Bone marrow examination remains a fundamental diagnostic modality in hematology, essential for evaluating both benign and malignant hematological disorders [1–3]. It is routinely employed in the assessment of anemia, leukemias, lymphomas, plasma cell dyscrasias, and myeloproliferative neoplasms, as well as in staging of non-hematological malignancies [2,4,5].

The two principal techniques—bone marrow aspiration (BMA) and bone marrow trephine biopsy (BMB)—provide complementary diagnostic information [3,6]. BMA allows detailed cytological examination, enabling evaluation of cell morphology, differential counts, and cytogenetic or molecular analyses [7,8]. However, its diagnostic utility may be limited in cases of marrow fibrosis, hypocellularity, or focal infiltration, often resulting in diluted or non-representative samples [6,9].

Trephine biopsy, in contrast, provides intact marrow architecture, allowing assessment of cellularity, stromal components, fibrosis, and infiltration patterns [10,11]. It is particularly valuable in diagnosing conditions such as myelofibrosis, granulomatous diseases, lymphomas, and metastatic malignancies [9,12].

Previous studies have demonstrated discordance between BMA and BMB findings, particularly in focal marrow involvement [13–15]. Aspiration may miss up to 30–40% of metastatic or lymphomatous infiltrates due to patchy distribution [14,16]. Conversely, BMA remains superior in identifying cytological abnormalities in acute leukemias and megaloblastic anemia [7,17].

Despite widespread use of both techniques, there remains variability in clinical practice regarding their combined or selective use [18,19]. Reported concordance rates range from 60% to 80%, indicating potential diagnostic gaps when only one modality is used [13,20].

Given these discrepancies, a systematic synthesis of available evidence is necessary to better define the comparative diagnostic performance of BMA and BMB. This study aims to evaluate and compare their diagnostic yield and determine their optimal role in hematological practice

MATERIALS & METHODS

Study Design

This systematic review and meta-analysis was conducted in accordance with PRISMA guidelines [21].

Search Strategy

A comprehensive search of PubMed, Scopus, Web of Science, and Google Scholar databases was performed using combinations of the following terms: “bone marrow aspiration,” “trephine biopsy,” “diagnostic yield,” and “hematological disorders” [1,3,6].

Manual cross-referencing of selected articles was also undertaken to identify additional relevant studies [2,4].

Inclusion Criteria

• Comparative studies evaluating both BMA and BMB [6,10]
• Studies involving hematological or marrow-infiltrative disorders [3,12]
• Studies reporting diagnostic yield, sensitivity, specificity, or concordance [13,14]

Exclusion Criteria

• Case reports and small case series (<10 patients) [9]
• Non-comparative studies [18]
• Animal studies [21]

Data Extraction

Two independent reviewers extracted data including:

• Study design and sample size [1]
• Diagnostic yield of BMA and BMB [10]
• Sensitivity and specificity [14]
• Concordance rates [13]

Disagreements were resolved by consensus.

Quality Assessment

Study quality was assessed using the Newcastle-Ottawa Scale (NOS) for observational studies [21,22].

Statistical Analysis

Pooled diagnostic yield was calculated using a random-effects model due to expected heterogeneity [21].

Heterogeneity was assessed using I² statistics:

• <25%: low
• 25–50%: moderate
• 50%: high [21]

Publication bias was evaluated using funnel plots and Egger’s test [22].

RESULT

Study Selection and Characteristics

A total of 1,248 records were identified through database searching, of which 1,012 remained after removal of duplicates. Following title and abstract screening, 78 articles were assessed for full-text eligibility. Finally, 14 studies fulfilling the inclusion criteria were included in the meta-analysis [1–5,10–15,23–26].

These studies collectively comprised approximately 1,800 patients, encompassing a wide spectrum of hematological and marrow-infiltrative disorders. Most studies were conducted in tertiary care centers and included both adult and mixed populations [3,10].

Figure 1: PRISMA Flow Diagram

Table 1: Characteristics of Included Studies

Overall Diagnostic Yield

Across all included studies, trephine biopsy demonstrated consistently higher diagnostic yield compared to aspiration. The pooled diagnostic yield for BMA ranged from 65% to 85%, whereas for BMB it ranged from 85% to 96% [3,7,10–12,24].

The difference was statistically and clinically significant, particularly in disorders with focal marrow involvement or altered architecture [11,12].

Table 2: Pooled Diagnostic Yield Comparison

Sensitivity and Specificity Analysis

Bone marrow aspiration demonstrated moderate sensitivity, ranging from 65% to 70%, with specificity varying widely between 40% and 85% across studies [14,16].

Trephine biopsy showed higher sensitivity, particularly in detecting infiltrative and fibrotic conditions, and was considered the reference standard in most studies [10,11].

Table 3: Sensitivity and Specificity

Concordance Between BMA and BMB

The concordance between aspiration and biopsy findings ranged from 68% to 78%, with a pooled average of approximately 72% [13,20,25].

This indicates that nearly one-third of cases demonstrated discordant findings, emphasizing the limitations of using a single diagnostic modality [13,15].

Table 4: Concordance Rates Across Studies

Disease-Specific Diagnostic Performance

1. Leukemias and Cytological Disorders

Bone marrow aspiration demonstrated high diagnostic accuracy in diffuse marrow disorders such as acute leukemias, megaloblastic anemia, and aplastic anemia [7,17,26].

Its superiority in these conditions is attributed to excellent cytological detail and the ability to perform ancillary tests including flow cytometry and molecular diagnostics [8].

2. Lymphoma and Metastatic Infiltration

Trephine biopsy was significantly superior in detecting focal marrow involvement such as lymphoma and metastatic disease [12,14,16].

Aspiration missed 23–40% of such cases, primarily due to patchy infiltration patterns [14].

3. Myelofibrosis and Marrow Fibrosis

Trephine biopsy was indispensable in diagnosing fibrotic marrow disorders, including primary myelofibrosis [9,11].

Aspiration frequently resulted in dry tap, limiting its diagnostic utility in these conditions [9].

Table 5: Disease-wise Diagnostic Superiority

Combined Diagnostic Yield

The combined use of BMA and BMB resulted in diagnostic accuracy exceeding 95% across multiple studies [10,24,25].

This synergistic effect arises from integration of cytological and architectural information, enabling comprehensive marrow evaluation [6,18].

Table 6: Combined Diagnostic Accuracy

Heterogeneity and Bias Assessment

Moderate heterogeneity was observed across studies (I² ≈ 40–60%), likely due to differences in study populations, disease spectrum, and operator expertise [21].

Funnel plot analysis suggested minimal publication bias, although small-study effects could not be completely excluded [22].

Key Findings Summary

• Trephine biopsy shows significantly higher diagnostic yield than aspiration
• Aspiration is superior for cytological evaluation
• Concordance between modalities is moderate (~70%)
• Biopsy is essential for focal, fibrotic, and infiltrative disorders
• Combined use provides maximum diagnostic accuracy (>95%)

Figure 2: Forest Plot of Diagnostic Yield – Bone Marrow Aspiration (BMA)

Figure 3: Forest plot demonstrating the diagnostic yield of bone marrow trephine biopsy (BMB) across included studies with 95% confidence intervals.

Figure 4: Summary Receiver Operating Characteristic (SROC) curve comparing diagnostic performance of bone marrow aspiration (BMA) and trephine biopsy (BMB).

DISCUSSION

The present systematic review and meta-analysis provides a comprehensive comparison of the diagnostic performance of bone marrow aspiration (BMA) and trephine biopsy (BMB) in hematological disorders. The findings demonstrate that while both techniques are complementary, trephine biopsy consistently exhibits a higher diagnostic yield, particularly in disorders characterized by focal infiltration or altered marrow architecture [10–12,24].

One of the most important observations of this study is the significant difference in diagnostic yield, with BMB achieving rates of 85–96% compared to 65–85% for BMA [3,7,10]. This disparity is largely attributable to the intrinsic limitations of aspiration, including hemodilution, inadequate sampling, and inability to assess marrow architecture [6,9]. In contrast, trephine biopsy provides intact tissue architecture, enabling evaluation of cellular distribution, stromal elements, fibrosis, and infiltrative patterns, which are critical for accurate diagnosis [11,12].

The moderate concordance rate (~68–78%) observed across studies further reinforces the complementary nature of these techniques [13,20,25]. Approximately one-third of cases showed discordant findings, indicating that reliance on a single modality may lead to missed or incomplete diagnoses [13,15]. Similar findings have been reported in previous studies, where discordance was primarily attributed to focal lesions and sampling variability [14,16].

From a disease-specific perspective, the superiority of each modality varies according to the underlying pathology. Bone marrow aspiration remains highly effective in diffuse hematological conditions, particularly acute leukemias, megaloblastic anemia, and aplastic anemia [7,17,26]. Its strength lies in providing detailed cytological information and facilitating ancillary investigations such as flow cytometry, cytogenetics, and molecular diagnostics, which are indispensable for classification and prognostication [8].

In contrast, trephine biopsy demonstrates clear superiority in detecting focal and infiltrative disorders, including lymphomas, metastatic malignancies, granulomatous diseases, and myelofibrosis [12,14,16]. The inability of aspiration to detect patchy marrow involvement results in false-negative findings in a significant proportion of cases, with studies reporting missed diagnoses in up to 30–40% of patients [14]. This limitation is particularly relevant in lymphoma staging, where accurate detection of marrow involvement has direct implications for disease staging and management [16].

Another critical area where BMB proves indispensable is in fibrotic marrow disorders, such as primary myelofibrosis. In these conditions, aspiration frequently results in a “dry tap,” rendering cytological evaluation inadequate or impossible [9]. Trephine biopsy, by contrast, allows direct visualization and grading of fibrosis, which is essential for diagnosis and prognostication [11].

The findings of this study are consistent with established hematology guidelines and standard textbooks, which emphasize the complementary roles of aspiration and biopsy in bone marrow evaluation [18,19,27,28]. The World Health Organization (WHO) classification of hematopoietic tumors also underscores the importance of integrating morphological, immunophenotypic, and molecular data—many of which rely on both aspiration and biopsy samples [18,31].

The combined diagnostic yield exceeding 95% observed in this analysis strongly supports the routine use of both procedures in clinical practice [10,24,25]. The integration of cytological and histological information enhances diagnostic accuracy, reduces the likelihood of false-negative results, and improves clinical decision-making [6,18].

From a practical standpoint, however, performing both procedures may not always be feasible due to patient discomfort, procedural time, and resource limitations. In such situations, a targeted approach based on clinical suspicion may be adopted. For example, in suspected leukemia or nutritional anemia, BMA may suffice, whereas in suspected lymphoma, metastasis, or fibrosis, BMB should be prioritized [2,6].

Another important consideration is operator expertise and technical quality. Both aspiration and biopsy are operator-dependent procedures, and inadequate sampling can significantly affect diagnostic accuracy [5]. Standardization of techniques, proper site selection, and adequate sample size are crucial for optimizing outcomes [5,29].

Despite the strengths of this meta-analysis, including comprehensive data synthesis and inclusion of multiple studies, certain limitations must be acknowledged. The included studies demonstrated heterogeneity in terms of patient populations, disease spectrum, and diagnostic criteria [21]. Additionally, most studies were observational, which may introduce selection bias [22]. Variations in operator expertise and institutional protocols may also have influenced diagnostic outcomes [5].

Future research should focus on prospective, multicenter studies with standardized protocols to better define the diagnostic roles of BMA and BMB in specific clinical scenarios. Advances in imaging-guided biopsy and molecular diagnostics may further enhance the diagnostic utility of bone marrow evaluation [8,29].

Overall, the findings of this study reinforce the concept that bone marrow aspiration and trephine biopsy are not competing but complementary techniques. Their combined use provides a more comprehensive evaluation of marrow pathology, ensuring accurate diagnosis and optimal patient management.

Limitations

The present analysis has several limitations. There was heterogeneity among studies in terms of patient populations and diagnostic criteria [21]. Most included studies were observational, which may introduce bias [22]. Additionally, limited data were available for subgroup analyses of specific hematological conditions [18].

CONCLUSION

Bone marrow trephine biopsy demonstrates higher diagnostic yield compared to aspiration, particularly in focal and infiltrative disorders. However, bone marrow aspiration remains indispensable for cytological assessment.

Combined use of BMA and BMB provides the highest diagnostic accuracy and should be considered the gold standard in hematological evaluation.

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