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Lymphoblastic lymphoma (LBL) with an early T-cell precursor phenotype has only been rarely reported. Nijmegen breakage syndrome (NBS) is an inherited chromosomal instability disorder with known predisposition to malignancies that is very rare as well. We report a case of early T-precursor LBL (ETP-LBL) in a patient with NBS, a rare combination that has not been reported. We raise the question of whether a chromosomal instability disorder such as NBS increases the propensity for early T-precursor acute lymphoblastic leukemia/lymphoma (ETP-ALL/LBL), given that ETP-ALL has been shown to have increased genomic instability compared to T-ALL. [ABSTRACT FROM AUTHOR]

Previous studies in patients with mature B-cell lymphomas (MBCL) have shown that pathogenic TP53 aberrations are associated with inferior chemotherapeutic efficacy and survival outcomes. In solid malignancies, p53 immunohistochemistry is commonly used as a surrogate marker to assess TP53 mutations, but this correlation is not yet well-established in lymphomas. This study evaluated the accuracy of p53 immunohistochemistry as a surrogate marker for TP53 mutational analysis in a large real-world patient cohort of 354 MBCL patients within routine diagnostic practice. For each case, p53 IHC was assigned to one of three categories: wild type (staining 1–50% of tumor cells with variable nuclear staining), abnormal complete absence or abnormal overexpression (strong and diffuse staining > 50% of tumor cells). Pathogenic variants of TP53 were identified with a targeted next generation sequencing (tNGS) panel. Wild type p53 expression was observed in 267 cases (75.4%), complete absence in twenty cases (5.7%) and the overexpression pattern in 67 cases (18.9%). tNGS identified a pathogenic TP53 mutation in 102 patients (29%). The overall accuracy of p53 IHC was 84.5% (95% CI 80.3–88.1), with a robust specificity of 92.1% (95% CI 88.0- 95.1), but a low sensitivity of 65.7% (95% CI 55.7–74.8). These results suggest that the performance of p53 IHC is insufficient as a surrogate marker for TP53 mutations in our real-world routine diagnostic workup of MBCL patients. By using p53 immunohistochemistry alone, there is a significant risk a TP53 mutation will be missed, resulting in misevaluation of a high-risk patient. Therefore, molecular analysis is recommended in all MBCL patients, especially for further development of risk-directed therapies based on TP53 mutation status. [ABSTRACT FROM AUTHOR]

Objectives To evaluate the utilization of hematopathology resources within our enterprise on axillary lymph node core biopsy (AxLNCB) specimens, particularly those obtained in the context of breast cancer screening. Methods The utilization of hematopathology resources was determined for all AxLNCB specimens over a 30-month period from across our enterprise, and chart review was performed for select patient demographics and radiographic features. The AxLNCB cases with benign histology were reviewed for subtyping of histologic patterns. Results Of the total 594 AxLNCB specimens, 61.6% were benign and 38.6% malignant. Of malignant cases, only 9.3% contained any hematologic malignancy, yet 94% of all cases received tissue triage for lymphoma, and 81% were reviewed at least in part by a hematopathologist. Six clinical parameters were found to independently predict risk of hematologic malignancy: male sex (P =.041), bilateral lymphadenopathy (P =.004), diffuse cortical thickening (P =.005), lack of breast cancer (P =.001), older age (P <.001), and history of hematologic malignancy (P <.001). Conclusions Our enterprise overused hematopathology resources in the evaluation of AxLNCB performed in the study period. Our process could improve from the application of a simple tool generated from this cohort to predict percent risk of the specimen containing hematologic malignancy using patient characteristics easily found via routine chart review. [ABSTRACT FROM AUTHOR]

Interfollicular Hodgkin lymphoma (IHL) has been rarely reported in the literature and is recognized by the WHO Classification as a morphologic pattern sometimes seen in mixed cellularity classic Hodgkin lymphoma (CHL). The changes may be subtle due to preservation of architecture. We report a case of a 9-year-old male with IHL showing preserved follicular architecture but with the presence of interfollicular infiltrates consisting of eosinophils, plasma cells, and Hodgkin-Reed-Sternberg (HRS) cells. Immunophenotyping confirmed the morphologic suspicion for IHL. A discussion and review of the literature are offered. We conclude that IHL is a variant that requires a high index of suspicion, as it may be easily missed due to the subtle morphologic features and preserved architecture seen in most cases. We further emphasize that unexplained interfollicular infiltrates of eosinophils may be clues that should prompt a search of HRS cells and consideration of immunohistochemical staining if needed. [ABSTRACT FROM AUTHOR]

Objectives VEXAS syndrome is an adult-onset autoinflammatory disease caused by a somatic pathogenic mutation in the UBA1 (ubiquitin-like modifier activating enzyme 1) gene. Patients present with rheumatologic manifestations and cytopenias and may have an increased predisposition to myelodysplastic syndrome (MDS) and plasma cell neoplasms. Prior studies have reported on the peripheral blood and bone marrow findings in patients with VEXAS syndrome. Due to the protean clinical presentation and lack of specificity of morphologic features (eg, vacuoles in early erythroid and granulocytic precursors), an optimal screening methodology to identify these patients in a timely fashion is desirable. Methods To further evaluate and describe the salient diagnostic morphologic features in VEXAS syndrome, we carried out a comprehensive study of the largest single-institution cohort to date. Diagnostic and follow-up bone marrow biopsy specimens from 52 male patients with molecularly identified VEXAS syndrome underwent central review. Results Cytopenias were common in all cases, primarily macrocytic anemia, monocytopenia, and thrombocytopenia. Bone marrow aspirate and biopsy were often hypercellular, with an increased myeloid/erythroid ratio, granulocytic hyperplasia with left shift, erythroid left shift, and megakaryocyte hyperplasia, which exhibited a range of striking morphologic findings. Distinctly vacuolated myeloid and erythroid precursors were seen in more than 95% of cases. Conclusions Our data reveal potential novel diagnostic features, such as a high incidence of monocytopenia and distinct patterns of atypical megakaryopoiesis, that appear different from dysmegakaryopoiesis typically associated with MDS. In our experience, those findings are suggestive of VEXAS, in the appropriate clinical context. [ABSTRACT FROM AUTHOR]

Intravascular large B-cell lymphoma (IVLBCL) is a rare lymphoma that affects the brain, skin, and bone marrow. We describe the case of a 75-year-old man who was admitted to the hospital after 4 h of stomach aches. A thorough physical examination indicated stomach discomfort and skin discoloration. Laboratory tests revealed thrombocytopenia and elevated lactate dehydrogenase levels. A computed tomography scan of the abdomen revealed that the small intestine wall was thickened, edematous, and necrotic. The necrotic small bowel was surgically removed, revealing many little round, homogenous, and unusual cells in the mesenteric vein. In-situ hybridization revealed that these cells were positive for PAX5, CD20, CD79a, CD10, and BCL2, as well as Epstein-Barr virus-encoded small RNA. After 1 week of hospitalization without treatment, the patient was diagnosed with IVLBCL and died of multiple organ dysfunction syndrome. IVLBCL is a rare illness that affects the small intestine and possibly the gastrointestinal system. It has an insidious start, a fast development, and a dismal prognosis. Knowing its clinicopathologic traits helps in understanding the illness, making an early diagnosis, and preventing rapid worsening. [ABSTRACT FROM AUTHOR]

BackgroundStudents’ ability to diagnose various blood disorders could be substantially improved by continuously reviewing approaches toward teaching hematology. This study aims to compare the effectiveness of light microscopes and projected images on students’ learning and determine medical students’ perception of these teaching methods.MethodsA randomized trial was conducted using a crossover design. Two groups, each with 30 students, were subjected to teaching methods based on light microscopes and projected images alternatively.ResultsNo differences were found in the two study groups’ baseline characteristics, such as median age, sex, and prior academic performance, as well as in the pre-test scores. Post-test scores were significantly higher among students subjected to the projection method than in the control group (Mean ± SD = 9.8 ± 1.7 vs. 5.1 ± 1.3, p

Flow cytometry is a vital diagnostic tool for hematologic and immunologic disorders, but manual analysis is prone to variation and time-consuming. Over the last decade, artificial intelligence (AI) has advanced significantly. In this study, we developed and validated an AI-assisted flow cytometry workflow using 379 clinical cases from 2021, employing a 3-tube, 10-color flow panel with 21 antibodies for primary immunodeficiency diseases and related immunological disorders. The AI software (DeepFlow™, version 2.1.1) is fully automated, reducing analysis time to under 5 min per case. It interacts with hematopatholoists for manual gating adjustments when necessary. Using proprietary multidimensional density–phenotype coupling algorithm, the AI model accurately classifies and enumerates T, B, and NK cells, along with important immune cell subsets, including CD4+ helper T cells, CD8+ cytotoxic T cells, CD3+/CD4−/CD8− double-negative T cells, and class-switched or non-switched B cells. Compared to manual analysis with hematopathologist-determined lymphocyte subset percentages as the gold standard, the AI model exhibited a strong correlation (r > 0.9) across lymphocyte subsets. This study highlights the accuracy and efficiency of AI-assisted flow cytometry in diagnosing immunological disorders in a clinical setting, providing a transformative approach within a concise timeframe. [ABSTRACT FROM AUTHOR]

Objectives Determination of bone marrow cellularity is a key part of bone marrow examination because it provides a small window into a patient's current state of hematopoietic well-being. Traditionally, bone marrow cellularity is estimated semiquantitatively through microscopic examination of core biopsy specimens harvested from the iliac crest of the pelvic bone. Bone marrow cellularity is then designated as hypercellular, normocellular, or hypocellular based on the patient's age. This assessment can have significant clinical impact, but the variation in the age-adjusted normocellularity range is not sufficiently characterized because of a lack of study data, especially in older patients (those older than 70 years of age). This study further established the normal range of bone marrow cellularity, particularly in older adults. Methods In this study, 570 benign staging and healthy donor bone marrows from patients 1 year to 93 years of age were analyzed for cellularity. Results Linear regression modeling demonstrates that cellularity in adults declines approximately 3% per decade, including after the seventh decade of life. The 90% reference interval for normocellularity in United States is 30% to 75% for those aged 18 to 90 years. Conclusions The findings revealed a more stable and slower rate of decline in cellularity with age in adults than the widely used linear model of "100% minus the patient age in decades." Normocellularity is better modeled based on age group. In those younger than 20 years of age, normocellularity ranges from 45% to 85% (mean [SD], 65% [20%]), as defined by Friebert et al in 1998. Based on our study finding of a little less than 3% decline per decade of age, the following is our recommendation for normocellularity range: For individuals 20 to 40 years of age, it ranges from 40% to 70% (mean [SD], 55% [15%]); for individuals 40 to 60 years of age, it ranges from 35% to 65% (mean [SD], 50% [15%]); and for individuals older than 60 years of age, it ranges from 30% to 60% (mean [SD], 45% [15%]). Interestingly, those older than 70 years of age do not show a significant decrease from those aged 60 to 69 years. [ABSTRACT FROM AUTHOR]

Objectives Leukemia diagnosis in Vietnam is limited by a lack of hematopathology training and expert consultation as well as the cost of high-magnification digitization of hematology slides. Screen-sharing software allows international collaboration with experienced hematopathologists for improved diagnostic accuracy. Methods A hematopathology education and consultation program was proposed for Vietnam hospitals. By appointment, pathologists in Vietnam with access to a microscope camera, imaging software, and high-speed internet were invited to review slides and data with a volunteer board-certified hematopathologist in the United States using secure videoconferencing software. A single hospital in southern Vietnam assigned a pathologist proficient in English to access this service. All consultations from this site with clinicopathologic information were logged. After a 2-year period of online consultation, case slides for selected diagnoses were reviewed under the microscope in Vietnam to assess concordance. Results In total, 135 consultations were logged, 53 of which were for blood and bone marrow. T-cell large granular lymphocytic leukemia (T-LGLL) was 1 of the most frequent bone marrow consultation-related diagnoses; all diagnoses of this entity were confirmed by in-person microscopy (100% concordance). A records search and physician surveys found no prior documented diagnoses of T-LGLL made in Vietnam before this education and consultation program. Conclusions Our virtual consultation model has improved patient care in Vietnam by providing correct diagnoses to inform best practices in treatment. As a result of our program, the first Vietnam diagnoses of T-LGLL were made and may help expand on the literature in this area. This model could provide cost-effective, real-time consultation and education services for pathologists in underserved communities. [ABSTRACT FROM AUTHOR]

Extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma) is an indolent non-Hodgkin lymphoma rarely seen in pediatric patients. MALT lymphoma most commonly involves the gastrointestinal tract or peri-orbital tissues, potentially as sequela of chronic antigenic stimulation or immune dysregulation. Rare cases of MALT lymphoma arising from the gynecologic tract have been reported in older adult patients. We present the unique case of a 16-year-old postpubescent female with MALT lymphoma localized to the gynecologic tract, who initially presented with abdominal fullness, abnormal uterine bleeding, and obstructive acute kidney injury secondary to urinary outflow obstruction. Intraoperatively, dense fibrosis of the uterus and left fallopian tube was noted which mimicked abdominal cocoon syndrome. She was treated with 6 cycles of bendamustine and rituximab with complete anatomic and metabolic remission. In this report we highlight a very unusual presentation of a rare malignancy in the pediatric population as well as unique treatment considerations given this patient's young age and tumor location. [ABSTRACT FROM AUTHOR]

ObjectivesSmall-volume biopsy-fine-needle aspiration biopsy (FNAB) with or without core biopsy-is in increasing use in diagnosis and management of lymphoma patients. Our objective was to survey the current practice in small-volume biopsy diagnosis of lymphoma, focusing on the interaction among hematopathologists and cytopathologists and the integration of FNAB, core biopsy, and flow cytometry studies at sign-out.MethodsThis study used a cross-sectional survey design employing the RedCap database distributed via nine pathology professional society email listservs. The survey consisted of 25 multiple-choice questions and several free text fields. In total, 128 pathologists participated.ResultsMost respondents indicated that FNAB specimens in which lymphoma is a diagnostic consideration (FNAB-L) are seen daily or weekly (68/116; 58.6%). However, most institutions have separate hematopathology and cytopathology services (72/116; 62.1%) with inconsistent communication. When communication occurred, respondents were frequently inclined to reconsider their original diagnoses. Barriers identified included lack of communication, inadequate access to diagnostic studies, no formal subspecialty training, and various opinions regarding FNAB in diagnosing lymphoma.ConclusionsThis survey showed that FNAB-L specimens are common, with a lack of uniformity in how complementary fine-needle aspiration and core biopsy specimens or flow immunophenotyping results are shared across hematopathology and cytopathology services.

Primary pulmonary Hodgkin’s lymphoma (PPHL) is a rare subtype of lymphoma that comprises a small percentage of primary pulmonary lymphomas. Due to its rarity and nonspecific symptoms, PPHL often presents diagnostic challenges. This case report presents a unique case of PPHL mimicking granulomatosis with polyangiitis, emphasizing the difficulties encountered during the diagnostic process. A 53-year-old female presented with vague symptoms including weakness, oedema, dry cough, and nasal cavity ulceration. Laboratory investigations revealed elevated C-reactive protein levels, a white blood cell count with neutrophilia, and lymphopaenia. Initial treatment with oral corticosteroids for suspected polyangiitis yielded no response. The patient subsequently developed a low-grade fever and pruritic erythematous rash. Diagnostic procedures, including bronchial brush biopsy, bronchial washing, mediastinal lymph node biopsy, nasal cavity ulceration biopsy, and initial lung biopsy, were inconclusive and resulted in exclusion of granulomatosis with polyangiitis. A subsequent computed tomography scan indicated disease progression in the left lung. A lung biopsy revealed fibrotic tissue with nodules containing Hodgkin- Reed-Sternberg cells, leading to the final diagnosis of classic Hodgkin lymphoma, nodular sclerosis subtype. Positron emission tomography scan findings confirmed PPHL. The patient received multiple chemotherapeutic regimens, with brentuximab vedotin demonstrating efficacy as the sole effective treatment. This exceptional case of PPHL underscores the extensive diagnostic and therapeutic workup involving a multidisciplinary team of clinicians, radiologists, and pathologists. Increased awareness of PPHL and its distinctive features will aid in the diagnosis of similar cases in the future, benefitting both clinicians and pathologists.

Introduction: Flow cytometry (FCM) is widely used in the diagnosis of mature B‐cell neoplasms (MBN), and FCM data are usually consistent with morphological findings. However, diffuse large B‐cell lymphoma (DLBCL), a common MBN, is sometimes not detected by FCM. This study aimed to explore factors that increase the likelihood of failure to detect DLBCL by FCM. Methods: Cases with a final diagnosis of DLBCL that were analysed by eight‐colour FCM were retrospectively collated. Clinical, FCM, histopathological and genetic data were compared between cases detected and cases not detected by FCM. Results: DLBCL cases from 135 different patients were analysed, of which 22 (16%) were not detected by FCM. In samples not detected by flow cytometry, lymphocytes were a lower percentage of total events (p = 0.02), and T cells were a higher percentage of total lymphocytes (p = 0.01). Cases with high MYC protein expression on immunohistochemistry were less likely to be missed by FCM (p = 0.011). Detection of DLBCL was not different between germinal centre B‐cell (GCB) and non‐GCB subtypes, not significantly affected by the presence of necrosis or fibrosis, and not significantly different between biopsy specimens compared to fine‐needle aspirates, or between samples from nodal compared to extranodal tissue. Conclusion: The study identifies several factors which affect the likelihood of DLBCL being missed by FCM. Even with eight‐colour analysis, FCM fails to detect numerous cases of DLBCL. [ABSTRACT FROM AUTHOR]

Background: A sensitive and specific donor screening strategy is essential for the prevention of transfusion-transmitted infections (TTI). The study was conducted to ascertain the comparative efficacy of ICT, CLIA and NAT methods. Methods: This cross-sectional analytical study was conducted in Regional Blood Center Abbottabad, Pakistan from 1st April to 25 August 2022. 6233 donors were screened for Hep B, C, and HIV by testing simultaneously with ICT, CLIA and NAT. Results: Active Hep B, C and HIV Infection was present in 0.51%, 0.28% and 0.00048% donors respectively. The sensitivity was found to be higher for HBV and HIV with CLIA as compared to ICT but was equal for HCV with both. whereas specificity was the same with both CLIA and ICT for all three viruses. PPV was higher with ICT for HBV and HCV, but for HIV it was found higher by CLIA. NPV was higher for all three viruses by CLIA as compared to ICT. Conclusion: In case rapid testing devices are used for the initial screening of blood in countries with limited resources, positive cases must be confirmed by CLIA and if possible, then by NAT because of missing cases in the window period and false positive cases. [ABSTRACT FROM AUTHOR]

The article discusses a case of Monomorphic Epitheliotropic Intestinal T-Cell Lymphoma (MEITL) relapse in a pericardial fluid. The patient initially underwent chemotherapy and stem cell transplant but experienced a relapse seven months later, leading to their unfortunate death due to tumoral pneumopathy. The study emphasizes the importance of histopathological, cytological examination, and flow cytometry in diagnosing and managing MEITL, which is a rare and aggressive form of T-cell lymphoma primarily affecting the gastrointestinal tract. [Extracted from the article]

B-cell and T-cell lymphomas and leukemias often have distinct genetic mutations that are diagnostically defining or prognostically significant. A subset of these mutations consists of specific point mutations, which can be evaluated using genetic sequencing approaches or point mutation specific antibodies. Here, we describe genes harboring point mutations relevant to B-cell and T-cell malignancies and discuss the current availability of these targeted point mutation specific antibodies. We also evaluate the possibility of generating novel antibodies against known point mutations by computationally assessing for chemical and structural features as well as epitope antigenicity of these targets. Our results not only summarize several genetic mutations and identify existing point mutation specific antibodies relevant to hematologic malignancies, but also reveal potential underdeveloped targets which merit further study.

Objectives This study compares the effectiveness of an interactive e-learning module with a traditional text-based method for teaching peripheral blood smear analysis. Methods Pathology trainees at Accreditation Council for Graduate Medical Education residency programs were asked to participate. Participants completed a multiple-choice test on peripheral blood smear findings. Trainees were randomized into completing an e-learning module or a PDF reading exercise with the same educational content. Respondents rated their experience and completed a postintervention test composed of the same questions. Results In total, 28 participants completed the study; 21 improved their score in the posttest (mean, 21.6 correct answers) compared with the pretest (19.8; P <.001). This improvement was seen in both the PDF (n = 19) and interactive (n = 9) groups, with no difference in performance between the 2 groups. Trainees with less clinical hematopathology experience showed a trend of having the largest performance improvement. Most participants completed the exercise within 1 hour, rated the exercise as easy to navigate, were engaged, and reported learning new information about peripheral blood smear analysis. All participants indicated that they would likely complete a similar exercise in the future. Conclusions This study suggests that e-learning is an effective tool for hematopathology education and equivalent to traditional narrative-based methods. This module could easily be incorporated into a curriculum. [ABSTRACT FROM AUTHOR]

The following fictional case is intended as a learning tool within the Pathology Competencies for Medical Education (PCME), a set of national standards for teaching pathology. These are divided into three basic competencies: Disease Mechanisms and Processes, Organ System Pathology, and Diagnostic Medicine and Therapeutic Pathology. For additional information, and a full list of learning objectives for all three competencies, see http://journals.sagepub.com/doi/10.1177/2374289517715040.1.

An increasing number of machine learning applications are being developed and applied to digital pathology, including hematopathology. The goal of these modern computerized tools is often to support diagnostic workflows by extracting and summarizing information from multiple data sources, including digital images of human tissue. Hematopathology is inherently multimodal and can serve as an ideal case study for machine learning applications. However, hematopathology also poses unique challenges compared to other pathology subspecialities when applying machine learning approaches. By modeling the pathologist workflow and thinking process, machine learning algorithms may be designed to address practical and tangible problems in hematopathology. In this article, we discuss the current trends in machine learning in hematopathology. We review currently available machine learning enabled medical devices supporting hematopathology workflows. We then explore current machine learning research trends of the field with a focus on bone marrow cytology and histopathology, and how adoption of new machine learning tools may be enabled through the transition to digital pathology. [ABSTRACT FROM AUTHOR]

The diagnosis of benign and neoplastic hematologic disorders relies on analysis of peripheral blood and bone marrow aspirate smears. As demonstrated by the widespread laboratory adoption of hematology analyzers for automated assessment of peripheral blood, digital analysis of these samples provides many significant benefits compared to relying solely on manual review. Nonetheless, analogous instruments for digital bone marrow aspirate smear assessment have yet to be clinically implemented. In this review, we first provide a historical overview detailing the implementation of hematology analyzers for digital peripheral blood assessment in the clinical laboratory, including the improvements in accuracy, scope, and throughput of current instruments over prior generations. We also describe recent research in digital peripheral blood assessment, particularly in the development of advanced machine learning models that may soon be incorporated into commercial instruments. Next, we provide an overview of recent research in digital assessment of bone marrow aspirate smears and how these approaches could soon lead to development and clinical adoption of instrumentation for automated bone marrow aspirate smear analysis. Finally, we describe the relative advantages and provide our vision for the future of digital assessment of peripheral blood and bone marrow aspirate smears, including what improvements we can soon expect in the hematology laboratory. [ABSTRACT FROM AUTHOR]

Myeloid leukemias are a broad group of hematological disorders, characterized by heterogeneous clinical and biological features. In recent years, unprecedented genetic discoveries and clinical–biological correlations have revolutionized the field of myeloid leukemias. The most relevant changes have specifically occurred in acute myeloid leukemia (AML), chronic myelomonocytic leukemia (CMML), chronic myeloid leukemia (CML) and myeloid neoplasms (MNs) with eosinophilia. The recently published International Consensus Classification (ICC) of myeloid neoplasms has addressed these changes, providing an updated framework and revised diagnostic criteria for such entities. This is also the aim of the 5th edition of the WHO classification of hematopoietic tumors, whose preliminary version was published in 2022. Parallel to this, new therapeutic options and novel molecular targets have changed the management of many myeloid entities, including AML and CML. This review aims to address the most relevant updates in the classification and diagnosis of AML, CMML, CML and MNs with eosinophilia. The state of the art of treatment and future therapeutic options for such disorders are also discussed. [ABSTRACT FROM AUTHOR]

The International Consensus Classification (ICC) and World Health Organization (WHO) proposed significant changes to the diagnostic criteria of myelodysplastic syndromes (MDS) in 2022. The impact of these criteria on hematopathology practice is uncertain. This study aims to evaluate the impact of the 2022 ICC and WHO 5th edition classifications on the diagnosis of cytopenias and MDS. Cases from 2021 performed for primary diagnosis of cytopenia(s)/MDS and their clinical, laboratory, and pathologic findings were reviewed and classified according to the new classification systems. The rate of major changes to the diagnosis was determined and potential pitfalls in the diagnostic approach, laboratory workflow, and clinical communication challenges were investigated. A total of 49 cases were recruited. Major changes to the diagnostic entities were made in 18/49 (37%) cases according to the WHO 5th edition, and 23/49 (47%) cases classified according to the ICC. The difference was accounted for by five cases of MDS-EB2 (revised WHO 4th edition) classified as MDS/AML (major change) in the ICC in contrast to no significant change (MDS-IB2) in the WHO 5th edition. MDS-SLD cases were not subject to major reclassification according to either system. The new molecularly defined categories of CCUS/CHIP, MDS-SF3B1, and MDS with biallelic TP53 mutations were almost identically represented in both systems in our cohort. A case of MDS-MLD was reclassified as CMML by both classification systems. There are few but important differences between the new MDS classification systems. A preimplementation assessment is helpful to identify diagnostic and potential clinical impacts of their adoption. [ABSTRACT FROM AUTHOR]

Fibroblastic reticulum cell tumor (FRCT) is a rare dendritic neoplasm arising from fibroblastic reticulum cells (FBRCs) and exhibiting peculiar cytokeratin expression. FRCTs usually involve the lymph nodes, although they can also be encountered in the spleen and soft tissues. FRCTs are composed of mildly atypical spindle or ovoid cells, arranged in loose whorls, which express almost invariably low-weight cytokeratins, smooth muscle actin, and CD68. An admixed lymphoplasmacytic infiltrate is also frequently present in solid organ sites. The clinical picture may vary from very indolent to aggressive disease exhibiting features of malignancy, such as cytological pleomorphism, necrosis, or high mitotic rate and metastatic potential. FRCT is a challenging diagnosis, due to its rarity and deceptive cytokeratin expression. Hereafter, we revise the most recent literature regarding such condition and report the case of an extremely indolent splenic FRCT, with no features of malignancy. [ABSTRACT FROM AUTHOR]

Hemophagocytic lymphohistiocytosis (HLH) is a complex, often under-recognized hyperinflammatory immune dysregulation syndrome arising in a diverse range of clinical scenarios and conditions. The accurate and timely diagnosis of HLH is crucial for patient survival, and usually requires a high level of clinical suspicion. The histologic corollary to clinical HLH – hemophagocytosis – is neither necessary or sufficient for the diagnosis of HLH, as it may be seen in a variety of reactive conditions, or may be absent in true HLH. Nevertheless, the finding of hemophagocytosis in specific clinical situations should prompt the consideration of HLH and further testing to exclude the condition. While traditionally described in bone marrow, identification of hemophagocytosis in other tissues, including lymphoid, splenic, liver, or neural tissue, can be an important asset to the overall recognition of HLH. In this review, we discuss the underlying pathophysiology and etiologies of, morphologic aspects hemophagocytosis and its associated histologic findings in different tissues and give a brief overview of diagnostic criteria and clinical evaluation. [ABSTRACT FROM AUTHOR]

Primary pulmonary Hodgkin’s lymphoma (PPHL) is a rare subtype of lymphoma that comprises a small percentage of primary pulmonary lymphomas. Due to its rarity and nonspecific symptoms, PPHL often presents diagnostic challenges. This case report presents a unique case of PPHL mimicking granulomatosis with polyangiitis, emphasizing the difficulties encountered during the diagnostic process. A 53-year-old female presented with vague symptoms including weakness, oedema, dry cough, and nasal cavity ulceration. Laboratory investigations revealed elevated C-reactive protein levels, a white blood cell count with neutrophilia, and lymphopaenia. Initial treatment with oral corticosteroids for suspected polyangiitis yielded no response. The patient subsequently developed a low-grade fever and pruritic erythematous rash. Diagnostic procedures, including bronchial brush biopsy, bronchial washing, mediastinal lymph node biopsy, nasal cavity ulceration biopsy, and initial lung biopsy, were inconclusive and resulted in exclusion of granulomatosis with polyangiitis. A subsequent computed tomography scan indicated disease progression in the left lung. A lung biopsy revealed fibrotic tissue with nodules containing Hodgkin-Reed-Sternberg cells, leading to the final diagnosis of classic Hodgkin lymphoma, nodular sclerosis subtype. Positron emission tomography scan findings confirmed PPHL. The patient received multiple chemotherapeutic regimens, with brentuximab vedotin demonstrating efficacy as the sole effective treatment. This exceptional case of PPHL underscores the extensive diagnostic and therapeutic workup involving a multidisciplinary team of clinicians, radiologists, and pathologists. Increased awareness of PPHL and its distinctive features will aid in the diagnosis of similar cases in the future, benefitting both clinicians and pathologists. [ABSTRACT FROM AUTHOR]

Flow cytometry is a vital diagnostic tool for hematologic and immunologic disorders, but manual analysis is prone to variation and time-consuming. Over the last decade, artificial intelligence (AI) has advanced significantly. In this study, we developed and validated an AI-assisted flow cytometry workflow using 379 clinical cases from 2021, employing a 3-tube, 10-color flow panel with 21 antibodies for primary immunodeficiency diseases and related immunological disorders. The AI software (DeepFlow™, version 2.1.1) is fully automated, reducing analysis time to under 5 min per case. It interacts with hematopatholoists for manual gating adjustments when necessary. Using proprietary multidimensional density–phenotype coupling algorithm, the AI model accurately classifies and enumerates T, B, and NK cells, along with important immune cell subsets, including CD4+ helper T cells, CD8+ cytotoxic T cells, CD3+/CD4−/CD8− double-negative T cells, and class-switched or non-switched B cells. Compared to manual analysis with hematopathologist-determined lymphocyte subset percentages as the gold standard, the AI model exhibited a strong correlation (r > 0.9) across lymphocyte subsets. This study highlights the accuracy and efficiency of AI-assisted flow cytometry in diagnosing immunological disorders in a clinical setting, providing a transformative approach within a concise timeframe.

Deep models for cell detection have demonstrated utility in bone marrow cytology, showing impressive results in terms of accuracy and computational efficiency. However, these models have yet to be implemented in the clinical diagnostic workflow. Additionally, the metrics used to evaluate cell detection models are not necessarily aligned with clinical goals and targets. In order to address these issues, we introduce novel, automatically generated visual summaries of bone marrow aspirate specimens called cell projection plots (CPPs). Encompassing relevant biological patterns such as neutrophil maturation, CPPs provide a compact summary of bone marrow aspirate cytology. To gauge clinical relevance, CPPs were inspected by 3 hematopathologists, who decided whether corresponding diagnostic synopses matched with generated CPPs. Pathologists were able to match CPPs to the correct synopsis with a matching degree of 85%. Our finding suggests CPPs can represent clinically relevant information from bone marrow aspirate specimens and may be used to efficiently summarize bone marrow cytology to pathologists. CPPs could be a step toward humancentered implementation of artificial intelligence (AI) in hematopathology, and a basis for a diagnostic-support tool for digital pathology workflows. [ABSTRACT FROM AUTHOR]

Amaç: Kemik iliği kor biyopsileri, kemik iliğinin hücresel özelliklerini, solid organ tümörü metastazlarını veya hematolojik malign tutulumlarını belirlemek için yapılan önemli incelemelerdir. Kor biyopsinin uzunluğu ve kalitesi doğru tanı konulmasını ve klinik süreci etkilemektedir. Bu çalışmada kemik iliği kor biyopsi uzunluğunun tanı sürecine olan etkisinin araştırılması amaçlanmıştır. Gereç ve Yöntem: Çalışmamızda bölümümüze son bir yıl içerisinde gelmiş olan kemik iliği biyopsi materyallerinin uzunlukları ve içerdikleri intertrabeküler alanlar mikroskop altında incelenmiş ve uzunlukları milimetre cinsinden ölçülmüştür. Kor biyopsiler; uzunlukları 15 milimetreye eşit ve/veya üzerinde ise yeterli grup, 15 milimetrenin altında ise yetersiz grup şeklinde iki gruba ayrılmıştır. Bulgular: Kor biyopsi uzunluğu 185 olguda (%48,9) yeterliydi. 194 olguda (%51,1) ise kemik iliği kor biyopsi uzunluğu 15 mm altında ölçüldü. Olguların 192 (%50,5) tanesine spesifik tanı (Miyeloproliferatif Neoplazi, Lenfoma tutulumu, Lösemi tanısı ve benzeri) konuldu. 188 olgunun (%49,5) ise selülaritesi değerlendirip görülen bulgular özetlendi. Spesifik tanı konabilen 192 olgunun 116 tanesinde (%62,4) biyopsi uzunluğu yeterli iken, spesifik tanı konulamayan 188 olgunun 118'inde (%62,8) biyopsi uzunluğu yetersizdi. Kor biyopsi uzunluğu ile spesifik tanı konulması arasında doğrudan kuvvetli bir ilişki vardı (p≤0,01). Sonuç: Kemik iliği kor biyopsi materyalleri güvenilir tanı için optimal büyüklükte alınmalı ve aspirasyon yaymaları ile birlikte değerlendirilmelidir. Ayrıca klinikopatolojik iş birliği tanı güvenirliğini artırmaktadır.

Deep models for cell detection have demonstrated utility in bone marrow cytology, showing impressive results in terms of accuracy and computational efficiency. However, these models have yet to be implemented in the clinical diagnostic workflow. Additionally, the metrics used to evaluate cell detection models are not necessarily aligned with clinical goals and targets. In order to address these issues, we introduce novel, automatically generated visual summaries of bone marrow aspirate specimens called cell projection plots (CPPs). Encompassing relevant biological patterns such as neutrophil maturation, CPPs provide a compact summary of bone marrow aspirate cytology. To gauge clinical relevance, CPPs were inspected by 3 hematopathologists, who decided whether corresponding diagnostic synopses matched with generated CPPs. Pathologists were able to match CPPs to the correct synopsis with a matching degree of 85%. Our finding suggests CPPs can represent clinically relevant information from bone marrow aspirate specimens and may be used to efficiently summarize bone marrow cytology to pathologists. CPPs could be a step toward human-centered implementation of artificial intelligence (AI) in hematopathology, and a basis for a diagnostic-support tool for digital pathology workflows.

Black cohosh is a readily available dietary supplement currently marketed as a remedy for dysmenorrhea and menopausal symptoms and is one of the top-selling herbal supplements in the United States. Black cohosh extract (BCE) was nominated to the National Toxicology Program (NTP) by the National Cancer Institute and the National Institute of Environmental Health Sciences due to its widespread use and lack of animal toxicity studies. Results of the NTP BCE subchronic mouse toxicity study revealed a dose-dependent, non-regenerative decrease in the erythron with an increase in the mean corpuscular volume (macrocytosis). Howell-Jolly bodies, or micronuclei, were significantly increased. These particular changes indicated an ineffective erythropoiesis consistent with a condition known as megaloblastic anemia. Megaloblastic anemia is due to disruptions in DNA synthesis during hematopoiesis and can be a result of an inherited or drug-induced disorder or a consequence of folate or cobalamin deficiency. Subsequent mouse studies revealed hematological and biochemical changes that were consistent with a functional cobalamin deficiency. This article will review basic mechanisms and laboratory features of megaloblastic anemia. The results of our studies including morphological abnormalities of the erythron and biomarkers of folate and cobalamin deficiencies, as well as hepatic microarray gene changes, are also discussed. [ABSTRACT FROM AUTHOR]

Objectives: The paucity of data regarding the availability and extent of diagnostic medical services across sub-Saharan Africa hinders appropriate allocation of resources to improve health care in these regions. We assessed anatomic pathology (AP) and clinical pathology (CP) services in Nigeria, one of the most populous and fastest-growing countries in the world., Methods: Two individual surveys (AP focused and CP focused) were developed by subject matter experts and administered to individuals involved in pathology and laboratory medicine diagnostic services at hospitals and laboratories across Nigeria between June and August 2022 using the American Society for Clinical Pathology email listserv., Results: A total of 75 responses (29 AP and 46 CP) were received from 48 unique laboratories. Twenty-four sites provided AP services and 35 provided CP services. Eleven respondents performed both AP and CP services. Among AP services, basic surgical and cytopathology capabilities were available at most sites; however, the availability of automated technologies (eg, automated sample processing and staining) was more variable. Advanced diagnostic techniques, (eg, immunohistochemistry, human papillomavirus testing, molecular diagnostics) were rarely performed. The most frequently available CP services included hematology, microbiology, and chemistry. Microbiology services appeared to be among the most robust laboratory medicine services, particularly parasitology and bacteriology testing. Similar to AP services, more advanced diagnostic assays, such as flow cytometry, cytogenetics, and molecular testing, were largely unavailable., Conclusions: These findings augment earlier studies and identify gaps that should be prioritized from a policy perspective to improve medical services and the overall health care infrastructure in Nigeria., (© American Society for Clinical Pathology, 2024.)

Previous studies in patients with mature B-cell lymphomas (MBCL) have shown that pathogenic TP53 aberrations are associated with inferior chemotherapeutic efficacy and survival outcomes. In solid malignancies, p53 immunohistochemistry is commonly used as a surrogate marker to assess TP53 mutations, but this correlation is not yet well-established in lymphomas. This study evaluated the accuracy of p53 immunohistochemistry as a surrogate marker for TP53 mutational analysis in a large real-world patient cohort of 354 MBCL patients within routine diagnostic practice. For each case, p53 IHC was assigned to one of three categories: wild type (staining 1-50% of tumor cells with variable nuclear staining), abnormal complete absence or abnormal overexpression (strong and diffuse staining > 50% of tumor cells). Pathogenic variants of TP53 were identified with a targeted next generation sequencing (tNGS) panel. Wild type p53 expression was observed in 267 cases (75.4%), complete absence in twenty cases (5.7%) and the overexpression pattern in 67 cases (18.9%). tNGS identified a pathogenic TP53 mutation in 102 patients (29%). The overall accuracy of p53 IHC was 84.5% (95% CI 80.3-88.1), with a robust specificity of 92.1% (95% CI 88.0- 95.1), but a low sensitivity of 65.7% (95% CI 55.7-74.8). These results suggest that the performance of p53 IHC is insufficient as a surrogate marker for TP53 mutations in our real-world routine diagnostic workup of MBCL patients. By using p53 immunohistochemistry alone, there is a significant risk a TP53 mutation will be missed, resulting in misevaluation of a high-risk patient. Therefore, molecular analysis is recommended in all MBCL patients, especially for further development of risk-directed therapies based on TP53 mutation status., (© 2023. The Author(s).)

Abstract Background Gastrointestinal complications are not uncommon in patients of Acute Leukemia. Intussusception as a complication in leukemia, although described, is exceedingly rare. Also, it is usually seen after chemotherapy and not as a part of the native disease process. This case report aims to highlight such a rare association which warrants clinical and pathological attention. Case presentation A 14 year old male presented with an acute abdomen. Initial routine investigations revealed a deranged blood picture. On further examination of bone marrow aspirate, biopsy and detailed immunohistochemical studies a diagnosis of B-Acute Lymphoblastic Leukemia (B-ALL) was made. Concurrent ultrasound of the abdomen to find a cause for severe abdominal pain revealed an Ileo-colic intussusception. The patient was started on steroids; however he succumbed to his illness after two days, before surgery could be attempted. Conclusion Rare presentations of relatively common diseases are a hurdle for timely and effective medical intervention. Although a rare condition in itself in leukemic patients, the occurrence of Intussusception in this particular patient, especially when no chemotherapy was initiated, is a very rare event. This case report was made to add to the relatively scarce literature available on this particular association. As it is a surgically treatable condition and since delay in diagnosis may lead to poorer prognosis, possibility of co-existence of ALL and intussusception should be borne in mind by all treating physicians and hematopathologists for effective patient care.

We describe a case of EBV-positive lymphoma with characterization of histological, immunophenotypic, and molecular features and a brief literature review of similar entities. Atypical large lymphoid cells with pleomorphic nuclei, moderate eosinophilic cytoplasm, and high mitotic activity were noted along with positivity for CD20, OCT2, CD79a, CD19, CD2, perforin, CD30, MUM1, c-MYC, BCL-2, and CD45. Dim positivity with PAX5 and weak cytoplasmic staining with CD3 was noted. These cells were negative for CD4, CD5, CD7, CD8, CD10, BCL-6, CD15, EMA, HHV-8, TdT, Cyclin-D1 and Granzyme B. EBV encoded RNA in situ hybridization was diffusely positive in atypical cells. Both T and B cell gene rearrangements were detected which demonstrates lineage overlap in EBV-positive large cell lymphomas, supported by B and T-cell receptor gamma gene rearrangement proven on molecular studies. The presence of similar entities may lead to potential misclassification of neoplasms. No prognostic significance of this finding was identified.

Hematopoietic disorders are serious diseases that threaten human health, and the diagnosis of these diseases is essential for treatment. However, traditional diagnosis methods rely on manual operation, which is time consuming and laborious, and examining entire slide is challenging. In this study, we developed a weakly supervised deep learning method for diagnosing malignant hematological diseases requiring only slide-level labels. The method improves efficiency by converting whole-slide image (WSI) patches into low-dimensional feature representations. Then the patch-level features of each WSI are aggregated into slide-level representations by an attention-based network. The model provides final diagnostic predictions based on these slide-level representations. By applying the proposed model to our collection of bone marrow WSIs at different magnifications, we found that an area under the receiver operating characteristic curve of 0.966 on an independent test set can be obtained at 10× magnification. Moreover, the performance on microscopy images can achieve an average accuracy of 94.2% on two publicly available datasets. In conclusion, we have developed a novel method that can achieve fast and accurate diagnosis in different scenarios of hematological disorders. [ABSTRACT FROM AUTHOR]

Introduction: Following bariatric and metabolic surgery (BMS), patients may develop persistent cytopenia(s) despite adequate micronutrient levels. A comprehensive analysis of laboratory and hematopathologic findings in BMS patients with unexplained cytopenia(s) has not been previously described. Methods: We reviewed the clinical and laboratory data, bone marrow histology, and used ancillary testing to characterize patients with a history of BMS who had subsequent bone marrow biopsies due to unexplained cytopenia(s). Results: All patients had anemia and 59% (23/39) had additional cytopenias. Myelodysplastic syndrome (MDS) and clonal cytopenia of unknown significance (CCUS) were diagnosed in 8% (3/39) and 10% (4/39), respectively. Remaining cases were classified as idiopathic cytopenia of unknown significance (ICUS) with anemia alone (ICUS‐A) in 47% (15/32) or multiple cytopenias (ICUS‐PAN) in 53% (17/32). Time since surgery, age, or amount of weight loss was not associated with a specific diagnosis. No patient was vitamin B12 or folate deficient. However, vitamin B6 and zinc were decreased in 47% (5/11) and 29% (9/29), respectively. Examination of bone marrow aspirates revealed slight erythroid dyspoiesis affecting <10% of precursors in 60% (9/15) ICUS‐A and 59% (10/17) ICUS‐PAN. Conclusion: Bone marrow findings in patients with unexplained cytopenia(s) after BMS are not specific in the majority of cases, and caution is advised when interpreting dyserythropoiesis. Levels of micronutrients and vitamins other than iron, folate and vitamin B12 are frequently disturbed in this patient cohort and warrant correction and close clinical follow‐up. [ABSTRACT FROM AUTHOR]

Histiocytic proliferations are heterogeneous lesions with distinct pathogenic and clinical-pathological features. While many of these conditions are nonspecific immune responses to variable causes, a minority of them is associated with specific etiological factors and unique clinical-pathological pictures. By presenting a rare case of Whipple adenopathy, we address the peculiar histological features of this condition and the differential diagnosis of nodal histiocytosis in general. [ABSTRACT FROM AUTHOR]

The story of Thomas Grogan, MD is one of the most compelling narratives in the modern history of pathology. Progressing from a quintessential academic pathologist to an entrepreneur and a renowned inventor, his remarkable journey is one of creativity, courage, and a keen focus on improving the care of cancer patients. By enabling precision health and empowering the pathologist in that mission, he transformed the landscape of diagnostic pathology. In this review, we describe some of his salient contributions and how his vision has shaped and continues to shape hematopathology today.

Hematopoietic disorders are serious diseases that threaten human health, and the diagnosis of these diseases is essential for treatment. However, traditional diagnosis methods rely on manual operation, which is time consuming and laborious, and examining entire slide is challenging. In this study, we developed a weakly supervised deep learning method for diagnosing malignant hematological diseases requiring only slide-level labels. The method improves efficiency by converting whole-slide image (WSI) patches into low-dimensional feature representations. Then the patch-level features of each WSI are aggregated into slide-level representations by an attention-based network. The model provides final diagnostic predictions based on these slide-level representations. By applying the proposed model to our collection of bone marrow WSIs at different magnifications, we found that an area under the receiver operating characteristic curve of 0.966 on an independent test set can be obtained at 10× magnification. Moreover, the performance on microscopy images can achieve an average accuracy of 94.2% on two publicly available datasets. In conclusion, we have developed a novel method that can achieve fast and accurate diagnosis in different scenarios of hematological disorders.

Lymphomatous infiltration of kidney parenchyma is a frequent complication of systemic hematologic malignancies and often shows subtle clinical presentation. Diffuse large B-cell lymphoma represents the most frequent form involving the kidney, with advanced stage at diagnosis, poor outcome, and risk for central nervous system relapse if not adequately treated. Kidney biopsy can provide specific and early detection of these cases, helping in the differential diagnosis with more frequent entities. Finally, further hematologic workup (bone marrow biopsy, complete blood cell count, and positron emission tomography) can distinguish secondary involvement of the kidney from the rarer kidney-limited forms, especially in patients without a previous diagnosis of lymphoma. Making a prompt and correct diagnosis directs the management of these cases and may improve the outcome, as described in the present report.

Hematologic neoplasms with germline predisposition have been increasingly recognized as a distinct category of tumors over the last few years. As such, this category was added to the World Health Organization (WHO) 4th edition as well as maintained in the WHO 5th edition and International Consensus Classification (ICC) 2022 classification systems. In practice, these tumors require a high index of suspicion and confirmation by molecular testing. Flow cytometry is a cost-effective diagnostic tool that is routinely performed on peripheral blood and bone marrow samples. In this review, we sought to summarize the current body of research correlating flow cytometric immunophenotype to assess its utility in diagnosis of and clinical decision making in germline hematologic neoplasms. We also illustrate these findings using cases mostly from our own institution. We review some of the more commonly mutated genes, including CEBPA, DDX41, RUNX1, ANKRD26, GATA2, Fanconi anemia, Noonan syndrome, and Down syndrome. We highlight that flow cytometry may have a role in the diagnosis (GATA2, Down syndrome) and screening (CEBPA) of some germline predisposition syndromes, although appears to show nonspecific findings in others (DDX41, RUNX1). In many of the others, such as ANKRD26, Fanconi anemia, and Noonan syndrome, further studies are needed to better understand whether specific flow cytometric patterns are observed. Ultimately, we conclude that further studies such as large case series and organized data pipelines are needed in most germline settings to better understand the flow cytometric immunophenotype of these neoplasms., (© 2024 International Clinical Cytometry Society.)

Fluorescence confocal microscopy (FCM) is an optical technique that uses laser light sources of different wavelengths to generate real-time images of fresh, unfixed tissue specimens. Unlike conventional histologic evaluation methods, FCM is able to assess fresh tissue samples without the associated cryo artifacts typically observed after frozen sectioning. The purpose of this study was to evaluate the utility of FCM imaging in the differential diagnosis of cervical lymphadenopathy. Twenty-two cervical lymph node specimens from patients with lymphadenopathy of unknown origin were imaged by FCM. Two pathologists independently evaluated the scans for suspicion of malignancy and preliminary diagnosis. Malignancy was reliably excluded or confirmed by both pathologists with a sensitivity of 90.9% for pathologist 1 and 100% for pathologist 2. The specificity was 100% for both pathologists. For the preliminary diagnosis, almost perfect agreement with the final diagnosis was observed for both pathologists (κ = 0.94 for pathologist 1 and κ = 1.00 for pathologist 2). This is the first study to investigate lymph node specimens with different diagnoses, including lymphoma, using FCM. Our results indicate that differential diagnosis of lymph node specimens is feasible in FCM images, thus encouraging further exploration of FCM imaging in lymph node specimens to accelerate diagnosis and open the possibility of digitizing diagnosis on fresh, unfixed tissue., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Students' ability to diagnose various blood disorders could be substantially improved by continuously reviewing approaches toward teaching hematology. This study aims to compare the effectiveness of light microscopes and projected images on students' learning and determine medical students' perception of these teaching methods., Methods: A randomized trial was conducted using a crossover design. Two groups, each with 30 students, were subjected to teaching methods based on light microscopes and projected images alternatively., Results: No differences were found in the two study groups' baseline characteristics, such as median age, sex, and prior academic performance, as well as in the pre-test scores. Post-test scores were significantly higher among students subjected to the projection method than in the control group (Mean ± SD = 9.8 ± 1.7 vs. 5.1 ± 1.3, p  < 0.001). In the post-cross-over assessment, 85% ( n  = 51) of students reported their satisfaction for the projected images, and 78% ( n  = 47) of students were willing to be taught by projection. Students perceived that the projection method facilitated participation and better involvement in discussions, improved learning, provided greater motivation, and eventually increased comprehension and efficiency., Conclusion: The projection-based teaching method is more effective in improving knowledge and achieving intended learning outcomes. Students tend to prefer the projection method over the laboratory-based method and perceive it as an effective method to enhance their learning of hematology., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Alqahtani, Al-Nasser, Agha and Mohamud.)