Can DLBCL Diagnosis Be Established from Bone Marrow Biopsy Only?
No, a bone marrow biopsy alone should not be used as the sole basis for establishing a diagnosis of DLBCL; a surgical excision biopsy of lymph node or extranodal tissue remains the optimal and recommended diagnostic method. 1
Why Surgical Excision Biopsy Is Required
Surgical excision biopsy is the gold standard because it allows assessment of nodal architecture and provides adequate material for comprehensive phenotypic and molecular studies that are essential for accurate DLBCL diagnosis. 1
The biopsy specimen should ideally be sent unfixed to the laboratory to enable flow cytometric studies and extraction of high-quality DNA and RNA for molecular characterization. 1
Immunohistochemistry must confirm B-cell lineage with a comprehensive panel (CD20, CD79a, BCL6, CD10, MYC, BCL2, Ki67, IRF4, CyclinD1, CD5, CD23) to distinguish DLBCL from morphologically similar entities such as Burkitt lymphoma, plasmablastic lymphoma, blastic mantle cell lymphoma, and Hodgkin's lymphoma. 1
When Core Biopsy May Be Acceptable
Needle-core and endoscopic biopsies should be reserved only for patients in whom a surgical approach is impractical or would entail excessive risk. 1
In emergency situations requiring rapid treatment initiation, a core needle biopsy can be used as the sole diagnostic procedure to avoid delay, but this is explicitly an exception to standard practice. 2
Core biopsies may be appropriate in rare patients requiring emergency treatment, but they remain suboptimal compared to excisional biopsy. 1
Critical Limitations of Bone Marrow Biopsy for Primary Diagnosis
Bone marrow involvement by DLBCL can be morphologically subtle, with tumor cells mimicking pronormoblasts (immature erythroid precursors), making initial diagnosis difficult without immunohistochemistry. 3
Low-level bone marrow involvement (≤10%) with sinusoidal and interstitial growth patterns may be missed on routine morphologic examination, requiring CD20 immunostaining for detection. 3
Bone marrow biopsy is performed for staging purposes after diagnosis is established, not as the primary diagnostic modality. 1, 4
PET/CT can miss bone marrow involvement in 9% of patients with negative scans who have positive bone marrow biopsies, but this finding is used for staging rather than initial diagnosis. 5
The Diagnostic Hierarchy
Fine-needle aspirate should never be used as the sole basis for a diagnosis of DLBCL under any circumstances. 1
When confidence in diagnosis is reduced due to small biopsy specimens, demonstration of B-cell monoclonality by PCR-based methods should be considered to supplement morphologic and immunophenotypic findings. 1
All morphological diagnoses of DLBCL must be confirmed by immunophenotypic investigations using either immunohistochemistry, flow cytometry, or both techniques. 1
Common Pitfall to Avoid
The most critical error would be attempting to diagnose DLBCL from bone marrow biopsy alone when lymph node or extranodal tissue is accessible, as this compromises the ability to perform comprehensive phenotypic and molecular characterization required for accurate diagnosis and subtype classification. 1 This is particularly important because DLBCL encompasses heterogeneous subtypes with different clinical implications that can only be distinguished with adequate tissue for full immunohistochemical panels and molecular studies. 1, 6