Real-world lymphoma cohort in the HIV-endemic setting: Impact of implementing novel reclassification standards

Background: Lymphoma real-world observational data and accurate diagnostic systems are lacking in low-resource settings. We established a diagnostic registry for lymphoma classification to generate internationally comparable, clinically validated data. Methods: The descriptive retrospective cohort included patients ≥13 years of age newly diagnosed with lymphoma from 2005 to 2020. Patients were enrolled at a single site in a registry with hierarchical groupings to capture, interrogate, and subtype lymphoma diagnoses. These were standardised on sequential versions of the World Health Organisation Classification of Haematolymphoid Tumours (WHO-HAEM) and correlated with the International Consensus Classification of mature lymphoid neoplasms (ICC). Differences due to nomenclature and diagnostic category were annotated. Results: The cohort consisted of 2354 incident lymphoma cases; 1891 (80.3%) non-Hodgkin lymphoma and 463 (19.7%) Hodgkin lymphoma (HL). Twenty-one lymphoma NOS cases were excluded due to inadequate specimen for standardised sub-classification. Overall reclassification according to WHO-HAEM5 was 25.8% (n=608). Major differences between WHO-HAEM5 and ICC included 44 (1.9%) transformations of indolent B-cell lymphomas; also 957 (40.7%) lymphoid proliferations and lymphomas associated with immune deficiency/dysregulation due to HIV (33.1%) and EBV (31.8%). EBV-association was highest among HL cases, 77 (50.3%) were HIV reactive. Conclusion: We report here the impact of adopting international lymphoma classification standards in an HIV-endemic setting. Our findings highlight the persistent prevalence of large B-cell lymphoma, confirm inadequate viral suppression as a key disease driver, and provide further evidence for EBV-associated HL as a distinct entity. Consolidating HIV-associated and other immune deficiency/dysregulation lymphomas into a unified framework could have significant implications and warrants further consideration for inclusion in future WHO-HAEM classifications.