Mature lymphomas in childhood, adolescent and young adult (CAYA) population are rare and exhibit unique clinical, immunophenotypic and genetic characteristics. Research focused on the investigation of biopathologic features of NHL in CAYA population are relatively sparse. Enhanced understanding of the pathobiologic mechanisms involved in lymphomas in this unique population will allow for improved recognition of these rare lymphomas. Elucidation of the pathobiologic differences between CAYA and adult lymphomas will also lead to the design of more rational and much needed, less toxic therapies for this population. There is an unmet clinical need for improved understanding of the pathogenetic mechanisms that contribute to the unique biology of lymphomas especially in CAYA as it will allow for more tailored therapies that are less toxic with minimal long-term effects and enhance long-term survival and prevent development of secondary neoplasms. However, while it is well accepted that lymphomas in this population exhibit distinct biologic behavior from those of the adults, the World Health Organization (WHO) classification of lymphoid neoplasms only recently recognized distinct clinicopathologic subtypes that may arise in the pediatric population. Furthermore, while the basis of subclassification of adult NHL is centered around the concept of cell of origin and that lymphoma subtypes represent neoplastic counterparts of lymphocytes in different phases of differentiation, the immunologic milieu of lymphomas of the CAYA population is likely different from those of the adults but remain unexplored. Emerging recognition of B-, T-cell subsets with distinct immunologic function and differentiation profiles may also be different in children relative to adults. Third, several studies, albeit limited in number, have shown that the mutational burden and overall genomic complexity observed in pediatric neoplasms are significantly lower than those in adults. Additionally, most lymphomas in the CAYA population occur as de novo lymphomas while transformation events from low grade into aggressive forms are rare. Finally, there is unrecognized contribution of constitutional germline genetic abnormalities that may contribute to altered immune response and the pathogenesis of lymphomas in the pediatric population. In this review, we summarize recent pathobiogic insights presented at the proceedings of the 7th International CAYA NHL Symposium held in New York City, New York October 20–23, 2022.

The basic outline of the 5th Edition of the WHO Classification of Haematolymphoid Tumours has been published in 2022 [1] and is available in full text form as an online beta-version (https://www.iarc.who.int/) with the print version expected to be published as the “Blue Book” by IARC in 2023. The chapters on NHL lymphomas commonly observed in the CAYA population have been co-authored by hematopathologists, geneticists as well as by leading clinical experts in the field of CAYA lymphomas (many of whom were active participants of the CAYA NHL Symposium in New York City). The definitions, descriptions and essential and desirable diagnostic criteria of several common CAYA lymphomas have been refined and entities previously considered as provisional entities have been “upgraded” to definitive entities. The biopathologic features of the most common NHL in the CAYA population are outlined in the following sections.