Juan C Hernandez-Prera, Nicole Riddle, Raul S Gonzalez, Sylvia L Asa
{"title":"Endocrine and Neuroendocrine Tumors.","authors":"Juan C Hernandez-Prera, Nicole Riddle, Raul S Gonzalez, Sylvia L Asa","doi":"10.5858/arpa.2024-0315-RA","DOIUrl":"https://doi.org/10.5858/arpa.2024-0315-RA","url":null,"abstract":"<p><strong>Context.—: </strong>The World Health Organization (WHO) Classification of Tumours series is a comprehensive guide to tumor classification in various organ systems. The digital release of the 5th edition on endocrine and neuroendocrine tumors occurred in 2022, while the print volume is still pending publication.</p><p><strong>Objective.—: </strong>To summarize the changes in the 5th edition of the Endocrine and Neuroendocrine Tumours Blue Book compared to the 2017 edition, highlighting updated diagnostic criteria and terminology.</p><p><strong>Data sources.—: </strong>The 2017 WHO Classification of Tumours of Endocrine and the 2022 WHO Classification of Endocrine and Neuroendocrine Tumours.</p><p><strong>Conclusions.—: </strong>The 5th edition refines the understanding of neuroendocrine cell relationships in various organs, incorporating the proposed International Agency for Research on Cancer/WHO classification for neuroendocrine neoplasms from 2018. This includes a more detailed cytogenesis-based classification of pituitary neuroendocrine tumors. Key revisions include the reclassification of thyroid neoplasms, based on cytogenesis and pathogenesis, particularly for follicular cell-derived tumors. The text introduces new terminology for benign endocrine proliferations, emphasizing the distinction between hyperplasia and neoplasia. Changes include the reclassification of multifocal, multiglandular parathyroid disease in primary hyperparathyroidism as multiple adenomas in genetic tumor syndromes. The terminologies thyroid follicular nodular disease and adrenocortical nodular disease are introduced. This edition underscores the critical role of accurate immunohistochemistry in endocrine pathology. Standards for quantifying cellular proliferations, including assessing mitotic activity and Ki-67 labeling indices, are discussed across various tumor types. The classification concludes with a chapter on genetic tumor syndromes associated with endocrine tumors. This edition advances our knowledge in endocrine tumors, incorporating cutting-edge molecular information and addressing essential technical considerations in diagnosis and classification.</p>","PeriodicalId":93883,"journal":{"name":"Archives of pathology & laboratory medicine","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144014310","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}
Olivia J Leung, Keshia E Mora, Alessandro Brunetti, Lauren E Schwartz
{"title":"Metastatic Malignancies to the Ovaries.","authors":"Olivia J Leung, Keshia E Mora, Alessandro Brunetti, Lauren E Schwartz","doi":"10.5858/arpa.2024-0502-RA","DOIUrl":"https://doi.org/10.5858/arpa.2024-0502-RA","url":null,"abstract":"<p><strong>Context.—: </strong>Between 5% and 30% of malignant neoplasms involving the ovary are metastatic. A variety of neoplasms can metastasize to the ovary, including those from the colorectum, endometrium, breast, appendix, stomach, and cervix.</p><p><strong>Objective.—: </strong>To summarize the clinical, gross, and histologic features that aid in distinguishing primary ovarian neoplasms from metastatic neoplasms. Additionally, to discuss the immunohistochemical features that help identify the primary site of origin.</p><p><strong>Data sources.—: </strong>Sources include literature review and cases identified from the authors' practice.</p><p><strong>Conclusions.—: </strong>There are many features that can help distinguish a primary ovarian neoplasm from a metastatic lesion. The patient's clinical symptoms and history may suggest the primary site. On radiology, the absence of ascites is suggestive of metastasis. Laboratory tests such as cancer antigen 125 (CA 125) and carcinoembryonic antigen (CEA) are helpful in distinguishing a primary versus metastatic neoplasm. Gross features that favor metastasis are bilaterality and small tumor size. Metastatic lesions often have multinodular growth and involve the surface or superficial cortex. Histologic features favoring metastasis include a nodular or infiltrative pattern, stromal desmoplasia, hilar involvement, lymphovascular invasion, and an absence of benign or borderline components. The presence of extracellular mucin and signet ring cells also suggests metastasis. Distinct histologic features can be suggestive of the primary site. Immunohistochemical stains, such as cytokeratin (CK) 7, CK20, SATB homeobox 2 (SATB2), p16, paired box 8 (PAX8), WT1 transcription factor (WT1), estrogen receptor (ER), progesterone receptor (PR), and GATA-binding protein 3 (GATA3), can also be useful in evaluating the site of origin. Distinguishing between a primary ovarian tumor and metastasis is critical for determining prognosis and treatment.</p>","PeriodicalId":93883,"journal":{"name":"Archives of pathology & laboratory medicine","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144055171","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}
Zaibo Li, Ann King, Rhona J Souers, Janie J Roberson, Shahla Masood, Deepu Alex, Martin J Magers, Poornima Hegde, Sana O Tabbara
{"title":"Breast Biomarker Cytology Practice in 2023: Results of a College of American Pathologists Survey.","authors":"Zaibo Li, Ann King, Rhona J Souers, Janie J Roberson, Shahla Masood, Deepu Alex, Martin J Magers, Poornima Hegde, Sana O Tabbara","doi":"10.5858/arpa.2025-0023-CP","DOIUrl":"https://doi.org/10.5858/arpa.2025-0023-CP","url":null,"abstract":"<p><strong>Context.—: </strong>The College of American Pathologists (CAP) surveys provide national benchmarks of pathology practice.</p><p><strong>Objective.—: </strong>To investigate breast biomarker cytology practice in domestic and international laboratories in 2023.</p><p><strong>Design.—: </strong>We analyzed data from the CAP Breast Biomarker Cytology Practice Supplemental Questionnaire that was distributed to laboratories participating in the 2023 CAP Nongynecologic Cytopathology Education Program.</p><p><strong>Results.—: </strong>Twenty-five percent (180 of 728) of responding laboratories routinely evaluated breast biomarkers in cytology specimens. Breast biomarkers evaluated in cytology specimens included estrogen receptor/progesterone receptor (98.9%; 175 of 177), human epidermal growth factor receptor 2 (HER2) (93.2%; 165 of 177), Ki-67 (48.6%; 86 of 177), programmed death ligand-1 (PD-L1) (20.9%; 37 of 177), and mismatch repair (19.8%; 35 of 177). Fine-needle aspiration was the most validated specimen type (85.3%; 133 of 156), followed by body fluids (82.1%; 128 of 156). All respondents validated cell blocks (100.0%; 165 of 165), with a few laboratories also validating cytospin slides (3.0%; 5 of 165), liquid-based slides (3.0%; 5 of 165), air-dried direct smears (2.4%; 4 of 165), and others. CytoLyt was the most used collection medium (55.4%; 87 of 157), followed by balanced salt solution (16.6%; 26 of 157), Roswell Park Memorial Institute Medium (13.4%; 21 of 157), and CytoRich Red (9.6%; 15 of 157). Almost all laboratories indicated routinely using formalin (90.4%; 151 of 167) as fixative, while a few laboratories used other types of fixative (ethanol [5.4%; 9 of 167], methanol [3.0%; 5 of 167]). Digital imaging platforms were used by only 12.9% (22 of 171) of responding laboratories. Forty-four laboratories (28.0%; 44 of 157) required cellularity adequacy for interpreting breast biomarkers on cytologic specimens. Additionally, some significant differences in breast biomarker testing practice were identified among different institution types and between domestic and international laboratories.</p><p><strong>Conclusions.—: </strong>This is the first survey from the CAP to investigate breast biomarker cytology practices. The findings reveal some differences among institution types and between domestic and international laboratories. These data provide a baseline for and support further studies and/or guidelines to promote and refine these practices.</p>","PeriodicalId":93883,"journal":{"name":"Archives of pathology & laboratory medicine","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144058794","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}
Autumn Sky Watson, Catherine Le, Anne Wertheimer, Spencer Escobedo, Lisa So, Bhavani Bagevalu Siddegowda, John Palting, Susan Marion, Steven P Stratton, Birte Aggeler
{"title":"Precision Detection of FGFR2b Protein Expression in Solid Tumors: A Comprehensive Assessment of Staining Parameters via Automated Immunohistochemistry.","authors":"Autumn Sky Watson, Catherine Le, Anne Wertheimer, Spencer Escobedo, Lisa So, Bhavani Bagevalu Siddegowda, John Palting, Susan Marion, Steven P Stratton, Birte Aggeler","doi":"10.5858/arpa.2024-0497-OA","DOIUrl":"https://doi.org/10.5858/arpa.2024-0497-OA","url":null,"abstract":"<p><strong>Context.—: </strong>Immunohistochemistry effectively reveals the heterogeneous nature of fibroblast growth factor receptor 2b (FGFR2b) expression and antigen accessibility across diverse tumor histologic types, a variability significantly influenced by tissue type and fixation quality, both of which profoundly impact target antigen accessibility within formalin-fixed, paraffin-embedded (FFPE) tissue specimens. Retrieval parameters on automated staining platforms can impact staining outcomes and assay sensitivity. A comprehensive optimization of staining procedures, encompassing antigen retrieval, proteolytic enzyme digestion, primary antibody incubation, and detection selections, yielded 2 distinct protocols designed for specific tumor types. The protocols were tailored to maximize performance on their respective tumor types, with one protocol optimized for gastric and gastroesophageal junction (G/GEJ) adenocarcinoma, and the other fine-tuned for non-small cell lung cancer (NSCLC) and a broader spectrum of solid tumors.</p><p><strong>Objective.—: </strong>To optimize an FGFR2b (FPR2-D) assay for NSCLC and a broader spectrum of solid tumors through modification of the established VENTANA FGFR2b (FPR2-D) Mouse Monoclonal Antibody assay, originally validated for G/GEJ adenocarcinoma.</p><p><strong>Design.—: </strong>Multiple FGFR2b assay protocols were used to stain sections of FFPE tissue from commercially procured specimens spanning 10 tumor types. Each specimen was evaluated to select the preferred protocol parameters that achieved strong specific staining with minimal background. The assay was then assessed for sensitivity, specificity, and repeatability.</p><p><strong>Results.—: </strong>The optimal gastric cancer tissue staining protocol for the VENTANA FGFR2b (FPR2-D) Mouse Monoclonal Antibody was referenced to develop an assay for other solid tumor types.</p><p><strong>Conclusions.—: </strong>This investigation shows the importance of parameter screening approaches when evaluating FGFR2b across tumor types in immunohistochemistry to ensure optimal staining performance.</p>","PeriodicalId":93883,"journal":{"name":"Archives of pathology & laboratory medicine","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144026403","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":"IgG4-Rich Lesions Associated With Intranasal Drug Use Can Mimic IgG4-Related Disease: A Distinct Clinicopathologic Scenario Represents a Potential Diagnostic Pitfall.","authors":"Andrew T Turk, David A Gudis","doi":"10.5858/arpa.2023-0474-OA","DOIUrl":"10.5858/arpa.2023-0474-OA","url":null,"abstract":"<p><strong>Context.—: </strong>Manifestations of immunoglobulin G4-related disease (IgG4-RD) occur in several organ systems and anatomic locations, including the nasal cavity and paranasal sinuses. Other processes affecting the sinonasal tract, such as chronic rhinosinusitis, aspirin-exacerbated respiratory disease, and nasal polyposis, also involve IgG4.</p><p><strong>Objective.—: </strong>To characterize an association between IgG4 and nasal lesions arising in the clinical context of intranasal drug use.</p><p><strong>Design.—: </strong>The cases of 3 patients (2 with histories of intranasal cocaine abuse, and 1 with intranasal heroin abuse) were evaluated. Clinical features of each case were compiled from the electronic medical record. Histologic morphology of surgical specimens was examined. Immunohistochemical staining was performed to assess involvement of/association with IgG4.</p><p><strong>Results.—: </strong>Clinical features of these lesions included diffuse necrotic fibrinous debris, scarring, and endoscopically evident inflammation. Tissue sections showed acutely and chronically inflamed respiratory-type mucosa with abundant IgG4-positive plasma cells. Although these cases share some aspects in common with IgG4-RD, other definitive characteristics are absent, and notable differences exist.</p><p><strong>Conclusions.—: </strong>This series provides the first demonstration of increased IgG4 expression in nasal lesions associated with intranasal drug use. Despite some similarities, the pathologic processes and IgG4-rich infiltrates in these 3 cases seem to represent a different phenomenon that is not IgG4-RD. Although these lesions contain abundant IgG4-positive cells, they should not be mistaken for or conflated with IgG4-RD.</p>","PeriodicalId":93883,"journal":{"name":"Archives of pathology & laboratory medicine","volume":" ","pages":"464-468"},"PeriodicalIF":0.0,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141728432","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}
Josef Rüschoff, Alexander Penner, Ian O Ellis, M Elizabeth Hale Hammond, Annette Lebeau, Robert Y Osamura, Fréderique Penault-Llorca, Federico Rojo, Chirag Desai, Akira Moh, Neil Atkey, Gudrun Baenfer, Andreas H Scheel, Corrado D'Arrigo, Hans-Ulrich Schildhaus, Giuseppe Viale
{"title":"Global Study on the Accuracy of Human Epidermal Growth Factor Receptor 2-Low Diagnosis in Breast Cancer.","authors":"Josef Rüschoff, Alexander Penner, Ian O Ellis, M Elizabeth Hale Hammond, Annette Lebeau, Robert Y Osamura, Fréderique Penault-Llorca, Federico Rojo, Chirag Desai, Akira Moh, Neil Atkey, Gudrun Baenfer, Andreas H Scheel, Corrado D'Arrigo, Hans-Ulrich Schildhaus, Giuseppe Viale","doi":"10.5858/arpa.2024-0052-OA","DOIUrl":"10.5858/arpa.2024-0052-OA","url":null,"abstract":"<p><strong>Context.—: </strong>Recently, a new type of antibody-drug conjugate, trastuzumab-deruxtecan (T-DXd), has been approved for the treatment of metastatic breast cancer with low level of human epidermal growth factor receptor 2 (HER2) gene expression. Thereby, eligibility relies on an accurate diagnosis of HER2-low status defined by immunohistochemistry IHC 1+/2+ with no gene amplification.</p><p><strong>Objective.—: </strong>To assess pathologists' accuracy and training efficacy in the diagnosis of HER2-low.</p><p><strong>Design.—: </strong>Agreement rates of HER2-low scoring in breast cancer tissue were assessed between expert consensus and real-world pathologists (n = 77 from 14 countries) before and after a specific 4-hour training program for HER2-low detection. Two assays were evaluated, the Ventana Pathway 4B5 CDx and the Dako HercepTest (polyclonal). Concordance of the pathologists with consensus score and efficacy of training were measured by Cohen κ, overall rater agreement, and receiver operating characteristic (ROC) curve statistics.</p><p><strong>Results.—: </strong>In the Ventana 4B5 HER2-low category, baseline agreement rates were >80% but <90%. Negative percentage agreement was improved from 80.6% to 91.1% by training. In the HER2-0 category, positive percentage agreement (74.6%) was the only parameter below the 80% benchmark but was significantly improved to 89.2% after training. Training efficacy was confirmed by ROC curve analysis, which shows improvement for the identification of HER2-0 and HER2-low cases. Finally, in-depth examination of cases with discordant HER2 status disclosed specific issues of HER2-low underscoring and overscoring.</p><p><strong>Conclusions.—: </strong>The ability of pathologists to achieve acceptable diagnostic accuracy in identifying patients with HER2-low breast cancer could be enhanced by short-term training. Potential routes to improve the quality of HER2-low scoring in clinical practice have been identified.</p>","PeriodicalId":93883,"journal":{"name":"Archives of pathology & laboratory medicine","volume":" ","pages":"431-438"},"PeriodicalIF":0.0,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141903869","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 Pathologic Diagnosis of Eosinophilic Esophagitis: Time for Reassessment.","authors":"Mamoun Younes, Dorina Gui","doi":"10.5858/arpa.2024-0392-ED","DOIUrl":"10.5858/arpa.2024-0392-ED","url":null,"abstract":"","PeriodicalId":93883,"journal":{"name":"Archives of pathology & laboratory medicine","volume":" ","pages":"396-399"},"PeriodicalIF":0.0,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143082620","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}
Kaede V Sullivan, Rhona J Souers, Erica Hillesland, Dylan Pillai, Daniel D Rhoads, Robin Rolf, Patricia J Simner, Christina M Wojewoda, Carol A Rauch
{"title":"High Prevalence of Multistep Algorithms in Diagnostic Clostridioides difficile Laboratory Testing.","authors":"Kaede V Sullivan, Rhona J Souers, Erica Hillesland, Dylan Pillai, Daniel D Rhoads, Robin Rolf, Patricia J Simner, Christina M Wojewoda, Carol A Rauch","doi":"10.5858/arpa.2023-0434-CP","DOIUrl":"10.5858/arpa.2023-0434-CP","url":null,"abstract":"<p><strong>Context.—: </strong>Laboratory testing practices for diagnosis of Clostridioides difficile infection (CDI) have evolved in response to published guidelines, availability of highly sensitive nucleic acid amplification tests (NAATs), perceived problems with the specificity of NAATs, and CDI reporting requirements.</p><p><strong>Objective.—: </strong>To assess the current state of laboratory practice for diagnostic CDI testing.</p><p><strong>Design.—: </strong>An optional 8-item supplemental questionnaire was distributed in December 2019 to the 1374 laboratories participating in the College of American Pathologists C difficile Detection (CDF) proficiency testing program challenge CDF-C.</p><p><strong>Results.—: </strong>Of 1374 CDF-C participants, 1160 (84.4%) responded, predominantly representing laboratories based in the United States (1077 of 1160; 92.8%). The majority reported using a multistep testing algorithm (684 of 1159; 59.0%). Initial testing with a glutamate dehydrogenase and toxin A/B combination test followed by NAAT for discrepant results was the most common testing method (360 of 1146; 31.4%). NAAT alone (299 of 1146; 26.1%) was next, then NAAT followed by an assay that included toxin A/B enzyme immunoassay if NAAT is positive (258 of 1146; 22.5%). Only 5.4% (62 of 1146) reported using toxin A/B immunoassay alone. Most respondents (1093 of 1131; 96.6%) reported rejecting CDI tests on formed stool, but rejection of CDI testing in pediatric patients was uncommon (211 of 1131; 18.7%). Rejection of CDI testing in patients using laxatives was reported more often by US-based respondents (379 of 1054 [36.0%] versus 9 of 77 [11.7%], P < .001).</p><p><strong>Conclusions.—: </strong>Multistep algorithms for CDI diagnosis are widely used in line with published recommendations. Most respondents reported rejection of formed stool for CDI testing, but few reported rejection of testing in infants and patients taking laxatives, suggesting these may be areas of opportunity for laboratories to pursue in improving CDI testing practices.</p>","PeriodicalId":93883,"journal":{"name":"Archives of pathology & laboratory medicine","volume":" ","pages":"405-409"},"PeriodicalIF":0.0,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141891249","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}
Jason R McFadden, Iman Salem, Mirjana Stevanovic, Rachael E Barney, Advaita S Chaudhari, Meagan Ann Chambers, Keegan O'Hern, Jeffrey M Cloutier, Shaofeng Yan, Alvaro J Ramos-Rodriguez, Darcy Arendt Kerr, Shabnam Momtahen, Robert E LeBlanc, Gregory J Tsongalis, Edward G Hughes, Aravindhan Sriharan
{"title":"A Droplet Digital Polymerase Chain Reaction-Based Tool to Aid in Melanoma Diagnosis: Development of a 4-Gene Panel Using 164 Melanocytic Neoplasms.","authors":"Jason R McFadden, Iman Salem, Mirjana Stevanovic, Rachael E Barney, Advaita S Chaudhari, Meagan Ann Chambers, Keegan O'Hern, Jeffrey M Cloutier, Shaofeng Yan, Alvaro J Ramos-Rodriguez, Darcy Arendt Kerr, Shabnam Momtahen, Robert E LeBlanc, Gregory J Tsongalis, Edward G Hughes, Aravindhan Sriharan","doi":"10.5858/arpa.2024-0027-OA","DOIUrl":"10.5858/arpa.2024-0027-OA","url":null,"abstract":"<p><strong>Context.—: </strong>Detecting copy number variations (CNVs) at certain loci can aid in the diagnosis of histologically ambiguous melanocytic neoplasms. Droplet digital polymerase chain reaction (ddPCR) is a rapid, automated, and inexpensive method for CNV detection in other cancers, but not yet melanoma.</p><p><strong>Objective.—: </strong>To evaluate the performance of a 4-gene ddPCR panel that simultaneously tests for ras responsive binding element protein 1 (RREB1) gain; cyclin-dependent kinase inhibitor 2A (CDKN2A) loss; MYC proto-oncogene, bHLH transcription factor (MYC) gain; and MYB proto-oncogene, transcription factor (MYB) loss in melanocytic neoplasms.</p><p><strong>Design.—: </strong>One hundred sixty-four formalin-fixed, paraffin-embedded skin samples were used to develop the assay, of which 65 were used to evaluate its performance. Chromosomal microarray analysis (CMA) data were used as the gold standard.</p><p><strong>Results.—: </strong>ddPCR demonstrated high concordance with CMA in detecting RREB1 gain (sensitivity, 86.7%; specificity, 88.9%), CDKN2A loss (sensitivity, 80%; specificity, 100%), MYC gain (sensitivity, 70%; specificity, 100%), and MYB loss (sensitivity, 71.4%; specificity, 100%). When one CNV was required to designate the test as positive, the 4-gene ddPCR panel distinguished nevi from melanomas with a sensitivity of 78.4% and a specificity of 71.4%. For reference, CMA had a sensitivity of 86.2% and a specificity of 78.6%. Our data also revealed interesting relationships with histology, namely (1) a positive correlation between RREB1 ddPCR copy number and degree of tumor progression; (2) a statistically significant correlation between MYC gain and nodular growth; and (3) a statistically significant correlation between MYB loss and a sheetlike pattern of growth.</p><p><strong>Conclusions.—: </strong>With further validation, ddPCR may aid both in our understanding of melanomagenesis and in the diagnosis of challenging melanocytic neoplasms.</p>","PeriodicalId":93883,"journal":{"name":"Archives of pathology & laboratory medicine","volume":" ","pages":"410-421"},"PeriodicalIF":0.0,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141861913","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}
Caitlin Raymond, Ashlie Atchison, Sri Bharathi Kavuri, Colby Elder, Scott Lick, David Guerra, Justin B L Halls, Stephen Cheney, Christoper J Zahner, Robert L Kruse
{"title":"Use of Low-Dose Platelets in Actively Bleeding Patients : A Retrospective Analysis of a Cardiac Surgery Cohort.","authors":"Caitlin Raymond, Ashlie Atchison, Sri Bharathi Kavuri, Colby Elder, Scott Lick, David Guerra, Justin B L Halls, Stephen Cheney, Christoper J Zahner, Robert L Kruse","doi":"10.5858/arpa.2024-0102-OA","DOIUrl":"10.5858/arpa.2024-0102-OA","url":null,"abstract":"<p><strong>Context.—: </strong>During platelet shortages, many hospitals produce low-dose platelets by splitting a standard platelet unit (>3 × 1011 platelets in the United States) in 2, then providing these low-dose units to patients. While low-dose units were previously found to be effective for prophylactic purposes in patients undergoing chemotherapy in the Prophylactic Platelet Dose (PLADO) trial, their use in actively bleeding patients has not yet been assessed.</p><p><strong>Objective.—: </strong>To assess the use and safety of low-dose platelets in actively bleeding patients.</p><p><strong>Design.—: </strong>We performed a retrospective review of cardiac surgery cases receiving platelet units for 18 months at 1 hospital. Two cohorts, those receiving only whole-dose platelets (37 cases) and those receiving only low-dose platelets (38 cases), were compared during the intraoperative and the 24-hour perioperative periods. Mean number of platelet transfusions, dose of other blood products, estimated blood loss, bleeding complications in index cases, and all-cause mortality within 30 days of discharge were compared.</p><p><strong>Results.—: </strong>There was no significant difference in mean number of intraoperative platelet transfusions between the cohorts (1.61 versus 1.53, P = .57). There was no significant increase in the transfusion of other blood products, estimated blood loss, bleeding complications in index cases, or all-cause mortality within 30 days of discharge in the low-dose platelet cohort, apart from a small increase in the requirement for fresh frozen plasma in the perioperative period.</p><p><strong>Conclusions.—: </strong>These results suggest that low-dose platelets are tentatively equivalent to whole-dose platelets in cardiac surgery during shortages, with similar transfusion requirements and clinical outcomes between groups. Future multicenter studies are needed to confirm these findings.</p>","PeriodicalId":93883,"journal":{"name":"Archives of pathology & laboratory medicine","volume":" ","pages":"476-482"},"PeriodicalIF":0.0,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142001566","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}