{"title":"How pro-inflammatory diets may create the right recipe for cancer","authors":"Bryn Nelson PhD, William Faquin MD, PhD","doi":"10.1002/cncy.70007","DOIUrl":"https://doi.org/10.1002/cncy.70007","url":null,"abstract":"<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","PeriodicalId":9410,"journal":{"name":"Cancer Cytopathology","volume":"133 4","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cncy.70007","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143762117","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}
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
{"title":"An integrated multi-omics biomarker approach using molecular profiling and microRNAs for evaluation of pancreatic cyst fluid","authors":"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","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":2.6,"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}
Robert A. Goulart MD, Ritu Nayar MD, Thomas Lorey MD, Nancy Joste MD, Mark H. Stoler MD
{"title":"Extended HPV genotyping and dual stain for the triage of primary HPV screen-positive cases: Practical guidance for the cytopathology laboratory","authors":"Robert A. Goulart MD, Ritu Nayar MD, Thomas Lorey MD, Nancy Joste MD, Mark H. Stoler MD","doi":"10.1002/cncy.70006","DOIUrl":"https://doi.org/10.1002/cncy.70006","url":null,"abstract":"<p>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.</p>","PeriodicalId":9410,"journal":{"name":"Cancer Cytopathology","volume":"133 4","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143571216","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}
{"title":"Hepatocellular carcinoma: Morphological spectrum and subtyping as per the World Health Organization classification on FNA biopsy with cell block samples","authors":"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","doi":"10.1002/cncy.70009","DOIUrl":"https://doi.org/10.1002/cncy.70009","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>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.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This was a retrospective analysis of all ultrasound-guided FNAB of liver mass lesions in patients with suspected HCC (<i>n</i> = 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 (<i>n</i> = 126).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>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.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>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.</p>\u0000 </section>\u0000 </div>","PeriodicalId":9410,"journal":{"name":"Cancer Cytopathology","volume":"133 4","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143554487","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}
{"title":"How an epidemic of untreated malnutrition is worsening cancer","authors":"Bryn Nelson PhD, William Faquin MD, PhD","doi":"10.1002/cncy.70002","DOIUrl":"https://doi.org/10.1002/cncy.70002","url":null,"abstract":"<p>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.</p><p>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.</p><p>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.”</p><p>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.</p><p>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.<span><sup>1</sup></span></p><p>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.<span><sup>2</sup></span> 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.</p><p>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","PeriodicalId":9410,"journal":{"name":"Cancer Cytopathology","volume":"133 3","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cncy.70002","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143535838","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}
{"title":"Future initiatives and approaches to reducing the impact of lung cancer","authors":"David Kim MD","doi":"10.1002/cncy.70005","DOIUrl":"https://doi.org/10.1002/cncy.70005","url":null,"abstract":"","PeriodicalId":9410,"journal":{"name":"Cancer Cytopathology","volume":"133 3","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143481450","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}
Karen Thomas MD, Haley Trinh, Anna Fei, Laila Khazai MD, Hongxia Sun MD, PhD, Qiong (Jenny) Gan MD, PhD
{"title":"Cytologic features of angiosarcoma in fluid specimens: A retrospective study of 22 cases","authors":"Karen Thomas MD, Haley Trinh, Anna Fei, Laila Khazai MD, Hongxia Sun MD, PhD, Qiong (Jenny) Gan MD, PhD","doi":"10.1002/cncy.70004","DOIUrl":"https://doi.org/10.1002/cncy.70004","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Although histologic and fine-needle aspiration cytologic features of angiosarcoma are well established, little is known about its cytologic features in fluids. This study presents the cytomorphologic features of 22 patients who had angiosarcoma involving pleural, pericardial, ascites, and liver cyst fluids.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Patient data, including clinical histories, radiology, pathology, treatments, and follow-up, were collected.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Twenty-two angiosarcoma fluid specimens (pleura, <i>n</i> = 17; pericardium, <i>n</i> = 2; ascites, <i>n</i> = 2; and liver cyst, <i>n</i> = 1) were identified. All patients had prior angiosarcoma diagnoses, and 10 (45%) had prior radiation exposure. Cellularity varied, with low cellularity predominant (73%). Cytologic architecture typically consisted of clusters of epithelioid cells (91%), single epithelioid cells (55%), and spindled cells (36%). Malignant nuclear characteristics, such as irregular nuclear membranes, chromatin clumping, and prominent nucleoli, were consistent (100%). Vasoformative features included endothelial wrapping (73%), intracytoplasmic lumina (18%), hemophagocytosis (9%), and intracytoplasmic lumina with cells (5%). Low cellularity samples usually lacked vasoformative features (27%). Prominent nucleoli, often with multiple or <i>club-shaped</i> forms, appeared in all cases (100%). Atypical mitotic figures (45%), associated fibromyxoid material (14%), and possible necrosis (5%) were also observed. The interval between cavity fluid involvement and primary diagnosis averaged 616 days (range, 14–2778 days). The mean time from the first positive fluid to death was 141 days (range, 3–568 days).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Angiosarcoma in fluids is rare. Cytomorphologic features, although nonspecific, include malignant nuclear features, prominent nucleoli, atypical mitoses, and occasional vasoformative features. Accurate diagnosis necessitates a careful review of the patient's history and judicious use of immunohistochemical staining.</p>\u0000 </section>\u0000 </div>","PeriodicalId":9410,"journal":{"name":"Cancer Cytopathology","volume":"133 3","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143481451","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}
Gennaro Acanfora MD, Antonino Iaccarino CT, PhD, Bruna Cerbelli MD, PhD, Claudio Di Cristofano MD, Claudio Bellevicine MD, PhD, Massimo Barberis MD, Emanuela Bonoldi MD, Lukas Bubendorf MD, Andreas Calaminus MD, MIAC, Severo Campione MD, PhD, Sule Canberk MD, Alberto Cavazza MD, Giorgio Cazzaniga MD, Obinna Chijioke MD, Eduardo Clery MD, Albino Eccher MD, Marianne Engels MD, Fiac, Vincenzo Fiorentino MD, Paolo Graziano MD, Izidor Kern MD, Ivana Kholova MD, PhD, MIAC, Jari Laatta MD, Tania Labiano MD, Martina Leopizzi CT, PhD, Maria D. Lozano MD, Rita Luis MD, Elisabetta Maffei MD, Alessandro Marando MD, Maurizio Martini MD, PhD, Elisabetta Merenda MD, Marco Montella MD, PhD, Allan Argueta Morales MD, Michiya Nishino MD, PhD, Fabio Pagni MD, Paul Hofman MD, PhD, Angelina Pernazza MD, PhD, Sinchita Roy-Chowdhuri MD, PhD, Mauro Saieg MD, PhD, MIAC, Spasenija Savic Prince MD, Momin T. Siddiqui MD, Tajana Stoos-Veic MD, PhD, Margareta Strojan Fležar MD, PhD, MIAC, Dinka Sundov MD, PhD, Paul VanderLaan MD, PhD, Danijela Vrdoljak-Mozetič MD, PhD, Pio Zeppa MD, PhD, Giancarlo Troncone MD, PhD, Elena Vigliar MD, PhD
{"title":"InterobServer AgreeMent in Pd-l1 evaLuatIoN on cytoloGical samples—SAMPLING project: A multi-institutional, international study","authors":"Gennaro Acanfora MD, Antonino Iaccarino CT, PhD, Bruna Cerbelli MD, PhD, Claudio Di Cristofano MD, Claudio Bellevicine MD, PhD, Massimo Barberis MD, Emanuela Bonoldi MD, Lukas Bubendorf MD, Andreas Calaminus MD, MIAC, Severo Campione MD, PhD, Sule Canberk MD, Alberto Cavazza MD, Giorgio Cazzaniga MD, Obinna Chijioke MD, Eduardo Clery MD, Albino Eccher MD, Marianne Engels MD, Fiac, Vincenzo Fiorentino MD, Paolo Graziano MD, Izidor Kern MD, Ivana Kholova MD, PhD, MIAC, Jari Laatta MD, Tania Labiano MD, Martina Leopizzi CT, PhD, Maria D. Lozano MD, Rita Luis MD, Elisabetta Maffei MD, Alessandro Marando MD, Maurizio Martini MD, PhD, Elisabetta Merenda MD, Marco Montella MD, PhD, Allan Argueta Morales MD, Michiya Nishino MD, PhD, Fabio Pagni MD, Paul Hofman MD, PhD, Angelina Pernazza MD, PhD, Sinchita Roy-Chowdhuri MD, PhD, Mauro Saieg MD, PhD, MIAC, Spasenija Savic Prince MD, Momin T. Siddiqui MD, Tajana Stoos-Veic MD, PhD, Margareta Strojan Fležar MD, PhD, MIAC, Dinka Sundov MD, PhD, Paul VanderLaan MD, PhD, Danijela Vrdoljak-Mozetič MD, PhD, Pio Zeppa MD, PhD, Giancarlo Troncone MD, PhD, Elena Vigliar MD, PhD","doi":"10.1002/cncy.70003","DOIUrl":"https://doi.org/10.1002/cncy.70003","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>The aim of this project is to assess interobserver agreement for programmed death-ligand 1 (PD-L1) scoring on of non–small cell lung cancer (NSCLC) on cytological specimens in a large-scale multicenter study, by exploiting the cell block-derived tissue microarray (cbTMA) approach.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A total of 65 cell blocks (CB) diagnosed as NSCLC were retrospectively collected and selected for TMA preparation. Hematoxylin–eosin and PD-L1 stained slides were digitized and uploaded on a free web sharing platform. Participants were asked to provide PD-L1 assessment by using the clinically relevant cutoff of tumor proportion score (TPS) (<1%; 1%–49%; >50%). Interobserver agreement was calculated using Fleiss’s κ.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Of 65 CBs, 11 were deemed not suitable; therefore, an overall number of 54 cores were used for the preparation of four TMAs. A total of 1674 evaluations were provided by 31 cytopathologists from 21 different institutions in nine countries. The statistical analysis showed a moderate overall agreement (κ = 0.49). The highest agreement was achieved in the TPS >50% category (κ = 0.57); moderate agreement was observed in TPS <1% category (κ = 0.51) and the lowest κ value was obtained for TPS 1%–49% category (k = 0.32).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>The overall moderate agreement observed showed that there is still room for improvement in inter-pathologist agreement for PD-L1 evaluation on cytological samples, highlighting the need for standardization in sample preparation, focused training in PD-L1 evaluation on cytological material, and the integration of machine learning tools to improve interobserver consistency.</p>\u0000 </section>\u0000 </div>","PeriodicalId":9410,"journal":{"name":"Cancer Cytopathology","volume":"133 3","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cncy.70003","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143481449","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}
{"title":"Cytomorphology and clinicopathologic correlation of TFE3-rearranged renal cell carcinoma","authors":"Tieying Hou MD, PhD, Xiaoqi Lin MD, PhD","doi":"10.1002/cncy.22933","DOIUrl":"https://doi.org/10.1002/cncy.22933","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p><i>TFE3</i>-rearranged renal cell carcinoma (<i>TFE3</i>-rRCC) harbors gene fusions involving <i>TFE3</i> with one of many different partner genes. Because of their diverse morphologies, the differential diagnosis is broad and challenging. Publications focusing on the cytomorphology of <i>TFE3</i>-rRCC are sparse.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Fifteen cytology cases of <i>TFE3</i>-rRCC from 12 patients were retrieved, comprising seven primary kidney cases and eight metastatic cases.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Cytology smears showed tumor cells with moderate granular or vacuolated cytoplasm, arranged in diverse patterns, such as three-dimensional clusters, nested/sheeted formations, isolated cells, papillary, and tubular/acinar structures. The tumor cells exhibited enlarged eccentric, round or oval nuclei, possibly situated peripherally, with small to prominent nucleoli and irregular nuclear membranes. Macrophages, hyalinized globules, or necrosis were occasionally seen. Core and cell block histology often showed papillae with surface-oriented nuclei. Tumor cells were also arranged in nested, sheeted, and tubular patterns. Tumor cells were immunoreactive to TFE3 (100%), AMACR (100%), PAX8 (88%), and CD10 (83%) and showed focal staining for CA9 (64%), CK7 (20%), and CD117 (25%). TFE3 rearrangement was confirmed in 13 of 15 cases through fluorescence in situ hybridization or RNA fusion next-generation sequencing testing. Metastasis was observed in nine of 12 patients (80%), with retroperitoneal lymph nodes being the most common site, followed by distant lymph nodes, lung, brain, adrenal gland, and bone. Six patients (50%) underwent nephrectomy alone, two patients (17%) received chemotherapy alone, and four patients (33%) received combined nephrectomy and chemotherapy.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Timely recognition of TFE3-rRCC’s distinct cytomorphologic and histomorphologic features is essential for accurate diagnosis and effective treatment.</p>\u0000 </section>\u0000 </div>","PeriodicalId":9410,"journal":{"name":"Cancer Cytopathology","volume":"133 2","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cncy.22933","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143248857","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}
Elie Tannous MD, Sana Malik BASc, Syed M. Gilani MD
{"title":"Pericardial fluid evaluation: Diagnostic yield and cytology–histology correlation","authors":"Elie Tannous MD, Sana Malik BASc, Syed M. Gilani MD","doi":"10.1002/cncy.70000","DOIUrl":"https://doi.org/10.1002/cncy.70000","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Pericardial effusion can be due to any etiology but may cause significant morbidity and mortality; however, malignant effusions are rare, and accurate and timely diagnosis is essential for appropriate further management. Data on the actual comparison of pericardial cytology and surgical specimens are limited, and this study was conducted to evaluate an institutional cohort and compare these two samples.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>The institutional electronic database system was retrospectively searched between January 2019 and December 2023 for pericardial biopsies/surgical specimens (PSSs) and cytology.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>A total of 202 surgical specimens of the pericardium were identified from patients with a median age of 67 years and a range of 18–97 years. Of these 202 cases, 190 specimens also underwent cytological evaluation, which included 153 cases that were negative for malignancy, nine cases that were indeterminate/atypical, and 28 cases that were positive for malignancy. Agreement between cytology and PSSs was reached in 172 cases, with 153 being benign and 19 being malignant. However, a cytology–histology discrepancy was found in 18 cases. Of these 18 cases, nine showed positive cytology but all had negative concurrent PSSs except for one with focal atypia, and the remaining nine were indeterminate/atypical on cytology. Eight of these nine indeterminate cases were negative on the PSS, whereas one atypical cytology case with low cellularity showed a positive PSS.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>If atypical cases are excluded, cytology demonstrates a better diagnostic yield for detecting malignancy compared to surgical specimens (<i>n</i> = 28 cases vs. <i>n</i> = 20 cases, respectively).</p>\u0000 </section>\u0000 </div>","PeriodicalId":9410,"journal":{"name":"Cancer Cytopathology","volume":"133 2","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143248858","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}