appropriate immunohistochemical stains. Patients' medical records were examined for data including stage of the disease at presentation, mode of treatment, and patient outcome. RESULTS: Among the 20 cases identified 14 had primary ocular adnexal lymphomas. 10 of the primary lymphomas had histological features of MALT lymphoma. One case was a primary ocular adnexal T cell lymphoma, one a follicular centre, follicular B cell lymphoma, and two were large cell B cell lymphomas. Six cases had systemic disease, four large B cell, one follicular centre, follicular B cell, and one mantle cell. A significantly higher proportion of patients with MALT lymphomas had early disease (p = 0.005), initially required local treatment (p = 0.005) and were alive at last follow up (p = 0.001) than those without. Two patients with MALT lymphoma had recurrence of lymphoma which responded to further treatment. CONCLUSIONS: Patients with primary ocular adnexal MALT lymphomas present with localised disease requiring local treatment and have a better outcome compared with patients with other types. As a small percentage of these tumours recur, patients should be followed up indefinitely.     

聚合酶链反应扩增IgH CDR-Ⅲ序列对眼部淋巴样增生病的诊断研究

目的从分子生物学角度探讨眼部淋巴样增生病的诊断、分类及肿瘤细胞的起源。方法应用聚合酶链反应（ｐｏｌｙｍｅｒａｓｅｃｈａｉｎｒｅａｃｔｉｏｎ,ＰＣＲ）对２９例（３１只眼）眼部淋巴样增生病的石蜡切片进行免疫球蛋白重链基因第三互补决定区（ＩｇＨＣＤＲ－Ⅲ）重排检测,并结合形态学及免疫表型进行分析检查。结果１７只眼恶性淋巴瘤、５只眼反应性增生均呈ＩｇＨ基因克隆性重排,电泳产物可见一明显的扩增窄带（１００～１２０ｂｐ）,其中２例双眼恶性淋巴瘤的两侧病变扩增带一致,１只眼恶性淋巴瘤、８只眼反应性增生均呈ＩｇＨ基因多克隆性重排。结论采用ＰＣＲ扩增ＩｇＨＣＤＲ－Ⅲ序列能确定此类疾病的克隆性质,并能发现免疫组化及形态学不能识别的小克隆Ｂ细胞病变,为诊断眼部淋巴样增生病提供了一个较为客观、敏感而又实用的手段。     

眼附属器MALT淋巴瘤的临床分析

目的 探讨黏膜相关组织淋巴瘤(MALT)在眼附属器包括眼睑、眼眶、泪腺等部位的特殊临床特征与治疗方法.方法 回顾性分析32例眼附属器MALT淋巴瘤患者的临床表现、B超、CT、MRI检查结果,病理组织学和免疫组织化学结果以及综合治疗疗效与预后情况.结果 32例眼附属器MALT淋巴瘤患者中男22例,女10例;年龄23.0～74.0岁,平均年龄64.1岁.18例发生于结膜,占56.3%(18/32);9例发生于眼眶,占28.1%(9/32);5例发生于泪腺,占15.6%(5/32).B超检查肿块多表现为内回声不均匀(84.4%,27/32)或内回声高(28.1%,9/32);CT检查多表现为中等密度(43.8±10.7)HU,密度均匀(84.6%,22/26);MRI检查T1WI及T2WI多呈等信号,信号均匀.影像学检查后均行手术治疗联合放疗.随访1～12年,复发率为12.5%(4/32).结论 影像学检查可辅助诊断眼附属器MALT淋巴瘤,术后病理活体检查及免疫组织化学分型检查可确诊本病,眼附属器MALT淋巴瘤若早期诊断和治疗(手术治疗联合术后放疗)则预后较好.     

眼部淋巴组织增生性病变PCNA和AgNORs的观察

目的：探讨眼部淋巴组织增生性病变的增殖活性与组织学分型的关系。方法：应用抗增殖细胞核抗原的单克隆抗体ＰＣ１０和ＡｇＮＯＲｓ技术，对３４例眼附属器淋巴组织增生性病变（包括良性淋巴组织增生１４例，不典型增生９例，恶性淋巴瘤１１例）的石腊切片进行检测。结果：良性淋巴组织增生与后二者ＰＣＮＡ及ＡｇＮＯＲｓ计数之间均有非常显著的差异（ＰＣＮＡ Ｐ〈０．００１，ＡｇＮＯＲｓＰ〈０．０１及Ｐ〈０．００１），不典