Sule Canberk, N. Paul Ohori, Rita Luis, Elena Vigliar, Vivian Weiss, Zubair Baloch
Imaging-driven detection of thyroid nodules has expanded the role of fine-needle aspiration (FNA) while demanding integration of molecular data into routine cytologic assessment. We present four illustrative cases spanning the contemporary diagnostic spectrum: (1) an Atypia of Undetermined Significance (AUS) nodule with dual low-level PTEN mutations managed by active surveillance; (2) an oncocytic follicular neoplasm upgraded to total thyroidectomy by concurrent HRAS and TERT promoter mutations; (3) an oncocytic subtype poorly differentiated thyroid carcinoma (O-PDTC) highlighting subtle high-grade cytologic cues and a distinct genomic profile; and (4) a pediatric poorly differentiated carcinoma harboring a DICER1 hotspot mutation, underscoring age-specific biology and the need for genetic consideration. These cases emphasize that morphology remains foundational, but mutation context, single versus co-alterations, allelic burden, and patient age ultimately direct management. Harmonized reporting that clearly conveys molecular findings is essential to translate limited cytology material into precise, patient-specific care.
{"title":"Diagnosing Thyroid Lesions Through A Morphology–Molecular Lens: Four Case-Based Lessons From 22nd International Congress of Cytology—Florence 2025","authors":"Sule Canberk, N. Paul Ohori, Rita Luis, Elena Vigliar, Vivian Weiss, Zubair Baloch","doi":"10.1002/dc.70022","DOIUrl":"10.1002/dc.70022","url":null,"abstract":"<div>\u0000 \u0000 <p>Imaging-driven detection of thyroid nodules has expanded the role of fine-needle aspiration (FNA) while demanding integration of molecular data into routine cytologic assessment. We present four illustrative cases spanning the contemporary diagnostic spectrum: (1) an Atypia of Undetermined Significance (AUS) nodule with dual low-level <i>PTEN</i> mutations managed by active surveillance; (2) an oncocytic follicular neoplasm upgraded to total thyroidectomy by concurrent <i>HRAS</i> and <i>TERT</i> promoter mutations; (3) an oncocytic subtype poorly differentiated thyroid carcinoma (O-PDTC) highlighting subtle high-grade cytologic cues and a distinct genomic profile; and (4) a pediatric poorly differentiated carcinoma harboring a <i>DICER1</i> hotspot mutation, underscoring age-specific biology and the need for genetic consideration. These cases emphasize that morphology remains foundational, but mutation context, single versus co-alterations, allelic burden, and patient age ultimately direct management. Harmonized reporting that clearly conveys molecular findings is essential to translate limited cytology material into precise, patient-specific care.</p>\u0000 </div>","PeriodicalId":11349,"journal":{"name":"Diagnostic Cytopathology","volume":"53 12","pages":"597-603"},"PeriodicalIF":1.0,"publicationDate":"2025-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145085405","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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 specimens are frequently utilized for ancillary studies to identify diagnostic and prognostic information. This case highlights diagnostic pitfalls and challenges in diagnosing NUTM1-rearranged neoplasia on pancreatic cytology. NUT carcinomas and sarcomas have highly variable cytomorphology, immunohistochemical staining profiles, and various gene partners involved in the fusion. Detecting these clinically relevant gene fusions in cytologic specimens can be particularly challenging as new diagnostic entities emerge. In cytologic specimens with a wide differential, maximizing the tissue for ancillary studies and selecting appropriate studies are critical. Finally, it highlights the importance of molecular cytopathology for patient care in complex and rare fusion-driven entities and the need for orthogonal testing when results are discordant and unexpected.
{"title":"Challenges and Pitfalls to Diagnosing NUTM1-Rearranged Neoplasia of the Pancreas by Cytology and Ancillary Studies.","authors":"Terrance J Lynn","doi":"10.1002/dc.70021","DOIUrl":"https://doi.org/10.1002/dc.70021","url":null,"abstract":"<p><p>Fine-needle aspiration cytology specimens are frequently utilized for ancillary studies to identify diagnostic and prognostic information. This case highlights diagnostic pitfalls and challenges in diagnosing NUTM1-rearranged neoplasia on pancreatic cytology. NUT carcinomas and sarcomas have highly variable cytomorphology, immunohistochemical staining profiles, and various gene partners involved in the fusion. Detecting these clinically relevant gene fusions in cytologic specimens can be particularly challenging as new diagnostic entities emerge. In cytologic specimens with a wide differential, maximizing the tissue for ancillary studies and selecting appropriate studies are critical. Finally, it highlights the importance of molecular cytopathology for patient care in complex and rare fusion-driven entities and the need for orthogonal testing when results are discordant and unexpected.</p>","PeriodicalId":11349,"journal":{"name":"Diagnostic Cytopathology","volume":" ","pages":""},"PeriodicalIF":1.0,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145079911","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Positive cerebrospinal fluid (CSF) cytology remains a cornerstone and irreplaceable diagnostic modality for the indication of leptomeningeal dissemination by primary as well as metastatic malignancies. Identification of tumor cells is fundamental for institution of aggressive treatment, such as radiotherapy, intrathecal chemotherapy, or systemic therapies, and will help increase overall survival. We did a retrospective analysis of CSF cytology in our center of all samples diagnosed as positive for malignant cells from January 2001 to December 2024 to find out about the spectrum of malignancies being detected in CSF cytology.
Methods
We searched the database of our Hospital from January 2001 to December 2024 and found 853 samples of CSF of different patients that were diagnosed as positive for malignant cells. All cases were reviewed independently by two cytopathologists, and no discrepancy was found.
Results
The diagnostic spectrum included cases of metastatic solid and hematolymphoid malignancies as well as dissemination of primary CNS tumors to CSF. Out of 853 cases, 550 cases were of CSF involvement by blast cells, 132 were of metastatic carcinomas, 78 were of hematological malignancies other than lymphoblastic lymphomas, 82 were of primary CNS tumors involving CSF, and 11 were of various other malignancies, including a spectrum of round blue cell tumors and sarcomas.
Conclusions
A broad spectrum of epithelial, mesenchymal, and hematolymphoid malignancies can be diagnosed on CSF cytology, and these are likely metastatic in origin. Hematolymphoid malignancies, especially lymphoblastic lymphoma in children, are most common. Likewise, metastatic carcinomas constitute the major bulk of the adult population.
{"title":"The Spectrum of Malignant Diagnoses in Cerebrospinal Fluid (CSF) Cytology in Both Pediatric and Adult Populations: A Single-Institutional Retrospective Review","authors":"Nida Babar, Asif Loya, Sajid Mushtaq, Maryam Hameed, Usman Hassan, Mudassar Hussain","doi":"10.1002/dc.70020","DOIUrl":"10.1002/dc.70020","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>Positive cerebrospinal fluid (CSF) cytology remains a cornerstone and irreplaceable diagnostic modality for the indication of leptomeningeal dissemination by primary as well as metastatic malignancies. Identification of tumor cells is fundamental for institution of aggressive treatment, such as radiotherapy, intrathecal chemotherapy, or systemic therapies, and will help increase overall survival. We did a retrospective analysis of CSF cytology in our center of all samples diagnosed as positive for malignant cells from January 2001 to December 2024 to find out about the spectrum of malignancies being detected in CSF cytology.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We searched the database of our Hospital from January 2001 to December 2024 and found 853 samples of CSF of different patients that were diagnosed as positive for malignant cells. All cases were reviewed independently by two cytopathologists, and no discrepancy was found.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The diagnostic spectrum included cases of metastatic solid and hematolymphoid malignancies as well as dissemination of primary CNS tumors to CSF. Out of 853 cases, 550 cases were of CSF involvement by blast cells, 132 were of metastatic carcinomas, 78 were of hematological malignancies other than lymphoblastic lymphomas, 82 were of primary CNS tumors involving CSF, and 11 were of various other malignancies, including a spectrum of round blue cell tumors and sarcomas.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>A broad spectrum of epithelial, mesenchymal, and hematolymphoid malignancies can be diagnosed on CSF cytology, and these are likely metastatic in origin. Hematolymphoid malignancies, especially lymphoblastic lymphoma in children, are most common. Likewise, metastatic carcinomas constitute the major bulk of the adult population.</p>\u0000 </section>\u0000 </div>","PeriodicalId":11349,"journal":{"name":"Diagnostic Cytopathology","volume":"53 12","pages":"620-626"},"PeriodicalIF":1.0,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145079931","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Suzana Harabajsa, Paula Gršković, Ivana Grgić, Lana Gorenec, Snježana Židovec Lepej, Sonja Badovinac, Marko Jakopović, Silvana Smojver-Ježek, Petra Korać
Background
Human cytomegalovirus (HCMV) has been proposed as a potential risk factor in lung cancer. This study aimed to investigate the relationship between the presence of HCMV in tumor cells and the immune response to HCMV in the peripheral blood of patients with EGFR-mutated and EGFR wild-type lung adenocarcinoma.
Methods
DNA was extracted from 102 May-Grünwald-Giemsa–stained cytological smears (51 EGFR-mutated and 51 EGFR wild-type). HCMV presence in tumor cells was assessed by PCR targeting viral genes MIE and gB. The immune response to HCMV was evaluated in 80 corresponding peripheral blood samples using the QuantiFERON-CMV ELISA test. Statistical analysis was performed using the chi-square test, with significance p < 0.05.
Results
HCMV MIE gene was detected in eight (15.7%) EGFR-mutated and one (2.0%) EGFR wild-type smear. The HCMV gB gene was identified in four (7.8%) EGFR wild-type smears and none of the EGFR-mutated smears. Immune response to HCMV was observed in 18 (62.1%) EGFR-mutated and 26 (50.9%) EGFR wild-type patients. Among those with detectable HCMV MIE, an immune response was found in two EGFR-mutated and one EGFR-negative patient. Among smears positive for HCMV gB, immune response was detected in three EGFR wild-type cases. One EGFR wild-type case showed no immune response despite the presence of HCMV gB.
Conclusion
No clear association was observed between HCMV in lung adenocarcinoma cells and the immune response to HCMV in peripheral blood, regardless of EGFR gene mutation status.
{"title":"Human Cytomegalovirus in EGFR-Mutated and Wild-Type Lung Adenocarcinoma: Detection in Cytological Smears and Associated Peripheral Immune Response","authors":"Suzana Harabajsa, Paula Gršković, Ivana Grgić, Lana Gorenec, Snježana Židovec Lepej, Sonja Badovinac, Marko Jakopović, Silvana Smojver-Ježek, Petra Korać","doi":"10.1002/dc.70024","DOIUrl":"10.1002/dc.70024","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Human cytomegalovirus (HCMV) has been proposed as a potential risk factor in lung cancer. This study aimed to investigate the relationship between the presence of HCMV in tumor cells and the immune response to HCMV in the peripheral blood of patients with EGFR-mutated and EGFR wild-type lung adenocarcinoma.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>DNA was extracted from 102 May-Grünwald-Giemsa–stained cytological smears (51 EGFR-mutated and 51 EGFR wild-type). HCMV presence in tumor cells was assessed by PCR targeting viral genes <i>MIE</i> and <i>gB</i>. The immune response to HCMV was evaluated in 80 corresponding peripheral blood samples using the QuantiFERON-CMV ELISA test. Statistical analysis was performed using the chi-square test, with significance <i>p</i> < 0.05.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>HCMV <i>MIE</i> gene was detected in eight (15.7%) EGFR-mutated and one (2.0%) EGFR wild-type smear. The HCMV <i>gB</i> gene was identified in four (7.8%) EGFR wild-type smears and none of the EGFR-mutated smears. Immune response to HCMV was observed in 18 (62.1%) EGFR-mutated and 26 (50.9%) EGFR wild-type patients. Among those with detectable HCMV <i>MIE</i>, an immune response was found in two EGFR-mutated and one EGFR-negative patient. Among smears positive for HCMV <i>gB</i>, immune response was detected in three EGFR wild-type cases. One EGFR wild-type case showed no immune response despite the presence of HCMV <i>gB</i>.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>No clear association was observed between HCMV in lung adenocarcinoma cells and the immune response to HCMV in peripheral blood, regardless of <i>EGFR</i> gene mutation status.</p>\u0000 </section>\u0000 </div>","PeriodicalId":11349,"journal":{"name":"Diagnostic Cytopathology","volume":"53 12","pages":"627-632"},"PeriodicalIF":1.0,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145079902","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Cytopathology in the Philippines: A Chronicle of Practice, Purpose, and Progress","authors":"Zubair Baloch","doi":"10.1002/dc.70023","DOIUrl":"10.1002/dc.70023","url":null,"abstract":"","PeriodicalId":11349,"journal":{"name":"Diagnostic Cytopathology","volume":"54 1","pages":"3-5"},"PeriodicalIF":1.0,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145074598","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Juanita E. Ferreira, Nikki Chiang, Xin Jing, Brian Smola, Richard L. Cantley, Judy C. Pang, Madelyn Lew
Background
There is a decreased cervical cancer screening rate among female to male transgender (FTMTG) patients. Data on the distinct cytologic features present in cervical cytology (CC) of those on testosterone therapy is limited.
Methods
An 2017–2023 electronic database search identified CC specimens from a cohort of FTMTG patients on testosterone therapy (TT). A morphologic retrospective review of CC for cellularity and presence of key morphologic features was performed. Records were reviewed for original cytologic diagnoses and concurrent HPV test results for comparison with a cisgender female (CF) cohort.
Results
106 of 132,363 (0.08%) identified CC specimens were from FTMTG patients on TT. Diagnostic rates were compared to the CF population. The most common diagnosis for both groups was “negative for intraepithelial lesion or malignancy”. The unsatisfactory rate was significantly higher in the FTMTG cohort at 21.7% (vs. 2.7%). The comparative HPV positivity rate of FTMTG and CF cohorts was 13.2% and 10.7%, respectively. Of 83 FTMTG satisfactory CC specimens, 67% showed low cellularity (narrowly meeting the adequacy threshold of 5000 well-visualized squamous cells) and 78% showed extensive squamous atrophy. Nuclear grooves and irregular contours (features associated with transitional cell metaplasia) were observed in 18% and 23%, respectively. High N:C ratio was noted in 20% of cases.
Conclusion
The higher unsatisfactory rate in FTMTG patients raises the question of whether adequacy criteria for this cohort should be adjusted. To enhance diagnostic accuracy, providing an accurate clinical history may prevent overinterpretation of features associated with transitional cell metaplasia.
{"title":"In-Depth Assessment of Cytologic Features in 106 Cervical Papanicolaou Tests of Transgender Male Patients on Testosterone: An Institutional Experience","authors":"Juanita E. Ferreira, Nikki Chiang, Xin Jing, Brian Smola, Richard L. Cantley, Judy C. Pang, Madelyn Lew","doi":"10.1002/dc.70018","DOIUrl":"10.1002/dc.70018","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>There is a decreased cervical cancer screening rate among female to male transgender (FTMTG) patients. Data on the distinct cytologic features present in cervical cytology (CC) of those on testosterone therapy is limited.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>An 2017–2023 electronic database search identified CC specimens from a cohort of FTMTG patients on testosterone therapy (TT). A morphologic retrospective review of CC for cellularity and presence of key morphologic features was performed. Records were reviewed for original cytologic diagnoses and concurrent HPV test results for comparison with a cisgender female (CF) cohort.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>106 of 132,363 (0.08%) identified CC specimens were from FTMTG patients on TT. Diagnostic rates were compared to the CF population. The most common diagnosis for both groups was “negative for intraepithelial lesion or malignancy”. The unsatisfactory rate was significantly higher in the FTMTG cohort at 21.7% (vs. 2.7%). The comparative HPV positivity rate of FTMTG and CF cohorts was 13.2% and 10.7%, respectively. Of 83 FTMTG satisfactory CC specimens, 67% showed low cellularity (narrowly meeting the adequacy threshold of 5000 well-visualized squamous cells) and 78% showed extensive squamous atrophy. Nuclear grooves and irregular contours (features associated with transitional cell metaplasia) were observed in 18% and 23%, respectively. High N:C ratio was noted in 20% of cases.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>The higher unsatisfactory rate in FTMTG patients raises the question of whether adequacy criteria for this cohort should be adjusted. To enhance diagnostic accuracy, providing an accurate clinical history may prevent overinterpretation of features associated with transitional cell metaplasia.</p>\u0000 </section>\u0000 </div>","PeriodicalId":11349,"journal":{"name":"Diagnostic Cytopathology","volume":"53 12","pages":"613-619"},"PeriodicalIF":1.0,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/dc.70018","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145063717","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Head and neck squamous cell carcinoma (HNSCC) frequently metastasizes to the cervical lymph nodes and is subjected to fine needle aspiration biopsy cytology (FNABC). The aim of this study was to describe the cytomorphological spectrum and explore the association with the primary site of origin and the short-term outcome following radiation therapy.
Methods
A retrospective cytomorphological evaluation was performed on 338 cases of metastatic squamous cell carcinoma to cervical lymph nodes from HNSCC primaries. The clinical details including the age, sex, primary site of origin confirmed on histopathology, composite stage, and outcome at 1-year follow-up (86) were obtained from the records. An exploratory analysis was performed to derive any association of the cytomorphological features with the primary site of origin and short-term outcome.
Results
The patients' age ranged from 28 to 89 years (mean, 56.6 years) with marked male preponderance, and the majority in Stage IV. The primary site was the oral cavity (45.2%) followed by the oropharynx (37%), hypopharynx (8.5%), nasopharynx (6.2%) and larynx (3.1%). Cytomorphology revealed keratinization of any degree in 86% of cases. The background was necroinflammatory, fluidy, or reactive lymphocytic with granulomatous reaction in 5% of cases. The chromatin pattern (vesicular, coarse or dense hyperchromatic), presence of nucleoli, and reactive lymphocytic background showed site-specific differences. However, no cytomorphological parameter showed any association with short-term outcome.
Conclusion
Metastatic HNSCC to the cervical lymph nodes presents a broad cytomorphological spectrum with no specific association with outcome.
{"title":"Metastatic Head and Neck Squamous Cell Carcinoma: Cytomorphological Spectrum on Fine Needle Aspiration Biopsy Cytology and Its Relevance","authors":"Dipanwita Biswas, Aadya Kerkar, Nuli Muni Kiran, Sushmita Ghoshal, Suvradeep Mitra, Nalini Gupta, Amanjit Bal, Radhika Srinivasan","doi":"10.1002/dc.70019","DOIUrl":"10.1002/dc.70019","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Head and neck squamous cell carcinoma (HNSCC) frequently metastasizes to the cervical lymph nodes and is subjected to fine needle aspiration biopsy cytology (FNABC). The aim of this study was to describe the cytomorphological spectrum and explore the association with the primary site of origin and the short-term outcome following radiation therapy.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A retrospective cytomorphological evaluation was performed on 338 cases of metastatic squamous cell carcinoma to cervical lymph nodes from HNSCC primaries. The clinical details including the age, sex, primary site of origin confirmed on histopathology, composite stage, and outcome at 1-year follow-up (86) were obtained from the records. An exploratory analysis was performed to derive any association of the cytomorphological features with the primary site of origin and short-term outcome.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The patients' age ranged from 28 to 89 years (mean, 56.6 years) with marked male preponderance, and the majority in Stage IV. The primary site was the oral cavity (45.2%) followed by the oropharynx (37%), hypopharynx (8.5%), nasopharynx (6.2%) and larynx (3.1%). Cytomorphology revealed keratinization of any degree in 86% of cases. The background was necroinflammatory, fluidy, or reactive lymphocytic with granulomatous reaction in 5% of cases. The chromatin pattern (vesicular, coarse or dense hyperchromatic), presence of nucleoli, and reactive lymphocytic background showed site-specific differences. However, no cytomorphological parameter showed any association with short-term outcome.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Metastatic HNSCC to the cervical lymph nodes presents a broad cytomorphological spectrum with no specific association with outcome.</p>\u0000 </section>\u0000 </div>","PeriodicalId":11349,"journal":{"name":"Diagnostic Cytopathology","volume":"53 12","pages":"604-612"},"PeriodicalIF":1.0,"publicationDate":"2025-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145052420","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Qi Liu, Xiaoyong Li, Tiejun Jin, Sibo Huo, Shuai Su, Nan Liu
Colorectal cancer (CRC) is a major global health burden, ranking among the leading causes of cancer-related deaths. Despite improvements in screening and treatment, challenges such as late-stage diagnosis, high recurrence rates, and therapy resistance continue to impede optimal outcomes. Liquid biopsy, a minimally invasive technique that analyzes tumor-derived components in bodily fluids—including circulating tumor DNA (ctDNA), circulating tumor cells (CTCs), and extracellular vesicles (EVs)—is emerging as a powerful tool to transform CRC management across the disease continuum. This review provides a comprehensive overview of liquid biopsy's current and emerging applications in CRC. We examine its role in early detection, where sensitive ctDNA-based assays and epigenetic biomarkers have demonstrated the ability to identify CRC at asymptomatic or early stages, potentially improving screening uptake and compliance. Furthermore, we explore how liquid biopsy enables dynamic monitoring of treatment response and clonal evolution, facilitating the timely identification of resistance mutations and supporting personalized therapy adjustments. Innovations in multi-omics integration, artificial intelligence, and ultra-sensitive sequencing technologies are also discussed as pivotal advancements that enhance the clinical utility of liquid biopsy. Despite significant progress, the widespread adoption of liquid biopsy faces several hurdles, including assay standardization, sensitivity for low-shedding tumors, regulatory approval, and cost-effectiveness. Continued research, validation in large prospective trials, and harmonization of testing protocols are essential to overcome these challenges. Ultimately, liquid biopsy holds the potential to become a cornerstone of precision oncology in CRC, enabling earlier intervention, more tailored treatment strategies, and improved patient outcomes.
{"title":"Liquid Biopsy in CRC Management: Early Detection, Minimal Residual Disease, and Therapy Optimization—Clinical Evidence and Challenges","authors":"Qi Liu, Xiaoyong Li, Tiejun Jin, Sibo Huo, Shuai Su, Nan Liu","doi":"10.1002/dc.70009","DOIUrl":"10.1002/dc.70009","url":null,"abstract":"<div>\u0000 \u0000 <p>Colorectal cancer (CRC) is a major global health burden, ranking among the leading causes of cancer-related deaths. Despite improvements in screening and treatment, challenges such as late-stage diagnosis, high recurrence rates, and therapy resistance continue to impede optimal outcomes. Liquid biopsy, a minimally invasive technique that analyzes tumor-derived components in bodily fluids—including circulating tumor DNA (ctDNA), circulating tumor cells (CTCs), and extracellular vesicles (EVs)—is emerging as a powerful tool to transform CRC management across the disease continuum. This review provides a comprehensive overview of liquid biopsy's current and emerging applications in CRC. We examine its role in early detection, where sensitive ctDNA-based assays and epigenetic biomarkers have demonstrated the ability to identify CRC at asymptomatic or early stages, potentially improving screening uptake and compliance. Furthermore, we explore how liquid biopsy enables dynamic monitoring of treatment response and clonal evolution, facilitating the timely identification of resistance mutations and supporting personalized therapy adjustments. Innovations in multi-omics integration, artificial intelligence, and ultra-sensitive sequencing technologies are also discussed as pivotal advancements that enhance the clinical utility of liquid biopsy. Despite significant progress, the widespread adoption of liquid biopsy faces several hurdles, including assay standardization, sensitivity for low-shedding tumors, regulatory approval, and cost-effectiveness. Continued research, validation in large prospective trials, and harmonization of testing protocols are essential to overcome these challenges. Ultimately, liquid biopsy holds the potential to become a cornerstone of precision oncology in CRC, enabling earlier intervention, more tailored treatment strategies, and improved patient outcomes.</p>\u0000 </div>","PeriodicalId":11349,"journal":{"name":"Diagnostic Cytopathology","volume":"53 11","pages":"580-591"},"PeriodicalIF":1.0,"publicationDate":"2025-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144991770","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
This case report presents the cytological characteristics of an extracranial anaplastic meningioma—an exceptionally rare entity rarely sampled via fine-needle aspiration. We aim to highlight specific cytomorphological features that may aid in the preoperative identification of the anaplastic subtype.
{"title":"Case Report: Cytopathological Diagnosis of Extracranial Anaplastic Meningioma Using Fine-Needle Aspiration","authors":"Burcu Özcan","doi":"10.1002/dc.70017","DOIUrl":"10.1002/dc.70017","url":null,"abstract":"<div>\u0000 \u0000 <p>This case report presents the cytological characteristics of an extracranial anaplastic meningioma—an exceptionally rare entity rarely sampled via fine-needle aspiration. We aim to highlight specific cytomorphological features that may aid in the preoperative identification of the anaplastic subtype.</p>\u0000 </div>","PeriodicalId":11349,"journal":{"name":"Diagnostic Cytopathology","volume":"53 12","pages":"E231-E234"},"PeriodicalIF":1.0,"publicationDate":"2025-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144946820","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Kei Tanaka, Kris Lami, Takuma Odate, Takashi Hori, Tsubasa Sato, Ethan N. Okoshi, Junya Fukuoka
Background
For applications of digital pathology in cytology, challenges such as focal precision and data volume remain. The goals of this validation study are to compare diagnostic accuracy, screening time, annotation counts, and inter- and intra-observer agreement between digital slides using Z-stack scanning (z-WSI) and conventional glass slides in liquid-based cervical cytology (LBC).
Methods
We collected 91 LBC samples, with an equal number of NILM, LSIL, HSIL, and SCC cases. Four cytotechnologists evaluated cases using glass slides and z-WSI separately. They classified cases under two separate schemas: (1) “Screening-2-Category”: NILM (normal) vs. other lesions (ASC-US and above); and (2) “Morpho-3-Category”: NILM vs. LSIL (mild dysplasia) vs. ASC-H and higher (moderate dysplasia to squamous cell carcinoma) to reflect lesion severity and treatment implications.
Results
For Screening-2-Category classifications, inter-observer agreement was 0.685 for glass slides and 0.637 for z-WSI, with intra-observer agreement ranging from 82.4% to 95.6%. For Morpho-3-Category classifications, inter-observer agreement was 0.700 for glass slides and 0.598 for z-WSI, indicating reduced agreement with z-WSI. Accuracy was 91.2% (glass slides) and 87.1% (z-WSI) for Screening-2-Category, and 86.5% and 81.0% for Morpho-3-Category, with no significant differences. In both modalities, cytotechnologists tended to apply more annotations in true positive cases but fewer in false negative cases. Screening time for z-WSI was 2–5 min longer on average for all cytotechnologists.
Conclusion
z-WSI is not completely equivalent to glass slides, but it has the potential to be used as a tool for cytology screening. Training specifically designed for WSI is expected to enhance diagnostic accuracy and improve workflow efficiency.
背景：对于数字病理学在细胞学中的应用，诸如焦点精度和数据量等挑战仍然存在。本验证研究的目的是比较在宫颈细胞学（LBC）中使用z-叠扫描（z-WSI）的数字载玻片与传统玻璃载玻片之间的诊断准确性、筛查时间、注释计数以及观察者之间和观察者内部的一致性。方法：我们收集了91例LBC样本，其中NILM， LSIL， HSIL和SCC病例数量相等。四名细胞技术专家分别使用玻片和z-WSI对病例进行评估。他们根据两种不同的模式对病例进行分类：(1)“筛查-2-类别”：NILM（正常）与其他病变（ASC-US及以上）；(2)“morphoo -3- category”：NILM vs. LSIL（轻度发育不良）vs. ASC-H及更高（中度发育不良至鳞状细胞癌），以反映病变严重程度和治疗意义。结果：对于筛选2类分类，玻片的观察者间一致性为0.685，z-WSI的观察者间一致性为0.637，观察者内一致性为82.4%至95.6%。对于Morpho-3-Category分类，玻片的观察者间一致性为0.700，z-WSI为0.598，表明与z-WSI的一致性降低。筛选2类准确率分别为91.2%（玻片）和87.1% (z-WSI)，形态3类准确率分别为86.5%和81.0%，差异无统计学意义。在这两种模式中，细胞技术学家倾向于在真阳性病例中应用更多的注释，而在假阴性病例中应用较少。所有细胞技术人员的z-WSI筛查时间平均延长2-5分钟。结论：z-WSI并不完全等同于玻片，但它具有作为细胞学筛查工具的潜力。专门为WSI设计的培训有望提高诊断的准确性，提高工作流程的效率。
{"title":"Cytology Screening Using Z-Stack Digital Slides: A Validation Study","authors":"Kei Tanaka, Kris Lami, Takuma Odate, Takashi Hori, Tsubasa Sato, Ethan N. Okoshi, Junya Fukuoka","doi":"10.1002/dc.70015","DOIUrl":"10.1002/dc.70015","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>For applications of digital pathology in cytology, challenges such as focal precision and data volume remain. The goals of this validation study are to compare diagnostic accuracy, screening time, annotation counts, and inter- and intra-observer agreement between digital slides using Z-stack scanning (z-WSI) and conventional glass slides in liquid-based cervical cytology (LBC).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We collected 91 LBC samples, with an equal number of NILM, LSIL, HSIL, and SCC cases. Four cytotechnologists evaluated cases using glass slides and z-WSI separately. They classified cases under two separate schemas: (1) “Screening-2-Category”: NILM (normal) vs. other lesions (ASC-US and above); and (2) “Morpho-3-Category”: NILM vs. LSIL (mild dysplasia) vs. ASC-H and higher (moderate dysplasia to squamous cell carcinoma) to reflect lesion severity and treatment implications.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>For Screening-2-Category classifications, inter-observer agreement was 0.685 for glass slides and 0.637 for z-WSI, with intra-observer agreement ranging from 82.4% to 95.6%. For Morpho-3-Category classifications, inter-observer agreement was 0.700 for glass slides and 0.598 for z-WSI, indicating reduced agreement with z-WSI. Accuracy was 91.2% (glass slides) and 87.1% (z-WSI) for Screening-2-Category, and 86.5% and 81.0% for Morpho-3-Category, with no significant differences. In both modalities, cytotechnologists tended to apply more annotations in true positive cases but fewer in false negative cases. Screening time for z-WSI was 2–5 min longer on average for all cytotechnologists.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>z-WSI is not completely equivalent to glass slides, but it has the potential to be used as a tool for cytology screening. Training specifically designed for WSI is expected to enhance diagnostic accuracy and improve workflow efficiency.</p>\u0000 </section>\u0000 </div>","PeriodicalId":11349,"journal":{"name":"Diagnostic Cytopathology","volume":"53 11","pages":"568-575"},"PeriodicalIF":1.0,"publicationDate":"2025-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144946797","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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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