由于组织病理学、免疫表型学和遗传数据的重叠，大B细胞淋巴瘤（LBCL）的亚分类是具有挑战性的。特别是，将弥漫性大B细胞淋巴瘤（DLBCL）和高级别B细胞淋巴瘤（HGBL）分离的标准在实践中很难应用。Lunenburg淋巴瘤生物标志物联盟先前报道了一个包括荧光原位杂交（FISH）数据的超过5000个LBCL队列。这个队列包含209个MYC重排列的病例，供八位专家造血病理学家验证不同组织病理学特征如何使用的研究。用苏木精-伊红染色切片的数字全幅图像使病理学家独立可视评分，并参加虚拟联合审查会议。制定了标准共识指南，对评分的组织病理学特征进行了规范，包括总体架构/生长模式，天空星图案的存在或缺失，细胞大小，核异常性，核仁突出和一系列细胞学特征。尽管使用了共识指南，但结果显示八位专家病理学家之间的不一致性很高。约50％的情况缺乏多数评分，这种不一致性涵盖了所有六个组织病理学特征。此外，没有任何组织学变量有助于预测MYC单重组与双/三重打击或IG合作伙伴FISH设计或临床结果措施。我们的研究结果表明，并没有特定的常规形态学参数有助于亚分类MYC重排列的LBCL或选择FISH分析的病例，其中导入FISH数据对于准确分类和预后是必不可少的。本文受版权保护。所有权利均受到保护。

Subclassification of large B-cell lymphoma (LBCL) is challenging due to the overlap in histopathologic, immunophenotypic, and genetic data. In particular, the criteria to separate diffuse large B-cell lymphoma (DLBCL) and high-grade B-cell lymphoma (HGBL) are difficult to apply in practice. The Lunenburg Lymphoma Biomarker Consortium previously reported a cohort of over 5000 LBCL that included fluorescent in situ hybridization (FISH) data. This cohort contained 209 cases with MYC rearrangement that were available for a validation study of how various histopathological features are used by a panel of eight expert hematopathologists.Digital whole slide images of hematoxylin and eosin-stained sections allowed the pathologists to visually score cases independently as well as participate in virtual joint review conferences. Standardized consensus guidelines were formulated for scoring histopathological features and included overall architecture/growth pattern, presence or absence of a starry-sky pattern, cell size, nuclear pleomorphism, nucleolar prominence and a range of cytologic characteristics. Despite the use of consensus guidelines, the results show a high degree of discordance among the eight expert pathologists. Approximately 50% of the cases lacked a majority score and this discordance spanned all six histopathological features. Moreover, none of the histological variables aided in prediction of MYC single versus double/triple-hit or IG-partner FISH-based designations or clinical outcome measures.Our findings indicate that there are no specific conventional morphological parameters that help subclassify MYC-rearranged LBCL or select cases for FISH analysis, and that incorporation of FISH data is essential for accurate classification and prognostication.This article is protected by copyright. All rights reserved.