For suspected lymphoma, should the initial diagnostic step be a fine‑needle aspiration (FNA) or an excisional/incisional (core‑needle) biopsy?

Excisional/Incisional Biopsy is the Best Initial Diagnostic Step for Suspected Lymphoma

For suspected lymphoma, you should perform an excisional or incisional biopsy as the first-line diagnostic approach—fine-needle aspiration (FNA) is explicitly inappropriate for reliable initial lymphoma diagnosis. 1, 2

Why Excisional/Incisional Biopsy is Superior

The NCCN and ESMO guidelines are unequivocal on this point:

• FNA is insufficient for initial lymphoma diagnosis because it cannot provide the tissue architecture and comprehensive immunophenotyping required for accurate WHO classification 1, 2

• Excisional biopsy preserves lymph node architecture, which is essential for distinguishing between lymphoma subtypes, determining grade, and identifying transformation patterns 1, 2

• Adequate tissue is critical for the full panel of ancillary studies needed: immunohistochemistry, flow cytometry, cytogenetics, FISH, and molecular studies that determine specific lymphoma subtype and guide treatment 2

• Diagnostic accuracy is measurably higher with surgical excision (98.1% definitive diagnosis) compared to core needle biopsy (92.3%), with lower discordance rates between referral and expert pathologists (21.2% vs 23.1%) 3

Algorithmic Approach to Biopsy Selection

First-Line: Excisional or Incisional Biopsy

• Use for all accessible lymph nodes in patients with suspected new lymphoma diagnosis 1, 2
• This is the gold standard and should not be bypassed when feasible 2

Second-Line: Core Needle Biopsy (CNB)

Only when excisional biopsy is not feasible:

• Inaccessible nodes (e.g., retroperitoneal, mediastinal bulk) 1
• Patient cannot tolerate surgery due to comorbidities 2
• Must be combined with comprehensive ancillary studies (immunohistochemistry, flow cytometry, molecular studies) 2, 4
• Be aware that CNB has limitations: difficulty appreciating FL grading heterogeneity, higher rates of inconclusive diagnoses requiring re-biopsy 1

When FNA May Be Acceptable (Very Limited)

• Documenting relapse in patients with previously diagnosed and classified lymphoma 2
• Never for initial diagnosis 1, 2

Critical Pitfalls to Avoid

• Never rely on FNA alone for initial diagnosis—this violates established guidelines and risks misclassification that directly impacts treatment selection and patient outcomes 1, 2

• Do not assume CNB is equivalent to excisional biopsy—while CNB can provide definitive diagnosis in 90-97% of cases, it still carries higher risk of diagnostic error and unclassified results 4, 5, 6, 3

• Re-biopsy may be required if initial CNB material is inadequate—this is explicitly acknowledged in guidelines and occurs more frequently than with excisional biopsy 1

• Grading cannot be reliably performed on FNA specimens, and heterogeneity within lymph nodes (particularly important for follicular lymphoma grade 3A vs 3B distinction) is difficult to appreciate on core biopsies 1

Nuances in the Evidence

While recent research suggests CNB has improved diagnostic accuracy (79-97% efficacy) with modern immunohistochemical and molecular techniques 4, 5, 6, the most recent large-scale multicenter study of 32,285 cases definitively showed surgical excision remains superior 3. The 2022 French Lymphopath network data demonstrated that CNB resulted in more unclassified lymphomas and equivocal lesions, with expert review able to reclassify only 81.4% of CNB cases versus 93.3% of surgical excisions 3.

The ESMO guidelines specifically note that even when CNB is used for inaccessible nodes, the "possible heterogeneity of FL grading difficult to appreciate on core biopsies" remains a significant limitation 1. This directly impacts treatment decisions, as FL grade 3B is treated as aggressive lymphoma while grades 1,2, and 3A are managed as indolent disease 1.

Special Considerations

• For Hodgkin lymphoma specifically, excisional biopsy is strongly recommended, though core needle biopsy may be adequate if diagnostic; FNA is insufficient except in unusual circumstances when combined with immunohistochemistry and judged adequate by an expert hematopathologist 2

• For chronic lymphocytic leukemia (CLL), the combination of CNB and FNA with ancillary techniques is more acceptable than for other lymphoma subtypes 2

• Cost considerations: While CNB offers >75% cost savings compared to open biopsy 4, this must be weighed against the risk of inconclusive diagnosis requiring repeat procedures, which negates cost benefits and delays treatment initiation