Bone Marrow Differential: Are Traditional Biopsies Becoming Obsolete?

Introduction

Bone marrow differential analysis represents a cornerstone diagnostic procedure in hematology, offering crucial insights that cannot be obtained through peripheral blood examination alone. Unlike complete blood counts (CBCs), which produce rapid results, a bone marrow analysis requires more in-depth examination and incorporates built-in redundancies to ensure the highest-quality diagnostic outcomes. The comprehensive nature of this procedure raises an essential question in contemporary hematology practice: Are traditional bone marrow biopsies becoming obsolete in the face of advancing molecular techniques?

A complete bone marrow biopsy examination typically involves four distinct specimens: marrow aspirate smears, core biopsies, clot sections, and touch imprint preparations. These components serve complementary roles in the bone marrow differential count, with each offering unique diagnostic advantages. Research has demonstrated that bone marrow aspirate and bone marrow biopsy results show a strong positive correlation in approximately 46% of cases. However, in specific conditions such as aplastic anaemia, different phases of myeloproliferative neoplasms, multiple myeloma, and hematolymphoid neoplasms, the bone marrow biopsy technique provides superior diagnostic information. Furthermore, when comparing bone marrow core biopsy with corresponding bone marrow aspirate samples, studies have found that core biopsies can reveal additional information in approximately 38% of cases. This comprehensive approach to bone marrow differential count remains essential despite advances in molecular testing.

The diagnostic value of traditional biopsies persists even as alternatives emerge. For instance, when bone marrow aspirate yields a “dry tap,” molecular diagnostic testing on bone marrow biopsy specimens has demonstrated substantial clinical impact, influencing therapeutic decisions in 37.5% of cases. Additionally, while aspirates excel in revealing individual cell morphology and detail, core biopsies provide critical architectural information that often proves decisive in complex hematological disorders. This article examines the evolving landscape of bone marrow differential techniques, evaluating both traditional approaches and emerging alternatives to determine whether conventional biopsies are truly becoming obsolete in modern hematological practice.

Understanding the Bone Marrow Differential Count

The bone marrow differential count serves as a fundamental diagnostic tool that examines the proportions of different cell types within the bone marrow. This meticulous cellular assessment involves counting and categorising various hematopoietic cells to establish their relative percentages, providing critical diagnostic information unavailable through other methods.

Bone marrow differential count vs peripheral smear

The bone marrow differential count demands considerably more detail than peripheral blood examination. Standard protocol requires a 500-cell differential count on bone marrow aspirate smears stained with Wright Giemsa or May-Grunwald-Giemsa stain. This comprehensive count enumerates bone marrow blasts and other marrow cellular elements while excluding megakaryocytes. Alternatively, if aspirate smears are limited, touch preparations can be used, though these require a reduced 300-cell differential. In contrast, peripheral blood smear analysis typically involves a 200-cell differential count.

The cellular assessment scope varies significantly between these two examinations. Peripheral blood smears primarily focus on five fully mature white blood cells—basophils, eosinophils, segmented neutrophils, monocytes, and lymphocytes. Bone marrow examination, conversely, considers a much broader spectrum of cells at various maturation stages, including:

Myeloid precursors (myeloblasts, promyelocytes, myelocytes, metamyelocytes)
Erythroid precursors (pronormoblasts through orthochromatic normoblasts)
Lymphoid cells (lymphoblasts, lymphocytes)
Monocytic lineage cells
Mature granulocytes (basophils, eosinophils)
Plasma cells

This extensive evaluation makes bone marrow differential counts particularly valuable yet technically challenging due to the subtle differences between maturation stages and higher cell density compared to peripheral blood. Moreover, many white blood cells in bone marrow smears touch one another, complicating individual cell identification.

Role in diagnosing cytopenias and hematologic malignancies

Bone marrow examination proves essential in diagnosing both benign and malignant hematological disorders. It provides complementary information to complete blood count analysis and peripheral blood morphology. This comprehensive approach becomes particularly crucial when evaluating persistent cytopenias (deficiencies in blood cellular components).

The differential count yields vital diagnostic clues for a wide range of hematologic conditions. Notably, the diagnosis of acute myeloid leukaemia (in the absence of specific genetic abnormalities) and blast phase of myeloproliferative neoplasms requires identifying at least 20% blasts in bone marrow or blood. Similarly, myelodysplastic syndrome subclassification depends on precise blast percentage ranges—MDS with excess blasts-1 (MDS-EB-1) requiring 6-9% myeloblasts and MDS-EB-2 requiring 10-19% blasts.

For plasma cell disorders, the differential count provides equally critical information. Monoclonal gammopathy of undetermined significance requires less than 10% plasma cells, whereas smouldering myeloma is characterized by 10-60% plasma cells without end-organ damage.

Bone marrow examination also plays a decisive role in evaluating reactive cytopenias, primarily by excluding conditions that displace normal hematopoiesis, such as acute leukaemias, lymphomas, or metastases. Additionally, it helps identify specific infectious or histiocytic diseases like hemophagocytic lymphohistiocytosis.

The diagnostic value extends beyond cell counting. Bone marrow biopsies performed after peripheral blood smear interpretation have demonstrated a higher diagnostic yield compared to those performed without prior smear review. Specifically, one study found biopsies were more likely to be diagnostic when hematologists used peripheral blood smear findings to determine biopsy necessity (p=0.0265) than when performed without prior smear review.

Although automated analyzers have improved accuracy for routine white blood cell quantification, they remain limited in identifying abnormal or immature cells. Consequently, despite technological advances, the skilled visual examination of bone marrow remains irreplaceable, particularly for detecting subtle morphological abnormalities that signal hematological disorders.

Traditional Biopsy Components and Their Diagnostic Roles

A comprehensive bone marrow evaluation relies on multiple specialized components that serve complementary diagnostic roles. Each element provides unique advantages while collectively forming a complete diagnostic picture.

Bone marrow aspirate: morphology and flow cytometry.

Bone marrow aspirate represents a fundamental component for detailed cytomorphologic analysis and precise cell enumeration. This liquid sample, typically obtained through negative pressure application via syringe, delivers approximately 5 mL of semi-liquid marrow content that undergoes immediate slide preparation with Giemsa family stains. The strength of aspirate lies in revealing individual cell morphology, making it superior for evaluating conditions where cellular detail proves essential, including myelodysplasia identification and detection of intracellular infectious agents.

For accurate interpretation, aspirate evaluation requires thorough examination of bone marrow spicules on well-spread, air-dried smears. These slides subsequently undergo standard staining procedures, enabling rapid assessment without elaborate processing. As a liquid sample, aspirate avoids decalcification requirements and proves invaluable for flow cytometry analysis, which demands unfixed cells.

Nonetheless, flow cytometry analysis plays a vital role in immunophenotyping and minimal residual disease (MRD) detection. This technique, conducted on isolated bone marrow mononuclear cells, utilizes monoclonal antibodies against various surface markers. In chronic lymphocytic leukaemia (CLL) cases, flow cytometry demonstrates exceptional sensitivity in diagnosis and MRD detection.

Core biopsy: architecture and fibrosis detection

The bone marrow core biopsy, typically 1-2 cm in length, undergoes fixation in neutral buffered formalin followed by decalcification and paraffin embedding before sectioning. This component excels at evaluating bone marrow cellularity, trilineage hematopoiesis, and overall marrow architecture. It remains particularly valuable in microorganism evaluation, aplastic anaemia diagnosis, myeloproliferative neoplasm phase identification, and assessment of granulomatous conditions.

Core biopsy provides superior architectural information regarding fibrosis, focal neoplastic infiltrates, and necrosis compared to aspirate alone. In cases of chronic myeloid leukaemia (CML), core biopsy proved essential or helpful in 25% of patients, primarily through facilitating disease phase identification and myelofibrosis evaluation. Besides, the initial grade of myelofibrosis associates with disease stage and treatment outcomes, further highlighting the core biopsy’s diagnostic value.

Clot section: backup for dry taps

Clot sections originate from unprocessed marrow specimens that naturally clot without anticoagulant addition. These specimens undergo formalin fixation before paraffin embedding and sectioning by histotechnologists. Unlike core biopsies, clot sections do not require decalcification, thereby preserving DNA integrity for potential molecular studies.

The diagnostic accuracy of clot sections becomes especially valuable in cases yielding inadequate aspirates (“dry taps”). Studies show that clot sections, together with touch imprints and core biopsies, should be systematically examined in dry tap cases to avoid missing underlying pathology. Indeed, a dry tap should serve as a warning sign rather than indicating a failed procedure, often signalling underlying conditions like myelofibrosis or densely packed marrow.

Touch imprint: rapid morphology assessment

Touch imprint cytology involves gently touching or rolling the core biopsy sample across glass slides, creating cellular impressions for rapid staining and assessment. This technique yields meticulously prepared smears that not only reveal cellular composition but also help define marrow architecture, especially in metastatic solid tumour cases.

The diagnostic accuracy of touch imprints (83.7%) significantly exceeds bone marrow aspirate (77.5%) in various hematological disorders, approaching the gold standard of trephine biopsy (99.2%). Touch imprints correctly diagnosed 93.3% of metastatic solid tumours compared to 70% with bone marrow aspirate. Furthermore, touch imprints provide considerably quicker turnaround times than core biopsies, which require decalcification and extensive processing.

Touch imprints prove especially valuable when aspirates yield dry taps or hemodiluted samples, offering excellent cell morphology assessment otherwise unavailable. Their immediate availability makes them invaluable for preliminary diagnosis while awaiting formal biopsy results.

Bone Marrow Aspirate vs Biopsy: When and Why

The selection between bone marrow aspirate and biopsy depends on specific clinical contexts and diagnostic goals. These procedures, often performed simultaneously, yield complementary information critical for accurate diagnosis and treatment planning.

Diagnostic yield in myelodysplastic syndromes

Myelodysplastic syndromes (MDS) represent a group of disorders where both aspiration and biopsy play crucial yet distinct roles. For establishing an MDS diagnosis, bone marrow aspirate smears remain essential for assessing individual cell morphology and dysplastic features. The aspirate enables the detection of cellular abnormalities, precise blast enumeration, and identification of ring sideroblasts through Prussian blue staining. This detailed cytomorphological examination forms the cornerstone of MDS diagnosis, allowing hematopathologists to evaluate specific lineage dysplasia.

In contrast, the trephine biopsy provides vital information about overall marrow cellularity and architectural disruptions often present in MDS. While the aspirate focuses on cellular details, the biopsy reveals the topographic arrangement of hematopoietic cells within the marrow framework. This comprehensive view becomes particularly valuable in MDS subtypes with increased fibrosis, where aspirate alone might yield inconclusive results.

The diagnostic accuracy rates underscore these complementary roles—bone marrow aspirate demonstrates approximately 77.18% diagnostic efficacy, whereas bone marrow biopsy achieves 90.6%. Hence, combining both approaches maximizes diagnostic precision in MDS evaluation.

Limitations in dry tap or fibrotic marrow

“Dry tap”—the inability to aspirate liquid marrow—represents a frequent challenge that necessitates alternative approaches. Far from indicating procedural failure, dry taps often signal underlying pathology requiring further investigation. Common causes include fibrosis, hypercellularity due to leukemic infiltration, or densely packed marrow in conditions like multiple myeloma.

When aspirate cannot be obtained due to fibrosis or cellular packing, touch preparations from unfixed core samples offer a practical alternative. These preparations, created by gently touching the biopsy specimen onto slides, can substitute for aspirate samples when evaluating cellular morphology. Additionally, obtaining two core biopsies becomes advisable in dry tap scenarios to ensure adequate material for comprehensive analysis.

For molecular studies in dry tap cases, specialized approaches prove necessary. A second core biopsy placed in sterile saline allows for mechanical disaggregation using sterile needles or dedicated systems to release viable marrow cells from fibrotic tissue. This approach facilitates flow cytometry and cytogenetic studies otherwise impossible with traditional aspirate techniques.

Complementary roles in staging and lineage analysis

The integration of aspirate and biopsy findings substantially enhances diagnostic accuracy across numerous hematological conditions. Studies demonstrate substantial agreement between these procedures, with kappa values reaching 0.6295. Nevertheless, each technique offers unique advantages in specific scenarios.

For accurate staging and lineage assessment in lymphoproliferative disorders, core biopsy provides essential architectural information that aspirates alone cannot deliver. Bone marrow examination in chronic lymphocytic leukaemia (CLL) should invariably include trephine biopsy since the aspirate yields limited information beyond peripheral blood analysis. Moreover, trephine biopsy allows assessment of infiltration patterns and reveals prognostically essential features.

For myeloproliferative neoplasms, both procedures demonstrate excellent correlation (100%). Yet, for blast enumeration, which is critical in distinguishing accelerated phase from blast crisis, aspirate smears permit more precise quantification. Meanwhile, biopsy reveals reticulin fibrosis patterns that determine prognosis and disease stage.

In aplastic anaemia, biopsy proves superior by accurately assessing marrow cellularity—a determination challenging with aspirate alone. Furthermore, biopsy enables evaluation of megakaryocyte distribution and reticulin fibrosis, both serving as important prognostic indicators for treatment response and follow-up.

In practice, these complementary roles translate to high concordance rates, with studies reporting positive correlation between both procedures in approximately 66% of cases. Therefore, simultaneous performance of both techniques represents the current standard of care for comprehensive bone marrow evaluation.

Limitations of Traditional Biopsy Techniques

Despite their diagnostic value, traditional bone marrow biopsy techniques present several inherent limitations that can impact clinical decision-making and patient care. These constraints range from procedural delays to sampling issues that may compromise diagnostic accuracy.

Turnaround time and decalcification delays

Traditional bone marrow core biopsies require extensive processing before microscopic examination becomes possible. Unlike aspirate smears that can be rapidly prepared and examined, core biopsies must undergo fixation, decalcification, dehydration, paraffin embedding, sectioning, and staining. This multi-step process significantly extends turnaround time. This processing sequence typically results in slides becoming available only the following day after collection.

The decalcification step presents a particular challenge. Conventional decalcification methods using hydrochloric acid (HCl) notably damage cellular RNA, DNA, and proteins. This degradation complicates subsequent molecular and immunohistochemical analyses, often rendering genetic testing impossible—even when such testing proves essential for diagnosis and treatment planning. Studies comparing decalcification methods found that EDTA protocols best preserve genetic material but require longer processing times, creating a complex trade-off between turnaround time and specimen quality.

For critically ill patients, these delays can be particularly problematic. Bone marrow results typically take anywhere from a few days to several weeks, with basic results sometimes available within 24-48 hours but comprehensive analysis requiring 1-2 weeks. Even when expedited, the complete battery of tests needed for hematologic malignancy diagnosis frequently extends beyond immediate clinical timeframes.

Sampling errors and hypocellular smears

Sampling errors represent another significant limitation of traditional bone marrow examination. These errors broadly fall into three categories: dry taps (where no marrow can be aspirated), aspicular samples (no focus of hematopoietic marrow obtained), and hemodilution (peripheral blood contamination).

The frequency of these sampling problems is considerable. Dry taps occur in approximately 6.8% of procedures, while aspicular samples have been reported in 20.6% of cases even with optimized technique. Hemodilution affects 27.6% of samples in some series, compromising diagnostic accuracy through dilution of marrow elements with peripheral blood cells.

These sampling issues create diagnostic uncertainty in nearly half (46%) of suboptimal specimens. The most common cause of uncertainty is the inability to perform representative blast quantitation—crucial for acute leukaemia diagnosis and myelodysplastic syndrome classification. In one study, 19 of 465 inadequate biopsies (4%) subsequently revealed clinically significant diagnoses on repeat procedures, with an average diagnostic delay of 51 days. Ten of these delayed diagnoses involved acute leukaemias, underscoring the clinical impact of sampling errors.

Additionally, core biopsy length often falls below recommended standards. Current guidelines suggest optimal trephine biopsy length between 15-25mm, yet practising pathologists frequently accept much shorter specimens. This acceptance of suboptimal samples may compromise the evaluation of conditions like myelofibrosis, where adequate length is essential for accurate assessment.

Invasiveness and patient discomfort

Beyond technical limitations, the invasive nature of bone marrow biopsies creates a significant patient burden. Despite being commonly described as “uncomfortable” or “mostly well-tolerated,” the procedure frequently causes substantial pain. In prospective studies, 70% of patients reported procedural pain, with 32% describing it as severe and 3% as “the worst possible”. Notably, pain persisted in 42% of patients three days post-procedure and in 12% after one week.

The discrepancy between clinician perception and patient experience appears substantial. One study revealed that doctors and nurses recognized severe pain in only one-third of cases where patients self-reported severe pain. Specific patient populations, primarily younger individuals and those with higher body mass index, experience greater procedural pain. Furthermore, patients with severe pain during previous biopsies tend to experience more intense pain in subsequent procedures.

Complications, while uncommon, can include bleeding, infection, and hematoma formation. In one series, 0.4% of patients experienced procedural complications related to hematoma. Procedural failure rates may reach 7%, occasionally requiring intervention under CT guidance. Even with successful procedures, 16.6% required more than one attempt, potentially increasing patient discomfort.

Emerging Alternatives to Traditional Biopsies

Recent advances in molecular testing have introduced promising alternatives to conventional bone marrow evaluation techniques. These innovations aim to address the limitations of traditional biopsies while maintaining diagnostic accuracy.

Peripheral blood NGS as a surrogate

Peripheral blood next-generation sequencing (NGS) has emerged as a viable non-invasive alternative to bone marrow sampling. Studies demonstrate remarkably high concordance between peripheral blood and bone marrow NGS results, with correlation rates reaching 95.3% and a strong kappa coefficient of 0.90. This approach maintains excellent sensitivity (98%) and specificity (92%) compared to bone marrow sampling.

When examining variable allele frequencies (VAFs) between paired samples, researchers found a strong correlation (r=0.85), suggesting peripheral blood accurately reflects the genetic landscape within the marrow. Interestingly, this correlation remains robust even in patients without circulating blasts (r=0.92) or with neutropenia (r=0.88), expanding potential applications to various clinical scenarios.

Molecular testing on FFPE core biopsies

Formalin-fixed paraffin-embedded (FFPE) bone marrow core biopsies offer an underutilized resource for molecular analysis, particularly valuable when aspirate yields inadequate material. In comparative studies, FFPE samples provided additional genetic information in 11 of 29 cases beyond what bone marrow aspirate detected. As a result, FFPE analysis can reveal mutations otherwise missed, fundamentally enhancing diagnostic yield without additional procedures.

Technical adaptations have overcome traditional FFPE limitations. Recent improvements in RNA extraction methodologies and standardized fixation protocols have substantially reduced unwanted variations in ischemia and fixation times, enabling more consistent preservation of genetic material. Through these refinements, FFPE specimens now serve as reliable substrates for comprehensive mutational profiling.

Liquid biopsy and circulating tumour DNA

Liquid biopsy, primarily analyzing circulating tumour DNA (ctDNA), represents the most promising advancement. This approach detects tumour-derived DNA fragments in peripheral blood, offering a comprehensive view of tumour genetics without invasive procedures. With a half-life of merely 1-2 hours, ctDNA provides real-time insight into disease dynamics, making it exceptionally valuable for treatment monitoring.

In multiple myeloma, ctDNA analysis has demonstrated superior predictive capability compared to conventional methods. One study reported that ctDNA positivity accurately predicted relapse with a 93.3% positive predictive value versus just 68.4% for multiparameter flow cytometry. Ultimately, researchers anticipate that ctDNA testing may eventually replace invasive bone marrow examinations in select clinical scenarios, potentially transforming how hematologic malignancies are monitored.

Clinical Scenarios Where Traditional Biopsies Still Matter

Even as molecular technologies advance, several clinical scenarios persist where traditional bone marrow examination remains indispensable. These situations showcase when conventional approaches continue to offer unique diagnostic value that newer methods cannot yet match.

Myelofibrosis and dry tap cases

In myelofibrosis, aspirate procedures frequently yield “dry taps” in up to 50% of patients. This absence of aspiratable material, rather than indicating procedural failure, typically signals underlying pathology requiring thorough investigation. Core biopsies reveal characteristic features including patchy hematopoietic cellularity, reticulin fibrosis, dysplastic megakaryocyte clusters, and distended marrow sinusoids containing intravascular hematopoiesis. Accordingly, performing a bone marrow biopsy becomes essential for confirming the diagnosis in these cases. Studies examining dry taps found that 93.7% of such cases had underlying bone marrow pathology, with leukaemia being the most common cause (40.3%).

Minimal residual disease monitoring

Bone marrow examination presently remains the standard approach for minimal residual disease (MRD) assessment. Current techniques include next-generation sequencing and flow cytometry, both requiring high-quality bone marrow samples. First-pull aspirates are preferred as second pulls show approximately a 50% reduction in leukemic cells. Ultimately, while peripheral blood testing offers convenience, studies demonstrate that 40% of patients achieving blood-based MRD negativity still had bone marrow MRD-positive disease, underscoring traditional biopsy’s continued importance in treatment response assessment.

Histotopographic assessment in lymphomas

For lymphoproliferative disorders, core biopsies provide irreplaceable architectural information. Forthwith, they allow evaluation of lymphoid aggregate formation and localization, plus assessment of histological patterns crucial for accurate classification. Classic Hodgkin lymphoma particularly relies on core biopsy evaluation, as aspirates alone cannot provide the necessary architectural context. Thus, despite advancing technologies, these clinical scenarios continue to necessitate traditional bone marrow biopsies.

Conclusion

Traditional bone marrow biopsies persist as essential diagnostic tools despite remarkable advances in molecular techniques. Throughout this examination of bone marrow differential procedures, evidence consistently demonstrates that conventional biopsies offer unique diagnostic advantages that newer methods cannot yet replicate. While peripheral blood NGS and liquid biopsies show promise as less invasive alternatives, they currently function best as complementary rather than replacement approaches.

The four components of traditional biopsies—aspirate smears, core biopsies, clot sections, and touch imprint preparations—each contribute distinct diagnostic value. Core biopsies excel at revealing architectural patterns crucial for lymphoma classification and myelofibrosis grading. Aspirates remain unmatched for detailed cytomorphologic assessment. Touch imprints provide rapid preliminary results when time constraints exist. Clot sections serve as vital backups when aspirates yield dry taps.

Undoubtedly, traditional biopsies face limitations including extended turnaround times, sampling errors, and patient discomfort. Nevertheless, for conditions like myelofibrosis, where aspirates frequently yield dry taps, core biopsies remain indispensable. Likewise, minimal residual disease assessment still requires bone marrow examination, as peripheral blood testing alone misses approximately 40% of cases with bone marrow involvement.

The future of hematologic diagnostics likely involves strategic integration of multiple approaches. Peripheral blood NGS, with its 95.3% concordance rate with bone marrow samples, offers a compelling non-invasive screening tool. Molecular testing on FFPE core biopsies has overcome previous technical limitations, now serving as reliable substrates for mutational profiling. Circulating tumour DNA analysis, with its short half-life, provides real-time insight into disease dynamics that traditional biopsies cannot match.

Therefore, rather than becoming obsolete, traditional bone marrow biopsies are evolving within a broader diagnostic framework. Hematologists must evaluate each clinical scenario individually, determining whether molecular alternatives suffice or if architectural and morphological information from traditional biopsies remains necessary. This balanced approach—selecting the proper test for the right patient at the right time—will ultimately enhance diagnostic precision while minimising unnecessary invasive procedures.

Key Takeaways

Traditional bone marrow biopsies remain essential despite molecular advances, with each component serving unique diagnostic roles that newer methods cannot fully replace.

Traditional biopsies aren’t obsolete: Core biopsies, aspirates, clot sections, and touch imprints each provide irreplaceable diagnostic information for hematologic disorders.
Molecular alternatives show promise but have limits: Peripheral blood NGS achieves 95.3% concordance with bone marrow, yet misses 40% of minimal residual disease cases.
Dry taps signal pathology, not failure: 93.7% of “dry tap” cases reveal underlying bone marrow disease, making core biopsies essential for diagnosis.
Integration beats replacement: The future involves a strategic combination of traditional biopsies with molecular testing rather than complete substitution.
Clinical context determines approach: Conditions like myelofibrosis, lymphomas, and MRD monitoring still require traditional biopsies for architectural and morphological assessment.

The evolving landscape suggests a complementary approach where hematologists select the most appropriate diagnostic method based on individual clinical scenarios, balancing invasiveness with diagnostic necessity to optimize patient care while maintaining diagnostic precision.

Frequently Asked Questions:

FAQs

Q1. Are there alternatives to traditional bone marrow biopsies? While alternatives like peripheral blood next-generation sequencing and liquid biopsies are emerging, they currently complement rather than replace traditional biopsies. These newer methods show promise but may miss certain diagnoses that traditional biopsies can detect.

Q2. What’s the difference between bone marrow aspiration and biopsy? Bone marrow aspiration involves extracting liquid marrow to examine individual cells, while a biopsy removes a small piece of bone with marrow inside to assess overall structure. Aspiration is better for detailed cell examination, whereas biopsy provides information on marrow architecture and cellularity.

Q3. Why are bone marrow biopsies still necessary? Bone marrow biopsies remain essential for diagnosing certain conditions, assessing disease progression, and monitoring treatment effectiveness. They provide unique information about marrow architecture and cell distribution that blood tests alone cannot offer, especially in cases of myelofibrosis or lymphomas.

Q4. Who typically performs bone marrow biopsies? Hematologists or oncologists usually perform bone marrow biopsies in a clinical setting. The procedure takes about 30 minutes total, with the actual biopsy lasting around 10 minutes. Local anaesthesia is applied to minimize discomfort during the procedure.

Q5. How accurate are newer blood-based tests compared to bone marrow biopsies? While newer blood-based tests like peripheral blood NGS show high concordance (around 95%) with bone marrow samples, they can miss some cases of minimal residual disease. For instance, about 40% of patients who test negative for residual disease in blood may still have detectable disease in their bone marrow.