Follicular lymphoma: Molecular features by age
Because of the excellent prognosis in pediatric-type FL, it is important to assess whether young adults with FL have adult-type or pediatric-type lesions, Dr. Louissaint said.
He cited many studies showing differences in adult and pediatric-type FL. In adult FL, the mutational landscape is characterized by frequent chromatin-modifying mutations in genes such as CREBBP, KM22D, and EP300.
In contrast, in pediatric-type FL, there are frequent activating MAPK pathway mutations, including mutations in the negative regulatory domain of MAP2K1. These mutations are not seen in adult FL.
Dr. Louissaint noted that there may be mutations in epigenetic modifiers (CREBBP, TNFRSF14) in both adult and pediatric-type FL. However, CREBBP is very unusual in pediatric-type FL and common in adult FL. This suggests the alterations in pediatric-type FL do not simply represent an early stage of the same disease as adult FL.
Despite a high proliferating fraction and absence of BCL2/BCL6/IRF4 rearrangements in pediatric-type FL, the presence of these features was associated with dramatic difference in progression-free survival, according to research published in Blood in 2012.
A distinct entity
In 2016, the World Health Organization recognized pediatric-type FL as a distinct entity, with the following diagnostic criteria (published in Blood):
- At least partial effacement of nodal architecture, expansile follicles, intermediate-size blastoid cells, and no component of diffuse large B-cell lymphoma.
- Immunohistochemistry showing BCL6 positivity, BCL2 negativity or weak positivity, and a high proliferative fraction.
- Genomic studies showing no BCL2 amplification.
- Clinical features of nodal disease in the head and neck region, early clinical stage, age younger than 40 years, typically in a male with no internal nodes involved.
When FL occurs in AYAs, the diagnostic findings of pediatric-type FL suggest the patient will do well with conservative management (e.g., excision alone), Dr. Louissaint noted.
Two sizes do not fit all
The strategies that have improved cancer outcomes since the 1970s for children and older adults have been much less successful for AYAs with cancer.
As an oncologic community, we should not allow the AYA gap to persist. As always, the solutions are likely to involve focused clinical research, education, and communication. Effort will need to be targeted specifically to the AYA population.
Since health-related mortality is high even when cancer-specific outcomes improve, adopting and maintaining a healthy lifestyle must be a key part of the discussion with these young patients.
The biologic differences associated with AYA lymphomas demand participation in clinical trials.
Oncologists should vigorously support removing impediments to the participation of AYAs in prospective clinical trials, stratified (but unrestricted) by age, with careful analysis of patient-reported outcomes, late adverse effects, and biospecimen collection.
As Dr. Kelly noted in the question-and-answer period, the Children’s Oncology Group has an existing biobank of paraffin-embedded tumor samples, DNA from lymphoma specimens, plasma, and sera with clinically annotated data that can be given to investigators upon request and justification.