{"title":"How I diagnose B-cell lymphoproliferative disorders with plasmacytic differentiation.","authors":"Jonathan H Young, Olga Pozdnyakova","doi":"10.1093/ajcp/aqae163","DOIUrl":"https://doi.org/10.1093/ajcp/aqae163","url":null,"abstract":"<p><strong>Objectives: </strong>B-cell lymphomas with plasmacytic differentiation is a broad category that includes small and large B-cell lymphomas. In this review, we focus on the small B-cell lymphomas, which include lymphoplasmacytic lymphoma and marginal zone lymphomas, among others. We aimed to review the diagnostic criteria of each entity and the features that distinguish them from each other.</p><p><strong>Methods: </strong>We discuss the clinical presentation, morphology, immunophenotype, molecular features, and potential pitfalls of diagnosing B-cell lymphomas with plasmacytic differentiation and provide 2 illustrative cases.</p><p><strong>Results: </strong>In some instances, small B-cell lymphomas with plasmacytic differentiation, particularly lymphoplasmacytic lymphoma and certain marginal zone lymphomas, have overlapping morphologic and immunophenotypic features. As a result, differentiating them may be difficult.</p><p><strong>Conclusions: </strong>In cases where classification is challenging, integration with clinical, radiologic, and laboratory findings may be helpful in arriving at a specific diagnosis. Instances remain, however, in which classification is difficult.</p>","PeriodicalId":7506,"journal":{"name":"American journal of clinical pathology","volume":" ","pages":""},"PeriodicalIF":2.3,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143555532","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}
Diane Wilcock, Deepika Sirohi, Joshua F Coleman, Parisa Adelhardt, Jong Taek Kim, Daniel Albertson, Kajsa Affolter, Cameron Beech, Jolanta Jedrzkiewicz, Ana L Ruano, Allison S Cleary, Jonathan Mahlow, Michael Balatico, H Evin Gulbahce
{"title":"HER2 fluorescence in situ hybridization groups 2-4 breast cancers classified as positive after targeted recounts following equivocal (2+) immunohistochemistry.","authors":"Diane Wilcock, Deepika Sirohi, Joshua F Coleman, Parisa Adelhardt, Jong Taek Kim, Daniel Albertson, Kajsa Affolter, Cameron Beech, Jolanta Jedrzkiewicz, Ana L Ruano, Allison S Cleary, Jonathan Mahlow, Michael Balatico, H Evin Gulbahce","doi":"10.1093/ajcp/aqaf006","DOIUrl":"https://doi.org/10.1093/ajcp/aqaf006","url":null,"abstract":"<p><strong>Objectives: </strong>To investigate the correlation between the extent of (percentage of tumor cells) immunohistochemistry (IHC) staining and final human epidermal growth factor receptor 2 (HER2)-positive result in fluorescence in situ hybridization (FISH) groups 2 to 4 with equivocal (2+) IHC requiring second, blinded FISH evaluation.</p><p><strong>Methods: </strong>Breast cancer cases submitted for HER2 FISH testing with group 2 to 4 results were included.</p><p><strong>Results: </strong>Of the 2548 cases with HER2 FISH groups 2 to 4 that had HER2 IHC performed, 1104 (43.3%) (76/182 [41.8%] of group 2, 94/161 [58.4%] of group 3, 934/2205 [42.4%] of group 4) had equivocal (2+) IHC. After second blinded, IHC-guided recounts, 217 of 1104 (19.7%) (17/76 [22.4%], 75/94 [79.8%], 125/934 [13.4%] of FISH groups 2, 3, 4 with IHC 2+, respectively) had final HER2-positive status. Only 13 of 217 (6%) of the cases with HER2-positive status had more than 50% circumferential staining of the tumor targeted for rescoring.</p><p><strong>Conclusions: </strong>In over 90% of HER2 FISH group 2 to 4 breast cancers with equivocal (2+) IHC followed by targeted, blinded second FISH evaluation and final HER2-positive result, the amplified population of tumor cells was limited (<50%). Current guidelines recommend cancers having 10% to 50% of the subpopulation with amplified cells classified as having genetic heterogeneity (GH), which have a poor response to targeted therapies. Identifying these tumors as having GH and/or repeat testing may be recommended.</p>","PeriodicalId":7506,"journal":{"name":"American journal of clinical pathology","volume":" ","pages":""},"PeriodicalIF":2.3,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143397760","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}
Jie Xu, Do Hwan Kim, Wei Wang, Shaoying Li, Pei Lin, Guilin Tang, Sergej Konoplev, Lianqun Qiu, Hong Fang, Sofia Garces, Vasiliki Leventaki, Shuyu E, L Jeffrey Medeiros, Sa A Wang
{"title":"Flow cytometric immunophenotypic features of acute myeloid leukemia with mast cell differentiation.","authors":"Jie Xu, Do Hwan Kim, Wei Wang, Shaoying Li, Pei Lin, Guilin Tang, Sergej Konoplev, Lianqun Qiu, Hong Fang, Sofia Garces, Vasiliki Leventaki, Shuyu E, L Jeffrey Medeiros, Sa A Wang","doi":"10.1093/ajcp/aqae116","DOIUrl":"10.1093/ajcp/aqae116","url":null,"abstract":"<p><strong>Objectives: </strong>Acute myeloid leukemia (AML) with mast cell (MC) differentiation was recently described as an aggressive subgroup of AML cases. The objectives of this study were to assess the flow cytometric immunophenotypic features of AML-MC cases.</p><p><strong>Methods: </strong>We characterized the immunophenotypic features of 21 AML-MC cases by flow cytometry and compared them to 20 reactive/regenerating bone marrow specimens.</p><p><strong>Results: </strong>The number of MCs detected by flow cytometry in AML-MC cases ranged from 0.4% to 21.1%, with a median of 3.5%, significantly higher than that of normal/reactive bone marrow (BM) (median, 0.01%; range, 0.000%-0.396%; P < .0001). Immunophenotypically, MCs in AML-MC cases demonstrated immaturity, differing from MCs in normal/reactive BMs, including dimmer CD45 (100% vs 0%), lower side scatter (100% vs 0%), more frequent CD34 (81% vs 20%), and CD123 (100% vs 10%) positivity, and more frequent uniform/increased CD38 expression (95% vs 20%) (all P ≤ .0001). CD2 (0/5) and CD25 (2/6, 1 uniform and 1 partial) were assessed in a subset of cases. The myeloblasts in AML-MC were typically CD34+CD117+HLA-DR+ with unusually frequent expression of CD56 (57%, all partial) and CD25 (63%, mostly partial), increased CD117 (62%), and decreased CD38 (86%). The MC percentage determined by flow cytometry correlated well with MCs detected by tryptase immunohistochemistry (r = 0.76, P < .001).</p><p><strong>Conclusions: </strong>The MCs in AML-MC cases are characterized by dim CD45, low side scatter, CD34 and CD123 positivity, and uniform and increased CD38 expression. Flow cytometry is an excellent tool for identifying AML-MC cases.</p>","PeriodicalId":7506,"journal":{"name":"American journal of clinical pathology","volume":" ","pages":"240-250"},"PeriodicalIF":2.3,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142153003","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}
Shuyu E, Jie Xu, Sa A Wang, Guilin Tang, Elias J Jabbour, Shaoying Li, M James You, L Jeffrey Medeiros, C Cameron Yin
{"title":"Blast phase of chronic myeloid leukemia presenting as early T-cell precursor acute lymphoblastic leukemia.","authors":"Shuyu E, Jie Xu, Sa A Wang, Guilin Tang, Elias J Jabbour, Shaoying Li, M James You, L Jeffrey Medeiros, C Cameron Yin","doi":"10.1093/ajcp/aqae115","DOIUrl":"10.1093/ajcp/aqae115","url":null,"abstract":"<p><strong>Objectives: </strong>The blasts in most cases of chronic myeloid leukemia blast phase (CML-BP) have a myeloid or precursor-B immunophenotype, with only a small subset having T-cell or natural killer-cell lineage. Patients with CML-BP having early T-cell precursor acute lymphoblastic leukemia (ETP-ALL) are extremely rare.</p><p><strong>Methods: </strong>We report the clinicopathologic, immunophenotypic, and molecular genetic features and outcome of 3 patients with CML-BP who had ETP-ALL, with a review of the literature.</p><p><strong>Results: </strong>Only patient 1 had a history of chronic myeloid leukemia chronic phase. Fluorescence in situ hybridization revealed BCR::ABL1 rearrangement in cells with round nuclei (blasts) and cells with segmented nuclei (neutrophils) in cases 2 and 3, supporting a diagnosis of CML-BP rather than de novo Ph+ ETP-ALL. The blasts were positive for cytoplasmic CD3, CD7, CD33, and CD117; were negative for CD1a and CD8; and had dim CD5 expression in 2 cases. Next-generation sequencing showed a TET2 mutation in case 1 and BCOR, RUNX1, and STAG2 mutations in case 3. All patients received chemotherapy and tyrosine kinase inhibitors. Patients 2 and 3 died 33 days and 39 days, respectively, after diagnosis. Patient 1 received stem cell transplantation and was alive 14 months after blast phase.</p><p><strong>Conclusions: </strong>Patients with CML-BP may have ETP-ALL. These patients usually have an aggressive clinical course, requiring intensive therapy, and may benefit from stem cell transplantation.</p>","PeriodicalId":7506,"journal":{"name":"American journal of clinical pathology","volume":" ","pages":"231-239"},"PeriodicalIF":2.3,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142138994","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":"Additional reporting of diffuse and homogeneous ROS-1 SP384 immunoreactivity enhances prediction of ROS1 fusion-positive non-small cell lung cancer.","authors":"Bokyung Ahn, Se Jin Jang, Hee Sang Hwang","doi":"10.1093/ajcp/aqae118","DOIUrl":"10.1093/ajcp/aqae118","url":null,"abstract":"<p><strong>Objectives: </strong>ROS-1 immunohistochemistry (IHC) is a common method for screening ROS1 fusion in the clinical management of non-small cell lung cancer. The interpretation criteria for ROS-1 SP384 IHC, however, remain unestablished.</p><p><strong>Methods: </strong>Sixty-five non-small cell lung cancer cases underwent AmoyDx ROS1 fusion real-time polymerase chain reaction (PCR) study and ROS-1 SP384 IHC tests, which were retrieved for analysis. ROS-1 IHC tests were interpreted based on the established classifiers as well as the presence of diffuse homogeneous immunoreactivity. The diagnostic accuracies of these ROS-1 IHC interpretation methods were evaluated by comparing them with the ROS1 real-time PCR results.</p><p><strong>Results: </strong>Previous ROS-1 IHC classifiers demonstrated high sensitivity for positive ROS1 real-time PCR results (100%), but they showed low specificities (25%-50%) and overall accuracies (58%-72%). In contrast, the diffuse homogeneous ROS-1 immunoreactivity predicted positive ROS1 real-time PCR results with much higher specificity (94%) and overall accuracy (95%), albeit with a slightly lower sensitivity (97%). Some cases that showed discrepancy between diffuse homogeneous ROS-1 immunoreactivity and real-time PCR results involved rare ROS1::LDLR fusion and suboptimal IHC staining.</p><p><strong>Conclusions: </strong>A 3-tier reporting system for ROS-1 SP384 IHC testing combining previous interpretation criteria and diffuse and homogeneous immunoreactivity may better predict ROS1 fusion status without decreasing specificity.</p>","PeriodicalId":7506,"journal":{"name":"American journal of clinical pathology","volume":" ","pages":"258-265"},"PeriodicalIF":2.3,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142278971","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":"Correction to: Escalation process of critical values when these cannot be communicated on first attempt: A hospital-wide process improvement project.","authors":"","doi":"10.1093/ajcp/aqae157","DOIUrl":"10.1093/ajcp/aqae157","url":null,"abstract":"","PeriodicalId":7506,"journal":{"name":"American journal of clinical pathology","volume":" ","pages":"323"},"PeriodicalIF":2.3,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142674883","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}