干燥综合征患者唾液腺活检有生发中心形成提示非霍奇金淋巴瘤
发表者：张颖健翻译
日期：2015-03-09
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摘要 背景：鉴于原发性干燥综合征（pSS）发生非霍奇金淋巴瘤（NHL）的风险增高，故寻找淋巴瘤形成的生物标记至关重要。
目的：了解pSS唾液腺活检有生发中心形成是否预示着NHL？生发中心形成是否与NHL的其他标记如低补体血症、CD4+T淋巴细胞血症、皮肤血管炎及腮腺肿大有关？
方法：瑞典两个干燥综合征研究中心对174例pSS分别进行了独立双盲的小唾液腺活检，并于Broegelmann研究中心镜下检测生发中心样结构（即细胞密集的暗区和正常腺体中典型的亮区）。由瑞典癌症登记处下属地方干燥综合征登记处确定NHL。观察期为唾液腺活检至淋巴瘤诊断或死亡或结束随访。确诊pSS至活检的时间平均为1周（0-16周），总的观察时间为1859患者年（1月-26年），唾液腺活检至NHL诊断的平均时间为8年（2年4个月-12年7个月）。通过Cox回归分析和Kaplan Meier统计检验比较有和无生发中心形成患者发生NHL的风险。X2检验分析生发中心形成与其他危险因素间的关系。
结果：136例活检示局部涎腺炎（浸润灶≥1），其中43例（32%）有生发中心样结构。发展为NHL的7例中6例（86%）有生发中心样结构，另一例为泪腺MALT-NHL，唇腺活检无涎腺炎。有生发中心样结构者发生NHL的风险是无生发中心样结构者的15倍（HR15.4%，CI：1.85-218，P=0.01；Log等级检验 P=0.001）。GC阳性与SSA/SSB+、淋巴结病、系统性疾病和高风险SS相关（出现下列情况至少一项为高风险SS：低补体血症，CD4+淋巴细胞减少症，皮肤血管炎，腮腺肿大）
结论：pSS患者唇腺生发中心样结构的出现高度预示淋巴瘤形成。这一标志与临床NHL发生高度相关，是评价pSS预后的新指标，可列入应用B细胞靶向治疗患者的筛选指南。
附原文（挪威）：Background: Due to increased risk of NHL in pSS the identification of better markers for lymphoma development is crucial. Objectives: Does GC formation in salivary gland biopsies from the time point of pSS diagnosis predict NHL? Does GC formation correlate with other markers of NHL such as hypocomplementemia, CD4+ -T lymphopenia, skin vasculitis, parotid swelling? Methods: 174 pSS minor salivary gland biopsies from the two Swedish SS centers underwent blind and independent re-evaluation by light-microscopy at the Broegelmann Research Laboratory, Bergen, Norway for the presence of GC-like structures, determined by a densely packed dark zone and a light zone combined with classical focal infiltration within otherwise normal salivary glands. The presence of NHL was determined by linkage of the local SS registries to the Swedish cancer registry. Observation time was defined as time from the salivary gland biopsy until lymphoma diagnosis, death (Swedish death registry) or end of follow-up. The median (IQ range) time between diagnosing pSS and biopsy was 1 week (0-16). The total observation time was 1859 patient years at risk (range:1 mo – 26 yrs).Time between salivary gland biopsy and NHL diagnosis was in median 8 yrs (range:2 yrs and 4 months -12 yrs and 7 months). Statistics: Risk of developing NHL in patients with or without GC formation was compared by Cox regression analysis and Kaplan Meier statistics/log rank test. Associations between GC formation and other risk variables were determined by χ2 statistics.Results: 136 biopsies showed focal sialadenitis (focus score ≥1) at reevaluation. In 43 (32%) of them GC-like structures were detected. Seven patients had developed NHL. Six of them (86%) had GC like-structures, while the seventh (Tear gland MALT-NHL) was judged as non focal sialadenitis in the lip biopsy. Patients with GC-like structures had 15 times increased risk of developing NHL compared to those without. Hazard Ratio 15.4, 95%CI: 1.85-128, p=0.01. Log-rank test: p=0.001. GC positivity correlated with autoantibodies to SSA/SSB, lymphadenopathy, systemic disease, high-risk type of SS (presence of at least one of the following: hypocomplementemia, CD4+lymphopenia, skin vasculitis or parotid swelling) (all p<0.05).Conclusion: The presence of GC-like structures in the diagnostic lip biopsies in pSS is highly predictive of lymphoma development. This marker shows a strong association with clinical NHL occurrence and is an important new prognostic factor in the care of pSS patients. It may be included in guidelines for selection of pSS patients for biological B-cell directed treatment.
引自：E. Theander1, L. Vasaitis2, E. Baecklund2, G. Nordmark2, G. Warfvinge3, R. Jonsson4, M. Jonsson4. 1Department of Rheumatology, Malmö University Hospital, Malmö; 2Department of Rheumatology, Uppsala University, Uppsala; 3Department of Oral Pathology, Malmö University Hospital, Malmö, Sweden; 4Broegelmann Research Laboratory, The Gade Institute, Bergen, Norway. [OP0065] GERMINAL CENTER (GC) FORMATION IN SALIVARY GLAND BIOPSIES IS A NEW AND STRONG PREDICTOR OF NON-HODGKIN'S LYMPHOMA (NHL) IN PRIMARY SJÖGREN'S SYNDROME (PSS). Ann Rheum Dis 2010;69(Suppl3):73 （注：干燥综合症病人或亲属可加QQ群交流，群号： 118194945 ，本网站站长私人微信号： ssgzz88 ）
目的：了解pSS唾液腺活检有生发中心形成是否预示着NHL？生发中心形成是否与NHL的其他标记如低补体血症、CD4+T淋巴细胞血症、皮肤血管炎及腮腺肿大有关？
方法：瑞典两个干燥综合征研究中心对174例pSS分别进行了独立双盲的小唾液腺活检，并于Broegelmann研究中心镜下检测生发中心样结构（即细胞密集的暗区和正常腺体中典型的亮区）。由瑞典癌症登记处下属地方干燥综合征登记处确定NHL。观察期为唾液腺活检至淋巴瘤诊断或死亡或结束随访。确诊pSS至活检的时间平均为1周（0-16周），总的观察时间为1859患者年（1月-26年），唾液腺活检至NHL诊断的平均时间为8年（2年4个月-12年7个月）。通过Cox回归分析和Kaplan Meier统计检验比较有和无生发中心形成患者发生NHL的风险。X2检验分析生发中心形成与其他危险因素间的关系。
结果：136例活检示局部涎腺炎（浸润灶≥1），其中43例（32%）有生发中心样结构。发展为NHL的7例中6例（86%）有生发中心样结构，另一例为泪腺MALT-NHL，唇腺活检无涎腺炎。有生发中心样结构者发生NHL的风险是无生发中心样结构者的15倍（HR15.4%，CI：1.85-218，P=0.01；Log等级检验 P=0.001）。GC阳性与SSA/SSB+、淋巴结病、系统性疾病和高风险SS相关（出现下列情况至少一项为高风险SS：低补体血症，CD4+淋巴细胞减少症，皮肤血管炎，腮腺肿大）
结论：pSS患者唇腺生发中心样结构的出现高度预示淋巴瘤形成。这一标志与临床NHL发生高度相关，是评价pSS预后的新指标，可列入应用B细胞靶向治疗患者的筛选指南。
附原文（挪威）：Background: Due to increased risk of NHL in pSS the identification of better markers for lymphoma development is crucial. Objectives: Does GC formation in salivary gland biopsies from the time point of pSS diagnosis predict NHL? Does GC formation correlate with other markers of NHL such as hypocomplementemia, CD4+ -T lymphopenia, skin vasculitis, parotid swelling? Methods: 174 pSS minor salivary gland biopsies from the two Swedish SS centers underwent blind and independent re-evaluation by light-microscopy at the Broegelmann Research Laboratory, Bergen, Norway for the presence of GC-like structures, determined by a densely packed dark zone and a light zone combined with classical focal infiltration within otherwise normal salivary glands. The presence of NHL was determined by linkage of the local SS registries to the Swedish cancer registry. Observation time was defined as time from the salivary gland biopsy until lymphoma diagnosis, death (Swedish death registry) or end of follow-up. The median (IQ range) time between diagnosing pSS and biopsy was 1 week (0-16). The total observation time was 1859 patient years at risk (range:1 mo – 26 yrs).Time between salivary gland biopsy and NHL diagnosis was in median 8 yrs (range:2 yrs and 4 months -12 yrs and 7 months). Statistics: Risk of developing NHL in patients with or without GC formation was compared by Cox regression analysis and Kaplan Meier statistics/log rank test. Associations between GC formation and other risk variables were determined by χ2 statistics.Results: 136 biopsies showed focal sialadenitis (focus score ≥1) at reevaluation. In 43 (32%) of them GC-like structures were detected. Seven patients had developed NHL. Six of them (86%) had GC like-structures, while the seventh (Tear gland MALT-NHL) was judged as non focal sialadenitis in the lip biopsy. Patients with GC-like structures had 15 times increased risk of developing NHL compared to those without. Hazard Ratio 15.4, 95%CI: 1.85-128, p=0.01. Log-rank test: p=0.001. GC positivity correlated with autoantibodies to SSA/SSB, lymphadenopathy, systemic disease, high-risk type of SS (presence of at least one of the following: hypocomplementemia, CD4+lymphopenia, skin vasculitis or parotid swelling) (all p<0.05).Conclusion: The presence of GC-like structures in the diagnostic lip biopsies in pSS is highly predictive of lymphoma development. This marker shows a strong association with clinical NHL occurrence and is an important new prognostic factor in the care of pSS patients. It may be included in guidelines for selection of pSS patients for biological B-cell directed treatment.
引自：E. Theander1, L. Vasaitis2, E. Baecklund2, G. Nordmark2, G. Warfvinge3, R. Jonsson4, M. Jonsson4. 1Department of Rheumatology, Malmö University Hospital, Malmö; 2Department of Rheumatology, Uppsala University, Uppsala; 3Department of Oral Pathology, Malmö University Hospital, Malmö, Sweden; 4Broegelmann Research Laboratory, The Gade Institute, Bergen, Norway. [OP0065] GERMINAL CENTER (GC) FORMATION IN SALIVARY GLAND BIOPSIES IS A NEW AND STRONG PREDICTOR OF NON-HODGKIN'S LYMPHOMA (NHL) IN PRIMARY SJÖGREN'S SYNDROME (PSS). Ann Rheum Dis 2010;69(Suppl3):73 （注：干燥综合症病人或亲属可加QQ群交流，群号： 118194945 ，本网站站长私人微信号： ssgzz88 ）