Dedicated diagnostic approaches for mature B-cell non-Hodgkin lymphomas occurring in children, adolescents, and young adults.

Non-Hodgkin lymphoma (NHL) represents the fourth most common malignant disease among children and adolescents. Current disease classifications, including the most recent World Health Organization (WHO) classification and the International Consensus Classification (ICC), rely on a combination of clinical, epidemiological, histologic, immunophenotypic, and molecular data to define discrete clinicopathologic entities. There is growing evidence that children, adolescents, and young adults (CAYA) with B-cell NHL display unique clinical and epidemiologic characteristics. This may be explained by distinct age-related developmental plasticity, immune and haematopoietic repertoires, environmental exposures and social determinants of health, and germline or acquired genetic and molecular features, including those associated with inborn errors of immunity (IEI). Here, we discuss the unique clinical and biological characteristics of several distinct paediatric B-cell NHL types to indicate a path forward in classification of these CAYA NHL to optimally support multidisciplinary patient care and personalized treatment. We propose a potential "arising in CAYA" classification qualifier to denote the distinct clinicopathologic characteristics of B-cell NHLs that, otherwise, histologically and immunophenotypically resemble those arising in middle-aged and older adults. We also discuss how haemopathology diagnoses are evolving to incorporate the most current scientific knowledge into future classification systems of CAYA B-cell NHL.