# Case Report: Sequential lymphomas: may HLA system play a role in this uncommon phenomenon?

**Authors:** Evgenia Verrou, Ioanna Diamanti, Asimina Fylaktou, Aikaterini Daiou, Dimitra Dalampira, Xanthippi Dimitriadou, Vassiliki Tara, Elissavet Karadrakonti, Theodora Triantafyllou, Aggeliki Sevastoudi, Efthimia Vlachaki, Nikolaos Karampatzakis, Theodosia Papadopoulou, Emmanouil Sinakos, Eirini Katodritou, Georgia Gioula

PMC · DOI: 10.3389/fonc.2025.1586454 · Frontiers in Oncology · 2025-06-24

## TL;DR

This case report explores the rare occurrence of sequential lymphomas and investigates whether HLA system variations might play a role in this phenomenon.

## Contribution

The study reports HLA class-I and class-II findings in patients with sequential lymphomas, highlighting potential associations with autoimmune alleles.

## Key findings

- Four out of eight patients were HLA-DQB1*03:01 positive, with three developing a third lymphoma.
- Three patients exhibited HLA-B*35:03, an allele linked to autoimmune conditions.
- HLA typing may be relevant for understanding sequential lymphoma occurrences.

## Abstract

The sequential occurrence of diffuse large B‐cell lymphoma (DLBCL) in a patient diagnosed with classical Hodgkin lymphoma (cHL) or vice versa represents a rare situation. In parallel, human leukocyte antigen (HLA) has been studied extensively about rising susceptibility in various lymphomas. Herein, we present clinical characteristics, the outcome and the results of HLA class-I and class-II investigation in patients sequentially diagnosed with the above-mentioned combination of lymphomas. We describe 8 patients (6 males/2 females) with median age at diagnosis of first and second lymphomas of 45.5 years (range: 25–74 years) and 57.5 years (range: 30–83 years), respectively. The median interval between the first and the second diagnosis was 6.5 years (range: 4–22 years). Regarding HLA investigation, we observed that four of our patients were HLA‐DQB1*03:01 positive. Interestingly, three of our patients displaying this HLA allele developed a third lymphoma. Notably, we observed that the HLA profile of three other patients revealed the presence of HLA-B*35:03. Interestingly, both above-mentioned HLA alleles have been associated with autoimmune manifestations. Although the presence of certain HLA alleles in our patients could be coincidental, our results suggest that HLA typing may be a field of investigational interest regarding patients with sequential lymphomas.

## Linked entities

- **Diseases:** diffuse large B-cell lymphoma (MONDO:0018905), classical Hodgkin lymphoma (MONDO:0009348)

## Full-text entities

- **Genes:** HLA-DQB1 (major histocompatibility complex, class II, DQ beta 1) [NCBI Gene 3119] {aka CELIAC1, HLA-DQB, IDDM1}
- **Diseases:** autoimmune manifestations (MESH:D012877), DLBCL (MESH:D016403), lymphoma (MESH:D008223), cHL (MESH:D006689)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Full text

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## References

25 references — full list in the complete paper: https://tomesphere.com/paper/PMC12234450/full.md

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Source: https://tomesphere.com/paper/PMC12234450