# Indolent primary cutaneous B-cell lymphomas resemble persistent antigen reactions without signs of dedifferentiation

## TL;DR

Indolent B-cell skin cancers resemble immune responses to antigens and lack signs of severe cell changes.

## Contribution

The study reveals that indolent B-cell lymphomas maintain germinal center activity and may be antigen-driven.

## Key findings

- Indolent pcMZL, pcFCL, and rB-LP show persistent germinal center reactions.
- pcMZL clones arise from naïve B cells, not post-germinal center B cells.
- pcMZL is classified as a lymphoproliferative disease rather than a true lymphoma.

## Abstract

Primary cutaneous B-cell lymphoma encompass clinically heterogeneous entities. While primary cutaneous diffuse large B-cell lymphoma, leg type (pcDLBCL-LT) is aggressive, primary cutaneous follicle centre lymphoma (pcFCL) and primary cutaneous marginal zone lymphoma (pcMZL) typically follow an indolent course. To clarify their pathophysiological basis, we perform single-cell RNA sequencing on pcFCL, pcMZL, and pcDLBCL-LT, alongside reactive B-cell rich lymphoid proliferations (rB-LP), gastric mucosa-associated lymphoid tissue (MALT) lymphoma, and systemic counterparts. Here we show that the indolent pcMZL, pcFCL, and rB-LP exhibit a persistent germinal centre reaction, not observed in pcDLBCL-LT or gastric MALT lymphoma. Further, pcMZL top expanded clones develop within lesions from naïve and not post-germinal centre B cells as currently presumed. Our data thus indicate that pcMZL and pcFCL, similar to rB-LP may be driven by (a yet unknown) antigen. While our data indicates that pcFCL exhibits some features of true lymphomas, it clearly supports the classification of pcMZL as a lymphoproliferative disease.

Primary cutaneous B-cell lymphoma encompass clinically heterogeneous entities, including indolent and aggressive subtypes. Here, the authors show that the two indolent subtypes exhibit a persistent germinal centre reaction and thus may be driven by (a yet unknown) antigen.