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Genotype profile of HPV in ASC-H cytology and histologic follow-up—prevalence, distribution, and risk: A retrospective study of 1414 cases ASC-H细胞学和组织学随访中的HPV基因型概况--流行率、分布和风险:1414 例病例的回顾性研究。
IF 2.6 3区 医学 Q3 ONCOLOGY Pub Date : 2024-06-16 DOI: 10.1002/cncy.22877
Yihua Sun MD, Tiannan Wang MD, PhD, Fangfang Zhong MD, David Starr MD, Xianxu Zeng MD, PhD, Hao Zhang MD, Jianan Xiao MD, Xianrong Zhou MD, Xiang Tao MD, PhD, Chengquan Zhao MD

Background

A cytologic diagnosis of atypical squamous cells, cannot exclude high-grade squamous lesion (ASC-H) poses a disproportionately high risk of cervical cancer development. The objective of this study was to analyze type-specific risks by mapping human papillomavirus (HPV) genotypes in ASC-H cytology.

Methods

In total, 1,048,581 Papanicolaou tests that had ASC-H cytology were retrieved. Concurrent HPV genotyping using proprietary multiplex real-time (MRT) and polymerase chain reaction (PCR) HPV tests and histologic follow-up findings were analyzed.

Results

Among 1678 patients who had ASC-H findings (0.16%), 1414 (84.3%) underwent concurrent HPV genotyping (MRT, 857; HPV PCR test, 557). The overall high-risk HPV (hrHPV)-positive rate was 84.4%. Of the 857 MRT cases, 63.9% were infected with a single hrHPV, and 24.4% had multiple genotypes. The most prevalent HPV types were HPV16/52/58/33/31. Lesions that were identified as cervical intraepithelial neoplasia 2 or worse (CIN2+) were detected in 498 of 906 cases (55.0%), including 81 cervical carcinomas (8.9%). The risk of CIN2+ for the composite group of HPV16/52/58/33/31-positive cases was 62.7%, representing 90.7% (264 of 291) of total CIN2+ lesions in ASC-H/hrHPV–positive cases by MRT. CIN2+ lesions were detected in 108 of 142 (76.1%) HPV16-positive and/or HPV18-positive women by the PCR the HPV test. Among 128 hrHPV-negative ASC-H cases by both methods, CIN2+ lesions were identified in 21 of 128 (16.4%), including five cervical carcinomas (3.9%). The sensitivity, specificity, positive predictive value, and negative predictive value for patients in the composite group with HPV16/52/58/33/31 were 88.0%, 40.8%, 62.7%, and 75.0%, respectively.

Conclusions

Papanicolaou tests classified as ASC-H are associated with a high CIN2+ rate and warrant colposcopy, regardless of HPV status. The extent to which the risk-stratification provided by comprehensive HPV genotyping can inform the management of ASC-H cytology remains to be explored.

背景:细胞学诊断为非典型鳞状细胞,但不能排除高级别鳞状病变(ASC-H)的患者罹患宫颈癌的风险极高。本研究的目的是通过绘制 ASC-H 细胞学检查中人乳头瘤病毒(HPV)基因型图谱,分析特定类型的风险:方法:总共检索了 1,048,581 份有 ASC-H 细胞学检查的巴氏涂片。采用专有的多重实时(MRT)和聚合酶链反应(PCR)HPV检测方法同时进行HPV基因分型,并对组织学随访结果进行分析:在1678例出现ASC-H结果的患者(0.16%)中,有1414例(84.3%)同时进行了HPV基因分型(MRT,857例;HPV PCR检测,557例)。高危 HPV (hrHPV) 阳性率为 84.4%。在 857 例 MRT 病例中,63.9% 感染了一种 hrHPV,24.4% 感染了多种基因型。最常见的 HPV 类型为 HPV16/52/58/33/31。906 例病例中有 498 例(55.0%)被确定为宫颈上皮内瘤变 2 或更严重(CIN2+),其中包括 81 例宫颈癌(8.9%)。HPV16/52/58/33/31阳性病例复合组的CIN2+风险为62.7%,占MRT检测的ASC-H/hrHPV阳性病例CIN2+病变总数的90.7%(291例中的264例)。通过 PCR 和 HPV 检测,142 名 HPV16 阳性和/或 HPV18 阳性女性中有 108 名(76.1%)检测出 CIN2+ 病变。在通过这两种方法检测的 128 例 hrHPV 阴性 ASC-H 病例中,有 21 例(16.4%)发现了 CIN2+ 病变,其中包括 5 例宫颈癌(3.9%)。HPV16/52/58/33/31复合组患者的敏感性、特异性、阳性预测值和阴性预测值分别为88.0%、40.8%、62.7%和75.0%:无论HPV状态如何,宫颈巴氏涂片检查归类为ASC-H与高CIN2+率有关,需要进行阴道镜检查。全面的 HPV 基因分型所提供的风险分级能在多大程度上为 ASC-H 细胞学检查的管理提供参考,还有待进一步探讨。
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引用次数: 0
Cytologic features of differentiated high-grade thyroid carcinoma: A multi-institutional study of 40 cases 分化型高级别甲状腺癌的细胞学特征:对40例病例的多机构研究。
IF 2.6 3区 医学 Q3 ONCOLOGY Pub Date : 2024-06-14 DOI: 10.1002/cncy.22874
Vanda F. Torous MD, Tikamporn Jitpasutham, Zubair Baloch, Richard L. Cantley, Darcy A. Kerr, Xiaoying Liu, Zahra Maleki MD, Ross Merkin, Vania Nosé, Liron Pantanowitz, Isabella Tondi Resta, Esther D. Rossi MD, PhD, William C. Faquin

Background

Differentiated high-grade thyroid carcinoma (DHGTC) is recently recognized by the World Health Organization (WHO) as a subgroup of thyroid carcinomas with high-grade features while retaining the architectural and/or cytologic features of well-differentiated follicular–cell-derived tumors. The cytomorphology of DHGTC is not well documented despite potential implications for patient triage and management.

Methods

The pathology archives of six institutions were searched for cases diagnosed on resection as “high-grade thyroid carcinoma” using WHO criteria. The fine-needle aspiration (FNA) cohort represents a 10-year period (2013–2023); all were reviewed to confirm DHGTC classification. The corresponding FNAs were assessed for 32 cytomorphologic features.

Results

Forty cases of DHGTC with prior FNA were identified. The mean patient age was 64.2 years. The average lesion size was 4.9 cm, and the majority demonstrated a TI-RADS score of 4 or 5 (95.2%). Three main high-grade subsets of DHGTC based on corresponding histology included papillary thyroid carcinoma (65%), follicular carcinoma (22.5%), and oncocytic carcinoma (12.5%). Over 97% of FNA cases were classified as Bethesda category IV or above. Approximately 25% of DHGTC showed cytologic features that included marked cytologic atypia, increased anisonucleosis, large oval nuclei, mitotic activity, or necrosis (p < .05); 68% of DHGTC cases were associated with high-risk molecular alterations. TERT mutations occurred in 41%, of which 89% of these were associated with a second mutation, usually RAS or BRAF p.V600E.

Conclusions

Cytology has a low sensitivity for DHGTC, although a subset of DHGTCs have cytologic features raising the possibility of a high-grade thyroid carcinoma. Other findings include high-risk molecular changes and clinicopathologic features such as older patient age and larger lesion size.

背景:分化型高级别甲状腺癌(DHGTC)最近被世界卫生组织(WHO)认定为具有高级别特征的甲状腺癌亚组,同时保留了分化良好的滤泡细胞源性肿瘤的结构和/或细胞学特征。尽管DHGTC的细胞形态学对患者分流和管理有潜在影响,但目前还没有很好的文献记载:方法:在六家机构的病理档案中搜索了根据世界卫生组织标准在切除术中被诊断为 "高级别甲状腺癌 "的病例。细针穿刺术(FNA)队列涵盖了10年的时间(2013-2023年);所有病例都经过了审查,以确认DHGTC分类。对相应的 FNA 进行了 32 项细胞形态学特征评估:结果:共发现40例DHGTC病例,均已进行过FNA检查。患者平均年龄为 64.2 岁。病灶平均大小为 4.9 厘米,大多数患者的 TI-RADS 评分为 4 分或 5 分(95.2%)。根据相应的组织学,DHGTC的三个主要高级别亚型包括甲状腺乳头状癌(65%)、滤泡状癌(22.5%)和肿瘤细胞癌(12.5%)。超过97%的FNA病例被归类为贝塞斯达IV类或以上。约 25% 的 DHGTC 表现出细胞学特征,包括明显的细胞学不典型性、异核增多、大卵圆形核、有丝分裂活动或坏死(P 结论):细胞学检查对DHGTC的敏感性较低,但有一部分DHGTC具有细胞学特征,因此有可能是高级别甲状腺癌。其他发现还包括高风险分子变化和临床病理学特征,如患者年龄较大、病变面积较大等。
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引用次数: 0
Reimagining the future of cancer clinical trials 重塑癌症临床试验的未来:改革者们正在寻找多种方法,以提高药物试验的效率、以患者为中心并使其更有可能取得成功。
IF 3.4 3区 医学 Q3 ONCOLOGY Pub Date : 2024-06-03 DOI: 10.1002/cncy.22837
Bryn Nelson PhD, William Faquin MD, PhD
<p>Oncology is facing a growing disconnect. Decades of advancement in basic research have spurred an unparalleled understanding of the pathology, molecular mechanisms, development, and immunology of cancers—spurring big dreams of personalized therapies and lasting cures. In 2024, however, taking a new anticancer drug from bench to bedside still requires nearly 8 years and $1.5 billion to $2.5 billion according to recent estimates, and the vast majority of efforts end in failure.<span><sup>1</sup></span> Meanwhile, clinical trial enrollment has lagged even at large academic medical centers, in part because information about particular trials often never reaches eligible patients.</p><p>New ideas are desperately needed, says Vivek Subbiah, MD, chief of early-phase drug development at the Sarah Cannon Research Institute in Nashville, Tennessee. The high cost and failure rate, “combined with the inherited inefficiencies and deficiencies that plague the siloed healthcare ecosystem, has led to a crisis in clinical research and drug development,” he says.</p><p>The coronavirus disease 2019 pandemic, interestingly, provided an unexpected opening for experimentation and reconsideration, Dr Subbiah and other experts note. Amid major disruptions to medical infrastructure and drug delivery systems, the US Food and Drug Administration (FDA) and other clinical trial sponsors permitted more flexible designs and a shift toward more patient-centric and intuitive evidence-generating strategies. The drug development community now is pondering whether some allowances could become permanent or least provide a framework for more flexibility in key areas without compromising patient safety.</p><p>One big trend is front-loading preclinical assessments and phase 1 trials to ramp up the early indications of a drug’s likelihood of success. Reformers have advocated leaning into the undeniably complex but rapidly expanding power of -omics technology—not just genomics and proteomics but also epigenetics, metabolomics, immunogenomics, and lipidomics—to make better sense of the data. The more granular information could give researchers a jump on understanding a drug’s promise in preclinical and early-phase trials and on identifying which patient subgroups are most likely to benefit. Phase 1 trials, for their part, traditionally have focused primarily on optimal dosage and safety. More recently, however, they also have begun to include demonstrations of a drug’s proof of mechanism or the treatment’s proof of concept.</p><p>“This upfront information, and all the information about the molecular portrait of every patient walking in the door with cancer, can enhance efficiency of trials by enrolling patients with a specific biomarker who have a higher likelihood of benefiting from an experimental drug—or any drug for that matter,” Dr Subbiah says.</p><p>Advances in precision medicine are adding new layers of complexity to the patient selection process. Clinicians are conducting incr
"Kummar博士说:"如果你在研究某个特定靶点时,发现有些东西在你的研发管线中并不奏效,或者你学到了一些东西,如果这些东西出现在科学文献中,那么下一个试图研究它的申办者最终可能会以不同的方式来考虑它,并制定不同的研发计划。自从美国食品及药物管理局启动旨在鼓励在临床药物试验中采用最有效剂量的 Optimus 项目以来,Kummar 博士说,她已经看到试验申办者在考虑优化推荐剂量方面发生了变化。联邦政府可以推动数据共享方面的类似变革,尽管她和其他专家都承认,让制药公司共享更多数据--无论是正面数据还是负面数据--同时又不过分规范和阻碍药物开发所需的大量投资,是一项挑战。Subbiah博士说,即便如此,美国食品和药物管理局在全球监管方面仍具有影响力;它在美国的要求往往也会对其他国家的试验产生重大影响。Subbiah博士说:"事实上,FDA正在通过Orbis项目等努力改善全球范围内的监管协调,目的是让更多人更早地获得合作国批准的抗癌药物。他补充说,国际合作还能为资源和专业知识有限的国家的患者提供更多临床试验机会。重启抗癌药物试验并非易事,但人们正在就根本性变革的必要性达成共识。"现状是不可持续的,"苏比亚博士说。
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引用次数: 0
The impact of different fixatives on immunostaining of lung adenocarcinomas in pleural effusion cell blocks 不同固定剂对胸腔积液细胞块中肺腺癌免疫染色的影响
IF 2.6 3区 医学 Q3 ONCOLOGY Pub Date : 2024-06-03 DOI: 10.1002/cncy.22833
Mohammed S. I. Mansour CT, PhD, Louise Pettersson MD, PhD, Tomas Seidal MD, PhD, Ulf Strömberg PhD, Ulrich Mager MD, Lana Ali BSc, Sana Kumbaric BSc, Kim Hejny BSc, Fereshteh Taheri-Eilagh BSc, Joudy Mufti CT, BSc, Dawla Nakdali BSc, Hans Brunnström MD, PhD

Background

Cell blocks (CBs) are widely used for biomarker analyses such as immunostaining. Although immunohistochemistry on formalin-fixed paraffin-embedded tissues is standardized, there are multiple preparation methods and fixatives for cytology. Our objective was to investigate the effect of different common fixatives on the immunoreactivity of pleural effusion CBs with metastatic lung adenocarcinomas.

Methods

This prospective study included 24 malignant pleural effusions from different patients with lung adenocarcinoma. From each case, four identical CBs were fixed in 10% neutral buffered formalin, PreservCyt, CytoLyt, and CytoRich Red (only 17 of the cases), respectively. Samples containing <100 malignant cells were excluded. All CBs were stained with thyroid transcription factor 1 (TTF-1; clones 8G7G3/1 and SPT24), napsin A, claudin 4, CEA, CK7, and epithelial cell adhesion molecule (EpCAM; clones BS14, Ber-Ep4, and MOC-31). The fraction and intensity of stained cells were evaluated.

Results

Of the investigated markers, a significant difference in staining proportion was seen for TTF-1 clone 8G7G3/1 and EpCAM clone MOC-31, especially with cases being negative in CytoLyt (33.3% and 83.3% positive, respectively) and PreservCyt (62.5% and 83.3%) whereas being positive in CytoRich Red (76.5% and 94.1%) and formalin (both 95.8%). A significantly weaker intensity of staining was seen for all alcohol-based fixatives compared to formalin for TTF-1 clone 8G7G3/1, napsin A, and EpCAM clone MOC-31, whereas EpCAM clone Ber-Ep4 was significantly weaker only in PreservCyt compared with formalin.

Conclusions

Immunocytochemical expression and concordance with formalin-fixed CBs differ depending on the used fixative as well as the antibody and clone, warranting investigation of the reliability of each biomarker for non–formalin-fixed cytology.

背景:细胞块(CB)被广泛用于免疫染色等生物标记分析。虽然福尔马林固定石蜡包埋组织的免疫组化已经标准化,但细胞学有多种制备方法和固定剂。我们的目的是研究不同的常用固定剂对转移性肺腺癌胸腔积液 CB 免疫反应性的影响:这项前瞻性研究包括来自不同肺腺癌患者的 24 例恶性胸腔积液。每个病例的 4 个相同的 CB 分别用 10% 中性缓冲福尔马林、PreservCyt、CytoLyt 和 CytoRich Red(仅 17 个病例)固定。含有结果的样本:在所研究的标记物中,TTF-1 克隆 8G7G3/1 和 EpCAM 克隆 MOC-31 的染色比例存在显著差异,尤其是 CytoLyt 阴性(阳性率分别为 33.3% 和 83.3%)和 PreservCyt 阴性(62.5% 和 83.3%),而 CytoRich Red 阳性(76.5% 和 94.1%)和福尔马林阳性(均为 95.8%)。与福尔马林相比,所有醇基固定液对TTF-1克隆8G7G3/1、napsin A和EpCAM克隆MOC-31的染色强度明显较弱,而EpCAM克隆Ber-Ep4仅在PreservCyt中的染色强度明显弱于福尔马林:免疫细胞化学表达和与福尔马林固定的 CB 的一致性因所使用的固定液、抗体和克隆而异,因此有必要研究每种生物标记物在非福尔马林固定细胞学中的可靠性。
{"title":"The impact of different fixatives on immunostaining of lung adenocarcinomas in pleural effusion cell blocks","authors":"Mohammed S. I. Mansour CT, PhD,&nbsp;Louise Pettersson MD, PhD,&nbsp;Tomas Seidal MD, PhD,&nbsp;Ulf Strömberg PhD,&nbsp;Ulrich Mager MD,&nbsp;Lana Ali BSc,&nbsp;Sana Kumbaric BSc,&nbsp;Kim Hejny BSc,&nbsp;Fereshteh Taheri-Eilagh BSc,&nbsp;Joudy Mufti CT, BSc,&nbsp;Dawla Nakdali BSc,&nbsp;Hans Brunnström MD, PhD","doi":"10.1002/cncy.22833","DOIUrl":"10.1002/cncy.22833","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Cell blocks (CBs) are widely used for biomarker analyses such as immunostaining. Although immunohistochemistry on formalin-fixed paraffin-embedded tissues is standardized, there are multiple preparation methods and fixatives for cytology. Our objective was to investigate the effect of different common fixatives on the immunoreactivity of pleural effusion CBs with metastatic lung adenocarcinomas.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This prospective study included 24 malignant pleural effusions from different patients with lung adenocarcinoma. From each case, four identical CBs were fixed in 10% neutral buffered formalin, PreservCyt, CytoLyt, and CytoRich Red (only 17 of the cases), respectively. Samples containing &lt;100 malignant cells were excluded. All CBs were stained with thyroid transcription factor 1 (TTF-1; clones 8G7G3/1 and SPT24), napsin A, claudin 4, CEA, CK7, and epithelial cell adhesion molecule (EpCAM; clones BS14, Ber-Ep4, and MOC-31). The fraction and intensity of stained cells were evaluated.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Of the investigated markers, a significant difference in staining proportion was seen for TTF-1 clone 8G7G3/1 and EpCAM clone MOC-31, especially with cases being negative in CytoLyt (33.3% and 83.3% positive, respectively) and PreservCyt (62.5% and 83.3%) whereas being positive in CytoRich Red (76.5% and 94.1%) and formalin (both 95.8%). A significantly weaker intensity of staining was seen for all alcohol-based fixatives compared to formalin for TTF-1 clone 8G7G3/1, napsin A, and EpCAM clone MOC-31, whereas EpCAM clone Ber-Ep4 was significantly weaker only in PreservCyt compared with formalin.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Immunocytochemical expression and concordance with formalin-fixed CBs differ depending on the used fixative as well as the antibody and clone, warranting investigation of the reliability of each biomarker for non–formalin-fixed cytology.</p>\u0000 </section>\u0000 </div>","PeriodicalId":9410,"journal":{"name":"Cancer Cytopathology","volume":"132 9","pages":"569-579"},"PeriodicalIF":2.6,"publicationDate":"2024-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cncy.22833","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141236838","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Use of ultrasensitive RNA in situ hybridization for kappa and lambda light chains assists in the differential diagnosis of B-cell non-Hodgkin and Hodgkin lymphomas in cytopathology practice 在细胞病理学实践中,使用超灵敏 RNA 原位杂交法检测 kappa 和 lambda 轻链有助于鉴别诊断 B 细胞非霍奇金淋巴瘤和霍奇金淋巴瘤。
IF 2.6 3区 医学 Q3 ONCOLOGY Pub Date : 2024-06-02 DOI: 10.1002/cncy.22834
Hatem Kaseb MD, PhD, MPH, Diane Davis Davey MD
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引用次数: 0
The role of the ThyGeNEXT oncogene panel used in combination with the expanded miRNA panel ThyraMIRv2 in Indeterminate thyroid nodules: A large, blinded, real-world, observational study ThyGeNEXT癌基因检测小组与扩展miRNA检测小组ThyraMIRv2联合使用在不确定甲状腺结节中的作用:一项大型、盲法、真实世界观察研究。
IF 2.6 3区 医学 Q3 ONCOLOGY Pub Date : 2024-05-30 DOI: 10.1002/cncy.22829
Tanvi Verma MD, Cody Marshall DO, Kossivi E. Dantey MD, Diane V. Thompson MS, Anna Banizs MD, Sydney D. Finkelstein MD, Joseph DelTondo DO

Background

Molecular analysis of fine-needle aspiration biopsies (FNAB) improves the diagnostic accuracy of cytologically indeterminate thyroid nodules (ITNs). Recently, the use of MPTXv2 has been shown to further improve the accuracy of risk stratification of ITNs.

Methods

A total of 338 patient samples with atypia of undetermined significance (n = 258) or follicular neoplasm (n = 80) cytology diagnosis and corresponding surgical outcomes or clinical follow-up, collected between 2016 and 2020 were included [Correction added on 19 June 2024, after first online publication: In the preceding sentence, the n values 260 and 78 have been changed to 258 and 80, respectively.]. All samples underwent multiplatform testing (MPTXv1), which includes an oncogene panel (ThyGeNEXT®) plus a microRNA risk classifier (ThyraMIR®). A blinded, secondary analysis was performed to assess the added utility of MPTXv2 (ThyraMIR®v2). The average length of follow-up for the surveillance group (n = 248) was 30 months.

Results

Sensitivity at moderate threshold was 96% and specificity at positive threshold was 99% for MPTXv2. At 14% disease prevalence, the negative predictive value at the moderate threshold was 99% and the positive predictive value at the positive threshold was 89% for MPTXv2. MPTXv2 had fewer patients classified into the moderate-risk group than MPTXv1, which was statistically significant (p < .001). Using surgical resection, the gold standard for outcomes, MPTXv2 showed a statistically greater area under the curve (p = .028) than MPTXv1, demonstrating greater accuracy for MPTXv2.

Conclusion

Both test versions demonstrated robust performance with low false-positive molecular results. Data suggest that incorporation of MPTXv1, and more recently MPTXv2, into clinical practice within our healthcare network resulted in improved accuracy of ITN risk stratification.

背景:细针穿刺活检(FNAB)的分子分析提高了细胞学不确定甲状腺结节(ITNs)的诊断准确性。最近的研究表明,使用 MPTXv2 可进一步提高 ITN 风险分层的准确性:方法:共纳入2016年至2020年间收集的338份细胞学诊断为意义未定的不典型性(n = 260)或滤泡性肿瘤(n = 78)的患者样本,以及相应的手术结果或临床随访。所有样本都进行了多平台检测(MPTXv1),其中包括一个癌基因面板(ThyGeNEXT®)和一个微RNA风险分类器(ThyraMIR®)。为了评估 MPTXv2 (ThyraMIR®v2) 的附加效用,我们进行了一项盲法二次分析。监测组(n = 248)的平均随访时间为30个月:MPTXv2在中度阈值时的灵敏度为96%,在阳性阈值时的特异性为99%。在疾病流行率为 14% 的情况下,MPTXv2 在中度阈值下的阴性预测值为 99%,在阳性阈值下的阳性预测值为 89%。与 MPTXv1 相比,MPTXv2 被归类为中度风险组的患者更少,这在统计学上具有显著意义(p 结论:MPTXv2 和 MPTXv1 的中度风险预测值均高于 MPTXv1:两种测试版本都表现出强大的性能,分子结果的假阳性率较低。数据表明,将 MPTXv1 和最近的 MPTXv2 纳入我们医疗保健网络的临床实践,提高了 ITN 风险分层的准确性。
{"title":"The role of the ThyGeNEXT oncogene panel used in combination with the expanded miRNA panel ThyraMIRv2 in Indeterminate thyroid nodules: A large, blinded, real-world, observational study","authors":"Tanvi Verma MD,&nbsp;Cody Marshall DO,&nbsp;Kossivi E. Dantey MD,&nbsp;Diane V. Thompson MS,&nbsp;Anna Banizs MD,&nbsp;Sydney D. Finkelstein MD,&nbsp;Joseph DelTondo DO","doi":"10.1002/cncy.22829","DOIUrl":"10.1002/cncy.22829","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Molecular analysis of fine-needle aspiration biopsies (FNAB) improves the diagnostic accuracy of cytologically indeterminate thyroid nodules (ITNs). Recently, the use of MPTXv2 has been shown to further improve the accuracy of risk stratification of ITNs.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A total of 338 patient samples with atypia of undetermined significance (<i>n</i> = 258) or follicular neoplasm (<i>n</i> = 80) cytology diagnosis and corresponding surgical outcomes or clinical follow-up, collected between 2016 and 2020 were included [Correction added on 19 June 2024, after first online publication: In the preceding sentence, the <i>n</i> values 260 and 78 have been changed to 258 and 80, respectively.]. All samples underwent multiplatform testing (MPTXv1), which includes an oncogene panel (ThyGeNEXT<sup>®</sup>) plus a microRNA risk classifier (ThyraMIR<sup>®</sup>). A blinded, secondary analysis was performed to assess the added utility of MPTXv2 (ThyraMIR<sup>®</sup>v2). The average length of follow-up for the surveillance group (<i>n</i> = 248) was 30 months.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Sensitivity at moderate threshold was 96% and specificity at positive threshold was 99% for MPTXv2. At 14% disease prevalence, the negative predictive value at the moderate threshold was 99% and the positive predictive value at the positive threshold was 89% for MPTXv2. MPTXv2 had fewer patients classified into the moderate-risk group than MPTXv1, which was statistically significant (<i>p</i> &lt; .001). Using surgical resection, the gold standard for outcomes, MPTXv2 showed a statistically greater area under the curve (<i>p</i> = .028) than MPTXv1, demonstrating greater accuracy for MPTXv2.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Both test versions demonstrated robust performance with low false-positive molecular results. Data suggest that incorporation of MPTXv1, and more recently MPTXv2, into clinical practice within our healthcare network resulted in improved accuracy of ITN risk stratification.</p>\u0000 </section>\u0000 </div>","PeriodicalId":9410,"journal":{"name":"Cancer Cytopathology","volume":"132 9","pages":"556-563"},"PeriodicalIF":2.6,"publicationDate":"2024-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cncy.22829","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141179113","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Utility and performance of cell blocks in cerebrospinal fluid cytology: Experience at two teaching hospitals 脑脊液细胞学中细胞块的用途和性能:两家教学医院的经验。
IF 2.6 3区 医学 Q3 ONCOLOGY Pub Date : 2024-05-29 DOI: 10.1002/cncy.22836
Hyeji Yoon CT, Constance V. Chen MD, Vimal Krishnan MD, Jill Grochowski CT, Gioia Iezza MD, Poonam Vohra MD, Ronald Balassanian MD, Nancy Y. Greenland MD PhD

Background

Cytology cell blocks (CBs) are not routinely made for cerebrospinal fluid (CSF) specimens. The goal of this study was to identify when CSF CB preparation improves diagnostic performance.

Materials and Methods

Under institutional review board approval, a retrospective review of CSF cytology cases was conducted at a tertiary university-based hospital and an affiliated county hospital. Patient history, CSF volume, final diagnosis, use of stains, and whether the CB was contributory was determined from the cytopathology report. CSF nucleated cell count data was obtained from the medical record.

Results

A total of 69 CSF specimens with CBs from January 2006 to March 2023 were identified from 61 patients. The median CSF volume was 8 mL (interquartile range, 4–13 mL; range, 1–800 mL), with immunohistochemical stains performed on 29 (42%) cases. Per cytology report, CB was contributory in 23 cases (33%), not contributory in 34 cases (49%), and not discussed in 12 cases (17%). The median volume was 8 mL for cases in which CB was contributory, not contributory, or not discussed. There was no difference in average nucleated cell counts between cases in which CB was contributory versus not contributory (73.9 vs. 40.0, p = .175).

Conclusions

CBs for CSF samples were contributory in a subset (33%) of cases. The authors were unable to identify any specific pre-analytic factors, including specimen volume and average nucleated cell counts, for cases in which CB was contributory. Further evaluation is needed to identify if there are scenarios in which CSF CBs should be routinely prepared.

背景:细胞学细胞块(CB)并非脑脊液(CSF)标本的常规制备方法。本研究的目的是确定 CSF CB 制备何时可提高诊断效果:经机构审查委员会批准,在一家大学附属三级医院和一家附属县医院对 CSF 细胞学病例进行了回顾性审查。根据细胞病理学报告确定患者病史、CSF 容量、最终诊断、染色剂的使用以及 CB 是否起作用。CSF 有核细胞计数数据来自病历:结果:从 2006 年 1 月至 2023 年 3 月,共从 61 名患者的 69 份 CSF 标本中发现了 CB。中位 CSF 容量为 8 mL(四分位间范围为 4-13 mL;范围为 1-800 mL),其中 29 例(42%)进行了免疫组化染色。根据细胞学报告,23 例(33%)为 CB 促成因素,34 例(49%)为非促成因素,12 例(17%)不予讨论。在促成、未促成或未讨论 CB 的病例中,中位体积为 8 毫升。有助于 CB 和不有助于 CB 的病例的平均有核细胞计数没有差异(73.9 vs. 40.0,p = .175):CSF 样本的 CBs 在部分病例(33%)中起作用。作者无法确定任何特定的分析前因素,包括标本量和平均有核细胞计数。需要进行进一步评估,以确定是否存在应常规制备 CSF CB 的情况。
{"title":"Utility and performance of cell blocks in cerebrospinal fluid cytology: Experience at two teaching hospitals","authors":"Hyeji Yoon CT,&nbsp;Constance V. Chen MD,&nbsp;Vimal Krishnan MD,&nbsp;Jill Grochowski CT,&nbsp;Gioia Iezza MD,&nbsp;Poonam Vohra MD,&nbsp;Ronald Balassanian MD,&nbsp;Nancy Y. Greenland MD PhD","doi":"10.1002/cncy.22836","DOIUrl":"10.1002/cncy.22836","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Cytology cell blocks (CBs) are not routinely made for cerebrospinal fluid (CSF) specimens. The goal of this study was to identify when CSF CB preparation improves diagnostic performance.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Materials and Methods</h3>\u0000 \u0000 <p>Under institutional review board approval, a retrospective review of CSF cytology cases was conducted at a tertiary university-based hospital and an affiliated county hospital. Patient history, CSF volume, final diagnosis, use of stains, and whether the CB was contributory was determined from the cytopathology report. CSF nucleated cell count data was obtained from the medical record.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>A total of 69 CSF specimens with CBs from January 2006 to March 2023 were identified from 61 patients. The median CSF volume was 8 mL (interquartile range, 4–13 mL; range, 1–800 mL), with immunohistochemical stains performed on 29 (42%) cases. Per cytology report, CB was contributory in 23 cases (33%), not contributory in 34 cases (49%), and not discussed in 12 cases (17%). The median volume was 8 mL for cases in which CB was contributory, not contributory, or not discussed. There was no difference in average nucleated cell counts between cases in which CB was contributory versus not contributory (73.9 vs. 40.0, <i>p</i> = .175).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>CBs for CSF samples were contributory in a subset (33%) of cases. The authors were unable to identify any specific pre-analytic factors, including specimen volume and average nucleated cell counts, for cases in which CB was contributory. Further evaluation is needed to identify if there are scenarios in which CSF CBs should be routinely prepared.</p>\u0000 </section>\u0000 </div>","PeriodicalId":9410,"journal":{"name":"Cancer Cytopathology","volume":"132 10","pages":"621-628"},"PeriodicalIF":2.6,"publicationDate":"2024-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cncy.22836","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141174666","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Research and scholarly mentoring: A guide for pathology faculty and program directors 研究与学术指导:病理学教师和项目主任指南。
IF 2.6 3区 医学 Q3 ONCOLOGY Pub Date : 2024-05-23 DOI: 10.1002/cncy.22835
R. Lane Coffee Jr. PhD, MS, Stephen John Cico MD, MEd
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引用次数: 0
Malignant risk of pediatric Bethesda category III thyroid nodules subcategorized by nuclear atypia and other: A single institution experience 按核不典型性和其他分类的小儿贝塞斯达III类甲状腺结节的恶性风险:单一机构的经验。
IF 2.6 3区 医学 Q3 ONCOLOGY Pub Date : 2024-05-21 DOI: 10.1002/cncy.22831
Xiaobing Jin MD, Xin Jing MD, Brian Smola BS, Amer Heider MD

Background

The 2023 Bethesda System for Reporting Thyroid Cytopathology (TBSRTC) divides AUS diagnoses into two major subcategories: atypia of undetermined significance (AUS) nuclear atypia (AUS-N) and other (AUS-O). This study aims to compare the histological outcome and malignant rate of pediatric AUS thyroid nodules classified into AUS-N and AUS-O subcategories.

Design

A search of our institutional electronic pathology database for the period from January 2012 to July 2023 was conducted to identify pediatric (<21 years old) thyroid nodules that were interpreted as AUS and subsequently had surgery. Cases were further divided into AUS-N and AUS-O subcategories. Results of follow-up surgical resections were collected. The malignant rate was calculated and compared between AUS-N and AUS-O groups.

Results

The study identified 62 thyroid nodules from 58 pediatric patients. Among these nodules, 29 and 33 were subcategorized as AUS-N and AUS-O, respectively. Both groups exhibited a female predominance and displayed a similar nodule size distribution. Histological analysis revealed 15 carcinomas in AUS-N nodules, including 11 cases of classic papillary thyroid carcinoma (PTC) and four cases of follicular type of PTC. In contrast, in the AUS-O group, a total of five carcinomas were documented, including two PTCs and three oncocytic thyroid carcinomas. Notably, the malignant rate of AUS-N nodules (52%) is significantly higher than that of AUS-O nodules (15%) (p = .002).

Conclusion

In pediatric AUS thyroid nodules, the malignant risk in AUS-N is significantly higher than that in AUS-O. These findings may guide more appropriate clinical triage and/or improve management of pediatric patients with AUS thyroid nodules.

背景:2023年贝塞斯达甲状腺细胞病理学报告系统(TBSRTC)将AUS诊断分为两大亚类:意义未定的不典型性(AUS)核不典型性(AUS-N)和其他(AUS-O)。本研究旨在比较分为AUS-N和AUS-O亚类的小儿AUS甲状腺结节的组织学结果和恶性率:设计:对本院2012年1月至2023年7月期间的电子病理数据库进行检索,以确定小儿AUS甲状腺结节的组织学结果和恶性率:研究发现了58名儿科患者的62个甲状腺结节。在这些结节中,29 个和 33 个分别被细分为 AUS-N 和 AUS-O。两组患者均以女性为主,结节大小分布相似。组织学分析显示,AUS-N结节中有15个癌瘤,包括11例典型甲状腺乳头状癌(PTC)和4例滤泡型PTC。而在AUS-O组中,共发现了5例癌症,包括2例PTC和3例肿瘤细胞甲状腺癌。值得注意的是,AUS-N结节的恶性率(52%)明显高于AUS-O结节(15%)(P = .002):结论:在小儿AUS甲状腺结节中,AUS-N结节的恶性风险明显高于AUS-O结节。这些发现可指导临床进行更适当的分诊,并/或改善儿科甲状腺AUS结节患者的治疗。
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引用次数: 0
Current role of cytopathology in the molecular and computational era: The perspective of young pathologists 细胞病理学在分子和计算时代的当前作用:年轻病理学家的视角。
IF 2.6 3区 医学 Q3 ONCOLOGY Pub Date : 2024-05-15 DOI: 10.1002/cncy.22832
Alessandro Caputo MD, Pasquale Pisapia MD, PhD, Vincenzo L'Imperio MD

Cytopathology represents a well established diagnostic approach because of its limited cost, reliability, and minimal invasiveness with respect to other methodologies. The evolving complexity of the different classifications systems and the implementation of ancillary techniques to refine the diagnosis is progressively helping in the risk of malignancy stratification, and the adoption of next-generation sequencing techniques contributes to enrich this valuable tool with predictive information, which is always more essential in the tailored medicine era. The recent introduction of digital and computational pathology is further boosting the potentialities of cytopathology, aiding in the interpretation of samples to improve the cost effectiveness of large screening programs and the diagnostic efficiency within intermediate/atypical categories. Moreover, the adoption of artificial intelligence tools is promising to complement molecular investigations, representing a stimulating perspective in the cytopathology field. In this work, the authors tried to summarize the multifaceted nature of this complex and evolving field of pathology, synthesizing the most recent advances and providing the young pathologists’ perspective on this fascinating world.

细胞病理学是一种成熟的诊断方法,因为与其他方法相比,细胞病理学具有成本有限、可靠性和微创性等特点。不同分类系统的复杂性不断提高,辅助技术的应用也使诊断更加精细,这都有助于对恶性肿瘤的风险进行分层,而下一代测序技术的采用则为这一宝贵的工具提供了更多的预测信息,这在量身定制医学时代显得尤为重要。最近引入的数字和计算病理学进一步提升了细胞病理学的潜力,有助于对样本进行解读,从而提高大型筛查项目的成本效益和中级/典型类别的诊断效率。此外,人工智能工具的采用有望补充分子研究的不足,为细胞病理学领域带来了新的发展前景。在这部著作中,作者试图总结这一复杂而不断发展的病理学领域的多面性,综合最新进展,为年轻病理学家提供这一迷人世界的视角。
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引用次数: 0
期刊
Cancer Cytopathology
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