American journal of clinical pathology最新文献_第6页

Follow the LINE: A novel case of dilated cardiomyopathy caused by a LINE-1 insertion in the TTN gene.

IF 2.3 4区医学

American journal of clinical pathology Pub Date : 2025-02-10 DOI: 10.1093/ajcp/aqae170

Qiliang Ding, Jenna Fine, Frank T Hoffman, Michelle L Kluge, Rhonda K Kuennen, Sarah M Thieke, Nicole L Hoppman, Cherisse A Marcou, Ross A Rowsey, Erik C Thorland, Linnea M Baudhuin, Ann M Moyer, Alessia Buglioni

{"title":"Follow the LINE: A novel case of dilated cardiomyopathy caused by a LINE-1 insertion in the TTN gene.","authors":"Qiliang Ding, Jenna Fine, Frank T Hoffman, Michelle L Kluge, Rhonda K Kuennen, Sarah M Thieke, Nicole L Hoppman, Cherisse A Marcou, Ross A Rowsey, Erik C Thorland, Linnea M Baudhuin, Ann M Moyer, Alessia Buglioni","doi":"10.1093/ajcp/aqae170","DOIUrl":"https://doi.org/10.1093/ajcp/aqae170","url":null,"abstract":"Objectives: Protein-truncating variants in the TTN gene are a well-established cause of dilated cardiomyopathy (DCM). We report a novel case of DCM caused by a mobile element insertion (MEI) in TTN, through which we highlight the key features of MEIs in next-generation sequencing data. Because of the rarity of MEIs, the next-generation sequencing data features associated with these events may be mistaken as noise, potentially leading to missed diagnoses.Methods: Next-generation sequencing gene panel testing for DCM was performed on a 17-year-old male patient presenting with severe left ventricular dilatation and systolic dysfunction. Manta was used for structural variant detection, followed by manual review of NGS data for potential structural variants.Results: Manta detected a potential insertion in TTN. Manual review identified hallmark features consistent with a LINE-1 MEI. This finding was orthogonally confirmed by long-range polymerase chain reaction and gel electrophoresis, which indicated an insertion of approximately 4 to 5 kilobase pairs. The insertion disrupted the reading frame of TTN within an A-band exon, resulting in protein truncation that was classified as likely pathogenic.Conclusions: This case expands the mutational spectrum of TTN protein-truncating variants. It also underscores the importance of recognizing rarer types of pathogenic variants (eg, MEIs) to produce accurate genetic diagnostics.","PeriodicalId":7506,"journal":{"name":"American journal of clinical pathology","volume":" ","pages":""},"PeriodicalIF":2.3,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143381569","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}

引用次数: 0

Pilot study: Urine cell-free DNA with low-pass whole genome sequencing can detect and molecularly type upper tract urothelial carcinomas.

IF 2.3 4区医学

American journal of clinical pathology Pub Date : 2025-02-09 DOI: 10.1093/ajcp/aqae175

Chaz Quinn, L Angelica Lerma, Alexander Zhu, Raymond J Monnat, Jonathan L Wright, Christina M Lockwood, Maria S Tretiakova

{"title":"Pilot study: Urine cell-free DNA with low-pass whole genome sequencing can detect and molecularly type upper tract urothelial carcinomas.","authors":"Chaz Quinn, L Angelica Lerma, Alexander Zhu, Raymond J Monnat, Jonathan L Wright, Christina M Lockwood, Maria S Tretiakova","doi":"10.1093/ajcp/aqae175","DOIUrl":"https://doi.org/10.1093/ajcp/aqae175","url":null,"abstract":"Objectives: Upper tract urothelial carcinoma (UTUC) is an aggressive disease that is challenging to biopsy and diagnose, frequently yielding nondiagnostic cytology and tissue specimens. Therefore, UTUC is often late stage when diagnosed, with poor outcomes. Cell-free tumor DNA (cfDNA) may improve UTUC early diagnosis and assessments of heterogeneity, treatment response, and recurrence but has not been studied in the urine from patients with UTUC. This study aimed to detect recurrent, diagnostic UTUC cytogenetic abnormalities by low-pass whole genome sequencing (LPWGS) and to compare urine-derived and plasma cfDNA against abnormalities identified in patient tumor tissue.Methods: Cell-free tumor DNA extracted from voided urine and plasma before nephroureterectomy in 4 patients with UTUC was compared with genomic DNA from formalin-fixed, paraffin-embedded tumor tissue after LPWGS.Results: Abnormal autosomal genomic regions were highest in tissue (n = 11,843), intermediate in urine (n = 5,072) and lowest in plasma (n = 763), with a high concordance of flagged regions identified in tissue and urine (r = 0.88). Pairwise analysis of whole chromosome gains/losses and subchromosomal alterations between tissue and urine showed nearly identical patterns in all 4 patients (r = 0.88-0.99) in contrast to plasma (r < 0.25). Abnormal genomic regions identified by LPWGS showed a high degree of overlap (100% for tumor tissue, 94% for urine cfDNA) with cBioPortal UTUC-associated genes.Conclusions: We demonstrated the superiority of urine vs plasma cfDNA when LPWGS was used to identify UTUC-associated gene abnormalities. Voided urine cfDNA molecular signatures are highly concordant with matched tumor tissue on chromosomal and subchromosomal levels, emphasizing its feasibility as a noninvasive biomarker for UTUC detection and surveillance.","PeriodicalId":7506,"journal":{"name":"American journal of clinical pathology","volume":" ","pages":""},"PeriodicalIF":2.3,"publicationDate":"2025-02-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143373465","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}

引用次数: 0

Correspondence: Integrating automated messaging with laboratory information systems for critical result communication.

IF 2.3 4区医学

American journal of clinical pathology Pub Date : 2025-02-08 DOI: 10.1093/ajcp/aqae164

Princess Morales, Andrés Pérez-López, Mohammed Suleiman, Carl Bjorkhammer

引用次数: 0

Reply to "Escalation process of critical values when these cannot be communicated on first attempt: a hospital-wide process improvement project".

IF 2.3 4区医学

American journal of clinical pathology Pub Date : 2025-02-08 DOI: 10.1093/ajcp/aqae165

Jeannette Guarner

引用次数: 0

Flow cytometry evaluation of acute myeloid leukemia minimal residual disease based on an understanding of the normal maturation patterns in the blast compartments.

IF 2.3 4区医学

American journal of clinical pathology Pub Date : 2025-02-08 DOI: 10.1093/ajcp/aqae187

Mikhail Roshal, Qi Gao

{"title":"Flow cytometry evaluation of acute myeloid leukemia minimal residual disease based on an understanding of the normal maturation patterns in the blast compartments.","authors":"Mikhail Roshal, Qi Gao","doi":"10.1093/ajcp/aqae187","DOIUrl":"https://doi.org/10.1093/ajcp/aqae187","url":null,"abstract":"Objective: Detection of minimal/measurable disease (MRD) in acute myeloid leukemia (AML) is critical for both clinical decision-making and prognostication, yet remains a challenge. Flow cytometry is a well-established method for MRD detection. Flow cytometric (FC) evaluation of MRD must consider a complex maturational pattern of normal hematopoietic development to separate normal from abnormal progenitors. Here, we offer an example of an interpretive approach based on a thorough understanding of stage- and lineage-specific hematopoietic maturation.Methods: We provide a comprehensive overview of blast maturation from early precursors (hematopoietic stem cells) to committed late-stage unilineage progenitors and commonly observed stage-specific abnormalities based on cases we have encountered in practice. We emphasize the importance of stage-specific comparisons for accurate MRD detection by flow cytometry.Results: The AML blasts almost invariably show abnormal phenotypes, and the phenotypes may evolve upon therapy. The detected phenotypes are necessarily confined to the target antigens included in the panel. It is therefore critical to evaluate a range of antigens to establish a specific stage/state of lineage commitment and detect potential common abnormalities. Moreover, enough cells must be acquired to allow for the detection of MRD at desired levels. Significant technical and analytical validation is critical.Conclusions: Flow cytometry offers a powerful single-cell-based platform for MRD detection in AML, and the results have been proven critical for disease management. Leukemia-associated phenotype-informed difference from the normal approach presented in this review presents an analytical framework for sensitive and accurate MRD detection.","PeriodicalId":7506,"journal":{"name":"American journal of clinical pathology","volume":" ","pages":""},"PeriodicalIF":2.3,"publicationDate":"2025-02-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143373523","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}

引用次数: 0

Laboratory-developed tests and in vitro diagnostics: A regulatory overview for anatomic pathology.

IF 2.3 4区医学

American journal of clinical pathology Pub Date : 2025-02-06 DOI: 10.1093/ajcp/aqae181

Jonathan R Genzen, Lauren J Miller, Anton V Rets, Kajsa E Affolter

{"title":"Laboratory-developed tests and in vitro diagnostics: A regulatory overview for anatomic pathology.","authors":"Jonathan R Genzen, Lauren J Miller, Anton V Rets, Kajsa E Affolter","doi":"10.1093/ajcp/aqae181","DOIUrl":"https://doi.org/10.1093/ajcp/aqae181","url":null,"abstract":"Objectives: The US Food and Drug Administration's Final Rule on laboratory-developed tests was published on May 6, 2024. The objective of this article is to explain the Final Rule and existing in vitro diagnostic regulations in the context of anatomic pathology.Methods: The Final Rule, US in vitro diagnostic regulations, guidance documents, government publications, websites, news articles, and publications were reviewed, with sources including the Federal Register, the Code of Federal Regulations, the US Code, statutory text, PubMed, and Internet resources. Regulations applicable to device classifications and product codes relevant to anatomic pathology were highlighted.Results: The Final Rule outlines requirements and enforcement discretion policies applicable to anatomic pathology, including the Food and Drug Administration's targeted enforcement discretion for \"1976-type\" laboratory-developed tests and partial enforcement discretion with laboratory-developed tests for unmet needs. Existing regulations, including the classification and requirements applicable to Class I, II, and III medical devices, are reviewed, including those for immunohistochemistry kits and reagents, analyte specific reagents, and research use only reagents and equipment.Conclusions: Pathologists, laboratory directors, managers, and supervisors responsible for anatomic pathology testing should be familiar with existing regulations and the Final Rule to ensure compliance with federal laws and regulations.","PeriodicalId":7506,"journal":{"name":"American journal of clinical pathology","volume":" ","pages":""},"PeriodicalIF":2.3,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143254154","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}

引用次数: 0

Diagnostic utility of lymphocyte enhancer factor 1 in aggressive B-cell lymphoma with MYC rearrangement.

IF 2.3 4区医学

American journal of clinical pathology Pub Date : 2025-02-06 DOI: 10.1093/ajcp/aqae189

Xin Wang, Maria Faraz, Anne Chen, Tipu Nazeer, Xiaoyan Huang

{"title":"Diagnostic utility of lymphocyte enhancer factor 1 in aggressive B-cell lymphoma with MYC rearrangement.","authors":"Xin Wang, Maria Faraz, Anne Chen, Tipu Nazeer, Xiaoyan Huang","doi":"10.1093/ajcp/aqae189","DOIUrl":"https://doi.org/10.1093/ajcp/aqae189","url":null,"abstract":"Objectives: We sought to investigate the diagnostic value of lymphocyte enhancer factor 1 (LEF1) expression in aggressive B-cell lymphomas (BCL) with MYC gene rearrangement (MYC-R).Methods: Sixty-seven cases of BCL were studied and included Burkitt lymphoma (BL) (23 cases); diffuse large B-cell lymphoma (DLBCL), not otherwise specified (NOS) with MYC-R (13 cases); and DLBCL/high-grade B-cell lymphoma with MYC, BCL2, and/or BCL6 rearrangements (double-hit [DH] or triple-hit [TH], 17 cases). Random DLBCL-NOS (14 cases) without MYC-R was recruited as a control group. By immunohistochemical stains, 3 patterns of LEF1 staining were recorded as pattern 0 (negative), pattern 1 (weak and heterogeneous staining, <80%), and pattern 2 (moderate/strong and uniform staining, ≥80%).Results: Pattern 1 can be seen in all BCLs with MYC-R included in this study and more commonly seen in DLBCL without MYC-R (8/14 cases). Pattern 2 is characteristic (positive predictive value = 86%) for Epstein-Barr virus (EBV)-negative BL, while pattern 0 was seen in 22 (76%) of 29 cases of DLBCL-MYC-R/DH/TH (P < .001). Seven of 8 EBV-positive BL cases showed pattern 0, which was completely opposite to the common pattern 2 in EBV-negative BL (12/15 cases). Pattern 2 was not detected in all DH/TH cases.Conclusions: Weak and heterogeneous staining of LEF1 can be seen in all the BCLs with and without MYC-R. Strong and uniform staining of LEF1 is highly characteristic of EBV-negative BL among all aggressive BCLs with MYC-R, while the negative staining of LEF1 is mostly suggestive of DLBCL-MYC-R/DH/TH. Lymphocyte enhancer factor 1 provides additional diagnostic value in the differentiation of BL from other aggressive BCLs with MYC-R, especially in a limited specimen.","PeriodicalId":7506,"journal":{"name":"American journal of clinical pathology","volume":" ","pages":""},"PeriodicalIF":2.3,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143254141","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}

引用次数: 0

Coagulation abnormalities following brown recluse spider (Loxosceles reclusa) envenomation: A description of 2 cases and review of the literature.

IF 2.3 4区医学

American journal of clinical pathology Pub Date : 2025-01-30 DOI: 10.1093/ajcp/aqaf001

Stephanie A Hart, David Gailani, Lorin A Bibb, Jeffrey P Zwerner, Garrett S Booth, Jeremy W Jacobs

{"title":"Coagulation abnormalities following brown recluse spider (Loxosceles reclusa) envenomation: A description of 2 cases and review of the literature.","authors":"Stephanie A Hart, David Gailani, Lorin A Bibb, Jeffrey P Zwerner, Garrett S Booth, Jeremy W Jacobs","doi":"10.1093/ajcp/aqaf001","DOIUrl":"https://doi.org/10.1093/ajcp/aqaf001","url":null,"abstract":"Objective: Hemostatic abnormalities, including disseminated intravascular coagulation (DIC), are often cited as a common finding in patients following Loxosceles spider envenomation (ie, loxoscelism). The prevalence and severity of coagulopathy, however, particularly following L reclusa (ie, brown recluse) envenomation, is not well described. This study aimed to characterize coagulation laboratory parameters and coagulopathy in patients following L reclusa envenomation.Methods: We evaluated the coagulation laboratory parameters (eg, prothrombin time, partial thromboplastin time, coagulation factor activity levels, lupus anticoagulant [LA] testing) of 2 patients seen at our institution following brown recluse spider envenomation. We also comprehensively reviewed the literature for all reported cases of brown recluse spider envenomation and assessed patient demographics, clinical presentations, coagulation laboratory parameters, and outcomes.Results: We identified 2 patients with loxoscelism (1 cutaneous only, 1 systemic with hemolysis) with prolonged partial thromboplastin times but with normal clotting factor levels following envenomation. Literature review identified 263 patients: 12 patients had at least 1 prolonged clotting time, 31 reported a platelet count below 150 × 109/L, and there was clinical concern for DIC in 12 cases. The odds of death were statistically significantly higher in patients with clinical concern for DIC than in cases without concern for DIC or coagulopathy (odds ratio, 82.9 [95% CI, 12.6-433.8]; P < .001).Conclusions: Following brown recluse spider envenomation, hemostatic perturbations are infrequent and clinical coagulopathy is uncommon, but the odds of death following a brown recluse spider bite are statistically significantly greater if DIC develops, even when compared to individuals with hemolysis without DIC.","PeriodicalId":7506,"journal":{"name":"American journal of clinical pathology","volume":" ","pages":""},"PeriodicalIF":2.3,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143063238","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}

引用次数: 0

Continued harmonization of the international normalized ratio across a large laboratory network: Evidence of sustained low interlaboratory variation and bias after a change in instrumentation. 在一个大型实验室网络中继续统一国际标准化比值：仪器更换后实验室间差异和偏差持续降低的证据。

IF 2.3 4区医学

American journal of clinical pathology Pub Date : 2025-01-28 DOI: 10.1093/ajcp/aqae090

Emmanuel J Favaloro, Sandya Arunachalam, Kent Chapman, Leonardo Pasalic

{"title":"Continued harmonization of the international normalized ratio across a large laboratory network: Evidence of sustained low interlaboratory variation and bias after a change in instrumentation.","authors":"Emmanuel J Favaloro, Sandya Arunachalam, Kent Chapman, Leonardo Pasalic","doi":"10.1093/ajcp/aqae090","DOIUrl":"10.1093/ajcp/aqae090","url":null,"abstract":"Objectives: Our objective was to maintain low interlaboratory variation and bias in international normalized ratio (INR) results following a network change in instrumentation and reagents, using a process of ongoing standardization and harmonization.Methods: Network-wide standardization to new common instrument and reagent platforms followed by network-wide application of a simple novel process of verification of international sensitive index and mean normal prothrombin time values for each new lot of prothrombin time (PT) reagent that does not require use of World Health Organization reference thromboplastin or INR calibration/certified plasma.Results: The network transitioned from mechanical hemostasis detection instruments with associated PT reagent (Diagnostica Stago; NeoPTimal) to optical detection (ACL TOPs) with associated PT reagent (Werfen; RecombiPlasTin 2G). Comparing 3 years of data for each situation, the network (n = 27 laboratories) maintained low INR variability and bias relative to general mechanical and optical groups and other laboratories.Conclusions: Harmonized support for patient management of vitamin K antagonists such as warfarin was continuously maintained in our geography, with potentially positive implications for other coagulation laboratories and geographies. For the United States in particular, paucity of US Food and Drug Administration-cleared INR certified plasmas potentially compromises INR test accuracy; our novel approach may provide workable alternatives for other laboratories/networks.","PeriodicalId":7506,"journal":{"name":"American journal of clinical pathology","volume":" ","pages":"28-41"},"PeriodicalIF":2.3,"publicationDate":"2025-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141722858","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}

引用次数: 0

A survey analysis of the adoption of large language models among pathologists. 病理学家采用大型语言模型的调查分析。

IF 2.3 4区医学

American journal of clinical pathology Pub Date : 2025-01-28 DOI: 10.1093/ajcp/aqae093

Thiyaphat Laohawetwanit, Daniel Gomes Pinto, Andrey Bychkov

{"title":"A survey analysis of the adoption of large language models among pathologists.","authors":"Thiyaphat Laohawetwanit, Daniel Gomes Pinto, Andrey Bychkov","doi":"10.1093/ajcp/aqae093","DOIUrl":"10.1093/ajcp/aqae093","url":null,"abstract":"Objectives: We sought to investigate the adoption and perception of large language model (LLM) applications among pathologists.Methods: A cross-sectional survey was conducted, gathering data from pathologists on their usage and views concerning LLM tools. The survey, distributed globally through various digital platforms, included quantitative and qualitative questions. Patterns in the respondents' adoption and perspectives on these artificial intelligence tools were analyzed.Results: Of 215 respondents, 100 (46.5%) reported using LLMs, particularly ChatGPT (OpenAI), for professional purposes, predominantly for information retrieval, proofreading, academic writing, and drafting pathology reports, highlighting a significant time-saving benefit. Academic pathologists demonstrated a better level of understanding of LLMs than their peers. Although chatbots sometimes provided incorrect general domain information, they were considered moderately proficient concerning pathology-specific knowledge. The technology was mainly used for drafting educational materials and programming tasks. The most sought-after feature in LLMs was their image analysis capabilities. Participants expressed concerns about information accuracy, privacy, and the need for regulatory approval.Conclusions: Large language model applications are gaining notable acceptance among pathologists, with nearly half of respondents indicating adoption less than a year after the tools' introduction to the market. They see the benefits but are also worried about these tools' reliability, ethical implications, and security.","PeriodicalId":7506,"journal":{"name":"American journal of clinical pathology","volume":" ","pages":"52-59"},"PeriodicalIF":2.3,"publicationDate":"2025-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141791605","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}

引用次数: 0