Department of Pathology, University Medical Center Utrecht, Utrecht University, Heidelberglaan 100, Utrecht, 3584 CX, The Netherlands.
Department of Pulmonology, University Medical Center Utrecht, Utrecht University, Heidelberglaan 100, Utrecht, 3584 CX, The Netherlands.
Virchows Arch. 2023 Apr;482(4):707-720. doi: 10.1007/s00428-022-03446-w. Epub 2022 Nov 12.
Programmed death ligand-1 (PD-L1) immunostaining, which aids clinicians in decision-making on immunotherapy for non-small cell lung cancer (NSCLC) patients, is sometimes performed on cytological specimens. In this study, differences in cytology fixation and cell block (CB) processing between pathology laboratories were assessed, and the influence of these differences on interlaboratory variation in PD-L1 positivity was investigated. Questionnaires on cytology processing were sent to all Dutch laboratories. Information gathered from the responses was added to data on all Dutch NSCLC patients with a mention of PD-L1 testing in their cytopathology report from July 2017 to December 2018, retrieved from PALGA (the nationwide network and registry of histo- and cytopathology in the Netherlands). Case mix-adjusted PD-L1 positivity rates were determined for laboratories with known fixation and CB method. The influence of differences in cytology processing on interlaboratory variation in PD-L1 positivity was assessed by comparing positivity rates adjusted for differences in the variables fixative and CB method with positivity rates not adjusted for differences in these variables. Twenty-eight laboratories responded to the survey and reported 19 different combinations of fixation and CB method. Interlaboratory variation in PD-L1 positivity was assessed in 19 laboratories. Correcting for differences in the fixative and CB method resulted in a reduction (from eight (42.1%) to five (26.3%)) in the number of laboratories that differed significantly from the mean in PD-L1 positivity. Substantial variation in cytology fixation and CB processing methods was observed between Dutch pathology laboratories, which partially explains the existing considerable interlaboratory variation in PD-L1 positivity.
程序性死亡配体-1（PD-L1）免疫组化有助于临床医生为非小细胞肺癌（NSCLC）患者的免疫治疗做出决策，有时会对细胞学标本进行检测。本研究评估了不同病理实验室之间在细胞学固定和细胞块（CB）处理方面的差异，并研究了这些差异对 PD-L1 阳性率的实验室间差异的影响。向所有荷兰实验室发送了有关细胞学处理的调查问卷。从答复中收集的信息被添加到 2017 年 7 月至 2018 年 12 月从 PALGA（荷兰全国性的组织病理学和细胞学网络和注册处）检索到的所有荷兰 NSCLC 患者的所有数据中，这些患者的细胞学报告中均提到了 PD-L1 检测。对于已知固定和 CB 方法的实验室，确定了经过病例组合调整的 PD-L1 阳性率。通过比较经过固定剂和 CB 方法差异调整的阳性率与未经过这些变量差异调整的阳性率，评估了细胞学处理差异对 PD-L1 阳性率的实验室间差异的影响。28 个实验室对调查做出了答复，并报告了 19 种不同的固定和 CB 方法组合。在 19 个实验室中评估了 PD-L1 阳性率的实验室间差异。对固定剂和 CB 方法的差异进行校正后，阳性率差异显著的实验室数量从 8 个（42.1%）减少到 5 个（26.3%）。荷兰病理实验室之间观察到细胞学固定和 CB 处理方法存在很大差异，这部分解释了 PD-L1 阳性率存在的相当大的实验室间差异。
