Clinicopathological, Genomic, and Transcriptomic Feature Analysis of Primary Adrenal Large B-cell Lymphoma

Primary large B-cell lymphoma of immune-privileged sites (IP-LBCL) is a newly categorized disease entity in the 5th WHO Classification of Tumors. Through an analysis of 53 primary adrenal large B-cell lymphoma (PA-LBCL) cases, we unraveled the similarity to IP-LBCL in clinical presentation, pathologic features, and genetic landscape. Our findings reveal a predominant immunophenotype of CD10-/BCL6+/MUM1+ in PA-LBCL, mirroring that observed in IP-LBCL, and a shared mutation spectrum characterized by the notable presence of PIM1, MYD88 L265P, and CD79B mutations. In addition, the results of RNA sequencing showed that there are significant differences in the expression profiles of PA-LBCL and SA-LBCL. The top 5 RNAs with the most significant expression differences were RPL23AP82, IGSF21, CMKLR, PTPRG, and PRKCA. Moreover, PA-LBCL exhibited a more favorable prognosis than DLBCL-NOS with secondary adrenal involvement. The results of this study indicate that PA-LBCL shares similar clinical features, immunophenotypes, and molecular genetic profiles with IP-LBCL, suggesting that it may belong to a subtype of IP-LBCL. This research has improved our understanding of lymphoma, especially those occurring in atypical sites, and reshaped our concept of lymphoma classification and management. We suggest considering incorporating PA-LBCL into IP-LBCL in the future classification of lymphoma.