Primary cutaneous B-cell lymphomas (CBCL) comprise a group of extranodal non-Hodgkin lymphomas that are primarily confined to the skin. Primary cutaneous marginal zone lymphoma (MZL) and follicle center lymphoma (FCL) are associated with a rather indolent tumor behavior, while diffuse large B-cell lymphoma, leg type (DLBCL-LT) shows an aggressive clinical course. Besides distinct clinical and immune-histological features, the underlying molecular tumor biology is still only insufficiently understood. Therefore, we performed single-cell RNA sequencing combined with B-cell receptor sequencing in different CBCL entities and B-cell pseudolymphoma. We observed the expansion of a single B-cell clone in CBCL only. So-called pseudolymphoma was identified to be polyclonal as expected. Expanded clones of MZL showed terminal differentiation along a physiological trajectory from unswitched towards switched immunoglobulin phenotypes that included large numbers of plasma cells. Overall transcriptomic profiles were indistinguishable from benign polyclonal B cells, in line with its indolent clinical course. FCL clones also exhibited a canonical B-cell marker profile, but only of proliferating and non-proliferating germinal center B cells. By contrast, DLBCL-LT cells uniquely exhibited multiple aberrant marker profiles including proliferative activity beyond conventional germinal center-like phenotypes, pursuant of aggressive clinical behavior. Moreover, the TME comprising polyclonal T- and B-cells decreased in number and diversity from MZL over FCL to DLBCL-LT as confirmed through multiplex in situ IF. Our data revealed that while FCL and DLBCL-LT show a transcriptionally distinct expanded clone, MZL tumor cells only differentiate along physiological B-cell trajectories, suggestive of a lymphoproliferative disorder rather than an overt lymphoma.

ESDR433 - Single-cell characterization of primary cutaneous B-cell lymphomas reveals distinct clonal properties of marginal zone, follicle center and leg-type lymphomas

The scientific meeting of the European Society for Dermatological Research (ESDR) is held yearly, usually in September. With an international attendance of more than 1000 skin scientists from around the globe, the four-day event includes short oral presentations from peer-reviewed abstracts, keynote lectures from international experts, sponsored symposia, satellite programs, educational events as well as an important focus on posters, networking and building collaborations amongst scientists. For more information about this year’s meeting visit our website.