Archives of pathology & laboratory medicine最新文献

{"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}

{"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}

{"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}

{"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}

{"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}

{"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}

{"title":"Thoracic Frozen Section Pitfalls: Lung Adenocarcinoma Versus Selected Mimics.","authors":"Sanjay Mukhopadhyay","doi":"10.5858/arpa.2024-0023-RA","DOIUrl":"10.5858/arpa.2024-0023-RA","url":null,"abstract":"<p><strong>Context.—: </strong>Intraoperative (frozen section) analysis of lung lesions (nodules, masses, ground-glass opacities) can occasionally be diagnostically challenging.</p><p><strong>Objective.—: </strong>To describe selected pitfalls in thoracic frozen sections with a focus on the differential diagnosis between adenocarcinoma and its mimics, and to provide tips to prevent misinterpretation.</p><p><strong>Data sources.—: </strong>Peer-reviewed literature and the author's experience.</p><p><strong>Conclusions.—: </strong>A common challenge in thoracic frozen sections is the differential diagnosis between lung adenocarcinoma and its mimics. Diagnostic difficulties arise because mimics of adenocarcinoma often entrap reactive lung epithelium that can appear atypical on frozen section slides. Entities that can be misinterpreted as adenocarcinoma include ciliated muconodular papillary tumor/bronchiolar adenoma, hamartoma, inflammatory myofibroblastic tumor, and pulmonary Langerhans cell histiocytosis. Knowledge of the key clinical, radiologic, and histologic features of these entities can help prevent overdiagnosis of adenocarcinoma. Pathologic findings that facilitate the distinction between adenocarcinoma and its mimics at frozen section include the appearance and contour of the lesion at low magnification, growth patterns, cilia, stromal features, shape of the epithelial cells (cuboidal versus columnar), nuclear features of malignancy (crowding, hyperchromasia, irregular contours), and abruptness of the junction between the lesion and adjacent uninvolved lung. Knowledge of the clinical context, imaging findings, and the surgical consequence of the intraoperative diagnosis can also prevent diagnostic errors. Finally, since adenocarcinomas of the lung are often relatively bland and lack the stromal desmoplasia seen in adenocarcinomas of other organs, familiarity with the morphologic spectrum of lung adenocarcinomas at frozen section analysis is important.</p>","PeriodicalId":93883,"journal":{"name":"Archives of pathology & laboratory medicine","volume":" ","pages":"e93-e99"},"PeriodicalIF":0.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141181641","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":"Adverse Prognostic Impact of Transitional and Pleomorphic Patterns in Pleural Nonepithelioid Mesothelioma: Insights From Comprehensive Analysis and Reticulin Stain.","authors":"Francesco Fortarezza, Federica Pezzuto, Sonia Maniglio, Andrea Marzullo, Antonio d'Amati, Domenica Cavone, Daniele Egidio Romano, Floriana Pentimone, Angela De Palma, Giuseppe Marulli, Teresa Lettini, Concetta Caporusso, Marcella Barbarino, Cecilia Salzillo, Andrea Quaranta, Fiorella Calabrese, Gabriella Serio, Luigi Vimercati","doi":"10.5858/arpa.2023-0523-OA","DOIUrl":"10.5858/arpa.2023-0523-OA","url":null,"abstract":"<p><strong>Context.—: </strong>Mesothelioma subtyping into epithelioid and nonepithelioid categories plays a crucial role in prognosis and treatment selection, with emerging recognition of the impact of various histologic patterns.</p><p><strong>Objective.—: </strong>To investigate the prognostic implications of transitional and pleomorphic patterns in sarcomatoid mesothelioma.</p><p><strong>Design.—: </strong>A total of 132 mesothelioma cases (87 biphasic, 45 sarcomatoid) were analyzed. Histologic slides were assessed, treatment data collected, and cases categorized into predominant epithelioid or sarcomatoid patterns. The sarcomatoid mesotheliomas were classified into usual, pleomorphic, and transitional patterns, with reticulin staining for the latter. Statistical analysis included Cox regression and Kaplan-Meier methods.</p><p><strong>Results.—: </strong>Younger age (P = .02) and receiving therapy (P < .001) correlated with improved survival for both histotypes. Advanced stage was associated with shorter survival in sarcomatoid cases (P = .02). Predominant epithelioid pattern in biphasic cases led to longer survival (P < .001). Transitional and pleomorphic patterns were indicative of worse prognosis, with significantly lower survival in cases with both patterns than in cases with the usual sarcomatoid pattern (P = .046). Multivariate analysis identified independent survival factors, including predominant epithelioid component in biphasic mesothelioma (P = .001) and chemotherapy (P < .001).</p><p><strong>Conclusions.—: </strong>Histologic subtyping in mesothelioma plays a pivotal role in prognosis. Transitional and pleomorphic patterns, even in low percentages, indicate poorer outcomes. This study highlights the need for standardized diagnostic support and suggests the potential utility of histochemical staining in identifying more aggressive morphologic aspects. Recognizing the significance of these patterns can guide treatment decisions and patient care strategies.</p>","PeriodicalId":93883,"journal":{"name":"Archives of pathology & laboratory medicine","volume":" ","pages":"347-353"},"PeriodicalIF":0.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141478115","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":"Neoadjuvant Therapy and Lung Cancer: Role of Pathologists.","authors":"Sanja Dacic","doi":"10.5858/arpa.2024-0203-RA","DOIUrl":"10.5858/arpa.2024-0203-RA","url":null,"abstract":"<p><strong>Context.—: </strong>Recent neoadjuvant clinical trials in lung cancer have demonstrated the survival benefits in carefully selected patients. Standardization of the assessment of pathologic response to neoadjuvant therapy in surgically resected specimens is required.</p><p><strong>Objective.—: </strong>To review the current pathology practices in the gross processing and microscopic assessment of surgically resected non-small cell lung carcinoma specimens after neoadjuvant therapy.</p><p><strong>Data sources.—: </strong>PubMed publications and experience of the author.</p><p><strong>Conclusions.—: </strong>Gross processing of the surgically resected lung carcinoma after neoadjuvant therapy needs further refinement and standardization in clinical trials and in a real-world clinical practice. Microscopic assessment of the response includes quantification of viable tumor, necrosis, and stroma. The best approach would be to use a single standardized and most reproducible scoring system. Published studies on gross processing of lung carcinoma specimens in the neoadjuvant setting and microscopic assessment of pathologic response provide a good foundation for the future standardization of pathology practice.</p>","PeriodicalId":93883,"journal":{"name":"Archives of pathology & laboratory medicine","volume":" ","pages":"e78-e81"},"PeriodicalIF":0.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142514518","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":"The Diagnostic Accuracy of Claudin-4 Immunochemistry in Differentiating Metastatic Carcinomas From Mesothelial Processes in Serous Effusion Cytology: A Systematic Review and Meta-analysis.","authors":"Maria Kleinaki, Johannes A Vey, Sinclair Awounvo, Angela Ishak, Maria Arnaouti, Han Suk Ryu, Ilias P Nikas","doi":"10.5858/arpa.2023-0560-RA","DOIUrl":"10.5858/arpa.2023-0560-RA","url":null,"abstract":"<p><strong>Context.—: </strong>Distinguishing metastatic carcinomas from mesotheliomas or reactive mesothelial cells in pleural, peritoneal, and pericardial effusions is a common diagnostic problem cytopathologists encounter.</p><p><strong>Objective.—: </strong>To perform the first meta-analysis on the pooled diagnostic accuracy of claudin-4 immunochemistry in serous effusion cytopathology.</p><p><strong>Design.—: </strong>This report followed the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines for diagnostic test accuracy studies. Three databases (PubMed, Scopus, and the Cochrane Library) were searched until October 9, 2023, followed by study selection using specific inclusion and exclusion criteria and data extraction. The study quality assessment was performed by using the Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2) tool. Statistical analysis was performed by using R to calculate the pooled sensitivity and specificity of claudin-4 immunochemistry. In addition, the diagnostic odds ratio was measured, representing the odds ratio of a positive result indicating a carcinoma rather than a mesothelial process in serous effusion cytology.</p><p><strong>Results.—: </strong>Fourteen observational studies, published between 2011 and 2023, fulfilled the selection criteria and were included. All 14 studies used the 3E2C1 clone. Claudin-4 immunochemistry showed a high diagnostic accuracy in serous effusion cytology. The pooled sensitivity and specificity were 98.02% (95% CI, 93.96%-99.37%) and 99.72% (95% CI, 97.36%-99.97%), respectively. Lastly, the pooled diagnostic odds ratio was 1660.5 (95% CI, 760.0-3627.8), and no evidence of statistical heterogeneity between the included studies was found (I2 = 0%, τ2 = 0).</p><p><strong>Conclusions.—: </strong>Claudin-4 may be used as a single pan-carcinoma immunochemical biomarker in the differential diagnosis between metastatic carcinomas and mesotheliomas or reactive mesothelial cells in serous effusion cytology.</p>","PeriodicalId":93883,"journal":{"name":"Archives of pathology & laboratory medicine","volume":" ","pages":"381-388"},"PeriodicalIF":0.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141319255","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}