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Expanding the spectrum of low-grade sinonasal adenocarcinoma with biphasic seromucinous differentiation and activating HRAS/AKT1 mutations. 扩大具有双相血清粘液分化和激活 HRAS/AKT1 突变的低级别鼻窦腺癌的范围。
IF 3.9 2区 医学 Q2 CELL BIOLOGY Pub Date : 2024-12-01 Epub Date: 2024-06-24 DOI: 10.1111/his.15251
Viktoria S Hadnagy, Meike Körner, Matthias Rössle, Patrick Dubach, Gunther Pabst, Alexandra Kotulova, Stefan Weder, Robert Seifert, Elisabeth J Rushing, David Holzmann, Martin Hüllner, Sandra N Freiberger, Niels J Rupp

Aims: Low-grade non-intestinal-type sinonasal adenocarcinoma (LGSNAC) is a rare heterogeneous and poorly characterised group of tumours, distinct from intestinal- and salivary-type neoplasms. Therefore, further characterisation is needed for clearer biological understanding and classification.

Methods and results: Clinical, histological and molecular characterisation of four cases of biphasic, low-grade adenocarcinomas of the sinonasal tract was performed. All patients were male, aged between 48 and 78 years, who presented with polypoid masses in the nasal cavity. Microscopically, virtually all tumours were dominated by tubulo-glandular biphasic patterns, microcystic, focal (micro)papillary, oncocytic or basaloid features. Immunohistochemical staining confirmed biphasic differentiation with an outer layer of myoepithelial cells. Molecular profiling revealed HRAS (p.G13R, p.Q61R) mutations, and concomitant AKT1 (p.E17K, p.Q79R) mutations in two cases. Two cases showed potential in-situ/precursor lesions adjacent to the tumour. Follow-up periods ranged from 1 to 30 months, with one case relapsing locally after 12 and > 20 years.

Conclusion: This study further corroborates a distinct biphasic low-grade neoplasm of the sinonasal tract with seromucinous differentiation. Although morphological and molecular features overlap with salivary gland epithelial-myoepithelial carcinoma, several arguments favour categorising these tumours within the spectrum of LGSNAC.

目的:低分化非肠型鼻窦腺癌(LGSNAC)是一种罕见的异质性肿瘤,特征不清,有别于肠型和唾液型肿瘤。因此,需要进一步确定其特征,以便更清楚地了解其生物学特性并进行分类:对四例鼻窦道双相低分化腺癌进行了临床、组织学和分子鉴定。所有患者均为男性,年龄在 48 至 78 岁之间,鼻腔内出现息肉样肿块。显微镜下,几乎所有肿瘤都以管状腺双相型、微囊性、局灶性(微)乳头状、肿瘤细胞或基底样特征为主。免疫组化染色证实肿瘤呈双相分化,外层为肌上皮细胞。分子图谱显示,两例患者存在HRAS(p.G13R、p.Q61R)突变和AKT1(p.E17K、p.Q79R)突变。有两个病例显示肿瘤附近有潜在的原位/前驱病变。随访时间从 1 个月到 30 个月不等,其中一个病例在 12 年和 20 年后局部复发:结论:这项研究进一步证实了鼻窦粘液性分化的独特双相低级别肿瘤。虽然形态学和分子特征与唾液腺上皮-肌上皮癌重叠,但有几种论点支持将这些肿瘤归类为 LGSNAC。
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引用次数: 0
Histopathological assessment of the viability of hepatic alveolar echinococcosis. 肝泡棘球蚴病生存能力的组织病理学评估。
IF 3.9 2区 医学 Q2 CELL BIOLOGY Pub Date : 2024-12-01 Epub Date: 2024-07-24 DOI: 10.1111/his.15280
Selina Robers, Michael Reinehr, Lillemor Haibach, Eva Furrer, Annina Cincera, Philipp Andreas Kronenberg, Ramon Marc Eichenberger, Peter Deplazes, Ansgar Deibel, Beat Müllhaupt, Achim Weber

Aims: Infections by the larval stage of the tape worms Echinococcus multilocularis and Echinococcus granulosus s.l. are potentially fatal zoonoses affecting humans as dead-end hosts. Histopathological evaluation of hepatic echinococcosis is an integral part of patient management, including the distinction between alveolar (AE) and cystic echinococcosis (CE), which are associated with different disease courses and treatments. To improve histopathological assessment of Echinococcus lesions, we aimed to develop robust criteria to evaluate their viability and decay.

Methods and results: Histomorphological criteria for determining parasitic viability based on the morphology of parasite structures and different stages of their decay were defined based on a clinically and molecularly defined cohort comprising 138 specimens from 112 patients (59 AE and 53 CE); 618 AE lesions were assessed for histopathological viability comparing haematoxylin and eosin (H&E) staining with mAbEm18 and mAbEm2G11 immunostaining. Moreover, parasite viability was systematically mapped in cross-sections of five additional AE lesions. Protoscoleces in CE and AE displayed variable states of degeneration. Albendazole had no significant effect on the morphology of parasite structures. Viability assessment revealed high agreement between H&E and mAbEm18, but not mAbEm2G11 staining, suggesting mAbEm18 staining as reliable for parasite viability assessment. H&E and mAbEm18 staining displayed a central-peripheral gradient of parasite viability and decay across parasitic lesions, with decayed cystic lesions located more towards the lesion centre while the most viable cystic lesions were located more peripherally.

Conclusions: Histopathological criteria corroborated by mAbEm18 staining provide a simple and reliable tool to assess the viability of AE lesions, knowledge of which is a valuable decision-making tool for further treatment.

目的:多形棘球蚴和肉眼棘球蚴的幼虫阶段感染可能是致命的人畜共患疾病,人类是致命宿主。肝棘球蚴病的组织病理学评估是患者管理不可或缺的一部分,包括区分肺泡棘球蚴病(AE)和囊状棘球蚴病(CE),这两种病的病程和治疗方法各不相同。为了改进对棘球蚴病病变的组织病理学评估,我们旨在制定可靠的标准来评估病变的存活率和腐烂程度:根据寄生虫结构的形态及其不同衰变阶段确定寄生虫存活能力的组织形态学标准,该标准基于临床和分子定义的队列,包括来自112名患者(59名AE和53名CE)的138份标本;将血涂片和伊红(H&E)染色与mAbEm18和mAbEm2G11免疫染色进行比较,评估了618个AE病变的组织病理学存活能力。此外,还对另外五个 AE 病变的横截面上的寄生虫存活率进行了系统分析。CE和AE中的原虫显示出不同的退化状态。阿苯达唑对寄生虫结构的形态没有明显影响。寄生虫存活率评估结果显示,H&E 和 mAbEm18 染色结果高度一致,而 mAbEm2G11 染色结果则不一致,这表明 mAbEm18 染色结果可用于寄生虫存活率评估。H&E和mAbEm18染色显示寄生虫的存活率和寄生虫病变的腐烂程度呈中心-外围梯度,腐烂的囊状病变多位于病变中心,而存活率最高的囊状病变多位于病变外围:组织病理学标准与 mAbEm18 染色法相互印证,为评估 AE 病变的存活率提供了一种简单可靠的工具,了解病变的存活率是进一步治疗的重要决策工具。
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引用次数: 0
The evolving molecular characterisation, histological criteria and nomenclature of adenoid ameloblastoma as a World Health Organisation tumour type. 腺样绒母细胞瘤作为世界卫生组织肿瘤类型的分子特征、组织学标准和命名的演变。
IF 3.9 2区 医学 Q2 CELL BIOLOGY Pub Date : 2024-12-01 Epub Date: 2024-06-24 DOI: 10.1111/his.15270
Edward W Odell, Carolina Cavalieri Gomes, Selvam Thavaraj

Adenoid ameloblastoma (AA) was recently recognised as a separate tumour type in the most recent World Health Organisation (WHO) classification of head and neck tumours. This decision has been considered controversial by several groups, who have described AA as a subtype of ameloblastoma, a hybrid odontogenic tumour or to fall within the spectrum of other recognised odontogenic tumours, including dentinogenic ghost cell tumour and adenomatoid odontogenic tumour. Here we review the reasons for the WHO decision to classify AA as a separate tumour type. We also critique molecular and histological findings from recent reports published since the WHO classification. While acknowledging that the classification of tumours is constantly evolving, the balance of current evidence suggests that AA should remain a distinct tumour type, and not a subtype of ameloblastoma, pending further molecular characterisation.

最近,在世界卫生组织(WHO)最新的头颈部肿瘤分类中,腺样釉母细胞瘤(AA)被认定为一种独立的肿瘤类型。这一决定引起了一些团体的争议,他们认为AA是釉母细胞瘤的一种亚型、一种混合性牙源性肿瘤,或者属于其他公认的牙源性肿瘤,包括牙本质鬼细胞瘤和腺瘤样牙源性肿瘤。在此,我们回顾了世界卫生组织决定将 AA 划分为单独肿瘤类型的原因。我们还对世卫组织分类后发表的最新报告中的分子和组织学发现进行了点评。我们承认肿瘤的分类在不断发展,但目前的证据表明,AA仍应是一个独立的肿瘤类型,而不是釉母细胞瘤的一个亚型,有待进一步的分子鉴定。
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引用次数: 0
Prediction of molecular subclasses of uveal melanoma by deep learning using routine haematoxylin-eosin-stained tissue slides. 利用常规血红素-伊红染色组织切片,通过深度学习预测葡萄膜黑色素瘤的分子亚类。
IF 3.9 2区 医学 Q2 CELL BIOLOGY Pub Date : 2024-12-01 Epub Date: 2024-07-01 DOI: 10.1111/his.15271
Farhan Akram, Daniël P de Bruyn, Quincy C C van den Bosch, Teodora E Trandafir, Thierry P P van den Bosch, Rob M Verdijk, Annelies de Klein, Emine Kiliç, Andrew P Stubbs, Erwin Brosens, Jan H von der Thüsen

Aims: Uveal melanoma has a high propensity to metastasize. Prognosis is associated with specific driver mutations and copy number variations, and these can only be obtained after genetic testing. In this study we evaluated the efficacy of patient outcome prediction using deep learning on haematoxylin and eosin (HE)-stained primary uveal melanoma slides in comparison to molecular testing.

Methods: In this retrospective study of patients with uveal melanoma, 113 patients from the Erasmus Medical Centre who underwent enucleation had tumour tissue analysed for molecular classification between 1993 and 2020. Routine HE-stained slides were scanned to obtain whole-slide images (WSI). After annotation of regions of interest, tiles of 1024 × 1024 pixels were extracted at a magnification of 40×. An ablation study to select the best-performing deep-learning model was carried out using three state-of-the-art deep-learning models (EfficientNet, Vision Transformer, and Swin Transformer).

Results: Deep-learning models were subjected to a training cohort (n = 40), followed by a validation cohort (n = 20), and finally underwent a test cohort (n = 48). A k-fold cross-validation (k = 3) of validation and test cohorts (n = 113 of three classes: BAP1, SF3B1, EIF1AX) demonstrated Swin Transformer as the best-performing deep-learning model to predict molecular subclasses based on HE stains. The model achieved an accuracy of 0.83 ± 0.09 on the validation cohort and 0.75 ± 0.04 on the test cohort. Within the subclasses, this model correctly predicted 70% BAP1-mutated, 61% SF3B1-mutated and 80% EIF1AX-mutated UM in the test set.

Conclusions: This study showcases the potential of the deep-learning methodology for predicting molecular subclasses in a multiclass manner using HE-stained WSI. This development holds promise for advanced prognostication of UM patients without the need of molecular or immunohistochemical testing. Additionally, this study suggests there are distinct histopathological features per subclass; mainly utilizing epithelioid cellular morphology for BAP1-classification, but an unknown feature distinguishes EIF1AX and SF3B1.

目的:葡萄膜黑色素瘤具有高度转移倾向。预后与特定的驱动基因突变和拷贝数变异有关,而这些只能通过基因检测获得。在这项研究中,我们评估了利用深度学习对血红素和伊红(HE)染色的原发性葡萄膜黑色素瘤切片进行患者预后预测的效果,并与分子检测进行了比较:在这项针对葡萄膜黑色素瘤患者的回顾性研究中,伊拉斯谟医学中心(Erasmus Medical Centre)在1993年至2020年期间对113名接受去核手术的患者的肿瘤组织进行了分子分类分析。对常规 HE 染色切片进行扫描,以获得全切片图像(WSI)。在对感兴趣区进行标注后,以 40 倍的放大率提取 1024 × 1024 像素的瓦片。使用三种最先进的深度学习模型(EfficientNet、Vision Transformer 和 Swin Transformer)进行了消融研究,以选择性能最佳的深度学习模型:对深度学习模型进行了训练队列(n = 40),然后是验证队列(n = 20),最后是测试队列(n = 48)。对验证队列和测试队列(n = 113,分为三类:BAP1、SF3B1、EIF1AX)进行的 k 倍交叉验证(k = 3)表明,Swin Transformer 是基于 HE 染色预测分子亚类的表现最佳的深度学习模型。该模型在验证组群中的准确率为 0.83 ± 0.09,在测试组群中的准确率为 0.75 ± 0.04。在亚类中,该模型正确预测了测试集中 70% 的 BAP1 突变、61% 的 SF3B1 突变和 80% 的 EIF1AX 突变 UM:本研究展示了深度学习方法在使用 HE 染色的 WSI 以多类方式预测分子亚类方面的潜力。这一研究成果有望在无需分子或免疫组化检测的情况下,为 UM 患者的晚期预后做出预测。此外,这项研究还表明,每个亚类都有不同的组织病理学特征;主要是利用上皮样细胞形态进行 BAP1 分类,但有一个未知特征可区分 EIF1AX 和 SF3B1。
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引用次数: 0
Defining angioinvasion and lymphatic invasion in papillary thyroid carcinoma: morphological criteria, utility of D2-40/CD31/ERG immunohistochemistry and correlation with clinicopathological characteristics. 界定甲状腺乳头状癌的血管侵犯和淋巴侵犯:形态学标准、D2-40/CD31/ERG 免疫组化的实用性以及与临床病理特征的相关性。
IF 3.9 2区 医学 Q2 CELL BIOLOGY Pub Date : 2024-12-01 Epub Date: 2024-07-18 DOI: 10.1111/his.15285
Bin Xu, Dibisha Roy, Rene Serrette, Ronald Ghossein

Aims: While CAP and ICCR protocols mandate the separation of angioinvasion (AI) and lymphatic invasion (LI) in thyroid carcinoma, distinction between them can be difficult. Because the presence of AI is used to stratify patients with papillary thyroid carcinoma (PTC), there is a need to accurately diagnose AI and LI.

Methods and results: AI and LI were evaluated in 162 cases of PTC (n = 155) and high-grade differentiated thyroid carcinoma, papillary phenotype (HGDTCp, n = seven) using haematoxylin and eosin (H&E), D2-40 and CD31/ERG. In encapsulated carcinomas, vascular invasion (VI) was only of AI nature. Infiltrative carcinomas showed LI (46 of 131, 35%) and AI (19 of 131, 16%). The frequency of nodal metastasis (NM) and large volume of NM was 93 and 85%, respectively, in tumours with LI, and 39 and 26%, respectively, in those without LI. Luminal red blood cells and smooth muscle in the wall of large-calibre vessels were not reliable criteria to exclude LI and were seen in 23 and 6% of LI, respectively. LI was an independent predictor for NM, whereas AI is an independent predictor for distant metastasis at presentation in PTC/HGDTCp.

Conclusion: VI in encapsulated carcinomas, including follicular variant PTC, is only of AI nature, confirming the position of this variant as a close entity to follicular carcinoma rather than classic PTC, whereas infiltrative PTC/HGDTCp may have LI or, less frequently, AI. As no morphological features reliably distinguish LI from AI, D2-40 and CD31/ERG immunostains should be considered for separating AI from LI when dealing with vascular invasion in an infiltrative PTC.

目的:虽然CAP和ICCR规程要求将甲状腺癌的血管侵犯(AI)和淋巴侵犯(LI)分开,但两者之间的区分却很困难。由于AI的存在可用于对甲状腺乳头状癌(PTC)患者进行分层,因此需要准确诊断AI和LI:使用血红素和伊红(H&E)、D2-40和CD31/ERG对162例PTC(n = 155)和高级别分化甲状腺癌乳头状表型(HGDTCp,n = 7)中的AI和LI进行了评估。在包裹性癌中,血管侵犯(VI)仅具有 AI 性质。浸润性癌表现为LI(131例中有46例,占35%)和AI(131例中有19例,占16%)。结节转移(NM)和大体积 NM 的发生率在有 LI 的肿瘤中分别为 93% 和 85%,在没有 LI 的肿瘤中分别为 39% 和 26%。管腔红细胞和大口径血管壁平滑肌不是排除LI的可靠标准,分别见于23%和6%的LI。LI是NM的独立预测因子,而AI则是PTC/HGDTCp发病时远处转移的独立预测因子:结论:包膜癌(包括滤泡变异型PTC)中的VI仅具有AI性质,这证实了该变异型与滤泡癌而非典型PTC接近,而浸润性PTC/HGDTCp可能具有LI或较少见的AI。由于没有形态学特征能可靠地区分 LI 和 AI,因此在处理浸润性 PTC 的血管侵犯时,应考虑使用 D2-40 和 CD31/ERG 免疫标记来区分 AI 和 LI。
{"title":"Defining angioinvasion and lymphatic invasion in papillary thyroid carcinoma: morphological criteria, utility of D2-40/CD31/ERG immunohistochemistry and correlation with clinicopathological characteristics.","authors":"Bin Xu, Dibisha Roy, Rene Serrette, Ronald Ghossein","doi":"10.1111/his.15285","DOIUrl":"10.1111/his.15285","url":null,"abstract":"<p><strong>Aims: </strong>While CAP and ICCR protocols mandate the separation of angioinvasion (AI) and lymphatic invasion (LI) in thyroid carcinoma, distinction between them can be difficult. Because the presence of AI is used to stratify patients with papillary thyroid carcinoma (PTC), there is a need to accurately diagnose AI and LI.</p><p><strong>Methods and results: </strong>AI and LI were evaluated in 162 cases of PTC (n = 155) and high-grade differentiated thyroid carcinoma, papillary phenotype (HGDTCp, n = seven) using haematoxylin and eosin (H&E), D2-40 and CD31/ERG. In encapsulated carcinomas, vascular invasion (VI) was only of AI nature. Infiltrative carcinomas showed LI (46 of 131, 35%) and AI (19 of 131, 16%). The frequency of nodal metastasis (NM) and large volume of NM was 93 and 85%, respectively, in tumours with LI, and 39 and 26%, respectively, in those without LI. Luminal red blood cells and smooth muscle in the wall of large-calibre vessels were not reliable criteria to exclude LI and were seen in 23 and 6% of LI, respectively. LI was an independent predictor for NM, whereas AI is an independent predictor for distant metastasis at presentation in PTC/HGDTCp.</p><p><strong>Conclusion: </strong>VI in encapsulated carcinomas, including follicular variant PTC, is only of AI nature, confirming the position of this variant as a close entity to follicular carcinoma rather than classic PTC, whereas infiltrative PTC/HGDTCp may have LI or, less frequently, AI. As no morphological features reliably distinguish LI from AI, D2-40 and CD31/ERG immunostains should be considered for separating AI from LI when dealing with vascular invasion in an infiltrative PTC.</p>","PeriodicalId":13219,"journal":{"name":"Histopathology","volume":null,"pages":null},"PeriodicalIF":3.9,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141731123","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
Diagnostic approach to hepatic vascular lesions: a paediatric perspective. 肝血管病变的诊断方法:儿科视角。
IF 3.9 2区 医学 Q2 CELL BIOLOGY Pub Date : 2024-12-01 Epub Date: 2024-06-24 DOI: 10.1111/his.15250
Juan Putra, Grace E Kim

The pathological evaluation of hepatic vascular lesions in children requires special consideration. Inconsistent terminology, rarity of pathology specimens and overlapping pathological features between various lesions may pose a serious diagnostic challenge. In this review, we highlight the importance of using the International Society for the Study of Vascular Anomalies (ISSVA) classification scheme to characterise these lesions. Selected entities are discussed, including hepatic vascular tumours exclusively seen in the paediatric age group, hepatic infantile haemangioma and hepatic congenital haemangioma. Vascular malformations, with emphasis on their syndromic associations (venous malformation in blue rubber bleb naevus syndrome) and complications (hepatocellular nodules in Abernethy malformation) are also covered.

儿童肝血管病变的病理评估需要特别考虑。术语的不一致、病理标本的罕见以及各种病变之间病理特征的重叠可能会给诊断带来严峻挑战。在这篇综述中,我们强调了使用国际血管异常研究学会(ISSVA)分类方案来描述这些病变特征的重要性。文中讨论了部分实体,包括专门见于儿科年龄组的肝血管瘤、肝婴幼儿血管瘤和肝先天性血管瘤。此外,还讨论了血管畸形,重点是其综合征(蓝橡皮痣综合征中的静脉畸形)和并发症(Abernethy 畸形中的肝细胞结节)。
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引用次数: 0
Can thyroid histomorphology identify patients with PTEN hamartoma tumour syndrome? 甲状腺组织形态学能否识别PTEN hamartoma肿瘤综合征患者?
IF 3.9 2区 医学 Q2 CELL BIOLOGY Pub Date : 2024-12-01 Epub Date: 2024-07-01 DOI: 10.1111/his.15278
Melad N Dababneh, Laura Rabinowitz, Gilman Plitt, Charis Eng, Christopher C Griffith

Aims: The phosphatase and tensin homologue (PTEN) hamartoma tumour syndrome (PHTS) is a genetic disorder with variable clinical presentation and increased lifetime risk of multiorgan malignancies. The thyroid gland is commonly affected with follicular nodular disease (FND) and follicular cell-derived carcinomas. Histopathological and immunohistochemical assessment of thyroid disease in PHTS is essential to identify patients at-risk.

Methods and results: In all, 30 PHTS patients with available thyroidectomy specimen material (2000-2023) and 31 control patients with FND and "adenomatous nodules" were retrieved. Histologic criteria, including the frequency of adenomatous-type nodules versus hyperplastic-type nodules, background and nodular lipomatous metaplasia, chronic lymphocytic thyroiditis, cytoplasmic clearing of follicular cells in nodules, nodule-in-nodule appearance, and spectrum of nuclear atypia between nodules were evaluated in both cohorts and a Thyroid Histomorphologic PHTS Score (THiPS) system was established with a cutoff of 4 points or higher being considered concerning for PHTS. In all, 27 PHTS (90%) and five control (16.1%) cases had THiPS ≥4. A PTEN immunohistochemical stain was evaluated in 25 cases of each cohort and showed nuclear and cytoplasmic loss of expression in all or most of the nodules of 24/25 PHTS cases. In 3/25 control cases, two with THiPS ≥4, had loss of expression in one to multiple nodules. Conventional papillary thyroid carcinomas in PHTS patients retained PTEN cytoplasmic expression.

Conclusions: Our study supports that, although not specific, the finding of multiple histologic features is found more frequently in patients with PHTS compared to the non-PHTS control group. The THiPS system has high sensitivity for thyroid specimens from patients with PHTS.

目的:磷酸酶和天丝蛋白同源物(PTEN)火腿肠瘤综合征(PHTS)是一种遗传性疾病,临床表现多变,终生罹患多器官恶性肿瘤的风险增加。甲状腺通常会受到影响,出现滤泡结节病(FND)和滤泡细胞衍生癌。对PHTS患者的甲状腺疾病进行组织病理学和免疫组化评估对于识别高危患者至关重要:共检索了30例PHTS患者的甲状腺切除术标本材料(2000-2023年)和31例FND及 "腺瘤结节 "对照组患者的标本材料。组织学标准包括腺瘤型结节与增生型结节的频率、背景和结节性脂肪瘤变、慢性淋巴细胞性甲状腺炎、结节中滤泡细胞的胞浆清除、甲状腺组织形态学PHTS评分(THiPS)系统已经建立,4分或4分以上为PHTS。共有27例PHTS病例(90%)和5例对照病例(16.1%)的THiPS≥4。对每个组群中的 25 个病例进行了 PTEN 免疫组化染色评估,结果显示 24/25 个 PHTS 病例的所有或大部分结节中均存在核和胞质表达缺失。在3/25个对照病例中,有两个THiPS≥4的病例在一个至多个结节中出现表达缺失。PHTS患者的常规甲状腺乳头状癌保留了PTEN的胞浆表达:我们的研究表明,尽管没有特异性,但与非PHTS对照组相比,PHTS患者更常发现多种组织学特征。THiPS系统对PHTS患者的甲状腺标本具有很高的灵敏度。
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引用次数: 0
Clinicopathologic and molecular study of superficial CD34-positive fibroblastic tumours mimicking atypical fibrous histiocytoma (dermatofibroma). 模仿非典型纤维组织细胞瘤(皮肤纤维瘤)的浅表 CD34 阳性成纤维细胞瘤的临床病理和分子研究。
IF 3.9 2区 医学 Q2 CELL BIOLOGY Pub Date : 2024-12-01 Epub Date: 2024-07-24 DOI: 10.1111/his.15282
Craig B Wakefield, Fredrik Mertens, Christopher D M Fletcher, William J Anderson

Aims: Superficial CD34-positive fibroblastic tumour (SCD34FT) is an uncommon but distinctive low-grade neoplasm of the skin and subcutis that shows frequent CADM3 expression by immunohistochemistry (IHC). In this study, prompted by an index case resembling 'atypical fibrous histiocytoma (FH)' that was positive for CADM3 IHC, we systematically examined a cohort of tumours previously diagnosed as 'atypical FH' by applying CADM3 and fluorescence in situ hybridization (FISH) for PRDM10 rearrangement, to investigate the overlap between these tumour types.

Methods and results: Forty cases of atypical FH were retrieved, including CD34-positive tumours (n = 20) and CD34-negative tumours (n = 20). All tumours were stained for CADM3. All CADM3-positive tumours were evaluated by FISH to assess for PRDM10 rearrangement. Eleven CD34-positive tumours (11/20, 55%) coexpressed CADM3 and were reclassified as SCD34FT. None (0/20) of the CD34-negative atypical FH were CADM3-positive. Reclassified SCD34FT (10/11) arose on the lower extremity, with frequent involvement of the thigh (n = 8). Features suggestive of atypical FH were observed in many reclassified cases including variable cellularity, spindled morphology, infiltrative tumour margins, collagen entrapment, epidermal hyperpigmentation, and acanthosis. Variably prominent multinucleate giant cells, including Touton-like forms, were also present. An informative FISH result was obtained in 10/11 reclassified tumours, with 60% (6/10) demonstrating PRDM10 rearrangement.

Conclusion: A significant subset of tumours that histologically resemble atypical FH, and are positive for CD34, coexpress CADM3 and harbour PRDM10 rearrangement, supporting their reclassification as SCD34FT. Awareness of this morphologic overlap and the application of CADM3 IHC can aid the distinction between SCD34FT and atypical FH.

目的:表皮 CD34 阳性成纤维细胞瘤(SCD34FT)是皮肤和皮下的一种不常见但很独特的低级别肿瘤,免疫组化(IHC)显示其经常表达 CADM3。在本研究中,由于一个类似于 "非典型纤维组织细胞瘤(FH)"的病例在 CADM3 IHC 中呈阳性,我们通过应用 CADM3 和荧光原位杂交(FISH)检测 PRDM10 重排,系统地检查了一组以前被诊断为 "非典型 FH "的肿瘤,以研究这些肿瘤类型之间的重叠:检索了40例非典型FH,包括CD34阳性肿瘤(20例)和CD34阴性肿瘤(20例)。所有肿瘤均进行了 CADM3 染色。所有CADM3阳性肿瘤均通过FISH评估PRDM10重排。11个CD34阳性肿瘤(11/20,55%)共表达CADM3,被重新归类为SCD34FT。CD34 阴性的非典型 FH 中没有一个(0/20)CADM3 阳性。重新分类的 SCD34FT(10/11)出现在下肢,大腿经常受累(n = 8)。在许多重新分类的病例中都观察到了提示非典型 FH 的特征,包括可变细胞性、纺锤形形态、肿瘤边缘浸润、胶原夹层、表皮色素沉着和棘皮症。此外,还出现了不同程度的突出多核巨细胞,包括 Touton 样细胞。10/11例重新分类的肿瘤都获得了有参考价值的FISH结果,其中60%(6/10)的肿瘤显示了PRDM10重排:结论:有相当一部分肿瘤在组织学上与非典型 FH 相似,CD34 阳性,同时表达 CADM3 和携带 PRDM10 重排,支持将其重新分类为 SCD34FT。对这种形态学重叠的认识和 CADM3 IHC 的应用有助于区分 SCD34FT 和非典型 FH。
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引用次数: 0
Quantitative comparison of immunohistochemical HER2-low detection in an interlaboratory study. 实验室间研究中免疫组化 HER2 低检测的定量比较。
IF 3.9 2区 医学 Q2 CELL BIOLOGY Pub Date : 2024-12-01 Epub Date: 2024-07-29 DOI: 10.1111/his.15273
Maaike Anna Hempenius, Maran A Eenkhoorn, Henrik Høeg, David J Dabbs, Bert van der Vegt, Seshi R Sompuram, Nils A 't Hart

Aims: Recently, human epidermal growth factor 2 (HER2)-low (i.e. HER2 score 1+ or 2+ without amplification) breast cancer patients became eligible for trastuzumab-deruxtecan treatment. To improve assay standardisation and detection of HER2-low in a quantitative manner, we conducted an external quality assessment-like study in the Netherlands. Dynamic range cell lines and immunohistochemistry (IHC) calibrators were used to quantify HER2 expression and to assess interlaboratory variability.

Methods and results: Three blank slides with a dynamic range cell line and an IHC calibrator were stained with routine HER2 assays by 35 laboratories. Four different antibody clones were used: 19 (54.3%) 4B5, six (17.1%) A0485, five (14.3%) DG44 (HercepTest) and five (14.3%) SP3. Laboratories used two different detection kits for 4B5 assays: 14 (73.7%) ultraView and five (26.3%) OptiView. Variability of HER2 expression in cell lines, measured with artificial intelligence software, was median (min-max) = negative core 0.5% (0.0-57.0), 1+ core 4.3% (1.6-71.3), 2+ core 42.8% (30.4-92.6) and 3+ core 96.2% (91.8-98.8). The calibrators DG44 and 4B5 OptiView had the highest analytical sensitivity, closely followed by 4B5 ultraView. SP3 was the least sensitive. Calibrators of A0485 assays were not analysable due to background staining.

Conclusions: As assays were validated for detecting HER2-amplified tumours, not all assays and antibodies proved suitable for HER2-low detection. Some tests showed distinct expression in the negative cell line. Dynamic range cell line controls and quantitative analysis using calibrators demonstrated more interlaboratory variability than commonly appreciated. Revalidation of HER2 tests by laboratories is needed to ensure clinical applicable HER2-low assays.

目的:最近,低人类表皮生长因子 2(HER2)(即 HER2 评分 1+ 或 2+,无扩增)乳腺癌患者开始有资格接受曲妥珠单抗-德鲁司康治疗。为了提高检测的标准化程度和定量检测 HER2-low,我们在荷兰开展了一项类似外部质量评估的研究。我们使用动态范围细胞系和免疫组化(IHC)校准物来定量检测HER2的表达,并评估实验室间的差异性:35 家实验室用常规 HER2 检测法对带有动态范围细胞系和 IHC 校准物的三张空白切片进行染色。使用了四种不同的抗体克隆:19个(54.3%)4B5、6个(17.1%)A0485、5个(14.3%)DG44(HercepTest)和5个(14.3%)SP3。实验室使用两种不同的检测试剂盒进行 4B5 检测:14 种(73.7%)ultraView 和 5 种(26.3%)OptiView。用人工智能软件测量细胞系中 HER2 表达的变异性,中位数(最小值-最大值)= 阴性核心 0.5% (0.0-57.0),1+ 核心 4.3% (1.6-71.3),2+ 核心 42.8% (30.4-92.6) 和 3+ 核心 96.2% (91.8-98.8)。校准器 DG44 和 4B5 OptiView 的分析灵敏度最高,紧随其后的是 4B5 ultraView。SP3 的灵敏度最低。A0485 检测方法的校准物因背景染色而无法分析:结论:由于检测HER2-扩增肿瘤的检测方法已经过验证,因此并非所有的检测方法和抗体都适用于HER2-低表达肿瘤的检测。一些检测方法在阴性细胞系中有明显的表达。动态范围细胞系对照和使用校准物进行的定量分析显示,实验室之间的变异性比人们通常认为的要大。实验室需要对 HER2 检测进行重新验证,以确保 HER2 低检测适用于临床。
{"title":"Quantitative comparison of immunohistochemical HER2-low detection in an interlaboratory study.","authors":"Maaike Anna Hempenius, Maran A Eenkhoorn, Henrik Høeg, David J Dabbs, Bert van der Vegt, Seshi R Sompuram, Nils A 't Hart","doi":"10.1111/his.15273","DOIUrl":"10.1111/his.15273","url":null,"abstract":"<p><strong>Aims: </strong>Recently, human epidermal growth factor 2 (HER2)-low (i.e. HER2 score 1+ or 2+ without amplification) breast cancer patients became eligible for trastuzumab-deruxtecan treatment. To improve assay standardisation and detection of HER2-low in a quantitative manner, we conducted an external quality assessment-like study in the Netherlands. Dynamic range cell lines and immunohistochemistry (IHC) calibrators were used to quantify HER2 expression and to assess interlaboratory variability.</p><p><strong>Methods and results: </strong>Three blank slides with a dynamic range cell line and an IHC calibrator were stained with routine HER2 assays by 35 laboratories. Four different antibody clones were used: 19 (54.3%) 4B5, six (17.1%) A0485, five (14.3%) DG44 (HercepTest) and five (14.3%) SP3. Laboratories used two different detection kits for 4B5 assays: 14 (73.7%) ultraView and five (26.3%) OptiView. Variability of HER2 expression in cell lines, measured with artificial intelligence software, was median (min-max) = negative core 0.5% (0.0-57.0), 1+ core 4.3% (1.6-71.3), 2+ core 42.8% (30.4-92.6) and 3+ core 96.2% (91.8-98.8). The calibrators DG44 and 4B5 OptiView had the highest analytical sensitivity, closely followed by 4B5 ultraView. SP3 was the least sensitive. Calibrators of A0485 assays were not analysable due to background staining.</p><p><strong>Conclusions: </strong>As assays were validated for detecting HER2-amplified tumours, not all assays and antibodies proved suitable for HER2-low detection. Some tests showed distinct expression in the negative cell line. Dynamic range cell line controls and quantitative analysis using calibrators demonstrated more interlaboratory variability than commonly appreciated. Revalidation of HER2 tests by laboratories is needed to ensure clinical applicable HER2-low assays.</p>","PeriodicalId":13219,"journal":{"name":"Histopathology","volume":null,"pages":null},"PeriodicalIF":3.9,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141792355","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
Detection of GRM1 gene rearrangements in chondromyxoid fibroma: a comparison of fluorescence in-situ hybridisation, RNA sequencing and immunohistochemical analysis. 软骨样纤维瘤中 GRM1 基因重排的检测:荧光原位杂交、RNA 测序和免疫组化分析的比较。
IF 3.9 2区 医学 Q2 CELL BIOLOGY Pub Date : 2024-12-01 Epub Date: 2024-06-18 DOI: 10.1111/his.15248
Dianne Torrence, Josephine K Dermawan, Yanming Zhang, Chad Vanderbilt, Sinchun Hwang, Kerry Mullaney, Achim Jungbluth, Mamta Rao, Kate Gao, Purvil Sukhadia, Konstantinos Linos, Narasimhan Agaram, Meera Hameed

Aims: Chondromyxoid fibroma (CMF) is a rare, benign bone tumour which arises primarily in young adults and is occasionally diagnostically challenging. Glutamate metabotropic receptor 1 (GRM1) gene encodes a metabotropic glutamate receptor and was recently shown to be up-regulated in chondromyxoid fibroma through gene fusion and promoter swapping. The aim of this study was to interrogate cases of CMF for the presence of GRM1 gene rearrangements, gene fusions and GRM1 protein overexpression.

Methods and results: Selected cases were subjected to testing by fluorescent in-situ hybridisation (FISH) with a GRM1 break-apart probe, a targeted RNA sequencing method and immunohistochemical study with an antibody to GRM1 protein. Two cases were subjected to whole transcriptomic sequencing. In 13 of 13 cases, GRM1 protein overexpression was detected by immunohistochemistry using the GRM1 antibody. Of the 12 cases successfully tested by FISH, nine of 12 showed GRM1 rearrangements by break-apart probe assay. Targeted RNA sequencing analysis did not detect gene fusions in any of the eight cases tested, but there was an increase in GRM1 mRNA expression in all eight cases. Two cases subjected to whole transcriptomic sequencing (WTS) showed elevated GRM1 expression and no gene fusions.

Conclusion: GRM1 gene rearrangements can be detected using FISH break-apart probes in approximately 75% of cases, and immunohistochemical detection of GRM1 protein over-expression is a sensitive diagnostic method. The gene fusion was not detected by targeted RNA sequencing, due most probably to the complexity of fusion mechanism, and is not yet a reliable method for confirming a diagnosis of CMF in the clinical setting.

目的:软骨瘤样纤维瘤(CMF)是一种罕见的良性骨肿瘤,主要发生于青壮年,有时在诊断上具有挑战性。谷氨酸代谢受体 1(GRM1)基因编码一种代谢型谷氨酸受体,最近通过基因融合和启动子交换被证明在软骨瘤纤维瘤中上调。本研究旨在检测 CMF 病例中是否存在 GRM1 基因重排、基因融合和 GRM1 蛋白过表达:对部分病例使用 GRM1 断裂探针进行荧光原位杂交(FISH)检测,采用靶向 RNA 测序方法,并使用 GRM1 蛋白抗体进行免疫组化研究。两例病例进行了全转录组测序。在 13 例病例中,有 13 例通过使用 GRM1 抗体进行免疫组化检测到 GRM1 蛋白过度表达。在通过 FISH 成功检测的 12 个病例中,有 9 个病例通过断裂探针检测发现了 GRM1 重排。在检测的 8 个病例中,靶向 RNA 测序分析均未检测到基因融合,但所有 8 个病例的 GRM1 mRNA 表达均有所增加。对两个病例进行了全转录组测序(WTS),结果显示 GRM1 表达升高,但没有发现基因融合:结论:约75%的病例可通过FISH断裂探针检测到GRM1基因重排,免疫组化检测GRM1蛋白过度表达是一种敏感的诊断方法。基因融合未能通过靶向 RNA 测序检测出来,很可能是由于融合机制的复杂性,目前还不是临床确诊 CMF 的可靠方法。
{"title":"Detection of GRM1 gene rearrangements in chondromyxoid fibroma: a comparison of fluorescence in-situ hybridisation, RNA sequencing and immunohistochemical analysis.","authors":"Dianne Torrence, Josephine K Dermawan, Yanming Zhang, Chad Vanderbilt, Sinchun Hwang, Kerry Mullaney, Achim Jungbluth, Mamta Rao, Kate Gao, Purvil Sukhadia, Konstantinos Linos, Narasimhan Agaram, Meera Hameed","doi":"10.1111/his.15248","DOIUrl":"10.1111/his.15248","url":null,"abstract":"<p><strong>Aims: </strong>Chondromyxoid fibroma (CMF) is a rare, benign bone tumour which arises primarily in young adults and is occasionally diagnostically challenging. Glutamate metabotropic receptor 1 (GRM1) gene encodes a metabotropic glutamate receptor and was recently shown to be up-regulated in chondromyxoid fibroma through gene fusion and promoter swapping. The aim of this study was to interrogate cases of CMF for the presence of GRM1 gene rearrangements, gene fusions and GRM1 protein overexpression.</p><p><strong>Methods and results: </strong>Selected cases were subjected to testing by fluorescent in-situ hybridisation (FISH) with a GRM1 break-apart probe, a targeted RNA sequencing method and immunohistochemical study with an antibody to GRM1 protein. Two cases were subjected to whole transcriptomic sequencing. In 13 of 13 cases, GRM1 protein overexpression was detected by immunohistochemistry using the GRM1 antibody. Of the 12 cases successfully tested by FISH, nine of 12 showed GRM1 rearrangements by break-apart probe assay. Targeted RNA sequencing analysis did not detect gene fusions in any of the eight cases tested, but there was an increase in GRM1 mRNA expression in all eight cases. Two cases subjected to whole transcriptomic sequencing (WTS) showed elevated GRM1 expression and no gene fusions.</p><p><strong>Conclusion: </strong>GRM1 gene rearrangements can be detected using FISH break-apart probes in approximately 75% of cases, and immunohistochemical detection of GRM1 protein over-expression is a sensitive diagnostic method. The gene fusion was not detected by targeted RNA sequencing, due most probably to the complexity of fusion mechanism, and is not yet a reliable method for confirming a diagnosis of CMF in the clinical setting.</p>","PeriodicalId":13219,"journal":{"name":"Histopathology","volume":null,"pages":null},"PeriodicalIF":3.9,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141418730","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
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Histopathology
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