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Livedoid skin reaction to 2nd dose of mRNA Covid-19 vaccine. 第二剂mRNA - Covid-19疫苗的类活体皮肤反应。
IF 3.5 Q1 PATHOLOGY Pub Date : 2022-08-01 DOI: 10.32074/1591-951X-746
Ilaria Girolami, Klaus Eisendle, Reinhard Walther Kluge, Esther Hanspeter, Albino Eccher, Leonardo Vizziello, Pierfrancesco Zampieri, Guido Mazzoleni

Skin often represents a target organ for adverse drug reactions and this also applies to the mRNA vaccines against Sars-CoV-2. Here we present a case of extensive livedoid reaction after 2nd dose of BNT162b-2 vaccine with massive blood skin extravasation and no systemic symptoms apart from anemization. The 30-year-old woman developed progressively enlarging livedoid lesions on limbs and abdomen. Histology showed a near-normal epidermis and a very mild interstitial mixed inflammatory infiltrate with extensive blood extravasation in mid- and deep dermis. Diagnosis was adverse reaction to vaccine with skin capillary hyperpermeability and anaemization with lower than diagnostic features of cutaneous small vessel vasculitis. To date, no cases of a livedoid skin reaction associated to Covid-19 vaccine have been reported, and this case illustrates that massive livedoid reaction can be another kind of skin reaction to mRNA Covid-19 vaccine.

皮肤通常是药物不良反应的靶器官,这也适用于针对Sars-CoV-2的mRNA疫苗。在此,我们报告一例在第二次接种BNT162b-2疫苗后出现广泛的类活体反应,大量血液皮肤外渗,除贫血外无全身症状。这名30岁的女性在四肢和腹部出现了逐渐扩大的活体样病变。组织学表现为表皮接近正常,真皮中深部有非常轻微的间质性混合性炎症浸润,伴大量血液外渗。诊断为疫苗不良反应,皮肤毛细血管通透性高,贫血,低于皮肤小血管炎的诊断特征。到目前为止,尚未报道与新冠病毒疫苗相关的类活体皮肤反应,该病例说明大量类活体皮肤反应可能是mRNA新冠病毒疫苗的另一种皮肤反应。
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引用次数: 3
In-house testing for homologous recombination repair deficiency (HRD) testing in ovarian carcinoma: a feasibility study comparing AmoyDx HRD Focus panel with Myriad myChoiceCDx assay. 卵巢癌同源重组修复缺陷(HRD)检测的内部检测:比较AmoyDx HRD焦点面板与Myriad myChoiceCDx检测的可行性研究
IF 3.5 Q1 PATHOLOGY Pub Date : 2022-08-01 DOI: 10.32074/1591-951X-791
Caterina Fumagalli, Ilaria Betella, Alberto Ranghiero, Elena Guerini-Rocco, Giulio Bonaldo, Alessandra Rappa, Davide Vacirca, Nicoletta Colombo, Massimo Barberis

Background: Homologous recombination repair (HRR) is the main mechanism of repair of DNA double-strand breaks. Its deficiency (HRD) is a common feature of epithelial ovarian cancers (EOCs). BRCA1/2 mutations and/or other aberrations in genes of HRR are well known causes of HRD and genomic instability. Poly ADP-ribose polymerase inhibitors (PARPi) have revolutionized the management of BRCA mutant EOCs and demonstrated activity in HRD tumor cells. Determining HRD status can provide informations on the magnitude of benefit for PARPi therapy. Myriad MyChoice CDx is a next generation sequencing- based in vitro diagnostic test that assesses the Genomic Instability Score (GIS) which is an algorithmic measurement of loss of heterozygosity, telomeric allelic imbalance, and large-scale state transitions using DNA isolated from formalin-fixed paraffin embedded tumor tissue specimens. However Myriad MyChoice CDx, is a centrally performed and costly assay, with no reimbursement scheduled, at least in Italy.

Methods: In this report, we described our experience in performing the HRD Focus AmoyDx (Amoy Diagnostics Ltd, Xiamen, Fujian, China) on the same samples of EOCs evaluated with Myriad MyChoiceCDx assay.

Results: The overall percent agreement between AmoyDx and Myriad was 87.8% (65 of 74 tumors tested). All the 36 AmoyDx negative cases were confirmed to be negative by Myriad (negative predictive value, 100%).

Conclusions: The concordance of the results with the gold standard Myriad MyChoice CDx assay suggest the feasibility and reliability of HRD testing in diagnostic laboratories with high-throughput NGS platforms and qualified personnel.

背景:同源重组修复(Homologous recombination repair, HRR)是DNA双链断裂修复的主要机制。其缺乏(HRD)是上皮性卵巢癌(EOCs)的共同特征。BRCA1/2突变和/或HRR基因的其他畸变是众所周知的HRD和基因组不稳定的原因。聚adp核糖聚合酶抑制剂(PARPi)已经彻底改变了BRCA突变型EOCs的管理,并在HRD肿瘤细胞中显示出活性。确定HRD状态可以提供PARPi治疗获益程度的信息。Myriad MyChoice CDx是下一代基于测序的体外诊断测试,评估基因组不稳定性评分(GIS),这是一种算法测量杂合性损失,端粒等位基因失衡,以及使用从福尔马林固定石蜡包埋的肿瘤组织标本中分离的DNA进行大规模状态转换。然而,Myriad MyChoice CDx是一种集中执行且昂贵的检测方法,至少在意大利没有报销计划。方法:在本报告中,我们描述了我们使用HRD Focus AmoyDx(厦大诊断有限公司,厦门,福建,中国)对用Myriad MyChoiceCDx检测的相同EOCs样品进行检测的经验。结果:AmoyDx和Myriad之间的总体一致性百分比为87.8%(74例肿瘤中有65例)。36例AmoyDx阴性病例经Myriad检测均为阴性(阴性预测值100%)。结论:结果与金标准Myriad MyChoice CDx法的一致性表明,在具有高通量NGS平台和合格人员的诊断实验室中检测HRD的可行性和可靠性。
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引用次数: 11
Pulmonary squamous cell carcinoma with a lepidic-pagetoid growth pattern. 肺鳞状细胞癌伴鳞片样样生长。
IF 3.5 Q1 PATHOLOGY Pub Date : 2022-08-01 DOI: 10.32074/1591-951X-450
Claudio Guerrieri, Mark Lindner, Joanna Sesti, Abhishek Chakraborti, Rachel Hudacko

We report a rare case of a peripheral squamous cell carcinoma (SCC) of the lung in which most of the tumor displayed a "lepidic" growth pattern. The tumor cells also appeared to grow along the alveolar walls between the overlying pneumocytes and underlying basement membrane, a form reminiscent of the "pagetoid" mode of spread. The neoplastic cells were positive for the squamous markers p63 and p40. TTF-1 and CK7 highlighted residual non-neoplastic pneumocytes, which either covered the lepidic tumor cells or lined pseudoglandular formations created by the filling of alveolar spaces by the tumor. CK7 also stained the tumor cells, albeit focally and weakly, a not uncommon finding in peripheral lung SCC. The tumor cells were negative for TTF-1 (clone 8G7G3/1), but did show focal weak reactivity with the less specific clone SPT24. The invasive area measured 2.5 mm while the overall size of the tumor including the lepidic-pagetoid component was 9.0 mm. Even though the invasive component was < 0.5 cm, the only option according to existing staging criteria was to stage it as pT1a. Since the current staging system does not account for the non-invasive lepidic component of pulmonary SCC, the increasing awareness of this variant may require its inclusion within the classification and pathological staging of lung carcinoma.

我们报告一例罕见的外周鳞状细胞癌(SCC)的肺,其中大部分肿瘤显示为“鳞状”生长模式。肿瘤细胞也沿着肺细胞和基底膜之间的肺泡壁生长,这种形式使人联想到“页状”扩散模式。肿瘤细胞呈鳞状标记物p63、p40阳性。TTF-1和CK7突出显示残留的非肿瘤性肺细胞,这些肺细胞要么覆盖在鳞状肿瘤细胞上,要么由肿瘤填充肺泡间隙形成的衬排假腺结构。CK7也染色肿瘤细胞,尽管是局部和微弱的,这在周围性肺鳞状细胞癌中并不罕见。肿瘤细胞对TTF-1(克隆8G7G3/1)呈阴性,但对特异性较低的克隆SPT24表现出局灶性弱反应。浸润面积为2.5 mm,肿瘤包括鳞片样叶成分的总尺寸为9.0 mm。即使侵入性成分小于0.5 cm,根据现有的分期标准,唯一的选择是将其分期为pT1a。由于目前的分期系统没有考虑到肺SCC的非侵袭性鳞状细胞成分,因此对这种变异的日益认识可能需要将其纳入肺癌的分类和病理分期。
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引用次数: 0
Extremely late-onset pulmonary metastasis from uterine PEComa. 子宫PEComa的极晚发性肺转移。
IF 3.5 Q1 PATHOLOGY Pub Date : 2022-08-01 Epub Date: 2022-09-08 DOI: 10.32074/1591-951X-762
Andrea Ascione, Guido Martignoni, Giulia d'Amati, Carlo Della Rocca, Paolo Graziano, Angelina Pernazza

A 79-year-old woman underwent surgical resection of a peripheral, solitary, pulmonary lesion that was diagnosed as malignant PEComa. Her clinical history was positive for uterine leiomyosarcoma, excised 20 years before. Re-evaluation of the primary uterine lesion led to the final diagnosis of lung metastasis from uterine PEComa. While long latency between primary tumour and metastasis is a known and characteristic feature of PEComas, a 20-year interval is unprecedented in the literature.

一位79岁的女性接受手术切除外周,孤立,肺部病变,诊断为恶性PEComa。她的临床病史为子宫平滑肌肉瘤阳性,20年前切除。重新评估原发子宫病变导致最终诊断为肺转移子宫PEComa。虽然原发性肿瘤和转移之间的长潜伏期是已知的PEComas的特征,但20年的间隔在文献中是前所未有的。
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引用次数: 0
Use of digital pathology and artificial intelligence for the diagnosis of Helicobacter pylori in gastric biopsies. 利用数字病理学和人工智能在胃活检中诊断幽门螺杆菌。
IF 3.5 Q1 PATHOLOGY Pub Date : 2022-08-01 DOI: 10.32074/1591-951X-751
Daniel S Liscia, Mariangela D'Andrea, Elena Biletta, Donata Bellis, Kejsi Demo, Franco Ferrero, Alberto Petti, Roberto Butinar, Enzo D'Andrea, Giuditta Davini

Objective: A common source of concern about digital pathology (DP) is that limited resolution could be a reason for an increased risk of malpractice. A frequent question being raised about this technology is whether it can be used to reliably detect Helicobacter pylori (HP) in gastric biopsies, which can be a significant burden in routine work. The main goal of this work is to show that a reliable diagnosis of HP infection can be made by DP even at low magnification. The secondary goal is to demonstrate that artificial intelligence (AI) algorithms can diagnose HP infections on virtual slides with sufficient accuracy.

Methods: The method we propose is based on the Warthin-Starry (W-S) silver stain which allows faster detection of HP in virtual slides. A software tool, based on regular expressions, performed a specific search to select 679 biopsies on which a W-S stain was done. From this dataset 185 virtual slides were selected to be assessed by WSI and compared with microscopy slide readings. To determine whether HP infections could be accurately diagnosed with machine learning. AI was used as a service (AIaaS) on a neural network-based web platform trained with 468 images. A test dataset of 210 images was used to assess the classifier performance.

Results: In 185 gastric biopsies read with DP we recorded only 4 false positives and 4 false negatives with an overall agreement of 95.6%. Compared with microscopy, defined as the "gold standard" for the diagnosis of HP infections, WSI had a sensitivity and specificity of 0.95 and 0.96, respectively. The ROC curve of our AI classifier generated on a testing dataset of 210 images had an AUC of 0.938.

Conclusions: This study demonstrates that DP and AI can be used to reliably identify HP at 20X resolution.

目的:对数字病理学(DP)的一个共同关注来源是有限的分辨率可能是医疗事故风险增加的原因。关于这项技术,人们经常提出的一个问题是,它能否可靠地用于胃活检中检测幽门螺杆菌(HP),这可能是日常工作中的一个重大负担。这项工作的主要目的是表明,即使在低倍率下,也可以通过DP可靠地诊断HP感染。第二个目标是证明人工智能(AI)算法可以足够准确地诊断虚拟载玻片上的HP感染。方法:我们提出的方法是基于Warthin-Starry (W-S)银染色,可以更快地检测虚拟载玻片中的HP。一个基于正则表达式的软件工具执行了一个特定的搜索,以选择679个活检组织进行W-S染色。从该数据集中选择185个虚拟载玻片进行WSI评估,并与显微镜载玻片读数进行比较。确定HP感染是否可以用机器学习准确诊断。人工智能作为一种服务(AIaaS)在一个基于神经网络的web平台上使用,该平台训练了468张图像。使用210张图像的测试数据集来评估分类器的性能。结果:在185例胃活检中,我们记录了4例假阳性和4例假阴性,总体一致性为95.6%。与被定义为HP感染诊断“金标准”的镜检相比,WSI的敏感性和特异性分别为0.95和0.96。我们的AI分类器在210张图像的测试数据集上生成的ROC曲线AUC为0.938。结论:本研究表明,DP和AI可以在20X分辨率下可靠地识别HP。
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引用次数: 8
Multidisciplinary investigation of an ancient renal stone in a mummy from Popoli, central Italy. 意大利中部波波里一具木乃伊的古代肾结石的多学科研究。
IF 3.5 Q1 PATHOLOGY Pub Date : 2022-08-01 DOI: 10.32074/1591-951X-260
Luca Ventura, Lorenzo Arrizza, Raimondo Quaresima, Mattia Capulli

The renal stone found in the natural mummy of an anonymous nobleman dating to 19th century was investigated using advanced imaging modalities and analytic investigations. By this multidisciplinary approach we were able to identify the chemical components and their distribution throughout the sample. These results allowed to understand the lifestyle habits of the subject, as well as the exact pathogenesis of his disease.

在一具19世纪匿名贵族的天然木乃伊中发现了肾结石,研究人员利用先进的成像技术和分析方法对其进行了研究。通过这种多学科方法,我们能够识别化学成分及其在整个样品中的分布。这些结果使我们能够了解受试者的生活习惯,以及他的疾病的确切发病机制。
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引用次数: 1
Fixation in histopathology: the mandate to renew. 组织病理学中的固定:更新的任务。
IF 3.5 Q1 PATHOLOGY Pub Date : 2022-08-01 DOI: 10.32074/1591-951X-782
Gianni Bussolati
This is an open access journal distributed in accordance with the CC-BY-NC-ND (Creative Commons AttributionNonCommercial-NoDerivatives 4.0 International) license: the work can be used by mentioning the author and the license, but only for non-commercial purposes and only in the original version. For further information: https://creativecommons. org/licenses/by-nc-nd/4.0/deed.en PATHOLOGICA 2022;114:4-6 DOI: 10.32074/1591-951X-782
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引用次数: 1
Alveolar adenoma and coexisting atypical adenomatous hyperplasia: a case report and literature review. 肺泡腺瘤伴非典型腺瘤增生1例并文献复习。
IF 3.5 Q1 PATHOLOGY Pub Date : 2022-08-01 DOI: 10.32074/1591-951X-755
Yen-Wen Lu, Shih-Lung Chang, Yi-Chen Yeh, Yei-San Hsieh

Alveolar adenoma is a rare tumour of the lung. It is typically found in asymptomatic adults as a peripheral or subplerual nodule on imaging examination. Microscopically, the tumour is composed of admixture of epithelial and mesenchymal component in variable sized cystic or alveolar structures. The tumour shows a benign nature. There have been no reported recurrences or metastases. Malignant transformation of alveolar adenoma and coexisting with lung carcinoma have been rarely described. In this article, we report a case of an alveolar adenoma and coexisting atypical adenomatous hyperplasia. This case, contributing to the limited numbers of cases described to date, illustrates the importance of awareness on the possibility of alveolar adenoma being associated with lung carcinoma and its precursor lesions especially when diagnosed by small biopsy specimens.

肺泡腺瘤是一种罕见的肺肿瘤。它通常在无症状的成年人中发现,影像学检查为外周或胸膜下结节。显微镜下,肿瘤由上皮和间质成分混合组成,呈大小不一的囊状或肺泡状结构。肿瘤呈良性。没有复发或转移的报道。肺泡腺瘤的恶性转化并与肺癌共存的报道很少。在这篇文章中,我们报告一例肺泡腺瘤与非典型腺瘤增生共存。本病例是迄今为止所描述的病例数量有限的病例,说明了认识肺泡腺瘤与肺癌及其前体病变相关的可能性的重要性,特别是当通过小活检标本诊断时。
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引用次数: 2
Immunohistochemistry with 3 different clones in anaplastic lymphoma kinase fluorescence in situ hybridization positive non-small-cell lung cancer with thymidylate synthase expression analysis: a multicentre, retrospective, Italian study. 3个不同克隆间变性淋巴瘤激酶荧光原位杂交阳性非小细胞肺癌胸苷合酶表达分析的免疫组织化学:一项多中心,回顾性,意大利研究。
IF 3.5 Q1 PATHOLOGY Pub Date : 2022-08-01 Epub Date: 2022-09-08 DOI: 10.32074/1591-951X-756
Paolo Bironzo, Laura Melocchi, Valentina Monica, Dario Trebeschi, Fausto Barbieri, Evaristo Maiello, Maria Rita Migliorino, Alessandra Lombardi, Marcello Tiseo, Luisella Righi, Paolo Graziano, Giulio Rossi, Silvia Novello

Introduction: ALK rearrangement is the only druggable oncogenic driver detectable by immunohistochemistry (IHC) not requiring further confirmation of positivity in accessing first-line specific inhibitors. ALK-positive patients experience clinical benefit from pemetrexed-based chemotherapy possibly due to lower thymidylate synthase (TS) levels. This study assesses agreement with three different ALK IHC clones in 37 FISH-positive NSCLC. TS expression by real time (RT)-PCR was compared with ALK FISH-negative cases.

Materials and methods: 37 ALK FISH-positive NSCLC cases diagnosed between 2010 and 2015 in 7 Italian centres were investigated with ICH using three different anti-ALK antibodies (ALK1, 5A4 and D5F3). Staining for ALK1 and 5A4 was graded as 0+,1+,2+, and 3+, while the scoring for D5F3 was recorded as negative or positive. Proportion agreement analysis was done using Cohen's unweighted kappa (k). TS and β-actin expression levels were analysed by quantitative RT-PCR. Comparison between TS expression in ALK FISH-positive specimens and a control cohort of ALK FISH-negative ones was performed with the Mann-Whitney and Kruskal-Wallis tests.

Results: Considering 2+ and 3+ as positive, the proportion of IHC agreement was 0.1691 (95% CI 0-0.4595) for ALK1/5A4, 0.1691 (95% CI 0-0.4595) for ALK1/D5F3, and 1 for D5F3/5A4. Considering 3+ as positive, it was 0.1543 (95% CI 0-0.4665) for ALK1/ 5A4, 0.0212 (95% CI 0-0.1736) for ALK1/D5F3, and 0.2269 (95% CI 0-0.5462) for 5A4/D5F3. Median TS expression was 6.07 (1.28-14.94) and ALK-positive cases had a significant lower TS expression than ALK-negative tumours (p = 0.002).

Conclusions: IHC proved to be a reliable tool for the diagnosis of ALK-rearranged NSCLC. D5F3 and 5A4 clones have the highest percentage of agreement. TS levels are significantly lower in FISH-positive patients.

ALK重排是免疫组化(IHC)检测到的唯一可用药的致癌驱动因素,在获得一线特异性抑制剂时无需进一步确认阳性。alk阳性患者从培美曲塞为基础的化疗中获益,可能是由于胸腺苷酸合成酶(TS)水平较低。本研究在37例fish阳性NSCLC中评估了三种不同的ALK IHC克隆的一致性。实时(RT)-PCR法比较ALK - fish阴性患者的TS表达情况。材料和方法:2010年至2015年间,意大利7个中心诊断的37例ALK fish阳性非小细胞肺癌患者使用三种不同的抗ALK抗体(ALK1, 5A4和D5F3)进行ICH调查。ALK1和5A4染色分为0+、1+、2+和3+,D5F3评分为阴性或阳性。采用Cohen's未加权kappa (k)进行比例一致性分析。采用定量RT-PCR分析TS和β-actin表达水平。采用Mann-Whitney和Kruskal-Wallis试验比较ALK fish阳性标本和ALK fish阴性对照标本中TS的表达。结果:考虑2+和3+为阳性,ALK1/ 5a4的IHC一致性比例为0.1691 (95% CI 0-0.4595), ALK1/D5F3为0.1691 (95% CI 0-0.4595), D5F3/ 5a4为1。考虑到3+为阳性,ALK1/ 5A4为0.1543 (95% CI 0-0.4665), ALK1/D5F3为0.0212 (95% CI 0-0.1736), 5A4/D5F3为0.2269 (95% CI 0-0.5462)。TS的中位表达量为6.07 (1.28-14.94),alk阳性患者的TS表达量显著低于alk阴性患者(p = 0.002)。结论:免疫组化是诊断alk重排非小细胞肺癌的可靠工具。D5F3和5A4克隆的一致性百分比最高。fish阳性患者的TS水平显著降低。
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引用次数: 0
An unexpected cause of recurrent pneumothorax. 复发性气胸的意外原因。
IF 3.5 Q1 PATHOLOGY Pub Date : 2022-08-01 DOI: 10.32074/1591-951X-377
Giulio Rossi, Anna Farnedi, Fabio Davoli, Adolfo D'Agostino, Tommaso Bizzarro, Paride D'Angelo, Rita Sargiacomo

The thoracic district is the most frequent visceral location of synovial sarcoma, generally involving lung and pleura as a large solid mass. We present herein a 57-year-old man with recurrent pneumothorax and a localized bulla at the lingula. The lesion was excised by a Video-Assisted-Thoracoscopic-Surgery (VATS) wedge resection and surprisingly consisted of a unilocular cyst with fibrous wall intermingled by a longitudinal proliferation of bland-looking, dense, monomorphic spindle cells diffusely expressing EMA, CD99, CD56 and focally staining with cytokeratins. Fluorescent in situ hybridization demonstrated the presence of SYT rearrangement and a diagnosis of pulmonary cystic monophasic synovial sarcoma was made. Only few similar cases have been reported in literature, mainly occurring in young male adults. A meticulous examination of all resected tissue from pneumothorax is the prerequisite to suspect this extremely challenging condition, while immuno-molecular studies are mandatory to achieve the correct diagnosis.

胸区是滑膜肉瘤最常见的内脏部位,通常累及肺和胸膜,呈大的实性肿块。我们在此报告一个57岁的男性复发性气胸和在舌部的局部大疱。病变通过视频辅助胸腔镜手术(VATS)楔形切除术切除,令人惊讶的是由一个单眼囊肿组成,纤维壁由纵向增生的外观单调,致密的单形梭形细胞混合,弥漫性表达EMA, CD99, CD56,并局部染色细胞角蛋白。荧光原位杂交显示SYT重排的存在,诊断为肺囊性单相滑膜肉瘤。文献中仅有少数类似病例报道,主要发生在年轻男性成年人中。对所有从气胸切除的组织进行细致的检查是怀疑这种极具挑战性的疾病的先决条件,而免疫分子研究是实现正确诊断的必要条件。
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引用次数: 1
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