Is nasopharyngeal involvement of diffuse large B‑cell lymphoma (DLBCL) considered extranodal?

Nasopharyngeal Involvement in DLBCL: Extranodal Classification

Yes, nasopharyngeal involvement of DLBCL is definitively considered extranodal disease. The nasopharynx is an extralymphatic organ, and any lymphoma arising from or involving this site falls under the extranodal category according to the Ann Arbor staging system.

Staging Classification

• According to the Ann Arbor staging system, localized involvement of a single extralymphatic organ or site is designated as stage IE, which explicitly includes sites like the nasopharynx 1.
• The nasopharynx, being part of Waldeyer's ring (which includes the tonsils, adenoids, and base of tongue), represents extranodal tissue rather than lymph node tissue 1.

Clinical Implications of Extranodal Classification

CNS Prophylaxis Consideration:

• Nasopharyngeal involvement qualifies as one extranodal site, and when combined with elevated LDH, this meets criteria for CNS prophylaxis (recommendation 1, level of evidence B) 1.
• The Spanish Lymphoma Group (GELTAMO) specifically recommends screening for CNS involvement and providing prophylaxis when there is increased serum LDH and involvement of >1 extranodal site 1.
• If the nasopharynx is the only extranodal site involved, CNS prophylaxis is not automatically indicated unless other high-risk features are present (such as elevated LDH with additional extranodal sites, high CNS-IPI score, or involvement of specific high-risk organs) 1.

High-Risk Extranodal Sites Requiring Special Attention

While nasopharyngeal involvement is extranodal, it is important to distinguish it from particularly high-risk extranodal sites that warrant more aggressive CNS prophylaxis:

• Mandatory CNS prophylaxis sites: testis, breast, kidney, adrenal gland, epidural space, bone marrow, and female genital system 1, 2, 3.
• Nasopharyngeal involvement does not carry the same inherently high CNS recurrence risk as these specific sites 3.

Common Pitfall to Avoid

Do not confuse nasopharyngeal involvement with cervical lymph node involvement. Enlarged cervical lymph nodes adjacent to the nasopharynx represent nodal disease, whereas direct nasopharyngeal tissue involvement is extranodal. This distinction affects staging (IE vs II) and risk stratification for CNS prophylaxis 1.

Practical Algorithm for CNS Prophylaxis Decision

For nasopharyngeal DLBCL, provide CNS prophylaxis if ANY of the following are present:

• Elevated LDH plus ≥2 total extranodal sites (including the nasopharynx) 1
• High CNS-IPI score (4-6 factors) 1
• Concurrent involvement of testis, breast, kidney, adrenal gland, epidural space, or female genital system 1, 3
• MYC rearrangements with BCL2 or BCL6 rearrangements (double/triple hit) 1