Pathology最新文献

英文中文

Update on methods used for mycological testing: wide diversity and opportunities for improvement persist 真菌学检测所用方法的最新情况：种类繁多，仍有改进机会。

IF 3.6 3区医学 Q1 PATHOLOGY

Pathology

Pub Date : 2024-08-18 DOI: 10.1016/j.pathol.2024.06.007

Arthur J. Morris , Sarah E. Kidd , Catriona L. Halliday , Sharon C-A. Chen , Wendy McKinney , Katherine Ryan , Juliet Elvy

Past analysis of laboratory methods used for mycology specimens revealed significant variation in practices, many of which fell short of recommended procedures. In 2016 these findings led to a set of recommendations for laboratories to consider modification of their methods where appropriate, to analyse current laboratory methods used by participants in the Royal College of Pathologists of Australasia Quality Assurance Programs (RCPAQAP) Mycology module, and to compare these to the 2016 recommendations.

Seven test items, with 105–107 participants each, were analysed. Several laboratories (7–12%) did not handle specimens as recommended in an appropriate biological safety cabinet. Direct microscopy was not performed on tissue specimens 23–25% of the time. The most used staining method was potassium hydroxide with an optical brightener for fluorescent microscopy (49%) followed by Gram stain (33%). While 17–25% of laboratories used three or more media, use of four or more was uncommon (<3%). Between 9–13% of participants used only a single non-inhibitory medium for cultures. Urine specimens were incubated longer than recommended with 57% of laboratories incubating for >7days and 24% >21 days. Duration of incubation was shorter than recommended for several specimen types with 36% of skin specimens and 37–48% of tissue specimens being kept ≤21 days. For cultures kept >7 days, 13% were inspected daily, but for those incubating >14 days only 3%.

The methods of several laboratories remain outside recommended practice. An updated set of recommendations are made.

过去对实验室处理真菌学标本的方法进行的分析表明，操作方法存在很大差异，其中许多方法都未达到推荐程序的要求。2016 年，这些研究结果提出了一系列建议，要求实验室考虑酌情修改其方法。我们对澳大拉西亚皇家病理学院质量保证计划（RCPAQAP）真菌学模块参与者目前使用的实验室方法进行了分析，并将这些方法与 2016 年的建议进行了比较。共分析了七个测试项目，每个项目有105-107名参与者参加。一些实验室（7-12%）没有按照建议在适当的生物安全柜中处理标本。23%-25%的实验室未对组织标本进行直接显微镜检查。最常用的染色方法是氢氧化钾加光学增白剂荧光显微镜（49%），其次是革兰氏染色法（33%）。有 17-25% 的实验室使用三种或更多培养基，但使用四种或更多培养基的情况并不常见（7 天和 24% >21 天）。几种标本的培养时间都比建议的时间短，36%的皮肤标本和 37-48% 的组织标本培养时间不足 21 天。对于保存时间超过 7 天的培养物，有 13% 的培养物需要每天进行检查，但对于保存时间超过 14 天的培养物，只有 3% 的培养物需要每天进行检查。一些实验室的方法仍不符合推荐做法。现提出一套最新建议。

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引用次数: 0

Combination of lentiginous junctional melanocytic naevus, Toker cell hyperplasia and pagetoid dyskeratosis of the nipple: a potential diagnostic pitfall 乳头皮样交界性黑素细胞痣、角化细胞增生症和页状角化异常的合并症：潜在的诊断陷阱

IF 3.6 3区医学 Q1 PATHOLOGY

Pathology

Pub Date : 2024-08-18 DOI: 10.1016/j.pathol.2024.06.008

Mark James Wilsher , James D. Bedford

引用次数: 0

The effect of Proteinase K treatment on GeoMx digital spatial profiling data quality from formalin-fixed, paraffin-embedded tissue 蛋白酶 K 处理对来自福尔马林固定、石蜡包埋组织的 GeoMx 数字空间剖析数据质量的影响。

IF 3.6 3区医学 Q1 PATHOLOGY

Pathology

Pub Date : 2024-08-14 DOI: 10.1016/j.pathol.2024.06.004

Kyle M. Hatton-Jones , Nicholas P. West , Jean Barcelon , Amanda J. Cox

The emergence of spatial profiling technologies in recent years has accelerated opportunities to profile in detail the molecular attributes of a wide range of tissue pathologies using archival specimens. However, tissue treatment for fixation and storage does not always support generation of high-quality genomic data. The purpose of this study was to investigate the impacts of Proteinase K (ProtK) treatment, as a way to increase target transcript exposure, on downstream sequencing data quality metrics for spatial transcriptomic data using formalin-fixed, paraffin-embedded samples. In a series of four independent assessments using different tissue types (nasal mucosa, tonsil, pancreas), varying concentrations of ProtK (ranging from 0.1 to 1 μg/mL) were used as part of the sample processing workflow to generate transcriptomic data using the Nanostring GeoMx DSP and Illumina NextSeq 2000 platforms. Use of higher concentrations of ProtK was generally found to increase total reads (2–4-fold). However, negative probe counts also tended to be increased (2–12-fold), resulting in reductions in the signal-to-noise ratio (10–70% lower) and the number of genes detected above background (50–80% lower). These effects were not seen in all tissues and impacts of tissue handling and processing, beyond ProtK treatment, on data quality metrics, also require consideration. Regardless, these observations highlight the need for careful consideration of a range of sample processing factors and benefits that may be achieved through the optimisation of sample processing workflows for specific tissues as a way to maximise the generation of quality data using spatial transcriptomic approaches.

近年来，空间剖析技术的出现加快了利用档案标本详细剖析各种组织病变的分子属性的机会。然而，组织的固定和储存处理并不总是支持生成高质量的基因组数据。本研究的目的是调查蛋白酶 K（ProtK）处理对使用福尔马林固定、石蜡包埋样本的空间转录组数据下游测序数据质量指标的影响。在使用不同组织类型（鼻粘膜、扁桃体、胰腺）进行的一系列四项独立评估中，不同浓度的 ProtK（0.1 至 1 μg/mL）被用作样本处理工作流程的一部分，使用 Nanostring GeoMx DSP 和 Illumina NextSeq 2000 平台生成转录组数据。使用较高浓度的 ProtK 通常会增加总读数（2-4 倍）。然而，负探针计数也有增加的趋势（2-12 倍），导致信噪比降低（降低 10-70%）和检测到的高于背景的基因数量减少（降低 50-80%）。这些影响并不是在所有组织中都能看到，除了 ProtK 处理之外，组织处理和加工对数据质量指标的影响也需要考虑。无论如何，这些观察结果都强调了仔细考虑一系列样本处理因素的必要性，以及通过优化特定组织的样本处理工作流程来最大限度地利用空间转录组方法生成高质量数据的好处。

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引用次数: 0

Lupoid cutaneous leishmaniasis in Pakistan: a case series in school children 巴基斯坦的鳞状皮肤利什曼病：学龄儿童病例系列。

IF 3.6 3区医学 Q1 PATHOLOGY

Pathology

Pub Date : 2024-08-14 DOI: 10.1016/j.pathol.2024.06.005

Asma Ashraf, Saima Qadeer, Ume Amara Bukhari, Umme Salma

引用次数: 0

ALK-positive large B-cell lymphoma: a clinicopathological and molecular characteristics analysis of seven cases ALK阳性大B细胞淋巴瘤：七例病例的临床病理学和分子特征分析。

IF 3.6 3区医学 Q1 PATHOLOGY

Pathology

Pub Date : 2024-08-13 DOI: 10.1016/j.pathol.2024.05.014

Xuan Wang , Hongmei Yi , Qingxiao Liu , Tuanjie Guo , Anqi Li , Binshen Ouyang , Yimin Li , Yuxiu Zhang , Haimin Xu , Lei Dong , Xu Wang , Chaofu Wang

Anaplastic lymphoma kinase-positive large B-cell lymphoma (ALK⁺ LBCL) is a rare and highly aggressive lymphoma with characteristic ALK rearrangements. Various fusion genes involving ALK have been demonstrated, but the influence of the ALK fusion partners on ALK protein expression and the genetic characteristics of ALK⁺ LBCL remain relatively unknown. In this study, we conducted an extensive clinicopathological and molecular analysis on seven cases of ALK⁺ LBCL to explore the correlation between ALK fusion genes and ALK protein expression, thereby enriching the genetic characteristics of this tumour. We integrated the findings from clinical, histopathological/immunophenotypic, and molecular studies, including three samples subjected to next-generation sequencing, and six cases underwent RNA-based ALK fusion gene detection. We identified five distinct types of ALK fusion genes, including CLTC, NPM1, PABPC1, SEC31A, and TFG. Notably, only the NPM1::ALK fusion showed nuclear and cytoplasmic ALK staining, and the remaining four fusion genes resulted in cytoplasmic ALK staining. Our analysis revealed that the CLTC::ALK fusion resulted in a unique cytoplasmic perinuclear Golgi zone focal granular heterogeneous staining pattern of ALK. Additionally, we identified six potentially clinically significant gene mutations, including TET2, CHD2, DTX1, KMT2D, LRP1B, and XPO1. Furthermore, in all cases, the absence of 5-hydroxymethylcytosine (5hmC) was observed. We present seven cases of ALK⁺ LBCL, discussing the correlation between fusion genes and ALK protein expression, and enhancing our understanding of the genetic attributes of this tumour. This study also shows the loss of 5hmC in nearly all seven ALK⁺ LBCL cases, independently of TET2 mutations.

无性淋巴瘤激酶阳性大B细胞淋巴瘤（ALK+ LBCL）是一种罕见的高侵袭性淋巴瘤，具有特征性的ALK重排。目前已证实有多种涉及ALK的融合基因，但ALK融合伙伴对ALK蛋白表达的影响以及ALK+ LBCL的遗传特征仍相对未知。在本研究中，我们对7例ALK+ LBCL进行了广泛的临床病理和分子分析，探讨了ALK融合基因与ALK蛋白表达之间的相关性，从而丰富了该肿瘤的遗传学特征。我们整合了临床、组织病理学/免疫表型和分子研究的结果，其中三例样本进行了新一代测序，六例进行了基于RNA的ALK融合基因检测。我们发现了五种不同类型的 ALK 融合基因，包括 CLTC、NPM1、PABPC1、SEC31A 和 TFG。值得注意的是，只有NPM1::ALK融合基因出现了细胞核和细胞质ALK染色，其余四种融合基因均出现了细胞质ALK染色。我们的分析表明，CLTC::ALK 融合基因会导致 ALK 独特的胞浆核周高尔基区局灶颗粒状异质染色模式。此外，我们还发现了六种具有潜在临床意义的基因突变，包括 TET2、CHD2、DTX1、KMT2D、LRP1B 和 XPO1。此外，在所有病例中都观察到了 5-羟甲基胞嘧啶（5hmC）的缺失。我们介绍了七例ALK+ LBCL病例，讨论了融合基因与ALK蛋白表达之间的相关性，加深了我们对这种肿瘤遗传属性的理解。本研究还显示，几乎所有七例ALK+ LBCL病例中都存在5hmC缺失，与TET2突变无关。

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引用次数: 0

TIGIT expression on neoplastic cells is a poor prognostic factor for adult T-cell leukaemia/lymphoma 肿瘤细胞上的 TIGIT 表达是成人 T 细胞白血病/淋巴瘤的不良预后因素

IF 3.6 3区医学 Q1 PATHOLOGY

Pathology

Pub Date : 2024-08-12 DOI: 10.1016/j.pathol.2024.06.003

Yuichi Yamada , Hiroaki Miyoshi , Mai Takeuchi , Kazutaka Nakashima , Kyohei Yamada , Takeharu Kato , Ken Tanaka , Kei Kohno , Yoshitaka Imaizumi , Yasushi Miyazaki , Koichi Ohshima

Adult T-cell leukaemia/lymphoma (ATLL) is an aggressive peripheral T-cell neoplasm with a poor prognosis. T-cell immunoreceptor with immunoglobulin and immunoreceptor tyrosine-based inhibitory motif domains (TIGIT) is an immune checkpoint receptor expressed on T and natural killer cells. Although increased TIGIT expression in the tumour microenvironment is associated with poor prognosis in various neoplasms, its relevance in ATLL remains unknown. Herein, we investigated the clinicopathological impact of TIGIT expression on ATLL using immunohistochemistry. TIGIT expression was detected in 21 of 84 patients (25%). A partial association between the clinical features and immune checkpoint molecules and the expression of TIGIT was found including sIL-2R, CD86 and GITR. TIGIT-positive patients [median survival time (MST) 8.9 months, 95% confidence interval (CI) 7.7–15.6] had inferior overall survival compared with TIGIT-negative patients (MST 18.7 months, 95% CI 12.0–36.4) (p=0.0124]. TIGIT expression maintained its prognostic value for overall survival in both univariate and multivariate analyses [hazard ratio (HR) 1.909; 95% CI 1.044–3.488; p=0.0356]. Further studies are required to clarify the clinical and biological significance of TIGIT expression in patients with ATLL.

成人 T 细胞白血病/淋巴瘤（ATLL）是一种侵袭性外周 T 细胞肿瘤，预后较差。具有免疫球蛋白和免疫受体酪氨酸抑制结构域的T细胞免疫受体（TIGIT）是一种免疫检查点受体，在T细胞和自然杀伤细胞上表达。虽然肿瘤微环境中 TIGIT 表达的增加与多种肿瘤的不良预后有关，但其与 ATLL 的相关性仍不清楚。在此，我们采用免疫组化方法研究了 TIGIT 表达对 ATLL 的临床病理影响。84 例患者中有 21 例（25%）检测到 TIGIT 表达。临床特征和免疫检查点分子与 TIGIT 表达之间存在部分关联，包括 sIL-2R、CD86 和 GITR。与TIGIT阴性患者（中位生存时间（MST）18.7个月，95% 置信区间（CI）12.0-36.4）相比，TIGIT阳性患者（中位生存时间（MST）8.9个月，95% 置信区间（CI）7.7-15.6）的总生存率较低（=0.0124）。在单变量和多变量分析中，TIGIT表达对总生存期仍有预后价值[危险比（HR）1.909；95% CI 1.044-3.488；=0.0356]。要明确TIGIT表达在ATLL患者中的临床和生物学意义，还需要进一步的研究。

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引用次数: 0

Benign prostatic hyperplasia and insignificant prostate cancer with very high levels of serum prostate specific antigen 血清前列腺特异性抗原水平非常高的良性前列腺增生和不明显的前列腺癌。

IF 3.6 3区医学 Q1 PATHOLOGY

Pathology

Pub Date : 2024-08-12 DOI: 10.1016/j.pathol.2024.05.013

Hemamali Samaratunga , Brett Delahunt , Mats Olsson , Markus Aly , Lars Egevad , John Yaxley

引用次数: 0

Deep learning-based diagnosis and survival prediction of patients with renal cell carcinoma from primary whole slide images 基于深度学习的原发性全切片图像肾细胞癌患者诊断与生存预测

IF 3.6 3区医学 Q1 PATHOLOGY

Pathology

Pub Date : 2024-08-03 DOI: 10.1016/j.pathol.2024.05.012

Siteng Chen , Xiyue Wang , Jun Zhang , Liren Jiang , Feng Gao , Jinxi Xiang , Sen Yang , Wei Yang , Junhua Zheng , Xiao Han

There is an urgent clinical demand to explore novel diagnostic and prognostic biomarkers for renal cell carcinoma (RCC). We proposed deep learning-based artificial intelligence strategies. The study included 1752 whole slide images from multiple centres.

Based on the pixel-level of RCC segmentation, the diagnosis diagnostic model achieved an area under the receiver operating characteristic curve (AUC) of 0.977 (95% CI 0.969–0.984) in the external validation cohort. In addition, our diagnostic model exhibited excellent performance in the differential diagnosis of RCC from renal oncocytoma, which achieved an AUC of 0.951 (0.922–0.972). The grade_risk for the recognition of high-grade tumour achieved AUCs of 0.840 (0.805–0.871) in the Cancer Genome Atlas (TCGA) cohort, 0.857 (0.813–0.894) in the Shanghai General Hospital (General) cohort, and 0.894 (0.842–0.933) in the Clinical Proteomic Tumor Analysis Consortium (CPTAC) cohort, for the recognition of high-grade tumour. The OS_risk for predicting 5-year survival status achieved an AUC of 0.784 (0.746–0.819) in the TCGA cohort, which was further verified in the independent general cohort and the CPTAC cohort, with AUCs of 0.774 (0.723–0.820) and 0.702 (0.632–0.765), respectively. Moreover, the competing-risk nomogram (CRN) showed its potential to be a prognostic indicator, with a hazard ratio (HR) of 5.664 (3.893–8.239, p<0.0001), outperforming other traditional clinical prognostic indicators. Kaplan–Meier survival analysis further illustrated that our CRN could significantly distinguish patients with high survival risk.

Deep learning-based artificial intelligence could be a useful tool for clinicians to diagnose and predict the prognosis of RCC patients, thus improving the process of individualised treatment.

探索肾细胞癌（RCC）的新型诊断和预后生物标志物仍然是临床的迫切需求。我们提出了基于深度学习的人工智能策略。研究包括来自多个中心的1752张全切片图像。

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引用次数: 0

Macaque liver substrate for evaluating dense fine speckled-like patterns on HEp2010 cells 用于评估 HEp2010 细胞上密集细小斑点状图案的猕猴肝脏基质

IF 3.6 3区医学 Q1 PATHOLOGY

Pathology

Pub Date : 2024-08-03 DOI: 10.1016/j.pathol.2024.05.011

Anthea Anantharajah , Roger A. Silvestrini , David Campbell , Suzanne Culican , Adrian Y.S. Lee , Ming Wei Lin

Antinuclear antibody (ANA) detection by indirect immunofluorescence (IIF) is instrumental in the evaluation of systemic autoimmune diseases (SADs). The dense fine speckled (DFS) ANA staining predominantly associates with anti-DFS70, an autoantibody that is thought to exclude the presence of SAD. However, the DFS pattern may mask the presence of other ANA patterns that may be clinically relevant. Our laboratory uses the HEp2010 substrate which contains both HEp2 and liver substates. The aim of this study was to determine whether negative liver nucleus immunofluorescence could exclude the presence of antibodies to extractable nuclear antigens (ENA) in sera with DFS-like patterns.

One hundred consecutive sera samples suspicious for DFS pattern, along with 15 sera of control patterns (positive metaphase bars) were included in the study. Each sample was examined separately on HEp2010 (Euroimmun) and liver by two independent readers. Anti-DFS70 was assessed by line and chemiluminescent immunoassays.

DFS-like sera were more likely to be liver nucleus-negative compared with control sera. Of the liver-negative sera, 61/64 (95.3%) were deemed anti-ENA negative. Using the liver substrate in the evaluation of anti-ENA had a sensitivity of 90.0% and a negative predictive value of 95.4%.

In our cohort, concurrent evaluation of sera with the liver substrate helped rule out the presence of other anti-ENA. This technique may be a safeguard for DFS-like ANA patterns that may mask underlying anti-ENA on IIF.

通过间接免疫荧光（IIF）检测抗核抗体（ANA）有助于评估全身性自身免疫性疾病（SAD）。致密细斑点（DFS）ANA 染色主要与抗DFS70 相关联，这种自身抗体被认为可以排除 SAD 的存在。然而，DFS 模式可能会掩盖其他可能与临床相关的 ANA 模式。我们实验室使用的 HEp2010 底物包含 HEp2 和肝脏底物。本研究的目的是确定阴性肝核免疫荧光能否排除 DFS 样本血清中存在的可提取核抗原（ENA）抗体。

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引用次数: 0

Imprecision of myositis line immunoassay attributable to batch variability 可归因于批次差异的肌炎系免疫测定不精确性

IF 3.6 3区医学 Q1 PATHOLOGY

Pathology

Pub Date : 2024-07-29 DOI: 10.1016/j.pathol.2024.05.009

Matthew Krummenacher , Brittany Stevenson , Chris Bundell , Andrew McLean-Tooke

引用次数: 0

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