Significance of E-lesions in Hodgkin lymphoma and the creation of a new consensus definition: A report from SEARCH.

The International Staging Evaluation and Response Criteria Harmonization for Childhood, Adolescent, and Young Adult Hodgkin Lymphoma (SEARCH for CAYAHL) seeks to provide an appropriate, universal differentiation between E-lesions and stage IV extranodal disease in Hodgkin lymphoma (HL). A literature search was performed through the PubMed database using the terms "Hodgkin disease," and "extranodal," "extralymphatic," "E lesions," "E stage," or "E disease." Publications were reviewed for the number of participants, median age and age range, diagnostic modalities used for staging, and the definition, incidence, and prognostic significance of E-lesions. Thirty-five articles describing 11,928 patients met the inclusion criteria. Most studies reported staging according to the Ann Arbor (74%) or Cotswolds modification of the Ann Arbor staging criteria (23%), and articles rarely defined E-lesions or disambiguated "extranodal disease." The overall incidence of E-lesions for patients with stage I-III HL was 12.6%. Available stage-specific incidence analysis of 3,175 patients showed the highest incidence of E-lesions in stage II (28%), followed by stage III (22%), with E-lesions rarely seen with stage I disease (1.3%). E-lesions likely remain predictive, but we cannot unequivocally conclude that identifying E-lesions in HL imparts prognostic value in the modern era of the more selective use of targeted radiation therapy. A harmonized definition was reached based on the available evidence and the consensus of the SEARCH working group. We recommend that this definition of E-lesion be applied in future clinical trials with explicit reporting to confirm the prognostic value of E-lesions.