Integrative diagnosis of primary cutaneous large B-cell lymphomas supports the relevance of cell of origin profiling

PLoS One. 2022 Apr 22;17(4):e0266978. doi: 10.1371/journal.pone.0266978. eCollection 2022.


Primary cutaneous large B-cell lymphomas (PCLBCL) represent a diagnostic challenge because they are classified as PCLBCL, leg type (PCLBCL, LT) or primary cutaneous follicle centre lymphoma, large cell (PCFCL, LC), which differ by prognosis and therapeutic requirement. Unclassified cases with discordant clinical presentations, morphologies, and immunophenotypes may be classified into the not otherwise specified (PCLBCL, NOS) category based on ancillary molecular analyses. Cell-of-origin profiling as germinal centre (GC) type or non-GC type by immunohistochemistry is not considered reproducible because of variable CD10 expression. In a series of 55 PCLBCL cases with > 80% large cells, we reported 21 PCFCL, LC cases as GC-type and 27 PCLBCL, LT as non-GC-type; 7 cases were considered PCLBCL, NOS. Here, we demonstrate the accuracy of molecular profiling of PCLBCL as GC or non-GC type using a reverse transcriptase multiplex ligation assay (RT-MLPA). RT-MLPA classified the seven PCLBCL, NOS cases in accordance with their mutational profile. An integrative principal component analysis confirmed the main criteria and the relevance of genomic profiling of PCFCL, LC as GC-derived, and PCLBCL, LT as non-GC-derived. Both the cell-of-origin classification of PCLBCL and the integrative analysis identified two clinically relevant subgroups according to overall survival, which may help to standardize PCLBCL diagnosis and patient management.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Germinal Center / metabolism
  • Humans
  • Immunohistochemistry
  • Lymphoma, Large B-Cell, Diffuse* / diagnosis
  • Lymphoma, Large B-Cell, Diffuse* / genetics
  • Lymphoma, Large B-Cell, Diffuse* / metabolism
  • Prognosis
  • Skin Neoplasms* / diagnosis
  • Skin Neoplasms* / genetics
  • Skin Neoplasms* / metabolism

Grants and funding

This work was supported by a PROTEOM grant from the Groupe Interrégional de Recherche Clinique et Innovation Cancéropôle Grand Sud-Ouest CHU de Bordeaux 2018/78 awarded to Audrey Gros, and a 2018 PROTEOM grant from the Société Française de Dermatologie awarded to Océane Ducharme. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.