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Correlation of different HPV genotype viral loads and cervical lesions: A retrospective analysis of 1585 cases 不同 HPV 基因型病毒载量与宫颈病变的相关性:对 1585 例病例的回顾性分析。
IF 2.6 3区 医学 Q3 ONCOLOGY Pub Date : 2024-11-18 DOI: 10.1002/cncy.22920
Yilu Zhou, Jiaxin Liu, Shuai Chen, Xianzhen Xin, Mohan Xiao, Xian Qiang, Lina Zhang

Background

To reduce unnecessary examinations and treatments, an effective detection method for differentiating human papillomavirus (HPV)-positive patients is urgently needed. This study aimed to explore the differences in HPV viral loads across various cervical lesions and identify the optimal cutoff value for high-grade squamous intraepithelial lesions (HSILs).

Methods

This retrospective study included patients with varying degrees of cervical lesions admitted to a hospital between January 1, 2023, and March 1, 2024. The HPV genotype and viral load were determined using BioPerfectus multiplex real-time assay. The differences in HPV genotype viral loads among cervical lesion classifications were analyzed to identify the most applicable type of viral load.

Results

The viral loads of HPV16, HPV31, HPV33, HPV35, and HPV58 were significantly associated with the grade of cervical lesions (p < .05), with the HPV16 group exhibiting the strongest correlation (p < .01). The HPV16 viral load demonstrated good sensitivity (Se) and specificity (Sp) for predicting HSIL (Se = 81.52%, Sp = 64.13%). The three most prevalent HPV genotypes associated with negative, low-grade squamous intraepithelial lesions (LSILs) and HSILs were HPV16, HPV52, and HPV58. HPV33 exhibited the highest prevalence of HSILs, followed by HPV16.

Conclusions

High-risk HPV viral load is associated with cervical lesion classification. HPV16 viral load can effectively differentiate HSIL from LSIL with good Se and Sp.

背景:为了减少不必要的检查和治疗,迫切需要一种有效的检测方法来区分人乳头瘤病毒(HPV)阳性患者。本研究旨在探讨不同宫颈病变中 HPV 病毒载量的差异,并确定高级别鳞状上皮内病变(HSIL)的最佳临界值:这项回顾性研究纳入了2023年1月1日至2024年3月1日期间入住医院的不同程度宫颈病变患者。HPV基因型和病毒载量采用BioPerfectus多重实时检测法进行测定。分析了不同宫颈病变分类中 HPV 基因型病毒载量的差异,以确定最适用的病毒载量类型:结果:HPV16、HPV31、HPV33、HPV35 和 HPV58 的病毒载量与宫颈病变的等级显著相关(p 结论:HPV16、HPV31、HPV33、HPV35 和 HPV58 的病毒载量与宫颈病变的等级显著相关:高危型 HPV 病毒载量与宫颈病变分级相关。HPV16病毒载量能有效区分HSIL和LSIL,且Se和Sp良好。
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引用次数: 0
Fine-needle aspiration and effusion cytology of thoracic SMARCA4–deficient undifferentiated tumor and SMARCA4-deficient non–small cell lung carcinoma: A multi-institutional experience with 27 patients 胸部SMARCA4缺失性未分化肿瘤和SMARCA4缺失性非小细胞肺癌的细针穿刺和渗出物细胞学:27例患者的多机构经验。
IF 2.6 3区 医学 Q3 ONCOLOGY Pub Date : 2024-11-18 DOI: 10.1002/cncy.22919
Nicole Zalles MD, PhD, Sanjay Mukhopadhyay MD, Swati Satturwar MD, Sigfred Lajara MD, Samer Khader MD, Liron Pantanowitz MD, Tarik M. Elsheikh MD

Background

Thoracic switch/sucrose nonfermentable–related, matrix-associated, actin-dependent regulator of chromatin, subfamily A, member 4 (SMARCA4)–deficient (SD) malignancies, including SD undifferentiated tumor (SD-UT) and SD non–small cell lung carcinoma (SD-NSCLC), have been recently described. The cytologic features of these neoplasms in fine-needle aspiration (FNA) and effusion specimens have rarely been reported in the literature. This study aimed to describe and compare the spectrum of cytologic, immunohistochemical, and clinical features of these high-grade malignancies recently encountered at the participating institutions.

Methods

This study documented clinical and imaging characteristics of tumors from 27 patients. Sixteen cytomorphologic features and immunohistochemical findings were compared between SD-UT and SD-NSCLC samples.

Results

Twenty three FNAs, two bronchial brushings, and two pleural fluids were evaluated, including 17 SD-UT cases (mean patient age, 70 years) and 10 SD-NSCLC cases (mean patient age, 62 years). Both malignancies presented with large thoracic masses and/or hilar/mediastinal lymphadenopathy. All SD-UT cytologic samples had a discohesive or mixed cohesive–discohesive architecture, and most (13 of 17) showed predominant rhabdoid or mixed rhabdoid–epithelioid features. Most SD-NSCLC cytologic samples (nine of 10) were either cohesive or mixed cohesive–discohesive and had a predominantly epithelioid morphology (eight of 10). Keratins and claudin-4 were negative or focally positive in SD-UT samples, whereas they were diffusely positive in SD-NSCLC samples. Both malignancies were negative for TTF-1 and p40/p63 and showed loss of expression of SMARCA4.

Conclusions

Although there is considerable clinical and cytopathologic overlap between SD-UT and SD-NSCLC, some key features allow for their distinction. SD-UT is mostly discohesive with rhabdoid or mixed rhabdoid–epithelioid features, whereas SD-NSCLC often has cohesive epithelioid morphology. The combination of clinical presentation, cytomorphology, and immunohistochemistry is essential for a definitive diagnosis.

背景:最近描述了胸腔开关/蔗糖不发酵相关、基质相关、染色质A亚家族成员4(SMARCA4)依赖性调节因子(SD)缺陷的恶性肿瘤,包括SD未分化肿瘤(SD-UT)和SD非小细胞肺癌(SD-NSCLC)。这些肿瘤在细针穿刺(FNA)和渗出标本中的细胞学特征在文献中鲜有报道。本研究旨在描述和比较参与研究机构最近发现的这些高级别恶性肿瘤的细胞学、免疫组化和临床特征:本研究记录了 27 名患者肿瘤的临床和影像学特征。比较了 SD-UT 和 SD-NSCLC 样本的 16 种细胞形态学特征和免疫组化结果:共评估了 23 份 FNA、2 份支气管刷片和 2 份胸腔积液,其中包括 17 例 SD-UT 病例(患者平均年龄 70 岁)和 10 例 SD-NSCLC 病例(患者平均年龄 62 岁)。这两种恶性肿瘤均伴有胸部大肿块和/或腹腔/纵隔淋巴结病。所有SD-UT细胞学样本都具有盘状或混合内聚-盘状结构,大多数样本(17例中的13例)显示出主要的横纹肌样或横纹肌样-上皮样混合特征。大多数SD-NSCLC细胞学样本(10个样本中的9个)为内聚型或内聚-粘连混合型,形态主要为上皮样(10个样本中的8个)。角蛋白和Claudin-4在SD-UT样本中呈阴性或局灶性阳性,而在SD-NSCLC样本中呈弥漫性阳性。这两种恶性肿瘤的TTF-1和p40/p63均为阴性,并显示SMARCA4表达缺失:结论:尽管SD-UT和SD-NSCLC在临床和细胞病理学上有相当多的重叠,但一些关键特征还是可以将它们区分开来。SD-UT多为盘状,具有横纹肌样或横纹肌样上皮样混合特征,而SD-NSCLC通常具有内聚性上皮样形态。结合临床表现、细胞形态学和免疫组化对明确诊断至关重要。
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引用次数: 0
Retrospective analysis of HPV infection: Cotesting and HPV genotyping in cervical cancer screening within a large academic health care system HPV感染的回顾性分析:在一个大型学术医疗保健系统中,宫颈癌筛查中的细胞检测和 HPV 基因分型。
IF 2.6 3区 医学 Q3 ONCOLOGY Pub Date : 2024-11-05 DOI: 10.1002/cncy.22916
Frances Xiuyan Feng MD, PhD, George G. Birdsong MD, Jane Wei MPH, Melad N. Dababneh MBBS, Michelle D. Reid MD, MS, Michael Hoskins BS, CT(ASCP), Qun Wang MD, PhD

Background

In 2019, the American Society for Colposcopy and Cervical Pathology introduced fundamental shifts toward “risk-based” guidelines, with human papillomavirus (HPV) genotyping as a principal test for investigating squamous intraepithelial lesions. This study aims to provide practice-based evidence and supplement the updated guidelines by investigating HPV demographic distribution and uncovering the pathological features of high-grade squamous intraepithelial lesions (HSILs) caused by high-risk HPV (hrHPV) subtypes.

Methods

Patients who underwent Papanicolaou screening and HPV testing in two hospital systems over the course of 4 years were recruited. The cytology results were categorized on the basis of the 2014 Bethesda classification. DNA sequences of 14 types of hrHPV were detected by Aptima test. The histological features of HSILs caused by different subtypes were compared between biopsies and excisions.

Results

A total of 63,709 cases were included. The HPV prevalence was 14.70%, predominantly in the 30 to 39-year-old age group, with slightly higher rates observed in African Americans. There was no significant racial distribution difference between HPV 16/18/45 and other types. HPV 16/18/45 infection was directly correlated with the severity of abnormal cytology, although the other subtypes were the major causes of cytological abnormalities. The trend for HPV prevalence was consistent across calendar years, and was associated with 8.77% negative for intraepithelial lesion or malignancy, 30.46% atypical squamous cell of undetermined significance, 64.62% low-grade squamous intraepithelial lesion, 66.75% atypical squamous cell-cannot exclude a high-grade squamous intraepithelial lesion, and 91.80% HSIL. Furthermore, 29.09% of HSILs associated with other subtypes were not detectable on subsequent resections.

Conclusions

Given the HPV demographic distribution and the histological features of HSILs caused by different subtypes, cotesting with reflex HPV genotyping in specific populations, or expanding the subtypes in the primary HPV screening test, should be considered.

背景:2019年,美国阴道镜和宫颈病理学学会推出了 "基于风险 "的基本指南,将人类乳头瘤病毒(HPV)基因分型作为调查鳞状上皮内病变的主要检测方法。本研究旨在通过调查 HPV 的人口分布和揭示高危型 HPV(hrHPV)亚型引起的高级别鳞状上皮内病变(HSIL)的病理特征,提供基于实践的证据并补充更新后的指南:方法:招募在两家医院系统接受巴氏筛查和 HPV 检测的患者,时间跨度为 4 年。细胞学结果根据 2014 年贝塞斯达分类法进行分类。通过 Aptima 测试检测了 14 种 hrHPV 的 DNA 序列。比较了活组织检查和切除术中不同亚型引起的HSIL的组织学特征:结果:共纳入 63 709 个病例。HPV感染率为14.70%,主要集中在30至39岁年龄组,非裔美国人的感染率略高。HPV 16/18/45 和其他类型在种族分布上没有明显差异。HPV 16/18/45 感染与细胞学异常的严重程度直接相关,尽管其他亚型是细胞学异常的主要原因。各历年的 HPV 感染率趋势一致,与 8.77% 上皮内病变或恶性肿瘤阴性、30.46% 重要性未定的非典型鳞状细胞、64.62% 低级别鳞状上皮内病变、66.75% 非典型鳞状细胞-不能排除高级别鳞状上皮内病变和 91.80% HSIL 相关。此外,29.09%与其他亚型相关的HSIL在随后的切除术中无法检测到:鉴于不同亚型引起的HPV人群分布和HSIL的组织学特征,应考虑在特定人群中与反射性HPV基因分型联合检测,或在HPV初筛检测中扩大亚型范围。
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引用次数: 0
Analysis of the sensitivity of high-grade squamous intraepithelial lesion Pap diagnosis and interobserver variability with the Hologic Genius Digital Diagnostics System 使用 Hologic Genius 数字诊断系统分析高级别鳞状上皮内病变巴氏诊断的敏感性和观察者之间的变异性。
IF 2.6 3区 医学 Q3 ONCOLOGY Pub Date : 2024-11-05 DOI: 10.1002/cncy.22918
Lakshmi Harinath MD, MPH, Esther Elishaev MD, Yuhong Ye MD, PhD, Jonee Matsko SCT, MB, Amy Colaizzi SCT, Stephanie Wharton SCT, Rohit Bhargava MD, Liron Pantanowitz MD, PhD, MHA, Chengquan Zhao MD

Background

Artificial intelligence (AI)–based systems are transforming cytopathology practice. The aim of this study was to evaluate the sensitivity of high-grade squamous intraepithelial lesion (HSIL) Papanicolaou (Pap) diagnosis assisted by the Hologic Genius Digital Diagnostics System (GDDS).

Methods

A validation study was performed with 890 ThinPrep Pap tests with the GDDS independently. From this set, a subset of 183 cases originally interpreted as HSIL confirmed histologically were included in this study. The sensitivity for detecting HSIL by three cytopathologists was calculated.

Results

Most HSIL cases were classified as atypical glandular cell/atypical squamous cell–high grade not excluded (AGC/ASC-H) and above by all cytopathologists. Of these cases, 11.5% were classified as low-grade squamous intraepithelial lesion (LSIL) by pathologist A (P-A), 6% by pathologist B (P-B), and 5.5% by pathologist C (P-C); 3.8%, 2.7%, and 1.6% of these cases were classified as atypical squamous cell of unknown significance (ASC-US) by P-A, P-B, and P-C, respectively. The sensitivity for detection of cervical intraepithelial neoplasia 2 and above (CIN2+) lesions was 100% if ASC-US and above (ASC-US+) abnormalities were counted among all three pathologists. The sensitivity for detection of CIN2+ lesions was 84.7%, 91.3%, and 92.9% by P-A, P-B, and P-C, respectively, for ASC-H and above abnormalities. The Kendall W coefficient was 0.722, which indicated strong agreement between all pathologists.

Conclusions

New-generation AI-assisted Pap test screening systems such as the GDDS have the potential to transform cytology practice. In this study, the GDDS aided in interpreting HSIL in ThinPrep Pap tests, with good sensitivity and agreement between the pathologists who interacted with this system.

背景:基于人工智能(AI)的系统正在改变细胞病理学实践。本研究旨在评估Hologic Genius数字诊断系统(GDDS)辅助诊断高级别鳞状上皮内病变(HSIL)巴氏涂片(Pap)的灵敏度:方法:利用 GDDS 独立对 890 项 ThinPrep 巴氏试验进行了验证研究。本研究从中选取了183例经组织学证实为HSIL的病例。计算了三位细胞病理学家检测 HSIL 的灵敏度:结果:大多数 HSIL 病例被所有细胞病理学家归类为不排除的非典型腺细胞/非典型鳞状细胞-高级别(AGC/ASC-H)及以上。在这些病例中,病理学家A(P-A)将11.5%的病例归类为低级别鳞状上皮内病变(LSIL),病理学家B(P-B)将6%的病例归类为低级别鳞状上皮内病变(LSIL),病理学家C(P-C)将5.5%的病例归类为低级别鳞状上皮内病变(LSIL);P-A、P-B和P-C分别将3.8%、2.7%和1.6%的病例归类为意义不明的非典型鳞状细胞(ASC-US)。如果所有三位病理学家都计算 ASC-US 及以上(ASC-US+)异常,则宫颈上皮内瘤变 2 及以上(CIN2+)病变的检测灵敏度为 100%。对于 ASC-H 及以上异常,P-A、P-B 和 P-C 检测 CIN2+ 病变的灵敏度分别为 84.7%、91.3% 和 92.9%。Kendall W系数为0.722,表明所有病理学家之间的一致性很高:结论:新一代人工智能辅助巴氏试验筛查系统(如 GDDS)有可能改变细胞学实践。在这项研究中,GDDS 有助于解释薄层子宫颈抹片检查中的 HSIL,其灵敏度很高,与该系统互动的病理学家之间的意见也很一致。
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引用次数: 0
Cancer-aiding elements begin illuminating the genome’s “dark matter” 癌症辅助元素开始照亮基因组的 "暗物质":在曾经被认为是无用的垃圾中,类似病毒的转座子、长非编码 RNA 和其他奇异分子已成为癌症研究人员的灯塔。
IF 2.6 3区 医学 Q3 ONCOLOGY Pub Date : 2024-11-02 DOI: 10.1002/cncy.22917
Bryn Nelson PhD, William Faquin MD, PhD
<p>When researchers set out to identify every protein-encoding gene in the human genome, initial estimates suggested that they might find up to 100,000. In reality, scientists have uncovered fewer than 20,000, which account for only 2% of the 3.1 billion letters of DNA.<span><sup>1</sup></span></p><p>The remaining 98% has been referred to as “junk DNA” or “dark matter,” which reflects the once-common assumption that it was little more than genomic filler. An estimated 14,000 pseudogenes, or defective copies of genes, may fall into that category, albeit with some exceptions. Recent studies, however, have cast a new spotlight on a menagerie of other molecules, including some with a lineage far older than the human species, that may play significant roles in the development and progression of cancer and other diseases.</p><p>Martin Taylor, MD, PhD, assistant professor of pathology and laboratory medicine at the Brown University Center on the Biology of Aging and the Legorreta Cancer Center in Providence, Rhode Island, began studying one kind of genomic dark matter, LINE-1 retrotransposons, approximately 15 years ago. “The overwhelming evidence says that these are just parasitic sequences that we’ve been evolving with for billions of years,” he says of the mobile elements. “They’re actually older than multicellular organisms.” The virus-like, self-copying sequences, in fact, may have given rise to viruses.</p><p>Astoundingly, LINE-1 has effectively written at least one-third of the human genome through its copy-and-paste mechanism. Most of its own 500,000 copies are “fossils” from when humans mutated and defeated the once full-length retrotransposons. However, an estimated 6000 elements are more or less still intact; of those, maybe 100–150 are still functional and capable of hopping around and inserting themselves into other sequences, Dr Taylor says. They are repressed in healthy tissues but can become activated in the event of diseases such as cancer and autoimmune diseases.</p><p>By sequencing cancers, researchers have found that LINE-1, on rare occasion, can insert itself into a tumor suppressor gene such as APC or P10 and promote cancer. Work by Dr Taylor and others suggests that LINE-1 also may contribute to cancer in other ways. Those cancer-abetting mechanisms, he says, “have to do with the fact that when LINE-1 gets turned on, the cell thinks it’s infected with a virus—or at least has a virus-like response—and that causes inflammation.” The defensive response, research suggests, can manipulate the tumor microenvironment and alter cell signaling pathways to promote carcinogenesis.</p><p>In addition, Dr Taylor says, “The transposons cause a huge amount of DNA damage, and the thinking in the field now is that they may contribute to the chromosomal instability that we see as a hallmark of cancer.” He sees LINE-1 not as a classic cancer driver but rather as an accelerator that more broadly contributes to cancer development and progression, thoug
约翰逊博士说,除了p53和KRAS等标志性癌症相关基因突变外,越来越多的证据表明,一些lncRNA的低频突变也可能促进肿瘤生长。然而,更多的lncRNAs似乎会随着肿瘤形成过程中广泛的细胞破坏而改变其活性水平,这种变化导致了不同肿瘤所特有的模式。"他说:"有些lncRNA在所有肿瘤中都具有普遍性,而另一些lncRNA的活性则对不同类型的肿瘤具有很强的特异性。"他说:"最大的挑战在于,在我们所知道的癌症中发生变化的所有这些因素中,哪些因素的变化实际上是导致疾病的原因,而不仅仅是疾病的结果?约翰逊博士说:"当你寻找治疗靶点时,你真正想做的是找到致病因子。"被称为CRISPR-Cas9的强大基因编辑工具的出现,为约翰逊博士的实验室提供了一种将相关性与因果关系区分开来的新方法。他说:"这种工具使我们能够扰乱癌细胞中的这些lncRNA基因,并直接提出问题:'这些lncRNA对癌细胞的生长或存活是否有积极作用?lncRNA上附着的独特基因标签可以指出哪些基因是癌细胞最依赖的,因为杀死宿主细胞的基因缺失会将相应的基因标签从保留下来的癌细胞的集合DNA序列中删除。5 约翰逊博士和他的同事们已经开始关注其中两个最有希望的靶点,并正在探索使用反义寡核苷酸,或设计的基因序列,通过与目标 lncRNA 结合并降解,发挥类似药物的作用。到目前为止,初步测试表明,靶向失活对多种肺癌细胞有很强的抑制作用;与基于LINE-1的疗法一样,制药公司开始注意并资助癌症药物设计工作。泰勒博士举例说,鉴于转座元件能够破坏整个基因组的DNA序列,它们与解剖变异、缺陷和疾病之间的联系可能比以前认为的要广泛得多。"他说:"许多正常的生物学现象实际上可能是由于LINE-1或我们还不了解的基因组的其他部分造成的。
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引用次数: 0
International perspective on pediatric cytology 儿科细胞学的国际视角。
IF 2.6 3区 医学 Q3 ONCOLOGY Pub Date : 2024-10-16 DOI: 10.1002/cncy.22911
Maren Y. Fuller MD, Sujan Shrestha MBBS, MD, Swikrity U. Baskota MBBS, MD
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引用次数: 0
Utility of The Paris System for Reporting Urinary Cytology in patients with HPV-positive urinary tract carcinoma 巴黎尿液细胞学报告系统对 HPV 阳性尿路癌患者的实用性。
IF 2.6 3区 医学 Q3 ONCOLOGY Pub Date : 2024-10-15 DOI: 10.1002/cncy.22914
Kara Tanaka MD, MFA, Neslihan Kayraklioglu MD, PhD, Emily Chan MD, PhD, Chien-Kuang C. Ding MD, PhD, Poonam Vohra MD

Background

Human papillomavirus (HPV)-positive urinary tract carcinomas (UTCas) have distinct morphology and molecular features with potential treatment implications. Cytomorphologic analysis of these tumors on urine cytology specimens has not yet been reported. The authors evaluated the cytomorphologic findings of HPV-positive UTCa on urine cytology using The Paris System for Reporting Urinary Cytology (TPS) criteria.

Methods

HPV-positive cases were identified by a retrospective review of surgical specimens that had UTCa confirmed by HPV in situ hybridization. Cases that had concurrent urine cytology were reviewed using TPS. Cytomorphologic features of high-grade urothelial carcinoma (HGUC) were evaluated as well as the presence of atypical squamous cells (ASCs) and basaloid features.

Results

Sixteen cytology specimens from eight patients with HPV-positive UTCa were included. On original diagnosis, none of the cytology specimens were suggested to be HPV-associated. TPS diagnostic criteria identified eight cases with at least atypical findings, including five HGUC cases, one case that was suspicious for HGUC, and two atypical urothelial cases. Common cytomorphologic features included basaloid clusters (six of eight cases; 75%) and ASCs (four of eight cases; 50%) that matched the corresponding surgical specimens. Most cases exhibited urothelial cell hyperchromasia (seven of eight cases; 88%), and hypochromasia was a frequently observed variant (four of eight cases; 50%), either alone or in addition to hyperchromasia.

Conclusions

HPV-positive UTCa can be identified reliably as HGUC by using TPS criteria; however, these cases may not be recognized as HPV-associated. The presence of basaloid cells or ASCs can help suggest screening for HPV in urine specimens. Larger scale studies are warranted to validate cytomorphologic differences and determine the impact of HPV infection on clinical outcomes for patients with UTCa.

背景:人乳头瘤病毒(HPV)阳性尿路癌(UTCas)具有独特的形态和分子特征,对治疗有潜在影响。尿液细胞学标本上的细胞形态学分析尚未见报道。作者采用巴黎尿液细胞学报告系统(TPS)标准评估了尿液细胞学中 HPV 阳性 UTCa 的细胞形态学结果。使用 TPS 对同时进行尿液细胞学检查的病例进行复查。对高级别尿路上皮癌(HGUC)的细胞形态学特征以及非典型鳞状细胞(ASC)和基底细胞特征进行了评估:结果:共纳入了8名HPV阳性UTCa患者的16份细胞学标本。在最初诊断时,没有一份细胞学标本被认为与 HPV 相关。TPS诊断标准确定了8例至少有非典型发现的病例,包括5例HGUC病例、1例疑似HGUC病例和2例非典型尿路上皮病例。常见的细胞形态学特征包括基底簇(8 例中的 6 例;75%)和 ASCs(8 例中的 4 例;50%),与相应的手术标本相符。大多数病例表现为尿路细胞色素沉着(8 例中的 7 例;88%),低色素沉着是一种经常观察到的变异(8 例中的 4 例;50%),可单独存在或与色素沉着同时存在:结论:HPV 阳性 UTCa 可以通过 TPS 标准可靠地识别为 HGUC;但是,这些病例可能无法识别为 HPV 相关病例。基底细胞或ASCs的存在有助于建议对尿液标本进行HPV筛查。有必要进行更大规模的研究,以验证细胞形态学上的差异,并确定 HPV 感染对UTCa 患者临床预后的影响。
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引用次数: 0
Single-cell multiplex immunocytochemistry in cell block preparations of metastatic breast cancer confirms sensitivity of GATA-binding protein 3 over gross cystic disease fluid protein 15 and mammaglobin 转移性乳腺癌细胞块制备中的单细胞多重免疫细胞化学证实,GATA 结合蛋白 3 对毛囊性疾病液蛋白 15 和乳红蛋白的敏感性高于对毛囊性疾病液蛋白 15 和乳红蛋白的敏感性。
IF 2.6 3区 医学 Q3 ONCOLOGY Pub Date : 2024-10-08 DOI: 10.1002/cncy.22910
Joshua J. X. Li MBChB, Hiu Yu Cheng MSc, Conrad H. C. Lee MSc, Joanna K. M. Ng MBBS, Julia Y. Tsang PhD, Gary M. Tse MBBS

Background

Metastatic breast cancers are frequently encountered in cytology and require immunocytochemistry (ICC). In this study, traditional and multiplex ICC (mICC) for GATA-binding protein 3 (GATA3), gross cystic disease fluid protein 15 (GCDFP15), and mammaglobin (MMG) were performed with the aim of validating mICC in cell blocks, with further single-cell expression pattern analysis to identify the single markers and combinations of markers most sensitive in subtypes of breast cancer.

Methods

GATA3, GCDFP15, and MMG were paired with OptiView 3,3′-diaminobenzidine and Ventana DISCOVERY Purple and Blue, respectively, with cyclical and serial staining. Bright-field imaging was performed with the Mantra 2 system and analyzed with the inForm Tissue Finder (Akoya Biosciences). Cell detection and phenotyping were further confirmed by two pathologists.

Results

In the 36 cases studied, traditional ICC and mICC demonstrated good concordance (kappa coefficient, >0.5; p < .01) at three cutoffs (1%, 5%, and 50%), except for GATA3 at the 1% cutoff. Single-marker positivity outnumbered double-marker positivity and the exceedingly rare triple-marker positivity (<3%). GATA3 was the leading single marker–positive phenotype in all breast cancer subtypes, except for MMG in estrogen receptor–positive, progesterone receptor–positive, and human epidermal growth factor receptor 2–positive (ER+/PR+/HER2+) breast cancers. Limited to two markers, GATA3/MMG included the greatest number of tumor cells for luminal breast cancers (ER+/PR+/HER2+, 60.6%; ER+/PR+/HER2+, 31.4%), whereas HER2-overexpressed breast cancers (27.4%) and triple-negative breast cancers (26.4%) favored the combination of GATA3/GCDFP15.

Conclusions

For a single marker, GATA3 displayed the highest sensitivity. The addition of MMG for hormone receptor-positive breast cancers and GCDFP15 for hormone receptor-negative breast cancers further increased sensitivity. The low proportion of multimarker-positive cells suggested that the coexpression observed with traditional ICC is attributable to intratumoral heterogeneity, not genuine coexpression.

背景:转移性乳腺癌经常在细胞学检查中遇到,需要进行免疫细胞化学(ICC)检查。本研究对 GATA 结合蛋白 3 (GATA3)、毛囊性疾病液蛋白 15 (GCDFP15) 和乳腺球蛋白 (MMG) 进行了传统和多重 ICC (mICC),目的是验证细胞块中的 mICC,并进一步进行单细胞表达模式分析,以确定对乳腺癌亚型最敏感的单一标记物和标记物组合:GATA3、GCDFP15和MMG分别与OptiView 3,3'-二氨基联苯胺和Ventana DISCOVERY Purple和Blue配对,进行周期性和连续染色。使用 Mantra 2 系统进行明视野成像,并使用 inForm Tissue Finder(Akoya Biosciences)进行分析。细胞检测和表型由两名病理学家进一步确认:在研究的 36 个病例中,传统的 ICC 和 mICC 显示出良好的一致性(卡帕系数大于 0.5;P 结论:传统的 ICC 和 mICC 的结果一致:就单一标记物而言,GATA3 的灵敏度最高。在激素受体阳性乳腺癌中加入 MMG,在激素受体阴性乳腺癌中加入 GCDFP15,可进一步提高灵敏度。多标志物阳性细胞比例较低,这表明传统 ICC 观察到的共表达是由于瘤内异质性造成的,而不是真正的共表达。
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引用次数: 0
Intraoperative peritoneal cytology for cervical gastric-type adenocarcinoma: Cytopathology and clinical impact 宫颈胃型腺癌术中腹膜细胞学检查:细胞病理学和临床影响。
IF 2.6 3区 医学 Q3 ONCOLOGY Pub Date : 2024-10-08 DOI: 10.1002/cncy.22915
Waku Takigawa MD, Hiroshi Yoshida MD, PhD, Shoichi Kitamura MD, Chika Tokutake CT, Madoka Kondo CT, Mizuho Fujima CT, Yasuo Shibuki CT, Mayumi Kobayashi-Kato MD, PhD, Yasuhito Tanase MD, PhD, Masaya Uno MD, PhD, Mitsuya Ishikawa MD, PhD

Background

The objective of this study was to elucidate the frequency and cytologic features of positive peritoneal washing cytology (PWC) in cervical gastric-type adenocarcinoma (GAS) and to clarify the clinical significance of positive PWC.

Methods

The authors analyzed cases from their institution between 1991 and 2023 in which patients underwent surgery and PWC. The study included 62 patients who had cervical GAS (1991–2023; including seven patients with adenocarcinoma in situ and 26, 15, nine, and five patients with International Federation of Gynecology and Obstetrics 2018 stage I, II, III, and IV disease, respectively) and 100 patients who had usual-type endocervical adenocarcinoma (2007–2023; including 65, 15, and 20 patients with stage I, II, and III disease, respectively). The frequency of positive PWC results and cytologic features was assessed, and correlations between positive PWC results and clinicopathologic factors were examined, including prognosis, in the GAS group.

Results

Positive PWC results were significantly more frequent in patients who had GAS at 24% (15 of 62 patients) compared with 7% (seven of 100 patients) in those who had usual-type endocervical adenocarcinoma. The cytologic features of GAS included distinct cellular atypia (enlarged nuclei, nuclear irregularity) and frequent formation of spherical clusters (10 of 15 cases) without the golden-yellowish mucus commonly seen in cervical smears. A positive PWC result in GAS was significantly correlated with larger tumor size, parametrium invasion, lymph node metastasis, and elevated carbohydrate antigen 19-9 levels. In patients with stage I GAS, the PWC-positive group had significantly shorter disease-free survival and overall survival compared with the PWC-negative group.

Conclusions

Positive PWC findings are frequent in cervical GAS and are associated with pathologic factors indicative of tumor growth and progression. In patients who have stage I GAS, positive PWC results may indicate a poor prognosis, warranting further investigation.

研究背景本研究旨在阐明宫颈胃型腺癌(GAS)腹膜冲洗细胞学(PWC)阳性的频率和细胞学特征,并明确PWC阳性的临床意义:作者分析了其所在机构在 1991 年至 2023 年期间接受手术和 PWC 的病例。研究纳入了 62 例宫颈 GAS 患者(1991-2023 年;包括 7 例原位腺癌患者和 26 例、15 例、9 例和 5 例国际妇产科联盟 2018 年 I、II、III 和 IV 期疾病患者)和 100 例普通型宫颈内膜腺癌患者(2007-2023 年;包括 65 例、15 例和 20 例 I、II 和 III 期疾病患者)。评估了PWC阳性结果的频率和细胞学特征,并研究了GAS组中PWC阳性结果与临床病理因素(包括预后)之间的相关性:结果:PWC阳性结果在GAS患者中的出现率明显更高,为24%(62例患者中的15例),而在普通型宫颈内膜腺癌患者中仅为7%(100例患者中的7例)。GAS 的细胞学特征包括明显的细胞不典型性(核增大、核不规则)和经常形成球形团块(15 例中有 10 例),而没有宫颈涂片中常见的金黄色粘液。GAS 患者的 PWC 阳性结果与肿瘤体积增大、宫旁侵犯、淋巴结转移和碳水化合物抗原 19-9 水平升高有显著相关性。在 I 期 GAS 患者中,PWC 阳性组的无病生存期和总生存期明显短于 PWC 阴性组:结论:PWC 阳性结果在宫颈 GAS 中很常见,并且与表明肿瘤生长和进展的病理因素相关。对于 I 期 GAS 患者,PWC 阳性结果可能预示着不良预后,值得进一步研究。
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引用次数: 0
Thank You to Reviewers 2024 感谢评审员2024
IF 2.6 3区 医学 Q3 ONCOLOGY Pub Date : 2024-10-07 DOI: 10.1002/cncy.22913
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引用次数: 0
期刊
Cancer Cytopathology
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