What is the best way to confirm the diagnosis in a pediatric patient presenting with multiple painless firm lymph nodes?

Lymph Node Biopsy is the Best Method to Confirm Diagnosis

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

Why Lymph Node Biopsy is Essential

The diagnosis of lymphoma (the primary concern in this presentation) requires comprehensive tissue architecture, immunophenotyping, flow cytometry, and cytogenetic analysis that only lymph node biopsy can provide. 2, 1

• Excisional or incisional biopsy provides the morphologic examination, immunohistochemistry, and genetic testing essential for accurate lymphoma classification. 1
• Fresh tissue should be sent in saline to ensure viability for touch preparation, flow cytometry, and molecular studies. 1
• Fine needle aspiration (FNA) alone is not acceptable for initial lymphoma diagnosis because it lacks the tissue architecture required by the WHO classification system. 2

Why CBC and Bone Marrow Biopsy Are Insufficient

CBC Limitations

• CBC with differential is listed as "essential" in workup algorithms, but only for staging and baseline assessment—not for diagnosis. 1
• Relying on CBC alone will miss the diagnosis in most cases of pediatric lymphoma. 1
• CBC cannot provide the histologic subtype, immunophenotype, or genetic features required for treatment planning. 2

Bone Marrow Biopsy Limitations

• Bone marrow biopsy is performed after lymphoma diagnosis is established by lymph node biopsy. 1
• Its role is to determine stage IV disease (>5% lymphoma cells in marrow) and guide treatment intensity—not to make the initial diagnosis. 1
• Performing bone marrow biopsy first is a critical error that delays definitive diagnosis. 1

Diagnostic Algorithm

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

Step 2: Send fresh tissue in saline for:

• Touch preparation and morphologic review 1
• Immunohistochemistry panel (CD20, CD3, CD5, CD10, BCL2, BCL6, cyclin D1, CD21, CD23) 2
• Flow cytometry (kappa/lambda, CD19, CD20, CD5, CD23, CD10) 2
• Cytogenetics or FISH for characteristic translocations 2

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

Critical Pitfalls to Avoid

• Never rely on CBC alone to diagnose lymphoma in a child with lymphadenopathy—this approach will miss the diagnosis in the majority of cases. 1
• Do not perform bone marrow biopsy first—the primary tissue diagnosis must come from the lymph node itself. 1
• Avoid FNA as the sole diagnostic procedure in suspected new lymphoma, as it lacks the tissue architecture needed for accurate classification. 2, 1
• Core needle biopsy is discouraged unless the clinical situation dictates this is the only safe means of obtaining tissue. 2

Clinical Context

In a child with multiple painless firm lymph nodes, the differential diagnosis includes:

• Hodgkin and non-Hodgkin lymphoma (primary concern) 3
• Chronic lymphocytic leukemia/small lymphocytic lymphoma 3
• Infectious causes (though less likely without fever) 3

The presentation of multiple painless firm nodes raises significant concern for malignancy, making definitive tissue diagnosis urgent. 3, 4 Lymph nodes >1.5 cm persisting >2 weeks place the patient at increased risk for malignancy or chronic infection. 5 Excisional biopsy has >95% diagnostic yield and remains the gold standard. 3