Diagnostic Management of Diffuse Large B-Cell Lymphoma (DLBCL)
Diagnosis of DLBCL should be made through surgical excisional lymph node or extranodal tissue biopsy with sufficient material for formalin-fixed samples, processed by an experienced pathology institute. 1
Initial Diagnostic Approach
Biopsy Requirements
- Surgical excisional biopsy is the optimal diagnostic method 1
- Core biopsies should be reserved only for patients where surgical approach is impractical or risky 1
- Fine-needle aspiration alone is inadequate and should not be used as the sole basis for diagnosis 1
Pathological Assessment
- Mandatory minimal immunohistochemistry: CD45, CD20, and CD3 1
- Morphological diagnosis must be confirmed by immunophenotypic investigations 1
- Collection of fresh frozen material for molecular characterization is recommended 1
- If diagnosis is uncertain, B-cell monoclonality should be demonstrated by PCR-based methods 1
- Assessment of MYC and BCL2 rearrangements using interphase FISH is recommended for newly diagnosed and relapsed patients 1
Staging and Risk Assessment
Laboratory Workup
- Complete blood count
- Routine blood chemistry including LDH and uric acid
- Screening tests for HIV, hepatitis B and C
- Protein electrophoresis 1
Imaging Studies
- FDG-PET/CT scan is the gold standard for staging DLBCL patients 1
- If PET/CT is unavailable, CT scan of chest and abdomen is required 1
- For suspected CNS lymphoma, MRI is the modality of choice 1
Bone Marrow Assessment
- Bone marrow aspirate and biopsy should be performed 1
- Biopsy may be avoided when PET/CT demonstrates bone/marrow involvement indicating advanced-stage disease 1
CNS Assessment
- Diagnostic lumbar puncture should be considered in high-risk patients 1
- High-risk features include: elevated LDH, >1 extranodal site, involvement of specific sites (testes, breast, paranasal sinuses, epidural space) 1
Cardiac Assessment
- Cardiac function (left ventricular ejection fraction) should be assessed before treatment 1
Risk Stratification
- Staging according to the Ann Arbor classification system 1
- International Prognostic Index (IPI) and age-adjusted IPI (aa-IPI) should be calculated 1
- Cell of origin determination (germinal center-like vs. activated B-cell-like subtypes) through immunohistochemistry 1
Response Evaluation
- Abnormal radiological tests at baseline should be repeated after 3-4 cycles and after the last cycle of treatment 1
- Bone marrow aspirate and biopsy should only be repeated at the end of treatment if initially involved 1
- PET is highly recommended for post-treatment assessment to define complete remission 1
- Histological confirmation of PET positivity is strongly recommended if therapeutic consequences are anticipated 1
Common Pitfalls and Caveats
Inadequate biopsy specimens: Core biopsies may be appropriate only in rare patients requiring emergency treatment; otherwise, surgical excisional biopsy is preferred 1
Incomplete immunohistochemical assessment: Failure to perform minimal required immunohistochemistry can lead to misdiagnosis 1
Overlooking molecular assessment: Assessment of MYC and BCL2 rearrangements is critical for proper risk stratification and treatment planning 1
Insufficient CNS evaluation: Failure to perform diagnostic lumbar puncture in high-risk patients can miss CNS involvement 1
Over-reliance on early PET: Early PET results (after 1-4 cycles) should not lead to treatment changes outside clinical trials, despite their prognostic value 1
Inadequate follow-up: Proper follow-up includes history and physical examination every 3 months for 1 year, every 6 months for 2 more years, and then annually, with attention to secondary tumors and long-term side effects 1
By following this diagnostic algorithm, clinicians can ensure accurate diagnosis, appropriate staging, and optimal risk stratification of DLBCL patients, which is essential for determining the most effective treatment approach and improving patient outcomes.