Digital morphology compared to the optical microscope: A validation study on reporting bone marrow aspirates.

INTRODUCTION: This study aims to evaluate the effectiveness and reliability of the utilization for clinical reporting of the evaluation of digital images of bone marrow aspirates by morphologists and their comparability with the classic microscopic morphological evaluation. METHODS: We scanned 180 consecutive bone marrow needle aspirates smears using the "Metafer4 VSlide" whole slide imaging (WSI) digital scanning system. We evaluated the statistical comparability and the risk of bias of the microscopic readings with those performed on the screen on the digitized medullary images. RESULTS: The evaluation of cellularity on the screen was equivalent, with a higher frequency of "normal" than the analysis of digital preparations. The means and medians of the percentage values obtained on the different cell populations with the microscopic and digital reading were comparable as the main categories are concerned, with an average difference equal to 0 for the neutrophilic and eosinophilic granulocytic series, at -0.2% for the total myeloid cells, at 1.2% for the erythroid series, at -0.4% for the lymphocytes and at -0.4% for the blasts. Dysplastic features were consistently identified in 69/71 cell lineages. CONCLUSION: Our study demonstrated that screen evaluation of digitized bone marrow needle aspirates provides quantitative and qualitative results comparable to traditional microscopic analysis of the corresponding slide smears. Digital images offer significant benefits in reducing the workload of experienced operators, reproducibility and sharing of observations, and image preservation. Even in routine diagnostic activities, their use does not alter the quality of the results obtained in evaluating bone marrow needle aspirates.

Predictive model for diagnostic yield of bone marrow examination in patients with HIV infection having fever of unknown origin.

OBJECTIVE: Bone marrow examination is valuable for identifying the cause of fever of unknown origin (FUO) in HIV-infected patients. Based on the outcomes of bone marrow examination of patients with FUO, we aimed to develop a predictive model for identifying the factors that can increase the diagnostic yield of bone marrow examination. DESIGN: For this retrospective cohort study, we enrolled HIV-infected patients, aged more than 15 years and diagnosed with FUO, at Songklanakarind Hospital in Southern Thailand, between January 2009 and December 2019. METHODS: Evaluations were based on bone marrow aspiration, biopsy, and culture; any missing data were imputed with regression imputation. RESULTS: Among the final 108 included patients, 44 (40.74%) showed positive bone marrow results. The diagnoses mainly comprised histoplasmosis, penicilliosis, and tuberculosis. Bone marrow examination led to treatment modifications in approximately 33% patients. Platelet count less than 150 000 cells/µl, alkaline phosphatase (ALP) level at least 200 U/l, and no previous antibiotic treatment were significantly associated with higher diagnostic yields. The HIV bone marrow (HIVBM) model, comprising of spleen size, hematocrit (Hct), platelet count before bone marrow examination, ALP level at admission, and previous antibiotic treatment, was generated as a nomogram to predict the diagnostic yield of bone marrow examination in HIV-infected patients with FUO. CONCLUSION: The results of this study indicate that the HIVBM model can be used to predict the diagnostic yield of bone marrow examination, and therefore assist in clinical decision-making regarding bone marrow procedures, to be performed for identifying the origin of fever in HIV-infected patients.

Determination of age-dependent bone marrow normocellularity.

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.

Hemophagocyte morphology and hypertriglyceridemia correlate with diagnosis of hemophagocytic lymphohistiocytosis in patients with bone marrow hemophagocytes.

OBJECTIVES: To investigate laboratory and bone marrow findings that can help predict a diagnosis of hemophagocytic lymphohistiocytosis (HLH) for patients who have demonstrated hemophagocytes (HPCs) in the bone marrow. METHODS: A total of 57 cases from 48 patients with HPCs present on bone marrow examination were included. The numbers and morphologic characteristics of HPCs with ingested nucleated cells (nHPC) were counted. Pertinent medical history, relevant laboratory values, and flow cytometry data at the time of bone marrow biopsy were collected. RESULTS: A total of 24 patients fulfilled diagnostic criteria for HLH, and the remaining 24 patients did not. By using HLH-2004 cutoffs, only hypertriglyceridemia (≥265 mg/dL) was significantly associated with HLH diagnosis. The HLH cases more frequently had nHPC-ingesting granulocytic cells (gHPC) (75.9% vs 24.1%, P = .009). The percentage of gHPC to all nHPC was also significantly higher in HLH cases (median, 15.4% vs 0%; P = .0002). Both triglyceride level (area under the curve [AUC] = 0.88, P < .0001) and gHPC percentage (AUC = 0.81, P = .0005) were significant in predicting HLH diagnosis. Finally, no overt immunophenotypic abnormality was noted for 19 HLH cases with available flow cytometry data. CONCLUSIONS: The presence of hypertriglyceridemia and more frequent gHPC has predictive value for HLH diagnosis in patients with bone marrow HPC.

Utility of bone marrow examination in retinoblastoma and their correlation with hematological features.

Retinoblastoma makes up about 3% of all childhood malignancies. The frequency of metastatic retinoblastoma ranges from 4.8 to 11%. Assessing the bone marrow status of newly diagnosed patients is crucial because of the advantages of autologous bone marrow transplants for high-risk patients. This study aimed to determine the utility of bone marrow examination in cases of retinoblastoma and its correlation with hematological findings. This retrospective study was conducted at the Department of Pathology, King George's Medical University, Lucknow, India. A total of 34 cases of retinoblastoma with bone marrow examination were included in the study. Bone marrow infiltration was present in 17.65% (6/34) cases of retinoblastoma. Bone marrow aspirate myelogram showed that marrow metastasis in retinoblastoma was significantly linked with a reduced percentage of total myeloid cells (p=0.001) and segmented cells (p=0.006). The present study demonstrated that 15% (3/20) of retinoblastoma patients previously classified as nonmetastatic before bone marrow examination (stages I to III based on histology, imaging, and bone scan) had bone marrow metastases following bone marrow examination and were upgraded to stage IV. To conclude, a diligent and exhaustive search for metastatic cells in bone marrow is advised if the myelogram shows a reduced percentage of total myeloid and segmented cells. All stage II and stage III cases of retinoblastoma must undergo bone marrow examination for early metastasis detection, as it may result in an upgrade to stage IV disease, impacting the prognosis and necessitating distinct treatment modalities.

Detection of focal lesions in the clot section with negative bone marrow aspirate and trephine biopsy-A series of 5 cases.

Bone marrow aspiration and trephine biopsies are commonly used procedures in clinical practice. The practice of making a clot section by using the leftover blood from the bone marrow aspirate material is not a commonly followed practice across centers. A clot section has the advantage of studying the added material with an increased possibility of detecting focal lesions such as myeloma, lymphoma, granuloma, and metastasis in the bone marrow. Bone marrow aspirate, trephine biopsy, and clot section were compared for the detection of focal lesions in a series of 5 patients, 3 of who presented with a history of fever and 2 were already diagnosed cases of Hodgkin lymphoma. Focal lesions were detected in the 5 cases in the clot section alone, whereas bone marrow aspirate and trephine biopsy did not show any focal lesion. Granulomatous infiltration was detected in 3 patients, and lymphomatous infiltration was detected in 2 patients in the clot section, whereas bone marrow aspirate and trephine biopsy were negative for any focal lesion in all 5 cases. A clot section is particularly useful in the detection of bone marrow lesions with a focal distribution. Hence, it must be studied alongside bone marrow aspirate smears, touch smears, and trephine biopsy to increase the diagnostic yield.

The value of bone marrow examinations performed in the investigation of HIV infected patients with cytopenias.

INTRODUCTION: Bone marrow examination (BME) is a reliable and effective tool in the diagnosis of many haematological and non-haematological diseases and may be used to investigate unexplained cytopenia in human immunodeficiency virus (HIV) infected patients. The objective of this study was to determine the diagnoses made, diagnostic yield and unique diagnostic yield of BMEs performed to investigate cytopenias in HIV infected patients. METHOD: A retrospective cross-sectional descriptive study was performed involving all BMEs performed on HIV-infected adult patients with the main indication of unexplained cytopenia over a period of 5 years and 4 months. Data was extracted from the National Health Laboratory Service's laboratory information system and clinicians' BME request forms. RESULTS: The study included 128 BMEs, performed on 124 patients. The diagnostic yield was 32% and the unique diagnostic yield was 30.5%. The most common diagnosis was pure red cell aplasia (10.9%), followed by immune thrombocytopenic purpura (ITP) (7%), iron deficiency anaemia (6.3%), malignancy (4.7%) and disseminated infection (3.9%). CONCLUSION: BME is a useful investigation for unexplained cytopenia in HIV-infected patients. Less invasive investigations to exclude haematinic deficiencies, haemolysis and sepsis are recommended on an individualised basis prior to BME. In HIV-infected patients with therapy refractory ITP or ITP with atypical clinicopathological findings, BME is strongly recommended. As Mycobacterial and other infections are common in this group of patients, staining and culture of specimens are advised if BME is undertaken.

CW-NET for multitype cell detection and classification in bone marrow examination and mitotic figure examination.

MOTIVATION: Bone marrow (BM) examination is one of the most important indicators in diagnosing hematologic disorders and is typically performed under the microscope via oil-immersion objective lens with a total 100× objective magnification. On the other hand, mitotic detection and identification is critical not only for accurate cancer diagnosis and grading but also for predicting therapy success and survival. Fully automated BM examination and mitotic figure examination from whole-slide images is highly demanded but challenging and poorly explored. First, the complexity and poor reproducibility of microscopic image examination are due to the cell type diversity, delicate intralineage discrepancy within the multitype cell maturation process, cells overlapping, lipid interference and stain variation. Second, manual annotation on whole-slide images is tedious, laborious and subject to intraobserver variability, which causes the supervised information restricted to limited, easily identifiable and scattered cells annotated by humans. Third, when the training data are sparsely labeled, many unlabeled objects of interest are wrongly defined as background, which severely confuses AI learners. RESULTS: This article presents an efficient and fully automatic CW-Net approach to address the three issues mentioned above and demonstrates its superior performance on both BM examination and mitotic figure examination. The experimental results demonstrate the robustness and generalizability of the proposed CW-Net on a large BM WSI dataset with 16 456 annotated cells of 19 BM cell types and a large-scale WSI dataset for mitotic figure assessment with 262 481 annotated cells of five cell types. AVAILABILITY AND IMPLEMENTATION: An online web-based system of the proposed method has been created for demonstration (see https://youtu.be/MRMR25Mls1A).

Digital assessment of peripheral blood and bone marrow aspirate smears.

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.

Retrospective study of 613 canine cytologically normal bone marrows associated to altered hemograms: description, possible interpretation, and review of the principal physiological hematopoietic mechanisms.

Background: In clinical routine, it can happen that to an abnormal hemogram corresponds an unexpected cytological normal bone marrow examination that can be difficult to interpret and to manage. Aim: This cytologically retrospective study wants to evaluate a consistent number of qualitative and quantitative normal bone marrow exams according to the hematological and clinical-pathological data to judge if this normality is by itself a pathologic state. Methods: Six hundred and thirteen bone marrow samples were examined. The bone marrow cytological examinations were performed using morphological and numerical criteria together with a complete hemogram, after the identification of clinical or hematological alterations such as multiple lymph nodes enlarged, positive leishmania serological result, staging of neoplasia, cytopenia, increased number of cells, or suspicion of malignant blood disorders. Results: Of the 613 bone marrow samples evaluated, 85 (14%) were classified as normal or without cytological abnormalities; however, only 28 (33%) of those cases had a normal hemogram associated, whereas 55 (65%) had one or more cytopenia and 2 (2%) had increased blood cells count. Conclusion: From this study emerges that cytological bone marrow examinations without any morphological or numerical abnormalities are often associated with altered hematological exams and for this reason, they should not be considered normal and should lead to other deepened investigations.

MarrowQuant 2.0: A Digital Pathology Workflow Assisting Bone Marrow Evaluation in Experimental and Clinical Hematology.

Bone marrow (BM) cellularity assessment is a crucial step in the evaluation of BM trephine biopsies for hematologic and nonhematologic disorders. Clinical assessment is based on a semiquantitative visual estimation of the hematopoietic and adipocytic components by hematopathologists, which does not provide quantitative information on other stromal compartments. In this study, we developed and validated MarrowQuant 2.0, an efficient, user-friendly digital hematopathology workflow integrated within QuPath software, which serves as BM quantifier for 5 mutually exclusive compartments (bone, hematopoietic, adipocytic, and interstitial/microvasculature areas and other) and derives the cellularity of human BM trephine biopsies. Instance segmentation of individual adipocytes is realized through the adaptation of the machine-learning-based algorithm StarDist. We calculated BM compartments and adipocyte size distributions of hematoxylin and eosin images obtained from 250 bone specimens, from control subjects and patients with acute myeloid leukemia or myelodysplastic syndrome, at diagnosis and follow-up, and measured the agreement of cellularity estimates by MarrowQuant 2.0 against visual scores from 4 hematopathologists. The algorithm was capable of robust BM compartment segmentation with an average mask accuracy of 86%, maximal for bone (99%), hematopoietic (92%), and adipocyte (98%) areas. MarrowQuant 2.0 cellularity score and hematopathologist estimations were highly correlated (R2 = 0.92-0.98, intraclass correlation coefficient [ICC] = 0.98; interobserver ICC = 0.96). BM compartment segmentation quantitatively confirmed the reciprocity of the hematopoietic and adipocytic compartments. MarrowQuant 2.0 performance was additionally tested for cellularity assessment of specimens prospectively collected from clinical routine diagnosis. After special consideration for the choice of the cellularity equation in specimens with expanded stroma, performance was similar in this setting (R2 = 0.86, n = 42). Thus, we conclude that these validation experiments establish MarrowQuant 2.0 as a reliable tool for BM cellularity assessment. We expect this workflow will serve as a clinical research tool to explore novel biomarkers related to BM stromal components and may contribute to further validation of future digitalized diagnostic hematopathology workstreams.

Diagnostic spectrum of hypereosinophilia based on bone marrow pathology: 10 years' experience at a tertiary care hospital.

BACKGROUND: Hypereosinophilia (HE) is defined as peripheral blood (PB) eosinophil count exceeding 1.5 × 109 /L. As the causes of HE can be diverse, the work-up of patients was complicated. In this study, we aimed to categorize the underlying diseases associated with HE and demonstrate minimum diagnostic approach. METHODS: Cases presenting with HE within 7 days of bone marrow (BM) examination conducted between 2008 and 2019 were selected. Cases were classified by the revised 2022 WHO and ICC classification. We also assessed morphologic features of unclassified persisting HE (>4 weeks) patients according to the morphologic criteria suggested a previous study by Wang et al. RESULTS: A total of 364 patients were included. The work-up confirmed primary HE in 38.7%, secondary HE in 48.9%, HE patients with insufficient evaluation in 13.7%. When conducted a slide review of HE patients with sustained HE more than 4 weeks among HE patients with insufficient evaluation, the morphological features showed abnormal eosinophils in PB/BM (69.0%/81.0%), hypercellularity (26.2%), myelofibrosis (7.1%), increased M:E ratio (5.3%), and dysmegakaryopoiesis (4.8%). Of these patients, 14 patients who met all morphologic criteria were suspected of CEL. CONCLUSIONS: This study demonstrates that HE is associated with variable conditions. BM morphological assessment based on a robust criterion can help to confirm a MN irrespective of the presence of clonal markers. The work-up of patients in whom ruled out the common secondary causes of HE requires a systematic but sufficient approach including at a minimum BM karyotyping, PDGFRA testing, lymphocyte immunophenotyping and TCR gene rearrangement.

Evaluation of an innovative new method for quantitation of plasma cells on CD138 immunohistochemistry.

AIM: To compare the frequently used CD138 immunohistochemistry-based method of plasma cell quantitation, to a proposed new method, using interobserver and intraobserver concordance parameters. METHODS: Archival CD138 immunohistochemically stained slides made from paraffin-embedded bone marrow biopsies of 33 patients with a confirmed diagnosis of multiple myeloma were used. Light microscopic examination was performed using low magnification lenses (10×) for both the overview estimation method (method A) and the new method (method B), and high magnification lenses (50×), for method B only. For method B, reviewers selected three areas with low, intermediate and high plasma cell densities using 10× lenses. Using a well-defined technique, the 50× lens was then used to count plasma cells as a percentage of all nucleated cells. After blinded relabelling of all the slides, the nine reviewers repeated the plasma cell quantitation using both methods. The plasma cell counts were obtained, and the review times were recorded. RESULTS: Overall intraobserver concordance was comparable for method A (concordance correlation coefficient (CCC)=0.840) and method B (CCC=0.733). Interobserver concordance for method A (intraclass correlation coefficient (ICC)=0.793 and 0.713) and method B (ICC=0.657 and 0.658) indicated high similarity between reviewers. Method A showed poor interobserver concordance (ICC=0.105) at low plasma cell densities. CONCLUSIONS: The new method is comparable to the frequently used overview estimation method in terms of intraobserver and interobserver concordance, and cost. The new method has superior interobserver concordance at low plasma cell densities. The new method appears more amenable to digital scanning and analysis.

A Primer for the Evaluation of Bone Marrow.

The traditional role of cytologic and histologic evaluation of bone marrow remains important in understanding diseases and conditions that affect this tissue. It is only through correlation of historical and clinical findings with hematologic, bone marrow, and other ancillary data that an accurate diagnosis can be made. Thus, the clinician is an essential link in helping establish a correct diagnosis. This article is a primer for understanding key features of bone marrow evaluation and provides practical tips for developing the best practices for optimal patient care.

Role of bone marrow examination in pyrexia of unknown origin.

A stepwise approach is essential to evaluating pyrexia of unknown origin (PUO). When other investigations are negative, bone marrow examination is a valuable diagnostic tool in PUO. It is particularly helpful in patients with involvement of reticuloendothelial organs (e.g. cytopenia, splenomegaly), immunodeficiency states, or older age.

Utility of bone marrow examination (BME) in the diagnosis of pyrexia of unknown origin (PUO).

INTRODUCTION: Bone marrow examination (BME) is a useful tool in the diagnosis of haematological and non-haematological diseases. It plays an important role in early diagnosis of the underlying cause of pyrexia of unknown origin (PUO) and can influence the management of patients. Bone marrow aspiration (BMA) plays a very important role in establishing a definitive diagnosis in cases of PUO. The aim of this study was to review the indications and usefulness of bone marrow aspirates sent for microbiological evaluation as a diagnostic tool with histopathological correlation. METHODOLOGY: A prospective study was conducted from 1 January 2017 to 30 September 2019 in the Department of Microbiology and Pathology on the bone marrow aspirates of patients of all groups. RESULTS: A total of 148 bone marrow aspirates were included. The cases were categorized as classical PUO (n = 81/148, 54.7%), nosocomial PUO (n = 4 /148, 2.7%), neutropenic PUO (n = 18/148, 12.1%), and immunocompromised PUO (n = 45/148, 30.4%), among which were systemic lupus erythematosus cases n = 8/45 (22.2%), human immunodeficiency virus positive cases n = 10/45 (17.7%), and renal transplant cases n = 27/45 (60%). A total of 28 BMAs were positive for microorganisms, out of which bacterial pathogens were n = 12 (42.8%), mycobacterial n = 12, 42.8%, fungal (n = 3, 10.7 %), and viruses (n = 1, 3.5%). CONCLUSIONS: This study helped in highlighting the role of bone marrow examination as an important diagnostic method in the diagnosis of infectious diseases.

Diagnostic Significance Of Bone Marrow Examination Amongst The Patients With Abnormal Haematological Parameters.

BACKGROUND: Bone Marrow examination is considered to be the most indispensable diagnostic tool for the evaluation of many neoplastic and non-neoplastic haematological disorders. After an initial assessment of suspicious cases on abnormal laboratory parameters along with the clinical presentation of the patient marrow examination is finally required for diagnosis as well as management of many haematological malignancies as it offers a clear cytological as well as histological picture of Bone Marrow aspirate and biopsy respectively. The Objective was to evaluate the significance of Bone Marrow examination in patients with abnormal haematological parameters. METHODS: A retrospective study conducted at the Pathology Department of Pak Emirates Military Hospital from (Jan-June 2022) On data from150 patients who were advised to undergo bone marrow examination due to abnormal lab parameters and peripheral smear findings after informed consent and approval from the ethics review committee, to find out the correlation of abnormal haematological parameters and aspirate findings which have led to a definitive diagnosis. Data comprising basic demographic variables (age, gender etc.), Abnormal Haematological Parameters (CBC), peripheral smear findings and Aspirate findings were analyzed using SPSS version 23.0. RESULTS: Out of 150 studied participants with abnormal haematological parameters 24 (16%) were diagnosed on bone marrow examination as acute leukaemia / Hodgkin's and Non-Hodgkin's lymphoma respectively, 13 (9%) cases of aplastic anaemia and Autoimmune HaemolyticAnaemia, 33 (22%)cases of hypersplenism, CML and multiple myeloma. While 22 (15%) cases were diagnosed with BME as CKD and reactive changes. Moreover, 22(15%) cases were found to have Iron Deficiency anaemia respectively. CONCLUSIONS: The study revealed that patients with abnormal haematological parameters should undergo bone marrow examination to ascertain the diagnosis for malignant as well as non-malignant conditions that could cause abnormal lab parameters.

The diagnostic role of complete MICM-P in metastatic carcinoma of bone marrow (MCBM) presented with atypical symptoms: A 7-year retrospective study of 45 cases in a single center.

Metastatic carcinoma of bone marrow (MCBM) tends to present with atypical symptoms and can be easily misdiagnosed or miss diagnosed. This study was conducted to investigate the clinical-pathological and hematological characteristics of MCBM patients in order to develop strategies for early detection, staging, treatment selection and prognosis predicting. We retrospectively analyzed 45 patients with MCBM diagnosed by bone marrow biopsy in our hospital during the past 7 years. The clinical symptoms, hemogram and myelogram features, Hematoxylin and eosin staining and immunohistochemistry staining of bone marrow biopsies, location of primary carcinoma and corresponding treatment of the 45 MCBM patients were analyzed in this study. In total, 35 (77.9%) of all patients presented pains including bone pain (73.3%) as the main manifestation, and 37 (82.2%) patients had anemia. Metastatic cancer cells were found in only 22 patients (48.9%) upon bone marrow smear examination, but in all 45 patients by bone marrow biopsy. The bone marrow of 18 (40.0%) patients was dry extraction. Distribution of metastatic carcinoma was diffuse in 20 (44.4%) patients and multi-focal in 25 (55.6%) patients, complicated with myelofibrosis in 34 (75.6%) patients. For bone marrow biopsy immunohistochemistry, 97.8% of the patients were CD45-negative, while 75.6% of the patients were Cytokeratin-positive. There were 30 patients (66.7%) identified with primary malignancies. The overall survival (OS) of 1 year for MCBM patients was 6.7%. There was a trend that patients with cancer of known primary obtained better prognosis according to the survival curve, but the finding was not statistically significant with Log-rank P = .160. Complete MICM-P plays a significant role in early diagnosis of MCBM. Bone marrow biopsy combined with immunohistochemistry is an underappreciated method for the diagnosis of MCBM, which should be taken as part of regular tests as well as bone marrow smear. Understanding the clinical-pathological and hematological characteristics of MCBM and conducting bone marrow biopsy in time are of great significance for early detection and treatment selection.

Bone marrow biopsy, an effective diagnostic modality for pancytopenia among paediatric and adult population.

OBJECTIVE: To determine the aetiologies of pancytopenia based on bone trephine biopsy among paediatric and adult patients. Method: The retrospective cross-sectional study was conducted at the Haematology Department of Aga Khan University Hospital, Karachi, and comprised data from June 1, 2016, to October 31, 2019 related to pancytopenia patients who underwent bone marrow biopsy. Data included age, gender, presenting symptoms, physical examination, complete blood count, peripheral smear, bone marrow aspirate and trephine biopsy findings and final diagnosis. Data was analysed using SPSS 19. RESULTS: Of the 2852bone marrow biopsies done, 255(9%) related to evaluation of pancytopenia. Of them, 208(82%) were adult and 47(18%) were paediatric patients. The median age for adults was 38.8 years (range: 16-92years) and that in paediatric patients was 10.9 years (range: 2-15 years). Presenting symptoms were available for 182(71.4%) patients, and the commonest symptom was generalised weakness 128(70.3%). Overall, pallor was the most frequent sign 233(93.2%). Anisocytosis was predominant blood smear finding 156(61.1%), while the commonest aetiology was aplastic anaemia in both paediatric 23(49%) and adult 57(27.4%) groups. Bone marrow biopsy established the diagnosis in 253(99.2%) cases, while 2(0.95%) adult cases were not diagnosed. Of the diagnosed cases, 103(40.4%) were malignant; 15(32%) paediatric patients and 88(42.3%) adults. The rest were benign; 31(67.4%) paediatric patients and 119(3%) adults. CONCLUSIONS: Bone marrow biopsy helped in diagnosing all but 2 pancytopenic patients. Aplastic anaemia was the commonest cause in both paediatric and adult patients.