Pathologists

病理学家
  • 文章类型: Journal Article
    背景:2022年,我们的团队启动了开创性的国家能力验证(PT)计划,用于乳腺癌的病理诊断,在整个中国迅速建立信誉。旨在不断监测和提高中国病理学家的乳腺病理学水平,第二轮PT计划于2023年启动,将扩大参与机构的数量,并将在全国范围内对HER20,1+的解释进行调查,和2+/FISH-类别在中国。
    方法:当前一轮PT方案中采用的方法与2022年上一周期的方法非常相似,该方法是根据“合格评估-能力测试的一般要求”(GB/T27043-2012/ISO/IEC17043:2010)设计和实施的。更重要的是,我们使用基于统计的方法来生成分配值,以增强其鲁棒性和可信度。
    结果:最终PT结果,发表在国家癌症质量控制中心网站(http://117.133.40.88:3927),表明所有参与者都通过了测试。然而,一些机构在对HER20,1+,和2+/FISH-精度低于59%,认为不满意。尤其是,HER20例的一致率仅为78.1%,表明在区分HER20和低HER2表达方面存在挑战。同时,还注意到组织学类型和等级解释改善的领域.
    结论:我们的PT方案在中国诊断乳腺癌方面表现出很高的水平。但它也发现了对HER20,1+,和2+/FISH-在一些机构。更重要的是,我们的研究强调了在HER2染色光谱的最低端评估中的挑战,这是进一步研究的关键领域。同时,它还表明需要改进组织学类型和等级的解释。这些发现加强了健全质量保证机制的重要性,就像这项研究中进行的全国性PT计划一样,保持高诊断标准,并确定需要进一步培训和增强的领域。
    BACKGROUND: In 2022, our team launched the pioneering national proficiency testing (PT) scheme for the pathological diagnosis of breast cancer, rapidly establishing its credibility throughout China. Aiming to continuously monitor and improve the proficiency of Chinese pathologists in breast pathology, the second round of the PT scheme was initiated in 2023, which will expand the number of participating institutions, and will conduct a nationwide investigation into the interpretation of HER2 0, 1+, and 2+/FISH- categories in China.
    METHODS: The methodology employed in the current round of PT scheme closely mirrors that of the preceding cycle in 2022, which is designed and implemented according to the \"Conformity assessment-General requirements for proficiency testing\"(GB/T27043-2012/ISO/IEC 17043:2010). More importantly, we utilized a statistics-based method to generate assigned values to enhance their robustness and credibility.
    RESULTS: The final PT results, published on the website of the National Quality Control Center for Cancer ( http://117.133.40.88:3927 ), showed that all participants passed the testing. However, a few institutions demonstrated systemic biases in scoring HER2 0, 1+, and 2+/FISH- with accuracy levels below 59%, considered unsatisfactory. Especially, the concordance rate for HER2 0 cases was only 78.1%, indicating challenges in distinguishing HER2 0 from low HER2 expression. Meanwhile, areas for histologic type and grade interpretation improvement were also noted.
    CONCLUSIONS: Our PT scheme demonstrated high proficiency in diagnosing breast cancer in China. But it also identified systemic biases in scoring HER2 0, 1+, and 2+/FISH- at some institutions. More importantly, our study highlighted challenges in the evaluation at the extreme lower end of the HER2 staining spectrum, a crucial area for further research. Meanwhile, it also revealed the need for improvements in interpreting histologic types and grades. These findings strengthened the importance of robust quality assurance mechanisms, like the nationwide PT scheme conducted in this study, to maintain high diagnostic standards and identify areas requiring further training and enhancement.
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  • 文章类型: Journal Article
    背景:基因组诊断测试对于指导非小细胞肺癌(NSCLC)患者的最佳治疗是必要的。根据基因组检测选择治疗的NSCLC患者的比例在许多国家仍然未知或需要进一步改进。这项调查旨在评估中国临床病理学家和医生对NSCLC基因组测试和靶向治疗的看法。
    方法:基于网络的调查是对150名临床病理学家和450名肿瘤科医生进行的,2020年5月至9月,中国135个城市的呼吸和胸外科。参与者在基因组测试方面有超过5年的临床经验,NSCLC的诊断或治疗。
    结果:临床病理学家报告了表皮生长因子受体(EGFR)的能力,间变性淋巴瘤激酶(ALK),ROS原癌基因1(ROS-1)检测为95.3%,94.7%,和84.7%,分别,但只有81.9%,75.5%,65.6%的医生认为医院病理科有能力进行检测。临床病理学家和医师报告的送检标本比例分别为21.0%和49.7%,分别。医生最常建议检测EGFR突变,其次是ALK和ROS-1重排。作为一线治疗,在新诊断的EGFR突变患者中,77%接受酪氨酸激酶抑制剂(TKIs)治疗(49%接受吉非替尼治疗);在ALK重排患者中,71%接受TKI(64%接受克唑替尼治疗);在ROS-1融合患者中,65%接受TKI(88%接受克唑替尼治疗)。
    结论:中国非三级医院病理科的检测能力和医师的认知能力有待提高,以提高非小细胞肺癌患者的基因组检测和靶向治疗率。
    BACKGROUND: Genomic diagnostic testing is necessary to guide optimal treatment for non-small cell lung cancer (NSCLC) patients. The proportion of NSCLC patients whose treatment was selected based on genomic testing is still unknown in many countries or needs further improvement. This survey aimed to assess perception of genomic testing and targeted therapy for NSCLC in clinical pathologists and physicians across China.
    METHODS: The web-based survey was conducted with 150 clinical pathologists and 450 physicians from oncology, respiratory and thoracic surgery departments from May to September 2020, across 135 cities in China. The participants had >5 years of clinical experience in genomic testing, diagnosis or treatment of NSCLC.
    RESULTS: Clinical pathologists reported capability of epidermal growth factor receptor (EGFR), anaplastic lymphoma kinase (ALK), and ROS proto-oncogene 1 (ROS-1) testing as 95.3%, 94.7%, and 84.7%, respectively, but only 81.9%, 75.5%, and 65.6% of physicians believed that the pathology department of the hospital is capable of performing the testing. The proportions of sending out specimens for testing were 21.0% and 49.7% as reported from clinical pathologists and physicians, respectively. Testing for EGFR mutation was recommended by physicians most often, followed by ALK and ROS-1 rearrangement. As first-line treatment, among the newly diagnosed patients with EGFR mutation, 77% received tyrosine kinase inhibitors (TKIs) therapy (49% treated with gefitinib); among patients with ALK rearrangement, 71% received TKI (64% treated with crizotinib); among patients with ROS-1 fusion, 65% received TKI (88% treated with crizotinib).
    CONCLUSIONS: The improvement of the non-tertiary hospital pathology departments\' detection capabilities and the physicians\' awareness are needed for enhancing the rate of genomic testing and targeted therapy in NSCLC patients in China.
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  • 文章类型: English Abstract
    WHO firstly published the classification of paediatric tumours, in which genetic tumour syndromes were introduced as a separate chapter, covering the clinicopathological features, molecular genetic alterations, and diagnostic criteria of various tumor susceptibility syndromes common in children. This article briefly introduces and interprets 5 hotspot genetic tumour syndromes (neurofibromatosis type 1, naevoid basal cell carcinoma syndrome, von Hippel-Lindau syndrome, familial adenomatous polyposis and xeroderma pigmentosum) based on relevant literature, in order to bring new perspectives and insights to pathologists and clinicians.
    WHO首次出版了儿童肿瘤分类,遗传性肿瘤综合征作为其独立章节被介绍,内容涵盖儿童常见各种肿瘤易感综合征的临床病理特征、分子遗传学改变以及诊断标准等。本文结合相关文献,对其中儿童好发的5种热点综合征(神经纤维瘤病1型、痣样基底细胞癌综合征、von Hippel-Lindau综合征、家族性腺瘤性息肉病和着色性干皮病)做简要介绍和解读,以使临床及病理医师对儿童肿瘤易感综合征有更多认识和了解。.
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  • 文章类型: Journal Article
    目的:鉴于程序性死亡-配体1(PD-L1)测试的现实局限性,需要进行PD-L1检测之间的一致性研究.我们在食管鳞状细胞癌(ESCC)的观察者中进行了PD-L1测定(DAKO22C3,VentanaSP263,VentanaSP142,E1L3N)的比较,以提供有关四种PD-L1IHC测定的分析和临床可比性的信息。
    方法:获取50例食管鳞癌石蜡包埋标本,用所有四种PD-L1测定进行饱和。来自19家不同医院的68名病理学家对PD-L1进行了评估。评估PD-L1表达的联合阳性评分(CPS)。
    结果:在ESCC中,SP263的表达敏感性最高,其次是22C3、E1L3N和SP142。以CPS10为临界值,在22C3、SP263、SP142和E1L3N测定中,评估了68名医生的CPS评分的观察者间一致性,产量值分别为0.777、0.790、0.758和0.782。在分析之间的比较中,22C3与SP263,SP142和E1L3N的总体CPS评分一致率分别为0.896,0.833和0.853.22C3和SP263有很高的一致性,OPA为0.896,而E1L3N和SP142的一致性最高,OPA为0.908。
    结论:在ESCC中,观察者之间PD-L1评估的一致性很好,免疫细胞评分仍是影响观察者判读一致性的重要因素。接近特定阈值的案例仍然是解释的难题。SP263在四个测定中具有最高的CPS评分。SP263不能识别所有22C3阳性病例,但与22C3有很好的一致性。E1L3N和SP142显示高度一致性。
    OBJECTIVE: Given real-world limitations in programmed death-ligand 1 (PD-L1) testing, concordance studies between PD-L1 assays are needed. We undertook comparisons of PD-L1 assays (DAKO22C3, Ventana SP263, Ventana SP142, E1L3N) among observers in esophageal squamous cell carcinoma (ESCC) to provide information on the analytical and clinical comparability of four PD-L1 IHC assays.
    METHODS: Paraffin embedded samples of 50 cases of esophageal squamous cell carcinoma were obtained, satined with all four PD-L1 assays. PD-L1 was evaluated by 68 pathologists from 19 different hospitals. PD-L1 expression was assessed for combined positive score (CPS).
    RESULTS: The expression sensitivity of SP263 was the highest in ESCC, followed by 22C3, E1L3N and SP142. Taking CPS 10 as the critical value, inter-observer concordance for CPS scores among 68 physicians was assessed for the 22C3, SP263, SP142, and E1L3N assays, yielding values of 0.777, 0.790, 0.758, and 0.782, respectively. In the comparison between assays, the overall CPS scores concordance rates between 22C3 and SP263, SP142, and E1L3N were 0.896, 0.833, and 0.853, respectively. 22C3 and SP263 have high concordance, with OPA of 0.896, while E1L3N and SP142 have the highest concordance, with OPA of 0.908.
    CONCLUSIONS: In ESCC, the concordance of PD-L1 evaluation among observers is good, and the immune cell score is still an important factor affecting the concordance of interpretation among observers. Cases near the specific threshold are still the difficult problem of interpretation. SP263 had the highest CPS score of the four assays. SP263 cannot identify all 22C3 positive cases, but had good concordance with 22C3.E1L3N and SP142 showed high concordance.
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  • 文章类型: Journal Article
    全球肾小球硬化百分比是决定肾转移手术结果的关键因素。目前,该比率通常由病理学家计算,这是劳动密集型和非标准化的。随着深度学习(DL)的发展,基于DL的分割模型可用于更好地识别和分割正常和硬化的肾小球。基于此,我们可以更好地量化全球肾小球硬化的百分比,以降低供体肾脏的丢弃率。我们使用了来自互联网上公开提供的不同机构的51张完整幻灯片图像(WSI)。然而,在不同的WSI中,硬化肾小球的数量远小于正常肾小球的数量,这可能会降低深度学习的有效性。为了更好的硬化肾小球识别和分割性能,我们修改并训练了基于GAN(生成对抗网络)的图像修复模型,以获得更多的合成硬化肾小球。我们提出的修补方法在生成的硬化肾小球区域中实现了0.8086的平均SSIM(结构相似性)和22.8943dB的平均PSNR(峰值信噪比)。我们通过添加合成的硬化肾小球图像来获得硬化肾小球分割性能的改善,并基于改进的Unet模型在不同测试集中实现了肾小球分割的最佳Dice。
    The percent global glomerulosclerosis is a key factor in determining the outcome of renal transfer surgery. At present, the rate is typically computed by pathologists, which is labour intensive and nonstandardized. With the development of Deep Learning (DL), DL-based segmentation models can be used to better identify and segment normal and sclerosed glomeruli. Based on this, we can better quantify percent global glomerulosclerosis to reduce the discard rate of donor kidneys. We used 51 whole slide images (WSIs) from different institutions that are publicly available on the internet. However, the number of sclerosed glomeruli is much smaller than that of normal glomeruli in different WSIs, which can reduce the effectiveness of Deep Learning. For better sclerosed glomerular identification and segmentation performance, we modified and trained a GAN (generative adversarial network)-based image inpainting model to obtain more synthetic sclerosed glomeruli. Our proposed inpainting method achieved an average SSIM (Structural Similarity) of 0.8086 and an average PSNR (Peak Signal-to-Noise Ratio) of 22.8943 dB in the area of generated sclerosed glomeruli. We obtained sclerosed glomerular segmentation performance improvement by adding synthetic sclerosed glomerular images and achieved the best Dice of glomerular segmentation in different test sets based on the modified Unet model.
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  • 文章类型: Journal Article
    PD-L1的过表达可能是经典霍奇金淋巴瘤(CHL)中抗PD-1治疗功效的预测指标;然而,不同IHC测定的协调仍有待完成,PD-L1免疫染色结果的解释在CHL中仍存在争议。在这项研究中,我们试图优化CHL中的PD-L1免疫组织化学(IHC)测定。所有测试均在从54例CHL病例建立的肿瘤组织微阵列上进行。使用RNAscope测定法半定量比较了三种用于检测PD-L1表达的IHC抗体(405.9A11,SP142,22C3)(编号:310035,ACD),以及分析之间背景免疫细胞(IC)表达的差异以及表达水平与TIL/TAM密度的关联。405.9A11在HRS细胞中表现出最佳特异性和在IC中表现出最佳灵敏度。PD-L1的阳性表达在IC中(85.2%)比在HRS细胞中(48.1%)更频繁。背景IC的不同子组,包括肿瘤相关巨噬细胞(TAMs),评估并评分CD4,CD8,FOXP3和CD163的表达。PD-L1在IC上的表达是与TAM密度最相关的因素。405.9A11提供了最令人信服的PD-L1表达结果。病理学家应以联合方式报告PD-L1表达,包括HRS细胞的状态和PD-L1阳性IC的百分比。
    Overexpression of PD-L1 can be a predictive marker for anti-PD-1 therapeutic efficacy in classic Hodgkin lymphoma (CHL); however, harmonization of different IHC assays remains to be accomplished, and interpretations of PD-L1 immunostaining results remain controversial in CHL. In this study, we sought to optimize the PD-L1 immunohistochemistry (IHC) assay in CHL. All tests were performed on a tumour tissue microarray established from 54 CHL cases. Three IHC antibodies (405.9A11, SP142, 22C3) for detecting PD-L1 expression were compared semi quantitatively with the RNAscope assay (No. 310035, ACD), and the difference in the expression in background immune cells (ICs) between assays and the associations of expression levels with densities of TILs/TAMs were also analysed. 405.9A11 demonstrated best specificity in HRS cells and best sensitivity in ICs. Positive expression of PD-L1 was more frequent in ICs (85.2%) than in HRS cells (48.1%). Different subgroups of background ICs, including tumour-associated macrophages (TAMs), were assessed and scored for CD4, CD8, FOXP3, and CD163 expression. PD-L1 expression on ICs was the factor most associated with the density of TAMs. 405.9A11 provided the most convincing PD-L1 expression results. Pathologists should report PD-L1 expression in a combined manner, including both the status of HRS cells and the percentage of PD-L1-positive ICs.
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  • 文章类型: Letter
    暂无摘要。
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  • 文章类型: Journal Article
    传统上,肺癌的生物标志物测试是由治疗肿瘤学家在确认适当的病理诊断后订购的。这带来的延迟进一步延长了已经很复杂的东西,多阶段,预处理途径和延迟一线全身治疗的开始,这对这种分析的结果至关重要。反射测试,其中,病理学家负责测试商定范围的生物标志物,已被证明可以标准化和加快这一进程。十二位专家讨论了将反射测试作为标准临床实践的基本原理和注意事项。
    Biomarker tests in lung cancer have been traditionally ordered by the treating oncologist upon confirmation of an appropriate pathological diagnosis. The delay this introduces prolongs yet further what is already a complex, multi-stage, pre-treatment pathway and delays the start of first-line systemic treatment, which is crucially informed by the results of such analysis. Reflex testing, in which the responsibility for testing for an agreed range of biomarkers lies with the pathologist, has been shown to standardise and expedite the process. Twelve experts discussed the rationale and considerations for implementing reflex testing as standard clinical practice.
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  • 文章类型: Journal Article
    目的:原发性肺腺癌的分类复杂多变。不同亚型的肺腺癌治疗方法不同,预后也不同。在这项研究中,我们收集了11个包含肺癌亚型的数据集,并提出了FL-STNet模型,为改善原发性肺腺癌病理分类的临床问题提供帮助.
    方法:从360例诊断为肺腺癌和其他肺部疾病亚型的患者中收集样本。此外,一种基于Swin-Transformer的辅助诊断算法,在训练中使用焦点丧失作为功能,已开发。同时,将Swin-Transformer的诊断准确性与病理学家进行了比较。
    结果:Swin-Transformer不仅可以捕获整体组织结构中的信息,还可以捕获肺癌病理图像中的局部组织细节。此外,用FocalLoss函数训练FL-STNet可以进一步平衡不同子类型之间数据量的差异,提高识别精度。平均分类精度,F1,拟议的FL-STNet的AUC达到85.71%,86.57%,和0.9903。FL-STNet的平均准确率分别提高了17%和34%,分别,高于高级病理学家和初级病理学家组。
    结论:开发了第一个基于11类分类器的深度学习,用于基于WSI组织病理学对肺腺癌亚型进行分类。针对目前CNN和Vit的不足,本研究通过引入焦点损耗并结合Swin-Transformer模型的优点,提出了FL-STNet模型。
    OBJECTIVE: The classification of primary lung adenocarcinoma is complex and varied. Different subtypes of lung adenocarcinoma have different treatment methods and different prognosis. In this study, we collected 11 datasets comprising subtypes of lung cancer and proposed FL-STNet model to provide the assistance for improving clinical problems of pathologic classification in primary adenocarcinoma of lung.
    METHODS: Samples were collected from 360 patients diagnosed with lung adenocarcinoma and other subtypes of lung diseases. In addition, an auxiliary diagnosis algorithm based on Swin-Transformer, which used Focal Loss for function in training, was developed. Meanwhile, the diagnostic accuracy of the Swin-Transformer was compared to pathologists.
    RESULTS: The Swin-Transformer captures not only information in the overall tissue structure but also the local tissue details in the images of lung cancer pathology. Furthermore, training FL-STNet with the Focal Loss function can further balance the difference in the amount of data between different subtypes, improving recognition accuracy. The average classification accuracy, F1, and AUC of the proposed FL-STNet reached 85.71%, 86.57%, and 0.9903. The average accuracy of the FL-STNet was higher by 17% and 34%, respectively, than in the senior pathologist and junior pathologist group.
    CONCLUSIONS: The first deep learning based on an 11-category classifier was developed for classifying lung adenocarcinoma subtypes based on WSI histopathology. Aiming at the deficiencies of the current CNN and Vit, FL-STNet model is proposed in this study by introducing Focal Loss and combining the advantages of Swin-Transformer model.
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  • 文章类型: Journal Article
    乳腺癌是全球女性癌症相关死亡的主要原因。尽管诊断技术和医学科学发展迅速,病理诊断仍被认为是疾病诊断的金标准。病理诊断对于病理学家来说是一项耗时的任务,需要深厚的专业知识和长期积累的诊断经验。因此,自动和精确的组织病理学图像分类的发展对于医学诊断至关重要。在这项研究中,使用改进的VGG网络对术中快速冰冻切片中的乳腺癌组织病理学图像进行分类.我们通过在训练阶段对交叉熵添加惩罚来采用变换的损失函数,将测试数据的准确度提高了4.39%。拉普拉斯-4用于图像的增强,这有助于提高精度。模型对训练数据和测试数据的准确率分别达到88.70%和82.27%,分别,在测试数据中,该模型的准确率比原始模型高9.39%。平均每个图像的处理时间小于0.25s。同时,给出了预测的热图,以显示组织病理学图像中的证据区域,这可以提高精度,速度,病理诊断的临床价值。除了帮助实际诊断,这项技术可能对病理学家有好处,外科医生,和病人。它可能被证明是未来病理学家的有用工具。
    Breast cancer is the leading cause of cancer-related mortality in women worldwide. Despite the rapid developments in diagnostic techniques and medical sciences, pathologic diagnosis is still recognized as the gold standard for disease diagnose. Pathologic diagnosis is a time-consuming task performed for pathologists, needing profound professional knowledge and long-term accumulated diagnostic experience. Therefore, the development of automatic and precise histopathological image classification is essential for medical diagnosis. In this study, an improved VGG network was used to classify the breast cancer histopathological image from intraoperative rapid frozen sections. We adopt a transformed loss function by adding a penalty to cross-entropy in our training stage, which improved the accuracy on test data by 4.39%. Laplacian-4 was used for the enhancement of images, which contributes to the improvement of the accuracy. The accuracy of the proposed model on training data and test data reached 88.70% and 82.27%, respectively, which outperforms the original model by 9.39% of accuracy in test data. The process time was less than 0.25 s per image on average. Meanwhile, the heat maps of predictions were given to show the evidential regions in histopathological images, which could drive improvements in the accuracy, speed, and clinical value of pathological diagnoses. In addition to helping with the actual diagnosis, this technology may be a benefit to pathologists, surgeons, and patients. It might prove to be a helpful tool for pathologists in the future.
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