Department of Rheumatology, Skåne University Hospital Malmö, Lund University, Lund, Sweden.
Ann Rheum Dis. 2011 Aug;70(8):1363-8. doi: 10.1136/ard.2010.144782.
The development of non-Hodgkin's lymphoma (NHL) confers a high risk of mortality in primary Sjögren's syndrome (pSS) patients, but the sensitivity and specificity of proposed lymphoma predictors are insufficient for practical use. The performance of lymphoid organisation in the form of germinal centre (GC)-like lesions was evaluated in labial salivary gland biopsies taken at pSS diagnosis as a potential lymphoma-predicting biomarker.
Labial salivary gland tissue biopsies available from two Swedish pSS research cohorts (n=175) were re-evaluated by light microscopy in a blind study in order to identify GC-like structures as a sign of ectopic lymphoid tissue formation and organisation. A linkage study was performed with the Swedish Cancer Registry for lymphoma identification. The risk of developing NHL in GC-positive patients in comparison with GC-negative patients was evaluated using Kaplan-Meier statistics and log-rank test. Associations between GC-like structures and clinical and/or laboratory disease markers were also determined using χ(2) or Fisher's exact tests.
At diagnosis, 25% of pSS patients had GC-like structures in their salivary glands. Seven of the 175 patients studied (14% GC+ and 0.8% GC-) developed NHL during 1855 patient-years at risk, with a median onset of 7 years following the initial diagnostic salivary gland biopsy. Six of the seven patients had GC-like structures at diagnosis; the remaining patient was GC negative at the time of diagnosis (p=0.001).
The detection of GC-like structures by light microscopy in pSS diagnostic salivary biopsies is proposed as a highly predictive and easy-to-obtain marker for NHL development. This allows for risk stratification of patients and the possibility to initiate preventive B-cell-directed therapy.
非霍奇金淋巴瘤(NHL)的发生会增加原发性干燥综合征(pSS)患者的死亡率,但目前提出的淋巴瘤预测因子的敏感性和特异性尚不足以为实际应用提供依据。本研究旨在评估在 pSS 诊断时的唇腺活检中以生发中心(GC)样病变形式出现的淋巴组织形成情况,作为潜在的淋巴瘤预测生物标志物。
对来自两个瑞典 pSS 研究队列(n=175)的唇腺组织活检进行了重新评估,在一项盲法研究中通过光镜观察以确定 GC 样结构是否为异位淋巴组织形成和组织的标志。对瑞典癌症登记处的淋巴瘤病例进行了连锁研究。采用 Kaplan-Meier 统计和对数秩检验评估 GC 阳性患者与 GC 阴性患者发生 NHL 的风险。还使用 χ(2)或 Fisher 确切检验确定 GC 样结构与临床和/或实验室疾病标志物之间的关联。
在诊断时,25%的 pSS 患者的唾液腺中存在 GC 样结构。在研究的 175 例患者中,有 7 例(14%的 GC+和 0.8%的 GC-)在 1855 患者年的风险中发生 NHL,中位发病时间为初次诊断性唾液腺活检后 7 年。6 例患者在诊断时存在 GC 样结构,其余 1 例患者在诊断时为 GC 阴性(p=0.001)。
在 pSS 诊断性唾液活检中通过光镜检测 GC 样结构被提议作为 NHL 发生的高度预测性和易于获得的标志物。这可以对患者进行风险分层,并有可能开始预防性 B 细胞靶向治疗。