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.
{"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}
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.
{"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}
<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
{"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
Background
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.
Methods
Patient data, including clinical histories, radiology, pathology, treatments, and follow-up, were collected.
Results
Twenty-two angiosarcoma fluid specimens (pleura, n = 17; pericardium, n = 2; ascites, n = 2; and liver cyst, n = 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 club-shaped 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).
Conclusions
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.
{"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
Introduction
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.
Methods
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.
Results
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).
Conclusions
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.
{"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}
TFE3-rearranged renal cell carcinoma (TFE3-rRCC) harbors gene fusions involving TFE3 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 TFE3-rRCC are sparse.
Methods
Fifteen cytology cases of TFE3-rRCC from 12 patients were retrieved, comprising seven primary kidney cases and eight metastatic cases.
Results
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.
Conclusions
Timely recognition of TFE3-rRCC’s distinct cytomorphologic and histomorphologic features is essential for accurate diagnosis and effective treatment.
{"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
Background
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.
Methods
The institutional electronic database system was retrospectively searched between January 2019 and December 2023 for pericardial biopsies/surgical specimens (PSSs) and cytology.
Results
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.
Conclusions
If atypical cases are excluded, cytology demonstrates a better diagnostic yield for detecting malignancy compared to surgical specimens (n = 28 cases vs. n = 20 cases, respectively).
{"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}
Fine-needle aspiration cytology (FNAC) has been used as the first line approach to lymphadenopathy, which is a common presentation in pediatric age group. The Sydney system for reporting of lymph node (LN) cytology has been proposed to assess the reliability, performance, and accuracy of the aspiration procedure. This study intends to assess the role of FNAC in the pediatric population according to the Sydney system.
Methods
This was a retrospective observational study from a tertiary care center in Eastern India. All the patients in the age group of 0–18 years evaluated during years 2016–2024 were reclassified according to the Sydney system. Based on the cytology and histology diagnoses, the cases were categorized into true-negative, true-positive, false-negative, and false-positive. The overall sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), accuracy, and risk of malignancy (ROM) was calculated for each category.
Results
Of 803 cases of pediatric LN-FNACs, 35 (4.35%) cases were reported as inadequate (L1), 689 (85.8%) cases as benign (L2), four (0.49%) cases as atypical cells of undetermined significance (L3), 22 cases as suspicious for malignancy (L4), and 53 (6.6%) cases as malignant (L5). The sensitivity, specificity, PPV, NPV, and accuracy was 72.34%, 98.48%, 97.14%, 83.33%, and 87.61%, respectively. The ROM was 16.67% for L2 and 100% for both L4 and L5 categories.
Conclusions
FNAC is a highly accurate and specific test for LN pathology, especially in the pediatric population. The incorporation of the Sydney system helps to achieve uniformity and reproducibility in LN cytology diagnosis.
{"title":"Assessment of risk of malignancy with application of Sydney classification for reporting of lymph node cytopathology in pediatric population: An institutional experience","authors":"Mukund Sable MD, Manisha Panda MBBS, Prapti Acharya MD, Pritinanda Mishra MD, Suvendu Purkait MD, Madhusmita Sethy MD, Pavithra Ayyanar MD, Amit Kumar Adhya MD, Susama Patra MD","doi":"10.1002/cncy.22936","DOIUrl":"https://doi.org/10.1002/cncy.22936","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Fine-needle aspiration cytology (FNAC) has been used as the first line approach to lymphadenopathy, which is a common presentation in pediatric age group. The Sydney system for reporting of lymph node (LN) cytology has been proposed to assess the reliability, performance, and accuracy of the aspiration procedure. This study intends to assess the role of FNAC in the pediatric population according to the Sydney system.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This was a retrospective observational study from a tertiary care center in Eastern India. All the patients in the age group of 0–18 years evaluated during years 2016–2024 were reclassified according to the Sydney system. Based on the cytology and histology diagnoses, the cases were categorized into true-negative, true-positive, false-negative, and false-positive. The overall sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), accuracy, and risk of malignancy (ROM) was calculated for each category.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Of 803 cases of pediatric LN-FNACs, 35 (4.35%) cases were reported as inadequate (L1), 689 (85.8%) cases as benign (L2), four (0.49%) cases as atypical cells of undetermined significance (L3), 22 cases as suspicious for malignancy (L4), and 53 (6.6%) cases as malignant (L5). The sensitivity, specificity, PPV, NPV, and accuracy was 72.34%, 98.48%, 97.14%, 83.33%, and 87.61%, respectively. The ROM was 16.67% for L2 and 100% for both L4 and L5 categories.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>FNAC is a highly accurate and specific test for LN pathology, especially in the pediatric population. The incorporation of the Sydney system helps to achieve uniformity and reproducibility in LN cytology diagnosis.</p>\u0000 </section>\u0000 </div>","PeriodicalId":9410,"journal":{"name":"Cancer Cytopathology","volume":"133 2","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143111918","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}
Melanie C. Kwan MD, Martha B. Pitman MD, M. Lisa Zhang MD
Background
Major mutations (e.g., KRAS, GNAS, TP53, SMAD4) in pancreatic cyst fluid (PCF) are useful for classifying and risk stratifying certain cyst types, particularly in cases with nondiagnostic cytology. However, the significance of uncommon minor mutations in PCF has yet to be reported.
Methods
In total, 127 PCF specimens (2014–2021) from 121 patients that underwent molecular analysis were identified, and detailed clinicopathologic data were recorded. Molecular testing was performed using a laboratory-developed next-generation sequencing panel.
Results
Forty-five variants other than KRAS, GNAS, RNF43, TP53, CDKN2A, and SMAD4 were detected. Variants that were detected in five or more cases included ARID1A (n = 28), VHL (n = 17), BRAF (n = 12), ATM (n = 8), APC (n = 8), MEN1 (n = 5), serine threonine kinase 11 (STK11; n = 5), PIK3CA (n = 5), and CDH1 (n = 5). Thirty-eight of 121 patients (31%) had histologic confirmation on follow-up resection. Twenty-seven of 28 cysts (96%) with ARID1A mutations had concurrent KRAS/GNAS mutations; 17 (61%) were diagnosed as neoplastic mucinous cysts on cytology, and 10 (36%) were diagnosed as intraductal papillary mucinous neoplasm (IPMN) on histology (80% low grade). No patients developed disease recurrence or died of disease. Cysts with STK11 mutations had RAS co-mutations (KRAS, n = 5; NRAS, n = 1), and four of those five cysts (80%) were mucinous neoplasms with high-grade atypia on cytology. All three resection specimens were IPMNs with high-grade dysplasia or invasive carcinoma, and two of those patients died of disease.
Conclusions
In PCFs, ARID1A mutations were consistently associated with IPMNs (predominantly low grade) with no recurrences or deaths from disease. STK11 mutations appeared to be associated with high-risk mucinous cysts. The detection of minor variants may provide useful preoperative information and add value beyond single-gene genotyping of major mutations.
{"title":"Cytologic, histologic, and clinical correlation of minor mutations in pancreatic cysts","authors":"Melanie C. Kwan MD, Martha B. Pitman MD, M. Lisa Zhang MD","doi":"10.1002/cncy.22935","DOIUrl":"10.1002/cncy.22935","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Major mutations (e.g., <i>KRAS</i>, <i>GNAS</i>, <i>TP53</i>, <i>SMAD4</i>) in pancreatic cyst fluid (PCF) are useful for classifying and risk stratifying certain cyst types, particularly in cases with nondiagnostic cytology. However, the significance of uncommon minor mutations in PCF has yet to be reported.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>In total, 127 PCF specimens (2014–2021) from 121 patients that underwent molecular analysis were identified, and detailed clinicopathologic data were recorded. Molecular testing was performed using a laboratory-developed next-generation sequencing panel.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Forty-five variants other than <i>KRAS</i>, <i>GNAS</i>, <i>RNF43</i>, <i>TP53</i>, <i>CDKN2A</i>, and <i>SMAD4</i> were detected. Variants that were detected in five or more cases included <i>ARID1A</i> (<i>n</i> = 28), <i>VHL</i> (<i>n</i> = 17), <i>BRAF</i> (<i>n</i> = 12), <i>ATM</i> (<i>n</i> = 8), <i>APC</i> (<i>n</i> = 8), <i>MEN1</i> (<i>n</i> = 5), serine threonine kinase 11 <i>(STK11</i>; <i>n</i> = 5), <i>PIK3CA</i> (<i>n</i> = 5), and <i>CDH1</i> (<i>n</i> = 5). Thirty-eight of 121 patients (31%) had histologic confirmation on follow-up resection. Twenty-seven of 28 cysts (96%) with <i>ARID1A</i> mutations had concurrent <i>KRAS</i>/<i>GNAS</i> mutations; 17 (61%) were diagnosed as neoplastic mucinous cysts on cytology, and 10 (36%) were diagnosed as intraductal papillary mucinous neoplasm (IPMN) on histology (80% low grade). No patients developed disease recurrence or died of disease. Cysts with <i>STK11</i> mutations had <i>RAS</i> co-mutations (<i>KRAS</i>, <i>n</i> = 5; <i>NRAS</i>, <i>n</i> = 1), and four of those five cysts (80%) were mucinous neoplasms with high-grade atypia on cytology. All three resection specimens were IPMNs with high-grade dysplasia or invasive carcinoma, and two of those patients died of disease.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>In PCFs, <i>ARID1A</i> mutations were consistently associated with IPMNs (predominantly low grade) with no recurrences or deaths from disease. <i>STK11</i> mutations appeared to be associated with high-risk mucinous cysts. The detection of minor variants may provide useful preoperative information and add value beyond single-gene genotyping of major mutations.</p>\u0000 </section>\u0000 </div>","PeriodicalId":9410,"journal":{"name":"Cancer Cytopathology","volume":"133 2","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-01-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143045556","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}
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