Ruimeng Yang, Harsimar Kaur, Minhua Wang, Xi Wang, Xuchen Zhang, Guoping Cai
{"title":"Claudin 18.2 Expression Concordance in Paired Cytology and Surgical Specimens of Gastric and Gastroesophageal Junction Adenocarcinomas.","authors":"Ruimeng Yang, Harsimar Kaur, Minhua Wang, Xi Wang, Xuchen Zhang, Guoping Cai","doi":"10.5858/arpa.2025-0466-OA","DOIUrl":"10.5858/arpa.2025-0466-OA","url":null,"abstract":"<p><strong>Context.—: </strong>Claudin 18.2 (CLDN18.2) is a clinically actionable target in gastric and gastroesophageal junction adenocarcinomas, with patient selection guided by CLDN18.2 immunohistochemistry assay. While surgical specimens are standard for testing, the reliability of cytology specimens for CLDN18.2 assessment remains unclear.</p><p><strong>Objective.—: </strong>To assess the concordance of CLDN18.2 expression between cytology and surgical specimens and to explore the possible causes of discrepancy.</p><p><strong>Design.—: </strong>CLDN18.2 immunohistochemistry was performed on paired cytology and surgical specimens. The diagnostic performance at the cutoff of 75% or greater was evaluated across clinicopathologic variables.</p><p><strong>Results.—: </strong>Positive CLDN18.2 expression was seen in 35% (13 of 37) of surgical and 32% (12 of 37) of cytology cases. Overall, 86% (32 of 37) of pairs were concordant (either positive or negative). At the cutoff of 75% or greater, cytology achieved 77% sensitivity, 92% specificity, 83% positive predictive value, and 88% negative predictive value. Subgroup analysis showed that specimen origin was the strongest determinant of accuracy: concordance was greatest when both cytology and surgical specimens were obtained from gastric primary tumors, with perfect agreement (prevalence-adjusted, bias-adjusted κ [PABAK] = 1.00). In contrast, cases where one or both specimens were derived from metastatic sites showed lower agreement (PABAK = 0.68; bootstrap P < .01).</p><p><strong>Conclusions.—: </strong>Cytology specimens could serve as a reliable source for CLDN18.2 biomarker testing when interpreted at the threshold of 75% or above. Although discrepancies occur in some cases, the findings support the incorporation of cytology into biomarker testing workflows to expand access to CLDN18.2-targeted therapies for patients lacking surgical specimens.</p>","PeriodicalId":93883,"journal":{"name":"Archives of pathology & laboratory medicine","volume":" ","pages":"689-695"},"PeriodicalIF":3.2,"publicationDate":"2026-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147792047","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yongjung Park, Beom Jin Lim, John Hoon Rim, Sang-Guk Lee, Jeong-Ho Kim
{"title":"Diagnostic Utility of Dysmorphic Erythrocyte Identification Using the Atellica 1500 Automated Urinalysis System in the Evaluation of Glomerular Hematuria.","authors":"Yongjung Park, Beom Jin Lim, John Hoon Rim, Sang-Guk Lee, Jeong-Ho Kim","doi":"10.5858/arpa.2025-0396-OA","DOIUrl":"10.5858/arpa.2025-0396-OA","url":null,"abstract":"<p><strong>Context.—: </strong>Dysmorphic red blood cells (dRBCs) in urine are useful noninvasive markers for distinguishing glomerular hematuria.</p><p><strong>Objective.—: </strong>To assess the diagnostic utility of dRBC identification, using image data from the Atellica 1500 Automated Urinalysis System (Siemens Healthineers).</p><p><strong>Design.—: </strong>We retrospectively evaluated 162 patients from Severance Hospital (n = 46; August 2019-February 2024) and Yongin Severance Hospital (n = 116; between March 2020 and February 2024) who underwent renal, urinary, and/or urogenital biopsies during periods when the same Atellica 1500 Automated Urinalysis System was in use. dRBCs were evaluated by trained medical technologists following recent literature criteria. Inclusion requires hematuria (≥2+ on dipstick) and dRBC testing within 3 months before biopsy. From biopsy, imaging, and clinical findings, patients were classified as having glomerular hematuria (n = 90) or nonglomerular diseases (n = 72).</p><p><strong>Results.—: </strong>The area under the receiver operating characteristic curve (AUROC) for %dRBC in diagnosing glomerular disease was 0.766. At cutoffs of 17% and 28% dRBCs, sensitivity was 32.2% and 21.1% with specificity of 95.8% and 97.2%, respectively. %G1-dRBC yielded an AUROC of 0.636, with sensitivities of 31.1% and 26.7% at 1% and 2% cutoffs, respectively, for corresponding specificities. In immunoglobulin A nephropathy (n = 67), %G1-dRBC was higher in cases with segmental glomerulosclerosis (n = 53). Multivariate analysis identified that younger age, higher %dRBC, lower dipstick blood/leukocyte esterase, and higher dipstick protein grades were independent predictors of glomerular diseases.</p><p><strong>Conclusions.—: </strong>dRBC identification using digital urine sediment analyzer provides high specificity and positive predictive value for glomerular hematuria, with advantages in efficiency, reproducibility, and image archiving.</p>","PeriodicalId":93883,"journal":{"name":"Archives of pathology & laboratory medicine","volume":" ","pages":"722-728"},"PeriodicalIF":3.2,"publicationDate":"2026-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147791994","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Liam Scott, Julia Benanto, Charles J Robbins, Katherine Bates, Mengni He, Nay Nwe Nyein Chan, David L Rimm
{"title":"Temperature-Dependent Long-term and Short-term Stability of Human Epidermal Growth Factor Receptor 2 Antigenicity on Pathology Slides.","authors":"Liam Scott, Julia Benanto, Charles J Robbins, Katherine Bates, Mengni He, Nay Nwe Nyein Chan, David L Rimm","doi":"10.5858/arpa.2025-0447-OA","DOIUrl":"10.5858/arpa.2025-0447-OA","url":null,"abstract":"<p><strong>Context.—: </strong>Immunohistochemistry-based assessment of human epidermal growth factor receptor 2 (HER2) is increasingly useful for clinical decision-making in breast, gastroesophageal, and other cancers. Retroactive use of cancer tissue for research purposes is increasing alongside increased understanding of HER2's role in determining cancer outcomes. Best practices for formalin-fixed, paraffin-embedded (FFPE) tissue handling are addressed in guidelines for diagnostic and scientific activities; however, preanalytic variables arising after tissue embedding and sectioning are minimally discussed.</p><p><strong>Objective.—: </strong>To quantify the loss of HER2 antigenicity that occurs on sectioned FFPE slides over long- and short-term timescales, in both room-temperature and freezer conditions.</p><p><strong>Design.—: </strong>Surplus FFPE microarray slides from years-prior experiments, stored either at room temperature or in a -80°C freezer, were paired with block-matched, freshly cut slides for analysis of postsectioning epitope degradation. To evaluate short-term changes in epitope availability, a set of FFPE slides was serially stained by immunofluorescence during a 2-month period, using standardization to mass spectrometry values to enable standardized quantification of antigen in amol (attomoles)/mm2.</p><p><strong>Results.—: </strong>Significant degradation of HER2 antigen on FFPE slides occurs over a period of years when slides are stored at room temperature, but not when stored at -80°C. In either condition, the amount of degradation that occurs within a 2-month timescale is negligible compared to variation attributable to tumor heterogeneity and interrun variability.</p><p><strong>Conclusions.—: </strong>Room-temperature storage of FFPE slides appears to be safe for HER2 measurement when staining will occur within 2 months. The \"shelf life\" of slides stored at -80°C is at least 1 year.</p>","PeriodicalId":93883,"journal":{"name":"Archives of pathology & laboratory medicine","volume":" ","pages":"707-712"},"PeriodicalIF":3.2,"publicationDate":"2026-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147719258","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Mélissande Cossutta, Birgit Truumees, Alexandre Papine, Heidi Lykke Kristoffersen, Ekaterina Tatarinova, Lise Emanuelsen, Charles Homsy, Françoise Soussaline, Søren Nielsen
{"title":"Computer-Aided Quantitative Image Analysis of Multiple Human Epidermal Growth Factor Receptor 2 Immunohistochemistry Assays in Breast Carcinoma.","authors":"Mélissande Cossutta, Birgit Truumees, Alexandre Papine, Heidi Lykke Kristoffersen, Ekaterina Tatarinova, Lise Emanuelsen, Charles Homsy, Françoise Soussaline, Søren Nielsen","doi":"10.5858/arpa.2025-0316-OA","DOIUrl":"10.5858/arpa.2025-0316-OA","url":null,"abstract":"<p><strong>Context.—: </strong>Quantitative image analysis (QIA) is increasingly applied for immunohistochemistry (IHC)-based biomarker assessment in pathology. With the introduction of drugs targeting breast carcinomas (BCs) with low human epidermal growth factor receptor 2 (HER2) expression levels, a need for more accurate and reproducible HER2 scoring is warranted. QIA has the potential to increase HER2 IHC scoring reproducibility. However, QIA reproducibility should be agnostic and uninfluenced by different IHC assays.</p><p><strong>Objective.—: </strong>To compare HER2 scoring accuracy and reproducibility by expert pathologists and QIA in BCs analyzed with different IHC assays.</p><p><strong>Design.—: </strong>Algorithm parameters of the QIA method were developed by using 183 slides from 6 Nordic immunohistochemical Quality Control (NordiQC) HER2 runs. The QIA method was then validated on 409 slides from 2 other runs. HER2 scores obtained by visual scoring, following 2023 European Society for Medical Oncology and American Society of Clinical Oncology/College of American Pathologists guidelines or by QIA, were compared.</p><p><strong>Results.—: </strong>Visual scoring and QIA reached 86% (κ = 0.81) overall scoring agreement for tissue cores in the final validation material. QIA showed 98% (95% CI, 97.8%-99.0%) sensitivity and 84% (95% CI, 80.3%-87.6%) specificity for the distinction between HER2 0 (no drug candidate) and HER2 1-3+ (drug candidates) scores. Ninety-nine percent (95% CI, 98.7%-99.9%) sensitivity and 100% (95% CI, 99.8%-100%) specificity were obtained for the separation between HER2 2-3+ in situ hybridization (ISH)-positive cores (HER2 classical overexpression) and HER2 0-2+ ISH-negative cores (HER2-low expression range).</p><p><strong>Conclusions.—: </strong>Our QIA method can be beneficial to use as a reliable HER2 scoring tool for HER2 classical overexpression and HER2-low in BCs. It was found to be agnostic and provided same accuracy irrespective of IHC assay applied.</p>","PeriodicalId":93883,"journal":{"name":"Archives of pathology & laboratory medicine","volume":" ","pages":"610-619"},"PeriodicalIF":3.2,"publicationDate":"2026-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147694167","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Total Versus Ionized Calcium: Valid Index of Calcium Status in Critically Ill Patients.","authors":"Madhumita Das, Argha Baruah","doi":"10.5858/arpa.2025-0488-OA","DOIUrl":"10.5858/arpa.2025-0488-OA","url":null,"abstract":"<p><strong>Context.—: </strong>Accurate evaluation of calcium status is essential in critically ill patients. However, reliance on total calcium (tCa) and albumin-corrected calcium often leads to misclassification, influencing clinical decisions.</p><p><strong>Objective.—: </strong>To compare various calcium measurement methods with ionized calcium (iCa), the gold standard, and evaluate their diagnostic and prognostic relevance in intensive care unit (ICU) patients.</p><p><strong>Design.—: </strong>A cross-sectional study was conducted for 1 year in 145 ICU patients at a tertiary care center. Measured parameters included tCa, iCa, albumin, total protein, and pH. Derived indices included albumin-corrected calcium (CtCa), calculated iCa (CiCa), pH-adjusted iCa (pHiCa), nonionized calcium (NiCa), and the iCa:CtCa ratio. Correlations, sensitivity/specificity, classification accuracy, and receiver operating characteristic (ROC) analyses were performed.</p><p><strong>Results.—: </strong>Abnormal iCa levels were observed in 82.07% (119 of 145) of patients, with hypercalcemia being rare. tCa, CtCa, CiCa, and NiCa significantly underestimated hypocalcemia when compared to iCa (P ≤ .01). Among methods, pHiCa showed the best diagnostic performance (95.2% accuracy; 86.3% sensitivity) and strongest correlation with iCa (r = 0.983). The iCa:CtCa ratio reflected physiological changes such as alkalosis and hypoalbuminemia, particularly in postoperative and septic patients. ROC analysis indicated poor prognostic value of iCa for prolonged ICU stay. The calculated areas under the curve for ICU stay and mortality were 0.51 and 0.54, respectively.</p><p><strong>Conclusions.—: </strong>Conventional calcium measurement methods frequently misclassify calcium status in critically ill patients. pHiCa demonstrated superior diagnostic accuracy and agreement with iCa. While iCa lacks prognostic utility for ICU outcomes, it remains indispensable for precise calcium assessment.</p>","PeriodicalId":93883,"journal":{"name":"Archives of pathology & laboratory medicine","volume":" ","pages":"729-735"},"PeriodicalIF":3.2,"publicationDate":"2026-04-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147694129","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Christoph Geisenberger, Solveig Kuss, Hans-Peter Horny, Susanna Müller
{"title":"Mast Cell Activation Syndrome: Quantification of Mast Cells Across Conditions Reveals Limited Diagnostic Utility of Mast Cell Counts and Tryptase Depletion Index.","authors":"Christoph Geisenberger, Solveig Kuss, Hans-Peter Horny, Susanna Müller","doi":"10.5858/arpa.2025-0007-OA","DOIUrl":"10.5858/arpa.2025-0007-OA","url":null,"abstract":"<p><strong>Context.—: </strong>Mast cell enumeration in gastrointestinal biopsies is commonly requested to diagnose mast cell activation syndrome (MCAS) or systemic mastocytosis (SM) with gastrointestinal (GI) involvement. However, mast cell numbers can be elevated in various disorders and quantities do not reflect functional states. A novel measure, the tryptase depletion index (TDI), was recently proposed as a surrogate measure for mediator release and mast cell activation.</p><p><strong>Objective.—: </strong>To evaluate the diagnostic utility of the TDI and mast cell counts for differentiating between MCAS, SM, and inflammatory disorders in GI biopsies.</p><p><strong>Design.—: </strong>GI biopsy samples from patients with SM or MCAS (n = 64), inflammatory disorders (n = 26), and healthy controls (n = 38) were examined. All sections were immunostained for c-Kit/CD117 and tryptase, and mast cells were quantified within the lamina propria. Testing for KIT D816V mutation and CD25 immunohistochemistry were performed for all cases with suspected SM or MCAS.</p><p><strong>Results.—: </strong>Infiltrates of atypical, CD25+ mast cells were confirmed in SM. Mast cell numbers were elevated in SM, MCAS, and inflammatory disorders as compared to healthy tissue. The TDI did not differ significantly among the groups, and fluctuations in TDI can be explained by measurement noise from counting performed on subsequent tissue sections. Receiver operating characteristic analysis showed low sensitivity and specificity for TDI or mast cell enumeration in diagnosing MCAS.</p><p><strong>Conclusions.—: </strong>While SM can be substantiated with markers such as CD25/CD30 or KIT mutations, counting mast cells appears of limited utility.</p>","PeriodicalId":93883,"journal":{"name":"Archives of pathology & laboratory medicine","volume":" ","pages":"637-644"},"PeriodicalIF":3.2,"publicationDate":"2026-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147694176","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Highly Skewed Immunohistochemical αβ:γδ Ratios for T-Cell Receptors Can Be Detected in Reactive Duodenal Biopsies: A Potential Pitfall in the Diagnosis of T-Cell Lymphoma.","authors":"George C de Castro, Gregory R Bean, Kwun Wah Wen","doi":"10.5858/arpa.2025-0446-OA","DOIUrl":"10.5858/arpa.2025-0446-OA","url":null,"abstract":"<p><strong>Context.—: </strong>T-cell receptors (TCRs) are classified as αβ- and γδ-chain groups. T-cell lymphoma (TCL) has been shown to express either αβ or γδ TCRs. Immunohistochemical stains for TCR-BetaF1 (TCR-BF1) (αβ) and TCR-delta (γδ) have been used clinically for classifying and diagnosing TCL in various organs. Outside of celiac disease, T-cell expression and distribution of TCR-BF1 and TCR-delta in the duodenum are largely unknown.</p><p><strong>Objective.—: </strong>To examine TCR-BF1 and TCR-delta expression in various duodenal pathologic processes.</p><p><strong>Design.—: </strong>We collected 50 duodenal biopsy specimens with various inflammatory and infectious etiologies, such as celiac disease, inflammatory bowel disease, protein-losing enteropathy, chimeric antigen receptor T-cell (CAR-T)-related enteritis, and immune checkpoint inhibition. Five cases with no pathologic findings and 3 TCL cases were included for comparison. We performed immunohistochemistry for CD3, TCR-BF1, and TCR-delta on biopsy tissue. Low-power field estimates and manual high-power field counts were performed to assess TCR-BF1:TCR-delta ratios in T cells and the relative distribution of T cells in duodenal mucosa.</p><p><strong>Results.—: </strong>In all non-TCL cases, TCR-BF1 T cells were more prevalent than TCR-delta T cells. Celiac disease showed less TCR-BF1:TCR-delta skewing than other conditions (mean, 1.97 versus 26.21-320).</p><p><strong>Conclusions.—: </strong>Expression of TCR-BF1 is more prevalent than TCR-delta in duodenal T cells in normal duodenum and across multiple nonneoplastic processes. Outside of celiac disease, the TCR-BF1:TCR-delta T-cell ratios can be highly skewed toward TCR-BF1 in such duodenal biopsy samples. As such, the assessment of TCR-BF1:TCR-delta T-cell ratios via immunohistochemistry can mistakenly infer T-cell monoclonality and thus should be interpreted with caution in the assessment of T-cell lymphoma.</p>","PeriodicalId":93883,"journal":{"name":"Archives of pathology & laboratory medicine","volume":" ","pages":"652-656"},"PeriodicalIF":3.2,"publicationDate":"2026-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147640986","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Katherine Drews-Elger, Merce Jorda, Melissa Stedman, Sophie Egea, Elena F Brachtel, Susan B Kesmodel, Jose M Net, Monica M Yepes, Carmen Gomez-Fernandez
{"title":"The Doctor's Doctor Is the Patient's Doctor: A Pilot Quality Improvement Study on Patient-Pathologist Consultations at a Single Institution.","authors":"Katherine Drews-Elger, Merce Jorda, Melissa Stedman, Sophie Egea, Elena F Brachtel, Susan B Kesmodel, Jose M Net, Monica M Yepes, Carmen Gomez-Fernandez","doi":"10.5858/arpa.2025-0433-OA","DOIUrl":"10.5858/arpa.2025-0433-OA","url":null,"abstract":"<p><strong>Context.—: </strong>Pathologists have traditionally worked behind the scenes, providing diagnostic information to clinicians. The 21st Century Cures Act grants patients immediate access to pathology reports, creating opportunities and challenges for patient-pathologist communication.</p><p><strong>Objective.—: </strong>To evaluate the feasibility, acceptance, educational value, and perceived impact of telehealth-based, language-concordant patient-pathologist consultations for patients with breast biopsies across the full diagnostic spectrum.</p><p><strong>Design.—: </strong>Prospective, single-institution quality improvement pilot study at a tertiary care cancer center involving a breast pathologist, 2 breast radiologists, 1 breast surgeon, and 1 pathology resident. Patients undergoing a breast biopsy were offered an optional 30-minute telehealth consultation with a breast pathologist and a pathology resident to review their findings and biopsy slides in their preferred language (English or Spanish). Postconsultation surveys assessed patient perceptions. Encounters were documented in pathology reports and shared with referring physicians.</p><p><strong>Results.—: </strong>Forty-three patients were offered the consultation and more than half elected to participate. Consultations spanned benign, premalignant, and malignant diagnoses and were integrated without disrupting existing care pathways. Surveys indicated high patient satisfaction, improved understanding of pathology results, and reduced anxiety. Patients valued slide review and direct discussion with the diagnosing pathologist. Telehealth delivery and language concordance were well received. Resident participation was acceptable and supported educational goals.</p><p><strong>Conclusions.—: </strong>Telehealth-based, language-concordant patient-pathologist consultations in breast pathology are feasible, well accepted, and enhance patient understanding. This model integrates into routine workflows, supports trainee education, and warrants broader evaluation as a scalable, patient-centered approach to diagnostic care.</p>","PeriodicalId":93883,"journal":{"name":"Archives of pathology & laboratory medicine","volume":" ","pages":"713-721"},"PeriodicalIF":3.2,"publicationDate":"2026-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147640971","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Tumor Budding as a Histologic Prognostic Parameter in Oral Squamous Cell Carcinoma: Comparison of Scoring Systems and Rationale for the Use of Immunohistochemistry.","authors":"Akhila Gopakumar, Smriti Panda, Rajeev Kumar Malhotra, Chirom Amit Singh, Kavneet Kaur, Rajeev Kumar, Kapil Sikka, Alok Thakar, Aanchal Kakkar","doi":"10.5858/arpa.2025-0520-OA","DOIUrl":"10.5858/arpa.2025-0520-OA","url":null,"abstract":"<p><strong>Context.—: </strong>Tumor budding (TB) is associated with nodal metastasis and worse outcomes in oral squamous cell carcinoma. However, there is a need for standardization of its assessment.</p><p><strong>Objective.—: </strong>To perform TB scoring using 2-tiered and 3-tiered systems, with and without pancytokeratin (CK) immunohistochemistry, and assess relationship with outcome parameters.</p><p><strong>Design.—: </strong>Tumor buds were scored by using 2-tiered (low: <5; high: ≥5) and 3-tiered (low: 0-4; intermediate: 5-9; high: ≥10) systems on hematoxylin-eosin- and CK-stained sections.</p><p><strong>Results.—: </strong>TB was evaluated in 400 oral squamous cell carcinomas, which were predominantly gingivobuccal (242; 61%), had aggressive worst patterns of invasion (WPOI) (WPOI-4: 59%; WPOI-5: 27%), and were late stage (298; 75%). Two-year disease-free survival (DFS) was 56.3%, and 2-year overall survival (OS) was 58.7%. Using 3-tiered scoring, 220 cases (55%) had low, 101 (25%) had intermediate, and 79 (20%) had high TB. With 2-tiered scoring, 220 cases (55%) had low and 180 (45%) had high TB. Greater concordance was seen between hematoxylin-eosin- and CK-stained sections with 2-tiered scoring: 14% were up-scored versus 25% with 3-tiered scoring. Cases with high and intermediate TB had significantly shorter DFS and OS. TB on CK-stained sections scored by both systems was an independent predictor of nodal metastasis. With all 4 scoring models, high TB was an independent predictor of recurrence. All 4 models showed similar predictive values for OS and DFS.</p><p><strong>Conclusions.—: </strong>TB is a significant predictor of nodal metastasis and recurrence, irrespective of site and stage. Three-tiered scoring does not show improved prediction of outcomes over 2-tiered scoring.</p>","PeriodicalId":93883,"journal":{"name":"Archives of pathology & laboratory medicine","volume":" ","pages":"620-629"},"PeriodicalIF":3.2,"publicationDate":"2026-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147596976","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Embryonal Carcinoma Involving the Ovary: A Morphologic Study of 55 Tumors Almost Never Pure, But Common Within Malignant Mixed Germ Cell Tumors.","authors":"Valentina Zanfagnin, Esther Oliva, Robert H Young","doi":"10.5858/arpa.2025-0482-OA","DOIUrl":"10.5858/arpa.2025-0482-OA","url":null,"abstract":"<p><strong>Context.—: </strong>Embryonal carcinoma (ECA) of the ovary is rare, particularly in pure form, with very limited available information.</p><p><strong>Objective.—: </strong>To expand on knowledge by reviewing our experience.</p><p><strong>Design.—: </strong>We report 55 tumors with an ECA component in patients from ages 3 to 57 years (median, 20.5 years), with emphasis on their pathologic features.</p><p><strong>Results.—: </strong>The tumors ranged from 2.5 cm to 31 cm (average, 15.4 cm), being predominantly solid and cystic with hemorrhagic necrosis. In all cases, the ECA was a component of a malignant mixed germ cell tumor (MMGCT) and represented less than 15% in 22 tumors (40%), 16% to 50% in 22 (40%), 51% to 75% in 6 (11%), and greater than 75% in 5 (9%). Components admixed with the ECA included yolk sac tumor (n = 49; 89%), immature teratoma (n = 34; 62%), dysgerminoma (n = 20; 36%), and choriocarcinoma (n = 5; 9%). The most common microscopic patterns of the ECA were glandular (n = 24; 45%), solid (n = 19; 35%), papillary (n = 5; 9%), and micropapillary (n = 1; 2%). Embryoid bodies, or remnants thereof, were present in 16 tumors (29%), and 6 (11%) had a diffuse embryoma pattern. Apoptotic bodies were commonly found. A lymphocytic infiltrate and granulomas were seen in 25 tumors (45%) and in 4 tumors (7%).</p><p><strong>Conclusions.—: </strong>Pure ovarian ECA is rare; none were identified in our series. Many purported pure examples are likely undersampled MMGCTs or other tumor types (yolk sac tumor, dysgerminoma [particularly when poorly fixed], small cell carcinoma of hypercalcemic type, juvenile granulosa cell tumor, and high-grade surface epithelial carcinomas). The diagnosis can be made on the basis of morphologic criteria and, in problematic cases, supported by immunohistochemistry.</p>","PeriodicalId":93883,"journal":{"name":"Archives of pathology & laboratory medicine","volume":" ","pages":"595-602"},"PeriodicalIF":3.2,"publicationDate":"2026-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147522977","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}