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Adult granulosa cell tumours of the testis analogous to ovarian counterparts are exceptionally rare: analysis of a multicentric series and review of the literature 成人睾丸颗粒细胞瘤类似于卵巢颗粒细胞瘤是非常罕见的:多中心系列分析和文献回顾。
IF 4.1 2区 医学 Q2 CELL BIOLOGY Pub Date : 2025-11-20 DOI: 10.1111/his.70048
Costantino Ricci, Dario de Biase, Thais Maloberti, Agnese Orsatti, Thomas M Ulbright, Muhammad T Idrees, Esther Oliva, Kristine Cornejo, João Lobo, Kvetoslava Michalova, Maria Rosaria Raspollini, Sean R Williamson, Geert JLH van Leenders, Chia-Sui Kao, Fiona Maclean, Ankur R Sangoi, Adeboye O Osunkoya, Michelangelo Fiorentino, Antonio De Leo, Giovanni Tallini, Andres Martin Acosta

Aims

Testicular adult granulosa cell tumours (AGCTs) are rare and show several clinical–pathological differences with their ovarian counterparts. In a limited number of prior studies, FOXL2 p.Cys134Trp, the hallmark molecular alteration of ovarian AGCT, appeared to be infrequent in testicular AGCTs. However, the number of cases analysed to date is relatively small.

Methods and results

Twenty testicular AGCTs were analysed de novo using two different next-generation sequencing (NGS) panels that cover sex cord-stromal tumour (SCST)–relevant genes, including FOXL2, CTNNB1, FH and DICER1. Among 12 tumours (12/20; 60%) that were sequenced successfully, none harboured FOXL2 mutations. Eight tumours (8/12, 66.7%) showed a wild-type (WT) status for all genes assessed with the panels. Three tumours harboured pathogenic or likely pathogenic CTNNB1 alterations. One of these exhibited predominant spindle cell morphology, while the other two showed focal tubular architecture. Immunohistochemistry performed in one of these tumours with available material showed β-catenin expression in ~70% of tumor cell nuclei. The remaining AGCTs showed variants of uncertain significance (likely benign) in KIT and MED12. Considering the tumors asseseed in this study and those previously reported in the literature, only 2 of 29 neoplasms classified as testicular AGCTs have shown a FOXL2 p.Cys134Trp mutation to date.

Conclusions

The present study confirms that SCSTs classified as AGCTs differ from their ovarian counterparts in that they largely lack FOXL2 mutations.

目的:睾丸成人颗粒细胞瘤(agct)是罕见的,并表现出一些临床病理差异与卵巢同行。在有限数量的先前研究中,卵巢AGCT的标志性分子改变FOXL2 p.Cys134Trp在睾丸AGCT中似乎并不常见。然而,迄今为止分析的病例数量相对较少。方法和结果:使用两种不同的下一代测序(NGS)面板重新分析了20例睾丸agct,该面板覆盖了性脐带间质瘤(SCST)相关基因,包括FOXL2, CTNNB1, FH和DICER1。在成功测序的12个肿瘤(12/20,60%)中,没有一个包含FOXL2突变。8个肿瘤(8/12,66.7%)的所有基因均显示野生型(WT)状态。三个肿瘤含有致病性或可能致病性CTNNB1改变。其中一个主要表现为梭形细胞形态,而另外两个表现为局灶管状结构。其中一个肿瘤的免疫组化显示,70%的肿瘤细胞核中表达β-catenin。其余agct在KIT和MED12中显示不确定意义的变异(可能是良性的)。考虑到本研究评估的肿瘤和先前文献报道的肿瘤,到目前为止,29例归类为睾丸agct的肿瘤中只有2例显示FOXL2 p.Cys134Trp突变。结论:目前的研究证实,被归类为agct的SCSTs与卵巢同类的不同之处在于,它们在很大程度上缺乏FOXL2突变。
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引用次数: 0
Apocrine carcinoma of the breast: distinctive metabolic reprogramming and high-frequency PIK3CA mutations revealed by molecular and immunohistochemical analysis 乳腺大汗腺癌:分子和免疫组织化学分析揭示的独特代谢重编程和高频PIK3CA突变。
IF 4.1 2区 医学 Q2 CELL BIOLOGY Pub Date : 2025-11-20 DOI: 10.1111/his.70024
Harumi Nakamura, Yoji Kukita, Nobuyoshi Kittaka, Hiroki Kusama, Takahiro Nakayama, Yasuhiro Tamaki, Ken-ichi Yoshida, Kei Kunimasa, Fumio Imamura, Toshinari Yagi

Aims

Apocrine carcinoma (AC) is a rare and distinct subtype of invasive breast carcinoma, typically characterized by androgen receptor (AR) positivity and negative expression of oestrogen and progesterone receptors. This study aimed to clarify the metabolic and molecular characteristics of AC, with a particular focus on protein expression related to lipid metabolism and the frequency and nature of PIK3CA mutations.

Methods

We analysed tissue specimens from 40 cases with AC and 59 cases with other breast cancer subtypes (ER+/HER2−, ER+/HER2+, ER−/HER2+ and triple-negative breast cancer [TNBC]). Immunohistochemistry was performed for a panel of lipid metabolism-related proteins including FASN, AMACR, ACOX1, ACSL1 and catalase. mRNA Expression of ACSL1 was assessed by RT-qPCR and PIK3CA mutations were analysed via targeted sequencing.

Results

AC showed significantly higher expression of enzymes involved in fatty acid synthesis and peroxisomal β-oxidation compared to other subtypes. Notably, ACSL1 was upregulated at both protein and mRNA levels, and catalase was upregulated at the protein level, indicating an increase in peroxisomes. PIK3CA Mutations, particularly the hotspot p.H1047R variant, were detected at a significantly higher frequency in AC (68.4%) compared to the other subtypes: ER+/HER2− (52.6%), ER+/HER2+ (27.3%), ER−/HER2+ (50.0%) and TNBC (33.3%) (P < 0.05).

Conclusions

AC is characterized by distinct metabolic reprogramming, with preferential upregulation of peroxisomal β-oxidation rather than mitochondrial pathways. These metabolic features are accompanied by a high prevalence of activating PIK3CA mutations, suggesting a link between genomic alterations and metabolic phenotype. These findings provide new insights into the pathobiology of AC and may assist in its histopathological differentiation from other breast cancer subtypes.

目的:大汗腺癌(Apocrine carcinoma, AC)是一种罕见而独特的浸润性乳腺癌亚型,其典型特征是雄激素受体(雄激素受体)阳性,雌激素和孕激素受体表达阴性。本研究旨在阐明AC的代谢和分子特征,特别关注与脂质代谢相关的蛋白表达以及PIK3CA突变的频率和性质。方法:对40例AC和59例其他乳腺癌亚型(ER+/HER2-、ER+/HER2+、ER-/HER2+和三阴性乳腺癌[TNBC])的组织标本进行分析。对脂质代谢相关蛋白进行免疫组化,包括FASN、AMACR、ACOX1、ACSL1和过氧化氢酶。RT-qPCR检测ACSL1 mRNA表达,靶向测序分析PIK3CA突变。结果:AC与其他亚型相比,其脂肪酸合成和过氧化物酶体β-氧化相关酶的表达显著增加。值得注意的是,ACSL1在蛋白质和mRNA水平上均上调,过氧化氢酶在蛋白质水平上上调,表明过氧化物酶体增加。与ER+/HER2-(52.6%)、ER+/HER2+(27.3%)、ER-/HER2+(50.0%)和TNBC(33.3%)等其他亚型相比,AC中PIK3CA突变的检测频率(68.4%)显著高于其他亚型:ER+/HER2-(52.6%)、ER+/HER2+(27.3%)、ER-/HER2+(50.0%)和TNBC(33.3%)。(P)结论:AC具有明显的代谢重编程特征,其优先上调过氧化物酶体β-氧化而不是线粒体途径。这些代谢特征伴随着激活PIK3CA突变的高流行率,表明基因组改变与代谢表型之间存在联系。这些发现为AC的病理生物学提供了新的见解,并可能有助于其与其他乳腺癌亚型的组织病理学区分。
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引用次数: 0
Testicular mass frozen section examination: Pathological insights and diagnostic accuracy 睾丸肿物冰冻切片检查:病理见解及诊断准确性。
IF 4.1 2区 医学 Q2 CELL BIOLOGY Pub Date : 2025-11-20 DOI: 10.1111/his.70049
Roselyne Choiniere, Willem P A Boellaard, Marij Dinkelman-Smit, Geert J L H van Leenders

Background and Objectives

Testicular frozen section examination on excisional biopsy (FSEB) is an underused pathological and surgical approach, considering the increasing number of small benign testicular lesions found on radical orchidectomy specimens. This study aims to determine the diagnostic accuracy of FSEB and to provide a pathological summary of the most frequent diagnoses and pitfalls.

Methods

We report the pathological findings and definitive outcome of 135 FSEB for small testicular masses performed between 2005 and 2024 in a single institute.

Results

The median tumour size was 0.9 cm (Interquartile Range [IQR] 0.5–1.3 cm). The most common FSEB diagnoses were Leydig cell hyperplasia/tumour (n = 37; 28%) and seminoma (n = 36; 27%). On FSEB, benign diagnoses represented 58% of cases which allowed us to avoid 81 unnecessary radical orchidectomies. The sensitivity and specificity of FSEB for malignancy were 100% and 96.3%, respectively. Excluding three indeterminate cases on FSEB, the concordance rate was 97.7% (129/132). On definitive assessment, the majority of cases were benign (84/135, 62%) and 51 (38%) cases were malignant. The three indeterminate cases were ultimately confirmed as benign. There were three false-positive diagnoses of (favoured) malignancy and no false negatives.

Conclusions

FSEB is accurate for patient management of small testicular lesions, allowing us to save young men from unnecessary radical orchidectomy. We provide an in-depth overview of the most prevalent pathological diagnoses encountered.

背景和目的:考虑到在根治性睾丸切除术标本中发现越来越多的小睾丸良性病变,睾丸冷冻切片活检(FSEB)是一种未被充分利用的病理和外科方法。本研究旨在确定FSEB的诊断准确性,并提供最常见的诊断和陷阱的病理总结。方法:我们报告了2005年至2024年间在同一研究所进行的135例小睾丸肿块的FSEB的病理表现和最终结果。结果:中位肿瘤大小为0.9 cm(四分位间距[IQR] 0.5 ~ 1.3 cm)。最常见的FSEB诊断为间质细胞增生/肿瘤(n = 37, 28%)和精原细胞瘤(n = 36, 27%)。在FSEB中,良性诊断占58%的病例,这使我们避免了81例不必要的根治性睾丸切除术。FSEB对恶性肿瘤的敏感性为100%,特异性为96.3%。排除3例FSEB不确定病例,符合率为97.7%(129/132)。在最终评估中,大多数病例为良性(84/135,62%),51例(38%)为恶性。三个不确定的病例最终被证实为良性。有3例(有利的)恶性肿瘤假阳性诊断,无假阴性。结论:FSEB对于小睾丸病变的患者治疗是准确的,使我们能够从不必要的根治性睾丸切除术中拯救年轻男性。我们提供了一个深入的概述最普遍的病理诊断遇到。
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引用次数: 0
Acellular mucin pools and neutrophil-to-lymphocyte ratio: unveiling hidden aggressiveness in pathological complete response after chemoradiotherapy for rectal cancer 脱细胞粘蛋白池和中性粒细胞/淋巴细胞比值:揭示直肠癌放化疗后病理完全缓解的隐藏侵袭性。
IF 4.1 2区 医学 Q2 CELL BIOLOGY Pub Date : 2025-11-20 DOI: 10.1111/his.70050
Zhenyu Xu, Heyuan Zhu, Xiaojie Wang, Yongqin Tang, Ying Huang, Pan Chi, Yanwu Sun

Background

Pathological complete response (pCR) following neoadjuvant chemoradiotherapy (nCRT) for locally advanced rectal cancer (LARC) does not eliminate tumor recurrence risk, with distant metastasis remaining a critical challenge. This study aimed to identify novel prognostic factors for risk stratification in pCR patients after nCRT.

Methods

We enrolled 149 LARC patients who achieved pCR between 2016 and 2020. Acellular mucin pools (AMP) were classified by the deepest tissue layer of AMP (A0: absent; A1: within the muscularis propria; A2: exceeding the muscularis propria). The primary endpoint was disease-free survival (DFS); secondary endpoints included overall survival (OS) and recurrence patterns.

Results

After a median follow-up of 75.3 months, the 5-year OS and DFS rates were 95.3% and 89.9%, respectively. Among 15 recurrence events, all were distant metastases (80% pulmonary). AMP were present in 17.4% (26/149) of patients. Multivariate analysis identified AMP exceeding the muscularis propria (HR = 3.996, 95% CI: 1.073–14.660, P = 0.039), preoperative neutrophil-to-lymphocyte ratio (NLR) >4.4 (HR = 3.658, 95% CI: 1.304–10.263, P = 0.014) and tumour distance from the anal verge on pretreatment magnetic resonance imaging (MRI) (HR = 0.667, 95% CI: 0.481–0.925, P = 0.015) as independent predictors of distant metastasis-free survival (DMFS). A nomogram integrating these factors showed robust discriminative performance for 1-, 3-, and 5-year DMFS (AUC = 0.689, 0.815, 0.795). Meanwhile, AMP exceeding the muscularis propria (HR = 6.632, P = 0.010) and pretreatment MRI-assessed tumour distance from the anal margin (HR = 0.614, P = 0.018) were independent predictors for pulmonary metastasis.

Conclusions

AMP exceeding the muscularis propria and high pretreatment NLR are complementary prognostic markers that refine risk stratification in pCR patients, enabling personalized surveillance and treatment strategies to improve outcomes.

背景:局部晚期直肠癌(LARC)的新辅助放化疗(nCRT)后病理完全缓解(pCR)并不能消除肿瘤复发的风险,远处转移仍然是一个关键的挑战。本研究旨在确定nCRT后pCR患者风险分层的新预后因素。方法:我们在2016年至2020年期间招募了149例实现pCR的LARC患者。脱细胞粘蛋白池(AMP)按AMP的最深组织层进行分类(A0:无;A1:在固有肌层内;A2:超过固有肌层)。主要终点为无病生存期(DFS);次要终点包括总生存期(OS)和复发模式。结果:中位随访75.3个月后,5年OS和DFS分别为95.3%和89.9%。在15例复发事件中,均为远处转移(80%为肺转移)。17.4%(26/149)的患者存在AMP。多因素分析发现,AMP超过固有肌层(HR = 3.996, 95% CI: 1.073-14.660, P = 0.039)、术前中性粒细胞与淋巴细胞比值(NLR) bbb4.4 (HR = 3.658, 95% CI: 1.304-10.263, P = 0.014)和前处理磁共振成像(MRI)肿瘤距离肛门边缘(HR = 0.667, 95% CI: 0.481-0.925, P = 0.015)是远处无转移生存(DMFS)的独立预测因子。综合这些因素的nomogram显示了1年、3年和5年DMFS的稳健判别性能(AUC = 0.689, 0.815, 0.795)。AMP超过固有肌层(HR = 6.632, P = 0.010)和预处理mri评估肿瘤距肛缘的距离(HR = 0.614, P = 0.018)是肺转移的独立预测因子。结论:AMP超过固有肌层和高预处理NLR是完善pCR患者风险分层的补充预后标志物,使个性化监测和治疗策略能够改善预后。
{"title":"Acellular mucin pools and neutrophil-to-lymphocyte ratio: unveiling hidden aggressiveness in pathological complete response after chemoradiotherapy for rectal cancer","authors":"Zhenyu Xu,&nbsp;Heyuan Zhu,&nbsp;Xiaojie Wang,&nbsp;Yongqin Tang,&nbsp;Ying Huang,&nbsp;Pan Chi,&nbsp;Yanwu Sun","doi":"10.1111/his.70050","DOIUrl":"10.1111/his.70050","url":null,"abstract":"<div>\u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Pathological complete response (pCR) following neoadjuvant chemoradiotherapy (nCRT) for locally advanced rectal cancer (LARC) does not eliminate tumor recurrence risk, with distant metastasis remaining a critical challenge. This study aimed to identify novel prognostic factors for risk stratification in pCR patients after nCRT.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We enrolled 149 LARC patients who achieved pCR between 2016 and 2020. Acellular mucin pools (AMP) were classified by the deepest tissue layer of AMP (A0: absent; A1: within the muscularis propria; A2: exceeding the muscularis propria). The primary endpoint was disease-free survival (DFS); secondary endpoints included overall survival (OS) and recurrence patterns.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>After a median follow-up of 75.3 months, the 5-year OS and DFS rates were 95.3% and 89.9%, respectively. Among 15 recurrence events, all were distant metastases (80% pulmonary). AMP were present in 17.4% (26/149) of patients. Multivariate analysis identified AMP exceeding the muscularis propria (HR = 3.996, 95% CI: 1.073–14.660, <i>P</i> = 0.039), preoperative neutrophil-to-lymphocyte ratio (NLR) &gt;4.4 (HR = 3.658, 95% CI: 1.304–10.263, <i>P</i> = 0.014) and tumour distance from the anal verge on pretreatment magnetic resonance imaging (MRI) (HR = 0.667, 95% CI: 0.481–0.925, <i>P</i> = 0.015) as independent predictors of distant metastasis-free survival (DMFS). A nomogram integrating these factors showed robust discriminative performance for 1-, 3-, and 5-year DMFS (AUC = 0.689, 0.815, 0.795). Meanwhile, AMP exceeding the muscularis propria (HR = 6.632, <i>P</i> = 0.010) and pretreatment MRI-assessed tumour distance from the anal margin (HR = 0.614, <i>P</i> = 0.018) were independent predictors for pulmonary metastasis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>AMP exceeding the muscularis propria and high pretreatment NLR are complementary prognostic markers that refine risk stratification in pCR patients, enabling personalized surveillance and treatment strategies to improve outcomes.</p>\u0000 </section>\u0000 </div>","PeriodicalId":13219,"journal":{"name":"Histopathology","volume":"88 4","pages":"854-867"},"PeriodicalIF":4.1,"publicationDate":"2025-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145563740","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
Novel NOTCH3 alteration expanding the molecular spectrum of pericytic tumours: report of two cases 新的NOTCH3改变扩大了周细胞肿瘤的分子谱:两例报告。
IF 4.1 2区 医学 Q2 CELL BIOLOGY Pub Date : 2025-11-20 DOI: 10.1111/his.70051
Irena Antonia Ungureanu, Megane Le Quang, Rihab Azmani, Marie Ancelle, Henri Margot, Guillaume Chotard, François Le Loarer, Nathalène Truffaux

Introduction

Myofibromas are part of the pericytic tumour family, which includes myopericytomas, glomus tumours and angioleiomyomas. While they typically display benign behaviour when arising in the skin and subcutaneous tissues of the head and neck, rare aggressive variants have been reported, particularly those with visceral or intracranial involvement. The most frequently identified molecular alterations in myofibromas are PDGFRB gain-of-function mutations, primarily single-nucleotide substitutions.

Case presentation

Herein, we report two cases of myofibroma: one aggressive case with central nervous system involvement in a newborn, exhibiting a monophasic morphology, and a second, subcutaneous case in an adult. RNA sequencing was performed on both tumours, and data analysis was conducted using a four-pipeline fusion-calling approach (Arriba, FusionCatcher, FusionMap and STAR-Fusion). This analysis identified a novel somatic internal tandem duplication (ITD) in the NOTCH3 gene, affecting exons 26 and 27, specifically involving the C-terminal heterodimerization domain of the NOTCH3 receptor. Unsupervised hierarchical clustering demonstrated that myofibromas with ITDs segregate distinctly from conventional myofibromas and other pericytic tumours.

Discussion and conclusion

Our findings suggest that NOTCH3 ITDs represent a novel oncogenic mechanism in pericytic tumour pathogenesis, likely driving constitutive activation of the NOTCH signalling pathway. Given the potential therapeutic relevance, particularly in aggressive or life-threatening cases with CNS involvement, our findings highlight the importance of extensive molecular profiling. Targeted therapy with NOTCH inhibitors may represent a promising strategy in the management of aggressive cases of ITD-driven pericytic tumours.

简介:肌纤维瘤是周细胞瘤家族的一部分,包括肌外皮细胞瘤、血管球瘤和血管平滑肌瘤。虽然它们在头颈部皮肤和皮下组织中通常表现为良性,但罕见的侵袭性变异已被报道,特别是那些累及内脏或颅内的变异。肌纤维瘤中最常见的分子改变是PDGFRB功能获得突变,主要是单核苷酸取代。病例介绍:在此,我们报告两个肌纤维瘤病例:一个侵袭性的病例与中枢神经系统在一个新生儿,表现为单相形态,和第二个,皮下病例在一个成年人。对两种肿瘤进行RNA测序,并使用四管道融合调用方法(Arriba, FusionCatcher, FusionMap和STAR-Fusion)进行数据分析。该分析在NOTCH3基因中发现了一种新的体细胞内部串联重复(ITD),影响外显子26和27,特别涉及NOTCH3受体的c端异二聚化结构域。无监督的分层聚类表明,伴有过渡段的肌纤维瘤与传统的肌纤维瘤和其他周细胞性肿瘤明显不同。讨论和结论:我们的研究结果表明,NOTCH3 ITDs在周细胞瘤发病机制中代表了一种新的致癌机制,可能驱动NOTCH信号通路的组成性激活。考虑到潜在的治疗相关性,特别是在侵袭性或危及生命的中枢神经系统病例中,我们的研究结果强调了广泛的分子谱分析的重要性。靶向治疗NOTCH抑制剂可能是治疗侵袭性itd驱动的周细胞肿瘤的一个很有前途的策略。
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引用次数: 0
WHO classification of skin tumours: key updates in the fifth edition 世卫组织皮肤肿瘤分类:第五版的重要更新。
IF 4.1 2区 医学 Q2 CELL BIOLOGY Pub Date : 2025-11-20 DOI: 10.1111/his.15562
Gabrielle Goldman-Lévy, Raymond Barnhill, Boris C. Bastian, Werner Kempf, David Elder MB, ChB, FRCPA, Pedram Gerami, Wayne Grayson, Dmitry Kazakov, Daniela Massi, Jane Messina, Arnaud de la Fouchardière, Alexander J. Lazar, Thomas Brenn, Brian Rous, Andrew Field, Anthony Gill, Jennelle C. Hodge, Joseph D Khoury, Katia Leite, Shahin Sayed, Puay Hoon Tan, Rosalie Elenitsas, Eduardo Calonje, Lyn M. Duncan, Liang Zhiyong, Holger Moch, Rajendra Singh, Harshima Wijesinghe, Ian Cree, Dilani Lokuhetty

The 5th edition of the World Health Organization Classification of Tumours (WCT) serves as a foundation for global diagnostic standards in tumour pathology. Similar to other volumes in this series, the Skin Tumours (Skin5) edition follows a standardized approach. This edition introduces two new chapters: ‘Tumours of the nail unit’ and ‘Metastases to skin’, along with new entities across relevant chapters. This review article provides an overview of the updates in Skin5 based on currently published evidence, with emphasis on newly introduced chapters and newly described entities that involve the skin, in particular, epidermal, melanocytic and appendageal tumours.

世界卫生组织第五版肿瘤分类(WCT)是全球肿瘤病理学诊断标准的基础。类似于本系列的其他卷,皮肤肿瘤(Skin5)版遵循标准化的方法。这个版本介绍了两个新的章节:“指甲单位的肿瘤”和“转移到皮肤”,以及相关章节的新实体。这篇综述文章根据目前发表的证据对Skin5的更新进行了概述,重点介绍了涉及皮肤的新章节和新描述的实体,特别是表皮、黑素细胞和附件肿瘤。
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引用次数: 0
Seven years as Editor: what I have learned 七年的编辑生涯:我所学到的
IF 4.1 2区 医学 Q2 CELL BIOLOGY Pub Date : 2025-11-11 DOI: 10.1111/his.70031
Daniel M Berney
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引用次数: 0
The validation of histological criteria from the IAIH-PG to distinguish AIH from drug-induced liver injury 从IAIH-PG中鉴别AIH与药物性肝损伤的组织学标准的验证。
IF 4.1 2区 医学 Q2 CELL BIOLOGY Pub Date : 2025-11-09 DOI: 10.1111/his.70027
Zikun Ma, Li Wang, Jimin Liu, Romil Saxena, Zongming Chen, Xuchen Zhang, Hanlin Wang, Mukul Vij, Mina Komuta, Gwyneth Soon, Wei Zheng, Jiping Zhang, Bin Wang, Min Li, Yongfeng Yang, Xinyan Zhao

Background and aims

To validate the applicability of the new histological criteria for autoimmune hepatitis (AIH) proposed by the International AIH Pathology Group (IAIH-PG) among Chinese patients with AIH and drug-induced liver injury (DILI).

Methods

The gold standard for diagnosis relied on clinical response: discontinuing treatment without relapse supported DILI, while relapse or ongoing immunosuppressive treatment confirmed AIH. This two-centre retrospective cohort study included inpatients with DILI or AIH from January 2002 to March 2023. Cases that underwent liver biopsy were selected according to inclusion and exclusion criteria. The diagnostic performance of the criteria was assessed by an area under the receiver operating characteristic curve (AUROC).

Results

Out of 69 patients: AIH (41, 59%) and DILI (28, 41%). The accuracy, sensitivity and specificity of the new histological criteria for likely and possible AIH were 70%, 98% and 29%, respectively, with an AUROC of 0.8236 [95% confidence interval (CI): 0.7533–0.8938]. For likely AIH, the accuracy, sensitivity and specificity were 73%, 61% and 89%, respectively, with an AUROC of 0.9177 [95% CI: 0.8757–0.9596]. Moreover, for possible AIH, significant differences were found in serum alanine aminotransferase levels [178.4 (87.0, 435.0) versus 536.5 (206.9, 930.4) U/L] and antinuclear antibody (ANA) ≥1:160 [10 (67%) versus 1 (6%)], as well as in lobular lymphoplasmacytic infiltrate [15 (100%) versus 12 (71%)] and more than mild inflammation [13 (87%)versus 6 (35%)] between AIH and DILI (all P values were <0.05).

Conclusion

The new histological criteria exhibit good diagnostic efficacy in distinguishing AIH from DILI in China, with high AUROC. Key discriminators include low aminotransferase, ANA ≥1:160, lobular lymphoplasmacytic infiltrate and more than mild inflammation, which may further improve diagnostic accuracy for AIH.

背景与目的:验证国际AIH病理组(IAIH-PG)提出的自身免疫性肝炎(AIH)新组织学标准在中国AIH合并药物性肝损伤(DILI)患者中的适用性。方法:诊断的金标准依赖于临床反应:停止治疗无复发支持DILI,而复发或持续免疫抑制治疗证实AIH。这项双中心回顾性队列研究纳入了2002年1月至2023年3月期间DILI或AIH住院患者。根据纳入和排除标准选择行肝活检的病例。通过受试者工作特征曲线下面积(AUROC)评估标准的诊断性能。结果:69例患者中:AIH(41.59%)和DILI(28.41%)。新组织学标准诊断疑似AIH和可能AIH的准确率、敏感性和特异性分别为70%、98%和29%,AUROC为0.8236[95%可信区间(CI): 0.7533-0.8938]。对于疑似AIH,准确率、敏感性和特异性分别为73%、61%和89%,AUROC为0.9177 [95% CI: 0.8757-0.9596]。此外,对于可能的AIH, AIH和DILI在血清丙氨酸转氨酶水平[178.4(87.0,435.0)比536.5 (206.9,930.4)U/L]和抗核抗体(ANA)≥1:160[10(67%)比1(6%)]、小叶淋巴浆细胞浸润[15(100%)比12(71%)]和轻度以上炎症[13(87%)比6(35%)]方面存在显著差异(P值均为:新的组织学标准在区分AIH和DILI方面表现出良好的诊断效果,AUROC较高。关键鉴别指标包括低转氨酶、ANA≥1:160、小叶淋巴浆细胞浸润和轻度以上炎症,可进一步提高AIH的诊断准确性。
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引用次数: 0
Pathologic assessment of resected stage III non-small cell lung cancer after neoadjuvant chemotherapy: identification of additional prognostic factors 新辅助化疗后切除的III期非小细胞肺癌的病理评估:确定其他预后因素。
IF 4.1 2区 医学 Q2 CELL BIOLOGY Pub Date : 2025-11-09 DOI: 10.1111/his.70025
Francesca Lunardi, Alessandra Ferro, Luca Vedovelli, Federica Pezzuto, Sofia-Eleni Tzorakoleftheraki, Asuman Kilitci, Yuliia Kuzyk, Simone Zanella, Marco Schiavon, Federico Rea, Giulia Pasello, Fiorella Calabrese

Background

Non-small cell lung cancer (NSCLC) patients undergoing neoadjuvant chemotherapy (NACT) followed by surgery represent an ideal clinical setting to identify prognostic factors. To date, major pathological response (MPR) and complete pathological response (pCR) have been used as surrogates of NACT response and clinical outcome. The aim of the study was to investigate the role of additional clinico-pathological features, taking advantage of morphometry and artificial intelligence (AI).

Methods

Seventy stage III NSCLC patients undergoing surgery after NACT were studied. A granular evaluation of histological parameters with morphometrical quantification of the stromal components (fibrosis/inflammation) in addition to the tumour bed analysis (2020 IASLC statement) was carried out in all cases. An AI algorithm of the different immunophenotypes was also applied on immunohistochemistry-stained whole-slide images. A ClinPATH combined score including MPR, baseline blood lymphocytes, perineural invasion, vascular invasion, proliferative index, fibrosis extension percentage and AI-quantified CD4+ cell % was tested.

Results

MPR and pCR were related to disease-free survival (DFS) and overall survival (OS) but also vascular/perineural/pleural invasion and Ki-67 were useful in stratifying the study population. Concerning the tumour bed stromal components, only morphometrical quantification highlighted the prognostic role of fibrosis and inflammation, particularly when distinguishing CD4+ and FOXP3+ cells, mainly in adenocarcinomas. Interestingly, the combination of the most impactful clinico-pathological parameters in a ClinPATH combined score correlated better with DFS and OS than any individual parameter, including MPR or pCR.

Conclusion

AI-based method can be used to accurately decipher the complexity of tumour bed stromal components, providing extra information for outcome prediction. The combination of different clinico-pathological features could be highly valuable in guiding therapeutic decisions and ultimately improve patient outcomes.

背景:接受新辅助化疗(NACT)后手术的非小细胞肺癌(NSCLC)患者是确定预后因素的理想临床环境。迄今为止,主要病理反应(MPR)和完全病理反应(pCR)已被用作NACT反应和临床结果的替代指标。该研究的目的是利用形态计量学和人工智能(AI)来研究其他临床病理特征的作用。方法:对70例经NACT手术的III期非小细胞肺癌患者进行研究。在所有病例中,除了肿瘤床分析(2020 IASLC声明)外,还对组织学参数进行了颗粒评估,并对基质成分(纤维化/炎症)进行了形态计量量化。不同免疫表型的AI算法也应用于免疫组织化学染色的全片图像。检测ClinPATH综合评分,包括MPR、基线血淋巴细胞、神经周围浸润、血管浸润、增殖指数、纤维化扩展百分比和ai量化CD4+细胞%。结果:MPR和pCR与无病生存(DFS)和总生存(OS)有关,而且血管/神经周围/胸膜浸润和Ki-67对研究人群分层有用。关于肿瘤床间质成分,只有形态计量量化强调了纤维化和炎症的预后作用,特别是在区分CD4+和FOXP3+细胞时,主要是在腺癌中。有趣的是,ClinPATH综合评分中最具影响力的临床病理参数的组合与DFS和OS的相关性优于任何单个参数,包括MPR或pCR。结论:基于人工智能的方法可准确解读肿瘤床间质成分的复杂性,为预后预测提供额外信息。不同临床病理特征的结合在指导治疗决策和最终改善患者预后方面具有很高的价值。
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引用次数: 0
The prognostic impact of blood vessel invasion in infiltrative papillary thyroid carcinoma: a retrospective case–control study 浸润性甲状腺乳头状癌血管浸润对预后的影响:回顾性病例对照研究。
IF 4.1 2区 医学 Q2 CELL BIOLOGY Pub Date : 2025-10-31 DOI: 10.1111/his.70032
Ronald A Ghossein, Dibisha Roy, Ashok Shaha, R Michael Tuttle, Bin Xu

Aims

Papillary thyroid carcinoma (PTC) with blood vessel invasion (BVI) is classified as intermediate risk by the American Thyroid Association (ATA). However, no publications have adequately distinguished between encapsulated follicular variant (EFV) of PTC and infiltrative PTC with regard to BVI. Recently, the WHO classification reclassified EFV of PTC, a RAS-like tumour, as a distinct entity from PTC. In this study, we aimed to investigate the prognostic impact of BVI in infiltrative PTC.

Methods and results

This retrospective matched case–control study included 134 cases of infiltrative PTC with BVI and at least 1 year of follow-up. A 1:1 matched control group of 134 infiltrative PTC without BVI, matched for PTC subtype and AJCC stage, was also included. CD31 and D2-40 immunohistochemistry were performed on 195 blocks to distinguish BVI from lymphatic vessel invasion (LI). BVI was defined as a CD31-positive/D2-40-negative endothelium-lined tumour embolus within a vessel wall, whereas LI was defined as a free-floating tumour plug lacking an endothelial lining within a CD31/D2-40-positive vessel. The median follow-up period was 5.3 years. Extensive BVI was the only independent adverse prognostic factor for disease-free survival (hazard ratio = 3.531) on multivariate survival analysis. On univariate analysis, infiltrative PTC with extensive BVI was associated with significantly decreased distant metastasis-free survival compared with those without BVI or with focal BVI.

Conclusions

Using CD31 and D2-40 as gold standard ancillary tools, we established reliable histologic criteria to differentiate BVI from LI. Extensive BVI is an independent adverse prognostic factor in infiltrative BRAF V600E-like PTC and should therefore be considered in initial risk stratification for infiltrative PTC.

目的:甲状腺乳头状癌(PTC)合并血管侵犯(BVI)被美国甲状腺协会(ATA)列为中度危险。然而,关于BVI,没有出版物充分区分PTC的囊化滤泡变异(EFV)和浸润性PTC。最近,世卫组织将PTC(一种ras样肿瘤)的EFV重新分类为与PTC不同的实体。在本研究中,我们旨在探讨BVI对浸润性PTC预后的影响。方法和结果:本回顾性匹配病例对照研究包括134例浸润性PTC伴BVI,随访至少1年。其中浸润性无BVI的PTC 134例,按PTC亚型和AJCC分期进行1:1匹配对照组。195块细胞进行CD31和D2-40免疫组化,以区分BVI和淋巴管侵袭(LI)。BVI被定义为血管壁内CD31阳性/ d2 -40阴性的内皮衬里肿瘤栓子,而LI被定义为CD31/ d2 -40阳性血管内缺乏内皮衬里的自由漂浮肿瘤栓子。中位随访期为5.3年。在多变量生存分析中,广泛的BVI是影响无病生存的唯一独立不良预后因素(风险比= 3.531)。在单因素分析中,与没有BVI或局灶性BVI的患者相比,浸润性PTC伴广泛BVI的患者无远处转移生存期显著降低。结论:使用CD31和D2-40作为金标准辅助工具,我们建立了区分BVI和LI的可靠组织学标准。广泛的BVI是浸润性BRAF v600样PTC的一个独立的不良预后因素,因此应在浸润性PTC的初始风险分层中予以考虑。
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引用次数: 0
期刊
Histopathology
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