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Thoughts on mastocytosis in COVID-19: an author's response 对 COVID-19 中乳突病的思考:作者的回应。
IF 3.9 2区 医学 Q2 CELL BIOLOGY Pub Date : 2024-10-20 DOI: 10.1111/his.15349
Boaz V Lopuhaä, Jan H von der Thüsen
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引用次数: 0
Mastocytosis and the trigger for pulmonary fibrosis and thrombosis in patients affected by COVID-19 肥大细胞增多症与 COVID-19 患者肺纤维化和血栓形成的诱因。
IF 3.9 2区 医学 Q2 CELL BIOLOGY Pub Date : 2024-10-20 DOI: 10.1111/his.15348
Hideki Zimermann Kamitani, Vanessa Ellen Silva Carmo, Afonso José Damásio Da Silva Filho, Lucas Mendes Reis de Moura, Bárbara Rocha Rodrigues, Rodrigo Mendes, Pedro Pereira Tenório
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引用次数: 0
4D pathology: translating dynamic epithelial tubulogenesis to prostate cancer pathology. 4D 病理学:将动态上皮管生成转化为前列腺癌病理学。
IF 3.9 2区 医学 Q2 CELL BIOLOGY Pub Date : 2024-10-20 DOI: 10.1111/his.15354
Hridya Harikumar, Martin E van Royen, Geert Jlh van Leenders

The Gleason score is the gold standard for grading of prostate cancer (PCa) and is assessed by assigning specific grades to different microscopical growth patterns. Aside from the Gleason grades, individual growth patterns such as cribriform architecture were recently shown to have independent prognostic value for disease outcome. PCa grading is performed on static tissue samples collected at one point in time, whereas in vivo epithelial tumour structures are dynamically invading, branching and expanding into the surrounding stroma. Due to the lack of models that are able to track human PCa microscopical developments over time, our understanding of underlying tissue dynamics is sparse. We postulate that human PCa expansion utilizes embryonic and developmental tubulogenetic pathways. The aim of this study is to provide a comprehensive overview of developmental pathways of normal epithelial tubule formation, elongation, and branching, and relate those to the static microscopical PCa growth patterns observed in daily clinical practise. This study could provide a rationale for the discerned pathological interobserver variability and the clinical outcome differences between PCa growth patterns.

格里森评分是对前列腺癌(PCa)进行分级的黄金标准,通过对不同的显微镜下生长模式划分特定等级来进行评估。除了格里森分级外,最近的研究表明,楔形结构等个别生长模式对疾病的预后也有独立的价值。PCa 的分级是在某一时点采集的静态组织样本上进行的,而体内的上皮肿瘤结构是动态侵入、分支并向周围基质扩展的。由于缺乏能够跟踪人类 PCa 显微发展的模型,我们对潜在组织动态的了解非常有限。我们推测人类 PCa 的扩张利用了胚胎和发育过程中的肾小管生成途径。本研究旨在全面概述正常上皮小管形成、伸长和分支的发育途径,并将其与日常临床实践中观察到的静态显微镜下 PCa 生长模式联系起来。这项研究可以为PCa生长模式之间的病理学观察者间差异和临床结果差异提供理论依据。
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引用次数: 0
Discordance of human epidermal growth factor receptor 2-low status between breast primary and distant metastases with clinical–pathological correlation 乳腺癌原发灶和远处转移灶的人类表皮生长因子受体 2 低水平状态不一致与临床病理相关性。
IF 3.9 2区 医学 Q2 CELL BIOLOGY Pub Date : 2024-10-17 DOI: 10.1111/his.15346
Ellen Yang, Timothy M D'Alfonso, Monica Morrow, Edi Brogi, Hannah Y Wen
<div> <section> <h3> Aims</h3> <p>Breast cancer with human epidermal growth factor receptor 2 (HER2) immunohistochemistry (IHC) 1+ or 2+ with negative <i>in-situ</i> hybridisation (ISH) (HER2-low) can now be targeted by HER2 antibody drug conjugates. We set out to compare HER2 status between matched primary invasive breast carcinoma (IBC) and distant metastases (DM) with clinical–pathological correlation, with specific interest in HER2-low.</p> </section> <section> <h3> Methods</h3> <p>Biomarker studies and clinical–pathological features of primary IBC with matched DM diagnosed between 2021 and 2022 were retrospectively analysed. HER2 status was assessed per 2023 American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP) guidelines for IHC (4B5) and ISH (IQFISH pharmDX). Bilateral breast primaries were excluded. HER2 IHC 0 to 1+ were reassessed.</p> </section> <section> <h3> Results</h3> <p>One hundred and forty-seven cases of primary IBC with matched DM were identified. Biomarkers were performed on core biopsy (<i>n</i> = 74) and resection (<i>n</i> = 73). One hundred and twenty-six (86%) were initially classified as ‘HER2-negative’; of these, 67 (46%) were reclassified as HER2-low. Patients with HER2-positive primaries were younger (<i>P</i> = 0.01) and had an increased incidence of micropapillary carcinoma (<i>P</i> = 0.02). HER2-low primaries also had an increased incidence of micropapillary carcinoma (<i>P</i> = 0.02) and oestrogen receptor (ER) positivity (<i>P</i> = 0.02) compared to HER2 0. One hundred and sixty-nine matched DM cases excluding bone metastasis were identified (range = one to seven metastases per IBC). The most common sites of metastases were liver (50 of 169, 30%), lung (36 of 169; 21%), distant lymph node (26 of 169, 15%); 138 DM cases (82%) were previously classified as ‘HER2-negative’, and 62 (37%) were reclassified as HER2-low. Like HER2-low primaries, HER2-low metastases were frequently ER-positive (52 of 62; 84%) (<i>P</i> = 0.02). Brain metastases were more frequently HER2-positive (five of 32; 16%) (<i>P</i> = 0.04). Comparing HER2 status in matched primaries and DM, HER2 status was discordant in 62 cases (37%). Most changes occurred from HER2-low to HER2 0 (33 of 169, 20%), HER2 0 to HER2-low (17 of 169, 10%) and HER2-low to positive (10 of 169, 6%). All HER2-low to HER2 0 changes were HER2 1+ to 0. In 30 patients with multiple DM sites (47 cases), HER2 status among different DM samples was discordant in 16 patients (53%), mainly from HER2-low to HER2 0 (16 of 47, 34%).</p> </section> <section> <h3> Conclusion</h3> <p>A significant proportion of previous ‘HER2-negative’ primaries and D
目的:人类表皮生长因子受体 2 (HER2) 免疫组化 (IHC) 1+ 或 2+ 且原位杂交 (ISH) 阴性的乳腺癌(HER2-low)现在可以通过 HER2 抗体药物共轭物进行靶向治疗。我们着手比较匹配的原发性浸润性乳腺癌(IBC)和远处转移瘤(DM)的 HER2 状态与临床病理学的相关性,特别关注 HER2-low:方法:回顾性分析了 2021 年至 2022 年期间确诊的原发性 IBC 和匹配 DM 的生物标志物研究和临床病理特征。HER2状态根据2023年美国临床肿瘤学会/美国病理学家学会(ASCO/CAP)IHC(4B5)和ISH(IQFISH pharmDX)指南进行评估。排除双侧乳腺原发癌。重新评估 HER2 IHC 0 至 1+:结果:共发现 147 例原发性 IBC 和匹配的 DM。对核心活检(74 例)和切除术(73 例)进行了生物标志物检测。126例(86%)最初被归类为 "HER2阴性";其中67例(46%)被重新归类为HER2低水平。HER2阳性原发患者更年轻(P = 0.01),微乳头状癌的发病率更高(P = 0.02)。与HER2为0的患者相比,HER2为低的原发灶微乳头状癌(P = 0.02)和雌激素受体(ER)阳性(P = 0.02)的发生率也有所增加。共发现 169 例匹配的 DM 病例(不包括骨转移)(范围 = 每个 IBC 1 到 7 例转移)。最常见的转移部位是肝(169 例中有 50 例,占 30%)、肺(169 例中有 36 例,占 21%)、远处淋巴结(169 例中有 26 例,占 15%);138 例 DM(82%)以前被归类为 "HER2 阴性",62 例(37%)被重新归类为 HER2 低。与HER2-低的原发病例一样,HER2-低的转移病例也经常是ER阳性(62例中有52例;84%)(P = 0.02)。脑转移瘤的 HER2 阳性率更高(32 例中有 5 例;16%)(P = 0.04)。比较匹配的原发灶和DM的HER2状态,62例(37%)的HER2状态不一致。大多数变化是从 HER2 低到 HER2 0(169 例中有 33 例,占 20%),HER2 0 到 HER2 低(169 例中有 17 例,占 10%),HER2 低到阳性(169 例中有 10 例,占 6%)。在30名有多个DM部位的患者(47例)中,有16名患者(53%)的不同DM样本的HER2状态不一致,主要是从HER2-低变为HER2-0(47人中有16人,占34%):结论:很大一部分以前的 "HER2阴性 "原发病例和DM病例被重新分类为HER2低。IBC原发灶和转移灶之间以及不同DM部位之间不一致的HER2状态显示了肿瘤的异质性,并强调了对远处转移灶进行HER2再检测的必要性。
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引用次数: 0
Global view of haematolymphoid tumor classifications and their application in low- and middle-income countries 血液淋巴肿瘤分类及其在中低收入国家应用的全球视角。
IF 3.9 2区 医学 Q2 CELL BIOLOGY Pub Date : 2024-10-17 DOI: 10.1111/his.15340
Yuri Fedoriw, Oscar Silva, Ariana Znaor, Elizabeth Macintyre

The accurate diagnosis of haematolymphoid malignancies is crucial for effective cancer care, but major obstacles to diagnosis exist in low- and middle-income countries (LMICs). This article explores the global applicability of current haematolymphoid classification systems, which are predominantly derived from data generated in high-income countries (HICs). Although disproportionately burdened with poor cancer outcomes, LMICs are generally faced with limited diagnostic resources, suboptimal access to therapeutics, and inadequate healthcare infrastructure. The article highlights the challenges faced by LMICs, including inconsistent access to high-quality pathology services, limited availability of advanced diagnostic techniques, and a lack of population-based cancer registry data. It also discusses the progress made in narrowing the gap between LMICs and HICs, such as the introduction of resource-adapted classifications, improved guidance on essential diagnostic tools, and strengthening of in-country professional pathology networks. Innovative diagnostic approaches, including gene expression profiling and machine learning, represent potential solutions for improving the diagnostic accuracy in LMICs, but addressable gaps remain. Recommendations are suggested for sustainable investments in diagnostic infrastructure, capacity-building, and population-based cancer registries to enhance the global applicability of haematolymphoid classification systems and improve outcomes for patients in LMICs.

准确诊断血淋巴细胞恶性肿瘤对有效的癌症治疗至关重要,但在中低收入国家(LMICs),诊断存在重大障碍。本文探讨了当前血液淋巴细胞分类系统的全球适用性,这些系统主要来自高收入国家(HICs)的数据。虽然低收入和中等收入国家癌症治疗效果不佳的比例过高,但这些国家普遍面临诊断资源有限、治疗手段不理想和医疗基础设施不足等问题。文章强调了低收入和中等收入国家所面临的挑战,包括难以获得高质量的病理服务、先进诊断技术有限以及缺乏基于人口的癌症登记数据。文章还讨论了在缩小低收入和中等收入国家与高收入国家之间差距方面所取得的进展,如引入适应资源的分类方法、改进对基本诊断工具的指导以及加强国内专业病理学网络。包括基因表达谱分析和机器学习在内的创新诊断方法是提高低收入和中等收入国家诊断准确性的潜在解决方案,但仍存在可解决的差距。建议对诊断基础设施、能力建设和基于人口的癌症登记进行可持续投资,以提高血液淋巴分类系统的全球适用性,改善低收入和中等收入国家患者的治疗效果。
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引用次数: 0
Closing the gap between biology and classification in splenic B-cell lymphomas 缩小脾脏 B 细胞淋巴瘤生物学与分类之间的差距。
IF 3.9 2区 医学 Q2 CELL BIOLOGY Pub Date : 2024-10-15 DOI: 10.1111/his.15323
Piers Blombery, Daphne de Jong, Judith A Ferry, Eric D Hsi, Sarah L Ondrejka, John F Seymour, Alberto Zamò, Alexandar Tzankov

The mature splenic B-cell lymphomas are an enigmatic group of lymphoid neoplasms that have long caused significant difficulty for the practicing pathologist due to overlapping diagnostic features among entities and the decreasing availability of splenic tissue for assessment. While some entities have highly characteristic and specific clinicopathological features (e.g. hairy cell leukaemia), others are substantially more difficult to recognise (e.g. splenic diffuse red pulp lymphoma). At the same time, classification systems have been evolving, resulting in multiple changes to the boundaries among these entities and even the existence of some entities in their own right. Moreover, unbiased multi-omic interrogation (whole genome/transcriptome sequencing, methylome) of the splenic B-cell lymphomas over the past decade has given us significant insights into the underling biology of these neoplasms. We present a clinicopathological perspective on the historical, current and future state of the diagnosis and classification of splenic B-cell lymphomas integrating multi-omic data and highlighting areas of focus for the field in order to continue to strive to improve patient outcomes through accurate diagnosis.

成熟的脾脏 B 细胞淋巴瘤是一组神秘的淋巴肿瘤,长期以来一直给病理学家带来很大的困难,因为不同实体的诊断特征相互重叠,而且用于评估的脾脏组织越来越少。一些实体具有高度特征性和特异性的临床病理特征(如毛细胞白血病),而另一些实体则更难识别(如脾弥漫性红髓淋巴瘤)。与此同时,分类系统也在不断发展,导致这些实体之间的界限发生了多种变化,甚至有些实体本身就不存在。此外,在过去的十年中,对脾脏 B 细胞淋巴瘤进行了无偏见的多组学研究(全基因组/转录组测序、甲基组),使我们对这些肿瘤的基本生物学特性有了更深入的了解。我们从临床病理学的角度介绍了脾B细胞淋巴瘤诊断和分类的历史、现状和未来,整合了多基因组数据,并强调了该领域的重点领域,以继续努力通过准确诊断改善患者预后。
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引用次数: 0
Accuracy of the LaserSAFE technique for detecting positive surgical margins during robot-assisted radical prostatectomy: blind assessment and inter-rater agreement analysis 在机器人辅助根治性前列腺切除术中检测手术边缘阳性的激光SAFE技术的准确性:盲法评估和评分者间一致性分析。
IF 3.9 2区 医学 Q2 CELL BIOLOGY Pub Date : 2024-10-15 DOI: 10.1111/his.15336
Ricardo Almeida-Magana, Matthew Au, Tarek Al-Hammouri, Manju Mathew, Kate Dinneen, Larissa S T Mendes, Eoin Dinneen, Willem Vreuls, Greg Shaw, Alex Freeman, Aiman Haider

Introduction and objectives

Fluorescence confocal microscopy (FCM) is a new imaging modality capable of generating digital microscopic resolution scans of fresh surgical specimens, and holds potential as an alternative to frozen section (FS) analysis for intra-operative assessment of surgical margins. Previously, we described the LaserSAFE technique as an application of FCM for margin assessment in robot-assisted radical prostatectomy (RARP) using the Histolog® scanner. This study describes the accuracy and inter-rater agreement of FCM imaging compared to corresponding paraffin-embedded analysis (PA) among four blinded pathologists for the presence of positive surgical margins (PSM).

Materials and methods

RARP specimens from patients enrolled in the control arm of the NeuroSAFE PROOF study (NCT03317990) were analysed from April 2022 to February 2023. Prostate specimens were imaged using the Histolog® scanner before formalin fixation and PA. Four trained assessors, blinded to PA, reviewed and analysed FCM images of the posterolateral prostatic surface.

Results

A total of 31 prostate specimens were included in the study. PA per lateral side of the prostate identified 11 instances of positive margins. Among the four histopathologists included in our study, FCM achieved a sensitivity of 73–91 and specificity of 94–100% for the presence of PSM. Fleiss’ Kappa for inter-rater agreement on PSM was 0.78 (95% confidence interval = 0.64–0.92), indicating substantial agreement.

Conclusion

This blinded analysis of FCM versus PA among histopathologists with different experience levels demonstrated high accuracy and substantial inter-rater agreement for diagnosing PSM. This supports the role of the FCM as an alternative to FS.

简介和目标:荧光共聚焦显微镜(FCM)是一种新的成像模式,能够生成新鲜手术标本的数字显微分辨率扫描,具有替代冷冻切片(FS)分析进行术中手术边缘评估的潜力。在此之前,我们曾介绍过 LaserSAFE 技术,该技术是 FCM 在机器人辅助前列腺癌根治术 (RARP) 中应用 Histolog® 扫描仪进行边缘评估的一种方法。本研究介绍了 FCM 成像与相应的石蜡包埋分析(PA)相比,四位盲法病理学家对手术切缘阳性(PSM)存在的准确性和评定者之间的一致性:从 2022 年 4 月到 2023 年 2 月,对 NeuroSAFE PROOF 研究(NCT03317990)对照组入组患者的 RARP 标本进行了分析。前列腺标本在福尔马林固定和 PA 前使用 Histolog® 扫描仪成像。四名训练有素的评估员对 PA 一无所知,他们审查并分析了前列腺后外侧表面的 FCM 图像:共有 31 份前列腺标本被纳入研究。前列腺每侧的 PA 发现了 11 例阳性边缘。在参与研究的四位组织病理学家中,FCM 对是否存在 PSM 的灵敏度为 73-91,特异度为 94-100%。关于 PSM 的评分者间一致性的 Fleiss' Kappa 为 0.78(95% 置信区间 = 0.64-0.92),表明评分者间的一致性非常高:这项由具有不同经验水平的组织病理学家进行的 FCM 与 PA 的盲法分析表明,诊断 PSM 的准确性很高,且评分者之间的一致性很高。这支持了 FCM 替代 FS 的作用。
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引用次数: 0
Molecular techniques in haematopathology: what and how? 血液病理学中的分子技术:内容和方法?
IF 3.9 2区 医学 Q2 CELL BIOLOGY Pub Date : 2024-10-15 DOI: 10.1111/his.15332
Gaurav Chatterjee, Rong He, Nikhil Patkar, David Viswanatha, Anton W Langerak

Here we review the ‘what and how’ of molecular techniques used in the context of haematopathological diagnostics of both lymphoid and myeloid neoplasms. Keeping in mind that the required resources for molecular testing are not universally available, we will not only discuss novel and emerging techniques that allow more high-throughput and sophisticated analyses of lymphoid and myeloid neoplasms, but also the more classical, low-cost alternatives and even some workarounds for molecular testing approaches. In this review we also address other key aspects around molecular techniques for haematopatholgy diagnostics, including preanalytics, data interpretation, and data management, bioinformatics, and interlaboratory precision and performance evaluation.

在此,我们将回顾淋巴肿瘤和骨髓肿瘤血液病理诊断中使用的分子技术的 "内容和方法"。考虑到分子检测所需的资源并非普遍可用,我们不仅将讨论可对淋巴肿瘤和骨髓肿瘤进行更高通量和更复杂分析的新兴技术,还将讨论更传统、低成本的替代方法,甚至是分子检测方法的一些变通方法。在这篇综述中,我们还讨论了血液病理诊断分子技术的其他关键方面,包括预分析、数据解读和数据管理、生物信息学以及实验室间精确度和性能评估。
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引用次数: 0
Diagnosis of acute lymphoblastic leukaemia: an overview of the current genomic classification, diagnostic approaches, and future directions 急性淋巴细胞白血病的诊断:当前基因组分类、诊断方法和未来方向概述。
IF 3.9 2区 医学 Q2 CELL BIOLOGY Pub Date : 2024-10-15 DOI: 10.1111/his.15338
Wencke Walter, Ilaria Iacobucci, Manja Meggendorfer

B-acute lymphoblastic leukaemia (B-ALL) is a haematological disease resulting from haematopoietic system dysfunction, leading to the unchecked growth of immature B lymphoblasts. The disease's complexity is underscored by the spectrum of genetic aberrations that underlie B-ALL entities, necessitating advanced genetic analyses for precise classification and risk determination. Prior to the adoption of next-generation sequencing into standard diagnostic practices, up to 30% of B-ALL cases were not assigned to specific entities due to the limitations of traditional diagnostic methods. The advent of comprehensive genomic analysis, especially whole-genome transcriptome sequencing, has significantly enhanced our understanding of B-ALL's molecular heterogeneity, paving the way for the exploration of novel, tailored treatment strategies. Furthermore, recent technological innovations, such as optical genome mapping, methylation profiling, and single-cell sequencing, have propelled forward the fields of cancer research and B-ALL management. These innovations introduce novel diagnostic approaches and prognostic markers, facilitating a deeper, more nuanced understanding of individual patient disease profiles. This review focuses on the latest diagnostic standards and assays for B-ALL, the importance of new technologies and biomarkers in enhancing diagnostic accuracy, and the expected role of innovative advancements in the future diagnosis and treatment of B-ALL.

B 型急性淋巴细胞白血病(B-ALL)是一种造血系统功能障碍导致未成熟 B 型淋巴细胞肆意生长的血液病。B-ALL 基因畸变的多样性凸显了这种疾病的复杂性,因此有必要进行先进的基因分析,以精确分类和确定风险。在标准诊断实践中采用新一代测序技术之前,由于传统诊断方法的局限性,多达 30% 的 B-ALL 病例无法归入特定的实体。全面的基因组分析,尤其是全基因组转录组测序的出现,大大提高了我们对 B-ALL 分子异质性的认识,为探索新型的、量身定制的治疗策略铺平了道路。此外,光学基因组图谱、甲基化分析和单细胞测序等最新技术创新也推动了癌症研究和 B-ALL 管理领域的发展。这些创新引入了新的诊断方法和预后标志物,有助于更深入、更细致地了解患者的个体疾病特征。本综述重点介绍 B-ALL 的最新诊断标准和检测方法、新技术和生物标记物在提高诊断准确性方面的重要性,以及创新进展在未来 B-ALL 诊断和治疗中的预期作用。
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引用次数: 0
Infiltrative epitheliosis of the breast; a pitfall for pathologists, a case report and a review focusing on the diagnostic approach and interpretative pitfalls 乳腺浸润性上皮细胞增多症;病理学家的一个陷阱,病例报告和综述,侧重于诊断方法和解释陷阱。
IF 3.9 2区 医学 Q2 CELL BIOLOGY Pub Date : 2024-10-15 DOI: 10.1111/his.15347
Michael Minkley, Zuzana Kos, Karen Ung, Patrick Wong, Billy Teng, Peyman Tavassoli
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引用次数: 0
期刊
Histopathology
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