Can lymphadenopathy in lymphoma fluctuate without treatment?

Lymphadenopathy in Lymphoma Can Fluctuate Without Treatment

Yes, lymphadenopathy in lymphoma can fluctuate in size without treatment, which may represent a tumor flare, immune response, or natural disease fluctuations rather than true progression. 1

Mechanisms of Lymph Node Size Fluctuation

Lymph node size in lymphoma can vary for several reasons without indicating true disease progression:

1. Immune Response:

   • Local immune responses can cause temporary enlargement of lymph nodes
   • This is similar to the "flare" phenomenon observed when treatment begins 1

2. Pseudo-progression:

   • Particularly noted with immunomodulating agents and immunotherapies
   • Can be related to recruitment of immune cells to disease sites 1

3. Natural Disease Fluctuations:

   • Small increases in lymph node size (up to 20%) may occur while other disease sites are stable or improving 1
   • These fluctuations should not be immediately classified as disease progression

Clinical Significance and Evaluation

According to the International Working Group Consensus Response Evaluation Criteria in Lymphoma (RECIL 2017), several important principles apply when evaluating lymph node changes:

• Minor Fluctuations: An increase in previously involved small lymph nodes by >20% while other lesions are decreasing should not be designated as progressive disease (PD) unless there is continued increase on subsequent imaging 1

• Measurement Thresholds: After an initial response, PD is defined as:

  • An increase of the nadir sum of diameters by >20%
  • For complete responders, at least one previously involved lymph node should increase to ≥15 mm in long diameter, with a minimum absolute increase of 5 mm from nadir 1

• Confirmatory Testing: When lymph node size changes are inconsistent with clinical status:

  • Biopsy should be considered for questionable lesions
  • Follow-up imaging is recommended to clarify the response 1

Practical Approach to Fluctuating Lymphadenopathy

When lymphadenopathy fluctuates in lymphoma patients not on treatment:

1. Monitor closely rather than immediately changing management

   • Follow-up imaging in 1-3 months to assess trend

2. Consider biopsy for:

   • New lesions
   • Disproportionate growth of one node compared to others
   • Lymph nodes with atypical features

3. Assess for other symptoms:

   • Constitutional symptoms (fever, night sweats, weight loss)
   • Disease-specific symptoms

4. Avoid premature treatment changes based solely on minor lymph node size fluctuations

Special Considerations

In Waldenström macroglobulinemia/lymphoplasmacytic lymphoma, serum IgM levels may not correlate with actual tumor burden. The NCCN guidelines note that "in circumstances where the serum IgM levels appear to be out of context with the patient's clinical progress, a bone marrow biopsy should be considered to clarify the patient's underlying disease burden." 1

Similarly, in chronic lymphocytic leukemia (CLL), progressive lymphocytosis is defined as an increase of ≥50% over a 2-month period or lymphocyte doubling time of <6 months, but factors contributing to lymphocytosis other than CLL should be excluded 1.

Conclusion

Lymphadenopathy in lymphoma can indeed fluctuate without treatment due to immune responses and natural disease variations. The key is distinguishing these fluctuations from true disease progression, which requires consistent increases in size over time, appearance of new lesions, or development of systemic symptoms.