{"title":"Reply to \"Extragenital self-collection testing for gonorrhea and chlamydia: a feasibility study for expanding STI screening in the Veterans Health Administration\".","authors":"Maria E Navas, J Stacey Klutts","doi":"10.1093/ajcp/aqae172","DOIUrl":"10.1093/ajcp/aqae172","url":null,"abstract":"","PeriodicalId":7506,"journal":{"name":"American journal of clinical pathology","volume":" ","pages":"483"},"PeriodicalIF":2.3,"publicationDate":"2025-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142920511","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Assessing CellaVision peripheral blood and advanced RBC application software's impact on hematologic morphology reporting: Real-world implementation experience in a large Veterans Affairs hospital.","authors":"Cory R Lundgren","doi":"10.1093/ajcp/aqae146","DOIUrl":"10.1093/ajcp/aqae146","url":null,"abstract":"<p><strong>Objectives: </strong>This quality improvement study, conducted at the Kansas City Veterans Affairs Medical Center in Kansas City, Missouri, examined the change in patient reporting after transitioning from manual to CellaVision software-guided differentials and slide reviews. The primary focus was blasts and schistocytes, given their clinical significance.</p><p><strong>Methods: </strong>Three months of manual and CellaVision patient data were examined between May 2022 and February 2023. Blast and schistocyte patients were standardized to the total specimens performed and compared using 2-sample proportion testing. Other red blood cell (RBC) morphologies were also compared using this statistical analysis.</p><p><strong>Results: </strong>Blast and schistocyte reporting after technologist review statistically increased after implementing the CellaVision software. This finding was most prevalent for low-percentage blasts. In addition, both morphologies experienced varying degrees of false-positive reporting, with 33% for low-percentage blasts and 91.7% for schistocytes. Other RBC morphologies displayed different levels of change, which could be clinically significant.</p><p><strong>Conclusions: </strong>The CellaVision software's increased sensitivity to blasts and schistocytes may benefit patient care, especially those with hematologic disorders. The software's high false-positive rate can be reduced by implementing quality metrics that prioritize clinically significant cells. This can be accomplished by implementing a CellaVision Champion to monitor reporting changes, perform patient lookbacks through the software, and provide technologist education. In addition, adopting a more stringent grading scale for schistocytes could also improve the high false-positive rate. Overall, CellaVision provides the ability to enhance hematology quality metrics by providing access to how patient cells are categorized and offering prompt education.</p>","PeriodicalId":7506,"journal":{"name":"American journal of clinical pathology","volume":" ","pages":"473-481"},"PeriodicalIF":2.3,"publicationDate":"2025-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142492852","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ming-Tseh Lin, Eric Christenson, Suping Chen, Emily Adams, Matthew Bayes, James R Eshleman
{"title":"Revision of interpretation criteria to define microsatellite instability in mismatch repair-deficient neoplasms with subtle electropherogram changes.","authors":"Ming-Tseh Lin, Eric Christenson, Suping Chen, Emily Adams, Matthew Bayes, James R Eshleman","doi":"10.1093/ajcp/aqaf011","DOIUrl":"https://doi.org/10.1093/ajcp/aqaf011","url":null,"abstract":"<p><strong>Objectives: </strong>To improve analytic performance characteristics of a microsatellite instability (MSI-V1.2) assay in endometrial cancers (ECs).</p><p><strong>Methods: </strong>Nonneoplastic and neoplastic DNA from colorectal cancers (CRCs) and ECs were compared to define MSI by calculating base shifting of the highest peak and the 5% peak (the leftmost peak with a peak height >5% of the highest peak).</p><p><strong>Results: </strong>We first demonstrated highly precise sizing by capillary electrophoresis. However, relative intensity of multiple peaks, characteristic for microsatellite amplicons, might show a 1-base, but not a 2-base or more, shift of the highest or 5% peak among duplicate runs of nonneoplastic DNA. This inherent bias of the polymerase chain reaction-based MSI assay may lead to false-positive interpretation if MSI was defined by a 1-base shift or more. Subsequently, MSI was evaluated by a 2-base shift or more of the highest peak (original criteria) or a 2-base shift or more of either the highest or 5% peak (revised criteria) without subjective interpretation of a subtle change of electropherogram configuration (the so-called shoulder pattern). While both criteria were highly sensitive in CRCs, the revised criteria improved sensitivity (83% vs 67%) and accuracy (89% vs 79%) and maintained 100% specificity in ECs.</p><p><strong>Conclusions: </strong>The revised criteria provided sensitive, specific, and objective interpretation to examine subtle changes of MSI.</p>","PeriodicalId":7506,"journal":{"name":"American journal of clinical pathology","volume":" ","pages":""},"PeriodicalIF":2.3,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143571763","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Natasha Hunter, Lisa Han, Haley Corbin, Eric Q Konnick, William R Gwin, Shaveta Vinayak, Hannah Linden, William Audeh, Lavanya Samraj, Andrea R Menicucci, T Rinda Soong
{"title":"Clinicopathologic and molecular characterization of low-grade, early-stage, and HER2-positive invasive breast carcinoma.","authors":"Natasha Hunter, Lisa Han, Haley Corbin, Eric Q Konnick, William R Gwin, Shaveta Vinayak, Hannah Linden, William Audeh, Lavanya Samraj, Andrea R Menicucci, T Rinda Soong","doi":"10.1093/ajcp/aqaf010","DOIUrl":"https://doi.org/10.1093/ajcp/aqaf010","url":null,"abstract":"<p><strong>Objectives: </strong>Breast carcinomas overexpressing human epidermal growth factor receptor 2 (HER2) are typically associated with higher tumor grade and faster progression. HER2 positivity is rare in low-grade breast carcinomas with unclear biological implications. We aimed to characterize their clinicopathologic and molecular profiles in this study.</p><p><strong>Methods: </strong>There were 2 cohorts of Nottingham grade 1, HER2-positive invasive breast carcinomas examined: (1) an institutional series (n = 14) and (2) tumors from patients (n = 59) enrolled in the FLEX multicenter clinical registry with MammaPrint and BluePrint profiling.</p><p><strong>Results: </strong>Most (79%) in the case series were both estrogen receptor (ER) and progesterone receptor (PR)-positive. Over half were pathologic or clinical T1N0 tumors. In the 9 cases with adequate material for next-generation sequencing, the majority (66%) demonstrated ERBB2 copy number variations. Most (66%) received HER2-targeted therapy. No recurrences were observed, with a median follow-up time of 43 months. In the FLEX cohort, most tumors were ER-positive (86%) and PR-positive (68%), and over half were clinical T1. Most (70%) were of the luminal phenotype, and over half (54%) were low-risk on MammaPrint.</p><p><strong>Conclusions: </strong>Low-grade HER2-positive breast carcinomas constitute mostly low-stage, luminal-type, and apparently low-risk tumors, warranting investigation into whether therapy de-escalation could achieve favorable outcomes with less toxicity in this population.</p>","PeriodicalId":7506,"journal":{"name":"American journal of clinical pathology","volume":" ","pages":""},"PeriodicalIF":2.3,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143565766","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Histopathologic and genetic distinction of well-differentiated grade 3 neuroendocrine tumor versus poorly-differentiated neuroendocrine carcinoma in high-grade neuroendocrine neoplasms.","authors":"Belinda L Sun, Hongxu Ding, Xiaoguang Sun","doi":"10.1093/ajcp/aqaf013","DOIUrl":"https://doi.org/10.1093/ajcp/aqaf013","url":null,"abstract":"<p><strong>Objectives: </strong>The classification of neuroendocrine neoplasms has evolved significantly. In the current World Health Organization (WHO) classification, well-differentiated grade 3 neuroendocrine tumors (G3-NETs) are distinguished from poorly-differentiated neuroendocrine carcinomas (NECs) based on morphology despite using the same proliferation indices, which poses diagnostic challenges. This review aims to assist pathologists in making an accurate diagnosis, which is crucial for patient management as G3-NETs and NECs have different prognoses and chemotherapy responses.</p><p><strong>Methods: </strong>A literature review and meta-analyses were conducted to summarize current knowledge of G3-NETs and NECs, focusing on histopathologic and genetic characteristics.</p><p><strong>Results: </strong>Grade 3 neuroendocrine tumors and NECs are distinct entities with differences in histopathology, genetics, and clinical presentations. Grade 3 neuroendocrine tumors have a lower Ki-67 proliferation index and tumor mutational burden compared to NECs. Distinct gene mutations and pathways have been identified in G3-NETs and NECs, offering potential for developing a diagnostic gene panel. The 2022 WHO classification recognizes the use of immunohistochemistry for somatostatin receptors 2/5, TP53, Rb, Menin, P27, ATRX, and DAXX to distinguish G3-NETs and NECs. In particular, TP53 and ATRX immunohistochemistry may be useful in routine diagnostics.</p><p><strong>Conclusions: </strong>Specific immunohistochemistry and genetic tests should be developed and incorporated into the classification to reliably distinguish G3-NETs from NECs.</p>","PeriodicalId":7506,"journal":{"name":"American journal of clinical pathology","volume":" ","pages":""},"PeriodicalIF":2.3,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143555530","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
M Natalia Chaves Rivera, Ibrahim Choucair, Michael A Vera, Edward S Lee, Joe M El-Khoury, Cristina A Figueroa Villalba
{"title":"Haptoglobin in pregnancy: Trimester-specific reference intervals.","authors":"M Natalia Chaves Rivera, Ibrahim Choucair, Michael A Vera, Edward S Lee, Joe M El-Khoury, Cristina A Figueroa Villalba","doi":"10.1093/ajcp/aqaf012","DOIUrl":"https://doi.org/10.1093/ajcp/aqaf012","url":null,"abstract":"<p><strong>Objectives: </strong>Pregnancy induces physiologic changes that can affect serologic and immunologic markers, potentially resulting in lower haptoglobin values than nonpregnant counterparts. Such variations may lead to concern for hemolysis in pregnancy. This study aims to analyze reference intervals (RIs) for haptoglobin in each trimester of pregnancy.</p><p><strong>Methods: </strong>We employed a quality improvement project to analyze a total of 401 remnant serum samples (BD Vacutainer SST) collected from routine outpatient pregnancy patients. Roche Cobas 8000 (c 502) systems were used to examine at least 80 samples per trimester: first trimester (86 samples), second trimester (230 samples), and third trimester (80 samples). Haptoglobin between trimesters was compared using the Mann-Whitney test.</p><p><strong>Results: </strong>Nonparametric RIs were calculated to be 27 to 196 mg/dL for the first trimester, 27 to 178 mg/dL for the second trimester, 34 to 191 mg/dL for the third trimester, and 30 to 185 mg/dL for the entire sample population. The distribution of second-trimester haptoglobin (median, 98 mg/dL) was significantly different compared to the first trimester (median, 113.5 mg/dL; P < .05) and the third trimester (median, 112.5 mg/dL; P < .05).</p><p><strong>Conclusions: </strong>Although overall haptoglobin RI during pregnancy aligned with the nonpregnant population, our study revealed a significant shift during the second trimester. This finding suggests that pregnant individuals in the second trimester may have lower haptoglobin values and potentially be misdiagnosed with intravascular hemolysis when consequent added factors further decrease haptoglobin below the level of detection without hemolysis.</p>","PeriodicalId":7506,"journal":{"name":"American journal of clinical pathology","volume":" ","pages":""},"PeriodicalIF":2.3,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143555526","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Bei Wang, Xiaowei Wang, Ziyi Chang, Dingrong Zhong
{"title":"Primary low-grade salivary gland-type intraductal carcinoma of the lung with CCDC6::RET fusion: Case presentation and literature review.","authors":"Bei Wang, Xiaowei Wang, Ziyi Chang, Dingrong Zhong","doi":"10.1093/ajcp/aqaf014","DOIUrl":"https://doi.org/10.1093/ajcp/aqaf014","url":null,"abstract":"<p><strong>Objectives: </strong>Salivary gland-type intraductal carcinoma (IC) is a rare type of low-grade salivary gland neoplasm. Given that the clinical and imaging features of primary lung IC are nonspecific, the diagnosis requires pathologic analysis.</p><p><strong>Methods: </strong>We report a 63-year-old woman with primary low-grade salivary gland-type IC of the lung, characterized by an origin from the bronchus submucosa, an intraductal or intracavity growth of ductal epithelium, an absence of interstitial infiltration, and harboring an RET::CCDC6 fusion.</p><p><strong>Results: </strong>Through case presentation and a literature review, we discuss the differential diagnosis and clinical management of salivary gland-type IC of the lung.</p><p><strong>Conclusions: </strong>Molecular testing is not necessary for histologic subtyping but can aid in the differential diagnosis of IC.</p>","PeriodicalId":7506,"journal":{"name":"American journal of clinical pathology","volume":" ","pages":""},"PeriodicalIF":2.3,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143555534","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ryan C Shean, Sabine Hellwig, Abdulrahman Saadalla, Tracy I George, Anton V Rets
{"title":"High-sensitivity KIT D816V variation analysis by droplet digital polymerase chain reaction: The reference laboratory perspective.","authors":"Ryan C Shean, Sabine Hellwig, Abdulrahman Saadalla, Tracy I George, Anton V Rets","doi":"10.1093/ajcp/aqaf008","DOIUrl":"https://doi.org/10.1093/ajcp/aqaf008","url":null,"abstract":"<p><strong>Objective: </strong>Systemic mastocytosis is a hematologic malignancy characterized by clonal expansion of neoplastic mast cells. Detection of this variation is critical for screening and diagnosis, with recent guidelines emphasizing the need for high-sensitivity assays that identify variants at a variant allele frequency below 0.05%. Our reference laboratory offers droplet digital polymerase chain reaction (ddPCR) for detection of KIT D816V at a limit of detection of 0.03% variant allele frequency-substantially higher sensitivity than next-generation sequencing (NGS).</p><p><strong>Methods: </strong>Because high-sensitivity KIT D816V testing is still not widely available, we present our 3-year experience with KIT D816V ddPCR in a clinical setting. From January 2021 to March 2024, KIT D816V variation was detected in 14.9% (1232/8272) of samples.</p><p><strong>Results: </strong>Peripheral blood and bone marrow positivity rates were 11.1% and 34.9%, respectively. Among 181 samples tested by both ddPCR and NGS, ddPCR identified 37.6% as positive, while NGS identified only 6.0% as positive. Next-generation sequencing showed 16% sensitivity and 100% specificity for KIT D816V detection compared with ddPCR as the gold standard, which detected the variant in 84% more samples because of its lower limit of detection. A 20-ng/mL serum tryptase threshold to screen for detecting KIT D816V by ddPCR had 73.7% sensitivity and 91.2% specificity, but lowering the serum tryptase threshold to 11.5 ng/mL increased sensitivity to 97.5%, with 70.7% specificity.</p><p><strong>Conclusions: </strong>Overall, ddPCR for detection of KIT D816V dramatically increases sensitivity over NGS tests used for myeloid malignancies, including systemic mastocytosis. Our findings also provide support for the use of a lower serum tryptase threshold (>11.4 ng/mL instead of >20ng/mL) to initiate workup for a mast cell neoplasm.</p>","PeriodicalId":7506,"journal":{"name":"American journal of clinical pathology","volume":" ","pages":""},"PeriodicalIF":2.3,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143555528","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Diyna Altrmanini, Ibrahim Hassan, Andrés Pérez-López, Mohammed Suleiman
{"title":"Implementing AI in clinical microbiology: Key challenges ahead.","authors":"Diyna Altrmanini, Ibrahim Hassan, Andrés Pérez-López, Mohammed Suleiman","doi":"10.1093/ajcp/aqaf003","DOIUrl":"https://doi.org/10.1093/ajcp/aqaf003","url":null,"abstract":"","PeriodicalId":7506,"journal":{"name":"American journal of clinical pathology","volume":" ","pages":""},"PeriodicalIF":2.3,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143472095","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Erin Graf, Amr Soliman, Mohamed Marouf, Anil V Parwani, Preeti Pancholi
{"title":"Reply to \"Implementing AI in clinical microbiology\": Key challenges ahead.","authors":"Erin Graf, Amr Soliman, Mohamed Marouf, Anil V Parwani, Preeti Pancholi","doi":"10.1093/ajcp/aqaf005","DOIUrl":"https://doi.org/10.1093/ajcp/aqaf005","url":null,"abstract":"","PeriodicalId":7506,"journal":{"name":"American journal of clinical pathology","volume":" ","pages":""},"PeriodicalIF":2.3,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143472103","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}