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Use of Mitotic Activity and the Size of Any Dedifferentiated Component for Risk Assessment in MDM2-Amplified Liposarcoma. 利用有丝分裂活性和任何已分化成分的大小来评估 MDM2 扩增脂肪肉瘤的风险
Archives of pathology & laboratory medicine Pub Date : 2025-05-01 DOI: 10.5858/arpa.2024-0098-OA
Hao Wu, Madina Sukhanova, Haiming Tang, Xinyan Lu, Minghao Zhong, Hari Deshpande, Seth M Pollack, William B Laskin, Borislav A Alexiev
{"title":"Use of Mitotic Activity and the Size of Any Dedifferentiated Component for Risk Assessment in MDM2-Amplified Liposarcoma.","authors":"Hao Wu, Madina Sukhanova, Haiming Tang, Xinyan Lu, Minghao Zhong, Hari Deshpande, Seth M Pollack, William B Laskin, Borislav A Alexiev","doi":"10.5858/arpa.2024-0098-OA","DOIUrl":"10.5858/arpa.2024-0098-OA","url":null,"abstract":"<p><strong>Context.—: </strong>The characteristic molecular signature for both atypical lipomatous tumor/well-differentiated liposarcoma and dedifferentiated liposarcoma is amplified sequences derived from chromosome 12q13-15, including MDM2 proto-oncogene (MDM2). As the progression of atypical lipomatous tumor/well-differentiated liposarcoma to the more aggressive dedifferentiated liposarcoma has the potential to adversely affect patient outcomes, the extent of the latter component might be important to evaluate.</p><p><strong>Objective.—: </strong>To investigate the correlation between clinicopathologic characteristics, including tumor size, modified Fédération Nationale des Centres de Lutte Contre le Cancer (FNCLCC) grade, molecular data, and outcomes in 123 surgically resected MDM2-amplified liposarcomas.</p><p><strong>Design.—: </strong>Pathology reports and clinical records were reviewed. A log-rank test was used to compare the survival trends, and univariate logistic regression was performed to identify variables associated with adverse events (distant metastasis and/or death), from which the P value was derived to construct a multivariate regression model.</p><p><strong>Results.—: </strong>In univariate analysis, the largest single dimension of the dedifferentiated component, the percentage of cells with gain of chromosome 12, mitotic count, and the presence of modified FNCLLC grade 3 were associated with adverse events. In multivariate analysis, the largest single dimension of the dedifferentiated component (odds ratio: 1.169; 95% CI: 1.053, 1.299; P = .003), and a higher mitotic count (odds ratio: 1.133; 95% CI: 1.037, 1.237; P = .006) were correlated with adverse events. There was no statistically significant association between current local recurrence status, overall largest tumor dimension, overall tumor volume, MDM2 copy number, or MDM2 to chromosome 12 centromere probe ratio and adverse outcomes.</p><p><strong>Conclusions.—: </strong>Staging dedifferentiated liposarcoma based on the size of the dedifferentiated component better predicts the outcome.</p>","PeriodicalId":93883,"journal":{"name":"Archives of pathology & laboratory medicine","volume":" ","pages":"422-430"},"PeriodicalIF":0.0,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142010096","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}
引用次数: 0
A Bottom-Up Liquid Chromatography-Tandem Mass Spectrometry Method for Therapeutic Drug Monitoring of Infliximab: Method Development, Comparison With 2 Enzyme-Linked Immunosorbent Assay Methods, and Evaluation of Anti-Drug Antibody Interference. 用于英夫利西单抗治疗药物监测的自下而上液相色谱-串联质谱法:方法开发、与两种酶联免疫吸附测定法的比较以及抗药抗体干扰的评估。
Archives of pathology & laboratory medicine Pub Date : 2025-05-01 DOI: 10.5858/arpa.2023-0573-OA
Sang-Mi Kim, Hyeonju Oh, Sung Noh Hong, Mi Jin Kim, Yon Ho Choe, Soo-Youn Lee
{"title":"A Bottom-Up Liquid Chromatography-Tandem Mass Spectrometry Method for Therapeutic Drug Monitoring of Infliximab: Method Development, Comparison With 2 Enzyme-Linked Immunosorbent Assay Methods, and Evaluation of Anti-Drug Antibody Interference.","authors":"Sang-Mi Kim, Hyeonju Oh, Sung Noh Hong, Mi Jin Kim, Yon Ho Choe, Soo-Youn Lee","doi":"10.5858/arpa.2023-0573-OA","DOIUrl":"10.5858/arpa.2023-0573-OA","url":null,"abstract":"<p><strong>Context.—: </strong>Therapeutic drug monitoring is recommended to optimize infliximab use and improve outcome in chronic inflammatory disorders.</p><p><strong>Objective.—: </strong>To describe a simple and affordable liquid chromatography-tandem mass spectrometry (LC-MS/MS) method to measure infliximab in serum.</p><p><strong>Design.—: </strong>Infliximab was measured using winged stable isotope-labeled peptides as internal standards. Linearity, lower limit of measuring interval, limit of detection, precision, accuracy, carryover, and ion suppression were evaluated. Method comparison against 2 enzyme-linked immunosorbent assay (ELISA) methods (Remsima Monitor and IDKmonitor Infliximab) and anti-drug antibody (ADA) interference were evaluated using clinical specimens from inflammatory bowel disease patients (N = 237).</p><p><strong>Results.—: </strong>Analytical run time and sample preparation time were 5 minutes per sample and 3 hours per batch, respectively. Analytical measurement interval and limit of detection were 0.50 to 50.0 μg/mL (R2 = 0.998) and 0.25 μg/mL, respectively. The intraday and interday imprecision percentage coefficients of variation were less than 6.1%. Accuracy was 94.2% to 98.7%. No significant ion suppression or carryover was observed. Infliximab concentrations measured by LC-MS/MS showed good agreement with those measured by Remsima Monitor (mean percentage difference, 5.7%; 95% CI, -1.2% to 12.6%) but were markedly lower than those measured by IDKmonitor (-32.6%; -35.8% to -29.4%), demonstrating significant bias between ELISAs. Although a good agreement between LC-MS/MS and ELISA was observed for ADA-negative samples (-3.5%; -12.8% to 5.9%), a significant bias was observed for ADA-positive samples (13.6%; 1.7% to 25.6%).</p><p><strong>Conclusions.—: </strong>This simple, fast, and affordable LC-MS/MS method for infliximab quantitation could improve standardization of infliximab quantitation and optimization of infliximab use in patients with high-titer ADA.</p>","PeriodicalId":93883,"journal":{"name":"Archives of pathology & laboratory medicine","volume":" ","pages":"448-456"},"PeriodicalIF":0.0,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141749891","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}
引用次数: 0
Reported Awareness and Use of Pyridoxal-5'-Phosphate Supplementation in Alanine Aminotransferase and Aspartate Aminotransferase Assay Reagents: A Survey by the College of American Pathologists Clinical Chemistry Committee. 丙氨酸氨基转移酶和天冬氨酸氨基转移酶检测试剂中吡哆醛-5'-磷酸补充剂的认知和使用报告:美国病理学家学会临床化学委员会调查。
Archives of pathology & laboratory medicine Pub Date : 2025-05-01 DOI: 10.5858/arpa.2024-0097-CP
Allison B Chambliss, Rhona J Souers, Jonathan R Genzen, David M Manthei
{"title":"Reported Awareness and Use of Pyridoxal-5'-Phosphate Supplementation in Alanine Aminotransferase and Aspartate Aminotransferase Assay Reagents: A Survey by the College of American Pathologists Clinical Chemistry Committee.","authors":"Allison B Chambliss, Rhona J Souers, Jonathan R Genzen, David M Manthei","doi":"10.5858/arpa.2024-0097-CP","DOIUrl":"10.5858/arpa.2024-0097-CP","url":null,"abstract":"<p><strong>Context.—: </strong>Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) assay reagents are available both with and without supplementation with pyridoxal-5'-phosphate (P5P; the active form of vitamin B6), a catalytic cofactor required for their enzymatic reactions. Nonsupplemented assays may miss ALT or AST elevations in patients with vitamin B6 deficiency.</p><p><strong>Objective.—: </strong>To assess awareness and adoption of ALT and AST reagents that are supplemented with P5P.</p><p><strong>Design.—: </strong>A 4-question survey about ALT and AST reagent supplementation with P5P was included in the College of American Pathologists General Chemistry and Therapeutic Drugs (C program) proficiency testing 2023 B mailing.</p><p><strong>Results.—: </strong>Overall, 38% (1651 of 4304) of responding laboratories reported using ALT and/or AST reagent supplemented with P5P. P5P supplementation was more common for nonacademic hospital/medical center laboratories (44%; 713 of 1629) relative to other settings. Of the laboratories that reported not using P5P-supplemented reagents, few (5%; 141 of 2611) cited plans to convert in the future. Despite the availability of P5P-supplemented reagents from several major assay manufacturers, the most common stated barrier for adoption was that the laboratory's reagent manufacturer does not provide P5P-supplemented reagents.</p><p><strong>Conclusions.—: </strong>There is a lack of awareness of the existence and benefits of P5P-supplemented ALT and AST reagents. There is a need for ALT and AST assay manufacturers to clarify and standardize the P5P status of ALT and AST reagents.</p>","PeriodicalId":93883,"journal":{"name":"Archives of pathology & laboratory medicine","volume":" ","pages":"400-404"},"PeriodicalIF":0.0,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141763189","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}
引用次数: 0
In Reply. 在回答。
Archives of pathology & laboratory medicine Pub Date : 2025-05-01 DOI: 10.5858/arpa.2025-0003-LE
Xiao Li, Hongyu Xie, Xinyu Wang
{"title":"In Reply.","authors":"Xiao Li, Hongyu Xie, Xinyu Wang","doi":"10.5858/arpa.2025-0003-LE","DOIUrl":"https://doi.org/10.5858/arpa.2025-0003-LE","url":null,"abstract":"","PeriodicalId":93883,"journal":{"name":"Archives of pathology & laboratory medicine","volume":"149 5","pages":"395"},"PeriodicalIF":0.0,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144044679","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}
引用次数: 0
Machine Learning Classifier Using Blood Count Parameters and Erythropoietin to Predict JAK2 Mutations in Patients With Erythrocytosis. 使用血细胞计数参数和促红细胞生成素的机器学习分类器预测红细胞增多症患者的JAK2突变。
Archives of pathology & laboratory medicine Pub Date : 2025-04-28 DOI: 10.5858/arpa.2023-0262-OA
Ron B Schifman, Keri Donaldson, Daniel Luevano, Raul Benavides, Jeffery A Hunt
{"title":"Machine Learning Classifier Using Blood Count Parameters and Erythropoietin to Predict JAK2 Mutations in Patients With Erythrocytosis.","authors":"Ron B Schifman, Keri Donaldson, Daniel Luevano, Raul Benavides, Jeffery A Hunt","doi":"10.5858/arpa.2023-0262-OA","DOIUrl":"https://doi.org/10.5858/arpa.2023-0262-OA","url":null,"abstract":"<p><strong>Context.—: </strong>Differentiating polycythemia vera from other causes of erythrocytosis is a diagnostic challenge. Although most patients with polycythemia vera have Janus kinase 2 (JAK2) mutations, extensive testing is impractical because this is an uncommon cause of erythrocytosis. Identifying polycythemic patients most likely to benefit from JAK2 testing would improve use of this test.</p><p><strong>Objective.—: </strong>To develop an artificial intelligence analysis/machine learning classifier using blood count parameters and erythropoietin to predict JAK2 results in patients with erythrocytosis.</p><p><strong>Design.—: </strong>Results from the Veterans Affairs data warehouse were used for training and validation. Cases with JAK2 results and hemoglobin values 15 g/dL or higher and 17 g/dL or higher in females and males respectively were included. Erythropoietin was optional. The highest performing model was evaluated with an out-of-sample data set.</p><p><strong>Results.—: </strong>Among 31 models trained on data from 8479 individuals, including 540 (6.4%) positive for JAK2, Light Gradient Boosted Trees Classifier performed best. When applied to 330 out-of-sample cases with 9 (2.7%) positive for JAK2, the classifier's sensitivity, specificity, positive predictive value, and negative predictive value, were 100%, 92.8%, 28.1%, and 100%, respectively. Among a subset of 183 out-of-sample cases, the model's algorithm would have potentially reduced JAK2 testing by 89% compared with 50% to 62% reduction using previously reported rule-based systems that similarly used blood count parameters. Platelet count had the greatest impact on the model, followed by relative distribution width and erythropoietin.</p><p><strong>Conclusions.—: </strong>These results show that a machine learning classifier may be beneficial as a decision support aid for JAK2 testing in polycythemic patients.</p>","PeriodicalId":93883,"journal":{"name":"Archives of pathology & laboratory medicine","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144048562","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}
引用次数: 0
Biomarkers in Cervical Squamous Neoplasia: Diagnostic, Prognostic, and Predictive. 宫颈鳞状瘤变的生物标志物:诊断、预后和预测。
Archives of pathology & laboratory medicine Pub Date : 2025-04-28 DOI: 10.5858/arpa.2024-0448-RA
Anne M Mills
{"title":"Biomarkers in Cervical Squamous Neoplasia: Diagnostic, Prognostic, and Predictive.","authors":"Anne M Mills","doi":"10.5858/arpa.2024-0448-RA","DOIUrl":"https://doi.org/10.5858/arpa.2024-0448-RA","url":null,"abstract":"<p><strong>Context.—: </strong>Cervical squamous neoplasia runs the gamut from low-risk intraepithelial processes to aggressive invasive malignancies. A variety of biomarkers can be enlisted to help diagnose, prognosticate, and inform treatment of these lesions. There are ongoing controversies about diagnostic and prognostic biomarker use in squamous intraepithelial lesions, and many pathologists are new to predictive biomarker interpretation in invasive cervical lesions.</p><p><strong>Objective.—: </strong>To provide practical guidance on the appropriate use of diagnostic, prognostic, and predictive biomarkers in cervical squamous intraepithelial lesions and invasive carcinomas.</p><p><strong>Data sources.—: </strong>Peer-reviewed literature and the author's personal experience.</p><p><strong>Conclusions.—: </strong>Diagnostic biomarkers such as p16 and human papillomavirus E6/E7 messenger RNA in situ hybridization can have value in the diagnosis of squamous intraepithelial neoplasia, but there are important caveats to their use and interpretation. No prognostic biomarkers have yet demonstrated statistically durable significance for risk stratification of low-grade squamous intraepithelial lesions. Programmed death ligand-1 immunohistochemistry and tumor mutational burden testing are US Food & Drug Administration-approved predictive biomarkers that can be enlisted for the identification of invasive cervical squamous carcinomas that may respond to checkpoint inhibitor-based immunotherapy, whereas human epidermal growth factor receptor 2 (HER2) immunohistochemistry can identify optimal candidates for conjugated anti-HER2 therapies.</p>","PeriodicalId":93883,"journal":{"name":"Archives of pathology & laboratory medicine","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144014271","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}
引用次数: 0
Reproducibility of Equivocal HER2 In Situ Hybridization Groups 3 and 4, and Comparison With HER2 mRNA Expression: The Thin Line Between Amplified and Nonamplified Breast Cancers. 模棱两可HER2原位杂交组3和4的可重复性,以及与HER2 mRNA表达的比较:扩增和非扩增乳腺癌之间的细线。
Archives of pathology & laboratory medicine Pub Date : 2025-04-28 DOI: 10.5858/arpa.2024-0499-OA
Ximena Baez-Navarro, Julia Riggi, David Zylberberg, Angelique van der Made, Dominique Dubois, Jonathan Vanderveken, Naima Benhaddi, Francois P Duhoux, Hilde Vernaeve, Maud Vassilieff, Martine Berlière, Christine Galant, Carolien H M van Deurzen, Mieke R van Bockstal
{"title":"Reproducibility of Equivocal HER2 In Situ Hybridization Groups 3 and 4, and Comparison With HER2 mRNA Expression: The Thin Line Between Amplified and Nonamplified Breast Cancers.","authors":"Ximena Baez-Navarro, Julia Riggi, David Zylberberg, Angelique van der Made, Dominique Dubois, Jonathan Vanderveken, Naima Benhaddi, Francois P Duhoux, Hilde Vernaeve, Maud Vassilieff, Martine Berlière, Christine Galant, Carolien H M van Deurzen, Mieke R van Bockstal","doi":"10.5858/arpa.2024-0499-OA","DOIUrl":"https://doi.org/10.5858/arpa.2024-0499-OA","url":null,"abstract":"<p><strong>Context.—: </strong>Breast carcinomas (BCs) with equivocal HER2 (human epidermal growth factor receptor 2) immunohistochemistry are subjected to in situ hybridization (ISH) to assess HER2 copy numbers. Infrequently, dual-probe ISH also provides equivocal results, designated as ISH groups 2, 3, or 4.</p><p><strong>Objective.—: </strong>To evaluate the reproducibility of HER2 ISH groups 3 and 4, and to compare the integrated immunohistochemistry/ISH HER2 result with HER2 mRNA expression.</p><p><strong>Design.—: </strong>Dual-probe ISH slides of 50 BCs were re-evaluated by 2 independent observers. mRNA was extracted from microdissected tumor cells. Quantitative real-time polymerase chain reaction (RT-qPCR) was performed for quantitative evaluation of HER2 mRNA, using the MammaTyper assay.</p><p><strong>Results.—: </strong>Reproducibility of ISH groups 1 (amplified; n = 5) and 5 (nonamplified; n = 4) was good with only 1 case differently classified. Many group 4 (n = 28) and group 3 (n = 13) tumors were reclassified after recounting: of 41 patients, 9 and 18 might have been treated differently as based on assessment by observers 1 and 2, respectively. Concordance for MammaTyper HER2 status was 56% (n = 18/32) for the original report; 59% (n = 19/32) for observer 1; 72% (n = 23/32) for observer 2; and 63% (n = 20/32) for the majority opinion.</p><p><strong>Conclusions.—: </strong>The reproducibility of equivocal ISH groups is limited. Although HER2 ISH has long been considered as the gold standard to establish the HER2 status in BC, the equivocal \"gray zone\" between amplified and nonamplified BCs is prone to interobserver variability. Potential solutions could comprise the involvement of at least 3 different observers for assessment of equivocal ISH cases, and/or evaluation of HER2 mRNA as a more objective alternative method.</p>","PeriodicalId":93883,"journal":{"name":"Archives of pathology & laboratory medicine","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144031036","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}
引用次数: 0
Analysis of Concurrent Intracholecystic Papillary Neoplasms and Biliary Intraepithelial Neoplasia Reveals Distinct Histologic and Molecular Profiles. 胆囊内乳头状瘤和胆道上皮内瘤的并发分析揭示了不同的组织学和分子特征。
Archives of pathology & laboratory medicine Pub Date : 2025-04-09 DOI: 10.5858/arpa.2024-0340-OA
Preeti Malik, Kritika Krishnamurthy, Fahad N Sheikh, Doctor Yitzchak Goldstein, Nicole C Panarelli
{"title":"Analysis of Concurrent Intracholecystic Papillary Neoplasms and Biliary Intraepithelial Neoplasia Reveals Distinct Histologic and Molecular Profiles.","authors":"Preeti Malik, Kritika Krishnamurthy, Fahad N Sheikh, Doctor Yitzchak Goldstein, Nicole C Panarelli","doi":"10.5858/arpa.2024-0340-OA","DOIUrl":"https://doi.org/10.5858/arpa.2024-0340-OA","url":null,"abstract":"<p><strong>Context.—: </strong>Intracholecystic papillary neoplasms (ICPNs) and biliary intraepithelial neoplasia (BilIN) are presumed precursors to gallbladder adenocarcinomas, but their relationship is incompletely understood.</p><p><strong>Objective.—: </strong>To perform morphologic and molecular characterization of concurrent ICPNs, nonpolypoid mucosa, and adenocarcinomas to determine whether these lesions are related at the DNA level.</p><p><strong>Design.—: </strong>Background mucosa and 36 ICPNs were graded by a pathologist blinded to original diagnoses. Separate areas of ICPNs, BilIN (n = 5), nondysplastic adjacent mucosa (n = 8), and invasive adenocarcinoma (n = 3) were amplified and sequenced on a next-generation sequencer. Data were manually curated to identify pathogenic somatic variants.</p><p><strong>Results.—: </strong>High-grade ICPNs were associated with low-grade (n = 1) or high-grade (n = 3) BilIN or no dysplasia (n = 5). Fifteen were associated with invasive adenocarcinoma. Low-grade ICPNs were associated with low-grade BilIN (n = 3) or no dysplasia (n = 9). Pathogenic variants included CTNNB1 (catenin beta 1) exon 3 (7); TP53 (tumor protein p53) (6); APC (APC regulator of WNT signaling pathway) (2); RB1 (RB transcriptional corepressor 1) (1); KRAS (KRAS proto-oncogene, GTPase) (1); and PIK3CA (phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) (1). Pathogenic variants in ICPNs were not detected in BilIN or nondysplastic mucosa. Mutations in invasive cancers included TP53, PIK3CA, and RB1, concordant with the ICPN, but not with BilIN, in all 3 cases.</p><p><strong>Conclusions.—: </strong>BilIN in the background of ICPNs was of the same or lower grade than ICPNs. Synchronous ICPNs and BilIN lacked concordant somatic mutations. Mutations in adenocarcinomas aligned with the ICPNs. This suggests that ICPN and BilIN are independent at the DNA level and that the presence of ICPNs may not imply risk for subsequent flat dysplasia elsewhere in the biliary tree.</p>","PeriodicalId":93883,"journal":{"name":"Archives of pathology & laboratory medicine","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144042131","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}
引用次数: 0
Diagnostic Utility of SATB2, CDX2, CD10, and β-Catenin Immunohistochemistry in WNT Pathway-Altered Odontogenic Tumors. SATB2、CDX2、CD10和β-Catenin免疫组化在WNT通路改变的牙源性肿瘤中的诊断价值
Archives of pathology & laboratory medicine Pub Date : 2025-04-09 DOI: 10.5858/arpa.2024-0416-OA
Kyu-Young Oh, Ji-Hoon Kim, Hye-Jung Yoon
{"title":"Diagnostic Utility of SATB2, CDX2, CD10, and β-Catenin Immunohistochemistry in WNT Pathway-Altered Odontogenic Tumors.","authors":"Kyu-Young Oh, Ji-Hoon Kim, Hye-Jung Yoon","doi":"10.5858/arpa.2024-0416-OA","DOIUrl":"https://doi.org/10.5858/arpa.2024-0416-OA","url":null,"abstract":"<p><strong>Context.—: </strong>Although WNT pathway-altered odontogenic tumors (WNT-OTs) are a genetically distinct group of odontogenic tumors (OTs), they may histologically resemble other OTs.</p><p><strong>Objective.—: </strong>To investigate the utility of immunohistochemical markers in the diagnosis of WNT-OTs.</p><p><strong>Design.—: </strong>Immunohistochemistry for SATB2 (SATB homeobox 2), CDX2 (caudal type homeobox 2), CD10, and β-catenin was performed in 37 OTs consisting of 19 WNT-OTs (10 calcifying odontogenic cysts, 7 dentinogenic ghost cell tumors [DGCTs]/adenoid ameloblastomas [AAs], 2 ghost cell odontogenic carcinomas) and 18 non-WNT-OTs (7 unicystic ameloblastomas, 7 solid/multicystic ameloblastomas, 4 ameloblastic carcinomas).</p><p><strong>Results.—: </strong>All WNT-OTs were positive for SATB2, whereas all but 1 of the non-WNT-OTs were SATB2-negative, resulting in a sensitivity of 100% (19 of 19) and a specificity of 94.4% (17 of 18) for WNT-OTs. About two-thirds of WNT-OTs were positive for CDX2, whereas all non-WNT-OTs were CDX2-negative, resulting in a lower sensitivity of 63.2% (12 of 19) and a specificity of 100% (18 of 18). Although both CD10 and β-catenin showed 100% sensitivity (19 of 19), their specificities were low at 16.7% (3 of 18) and 44.4% (8 of 18), respectively; nevertheless, CD10 highlighted morular structures in most WNT-OTs. No differences in immunohistochemical profiles were observed between DGCT and AA.</p><p><strong>Conclusions.—: </strong>This study presents novel findings on the immunoreactivity of intestinal markers SATB2 and CDX2 in WNT-OTs. SATB2 is a sensitive and specific marker for the diagnosis of WNT-OTs, and CDX2 and CD10 may serve as additional markers for WNT-OTs. Additionally, the immunohistochemical similarities between DGCT and AA further support the view that these 2 tumors represent the histologic spectrum of the same entity.</p>","PeriodicalId":93883,"journal":{"name":"Archives of pathology & laboratory medicine","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144025897","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}
引用次数: 0
Uncommon Tumors of the Lung: Recently Described and Rediscovered Tumors. 肺部不常见肿瘤:最近描述和重新发现的肿瘤。
Archives of pathology & laboratory medicine Pub Date : 2025-04-01 DOI: 10.5858/arpa.2023-0414-RA
Cesar A Moran
{"title":"Uncommon Tumors of the Lung: Recently Described and Rediscovered Tumors.","authors":"Cesar A Moran","doi":"10.5858/arpa.2023-0414-RA","DOIUrl":"10.5858/arpa.2023-0414-RA","url":null,"abstract":"<p><strong>Context.—: </strong>The great majority of primary pulmonary neoplasms are represented by non-small cell carcinomas-adenocarcinoma and squamous cell carcinoma. In addition, there is another group of neoplasms such as those of neuroendocrine origin that also represent a meaningful subset of primary lung neoplasms. Basically, any other tumor that is not in these groups of tumors may represent an unusual lung neoplasm.</p><p><strong>Objective.—: </strong>To highlight more recently described unusual tumoral entities that may represent a challenge in diagnosis and that require awareness of their existence.</p><p><strong>Data sources.—: </strong>This is a review of 3 different entities: bronchiolar adenoma, adenofibroma, and hemangioblastoma-like clear cell stromal tumor. These tumoral conditions are rare, and a review of the literature is presented. The most relevant morphologic, immunohistochemical, and molecular aspects of bronchiolar adenoma, adenofibroma, and hemangioblastoma-like clear cell stromal tumor are presented. The difficulty of arriving at an unequivocal diagnosis in small biopsies is highlighted.</p><p><strong>Conclusions.—: </strong>The 3 entities represent uncommon tumors occurring primarily in the lung and a diagnostic challenge not only in biopsy specimens but also often in surgically resected specimens. The use of immunohistochemical stains and in some cases of molecular diagnostics is of aid in arriving at final interpretation.</p>","PeriodicalId":93883,"journal":{"name":"Archives of pathology & laboratory medicine","volume":" ","pages":"e87-e92"},"PeriodicalIF":0.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140133482","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}
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