What is the best way to confirm a diagnosis in a child presenting with multiple painless firm lymph nodes: Complete Blood Count (CBC), bone marrow biopsy, or lymph node biopsy?

Lymph Node Biopsy is the Best Method to Confirm Diagnosis

In a child presenting with multiple painless firm lymph nodes, excisional or incisional lymph node biopsy is the definitive diagnostic approach—not CBC or bone marrow biopsy. 1, 2

Why Lymph Node Biopsy is Essential

Lymph node biopsy provides the tissue architecture and comprehensive immunophenotyping required for accurate lymphoma classification, which neither CBC nor bone marrow biopsy can reliably deliver. 1, 2

• The NCCN explicitly states that excisional or incisional biopsy of the most accessible lymph node is the preferred diagnostic method for pediatric aggressive B-cell lymphomas, with fresh tissue sent in saline to ensure viability 1
• Morphologic examination, immunohistochemistry, immunophenotyping, and cytogenetics are all essential to establish a definitive diagnosis of Burkitt lymphoma or diffuse large B-cell lymphoma 1
• Fine needle aspiration or core biopsy alone is generally not suitable for initial lymphoma diagnosis in children 1, 2

Role of CBC (Limited Utility)

CBC is part of the initial workup but cannot establish a diagnosis of lymphoma in a child with lymphadenopathy 1:

• CBC with differential and platelets is listed as "essential" in the workup algorithm, but only for staging and baseline assessment—not diagnosis 1
• Flow cytometry of blood is adequate for diagnosis only in chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), which is exceedingly rare in children 1

Role of Bone Marrow Biopsy (Staging, Not Diagnosis)

Bone marrow biopsy is performed after lymphoma diagnosis is established by lymph node biopsy 1:

• Bilateral bone marrow aspirate and biopsy is part of the staging workup for pediatric Burkitt and DLBCL, used to determine if there is stage IV disease (>5% lymphoma cells in marrow) 1
• Bone marrow involvement affects risk stratification and treatment intensity, but the primary diagnosis must come from lymph node tissue 1
• Performing bone marrow biopsy before establishing the diagnosis via lymph node biopsy puts the cart before the horse 1

Critical Diagnostic Algorithm

Step 1: Obtain excisional or incisional biopsy of the most accessible enlarged lymph node 1, 2

Step 2: Send fresh tissue in saline for:

• Touch preparation for cytologic examination 1
• Morphologic review 1
• Immunohistochemistry (CD3, CD5, CD10, CD20, CD23, cyclin D1) 1
• Flow cytometry for immunophenotyping 1
• Cytogenetics and FISH for translocations (MYC, BCL2, BCL6) 1

Step 3: Once diagnosis is confirmed, proceed with staging workup including CBC, bone marrow biopsy, lumbar puncture, and imaging 1

Common Pitfalls to Avoid

• Never rely on CBC alone to diagnose lymphoma in a child with lymphadenopathy—this will miss the diagnosis in most cases 1, 2
• Do not perform bone marrow biopsy first—the primary tissue diagnosis must come from the lymph node itself 1
• Avoid fine needle aspiration as the sole diagnostic procedure in suspected new lymphoma, as it lacks tissue architecture needed for classification 1, 2
• In children with persistent lymphadenopathy initially reported as reactive hyperplasia, consider repeat biopsy as there is >75% probability of detecting disease on second biopsy 3

When to Suspect Lymphoma and Proceed Urgently to Biopsy

Specific high-risk features warrant immediate lymph node biopsy 4, 5, 6:

• Supraclavicular location of lymphadenopathy 4, 6
• Lymph node size >2 cm 5, 6
• Firm, non-tender, fixed lymph nodes 4, 6
• Absence of ear, nose, throat symptoms 5
• Abnormal chest X-ray 5, 6
• Constitutional symptoms (fever >1 week, weight loss) without obvious infectious cause 4