Christine M Cahill, Bianca Santonastaso, Madelyn Gatchell, Hannah Spector, Neil Blumberg, Phuong-Lan T Nguyen, Akua Asante, Debra Masel, Aimee Kievitt, Kelly Henrichs, Majed A Refaai
{"title":"Prophylactic half-dose platelet transfusion effect on thrombocytopenia, transfusion, and bleeding occurrence in patients with hematologic disease.","authors":"Christine M Cahill, Bianca Santonastaso, Madelyn Gatchell, Hannah Spector, Neil Blumberg, Phuong-Lan T Nguyen, Akua Asante, Debra Masel, Aimee Kievitt, Kelly Henrichs, Majed A Refaai","doi":"10.1093/ajcp/aqag032","DOIUrl":"https://doi.org/10.1093/ajcp/aqag032","url":null,"abstract":"<p><strong>Objectives: </strong>To provide the lowest effective dose and minimize toxicity, our transfusion service initiated the use of a half-dose for all prophylactic inpatient platelet transfusions. The main rationale for this change in dose was the lack of evidence of increased bleeding and mortality in lower-dose platelet transfusion. Since the current platelet dose is not evidence based, and dose and toxicity are linked for most therapeutics, this approach to reducing adverse effects made scientific and clinical sense. In addition, many blood centers have experienced platelet shortages.</p><p><strong>Methods: </strong>This retrospective study included nonbleeding patients older than 50 years with a diagnosed hematologic disease who received prophylactic platelet transfusions and were admitted to our inpatient cancer center between November 1, 2023, and January 1, 2024.</p><p><strong>Results: </strong>Significantly lower volumes of platelets (153 vs 313 mL, P < .0001; 95% CI, 153-166) were administered to the study cohort (n = 310) vs the control (n = 301). No significant differences were seen in the number of transfusion events per hospitalization of platelets (4.4 vs 4.1, P = .7; 95% CI, -2.2 to 1.5) and red blood cells (5.9 vs 7.5, P = .29; 95% CI, -1.4 to 4.7). The mean platelet counts were similar between both groups in pretransfusion (10.3 vs 10 × 109/L, P = .73; 95% CI, -1.8 to 1.3) and posttransfusion (13.8 vs 15.9 × 109/L, P = .16; 95% CI, -0.88 to 5.1). Bleeding event frequency was also similar between both groups (1.6% vs 1.3%, respectively).</p><p><strong>Conclusions: </strong>Half-dose platelets appear to be safe and effective in nonbleeding patients receiving prophylactic transfusions. This strategy reduces patient exposure to potentially harmful higher-dose transfusions without increasing bleeding events or red blood cell transfusions.</p>","PeriodicalId":7506,"journal":{"name":"American journal of clinical pathology","volume":"165 5","pages":""},"PeriodicalIF":1.9,"publicationDate":"2026-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147832265","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":"Comment on \"Reflex somatic testing for the detection of FGFR alterations in urinary tract carcinomas: a dual-institutional experience\".","authors":"Shyam Sundar Sah, Abhishek Kumbhalwar","doi":"10.1093/ajcp/aqaf150","DOIUrl":"10.1093/ajcp/aqaf150","url":null,"abstract":"","PeriodicalId":7506,"journal":{"name":"American journal of clinical pathology","volume":"165 4","pages":""},"PeriodicalIF":1.9,"publicationDate":"2026-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147615495","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":"Immunohistochemical expression of POC1A, NUF2, and Ki-67 in invasive ductal carcinoma of the breast: prognostic significance with insights into triple-negative breast cancer.","authors":"Dina M Thabit","doi":"10.1093/ajcp/aqag011","DOIUrl":"10.1093/ajcp/aqag011","url":null,"abstract":"","PeriodicalId":7506,"journal":{"name":"American journal of clinical pathology","volume":"165 4","pages":""},"PeriodicalIF":1.9,"publicationDate":"2026-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147669870","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":"Methodological and reporting concerns on paired analyses and survival modeling in a prognostic biomarker study of POC1A and NUF2.","authors":"Yang Chen, Gang Tian","doi":"10.1093/ajcp/aqag010","DOIUrl":"10.1093/ajcp/aqag010","url":null,"abstract":"","PeriodicalId":7506,"journal":{"name":"American journal of clinical pathology","volume":"165 4","pages":""},"PeriodicalIF":1.9,"publicationDate":"2026-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147669902","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}
Sounak Gupta, Farhad Kosari, Prabin Thapa, Stephen J Murphy, Sarah H Johnson, Patricia T Greipp, Nooshin K Dashti, Burak Tekin, Jabra G Zarka, Surendra Dasari, Benjamin R Kipp, Vidit Sharma, Paras H Shah, Jacob J Orme, Igor Frank, R Jeffrey Karnes, Stephen A Boorjian, George Vasmatzis, John C Cheville
{"title":"Sarcomatoid urothelial carcinoma with constitutive PD-L1 overexpression.","authors":"Sounak Gupta, Farhad Kosari, Prabin Thapa, Stephen J Murphy, Sarah H Johnson, Patricia T Greipp, Nooshin K Dashti, Burak Tekin, Jabra G Zarka, Surendra Dasari, Benjamin R Kipp, Vidit Sharma, Paras H Shah, Jacob J Orme, Igor Frank, R Jeffrey Karnes, Stephen A Boorjian, George Vasmatzis, John C Cheville","doi":"10.1093/ajcp/aqag023","DOIUrl":"10.1093/ajcp/aqag023","url":null,"abstract":"<p><strong>Objectives: </strong>Sarcomatoid urothelial carcinoma (sUC) is associated with poor clinical outcomes. Herein, we evaluated clinicopathologic features (including PD-L1 expression) for institutional cases.</p><p><strong>Methods: </strong>Sixty-five patients with sUC treated by radical cystectomy were matched for age, sex, and pathologic stage to 190 patients with pure urothelial carcinoma (UC). Outcomes were evaluated using the Kaplan-Meier method. Immunohistochemistry (IHC) results for tumor-specific PD-L1 expression in sUC were quantified using H-scores (range, 0-300). Cases with constitutive PD-L1 expression (cPD-L1; H-score ≥240) were evaluated for amplification events using fluorescence in situ hybridization (n = 28), mate-pair sequencing (Mpseq; n = 6), RNA sequencing (n = 5), and targeted next-generation sequencing (n = 8). PD-L1 regulatory pathways were evaluated using gene set enrichment analysis in the Cancer Hallmark dataset.</p><p><strong>Results: </strong>Most patients with sUC had advanced disease (≥pT2, 62/65, 95%), without significant differences in overall and cancer-specific survival, when matched to pure UC. Median PD-L1 H-scores using different clones were 100 (SP142), 120 (SP263), and 195 (22C3). cPD-L1 was seen in 43% (28/65) of cases of sUC that were enriched for TP53, TERT, and CDKN2A/B alterations. PD-L1 amplification was identified in 7 (of 28, 25%) of these cases. Bionformatics analysis consistently identified IL6-JAK-STAT3 and interferon α/γ signaling in sUC with cPD-L1 expression.</p><p><strong>Conclusions: </strong>Our results suggest that cPD-L1 expression in most sUC occurs secondary to IL6-JAK-STAT3 and interferon α/γ signaling. This provides a biologic rationale for evaluating response to immunotherapy in this patient population.</p>","PeriodicalId":7506,"journal":{"name":"American journal of clinical pathology","volume":"165 4","pages":""},"PeriodicalIF":1.9,"publicationDate":"2026-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147669926","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}
Leonie Saft, Alexandar Tzankov, Alexandra Traverse-Glehen, Anna Green, Roos Leguit, Olga Weinberg
{"title":"Myeloid/lymphoid precursor cell neoplasms and mixed phenotype acute leukemias: A Bone Marrow Workshop Report from the 22nd European Association for Hematopathology/Society of Hematopathology Meeting, Dubrovnik, 2024.","authors":"Leonie Saft, Alexandar Tzankov, Alexandra Traverse-Glehen, Anna Green, Roos Leguit, Olga Weinberg","doi":"10.1093/ajcp/aqag019","DOIUrl":"10.1093/ajcp/aqag019","url":null,"abstract":"<p><strong>Objectives: </strong>The bone marrow workshop (session 3), held at the 22nd Meeting of the European Association for Hematopathology/Society of Hematopathology in Dubrovnik, was dedicated to myeloid/lymphoid precursor cell neoplasms and mixed-phenotype acute leukemias (MPALs). We hereby report the clinicopathologic, immunophenotypic, and genetic features of the submitted cases.</p><p><strong>Methods: </strong>The workshop report includes 55 cases; 37 cases represented acute myeloid leukemia (AML) and acute leukemia of ambiguous lineage. Other cases included blast phase of chronic myeloid leukemia (CML), myeloid/lymphoid neoplasms with TK gene fusions (M/LN-TK), and myelodysplastic syndrome (MDS). Additionally, cases of early T-precursor lymphoblastic leukemia (ETP-ALL) and B-precursor lymphoblastic leukemia (B-ALL) were reviewed.</p><p><strong>Results: </strong>Among acute leukemia cases, 4 of 8 with the undifferentiated phenotype were reclassified as AML, myelodysplasia related (AML-MR) due to the presence of MDS-related gene mutations or complex karyotype. Thirteen of 20 MPAL cases were reclassified as AML-MR and/or AML with mutated TP53 (fifth edition of the World Health Organization classification/International Consensus Classification). Two cases had complex karyotypes and TP53 mutations, manifesting in the postcytotoxic treatment setting. TP53 mutations were absent in immunophenotypically defined MPAL and in MPAL with BCR::ABL1. Mixed phenotypes were also described in the blast phase of M/LN-TK, CML, and MDS.</p><p><strong>Conclusions: </strong>Mixed phenotype is frequently identified in AML-MR. Future studies are needed to clarify how cases with MR gene mutations and TP53 mutations should be best classified. Additionally, MPAL, T/myeloid, and ETP-ALL and some genetically defined MPAL, B/myeloid, and B-ALL show phenotypic/genetic overlap and are challenging to diagnose. A genomic classification framework is proposed to separate AML-MR and precursor lymphoid neoplasms from MPAL.</p>","PeriodicalId":7506,"journal":{"name":"American journal of clinical pathology","volume":"165 4","pages":""},"PeriodicalIF":1.9,"publicationDate":"2026-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147632274","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}
Attila Molnar, Diego Montoya-Cerrillo, Elizabeth A Montgomery, Oleksandr N Kryvenko
{"title":"The ancillary role of D2-40 in demonstration of muscularis propria invasion vs desmoplastic reaction in invasive urothelial carcinoma of the bladder.","authors":"Attila Molnar, Diego Montoya-Cerrillo, Elizabeth A Montgomery, Oleksandr N Kryvenko","doi":"10.1093/ajcp/aqag025","DOIUrl":"10.1093/ajcp/aqag025","url":null,"abstract":"<p><strong>Objectives: </strong>The presence or absence of muscularis propria (MP) invasion carries significant implications in bladder carcinoma treatment. Identification of MP is mainly based on morphology, with occasional application of immunohistochemical stains, including desmin, H-caldesmon, and smooth muscle actin (SMA), all aimed to stain smooth muscle. The specificity of these stains is imperfect. We evaluate the ancillary role of D2-40 in separating MP from desmoplastic reaction.</p><p><strong>Methods: </strong>We first examined immunoreactivity of muscularis mucosae and MP with the above markers in nonneoplastic specimens to establish their staining patterns. We then studied 33 cases of muscle-invasive urothelial carcinoma in which a desmoplastic reaction and MP were both present and clearly identifiable by routine hematoxylin and eosin morphology, with the goal of determining the sensitivity and specificity of these stains in identifying MP vs desmoplastic reaction.</p><p><strong>Results: </strong>Both muscularis mucosae and MP stained uniformly positive for desmin, H-caldesmon, and SMA and lacked expression of D2-40. The desmoplastic reaction showed positivity with desmin in 30 cases (91%), H-caldesmon in 29 cases (88%), SMA in 33 cases (100%), and D2-40 in 33 cases (100%). Expression of desmin, H-caldesmon, and SMA identified MP with 100% sensitivity, but their specificity dropped to 9%, 12%, and 0%, respectively. In contrast, D2-40 demonstrated 100% sensitivity and specificity in distinguishing MP vs desmoplastic reaction.</p><p><strong>Conclusions: </strong>We suggest using an immunohistochemical panel composed of D2-40 and a smooth muscle marker, preferably desmin or H-caldesmon, to help distinguish muscularis propria from desmoplastic reaction when morphology alone is equivocal.</p>","PeriodicalId":7506,"journal":{"name":"American journal of clinical pathology","volume":"165 4","pages":""},"PeriodicalIF":1.9,"publicationDate":"2026-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147669860","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}
Miguel Gonzalez Mancera, Aaron J Wilk, Jean Oak, Yasodha Natkunam, Oscar Silva
{"title":"TP53 genetic alterations are highly recurrent in Epstein-Barr virus-negative aggressive NK-cell leukemia: insights from an institutional experience and comprehensive literature review.","authors":"Miguel Gonzalez Mancera, Aaron J Wilk, Jean Oak, Yasodha Natkunam, Oscar Silva","doi":"10.1093/ajcp/aqag027","DOIUrl":"https://doi.org/10.1093/ajcp/aqag027","url":null,"abstract":"<p><strong>Objective: </strong>The differences between EBV-positive and EBV-negative aggressive NK-cell leukemia (ANKL) remain po orly understood. Herein, we sought to investigate the clinicopathologic and molecular differences between EBV-positive and EBV-negative ANKL.</p><p><strong>Methods: </strong>We retrospectively analyzed 14 ANKL cases (9 EBV-positive, 5 EBV-negative), assessing clinicopathologic, cytogenetic, and mutational features. In addition, we searched the published literature to further analyze the distribution of genetic variation between EBV-positive (n=116) and EBV-negative-ANKL (n=14). Lastly, we assessed the utility of p53 immunohistochemistry to screen for EBV-negative-ANKL.</p><p><strong>Results: </strong>Demographically, EBV-negative-ANKL patients were older (median age 64 vs. 37 years) and showed longer survival (median 13 vs. 1 month) than EBV-positive counterparts. Morphologic and immunophenotypic features were similar between groups. All EBV-negative cases assessed in our cohort harbored TP53 mutations (3/3). Combining our data with all reported ANKL cases with comprehensive mutational assessment of TP53, JAK/STAT and epigenetic modifier genes in the literature we find TP53 mutations or copy number alterations present in 82% of EBV-negative-ANKL (14/17) but in only 25% (29/116) of EBV-positive cases. In contrast, EBV-negative-ANKL showed less JAK/STAT and epigenetic modifier gene mutations compared to EBV-positive ANKL. Given the high frequency of TP53 genetic alteration, we show that p53 immunohistochemistry overexpression is present in all but one EBV-negative-ANKL case assessed thus far.</p><p><strong>Conclusions: </strong>Our findings suggest that EBV-negative-ANKL is a distinct subtype of ANKL, highly enriched for TP53 genetic alterations and showing different epidemiologic and prognostic features compared to EBV-positive-ANKL. In addition, p53 immunohistochemistry may serve as a screening tool for EBV-negative-ANKL.</p>","PeriodicalId":7506,"journal":{"name":"American journal of clinical pathology","volume":"165 4","pages":""},"PeriodicalIF":1.9,"publicationDate":"2026-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147759714","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}
Lijun Hao, Teng Xu, Yuanyuan Yu, Qin Huang, Li An, Yanjie Cui
{"title":"S1PR3 expression independently predicts the cumulative incidence of relapse in adult B-cell acute lymphoblastic leukemia: a single-center retrospective analysis.","authors":"Lijun Hao, Teng Xu, Yuanyuan Yu, Qin Huang, Li An, Yanjie Cui","doi":"10.1093/ajcp/aqag026","DOIUrl":"10.1093/ajcp/aqag026","url":null,"abstract":"<p><strong>Objectives: </strong>This study aims to investigate the predictive value of S1PR3 for the 3-year cumulative incidence of relapse (CIR) in adult patients with B-cell acute lymphoblastic leukemia (B-ALL).</p><p><strong>Methods: </strong>This retrospective study enrolled 285 adult patients with B-ALL and 13 healthy controls from January 2019 through January 2022. S1PR3 expression was analyzed in leukemia cell lines and peripheral blood mononuclear cells (MCs) using reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and Western blot. S1PR3 expression in bone marrow MCs was also measured by RT-qPCR. Predictive value was assessed using receiver operating characteristic curve analysis. Spearman correlation analysis was performed for correlation studies. Kaplan-Meier curves were employed for survival analysis. Cox regression was conducted for risk factor analysis.</p><p><strong>Results: </strong>S1PR3 was upregulated in leukemia cell lines and B-ALL patient MCs compared with controls (P < .001). Relapsed patients demonstrated elevated S1PR3 levels compared with nonrelapsed patients (P < .001). S1PR3 expression predicted B-ALL relapse with an area under the curve of 0.887. Patients with high S1PR3 had a significantly higher relapse rate than those with low S1PR3 (P < .001). S1PR3 expression was closely associated with clinicopathologic characteristics. High S1PR3 expression was associated with a leftward shift in Kaplan-Meier curves and significantly increased CIR in patients (P < .001). High S1PR3 expression was an independent risk factor for relapse within 3 years in patients with B-ALL (P < .05).</p><p><strong>Conclusions: </strong>Elevated S1PR3 expression is an independent predictor of relapse in adult B-ALL, providing a novel biomarker to enhance risk stratification and guide potential targeted interventions.</p>","PeriodicalId":7506,"journal":{"name":"American journal of clinical pathology","volume":"165 4","pages":""},"PeriodicalIF":1.9,"publicationDate":"2026-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147715745","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}