Blood Research最新文献

{"title":"Danicopan add-on therapy for extravascular hemolysis in a patient with paroxysmal nocturnal hemoglobinuria receiving ravulizumab.","authors":"Yewon Park, Hyunjung Lee","doi":"10.1007/s44313-026-00186-7","DOIUrl":"https://doi.org/10.1007/s44313-026-00186-7","url":null,"abstract":"<p><strong>Introduction: </strong>Paroxysmal nocturnal hemoglobinuria (PNH) is characterized by complement-mediated hemolysis. Although C5 inhibitors effectively control intravascular hemolysis, some patients develop clinically significant extravascular hemolysis (EVH) because of upstream C3 deposition.</p><p><strong>Case: </strong>A 56-year-old woman was diagnosed with PNH in 2019 and managed with intermittent transfusions. In October 2024, she developed progressive renal dysfunction; the PNH clone size was 95.72%. Ravulizumab was initiated in March 2025. Although the lactate dehydrogenase (LDH) level normalized after ravulizumab initiation, her hemoglobin (Hb) level remained below 10 g/dL, with marked reticulocytosis and continued transfusion requirements after more than 6 months of treatment. Danicopan, a factor D inhibitor, was added in November 2025. Subsequently, her Hb level exceeded 10 g/dL, reticulocyte counts gradually decreased, and transfusion dependence declined.</p><p><strong>Discussion: </strong>This case demonstrates that adding danicopan to ravulizumab can reduce residual EVH and improve anemia in patients with PNH receiving C5 inhibitor therapy.</p>","PeriodicalId":46224,"journal":{"name":"Blood Research","volume":"61 1","pages":""},"PeriodicalIF":3.7,"publicationDate":"2026-10-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149275444","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":"Post-transplant monitoring of NGS-based measurable residual disease and donor chimerism as a prognostic tool in older patients with AML/MDS.","authors":"Se Hyung Kim, Jina Yun, Kyoung Ha Kim, Seug Yun Yoon, Chan Kyu Kim, Seong Kyu Park","doi":"10.1007/s44313-026-00187-6","DOIUrl":"https://doi.org/10.1007/s44313-026-00187-6","url":null,"abstract":"<p><strong>Purpose: </strong>To evaluate the prognostic value of integrated post-transplant monitoring of NGS-based measurable residual disease (MRD) and donor chimerism in older patients with acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS), undergoing reduced-intensity conditioning (RIC) allogeneic stem cell transplantation (allo-SCT).</p><p><strong>Materials and methods: </strong>This retrospective study analyzed the clinical outcomes of 113 patients with AML or MDS, aged ≥ 60 years or ≥ 55 years if deemed unfit for standard-intensity conditioning, who underwent RIC allo-SCT. NGS-based MRD testing and donor chimerism were assessed at 3 months post-transplant.</p><p><strong>Results: </strong>A total of 113 patients participated in the study (median age 63 years; 69.9% with AML); among the 105 patients evaluable at 3 months post-transplantation, MRD positivity occurred in 28 patients (26.7%) and predicted inferior overall survival (hazard ratio [HR] 6.373, 95% confidence interval [CI] 3.005-13.517; P < 0.001), while complete donor chimerism (CDC), achieved in 82 patients (78.1%), predicted improved survival (HR 0.356, 95% CI 0.195-0.916; P = 0.028). MRD positivity remained an independent predictor of survival on multivariate analysis (HR 3.315, 95% CI 1.423-7.230, P = 0.005), while CDC showed a trend toward improved survival that did not reach statistical significance (HR 0.494, 95% CI 0.306-1.009, P = 0.051). Two-year overall survival differed markedly across the four MRD/CDC subgroups, ranging from 85.6% [MRD(-)/CDC( +)] to 13.6% [MRD( +)/CDC(-)] (P < 0.001), with the MRD( +)/CDC(-) group showing the highest 2-year relapse incidence (69.7%).</p><p><strong>Conclusion: </strong>The combination of NGS-based MRD and chimerism monitoring is a critical prognostic strategy for older patients with AML/MDS undergoing RIC allo-SCT. Early identification of MRD positivity or mixed chimerism allows timely, risk-adapted interventions, including donor lymphocyte infusion, hypomethylating agents, and targeted therapies to reduce relapse and improve survival.</p>","PeriodicalId":46224,"journal":{"name":"Blood Research","volume":"61 1","pages":""},"PeriodicalIF":3.7,"publicationDate":"2026-10-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149275430","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":"Next-generation digital polymerase chain reaction assay for BCR::ABL1 in chronic myeloid leukemia: comprehensive validation for standardized measurable residual disease detection.","authors":"Yong-Hwi Kim, Min-Sik Jang, Shin-Hyun Kim, In-Young Roh, Bong-Suk Kim, Kyung-Mi Kee, Soo-Hyun Kim, Dong-Wook Kim, Jae-Hoon Kim","doi":"10.1007/s44313-026-00188-5","DOIUrl":"10.1007/s44313-026-00188-5","url":null,"abstract":"<p><strong>Purpose: </strong>The sensitivity of real-time quantitative reverse-transcription polymerase chain reaction (RT-qPCR) for detecting measurable residual disease (MRD) in patients with chronic myeloid leukemia (CML) who have achieved a deep molecular response is limited. We validated a digital PCR (dPCR) assay (LQ Check BCR::ABL1 Major %IS Kit) for MRD quantification.</p><p><strong>Methods: </strong>Validation was performed according to CLSI guidelines EP17-A2, EP06, EP05-A3, and EP07 using BCR::ABL1-positive and -negative materials and the World Health Organization (WHO) 1st International Standard. A nonparametric analysis of the limit of blank was used to establish a positivity cutoff of ≥ 2 droplets. The limit of detection (LoD) was verified using a detection criterion of ≥ 95%, and the limit of quantitation (LoQ) was defined as the lowest level meeting ≥ 95% detection and a study-defined %CV of ≤ 76%. Clinical validation included 72 CML specimens for molecular response (MR) category comparisons and 67 specimens for paired quantitative comparisons.</p><p><strong>Results: </strong>The LoD and LoQ were both 0.0025% on the International Scale (IS) with a detection rate of 95.8%. The assay showed linearity over 5 logs (R² = 0.9916-0.9972), within-run %CV ≤ 1.52%, cross-condition %CV ≤ 2.76%, and WHO-traceable accuracy. In 67 paired specimens, the correlation coefficient was r = 0.9740, with a Passing-Bablok slope of 1.0189, intercept of -0.2552, and Bland-Altman mean bias of 0.2266. Among the 72 specimens, dPCR classified 20 as having a deeper MR than RT-qPCR. Reproducibility was characterized by r = 0.99 and a mean bias of 0.0967. Whole blood was preferably processed within 48 h, with processing at 72 h considered acceptable only when BCR QC criteria were met.</p><p><strong>Conclusion: </strong>The LQ Check BCR::ABL1 Major %IS Kit enabled sensitive, precise, and reproducible BCR::ABL1 quantification at MR4.6. The clinical significance of a deeper MR classification using dPCR, particularly for treatment-free remission, requires longitudinal validation.</p>","PeriodicalId":46224,"journal":{"name":"Blood Research","volume":"61 1","pages":""},"PeriodicalIF":3.7,"publicationDate":"2026-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13675441/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149208054","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Toward integrated multimodal artificial intelligence in bone marrow examination: current state and open challenges.","authors":"Seung Yeob Lee","doi":"10.1007/s44313-026-00177-8","DOIUrl":"10.1007/s44313-026-00177-8","url":null,"abstract":"<p><p>Bone marrow (BM) examinations are intrinsically multimodal: hematopathologists integrate peripheral blood, aspirate cytomorphology, trephine histology, flow cytometry, cytogenetics, and molecular genetics data into a single interpretation. Because WHO-HAEM5 and ICC 2022 define entities through integrated morphological, immunophenotypic, cytogenetic, and molecular criteria, multimodal diagnostic reasoning embedded in a procedural workflow, not isolated image classification, represents the appropriate target for the use of artificial intelligence (AI). We review the existing research on integrated multimodal AI systems for BM examination by classifying these systems into three categories: mature single-modality tools; systems that perform cross-modal prediction, in which one modality is estimated from another; and genuine multimodal fusion systems, in which several modalities are jointly ingested by a single model. Evidence is stronger at the single-modality level, where deep learning approaches expert performance in aspirate cytology, trephine histology, and flow cytometry assessments, and the first Food and Drug Administration (FDA) De Novo-authorized all-digital bone marrow aspirate (BMA) application has defined a new device category. On the other hand, while cross-modal prediction is rapidly expanding, genuine multimodal fused systems that jointly ingest matched morphology, flow, molecular, and clinical data to yield unified guideline-aligned recommendations remain unrealized. Direct head-to-head evidence is sparse and endpoint-dependent; nevertheless, the lack of demonstrated superiority over the strongest single-modality comparator does not automatically imply the absence of benefits. The dominant obstacles are fusion of heterogeneous modalities with missing data, absence of large paired multi-institutional datasets and harmonized nomenclature, class imbalances, batch-effect-driven generalization failures, immature explainability, uncertainty quantification, and regulatory pathways. Nevertheless, integrated multimodal AI systems for BM examinations have entered a promising early translational phase, and the field should aim to pursue integration using paired datasets, explicit fusion architectures, calibrated abstention-aware models, and staged prospective validation.</p>","PeriodicalId":46224,"journal":{"name":"Blood Research","volume":"61 1","pages":""},"PeriodicalIF":3.7,"publicationDate":"2026-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13675459/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149208012","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Venetoclax combined with olverembatinib and prednisone as a frontline therapeutic strategy for Philadelphia chromosome-positive mixed-phenotype acute leukemia.","authors":"Xia Li, Yile Zhou, Xiangjie Lin, Hongyan Tong, Jie Jin, Huafeng Wang","doi":"10.1007/s44313-026-00180-z","DOIUrl":"10.1007/s44313-026-00180-z","url":null,"abstract":"<p><p>Mixed-phenotype acute leukemia (MPAL) is a rare hematological malignancy with poor prognosis, for which there are currently no standardized therapeutic guidelines. Preclinical and clinical studies have shown that venetoclax and BCR::ABL1 tyrosine kinase inhibitors have synergistic effects on Philadelphia chromosome-positive (Ph +) leukemias. We retrospectively analyzed five patients with de novo Ph + MPAL who received venetoclax, olverembatinib, and prednisone (VOP) therapy. All patients achieved complete remission after the initial induction therapy and tested negative for measurable residual disease. During consolidation therapy, two patients developed severe myelosuppression and died of respiratory failure due to pulmonary infections. The remaining three patients underwent allogeneic hematopoietic stem cell transplantation and maintained durable complete molecular remission. These findings suggest that the VOP regimen may be effective in patients with Ph + MPAL. However, they also underscore the need to optimize venetoclax dosing during consolidation to reduce the risk of life-threatening myelosuppression and infectious complications.</p>","PeriodicalId":46224,"journal":{"name":"Blood Research","volume":"61 1","pages":""},"PeriodicalIF":3.7,"publicationDate":"2026-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13661861/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149185303","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Understanding and clinical approach to early T-cell precursor acute lymphoblastic leukemia.","authors":"Hee Young Ju","doi":"10.1007/s44313-026-00181-y","DOIUrl":"10.1007/s44313-026-00181-y","url":null,"abstract":"<p><p>Early T-cell precursor acute lymphoblastic leukemia (ETP-ALL) is a distinct biological subtype of T-cell acute lymphoblastic leukemia (T-ALL) that was first described in 2009 based on a gene expression profile resembling that of early T-cell precursors in the thymus. ETP-ALL is characterized by an immature immunophenotype featuring positivity for CD7 and cytoplasmic CD3, with co-expression of myeloid/stem cell markers, and absence of CD1a, CD8, with weak or absent CD5 expression. ETP-ALL accounts for 5.5%-17.1% of pediatric and 15.8%-47.3% of adult T-ALL cases. Early studies identified ETP-ALL as a high-risk entity associated with induction failure and poor outcomes. However, subsequent prospective clinical trials demonstrated that outcomes with contemporary intensive chemotherapy were not significantly inferior to those of non-ETP T-ALL, challenging its designation as a uniformly high-risk disease. Recent large-scale genomic studies have identified molecularly defined subtypes that supersede immunophenotypic classifications, including ETP-like, BCL11B-rearranged, and SPI1-rearranged subtypes, with markedly different prognostic implications. Minimal residual disease (MRD) response remains the most robust prognostic indicator for guiding treatment intensification. Allogeneic hematopoietic stem cell transplantation (HSCT) is recommended for patients with persistent MRD positivity after consolidation. For relapsed/refractory disease, novel agents, including daratumumab, venetoclax, and bortezomib, have demonstrated promising activity, with allogeneic HSCT in the second complete remission remaining the treatment goal. This review provides an overview of the definitions, genomic classifications, clinical outcomes, and evolving treatment approaches for ETP-ALL.</p>","PeriodicalId":46224,"journal":{"name":"Blood Research","volume":"61 1","pages":""},"PeriodicalIF":3.7,"publicationDate":"2026-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13658697/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149165857","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correspondence on: \"Targeting the HERV-K102 envelope elicits pyroptosis and represents a novel therapeutic strategy for acute myeloid leukemia\".","authors":"Maajid Mohi Ud Din Malik, Rajesh Prasad Jayaswal","doi":"10.1007/s44313-026-00151-4","DOIUrl":"10.1007/s44313-026-00151-4","url":null,"abstract":"<p><p>Zong et al. reported that CRISPR-Cas9-mediated deletion of the HERV-K102 envelope (K-Env) induces apoptosis and pyroptosis in acute myeloid leukemia cells via S100A9/NLRP3 inflammasome activation. We examine four methodological concerns: the absence of evidence using a pathway-specific inhibitor to distinguish pyroptosis from secondary necrosis; the lack of a mechanistic rescue experiment confirming S100A9 as the proximal driver; the non-specificity of primers at the mRNA level; and the inability of the immunocompromised xenograft model to capture immune evasion by K-Env. The prognostic and therapeutic implications of the study require qualification.</p>","PeriodicalId":46224,"journal":{"name":"Blood Research","volume":"61 1","pages":""},"PeriodicalIF":3.7,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13646210/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149128911","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Interest of luspatercept in treatment of anemia in lower-risk of myelodysplastic syndrome anemia: a single center study of 26 patients.","authors":"A Elalaoui, C Girault, T Cluzeau","doi":"10.1007/s44313-026-00170-1","DOIUrl":"10.1007/s44313-026-00170-1","url":null,"abstract":"<p><strong>Background: </strong>Myelodysplastic syndromes (MDS) are heterogeneous clonal hematological disorders characterized by ineffective hematopoiesis resulting in peripheral cytopenias. Luspatercept, an erythroid maturation agent, represents a novel therapeutic option for the management of anemia associated with low-risk MDS, particularly in patients with ring sideroblasts and/or SF3B1 mutations.</p><p><strong>Methods: </strong>We retrospectively studied 26 adults with low- or intermediate-risk MDS who were treated with luspatercept from 2021 to 2024 at the Nice University Hospital. Data were collected from ORBIS and CLINICOM and analyzed using Microsoft Excel. Treatment was initiated at 1 mg/kg, depending on the patient.</p><p><strong>Results: </strong>The median age was 74 years, and 38.5% of patients had the SF3B1 mutation. Erythroid response was achieved in 53.8% of patients according to International Working Group (IWG) 2023. Treatment was generally well tolerated, with fatigue being the most common side effect (26.9%).</p><p><strong>Conclusion: </strong>Luspatercept appears to be effective in improving red blood cell production and reducing transfusion requirements in low-risk patients with MDS, with a favorable safety profile.</p>","PeriodicalId":46224,"journal":{"name":"Blood Research","volume":"61 1","pages":""},"PeriodicalIF":3.7,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13646230/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149128895","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sitosterolemia presenting as unexplained cytopenias: hematologic manifestations and genetic spectrum.","authors":"Navneet Mishra, Nitin Gupta, Naman Bansal, Meena Verma, Jyoti Kotwal","doi":"10.1007/s44313-026-00176-9","DOIUrl":"https://doi.org/10.1007/s44313-026-00176-9","url":null,"abstract":"<p><strong>Background: </strong>Sitosterolemia is a rare autosomal recessive disorder caused by pathogenic variants in the ATP-binding cassette subfamily G member 5 (ABCG5) or ATP-binding cassette subfamily G member 8 (ABCG8) gene, which increase the intestinal absorption of plant sterols and reduce their biliary excretion. It is classically linked to xanthomas and premature cardiovascular disease; however, many patients first present with haematologic abnormalities, often leading to diagnostic delay.</p><p><strong>Methods: </strong>We retrospectively reviewed six consecutive patients with clinical features suggestive of sitosterolemia and molecular variants in the ABCG5 or ABCG8 gene who were treated at a tertiary referral center between January 2024 and June 2026. We analyzed their clinical features, hematologic findings, genetic variants, treatment, and follow-up outcomes.</p><p><strong>Results: </strong>Six patients (three men and three women; median age, 40 years [range, 22-55 years]) presented with anemia, thrombocytopenia, and splenomegaly but were initially misdiagnosed with more common disorders, such as immune thrombocytopenia, iron-deficiency anemia, megaloblastic anemia, and Evans syndrome. All patients had stomatocytes and giant platelets on peripheral blood smears; three also had tendon xanthomas, and one had premature coronary artery disease. Genetic testing predominantly identified ABCG8 variants, as well as two ABCG5 variants, including a homozygous ABCG5 c.1724 T > G (p.Leu575Arg) variant that has not been previously reported and is currently classified as a variant of uncertain significance. All patients were advised to follow a phytosterol-restricted diet, and five received ezetimibe. Four patients with available follow-up data showed improvements in hemoglobin, platelet count, and spleen size during 4-12 months of follow-up. One patient was lost to follow-up, and one patient had insufficient follow-up for outcome assessment.</p><p><strong>Conclusion: </strong>Sitosterolemia should therefore be considered in patients with unexplained cytopenias, stomatocytosis, macrothrombocytopenia, and splenomegaly. Early recognition and genetic confirmation of this condition allows timely treatment with dietary modification and ezetimibe, thereby improving hematologic outcomes and preventing unnecessary investigations.</p>","PeriodicalId":46224,"journal":{"name":"Blood Research","volume":"61 1","pages":""},"PeriodicalIF":3.7,"publicationDate":"2026-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13633219/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149116347","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Diagnostic challenges posed by the wide morphological and immunophenotypic spectrum of plasma cell neoplasms.","authors":"Shih-Sung Chuang, Chung-Che Chang","doi":"10.1007/s44313-026-00179-6","DOIUrl":"https://doi.org/10.1007/s44313-026-00179-6","url":null,"abstract":"<p><p>Plasma cell neoplasms (PCNs) are a group of malignant neoplasms originating from the monoclonal expansion of immunoglobulin-secreting, terminally differentiated B cells, i.e., plasma cells (PCs). PCNs include monoclonal gammopathy of undetermined significance (MGUS), plasmacytoma (solitary plasmacytoma of the bone and extramedullary plasmacytoma), multiple myeloma (MM)/plasma cell myeloma, and rare PCNs associated with paraneoplastic syndromes. MM is a multifocal, bone marrow-based clonal PCN associated with end-organ damage and a monoclonal paraprotein (M protein) in the serum and/or urine. Morphologically, MMs are typically composed of mature to atypical PCs with a typical immunophenotype (CD38 + bright, CD138 + , CD19-, and monotypic light-chain expression), which are usually diagnostically straightforward. However, rare cases with morphological variants or immunophenotypic aberrancies may pose diagnostic challenges. Small, mature-appearing PC variants of MM at times may be difficult to differentiate from mature B-cell lymphomas with plasmacytic differentiation, such as lymphoplasmacytic lymphoma and marginal zone lymphoma, particularly in core needle biopsies. CD20 + and cyclin D1 + MM may mimic mantle cell lymphoma. Plasmablastic and pleomorphic/anaplastic variants are prone to present as extramedullary lesions mimicking plasmablastic lymphoma (PBL) or various types of lymphomas with pleomorphic/anaplastic morphology. Moreover, neoplastic PCs may exhibit aberrant expression of CD3, CD4, CD117, and cyclin D1, leading to potential diagnostic pitfalls. Diffuse CD30 expression with anaplastic morphology may be mistaken for anaplastic large-cell lymphoma. In rare instances, the neoplastic cells of PCNs are positive for Epstein-Barr virus (EBV), more frequently in cases with plasmablastic morphology and extramedullary involvement, which may raise suspicion for PBL. In this review, we emphasize the rare morphological and immunophenotypic features and variants of PCNs and utilize a few examples to highlight the diagnostic challenges.</p>","PeriodicalId":46224,"journal":{"name":"Blood Research","volume":"61 1","pages":""},"PeriodicalIF":3.7,"publicationDate":"2026-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13633204/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149116356","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}