Mature lymphomas of the adolescent and young adult population (AYA) are rare and clinically and pathobiologically distinct from those in the adult population. The pathobiologic aspects of lymphomas in the AYA population are largely unknown as most studies do not specify age groups and use diagnostic criteria that have been established for lymphomas in the adult population. B-cell lymphomas make up the majority of lymphomas in the AYA population and many are aggressive including Burkitt lymphoma, large/high grade B-cell lymphoma with 11q aberrations and diffuse large B-cell lymphoma (DLBCL), NOS. Most DLBCL, NOS arise as de novo lymphomas. They may occur as a secondary neoplasm after childhood cancer or in cancer predisposition syndromes, primary immunodeficiencies or other inherited genetic diseases (inborn error of immunity-associated lymphoid proliferations and lymphomas). Most DLBCL, NOS in the AYA population are of germinal center derivation, exhibit high proliferation index and while comprehensive studies are lacking, they are biologically distinct from adult diffuse large B-cell lymphomas with less cytogenetic complexity. Mature T-cell lymphomas are extremely rare in the AYA population and composed primarily of those driven by a dominant oncogenic tyrosine kinase (ALK+ anaplastic large cell lymphoma) or Epstein-Barr virus and most arise from T cells of the innate immune system. T-cell lymphomas arising from the adaptive immune system (nodal T follicular helper (TFH) cell lymphoma, peripheral T cell lymphoma, NOS) which are common in the adult population are rare in AYA. The most recent WHO Classification of Paediatric Tumors recognizes specific entities that are enriched in the AYA population with distinct genetic features including indolent B-cell lymphoma including pediatric-type follicular lymphomas, pediatric nodal marginal zone lymphoma and large B-cell lymphomas with IRF4 rearrangement, and EBV-associated T cell lymphoma such as systemic EBV-positive T-cell lymphoma of childhood, systemic chronic active EBV-positive disease and hydroa vacciniforme lymphoproliferative disorder. The distinct clinical and pathobiologic features of lymphomas in the AYA population provide unique opportunities for translational discoveries leveraging innovative technologies such as single cell sequencing, B and T cell immune repertoire analyses and circulating tumor DNA, that will provide insights into the interplay between the immune system, epigenetics, germline predisposition and viruses. These studies are poised to yield actionable information that impacts therapies and improve patient outcomes.
Citation Format: Megan S. Lim. Pathology of AYA lymphomas: Creating a roadmap for translational research [abstract]. In: Proceedings of the Third AACR International Meeting: Advances in Malignant Lymphoma: Maximizing the Basic-Translational Interface for Clinical Application; 2022 Jun 23-26; Boston, MA. Philadelphia (PA): AACR; Blood Cancer Discov 2022;3(5_Suppl):Abstract nr IA39.