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Digital Pathology Applications for PD-L1 Scoring in Head and Neck Squamous Cell Carcinoma: A Challenging Series

JOURNAL OF CLINICAL MEDICINE(2024)

Univ Milano Bicocca | Univ Modena & Reggio Emilia | Sapienza Univ Roma | European Inst Oncol IRCCS | Univ Messina | Univ Sassari

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Abstract
The assessment of programmed death-ligand 1 (PD-L1) combined positive scoring (CPS) in head and neck squamous cell carcinoma (HNSCC) is challenged by pre-analytical and inter-observer variabilities. An educational program to compare the diagnostic performances between local pathologists and a board of pathologists on 11 challenging cases from different Italian pathology centers stained with PD-L1 immunohistochemistry on a digital pathology platform is reported. A laboratory-developed test (LDT) using both 22C3 (Dako) and SP263 (Ventana) clones on Dako or Ventana platforms was compared with the companion diagnostic (CDx) Dako 22C3 pharm Dx assay. A computational approach was performed to assess possible correlations between stain features and pathologists’ visual assessments. Technical discordances were noted in five cases (LDT vs. CDx, 45%), due to an abnormal nuclear/cytoplasmic diaminobenzidine (DAB) stain in LDT (n = 2, 18%) and due to variation in terms of intensity, dirty background, and DAB droplets (n = 3, 27%). Interpretative discordances were noted in six cases (LDT vs. CDx, 54%). CPS remained unchanged, increased, or decreased from LDT to CDx in three (27%) cases, two (18%) cases, and one (9%) case, respectively, around relevant cutoffs (1 and 20, k = 0.63). Differences noted in DAB intensity/distribution using computational pathology partly explained the LDT vs. CDx differences in two cases (18%). Digital pathology may help in PD-L1 scoring, serving as a second opinion consultation platform in challenging cases. Computational and artificial intelligence tools will improve clinical decision-making and patient outcomes.
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PD-L1,digital pathology,head and neck squamous cell carcinoma,combined positive score
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要点】:本研究通过对比本地病理学家与专家病理学家在数字病理学平台上对11个具有挑战性的头颈鳞癌病例的PD-L1免疫组化染色结果,评估了PD-L1综合阳性评分(CPS)的预分析变异性和观察者间变异性的挑战,并采用计算方法探讨了染色特征与病理学家视觉评估之间的可能相关性。

方法】:采用实验室开发的测试(LDT)和伴随诊断(CDx)Dako 22C3 pharm Dx试剂,在Dako或Ventana平台上的22C3(Dako)和SP263(Ventana)克隆进行免疫组化染色。

实验】:结果显示,在5例(LDT对比CDx,45%)技术不一致的案例中,有2例(18%)因LDT中的异常核质DAB染色,3例(27%)因染色强度、背景污染和DAB滴落 variation而出现差异;在6例(LDT对比CDx,54%)解读不一致的案例中,CPS在从LDT到CDx的过程中有3例(27%)保持不变,2例(18%)增加,1例(9%)减少,主要围绕相关截止值(1和20,k = 0.63)。计算病理学中DAB强度/分布的差异在两个案例(18%)中部分解释了LDT与CDx之间的差异。

创新点:数字病理学平台可作为第二意见咨询工具,帮助解决具有挑战性的病例中的PD-L1评分问题,计算和人工智能工具将改善临床决策和患者预后。