TET2 and LILRB1 mutations are frequent in Epstein–Barr virus-positive diffuse large B-cell lymphoma especially in elderly patients

Menée à partir de l'analyse immunohistochimique et génétique d'échantillons tissulaires fixés au formaldéhyde et inclus en paraffine après prélèvement sur des patients atteints d'un lymphome diffus à grandes cellules B, cette étude met en évidence, chez les patients âgés dont le lymphome est positif au virus d'Epstein-Barr, la présence fréquente de mutations au niveau des gènes TET2 et LILRB1

Résumé en anglais

Background : Diffuse large B-cell lymphoma (DLBCL) harboring Epstein–Barr virus (EBV) primarily occurs in patients who have underlying immunodeficiency or in elderly patients but is also reported in young, immunocompetent patients. The authors investigated the pathologic differences in EBV-positive DLBCL in these three groups of patients.

Methods : In total, 57 patients with EBV-positive DLBCL were included in the study; of these, 16 patients had associated immunodeficiency, 10 were young (younger than 50 years), and 31 were elderly (aged 50 years or older). Immunostaining for CD8, CD68, PD-L1, and EBV nuclear antigen 2, and panel-based next-generation sequencing was performed on formalin-fixed, paraffin-embedded blocks.

Results : Immunohistochemistry revealed EBV nuclear antigen 2 positivity in 21 of the 49 patients. The degree of CD8-positive and CD68-positive immune cell infiltration and PD-L1 expression did not differ significantly in each group. Extranodal site involvement was more common in young patients (p = .021). In mutational analysis, the genes with the highest mutation frequency were PCLO (n = 14), TET2 (n = 10), and LILRB1 (n = 10). For the TET2 gene, all 10 mutations were found in elderly patients (p = .007). Compared with a validation cohort, both TET2 and LILRB1 showed a higher mutation frequency in EBV-positive patients than in EBV-negative patients.

Conclusions : EBV-positive DLBCL occurring in three different age and immune status groups showed similar pathologic characteristics. Notably, a high frequency of TET2 and LILRB1 mutations was characteristic of this disease in elderly patients. Further studies are needed to determine the role of TET2 and LILRB1 mutations in the development of EBV-positive DLBCL along with immune senescence.