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Making routine head and neck pathology Easy: From dissection to diagnosis. 简化常规头颈部病理:从解剖到诊断。
IF 2.6 2区 医学 Q2 PATHOLOGY Pub Date : 2025-12-29 DOI: 10.1016/j.humpath.2025.106030
Jasmine Siaw, Timothy Fielder, Sebastian Senff, Carsten E Palme, Jonathan R Clark, Caroline L Cooper, Ruta Gupta

Resections from the mobile tongue, the oropharynx and neck dissections constitute a large proportion of routine head and neck pathology workload. Histologically detected proximity to margins and prognostic factors like depth of invasion, perineural or lymphovascular invasion, or extranodal extension guide adjuvant radiotherapy and/or chemotherapy. This review discusses practical approaches to macroscopic examination of the various types of tongue and oropharyngeal resections and neck dissections. Differential inking and radial sections demonstrate proximity of tumour to margins. The macroscopic examination and sampling should then be directed towards identifying remaining adverse prognostic features including the maximum extent of invasion at the primary site and extranodal extension, nodal matting or soft tissue deposits in the neck dissections. The diagnostic challenges differ in the tongue and oropharynx. The diagnosis of tongue SCC is relatively easy, however, precursor oral epithelial dysplasia can be challenging. Architectural and cytologic clues assisting in identifying dysplasia and practical clues distinguishing it from reactive changes are discussed. In contrast, dysplasia is not diagnosed in the oropharynx. p16 immunostaining and detection of human papillomavirus (HPV) play a critical role in the diagnosis and prognosis of oropharyngeal SCC. Nuances in the implementation and interpretation of p16 immunostaining and HPV assays are discussed.

活动舌的切除、口咽和颈部解剖在常规头颈部病理工作量中占很大比例。组织学检测的预后因素如浸润深度、神经周围或淋巴血管浸润、靠近边缘或结外延伸可指导辅助放疗和/或化疗。这篇综述讨论了各种类型的舌和口咽切除和颈部解剖的宏观检查的实用方法。鉴别染色和放射切片显示肿瘤靠近边缘。然后,宏观检查和取样应直接用于确定进一步的不良预后特征,包括原发部位的最大程度侵犯和结外延伸,以及颈部解剖中的淋巴结消斑或软组织沉积。在舌头和口咽部的诊断挑战不同。舌鳞状细胞癌的诊断相对容易,然而,前体口腔上皮发育不良可能具有挑战性。建筑和细胞学线索协助识别非典型增生和实际线索区分它与反应性变化进行了讨论。相反,口咽部不典型增生未被诊断。p16免疫染色及人乳头瘤病毒(HPV)检测对口咽鳞状细胞癌的诊断和预后具有重要作用。在实施和解释p16免疫染色和HPV检测的细微差别进行了讨论。
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引用次数: 0
What's new in upper gastrointestinal pathology: Key updates and evolving challenges in 2026. 上消化道病理学的新进展:2026年的关键更新和不断变化的挑战。
IF 2.6 2区 医学 Q2 PATHOLOGY Pub Date : 2025-12-25 DOI: 10.1016/j.humpath.2025.106025
Domenika Ortiz Requena, Elizabeth A Montgomery

Diagnostic pathology of the upper gastrointestinal tract continues to evolve as molecular insights, clinical practices, and updated international standards improve our understanding of disease. The World Health Organization (WHO) classification of digestive system tumors, now in its 6th edition, includes several important changes, including incorporating esophageal epidermoid metaplasia as a separate section, and modifying the approach to metaplastic and dysplastic gastric lesions. These updates reflect a broader trend toward simplified terminology, clearer definitions of precursor lesions, and more consistent grading systems across the digestive tract. At the same time, increased use of immunotherapy has introduced new patterns of injury. Beyond immune checkpoint inhibitors, several agents, including rituximab and chimeric antigen receptor T-cell therapy have been associated with distinctive upper-GI mucosal alterations that can resemble infectious or immunologic diseases. Failure to recognize these patterns of injury can carry significant clinical implications, including treatment delay or discontinuation, and require careful histologic evaluation to avoid misclassification. This review summarizes select upper-GI updates from the 6th edition of the WHO classification and outlines emerging therapy-related injuries with a focus on rituximab- and CAR-T-associated changes. The aim is to provide a practical and contemporary guide for pathologists navigating these evolving diagnostic challenges.

随着对分子的认识、临床实践和更新的国际标准提高了我们对疾病的理解,上胃肠道的诊断病理学不断发展。世界卫生组织(WHO)的消化系统肿瘤分类,现在是第6版,包括几个重要的变化,包括将食管表皮样化生作为一个单独的部分,并修改了胃化生和发育不良病变的方法。这些更新反映了一种更广泛的趋势,即简化术语,更清晰的前体病变定义,以及更一致的消化道分级系统。与此同时,免疫疗法的使用增加,引入了新的损伤模式。除了免疫检查点抑制剂,包括利妥昔单抗和嵌合抗原受体t细胞治疗在内的一些药物与独特的上消化道粘膜改变有关,这些改变可能类似于感染性或免疫性疾病。未能识别这些损伤模式可能具有重要的临床意义,包括治疗延迟或停止,并且需要仔细的组织学评估以避免错误分类。本综述总结了世卫组织第6版分类中精选的上消化道最新信息,并概述了新出现的治疗相关损伤,重点是利妥昔单抗和car - t相关的变化。目的是为病理学家导航这些不断发展的诊断挑战提供实用和现代的指南。
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引用次数: 0
Colloid cysts of the third ventricle show consistent expression of PAX8 but lack other features of thyroid, müllerian or intestinal differentiation 第三脑室胶质囊肿的PAX8表达一致,但缺乏甲状腺、<s:1>勒氏管或肠分化的其他特征
IF 2.6 2区 医学 Q2 PATHOLOGY Pub Date : 2025-12-24 DOI: 10.1016/j.humpath.2025.106028
Jiri Soukup , Eva Traboulsi , Sarka Lopatova , Martin Syrucek , Miroslav Koblizek , Michal Hendrych , Marian Svajdler , Kristyna Sichova , Michaela May , David Netuka
Colloid cyst of the 3rd ventricle (CC) is an unusual cystic lesion of uncertain histogenesis, occurring exclusively in the 3rd ventricle close to the foramen Monro. In the past, its pathogenic relationship to neurenteric cyst (NEC) of central nervous system or Rathke cleft cyst (RCC) has been suggested. Thus, we evaluated expression of selected tissue-specific transcription factors and other proteins to assess its putative origin. Tissue samples of 15 CCs (8 females and 7 males, mean age 46.7 years), 7 RCCs (7 females, mean age 45.6 years), 8 neurenteric cysts (5 females and 2 males, mean age 42.1 years, including 1 recurrent case), and 10 craniopharyngiomas (2 papillary and 8 adamantinomatous) were included. Immunohistochemical detections of PAX8 with C-terminus specific antibody, TTF1, SOX17, and cadherin 17 were performed in all the samples. The immunoreactivity was scored based on extent (0 %; <10 %; 10–50 %; >50 %) and intensity (weak, moderate, strong). All 15 cases of CCs were PAX8 positive (moderate to strong expression in >50 % in 13/15 cases), while no RCC, NEC or craniopharyngioma showed PAX8 immunoreactivity. Rare PAX8-positive cells were also observed in single cells of 50 % (3/6) of the choroid plexuses. No expression of TTF1 or SOX17 was detected in any of the cases and weak cadherin 17 expression was seen in scattered cells (<10 %) of one CC and RCC. Colloid cysts of the 3rd ventricle are consistently PAX8-positive, while they lack signs of thyroid, müllerian or enteric differentiation. Furthermore, PAX8 can be used to distinguish CC from NEC, RCC, and craniopharyngiomas.
第三脑室胶质囊肿(CC)是一种不寻常的囊性病变,组织发生不确定,仅发生在靠近门孔的第三脑室。以往有文献认为其与中枢神经系统神经肠囊肿(NEC)或Rathke裂隙囊肿(RCC)有致病关系。因此,我们评估了选定的组织特异性转录因子和其他蛋白质的表达,以评估其假定的起源。本研究包括15例cc(8女7男,平均年龄46.7岁)、7例rcc(7女,平均年龄45.6岁)、8例神经肾囊肿(5女2男,平均年龄42.1岁,其中1例复发)、10例颅咽管瘤(2例乳头状瘤,8例硬瘤)。所有样品均采用c端特异性抗体、TTF1、SOX17和cadherin 17进行PAX8免疫组化检测。免疫反应性根据程度(0 %;< 10%;10 - 50%; > 50%)和强度(弱、中、强)进行评分。15例cc均为PAX8阳性(13/15例中有50%中至强表达),而RCC、NEC和颅咽管瘤均无PAX8免疫反应。50%(3/6)脉络膜丛单细胞中也观察到罕见的pax8阳性细胞。在所有病例中均未检测到TTF1或SOX17的表达,在1例CC和RCC的分散细胞(< 10%)中可见弱cadherin 17的表达。第三脑室胶质囊肿始终呈pax8阳性,但缺乏甲状腺、勒氏管或肠分化的征象。此外,PAX8可用于区分CC与NEC、RCC和颅咽管瘤。
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引用次数: 0
B72.3 serves as a new diagnostic marker for testicular Leydig cell tumor B72.3作为睾丸间质细胞瘤新的诊断标志物
IF 2.6 2区 医学 Q2 PATHOLOGY Pub Date : 2025-12-22 DOI: 10.1016/j.humpath.2025.106026
Jianping Zhao , William Mi , Varsha Nair , Barrett C. Lawson , Charles C. Guo , Elizabeth M. Jacobi , Qingqing Ding
Leydig cell tumors (LCTs) and Sertoli cell tumors (SCTs) are the two most common sex cord–stromal tumors of the testis, and can exhibit overlapping histologic and immunophenotypic features, creating diagnostic challenges. Currently, differential diagnosis of these two tumors relies primarily on histological features, with no reliable immunohistochemical markers available. B72.3 is a widely used immunohistochemical antibody recognizing tumor-associated glycoprotein 72 (TAG-72) expressed in a broad range of normal and tumor tissues. Incidentally, we observed that B72.3 specifically stains the Leydig cells, but not Sertoli cells, in normal testis, suggesting its potential utility as a diagnostic marker for testicular LCTs. In this study, we identified 35 patients with testicular LCTs (primary: n = 28; metastatic: n = 7) and 12 with testicular SCTs (primary: n = 10; metastatic: n = 2). B72.3 immunohistochemistry was performed on 17 testicular LCTs and 7 SCTs. Positive B72.3 staining was observed in 9 of 17 LCTs (53 %), including 8 of 12 primary tumors (67 %) and 1 of 5 metastatic tumors (20 %). Among the positive LCTs, 2 exhibited diffuse staining, 2 showed patchy positivity, and 5 had focal staining. By contrast, all 7 SCTs and 1 Sertoli cell nodule were negative for B72.3. These findings indicate that B72.3 may serve as a useful diagnostic marker for testicular LCTs and can aid in distinguishing LCTs from SCTs in challenging cases.
睾丸间质细胞瘤(lct)和支持细胞瘤(sct)是睾丸两种最常见的性索间质肿瘤,它们可以表现出重叠的组织学和免疫表型特征,这给诊断带来了挑战。目前,这两种肿瘤的鉴别诊断主要依赖于组织学特征,没有可靠的免疫组织化学标志物。B72.3是一种广泛使用的免疫组织化学抗体,可识别肿瘤相关糖蛋白72 (TAG-72),在正常组织和肿瘤组织中广泛表达。顺便说一下,我们观察到B72.3特异性地染色睾丸间质细胞,而不是正常睾丸的支持细胞,这表明它可能作为睾丸lct的诊断标记物。在这项研究中,我们确定了35例睾丸LCTs患者(原发性:n=28,转移性:n=7)和12例睾丸sct患者(原发性:n=10,转移性:n=2)。17例睾丸LCTs和7例SCTs行B72.3免疫组化。17例LCTs中有9例(53%)B72.3阳性,其中12例原发肿瘤中有8例(67%),5例转移性肿瘤中有1例(20%)。阳性LCTs中弥漫染色2例,斑片状阳性2例,局灶性染色5例。相比之下,7例sct和1例支持细胞结节均为B72.3阴性。这些发现表明B72.3可能作为睾丸LCTs的有用诊断标记物,并有助于在挑战性病例中区分LCTs和sct。
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引用次数: 0
Granulomatous variant of extranodal NK/T-cell lymphoma: Mimicking inflammatory or infective lesions 结外NK/ t细胞淋巴瘤的肉芽肿变异型:模拟炎症或感染性病变。
IF 2.6 2区 医学 Q2 PATHOLOGY Pub Date : 2025-12-22 DOI: 10.1016/j.humpath.2025.106027
Mansi Yu , Xuankai Zeng , Weixin Luo , Qitao Huang , Yinli Zheng , Yuhua Huang

Objective

A heavy admixture of inflammatory cells is observed in extranodal NK/T-cell lymphoma (ENKTL), but granuloma formation is typically absent. We aimed to describe the clinicopathological features of this rare granulomatous variant of ENKTL.

Methods

Four cases of the granulomatous variant of ENKTL were retrospectively analyzed, combined with a review of four cases reported in the literature.

Results

The four cases in our institution comprised one female and three male patients aged 57–65 years (median: 61 years). One patient had a nasal lesion, while three exhibited extranasal disease. All were diagnosed at stage III/IV. Histopathology showed extensive epithelioid granulomas, but lacked typical features such as angiocentricity and angiodestruction. Scattered atypical lymphoid cells with varying degrees of cytological atypia were observed between granulomas. Immunohistochemistry confirmed T or NK cell lineage with expression of CD3ε and cytotoxic markers. Epstein-Barr virus-encoded small RNA (EBER) in situ hybridization (ISH) confirmed an Epstein-Barr virus (EBV) association in all cases. Three cases were CD56-positive, and two were CD5-negative. Three showed CD4-/CD8-, and one showed CD4-/CD8+. Mutations in DNMT3A, KMT2D, and KMT2A in Case #3 and a B2M mutation in Case #4 were revealed by next-generation sequencing (NGS). Combined with literature, granulomatous ENKTL most frequently involved the skin (6/8 cases). Notably, five of these eight cases were initially misdiagnosed as chronic inflammation.

Conclusions

ENKTL encompasses a variety of morphological features and a broad biological spectrum. Heightened awareness of this granulomatous variant is critical for preventing diagnostic delays and ensuring timely therapeutic intervention.
目的:在结外NK/ t细胞淋巴瘤(ENKTL)中观察到大量炎症细胞的混合,但通常没有肉芽肿的形成。我们的目的是描述这种罕见的肉芽肿型ENKTL的临床病理特征。方法:回顾性分析4例肉芽肿型ENKTL,并结合文献报道的4例病例进行复习。结果:本院4例患者包括1女3男,年龄57 ~ 65岁,中位年龄61岁。1例患者有鼻腔病变,3例患者有鼻外病变。所有患者均诊断为III/IV期。组织病理学表现为广泛的上皮样肉芽肿,但缺乏血管中心性和血管破坏等典型特征。肉芽肿间可见分散的非典型淋巴细胞,不同程度的细胞异型性。免疫组织化学证实T或NK细胞系表达CD3ε和细胞毒性标志物。Epstein-Barr病毒编码小RNA (EBER)原位杂交(ISH)证实在所有病例中存在Epstein-Barr病毒(EBV)关联。cd56阳性3例,cd5阴性2例。3例显示CD4-/CD8-, 1例显示CD4-/CD8+。通过下一代测序(NGS)发现,病例#3中存在DNMT3A、KMT2D和KMT2A突变,病例#4中存在B2M突变。结合文献,肉芽肿性ENKTL最常累及皮肤(6/8)。值得注意的是,这8例中有5例最初被误诊为慢性炎症。结论:ENKTL包括多种形态特征和广泛的生物学谱。提高对这种肉芽肿变异的认识对于预防诊断延误和确保及时的治疗干预至关重要。
{"title":"Granulomatous variant of extranodal NK/T-cell lymphoma: Mimicking inflammatory or infective lesions","authors":"Mansi Yu ,&nbsp;Xuankai Zeng ,&nbsp;Weixin Luo ,&nbsp;Qitao Huang ,&nbsp;Yinli Zheng ,&nbsp;Yuhua Huang","doi":"10.1016/j.humpath.2025.106027","DOIUrl":"10.1016/j.humpath.2025.106027","url":null,"abstract":"<div><h3>Objective</h3><div>A heavy admixture of inflammatory cells is observed in extranodal NK/T-cell lymphoma (ENKTL), but granuloma formation is typically absent. We aimed to describe the clinicopathological features of this rare granulomatous variant of ENKTL.</div></div><div><h3>Methods</h3><div>Four cases of the granulomatous variant of ENKTL were retrospectively analyzed, combined with a review of four cases reported in the literature.</div></div><div><h3>Results</h3><div>The four cases in our institution comprised one female and three male patients aged 57–65 years (median: 61 years). One patient had a nasal lesion, while three exhibited extranasal disease. All were diagnosed at stage III/IV. Histopathology showed extensive epithelioid granulomas, but lacked typical features such as angiocentricity and angiodestruction. Scattered atypical lymphoid cells with varying degrees of cytological atypia were observed between granulomas. Immunohistochemistry confirmed T or NK cell lineage with expression of CD3ε and cytotoxic markers. Epstein-Barr virus-encoded small RNA (EBER) in situ hybridization (ISH) confirmed an Epstein-Barr virus (EBV) association in all cases. Three cases were CD56-positive, and two were CD5-negative. Three showed CD4-/CD8-, and one showed CD4-/CD8+. Mutations in <em>DNMT3A</em>, <em>KMT2D</em>, and <em>KMT2A</em> in Case #3 and a <em>B2M</em> mutation in Case #4 were revealed by next-generation sequencing (NGS). Combined with literature, granulomatous ENKTL most frequently involved the skin (6/8 cases). Notably, five of these eight cases were initially misdiagnosed as chronic inflammation.</div></div><div><h3>Conclusions</h3><div>ENKTL encompasses a variety of morphological features and a broad biological spectrum. Heightened awareness of this granulomatous variant is critical for preventing diagnostic delays and ensuring timely therapeutic intervention.</div></div>","PeriodicalId":13062,"journal":{"name":"Human pathology","volume":"168 ","pages":"Article 106027"},"PeriodicalIF":2.6,"publicationDate":"2025-12-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145827208","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Deep learning-based classification of lung adenocarcinoma subtypes in histopathological images using DS-EffNet 基于DS-EffNet的组织病理图像中肺腺癌亚型的深度学习分类
IF 2.6 2区 医学 Q2 PATHOLOGY Pub Date : 2025-12-18 DOI: 10.1016/j.humpath.2025.106020
Peihe Jiang , Weilong Chen , Xiaogang Song , Xinna Li
The classification of lung adenocarcinoma (LADC) subtypes is important for understanding disease heterogeneity and has potential implications for diagnosis and treatment planning, yet the complexity and heterogeneity of histopathological images pose significant challenges for automated classification. This study proposes an efficient deep learning model that integrates Depthwise Separable Residual Block (DSResBlock), RefConv, Channel Attention Pooling (CAP), and Multidimensional Collaborative Attention (MCA) modules into the EfficientNetV2-S architecture to improve subtype classification of LADC histopathological images. DS-EffNet model optimizes feature extraction and modeling of complex pathological patterns through depthwise separable convolutions and attention mechanisms. Experimental results demonstrate that the model achieves an accuracy of 95.1 %, an F1-score of 0.938, and an area under the curve (AUC) of 0.994 on the primary experimental dataset, outperforming other baseline models. Furthermore, the model attains 100 % generalization accuracy on the LC25000 dataset, indicating promising cross-institutional performance. Ablation studies demonstrate the synergistic contributions of each module, with MCA particularly effective in modeling complex features and RefConv significantly reducing computational complexity. This study provides a novel design paradigm for medical image classification, extendable to other histological tasks, and may assist pathologists by providing rapid subtype-level information, potentially supporting future diagnostic research and aiding treatment stratification studies.
肺腺癌(LADC)亚型的分类对于了解疾病的异质性非常重要,并且对诊断和治疗计划具有潜在的意义,然而组织病理学图像的复杂性和异质性对自动分类构成了重大挑战。本研究提出了一种高效的深度学习模型,该模型将深度可分离残块(DSResBlock)、RefConv、通道注意池(CAP)和多维协作注意(MCA)模块集成到EfficientNetV2-S架构中,以改进LADC组织病理图像的亚型分类。DS-EffNet模型通过深度可分离卷积和注意机制优化了复杂病理模式的特征提取和建模。实验结果表明,该模型在主实验数据集上的准确率为95.1%,f1得分为0.938,曲线下面积(AUC)为0.994,优于其他基线模型。此外,该模型在LC25000数据集上达到了100%的泛化精度,表明有前景的跨机构性能。消融研究证明了每个模块的协同贡献,MCA在建模复杂特征方面特别有效,而RefConv显著降低了计算复杂性。该研究为医学图像分类提供了一种新的设计范例,可扩展到其他组织学任务,并可能通过提供快速的亚型水平信息来帮助病理学家,潜在地支持未来的诊断研究和辅助治疗分层研究。
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引用次数: 0
Circulating tumour DNA as a prognostic tool for surgically treated pancreatic ductal adenocarcinoma 循环肿瘤DNA作为手术治疗胰腺导管腺癌的预后工具。
IF 2.6 2区 医学 Q2 PATHOLOGY Pub Date : 2025-12-18 DOI: 10.1016/j.humpath.2025.106024
Trine Aaquist , Tenna Vesterman Henriksen , Lea Lecanda Mariager Jakobsen , Claus Wilki Fristrup , Per Pfeiffer , Karin de Stricker , Ernesto Sparrelid , Carlos Fernández Moro , Frank Mortensen , Anders Riegels Knudsen , Stephen Hamilton-Dutoit , Jörg Kleeff , Michael Bau Mortensen , Claus Lindbjerg Andersen , Sönke Detlefsen

Introduction

Pancreatic ductal adenocarcinoma (PDAC) has a high risk of early recurrence after surgery. We evaluated the utility of circulating tumour DNA (ctDNA) analysed at different time points as a prognostic tool. Secondary aims were prognostic value of ctDNA combined with plasma carbohydrate antigen (CA) 19-9 and prognostic value of peritoneal tumour DNA (ptDNA).

Methods

A total of 75 patients were included. Plasma samples were obtained preoperatively, 1 month, and 7–9 months after resection. Peritoneal lavage fluid (PLF) was collected preoperatively and 7–9 months after resection. Cell-free DNA (cfDNA) from plasma and ptDNA were analysed using mutation specific digital droplet PCR assays in a tumour-informed apprach. Kaplan-Meier survival curves, univariable, and multivariable Cox proportional hazard models were used to assess overall survival (OS) and recurrence-free survival (RFS).

Results

Preoperatively, detectable ctDNA was an independent risk factor for OS (HR = 1.88, p = 0.047). Detectable ctDNA 7–9 months after surgery was an independent risk factor for RFS (HR = 4.48, p = 0.017). Detectable ctDNA 1 month after surgery showed decreased RFS (HR = 1.98, p = 0.055). Preoperative, 1-month, and 7–9 months postoperative positivity for ctDNA and/or CA 19-9 showed a significantly worse median OS (p = 0.024, p = 0.008, and p = 0.0003). We did not find association of ptDNA with OS or RFS, but ptDNA detection 7–9 months after surgery was associated with peritoneal RFS (p = 0.003).

Conclusion

Our data indicate that detectable ctDNA in plasma taken before and 7–9 months after surgery holds independent prognostic value in PDAC. Combination of ctDNA with CA-19–9 may be a particularly strong prognosticator, which should be confirmed in future studies.
摘要胰导管腺癌(Pancreatic ductal adencarcinoma, PDAC)具有术后早期复发的高风险。我们评估了在不同时间点采集循环肿瘤DNA (ctDNA)作为预后工具的效用。次要目的是ctDNA联合血浆碳水化合物抗原(CA)-19-9和腹膜肿瘤DNA (ptDNA)的预后价值。方法:纳入75例患者。术前、术后1个月和术后7-9个月采集血浆样本。术前及术后7-9个月采集腹腔灌洗液(PLF)。在肿瘤知情的方法中,使用突变特异性数字液滴PCR分析血浆和ptDNA的游离DNA (cfDNA)。Kaplan-Meier生存曲线、单变量和多变量Cox比例风险模型用于评估总生存期(OS)和无复发生存期(RFS)。结果:术前ctDNA检测是OS的独立危险因素(HR=1.88, p=0.047)。术后7-9个月检测到的ctDNA是RFS的独立危险因素(HR=4.48, p=0.017)。术后1个月ctDNA检测显示RFS下降(HR=1.98, p=0.055)。术前、术后1个月和7-9个月ctDNA和/或CA 19-9阳性显示中位OS明显较差(p=0.024、p=0.008和p=0.0003)。我们没有发现ptDNA与OS或RFS相关,但术后7-9个月ptDNA检测与腹膜RFS相关(p=0.003)。结论:我们的数据表明,术前和术后7-9个月血浆中检测到的ctDNA对手术治疗的PDAC具有独立的预后价值。ctDNA与CA-19-9的结合可能是一个特别强的预测因子,这需要在未来的研究中得到证实。
{"title":"Circulating tumour DNA as a prognostic tool for surgically treated pancreatic ductal adenocarcinoma","authors":"Trine Aaquist ,&nbsp;Tenna Vesterman Henriksen ,&nbsp;Lea Lecanda Mariager Jakobsen ,&nbsp;Claus Wilki Fristrup ,&nbsp;Per Pfeiffer ,&nbsp;Karin de Stricker ,&nbsp;Ernesto Sparrelid ,&nbsp;Carlos Fernández Moro ,&nbsp;Frank Mortensen ,&nbsp;Anders Riegels Knudsen ,&nbsp;Stephen Hamilton-Dutoit ,&nbsp;Jörg Kleeff ,&nbsp;Michael Bau Mortensen ,&nbsp;Claus Lindbjerg Andersen ,&nbsp;Sönke Detlefsen","doi":"10.1016/j.humpath.2025.106024","DOIUrl":"10.1016/j.humpath.2025.106024","url":null,"abstract":"<div><h3>Introduction</h3><div>Pancreatic ductal adenocarcinoma (PDAC) has a high risk of early recurrence after surgery. We evaluated the utility of circulating tumour DNA (ctDNA) analysed at different time points as a prognostic tool. Secondary aims were prognostic value of ctDNA combined with plasma carbohydrate antigen (CA) 19-9 and prognostic value of peritoneal tumour DNA (ptDNA).</div></div><div><h3>Methods</h3><div>A total of 75 patients were included. Plasma samples were obtained preoperatively, 1 month, and 7–9 months after resection. Peritoneal lavage fluid (PLF) was collected preoperatively and 7–9 months after resection. Cell-free DNA (cfDNA) from plasma and ptDNA were analysed using mutation specific digital droplet PCR assays in a tumour-informed apprach. Kaplan-Meier survival curves, univariable, and multivariable Cox proportional hazard models were used to assess overall survival (OS) and recurrence-free survival (RFS).</div></div><div><h3>Results</h3><div>Preoperatively, detectable ctDNA was an independent risk factor for OS (HR = 1.88, p = 0.047). Detectable ctDNA 7–9 months after surgery was an independent risk factor for RFS (HR = 4.48, p = 0.017). Detectable ctDNA 1 month after surgery showed decreased RFS (HR = 1.98, p = 0.055). Preoperative, 1-month, and 7–9 months postoperative positivity for ctDNA and/or CA 19-9 showed a significantly worse median OS (p = 0.024, p = 0.008, and p = 0.0003). We did not find association of ptDNA with OS or RFS, but ptDNA detection 7–9 months after surgery was associated with peritoneal RFS (p = 0.003).</div></div><div><h3>Conclusion</h3><div>Our data indicate that detectable ctDNA in plasma taken before and 7–9 months after surgery holds independent prognostic value in PDAC. Combination of ctDNA with CA-19–9 may be a particularly strong prognosticator, which should be confirmed in future studies.</div></div>","PeriodicalId":13062,"journal":{"name":"Human pathology","volume":"168 ","pages":"Article 106024"},"PeriodicalIF":2.6,"publicationDate":"2025-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145800478","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
A practical approach for assessing high-grade diffuse gliomas and meningiomas. 一种评估胶质瘤和脑膜瘤的实用方法。
IF 2.6 2区 医学 Q2 PATHOLOGY Pub Date : 2025-12-17 DOI: 10.1016/j.humpath.2025.106022
Yi Zhu, Mark A Rudolf, Kyle Conway, Jorge A Trejo-Lopez, Sandra Camelo-Piragua, Aditya Raghunathan

The field of central nervous system (CNS) tumor diagnostics continues to evolve and expand with the emergence and integration of diagnostic, prognostic, and predictive genomic markers. Despite such ever-increasing complexity, it remains within the ability of practicing surgical pathologists to perform an informed assessment of a majority of CNS tumors. In this review, we provide practical guidelines to evaluate the most common primary malignant and benign CNS tumor entities - high-grade diffuse glioma and meningioma.

随着诊断、预后和预测基因组标记的出现和整合,中枢神经系统(CNS)肿瘤诊断领域不断发展和扩展。尽管复杂性不断增加,但实践外科病理学家仍有能力对大多数中枢神经系统肿瘤进行知情评估。在这篇综述中,我们提供了实用的指南来评估最常见的恶性和良性原发性中枢神经系统肿瘤实体-高级别弥漫性胶质瘤和脑膜瘤。
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引用次数: 0
Practice updates: Emerging entities in bone and soft tissue pathology. 实践更新:骨和软组织病理学中的新兴实体。
IF 2.6 2区 医学 Q2 PATHOLOGY Pub Date : 2025-12-17 DOI: 10.1016/j.humpath.2025.106023
Nooshin K Dashti, Scott E Kilpatrick

In last few decades our understanding of bone and soft tissue tumors has evolved significantly, expanding and clarifying our current classification system. Due largely to increased utilization of ancillary testing, particularly molecular tools, new entities are continually emerging and/or being further refined. In addition to morphological and molecular differences, in many instances, the recognition of a new entity carries significant prognostic and potentially therapeutic relevance. In this review on practice updates, we endeavor to discuss five recently described tumors including pseudoendocrine sarcoma, NUT-rearranged sarcoma, VGLL3-rearranged spindle cell rhabdomyosarcoma of head and neck, superficial neurocristic FET::ETS fusion tumors, and NFATC1/2-rearranged epithelioid vascular tumors.

在过去的几十年里,我们对骨和软组织肿瘤的理解有了显著的发展,扩展和澄清了我们目前的分类系统。主要是由于辅助测试的使用增加,特别是分子工具,新的实体不断出现和/或进一步完善。除了形态学和分子差异外,在许多情况下,新实体的识别具有重要的预后和潜在的治疗相关性。在本文中,我们试图讨论最近报道的五种肿瘤,包括假内分泌肉瘤、nut重排肉瘤、vgll3重排的头颈部梭形细胞横纹肌肉瘤、浅表神经系统性FET::ETS融合肿瘤和nfatc1 /2重排的上皮样血管肿瘤。
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引用次数: 0
Updates in bladder and prostate pathology: Diagnostic consensus and clinical relevance. 膀胱和前列腺病理的最新进展:诊断共识和临床相关性。
IF 2.6 2区 医学 Q2 PATHOLOGY Pub Date : 2025-12-16 DOI: 10.1016/j.humpath.2025.106018
Katrina Collins, Sounak Gupta, Liang Cheng

Accurate grading, staging, and classification are essential components of bladder and prostate cancer pathology, directly influencing clinical management and patient outcomes. Recent initiatives by the International Society of Urological Pathology (ISUP) and the Genitourinary Pathology Society (GUPS) have produced key consensus updates aimed at refining diagnostic criteria and resolving long-standing controversies. This review highlights high-impact developments in bladder and prostate pathology, including updated grading systems and T1 substaging in bladder tumors, the proposed hybrid grading approach, and the classification of urachal carcinoma. Evolving perspectives in prostate pathology are also discussed, encompassing intraductal carcinoma of the prostate (IDC-P), neuroendocrine and aggressive variant tumors, and the clinical relevance of Grade Group 1 (GG1) disease in the context of active surveillance. Recent literature and consensus statements are summarized with attention to diagnostic challenges and practical implementation. These focused updates highlight the dynamic nature of urologic pathology and reflect a broader movement toward greater diagnostic precision, reproducibility, and clinical relevance, with adoption of ISUP and GUPS frameworks essential for improving patient outcomes.

准确的分级、分期和分类是膀胱癌和前列腺癌病理的重要组成部分,直接影响临床管理和患者预后。国际泌尿病理学会(ISUP)和泌尿生殖病理学会(GUPS)最近的倡议已经产生了关键的共识更新,旨在完善诊断标准和解决长期存在的争议。这篇综述强调了膀胱和前列腺病理学的重大进展,包括膀胱肿瘤的最新分级系统和T1亚分期、拟议的混合分级方法和尿管癌的分类。本文还讨论了前列腺病理学的发展前景,包括前列腺导管内癌(IDC-P)、神经内分泌和侵袭性变异肿瘤,以及在主动监测背景下1级组疾病的临床相关性。总结了最近的文献和共识声明,关注诊断挑战和实际实施。这些重点更新强调了泌尿系统病理学的动态性质,反映了更广泛的运动,以提高诊断的准确性、可重复性和临床相关性,采用ISUP和GUPS框架对改善患者的预后至关重要。
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