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Cytology of cystic lesions of the pancreas: Practical insights, pearls, and pitfalls 胰腺囊性病变的细胞学:实用的见解,珍珠和陷阱
IF 3.2 3区 医学 Q3 ONCOLOGY Pub Date : 2025-04-18 DOI: 10.1002/cncy.70011
M. Lisa Zhang MD, Martha B. Pitman MD

Pancreatic cyst fluid (PCF) specimens present significant interpretive challenges. Accurate preoperative diagnosis is essential for guiding patient management, as pancreatic cysts vary from benign to pre-malignant and malignant. Appropriate triage differentiates low-risk cysts requiring surveillance from high-risk cysts necessitating surgical resection, the latter of which have increased likelihood of progressing to or harboring invasive carcinoma. Optimal PCF assessment integrates radiological, cytological, biochemical, and molecular findings if available. Key biochemical markers such as carcinoembryonic antigen and glucose can improve the detection of neoplastic mucinous cysts. However, cytology remains the most specific modality for identifying high-risk cysts. Cytomorphologic interpretation is particularly challenging due to the scant cellularity and degenerative changes often present in these specimens. This review provides practical insights to improve the evaluation of pancreatic cysts, emphasizing the importance of a multidisciplinary approach and highlighting diagnostic pearls and common pitfalls to aid in accurate interpretation and optimal patient care.

胰腺囊肿液(PCF)标本提出了重大的解释挑战。准确的术前诊断对于指导患者治疗至关重要,因为胰腺囊肿从良性到恶性和恶性不等。适当的分诊区分需要监测的低风险囊肿和需要手术切除的高风险囊肿,后者更有可能发展为浸润性癌。最佳的PCF评估综合了放射学、细胞学、生化和分子检查结果。癌胚抗原、葡萄糖等关键生化指标可提高肿瘤黏液囊肿的检出率。然而,细胞学检查仍然是鉴别高危囊肿最具体的方法。细胞形态学的解释是特别具有挑战性的,由于缺乏细胞和退行性变化经常出现在这些标本。本综述为改进胰腺囊肿的评估提供了实用的见解,强调了多学科方法的重要性,并强调了诊断珍珠和常见陷阱,以帮助准确解释和最佳的患者护理。
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引用次数: 0
Introducing Cancer Cytopathology Practice Essentials: A new series of practical and up-to-date reviews 介绍癌症细胞病理学实践要领:一系列新的实用和最新的评论
IF 3.2 3区 医学 Q3 ONCOLOGY Pub Date : 2025-04-18 DOI: 10.1002/cncy.70010
Michiya Nishino MD, PhD, Mauro Saieg MD, PhD, FIAC
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引用次数: 0
Cytology-Radiology Correlation Series: Pancreatic cytopathology 细胞学-放射学相关系列:胰腺细胞病理学
IF 3.2 3区 医学 Q3 ONCOLOGY Pub Date : 2025-04-15 DOI: 10.1002/cncy.70012
Judy Trieu MD, Andrew Gilman MD, Katerina Konstantinoff MD, Maria D. Lozano MD, Mauro Saieg MD, PhD

The prevalence of pancreatic lesions has increased over the years because of an increase in accessibility to and the quality of cross-sectional imaging. This commentary describes the common non-neoplastic and neoplastic pancreatic lesions. The images in this commentary depict classic cross-sectional images, sonographic findings, and the cytopathologic diagnosis of each lesion. Most common non-neoplastic lesions include pseudocysts, autoimmune pancreatitis, and chronic pancreatitis. Most common neoplastic lesions include serous cystadenomas, intraductal papillary mucinous neoplasms, mucinous cystic neoplasms, solid pseudopapillary neoplasms, neuroendocrine tumors, pancreatic ductal adenocarcinoma, acinar cell carcinoma, and metastases to the pancreas. The aim of this Cytoimaging Correlation Series is to demonstrate the multidisciplinary involvement in the diagnosis of pancreatic pathology and to highlight main findings in the most common entities found in everyday practice.

近年来,由于横断面成像的可及性和质量的提高,胰腺病变的患病率有所增加。本文介绍了常见的非肿瘤性和肿瘤性胰腺病变。本评论中的图像描述了典型的横断面图像、超声检查结果和每个病变的细胞病理学诊断。最常见的非肿瘤性病变包括假性囊肿、自身免疫性胰腺炎和慢性胰腺炎。最常见的肿瘤病变包括浆液性囊腺瘤、导管内乳头状黏液性肿瘤、黏液性囊性肿瘤、实性假乳头状肿瘤、神经内分泌肿瘤、胰腺导管腺癌、腺泡细胞癌和胰腺转移瘤。本细胞成像相关系列的目的是展示胰腺病理诊断的多学科参与,并强调在日常实践中发现的最常见实体的主要发现。
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引用次数: 0
Clinicopathological and molecular characterization of non–small cell lung cancer with pericardial effusions 伴有心包积液的非小细胞肺癌的临床病理学和分子特征描述
IF 3.2 3区 医学 Q3 ONCOLOGY Pub Date : 2025-04-14 DOI: 10.1002/cncy.70015
Weijie Ma MD, Nathalie J. Rodrigues Simoes MD, Peter P. Seery, Tianhong Li MD, PhD, Laura J. Tafe MD, Darcy A. Kerr MD, Xiaoying Liu MD

Background

Cytological evaluation is essential for assessing pericardial effusions (PEs) in non–small cell lung cancer (NSCLC). This study retrospectively examined the clinicopathological, molecular, and prognostic characteristics of patients with NSCLC with PE.

Methods

Clinical data from 80 patients with NSCLC with PE treated at an academic center over the course of 15 years were reviewed. PE specimens were categorized according to the International System for Reporting Serous Fluid Cytopathology (ISRSFC). The analysis included patient demographics, molecular alterations, cytopathology, histology, and survival outcomes.

Results

Of the 80 patients, 36 (45%) were female and 90% had stage IV disease. A smoking history was noted in 58 patients (72.5%), and 22 patients (27.5%) presented with tamponade. Lung adenocarcinoma predominated (87.5%). The ISRSFC categorized 25% of the specimens as negative for malignancy (NFM), 7.5% as atypia of undetermined significance (AUS), 3.75% as suspicious for malignancy (SFM), and 63.75% as malignant (MAL). Immunohistochemistry in 57 specimens identified thyroid transcription factor 1 (65%) as the most frequently positive marker. Molecular analysis revealed p53 mutations (59.1%) as the most prevalent, followed by KRAS (34.1%) and EGFR (15.9%). Kaplan–Meier analysis showed significantly better survival for NFM patients than non-NFM patients (MAL, SFM, and AUS; p = .0036). Bloody PEs and tamponade were associated with worse outcomes. The immunotherapy group achieved the most prolonged survival among stage IV patients (9.07 months; p = .017). Cox regression confirmed cytology-negative status as an independent prognostic factor.

Conclusions

Cytological evaluation and ISRSFC classification are crucial for NSCLC-associated PEs. A multidisciplinary approach integrating cytology, immunohistochemistry, and molecular profiling is essential for optimal management and prognosis.

背景:细胞学评估是非小细胞肺癌(NSCLC)的心包积液(PEs)是必要的。本研究回顾性分析了非小细胞肺癌合并PE患者的临床病理、分子和预后特征。方法回顾某学术中心15年来收治的80例非小细胞肺癌合并肺栓塞患者的临床资料。PE标本按照国际浆液细胞病理学报告系统(ISRSFC)分类。分析包括患者人口统计学、分子改变、细胞病理学、组织学和生存结果。结果80例患者中,36例(45%)为女性,90%为IV期。58例(72.5%)患者有吸烟史,22例(27.5%)患者有填塞。肺腺癌居多(87.5%)。ISRSFC将25%的标本分类为恶性阴性(NFM), 7.5%为不确定意义的异型(AUS), 3.75%为可疑恶性(SFM), 63.75%为恶性(MAL)。57例标本的免疫组化鉴定甲状腺转录因子1(65%)为最常见的阳性标记物。分子分析显示p53突变最为常见(59.1%),其次是KRAS(34.1%)和EGFR(15.9%)。Kaplan-Meier分析显示,NFM患者的生存率显著高于非NFM患者(MAL、SFM和AUS;p = .0036)。血肿和填塞与较差的预后相关。免疫治疗组在IV期患者中获得了最长的生存期(9.07个月;p = .017)。Cox回归证实细胞学阴性状态是一个独立的预后因素。结论细胞学评估和ISRSFC分级对非小细胞肺癌相关pe至关重要。结合细胞学、免疫组织化学和分子谱的多学科方法对于优化管理和预后至关重要。
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引用次数: 0
Comparison of conventional and novel rotational FNA needles using conventional microscopy and image analysis to quantitatively assess yield 比较传统和新型旋转FNA针使用常规显微镜和图像分析定量评估收率
IF 3.2 3区 医学 Q3 ONCOLOGY Pub Date : 2025-04-09 DOI: 10.1002/cncy.70014
Mohammed Amer Swid MD, Alivia E. Shen, Amanda J. Young MS, Tariq Rahman MD, Sara E. Monaco MD

Background

There is increasing interest in designing new fine-needle aspiration (FNA) needles to maximize tissue acquisition. This study compares cytological preparations from a new rotating FNA needle (CytoCore) with conventional FNA (ConvFNA) using semiquantitative evaluation and quantitative image analysis (IA).

Methods

FNA were performed on ex vivo tissue in quadruplicate for each needle type (ConvFNA and CytoCore), including different sizes (22 G and 25 G) and variable procedure time (5 and 20 s). The Nikon Elements (v5.41.02) was used to quantify the cellularity and size of the largest tissue fragment on cell blocks.

Results

A total of 96 cytology specimens were evaluated were evaluated from benign and malignant specimens. For both ConvFNA and CytoCore, a longer procedure time (20 s) tended to produce greater cellularity and larger tissue fragments in the cell block specimens for both needles when analyzed with image analysis and was statistically significant for the CytoCore needle (p < .01). The ConvFNA tended to perform better with short procedure time. There was no statistically significant difference using different needle gauges.

Conclusion

This study shows that IA can help to quantitatively evaluate sample cellularity in the cell blocks from specimens acquired with different needles. A longer procedure time tended to produce more cellular samples and larger tissue fragments in the cell block for both ConvFNA and CytoCore needles and was statistically significant for CytoCore. Additional larger studies, including those with true clinical cases, should be considered to evaluate the different needle types further.

设计新的细针抽吸(FNA)针以最大限度地获取组织的兴趣越来越大。本研究使用半定量评价和定量图像分析(IA)比较了新型旋转FNA针(CytoCore)和传统FNA (ConvFNA)的细胞学制备。方法采用不同针型(ConvFNA和CytoCore)对离体组织进行不同针型(22 G和25 G)和不同针型(5 s和20 s)的四份FNA,使用Nikon Elements (v5.41.02)定量细胞块上最大组织片段的细胞密度和大小。结果共对96份细胞学标本进行了良性和恶性评价。对于ConvFNA和CytoCore,较长的操作时间(20 s)在两种针的细胞块标本中倾向于产生更大的细胞和更大的组织片段,并且在CytoCore针中具有统计学意义(p <;. 01)。在较短的手术时间内,ConvFNA往往表现较好。使用不同的针规,差异无统计学意义。结论本研究表明,IA可以定量评价不同针法获得的细胞块的细胞结构。对于ConvFNA和CytoCore针,较长的操作时间倾向于在细胞块中产生更多的细胞样本和更大的组织片段,并且在CytoCore针中具有统计学意义。应该考虑其他更大规模的研究,包括那些有真实临床病例的研究,以进一步评估不同类型的针头。
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引用次数: 0
How pro-inflammatory diets may create the right recipe for cancer 促炎饮食如何可能为癌症创造正确的配方
IF 3.2 3区 医学 Q3 ONCOLOGY Pub Date : 2025-04-02 DOI: 10.1002/cncy.70007
Bryn Nelson PhD, William Faquin MD, PhD
<p>Over the past few decades, the phrase <i>heart-healthy diet</i> has become ubiquitous in public health messages urging people to reduce their sodium and saturated fat intake to help to prevent heart disease. Although the science behind a cancer-conscious diet is not as clear-cut, research has identified some risk-lowering foods such as plant-based proteins and more dangerous foods such as processed meats.</p><p>Ongoing studies have investigated a range of potential oncogenic mechanisms. For many foods and food additives linked to cancer, however, “a common underlying mechanistic theme seems to be inflammation,” says Lorne Hofseth, PhD, professor and associate dean for research in the College of Pharmacy at the University of South Carolina in Columbia. Accordingly, more scientists are keying in on foods and additives that may either promote or resolve inflammation.</p><p>In one recent study, researchers conducted an extensive analysis of the lipidome, or the entire collection of lipid molecules, in tissue samples from 81 colorectal cancer tumors.<span><sup>1</sup></span> Compared to samples from healthy volunteers, the tumor samples revealed a significant pro-inflammatory signature that included multiple products of arachidonic acid, an omega-6 fatty acid that the body can derive from a separate omega-6 fatty acid called linoleic acid.</p><p>Conversely, the tumor samples rev-ealed a relative dearth of inflammation-quenching molecules. “Long story short, we think cancer, colon cancer in particular, is a chronic inflammatory disease,” says senior author Timothy Yeatman, MD, FACS, professor of surgery at the University of South Florida and associate center director for translational research and innovation at the Tampa General Hospital Cancer Institute. That inflammation, in turn, may cause immunosuppression that aids the development of tumor cells.</p><p>Dr Yeatman and his colleagues support the long-standing idea that cancer is like a “chronically inflamed, poorly healing wound.” Under that hypothesis, cancer is not only a genetic disease marked by mutations in tumor suppressor genes but also a metabolic one in which chronic inflammation and insufficient immune surveillance allow mutation-harboring cells to gain a critical foothold.</p><p>What is the link to diet? Multiple studies have characterized Western diets, such as those in the United States, as low in fiber but high in fat—especially in omega-6 fatty acids, which predominate in common food ingredients such as soybean, sunflower, safflower, corn, and other seed oils. Although omega-6, like its omega-3 counterpart, is considered an essential fatty acid, Dr Yeatman says that the cancer connection may be due to a wild overabundance of the former compared to the latter in what we eat. “Consequently, our ratios of omega-6 to omega-3 are out of whack,” he says. “They should be 1:1 ideally, and now people are averaging 25:1.”</p><p>A big contributor to the dramatic rise in levels of omega-6 fatt
在过去的几十年里,“心脏健康饮食”这个词在公共卫生信息中无处不在,敦促人们减少钠和饱和脂肪的摄入量,以帮助预防心脏病。尽管对癌症有意识的饮食背后的科学并不明确,但研究已经确定了一些降低风险的食物,如植物性蛋白质和更危险的食物,如加工肉类。正在进行的研究已经调查了一系列潜在的致癌机制。然而,对于许多与癌症有关的食品和食品添加剂,“一个共同的潜在机制主题似乎是炎症,”哥伦比亚南卡罗来纳大学药学院教授兼研究副院长洛恩·霍夫塞思博士说。因此,越来越多的科学家开始关注可能促进或消除炎症的食物和添加剂。在最近的一项研究中,研究人员对81例结直肠癌肿瘤组织样本中的脂质组或脂质分子的全部集合进行了广泛的分析与健康志愿者的样本相比,肿瘤样本显示出显著的促炎特征,其中包括花生四烯酸的多种产物,这是一种omega-6脂肪酸,人体可以从另一种omega-6脂肪酸亚油酸中提取。相反,肿瘤样本显示出炎症猝灭分子的相对缺乏。“长话短说,我们认为癌症,尤其是结肠癌,是一种慢性炎症性疾病,”资深作者Timothy Yeatman博士说,他是南佛罗里达大学外科教授,坦帕综合医院癌症研究所转化研究和创新中心副主任。这种炎症反过来可能导致免疫抑制,从而帮助肿瘤细胞的发展。Yeatman博士和他的同事支持一个长期存在的观点,即癌症就像一个“长期发炎,难以愈合的伤口”。在这种假设下,癌症不仅是一种以肿瘤抑制基因突变为特征的遗传性疾病,也是一种代谢疾病,慢性炎症和免疫监测不足使携带突变的细胞获得了关键的立足点。这和饮食有什么关系?多项研究表明,西方饮食,如美国饮食,纤维含量低,脂肪含量高,尤其是omega-6脂肪酸,它主要存在于常见的食品原料中,如大豆、向日葵、红花、玉米和其他种子油中。虽然omega-6和omega-3一样被认为是一种必需脂肪酸,但Yeatman博士说,与癌症的联系可能是由于我们所吃的食物中omega-6的含量远远高于omega-3。“因此,我们体内omega-6和omega-3的比例是不正常的,”他说。“理想情况下,比例应该是1:1,而现在的平均比例是25:1。”他认为,自20世纪60年代以来,人体脂肪中omega-6脂肪酸含量急剧上升的一个重要原因是廉价、大规模生产的种子油的大量使用,这种油现在在高度加工的食品中无处不在。“我的观点是,这些事情本质上并不坏。但如果你每天吃的东西里都含有它们,那么好东西吃太多就会变成不好的东西。”与他的观点一致的是,最近一项在英国生物银行生物医学数据库中对85,000多人进行的长期研究发现,循环中omega-6与omega-3水平的较高比例与全因死亡率、癌症和心血管死亡率密切相关。在2022年的另一项研究中,研究人员将大量食用超加工食品(通常含有大量添加糖、脂肪、精制淀粉以及染料和防腐剂等添加剂)与结直肠癌的风险增加联系起来Hofseth博士正在研究美国仍在使用的九种合成食用色素的潜在作用。他说,超加工食品中的大多数染料和其他成分都是外来的,这意味着它们对身体来说是外来的。“对身体来说陌生的东西有什么作用?”它们刺激了炎症机制,”他说。在很长一段时间内,它们引发的“炎症”可能会破坏人体的癌症预防机制和其他关键机制。今年1月,美国食品和药物管理局(fda)正式禁止在食品和制药产品中使用樱桃红色着色剂红3染料,原因是动物研究表明,这种合成化合物与甲状腺腺癌有关,尽管只是在雄性大鼠身上。为了更好地了解最广泛使用的合成染料Red 40对健康的潜在影响,Hofseth博士和他的同事们正计划测试它对实验室培养的人类类器官的影响。专家警告说,就其本身而言,大多数食品和食品添加剂可能不会直接致癌。Yeatman博士说,相反,它与炎症的潜在联系及其缺乏解决可能会以与红肉相同的方式促进肿瘤的发生。 在这一点上,故事也远未完成。例如,未加工的草饲牛肉和谷物饲牛肉之间缺乏区别,可能会导致癌症风险相对较弱的关联。根据Yeatman博士的假设,谷物饲养的牛肉(其omega-6与omega-3的比例要高得多)与草饲牛肉的相关性要强得多。从饮食的宏观角度来看,格林利博士说:“真正令人担忧的不仅仅是个别成分,而是超加工食品对饮食的整体影响——也就是说,它们取代了对健康至关重要的营养丰富的天然食品。”我们对微生物群的了解越来越深入,这为研究饮食与癌症之间的关系增添了新的亮点。对小鼠的研究表明,山梨醇和赤藓糖醇等人工甜味剂可以显著改变微生物群,而微生物群反过来在调节肠道免疫系统和相关炎症机制方面起着关键作用。耶特曼博士说,对于超加工食品中的添加剂和成分以及我们摄入的其他东西,一个重要的新问题正在出现:“它们对肠道的免疫系统有什么影响?”他和其他研究人员说,在基本层面上,相对健康的地中海饮食——以新鲜农产品、橄榄油、全谷物、海鲜、坚果和豆类为主,而不是加工食品——可以被视为一种抗炎饮食。利用饮食炎症指数(Dietary Inflammatory Index,一种根据饮食的炎症潜力对其进行评分的算法),科学家们对地中海饮食的评价远远高于一般的西方饮食,并将其与较低的肺癌风险联系起来,尤其是在吸烟者中。营养流行病学家、弗雷德·哈奇癌症中心癌症预防项目负责人玛丽安·纽豪斯博士同意有证据表明地中海饮食与较低的癌症风险有关。即便如此,她说,“我们还不能确定精确的机制。”这种饮食能够降低炎症是一种可能性,尽管她指出橄榄油也富含抗氧化剂。她补充说:“由于注重水果、蔬菜、豆类和全谷物,地中海饮食富含许多有益的植物化合物和纤维。”对炎症的关注,即使它只是许多潜在的促癌机制之一,也进一步促使Yeatman博士和他的同事们开始推广“解决医学”的概念。他们的想法是,一些正在研究的化合物,如乳香和大麻二酚油,可能有助于开启人体自身的炎症解决过程。另一种选择是,被称为专门的促分解介质的补充剂——基于通常由身体产生的分子——可以绕过受损的机制,帮助抑制慢性炎症。与此同时,霍夫塞思博士说,有两件事是明确的:美国消费者需要在食品标签上增加透明度,而变得更健康的一个关键部分是更加关注我们所消费的东西。■
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引用次数: 0
An integrated multi-omics biomarker approach using molecular profiling and microRNAs for evaluation of pancreatic cyst fluid 一种综合的多组学生物标志物方法,使用分子分析和microrna来评估胰腺囊肿液。
IF 3.2 3区 医学 Q3 ONCOLOGY Pub Date : 2025-03-19 DOI: 10.1002/cncy.70008
Mohamed H. Maher PharmD, PhD, Warapen Treekitkarnmongkol PhD, Sayak Ghatak MD, Jianliang Dai PhD, Suyu Liu PhD, Tristian Nguyen BSc, Dzifa Y. Duose PhD, Michael P. Kim MD, Tony Y. Hu PhD, Mark W. Hurd PhD, Pamela L. Paris PhD, Kimberly S. Kirkwood MD, Anirban Maitra MBBS, Rajyalakshmi Luthra PhD, Subrata Sen PhD, Sinchita Roy-Chowdhuri MD, PhD

Background

Classification and risk stratification of pancreatic cysts are challenging because of limited radiographic and cytomorphologic features. Although molecular profiling has emerged as an ancillary test for pancreatic cyst fluid (PCF), additional high-sensitivity and -specificity biomarkers are still needed for improved classification.

Methods

In this study, PCF from 93 patients, including intraductal papillary mucinous neoplasms (n = 65), mucinous cystic neoplasms (n = 9), serous cystadenomas (n = 9), pancreatic cyst not otherwise specified (n = 8), and pseudocysts (n = 2), were evaluated for biomarkers. Molecular profiling by next-generation sequencing was performed, and a subset of the cases (n = 32) were interrogated with 2083 microRNAs (miRNAs) to evaluate their use for pancreatic cyst risk stratification.

Results

As independent PCF biomarkers in 32 cases with histologic diagnoses, three miRNAs performed significantly better than mutant KRAS, mutant GNAS, carcinoembryonic antigen (CEA), and serum carbohydrate antigen 19-9 (CA19-9) in discriminating high-risk from low-risk cysts. The three elevated miRNAs in combination with mutant KRAS, mutant GNAS, and serum CA19-9 displayed similar diagnostic performance (miR-4461: area under the curve [AUC], 0.950; 95% confidence interval [CI], 0.800–1; miR-6723-5p: AUC, 0.958; 95% CI, 0.850–1; miR-6755-3p: AUC, 0.942; 95% CI, 0.816–1) in discriminating high-risk from low-risk cysts, when compared to mutant KRAS, mutant GNAS, CEA, and serum CA19-9 (AUC, 0.950; 95% CI, 0.825–1). In the absence of CA19-9, the three-marker panel of KRAS, GNAS, and miRNAs showed marginally improved performance compared with KRAS, GNAS, and CEA, which highlights the potential utility of miRNAs as biomarkers in PCF analysis.

Conclusions

These findings demonstrate that a multiomics biomarker approach with elevated PCF miRNAs with mutant KRAS, mutant GNAS, and serum CA19-9 may help in better detecting high-risk cysts for early clinical intervention.

背景:由于放射学和细胞形态学特征有限,胰腺囊肿的分类和风险分层具有挑战性。尽管分子谱分析已成为胰腺囊肿液(PCF)的辅助检测,但仍需要额外的高灵敏度和特异性生物标志物来改进分类。方法:在本研究中,对93例PCF患者进行生物标志物评估,包括导管内乳头状黏液性肿瘤(n = 65)、黏液性囊性肿瘤(n = 9)、浆液性囊腺瘤(n = 9)、未明确说明的胰腺囊肿(n = 8)和假性囊肿(n = 2)。通过下一代测序进行分子谱分析,并使用2083个microrna (mirna)对一部分病例(n = 32)进行询问,以评估其在胰腺囊肿风险分层中的应用。结果:作为32例组织学诊断的独立PCF生物标志物,3种mirna在区分高危和低风险囊肿方面明显优于突变型KRAS、突变型GNAS、癌胚抗原(CEA)和血清碳水化合物抗原19-9 (CA19-9)。三种升高的mirna与突变体KRAS、突变体GNAS和血清CA19-9联合表现出相似的诊断性能(miR-4461:曲线下面积[AUC], 0.950;95%置信区间[CI], 0.800-1;miR-6723-5p: AUC, 0.958;95% ci, 0.850-1;miR-6755-3p: AUC, 0.942;与突变型KRAS、突变型GNAS、CEA和血清CA19-9相比,95% CI, 0.816-1)区分高风险和低风险囊肿(AUC, 0.950;95% ci, 0.825-1)。在缺少CA19-9的情况下,与KRAS、GNAS和CEA相比,KRAS、GNAS和miRNAs的三标记面板的性能略有提高,这突出了miRNAs作为生物标记物在PCF分析中的潜在效用。结论:这些发现表明,结合突变KRAS、突变GNAS和血清CA19-9的PCF mirna升高的多组学生物标志物方法可能有助于更好地检测高危囊肿,以便进行早期临床干预。
{"title":"An integrated multi-omics biomarker approach using molecular profiling and microRNAs for evaluation of pancreatic cyst fluid","authors":"Mohamed H. Maher PharmD, PhD,&nbsp;Warapen Treekitkarnmongkol PhD,&nbsp;Sayak Ghatak MD,&nbsp;Jianliang Dai PhD,&nbsp;Suyu Liu PhD,&nbsp;Tristian Nguyen BSc,&nbsp;Dzifa Y. Duose PhD,&nbsp;Michael P. Kim MD,&nbsp;Tony Y. Hu PhD,&nbsp;Mark W. Hurd PhD,&nbsp;Pamela L. Paris PhD,&nbsp;Kimberly S. Kirkwood MD,&nbsp;Anirban Maitra MBBS,&nbsp;Rajyalakshmi Luthra PhD,&nbsp;Subrata Sen PhD,&nbsp;Sinchita Roy-Chowdhuri MD, PhD","doi":"10.1002/cncy.70008","DOIUrl":"10.1002/cncy.70008","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Classification and risk stratification of pancreatic cysts are challenging because of limited radiographic and cytomorphologic features. Although molecular profiling has emerged as an ancillary test for pancreatic cyst fluid (PCF), additional high-sensitivity and -specificity biomarkers are still needed for improved classification.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>In this study, PCF from 93 patients, including intraductal papillary mucinous neoplasms (<i>n</i> = 65), mucinous cystic neoplasms (<i>n</i> = 9), serous cystadenomas (<i>n</i> = 9), pancreatic cyst not otherwise specified (<i>n</i> = 8), and pseudocysts (<i>n</i> = 2), were evaluated for biomarkers. Molecular profiling by next-generation sequencing was performed, and a subset of the cases (<i>n</i> = 32) were interrogated with 2083 microRNAs (miRNAs) to evaluate their use for pancreatic cyst risk stratification.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>As independent PCF biomarkers in 32 cases with histologic diagnoses, three miRNAs performed significantly better than mutant <i>KRAS</i>, mutant <i>GNAS</i>, carcinoembryonic antigen (CEA), and serum carbohydrate antigen 19-9 (CA19-9) in discriminating high-risk from low-risk cysts. The three elevated miRNAs in combination with mutant <i>KRAS</i>, mutant <i>GNAS</i>, and serum CA19-9 displayed similar diagnostic performance (miR-4461: area under the curve [AUC], 0.950; 95% confidence interval [CI], 0.800–1; miR-6723-5p: AUC, 0.958; 95% CI, 0.850–1; miR-6755-3p: AUC, 0.942; 95% CI, 0.816–1) in discriminating high-risk from low-risk cysts, when compared to mutant <i>KRAS</i>, mutant <i>GNAS</i>, CEA, and serum CA19-9 (AUC, 0.950; 95% CI, 0.825–1). In the absence of CA19-9, the three-marker panel of <i>KRAS</i>, <i>GNAS</i>, and miRNAs showed marginally improved performance compared with <i>KRAS</i>, <i>GNAS</i>, and CEA, which highlights the potential utility of miRNAs as biomarkers in PCF analysis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>These findings demonstrate that a multiomics biomarker approach with elevated PCF miRNAs with mutant <i>KRAS</i>, mutant <i>GNAS</i>, and serum CA19-9 may help in better detecting high-risk cysts for early clinical intervention.</p>\u0000 </section>\u0000 </div>","PeriodicalId":9410,"journal":{"name":"Cancer Cytopathology","volume":"133 4","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143662444","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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
Extended HPV genotyping and dual stain for the triage of primary HPV screen-positive cases: Practical guidance for the cytopathology laboratory 扩展HPV基因分型和双重染色对原发性HPV筛查阳性病例的分类:细胞病理学实验室的实用指南
IF 3.2 3区 医学 Q3 ONCOLOGY Pub Date : 2025-03-08 DOI: 10.1002/cncy.70006
Robert A. Goulart MD, Ritu Nayar MD, Thomas Lorey MD, Nancy Joste MD, Mark H. Stoler MD

Because of many factors, the landscape of cervical cancer prevention is again at a pivot point within the United States. Primary human papillomavirus (HPV) screening has been recommended as the preferred testing method by the American Cancer Society since 2020. Although primary HPV testing provides high negative predictive value in screening, women who screen positive for HPV need triage using methods that have an optimal balance between sensitivity for precancer and the number of colposcopies required for detection. The triage test ideally should maximize specificity while also reassuring patients who test negative, although it should be acknowledged that no screening or triage test can entirely exclude disease in a screen-positive patient. While cervical cytology (the Papanicolaou test) triage of primary HPV screen-positive patients is currently recommended by most screening strategies, additional triage tests, specifically extended HPV genotyping and combined p16/Ki-67 dual-stain immunocytochemistry, are now approved by the US Food and Drug Administration and incorporated into cervical cancer screening and management guidelines. Incorporating these triage methods into practice should be achieved by using appropriate validation/verification and implementation steps and, in the case of dual-stain immunocytochemistry, appropriate cytologist/cytopathologist training. The US Food and Drug Administration approval of vaginal self-collection in May 2024 is another significant advance for increasing access to screening. These samples can only be tested using primary HPV screening platforms, and guidance for management has been endorsed by the ASCCP's enduring guidelines process. This review discusses issues that warrant consideration before implementation and provides practical guidance for the incorporation of self-collected specimens and extended genotyping/dual-stain tests into the workflow of the cytopathology laboratory.

由于许多因素,宫颈癌的预防在美国再次处于一个支点。自2020年以来,原发性人乳头瘤病毒(HPV)筛查已被美国癌症协会推荐为首选检测方法。虽然原发性HPV检测在筛查中提供了很高的阴性预测价值,但筛查HPV阳性的妇女需要使用在癌前病变敏感性和检测所需阴道镜次数之间取得最佳平衡的方法进行分诊。理想情况下,分诊测试应该最大限度地提高特异性,同时也让检测结果阴性的患者放心,尽管应该承认,没有筛查或分诊测试可以完全排除筛查阳性患者的疾病。虽然目前大多数筛查策略推荐对原发性HPV筛查阳性患者进行宫颈细胞学(Papanicolaou试验)分诊,但美国食品和药物管理局(fda)现在批准了额外的分诊试验,特别是扩展HPV基因分型和联合p16/Ki-67双染色免疫细胞化学,并将其纳入宫颈癌筛查和管理指南。将这些分类方法纳入实践应该通过使用适当的验证/验证和实施步骤来实现,并且在双染色免疫细胞化学的情况下,适当的细胞学家/细胞病理学家培训。美国食品和药物管理局(fda)于2024年5月批准阴道自我采集是增加筛查可及性的又一重大进展。这些样本只能使用初级HPV筛查平台进行检测,并且管理指南已得到ASCCP持久指南过程的认可。本综述讨论了在实施前需要考虑的问题,并为将自我收集的标本和扩展的基因分型/双染色试验纳入细胞病理学实验室的工作流程提供了实用指导。
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引用次数: 0
Hepatocellular carcinoma: Morphological spectrum and subtyping as per the World Health Organization classification on FNA biopsy with cell block samples 肝细胞癌:根据世界卫生组织对细胞块样本的FNA活检分类的形态学谱和亚型
IF 3.2 3区 医学 Q3 ONCOLOGY Pub Date : 2025-03-05 DOI: 10.1002/cncy.70009
Bhawana Dhiman MD, Reetu Kundu MD, Suvradeep Mitra MD, Naveen Kalra MD, Madhumita Premkumar MD, DM, Ajay Kumar Duseja MD, DM, Radhika Srinivasan MD, PhD

Background

Hepatocellular carcinoma (HCC) may be diagnosed and further subclassified in surgical specimen as per the recent World Health Organization (WHO) classification into several distinct subtypes with prognostic implications. The aim of this study was to apply this WHO classification on fine-needle aspiration biopsy (FNAB) samples of HCC and describe their features.

Methods

This was a retrospective analysis of all ultrasound-guided FNAB of liver mass lesions in patients with suspected HCC (n = 164) over a 7-year period. Detailed morphological assessment of cytopathological features and grading was done and correlated with each other. HCC was subtyped further in cases with available cell blocks (n = 126).

Results

A total of 164 cases of HCC were evaluated on FNAB with age range of 18–88 years (mean, 60 years), and with 140 (85.4%) male and 24 (14.6%) female patients. Grading performed on 160 cases of HCC (after excluding fibrolamellar HCC) revealed 23 well differentiated, 127 moderately differentiated, and 10 poorly differentiated HCCs. Subtyping was feasible in 126 cases, of which 26 cases (20.6%) showed specific subtypes that were steatohepatitic (8), lymphocyte-rich (8), fibrolamellar (4), neutrophil-rich (3), macrotrabecular massive (2), and clear cell HCC (1) with remaining cases (100) being conventional HCC, no special type.

Conclusion

The study demonstrates the feasibility of subtyping HCC (as per the current WHO classification) for the first time on FNAB with cell blocks that carries implication for prognostication and emphasizes the importance of obtaining tissue diagnosis by FNAB with cell blocks.

背景肝细胞癌(HCC)可以被诊断出来,并根据最近世界卫生组织(WHO)的分类,在手术标本中进一步细分为几种具有预后意义的不同亚型。本研究的目的是将WHO分类应用于细针穿刺活检(FNAB) HCC样本,并描述其特征。方法回顾性分析7年来所有超声引导下疑似HCC患者(n = 164)肝肿块病变的FNAB。对细胞病理特征和分级进行了详细的形态学评价,并相互关联。在有可用细胞块的病例中,HCC进一步分型(n = 126)。结果FNAB检测HCC共164例,年龄18 ~ 88岁,平均60岁,其中男性140例(85.4%),女性24例(14.6%)。对160例HCC进行分级(排除纤维板层性HCC),结果显示23例为高分化,127例为中度分化,10例为低分化HCC。126例可进行亚型分型,其中26例(20.6%)表现出特异性亚型,分别为脂肪肝型(8例)、富淋巴细胞型(8例)、纤维板层型(4例)、富中性粒细胞型(3例)、大小梁块状(2例)和透明细胞型(1例),其余100例为常规HCC,无特殊类型。结论本研究首次证明了FNAB结合细胞块对HCC进行分型(按照WHO现行分类)的可行性,具有预测意义,并强调了FNAB结合细胞块获得组织诊断的重要性。
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引用次数: 0
How an epidemic of untreated malnutrition is worsening cancer 未经治疗的营养不良是如何使癌症恶化的
IF 3.2 3区 医学 Q3 ONCOLOGY Pub Date : 2025-03-04 DOI: 10.1002/cncy.70002
Bryn Nelson PhD, William Faquin MD, PhD

Physicians have long observed that patients who have cancer and are also malnourished are more likely to die. Beyond making treatments less effective and more toxic, malnutrition can reduce a patient’s functional abilities and quality of life while increasing the risk of complications. For many decades, however, the surprisingly common and largely unresolved phenomenon of malnutrition in patients with cancer was seen as an inevitability.

Jann Arends, MD, a gastroenterologist, hematologist, and medical oncologist at the University of Freiburg in Germany, says that weight loss and emaciation were once taken for granted as a standard feature of intractable cancers. “Most cancers would not respond to even aggressive anticancer treatments, and weight loss was seen as a harbinger of death and not as a condition requiring supportive care,” Dr Arends says.

That mindset further solidified, he says, when clinical trials testing routine artificial nutrition (delivered via feeding tubes or intravenous lines) yielded no discernable benefits for patients but higher complication rates than oral feeding. In response, the American Society for Parenteral and Enteral Nutrition recommended not using artificial nutrition to treat patients with cancer and thus furthered what Dr Arends calls “nutritional nihilism in an age of only rare oncological success.”

As cancer treatment successes have multiplied during the past 15 years, however, more research has helped to change recommendations, refine the benefits and limitations of nutritional care in patients, and provide better estimates of just how common malnutrition can be.

One eye-opening 2014 study of approximately 1900 patients with cancer in 154 hospitals throughout France found that 39% were malnourished, including more than 60% of patients diagnosed with pancreatic, esophageal, or stomach cancer.1

Although malnutrition rates tend to be higher in hospitalized patients, the condition also is common even in newly diagnosed patients. In 2017, the Prevalence of Malnutrition in Oncology study in Italy sought to get a better view of the nutritional status of adult patients at their first visit to a medical oncology center after being diagnosed with a solid tumor.2 Conducted at 22 centers across the country, the observational study enrolled nearly 2000 patients. Oncologists used several scales, including the Mini Nutritional Assessment, to assess the patients for signs of nutritional impairment.

Collectively, they found that 51% of the patients had a nutritional impairment, 9% were overtly malnourished, and 43% were at risk for malnutrition. More than 40% had anorexia, or an abnormal loss of appetite, while 64% had lost weight during the previous 6 months. The results, the authors asserted, supported a “call to action” for oncologists to be more aware of the significant risk of malnutrition, even in patients with nonmetastatic cancer, a

医生们长期以来观察到,患有癌症且营养不良的患者更有可能死亡。除了使治疗效果降低和毒性增加之外,营养不良还会降低患者的功能能力和生活质量,同时增加并发症的风险。然而,几十年来,癌症患者营养不良这一令人惊讶的普遍现象被视为一种不可避免的现象。德国弗莱堡大学(University of Freiburg)的胃肠病学家、血液学家和医学肿瘤学家Jann Arends医学博士说,体重减轻和消瘦一度被认为是难治性癌症的标准特征。“大多数癌症甚至对积极的抗癌治疗都没有反应,体重减轻被视为死亡的预兆,而不是需要支持性治疗的情况,”阿伦兹博士说。他说,当临床试验测试常规人工营养(通过喂食管或静脉输送)对患者没有明显的好处,但并发症发生率高于口服喂养时,这种心态进一步固化。作为回应,美国肠外和肠内营养学会建议不要使用人工营养来治疗癌症患者,这进一步推动了阿伦兹博士所说的“在肿瘤治疗取得罕见成功的时代,营养虚无主义”。然而,在过去的15年里,随着癌症治疗的成功成倍增加,更多的研究帮助改变了建议,完善了患者营养护理的好处和局限性,并更好地估计了营养不良的普遍程度。2014年对法国154家医院约1900名癌症患者进行的一项令人大开眼界的研究发现,39%的患者营养不良,其中超过60%的患者被诊断患有胰腺癌、食道癌或胃癌。虽然住院病人的营养不良率往往较高,但这种情况在新诊断的病人中也很常见。2017年,意大利的肿瘤营养不良患病率研究试图更好地了解成年患者在被诊断患有实体瘤后首次前往肿瘤医学中心时的营养状况这项观察性研究在全国22个中心进行,招募了近2000名患者。肿瘤学家使用了几种量表,包括迷你营养评估,来评估患者营养不良的迹象。总的来说,他们发现51%的患者营养不良,9%的患者明显营养不良,43%的患者有营养不良的风险。超过40%的人患有厌食症,或食欲异常下降,而64%的人在过去6个月内体重减轻。作者断言,研究结果支持了一项“行动呼吁”,即肿瘤学家要更多地意识到营养不良的重大风险,甚至是非转移性癌症患者,并将早期筛查和积极治疗作为支持性癌症护理的常规部分。正如法国的研究表明的那样,一些癌症与营养不良的关系比其他癌症更大。事实上,在2021年的一项综述中,另一组意大利研究人员得出结论,肿瘤亚位点是最大的决定因素之一经过10年的研究,他们发现,与法国的研究结果一致,胰腺癌、食道癌和其他肠胃癌;头颈部癌症;肺癌的发病率最高。不出所料,他们还将癌症晚期与更高的营养不良风险联系起来,这是肿瘤负担、炎症状态、热量摄入减少和吸收不良的综合影响的表现。反过来,营养缺乏会干扰从化疗到手术的癌症治疗。以后者为重点,一项国际多中心研究招募了来自75个国家381家医院的5700多名患者。研究人员发现,“严重营养不良在接受胃肠道癌症手术的患者中很常见,也是结直肠癌或胃癌选择性手术后30天死亡率的一个危险因素。”研究结果使作者得出结论:“迫切需要研究围手术期营养干预是否能改善全球胃肠道癌症手术后的早期预后。”同样,癌症治疗也会增加营养缺乏的风险,并形成一种负反馈循环,在这种循环中,不断升级的营养不良会干扰治疗,进一步削弱患者,并使结果恶化。为了应对这种下降趋势,Arends博士等专家现在呼吁采用更加个性化的营养和代谢方法来提供有针对性的护理,包括肌肉训练和心理支持。营养不良的形式多种多样,使其更加复杂。 例如,在一个健康的人身上,食物摄入不足会引发饥饿代谢,包括酮症,在这种情况下,身体燃烧脂肪,以便使用分解化合物——酮——作为燃料。正如Arends博士解释的那样,在缺乏可用或足够食物的情况下,身体的主要目标是避免蛋白质被用作燃料,并帮助维持关键的身体功能。相比之下,系统性炎症相关的营养不良,或恶病质,可能是由疾病相关的炎症引起的,无论是急性还是慢性,以及身体对严重损伤的基本反应。Arends博士说:“炎症会导致疲劳、厌食和分解代谢,所有这些都会导致体重减轻、细胞和肌肉量减少。”到目前为止,还没有通用的筛查工具能够评估患者的营养状况,尽管最近的研究和评论比较了多种筛查的相对优势和预测能力以及几种营养支持系统的益处。多个组织也发布了临床实践指南,以识别和治疗癌症相关的恶病质。5,6 Arends博士说:“为了改变忽视营养不良的时代,我们敦促在所有肿瘤治疗环境和机构中实施营养不良常规筛查。”“我们还敦促在医学院更广泛地纳入高质量的营养教育。”这种情况仍然困扰着研究人员。Arends博士说,让他特别惊讶的是,要证明对癌症患者进行营养治疗的好处是多么困难,而且研究人员花了这么长时间才认识到恶病质的代谢基础,这是需要多目标治疗的根本原因。到目前为止,还没有药物被批准用于针对癌症相关恶病质的代谢基础,尽管Arends博士指出,一些有希望的候选药物正在测试中。然而,对于患者和医疗保健系统来说,研究一再表明,早期识别和营养支持至关重要。在一项针对西班牙400名肿瘤患者的研究中,研究人员发现,在住院期间,有营养风险的患者比例实际上有所增加,从34%增加到36%以上他们发现:“只有三分之一有营养不良风险的患者在出院时接受了任何形式的营养支持。”很明显,这种情况与更长的住院时间和更高的医疗费用有关。阿伦兹博士说,尽管仍然存在未知因素,但不断积累的研究已经得出了一些关键的关键信息。首先,癌症提供者应该对所有癌症患者进行常规和反复的营养不良筛查。接下来,他们应该对所有筛查结果显示营养病理的患者进行营养和代谢评估。这种评估可以帮助诊断每个患者营养不良的原因以及营养和代谢缺陷的程度,并随后帮助设计个性化的营养和代谢护理。
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Cancer Cytopathology
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