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IF 2.6 2区 医学 Q2 PATHOLOGY Pub Date : 2026-02-01 Epub Date: 2026-02-03 DOI: 10.1016/S0046-8177(26)00037-7
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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 : 2026-02-01 Epub 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。
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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 : 2026-02-01 Epub 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
Targeted RNA sequencing enhances the integrated diagnosis of bone and soft tissue tumors 靶向RNA测序提高了骨和软组织肿瘤的综合诊断
IF 2.6 2区 医学 Q2 PATHOLOGY Pub Date : 2026-02-01 Epub Date: 2026-01-07 DOI: 10.1016/j.humpath.2026.106036
Harumi Nakamura , Yoji Kukita , Toru Wakamatsu , Sho Nakai , Hironari Tamiya , Kei Kunimasa , Toru Kumagai , Fumio Imamura , Kazumi Nishino , Satoshi Takenaka , Yoshiko Hashii , Toshinari Yagi

Background

The diagnosis of bone and soft tissue tumors is challenging due to their rarity, overlapping morphology, and limited access to specialized immunohistochemistry (IHC) in routine practice. Because many of these tumors are fusion-driven, targeted RNA sequencing may improve diagnostic accuracy, but its use is not yet established in Japan.

Methods

We retrospectively analyzed 90 cases of bone and soft tissue tumors, including benign lesions, using the TruSight RNA Pan-Cancer Panel (1385 genes) on FFPE samples. Fusion detection was combined with expression-based clustering. Diagnostic impact was assessed by comparing initial histological impressions with integrated diagnoses incorporating targeted RNA panel findings.

Results

Fusion transcripts were detected in 63 cases (69.2 %), of which 46 were in-frame. Twenty-five cases harbored well-characterized pathogenic fusions that directly contributed to diagnostic confirmation or refinement. Twenty-one cases showed fusion transcripts of uncertain significance, and ten of these were reclassified as likely pathogenic after additional validation. Three cases exhibited complex fusion patterns suggestive of chromothripsis or chromoplexy, warranting further genome-wide analysis. RNA expression clustering distinguished several tumor subtypes and provided complementary support for diagnostically challenging cases, such as undifferentiated pleomorphic sarcoma.

Conclusions

Targeted RNA panel testing enabled robust detection of clinically relevant fusions and provided expression-based insights into tumor classification. When integrated with histopathology, this approach improved diagnostic accuracy in rare tumors and offered a practical triage strategy for extended genomic analysis, highlighting its clinical utility in pathology practice.
背景:骨和软组织肿瘤的诊断具有挑战性,因为它们罕见,形态重叠,并且在常规实践中缺乏专门的免疫组织化学(IHC)。由于许多这些肿瘤是融合驱动的,靶向RNA测序可能会提高诊断的准确性,但它的使用尚未在日本建立。方法回顾性分析90例骨和软组织肿瘤(包括良性病变),采用TruSight RNA Pan-Cancer Panel(1385个基因)对FFPE样本进行分析。融合检测与基于表达的聚类相结合。通过比较最初的组织学印象和结合靶向RNA小组结果的综合诊断来评估诊断的影响。结果63例(69.2%)检测到融合转录本,其中框架内46例。25例具有明确特征的病原融合,直接有助于诊断确认或改进。21例显示不确定意义的融合转录本,其中10例在进一步验证后被重新分类为可能致病。三个病例表现出复杂的融合模式,提示染色体断裂或染色体丛状,需要进一步的全基因组分析。RNA表达聚类区分了几种肿瘤亚型,并为诊断上具有挑战性的病例(如未分化多形性肉瘤)提供了补充支持。结论靶向RNA面板检测能够检测出临床相关的融合体,并为肿瘤分类提供基于表达的见解。当与组织病理学相结合时,该方法提高了罕见肿瘤的诊断准确性,并为扩展基因组分析提供了实用的分诊策略,突出了其在病理实践中的临床应用。
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引用次数: 0
High fidelity of Claudin-18.2 expression in primary and matched metastatic (lymph nodes, peritoneum, and liver) pancreatic ductal adenocarcinoma: a foundation for targeted therapy Claudin-18.2在原发性和匹配转移性(淋巴结、腹膜和肝脏)胰腺导管腺癌中的高保真表达:靶向治疗的基础。
IF 2.6 2区 医学 Q2 PATHOLOGY Pub Date : 2026-02-01 Epub Date: 2025-12-11 DOI: 10.1016/j.humpath.2025.106014
Carlotta Franzina , Michele Bevere , Samantha Bersani , Paola Mattiolo , Carlotta Ceccon , Paola Piccoli , Giuseppe Malleo , Rita T. Lawlor , Roberto Salvia , Michele Milella , Matteo Fassan , Aldo Scarpa , Claudio Luchini
Claudin-18.2 (CLDN18.2) is a tight-junction protein that can be expressed in various neoplasms, including pancreatic ductal adenocarcinoma (PDAC). Anti-CLDN18.2 targeted therapies have already been approved for CLDN18.2-positive gastric cancer and are currently being tested in clinical trials for PDAC. This study aims to define the expression patterns and concordance rate of CLDN18.2 in primary and matched metastatic PDAC.
Whole-slide immunohistochemistry for CLDN18 was performed on primary PDAC and matched metastases, and was assessed by cell percentage (range: 0–100 %) and intensity of CLDN18-positivity (scores 0, 1+, 2+, and 3+), and also using the H-score. Tumor positivity for CLDN18 was determined if ≥ 75 % of tumor cells exhibited 2+/3+ staining.
The study's cohort was composed of 20 patients with PDAC and concomitant lymph node metastases (LNM), 30 patients with PDAC and matched peritoneal metastases (PM), and 12 patients with PDAC and concomitant liver metastases (LIVM). The mean value of the percentages of 2+/3+ cells for primary tumors was 46.5 %, for LNM was 60 %, for PM was 31 %, and for LIVM was 22 %. The mean value of the H-score for primary tumors was 123.9, for LNM was 183, for PM was 89.1, and for LIVM was 54.6. The correspondence rate between primary PDAC and the matched metastatic sites was: 70.0 % for PDAC/LNM, 93.3 % for PDAC/PM, and 100.0 % for PDAC/LIVM.
This study shows a high rate of correspondence of CLDN18-positivity between primary PDAC and different metastatic sites, providing a strong rationale for further exploring and testing anti-CLDN18.2 therapeutic strategies in this lethal malignancy.
Claudin-18.2 (CLDN18.2)是一种紧密连接蛋白,可在包括胰腺导管腺癌(PDAC)在内的多种肿瘤中表达。抗cldn18.2靶向治疗已经被批准用于cldn18.2阳性胃癌,目前正在PDAC的临床试验中进行测试。本研究旨在确定CLDN18.2在原发性和匹配性转移性PDAC中的表达模式和一致性率。对原发性PDAC和匹配的转移瘤进行了CLDN18的全切片免疫组化,并通过细胞百分比(范围:0-100%)和CLDN18阳性强度(评分0、1+、2+和3+)进行评估,并使用h评分。如果≥75%的肿瘤细胞呈现2+/3+染色,则确定CLDN18呈肿瘤阳性。该研究的队列包括20例PDAC伴发淋巴结转移(LNM)患者,30例PDAC伴发腹膜转移(PM)患者,12例PDAC伴发肝转移(LIVM)患者。原发肿瘤中2+/3+细胞百分比的平均值为46.5%,LNM为60%,PM为31%,LIVM为22%。原发肿瘤的h评分平均值为123.9,LNM为183,PM为89.1,LIVM为54.6。原发PDAC与匹配转移部位的对应率为:PDAC/LNM为70.0%,PDAC/PM为93.3%,PDAC/LIVM为100.0%。本研究显示原发性PDAC与不同转移部位之间cldn18阳性的高对应率,为进一步探索和测试这种致命恶性肿瘤的抗cldn18.2治疗策略提供了强有力的理论依据。
{"title":"High fidelity of Claudin-18.2 expression in primary and matched metastatic (lymph nodes, peritoneum, and liver) pancreatic ductal adenocarcinoma: a foundation for targeted therapy","authors":"Carlotta Franzina ,&nbsp;Michele Bevere ,&nbsp;Samantha Bersani ,&nbsp;Paola Mattiolo ,&nbsp;Carlotta Ceccon ,&nbsp;Paola Piccoli ,&nbsp;Giuseppe Malleo ,&nbsp;Rita T. Lawlor ,&nbsp;Roberto Salvia ,&nbsp;Michele Milella ,&nbsp;Matteo Fassan ,&nbsp;Aldo Scarpa ,&nbsp;Claudio Luchini","doi":"10.1016/j.humpath.2025.106014","DOIUrl":"10.1016/j.humpath.2025.106014","url":null,"abstract":"<div><div>Claudin-18.2 (CLDN18.2) is a tight-junction protein that can be expressed in various neoplasms, including pancreatic ductal adenocarcinoma (PDAC). Anti-CLDN18.2 targeted therapies have already been approved for CLDN18.2-positive gastric cancer and are currently being tested in clinical trials for PDAC. This study aims to define the expression patterns and concordance rate of CLDN18.2 in primary and matched metastatic PDAC.</div><div>Whole-slide immunohistochemistry for CLDN18 was performed on primary PDAC and matched metastases, and was assessed by cell percentage (range: 0–100 %) and intensity of CLDN18-positivity (scores 0, 1+, 2+, and 3+), and also using the H-score. Tumor positivity for CLDN18 was determined if ≥ 75 % of tumor cells exhibited 2+/3+ staining.</div><div>The study's cohort was composed of 20 patients with PDAC and concomitant lymph node metastases (LNM), 30 patients with PDAC and matched peritoneal metastases (PM), and 12 patients with PDAC and concomitant liver metastases (LIVM). The mean value of the percentages of 2+/3+ cells for primary tumors was 46.5 %, for LNM was 60 %, for PM was 31 %, and for LIVM was 22 %. The mean value of the H-score for primary tumors was 123.9, for LNM was 183, for PM was 89.1, and for LIVM was 54.6. The correspondence rate between primary PDAC and the matched metastatic sites was: 70.0 % for PDAC/LNM, 93.3 % for PDAC/PM, and 100.0 % for PDAC/LIVM.</div><div>This study shows a high rate of correspondence of CLDN18-positivity between primary PDAC and different metastatic sites, providing a strong rationale for further exploring and testing anti-CLDN18.2 therapeutic strategies in this lethal malignancy.</div></div>","PeriodicalId":13062,"journal":{"name":"Human pathology","volume":"168 ","pages":"Article 106014"},"PeriodicalIF":2.6,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145751797","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
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 : 2026-02-01 Epub 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。
{"title":"B72.3 serves as a new diagnostic marker for testicular Leydig cell tumor","authors":"Jianping Zhao ,&nbsp;William Mi ,&nbsp;Varsha Nair ,&nbsp;Barrett C. Lawson ,&nbsp;Charles C. Guo ,&nbsp;Elizabeth M. Jacobi ,&nbsp;Qingqing Ding","doi":"10.1016/j.humpath.2025.106026","DOIUrl":"10.1016/j.humpath.2025.106026","url":null,"abstract":"<div><div>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.</div></div>","PeriodicalId":13062,"journal":{"name":"Human pathology","volume":"168 ","pages":"Article 106026"},"PeriodicalIF":2.6,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145827683","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
Inside front cover - Masthead 内前盖-报头
IF 2.6 2区 医学 Q2 PATHOLOGY Pub Date : 2026-02-01 Epub Date: 2026-02-03 DOI: 10.1016/S0046-8177(26)00030-4
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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 : 2026-02-01 Epub 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
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 : 2026-02-01 Epub 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":"2026-02-01","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
Prognostic value of baseline peritoneal fluid cytology in 224 patients with unresectable peritoneal metastasis treated with Pressurized IntraPeritoneal Aerosol Chemotherapy (PIPAC) 224例不可切除腹膜转移患者接受加压气雾化疗(PIPAC)的基线腹膜液细胞学检查的预后价值。
IF 2.6 2区 医学 Q2 PATHOLOGY Pub Date : 2026-02-01 Epub Date: 2025-12-14 DOI: 10.1016/j.humpath.2025.106017
Magnus Skov Jørgensen , Alan Patrick Ainsworth , Claus Wilki Fristrup , Michael Bau Mortensen , Martin Graversen , Sönke Detlefsen
Patients with peritoneal metastasis (PM) from gastrointestinal and gynecological cancer can be treated palliatively with Pressurized IntraPeritoneal Aerosol Chemotherapy (PIPAC). Only few prognostic markers for stratification of PM-patients treated with PIPAC exist. The prognostic value of peritoneal fluid (PF) cytology has only been examined to a limited extent. Our primary aim was to investigate the prognostic value of baseline PF cytology in unresectable PM treated with PIPAC. We performed a retrospective analysis of prospectively collected data from all PM patients treated with PIPAC at Odense PIPAC Center from 2015 to 2024. Positive baseline PF cytology was defined as malignant cells or cells suspicious of malignancy. Survival data were analyzed using the Kaplan–Meier graphs, log rank test and multivariable Cox proportional hazards regression. Inclusion criteria were fulfilled by 224 patients, of which 139 (61 %) had positive cytology at PIPAC 1. Patients with positive baseline cytology had a significantly higher ascites volume (150 mL vs. 20 mL, p < 0.001), higher peritoneal cancer index (PCI) (15 vs. 3.5, p < 0.001) and higher mean histological Peritoneal Regression Grading Score (PRGS) (3.0 vs. 1.0, p < 0.001), compared to patients with negative baseline cytology. Positive baseline cytology was associated with shorter overall survival (OS) for the entire cohort (P < 0.01), PM from gastric cancer (GC-PM) (P = 0.007), and PM from colon cancer (CC-PM) (P = 0.02), but not for PM from ovarian cancer (OC-PM) or pancreatic cancer (PC-PM). However, at multivariate analysis, baseline PF cytology had no independent prognostic value. The PRGS, on the other hand, showed independent prognostic value in all multivariable models used. In conclusion, our data from this retrospective cohort study indicate that baseline PF cytology holds no independent prognostic value. However, for classification of a given patient as having complete response to treatment, this modality is still recommended, together with histological response assessment (PRGS).
胃肠道和妇科肿瘤腹膜转移(PM)患者可以采用加压腹腔气溶胶化疗(PIPAC)进行姑息性治疗。对于PIPAC治疗的pm患者,只有很少的预后标记物存在。腹膜液(PF)细胞学的预后价值仅在有限的范围内进行了检查。我们的主要目的是研究基线PF细胞学对PIPAC治疗的不可切除PM的预后价值。我们对2015年至2024年在欧登塞PIPAC中心接受PIPAC治疗的所有PM患者的前瞻性数据进行了回顾性分析。基线PF细胞学阳性定义为恶性细胞或可疑恶性细胞。生存资料分析采用Kaplan-Meier图、对数秩检验和多变量Cox比例风险回归。224例患者符合纳入标准,其中139例(61%)PIPAC 1细胞学阳性。基线细胞学阳性的患者腹水容量明显更高(150 mL vs. 20 mL, p
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Human pathology
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