Aida Molero, Pilar Ortega de la Obra, Mónica Mate, Purificación Manzanares
{"title":"Validation of the Idylla KRAS Mutation Test on Fine-Needle Aspiration Needle Rinses in Saline and Cytolyt Solution Without DNA Extraction: A Comparison With Paired FFPE Tumor Samples.","authors":"Aida Molero, Pilar Ortega de la Obra, Mónica Mate, Purificación Manzanares","doi":"10.1002/dc.70039","DOIUrl":"https://doi.org/10.1002/dc.70039","url":null,"abstract":"<p><p>Molecular testing on FNA rinses offers a simple, minimally invasive, and cost-effective alternative to tissue biopsies. Among clinically relevant biomarkers, KRAS mutations are key in guiding targeted therapy across several cancer types. The fully automated Idylla platform provides rapid analysis directly from FFPE samples, without DNA extraction. In this study, we assessed the feasibility of applying the Idylla KRAS Mutation Test to FNA needle rinses collected in saline and Cytolyt. We analyzed 30 FNA rinses from resection specimens of 27 colorectal adenocarcinomas and three pancreatic adenocarcinomas (simulated FNAs). All 30 rinses were collected in saline, and 18 were additionally collected in Cytolyt without Preservcyt transfer. After cytospin preparation to assess cellularity and tumor percentage, the rinse was centrifuged at 2500 rpm for 5 min to obtain a pellet. A 50 μL aliquot of the pellet was directly loaded into the Idylla cartridge. Results from all rinses were compared with the Idylla KRAS Mutation Test on the corresponding FFPE tumor tissue. KRAS mutations were consistently detected in FNA rinses, with no false negatives or false positives observed. A single case, a saline rinse, was misclassified by the automated variant caller (reported as Q61K instead of the true G12D). However, amplification curve review confirmed a clear G12D, while the Q61K signal was aberrant. The Idylla KRAS Mutation Test can be reliably applied to FNA needle rinses in both saline and Cytolyt, yielding robust results in samples with high tumor content. Nevertheless, careful review of amplification curve patterns is essential in this setting.</p>","PeriodicalId":11349,"journal":{"name":"Diagnostic Cytopathology","volume":" ","pages":""},"PeriodicalIF":1.0,"publicationDate":"2025-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145367576","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":"Peritoneal Metastatic Lobular Breast Carcinoma Cells Masquerading in Atypical Hyperplastic Mesothelial Cell Clusters: Pitfalls Mitigated by Cellblock Immunocytochemistry.","authors":"Badr AbdullGaffar, Tasnim Keloth, Zulfiqar Ahmad","doi":"10.1002/dc.70040","DOIUrl":"https://doi.org/10.1002/dc.70040","url":null,"abstract":"<p><p>Metastatic lobular carcinoma of the breast in serous effusions is diagnostically challenging because the tumor cells simulate histiocytes and mesothelial cells. The typical metastatic pattern is isolated dispersed tumor cells which are unrelated to surrounding mesothelial cells. Metastatic deposits of lobular carcinoma cells within mesothelial cell clusters have not been previously reported. We report our findings of peritoneal metastatic lobular breast carcinoma cells masquerading in atypical hyperplastic mesothelial cell clusters found in cellblock sections, but were not present in ThinPrep slides. Three patients out of 10 patients diagnosed with breast lobular carcinoma showed infrequent large atypical cell clusters in cellblock sections. They were not identified in ThinPrep slides which showed chronic lymphohistiocytic inflammatory hemorrhagic effusion fluids, that initially were reported as negative for malignant cells and disregarded as mixed inflammatory infiltrates of lymphocytes, plasma cells and histiocytes. However, cellblock sections showed occasional large cell clusters that were confused with atypical mesothelial cell clusters and metastatic adenocarcinoma. Cellblock immunocytochemistry showed peculiar staining patterns. BerEP3 and CEA showed scattered single mononuclear epithelial cells intimately dispersed within WT1 and calretinin-positive mesothelial cell clusters. An extended panel showed intramesothelial epithelial tumor cells expressing GATA3, but were negative for TTF1, Napsin-A, PAX8, CDX2. The tumor cells also expressed ER and mammaglobin. They did not express E-cadherin. The cytologic diagnosis was metastatic lobular carcinoma of the breast. This was confirmed by breast core needle biopsies. Because this phenomenon is not always apparent in ThinPrep slides, cellblock sections supplemented with immunocytochemistry are a valuable diagnostic tool. The remaining seven patients showed the usual dispersed patterns of metastatic lobular carcinoma in ThinPrep slides and cellblock sections in pleural and peritoneal effusions.</p>","PeriodicalId":11349,"journal":{"name":"Diagnostic Cytopathology","volume":" ","pages":""},"PeriodicalIF":1.0,"publicationDate":"2025-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145353742","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":"Performance of Two-Tiered Subclassification of Atypia of Undetermined Significance in Thyroid Fine-Needle Aspiration Without Routine Molecular Testing.","authors":"Pocholo D Santos, Chiung-Ru Lai, Jen-Fan Hang","doi":"10.1002/dc.70034","DOIUrl":"https://doi.org/10.1002/dc.70034","url":null,"abstract":"<p><strong>Background: </strong>The third edition of the Bethesda system for reporting thyroid cytopathology recommends a simplified two-tiered subclassification of atypia of undetermined significance (AUS), dividing cases into AUS with nuclear atypia (AUS-Nuclear) and other atypia (AUS-Other). This study aims to evaluate the performance of these subcategories in estimating the risk of malignancy (ROM) in a setting without routine molecular testing.</p><p><strong>Methods: </strong>A retrospective review was conducted on consecutive thyroid fine-needle aspiration (FNA) cases diagnosed as AUS between 2018 and 2023. Surgical pathology reports were matched with the FNA-targeted nodules to enable cyto-histologic correlation. ROM and risk of neoplasm (RON) were calculated for all AUS cases and for each subcategory.</p><p><strong>Results: </strong>Among 16,030 thyroid FNA cases, 617 (3.8%) were diagnosed as AUS. Histologic follow-up was available in 190 cases. Final diagnoses included non-neoplastic lesions (42.6%), benign neoplasms (17.4%), low-risk neoplasms (5.3%), and malignant neoplasms (34.7%). The ROM for AUS-Nuclear was significantly higher at 54.7%, compared to 14.7% for AUS-Other (p < 0.001). Similarly, the RON was significantly higher in the AUS-Nuclear group (67.4%) than in the AUS-Other group (47.4%) (p = 0.005).</p><p><strong>Conclusion: </strong>AUS-Nuclear carries a substantially higher ROM than AUS-Other, with a ROM (54.7%) comparable to the reported positive predictive values of molecular assays such as Afirma GSC (47%, 95% CI: 36%-58%) and ThyroSeq v3 (66%, 95% CI: 56%-75%). These findings support the clinical utility of the two-tiered AUS subclassification in enhancing risk stratification, particularly in settings where molecular testing is not routinely available.</p>","PeriodicalId":11349,"journal":{"name":"Diagnostic Cytopathology","volume":" ","pages":""},"PeriodicalIF":1.0,"publicationDate":"2025-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145344072","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":"Dr. Leena Krogerus: A Grand Old Lady of the Finnish Cytopathology and My Cytopathology Mum.","authors":"Ivana Kholová","doi":"10.1002/dc.70036","DOIUrl":"https://doi.org/10.1002/dc.70036","url":null,"abstract":"<p><p>The communication introduces former President of the Finnish Society of Clinical Cytology and organizer of the European Congress of Cytology in Rovaniemi, Dr. Leena Krogerus. She played an important role in the formation of my cytopathology career as she led my path in cytopathology education, research, and leadership.</p>","PeriodicalId":11349,"journal":{"name":"Diagnostic Cytopathology","volume":" ","pages":""},"PeriodicalIF":1.0,"publicationDate":"2025-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145336664","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}
Havva Gokce Terzioglu, Alessa Aragao, Julieta E Barroeta
{"title":"\"Atypical Glandular Cells\" on Cervical Cytology: Correlation Between Glandular Cell Component Volume and Histological Follow-Up.","authors":"Havva Gokce Terzioglu, Alessa Aragao, Julieta E Barroeta","doi":"10.1002/dc.70033","DOIUrl":"https://doi.org/10.1002/dc.70033","url":null,"abstract":"<p><strong>Background: </strong>Atypical glandular cells (AGC) in cervical cytology, as defined by the Bethesda System, indicate nuclear atypia beyond reactive changes but without definitive features of malignancy. Although clinically significant because it prompts follow-up procedures, no quantitative threshold exists for AGC diagnosis. This study evaluated whether the volume of glandular cell clusters (GCC), regardless of atypia, influences AGC interpretation and may contribute to unnecessary sampling.</p><p><strong>Methods: </strong>Following IRB approval, all cervical cytology cases diagnosed as AGC between January 2014 and June 2024 were retrieved, along with 100 random negative for intraepithelial lesion or malignancy (NILM) cases, and were manually re-screened with quantification of glandular cell clusters (GCC) defined as a group of ≥ 6 cohesive glandular cells irrespective of origin (endocervical versus endometrial) and the results were correlated with follow-up findings including endocervical and endometrial sampling.</p><p><strong>Results: </strong>Of 301 AGC cases, 186 cases had slides available for review and follow-up data; two were excluded due to unsatisfactory quality. Eight cases were reclassified as unsatisfactory because of insufficient squamous cells and absence of atypia, most of which exhibited high GCC (mean 59). Notably, 140 cases (76.6%) showed no significant glandular pathology on follow-up, and in 111 cases (60.6%) the follow-up was negative. Overall, increased GCC correlated significantly with AGC interpretation compared to NILM cases (p = 0.01), even when histologic follow-up was negative.</p><p><strong>Conclusion: </strong>Higher GCC volumes may influence AGC diagnoses, even in cases lacking true cytologic atypia, potentially leading to unnecessary interventions. Greater awareness of this tendency and adherence to established cytologic criteria may improve diagnostic precision within the AGC category.</p>","PeriodicalId":11349,"journal":{"name":"Diagnostic Cytopathology","volume":" ","pages":""},"PeriodicalIF":1.0,"publicationDate":"2025-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145328417","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":"Primary Synovial Sarcoma of the Parotid Gland: A Diagnostic Challenge With Cyto-Histological Correlation and Review of Literature.","authors":"Chayasmita Mali, Naveen Kumar Ramachandran, Yookarin Khonglah, Biswajit Dey, Donboklang Lynser, Vandana Raphael, Sumanta Das","doi":"10.1002/dc.70035","DOIUrl":"https://doi.org/10.1002/dc.70035","url":null,"abstract":"<p><p>Synovial sarcoma is a malignant mesenchymal tumor of uncertain histogenesis that most commonly affects young adults' distal extremities, with the parotid being a very uncommon site. With fewer than 50 cases being reported in the literature and morphological similarities to many benign and malignant parotid lesions, it is challenging to diagnose this lesion. We report a 30-year-old female who presented with a rapidly enlarging, painful mass in the left parotid region with facial nerve palsy. The initial FNAC performed outside was interpreted as a pleomorphic adenoma. Repeat FNAC at our institution revealed a cellular spindle cell neoplasm with raised mitotic activity, suggesting a malignant spindle cell tumor. Histological features from trucut biopsy showed a highly cellular cell tumor comprising tumor cell arrangement in a predominantly fascicular pattern with positive immunostaining for EMA and BCL2, with negative myogenic, melanocytic, neural, and myoepithelial markers. Considering synovial sarcoma as our top differential diagnosis, fluorescence in situ hybridization (FISH) was performed using the SS18 dual color break-apart probe. FISH revealed SS18 break-apart in 60% of tumor cell nuclei, establishing the diagnosis of synovial sarcoma. Given its treatment consequences, which include surgery with post-operative radiotherapy and chemotherapy, it is imperative to identify this entity at an early stage, even though the prognosis is still uncertain. This case highlights the importance of a multimodal strategy incorporating cytology, histology, and molecular for definite diagnosis and patient management.</p>","PeriodicalId":11349,"journal":{"name":"Diagnostic Cytopathology","volume":" ","pages":""},"PeriodicalIF":1.0,"publicationDate":"2025-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145312561","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}
Sofia Veríssimo Pedrosa, João Almeida, Helena Barroca
{"title":"Cytomorphology Subtypes of the Salivary Gland Neoplasm of Unknown Malignant Potential (SUMP) Category in the Milan System and Histologic Correlation.","authors":"Sofia Veríssimo Pedrosa, João Almeida, Helena Barroca","doi":"10.1002/dc.70037","DOIUrl":"https://doi.org/10.1002/dc.70037","url":null,"abstract":"<p><strong>Introduction: </strong>The Milan System for Reporting Salivary Gland Cytopathology (MSRSGC) offers a reliable framework for stratifying malignancy risk of salivary gland lesions. Salivary gland neoplasms of uncertain malignant potential (SUMP) are a heterogeneous group of lesions displaying neoplastic characteristics that cannot be definitively categorized as benign or malignant. This study evaluates the cytomorphologic characteristics of SUMP cases at our institution and correlates them with final histopathological outcomes.</p><p><strong>Material and methods: </strong>A retrospective review of all SUMP cases diagnosed in our department from January 2018 to October 2024 was conducted. Cytology slides available were re-examined by three experienced cytopathologists and categorized into four subgroups based on key cytomorphologic features: (1) basaloid, (2) oncocytic, (3) clear cell, and (4) mixed features. Surgical follow-up diagnoses performed at our institution were collected.</p><p><strong>Results: </strong>From a total of 495 salivary gland FNA specimens, 39 (7.9%) were initially diagnosed as SUMP. After reassessment, 35 cases of SUMP were confirmed, and 27 had surgical follow-up. The overall risk of a neoplastic lesion was 92.5%, with a malignancy risk of 18.5%. The subgroup with clear cell features exhibited the highest risk of malignancy, at 66.7%, while the oncocytic/oncocytoid and basaloid subgroups showed low malignancy risk (up to 10%).</p><p><strong>Discussion and conclusion: </strong>This study supports the subclassification of SUMP lesions based on key cytomorphologic features, as it aids in refining the risk assessment and management of these ambiguous lesions. The identification of high-risk groups can help guide clinical decisions regarding follow-up.</p>","PeriodicalId":11349,"journal":{"name":"Diagnostic Cytopathology","volume":" ","pages":""},"PeriodicalIF":1.0,"publicationDate":"2025-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145312565","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":"Clinical Utility and Limitations of Ultrasound-Guided Axillary Lymph Node Fine-Needle Aspiration Cytology in Breast Cancer Management.","authors":"Aoi Morishita, Tomoyuki Shimada","doi":"10.1002/dc.70032","DOIUrl":"https://doi.org/10.1002/dc.70032","url":null,"abstract":"<p><strong>Background: </strong>Accurate axillary staging is critical for selecting appropriate treatment strategies in breast cancer. Ultrasound (US) and ultrasound-guided fine-needle aspiration cytology (US + FNAC) are widely used to evaluate axillary lymph nodes. The study assessed the diagnostic accuracy of US and US + FNAC and examined whether axillary dissection (AD) is necessary in patients with positive US + FNAC findings.</p><p><strong>Methods: </strong>We analyzed 646 axillae from 642 breast cancer patients who underwent surgery at Hiraka General Hospital between 2013 and 2024. All patients underwent axillary US, and US + FNAC was performed on morphologically suspicious nodes. Sensitivity, specificity, PPV, and NPV of US and US + FNAC were determined using postoperative pathology as the reference standard. The number of nodal metastases was compared between patients undergoing primary surgery and those receiving primary systemic therapy (PST).</p><p><strong>Results: </strong>In the primary surgery group (n = 516), US sensitivity, specificity, PPV, and NPV were 30.9% (38/123), 94.1% (370/393), 62.3% (38/61), and 81.3% (370/455), respectively. Corresponding values for US + FNAC were 80.6% (29/36), 100% (22/22), 100% (29/29), and 75.9% (22/29). US + FNAC showed significantly higher sensitivity and PPV than US alone. Among US + FNAC-positive cases, 55.2% (16/29) had ≥ 3 metastatic nodes, compared with 6.9% (2/29) of negative cases. In the PST group (n = 130), US sensitivity was ≤ 88.1% (37/42), and US + FNAC sensitivity was ≤ 92.6% (25/27). Of the 46 US + FNAC-positive patients, 45.7% (21/46) became node-negative after PST, whereas 26.1% (12/46) had ≥ 3 positive nodes.</p><p><strong>Conclusion: </strong>US + FNAC improves diagnostic accuracy for axillary staging; however, standard AD may constitute overtreatment in some FNAC-positive patients. Selective de-escalation of axillary surgery should therefore be considered.</p>","PeriodicalId":11349,"journal":{"name":"Diagnostic Cytopathology","volume":" ","pages":""},"PeriodicalIF":1.0,"publicationDate":"2025-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145299205","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}
Ambili R Nath, Sonia Mary Thomas, Betsy Jose, Lillykutty Pothen, Jessy Mathew Mangalathil
{"title":"High-Grade Non-Hodgkin Lymphoma, Diffuse Large B-Cell Lymphoma Type Masquerading as Thyroid Malignancy and Inflammatory Breast Carcinoma: A Case Report.","authors":"Ambili R Nath, Sonia Mary Thomas, Betsy Jose, Lillykutty Pothen, Jessy Mathew Mangalathil","doi":"10.1002/dc.70030","DOIUrl":"https://doi.org/10.1002/dc.70030","url":null,"abstract":"<p><p>This case report describes a 75-year-old female who presented with generalized tiredness and neck swelling, initially raising suspicion of a primary thyroid malignancy. Fine-needle aspiration of the thyroid nodule was suspicious for malignancy (Bethesda Category V). Further evaluation revealed an inflammatory mass lesion in the right breast which was clinically diagnosed as inflammatory carcinoma and multiple enlarged lymph nodes including axillary, cervical, supraclavicular, and inguinal nodes. Immunocytochemistry on fine needle aspiration cytology (FNAC) and biopsies and immunohistochemistry of the breast lesion and lymph nodes in the patient ultimately revealed disseminated High-Grade Non-Hodgkin Lymphoma (NHL), Diffuse Large B-Cell Lymphoma (DLBCL) type. This case highlights the diagnostic challenges linked to atypical presentations of lymphoma mimicking other primary malignancies of solid organs.</p>","PeriodicalId":11349,"journal":{"name":"Diagnostic Cytopathology","volume":" ","pages":""},"PeriodicalIF":1.0,"publicationDate":"2025-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145291483","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}
Emily Wheeler, Jennifer Kernodle-Zimmer, Melissa Randolph, Harvey Cramer, Hector Mesa
{"title":"Reproducibility and Diagnostic Utility of a Simplified Oil Red O Test in Infant Bronchoalveolar Lavage Samples.","authors":"Emily Wheeler, Jennifer Kernodle-Zimmer, Melissa Randolph, Harvey Cramer, Hector Mesa","doi":"10.1002/dc.70031","DOIUrl":"https://doi.org/10.1002/dc.70031","url":null,"abstract":"<p><strong>Introduction: </strong>Aspiration in infants is a diagnostic challenge. The lipid-laden macrophage index (LLMI) developed in 1987 has been used as a supportive test; however, numerous recent studies have questioned its value and reproducibility. We evaluated a simplified LLMI in bronchoalveolar lavage (BAL) specimens from a pediatric cohort to assess its diagnostic utility.</p><p><strong>Methods: </strong>BALs from infants were prospectively collected over a 6-month period for Oil Red O (ORO) staining to evaluate aspiration. BALs from adults with non-aspiration pathologies were simultaneously collected for comparison. Clinical and demographic data were gathered to assess the diagnostic accuracy of the test. Only samples containing ≥ 100 evaluable macrophages and free of obscuring blood or inflammation were included. Positive staining was assessed at low magnification (10×), with only clearly positive cells (Colombo-Hallberg scores 3 and 4) considered. A dichotomous threshold of < 50% or ≥ 50% positive macrophages was established through multidisciplinary consensus. To ensure consistency, a training session was conducted for the entire cytopathology division on the newly developed interpretation criteria.</p><p><strong>Results: </strong>88/134 (66%) pediatric BAL samples with suspected aspiration and 63/75 (84%) adult samples with various non-aspiration pathologies were adequate for analysis. Aspiration status in children was determined using multidisciplinary aerodigestive group evaluation (MAGE) and videofluoroscopic swallow study (VFSS). Test performance was assessed at various cutoffs. In the pediatric cohort (mean age 16.5 months, 58% male), aspiration was diagnosed in 47% by MAGE. Strong associations were seen with atopia/asthma (83%), functional dysphagia (64%), and congenital/developmental disorders (43%). A significant difference in ≥ 50% lipid-laden macrophage involvement was observed between pediatric (12%) and adult (51%) samples (p < 0.00001). Using MAGE and VFSS as gold standards, the test showed poor discriminatory power for detecting aspiration in infants (AUC 0.506-0.587). A 10% cutoff yielded the best performance (AUC 0.587, sensitivity 27%, specificity 93%), while a 50% cutoff offered practical advantages in workflow and reproducibility.</p><p><strong>Conclusions: </strong>The modified LLMI demonstrates limited diagnostic value for aspiration in infants. While a 10% cutoff offers slightly improved performance, the test may be phased out in favor of more reliable diagnostic methods.</p>","PeriodicalId":11349,"journal":{"name":"Diagnostic Cytopathology","volume":" ","pages":""},"PeriodicalIF":1.0,"publicationDate":"2025-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145279204","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}