Abstract / Summary
Abstract Rosai-Dorfman disease (RDD) is a rare histiocytic disorder characterized by accumulation of large histiocytes in nodal and/or extranodal sites. The underlying biology of RDD and factors that distinguish it from the other histiocyte disorders are poorly understood. To better understand the disease biology, we employed whole transcriptome RNA sequencing to study the gene expression profiles of RDD as part of the Atlas of Blood Cancer Genomes (ABCG) initiative. Gene expression profiles of RDD (N=23) were then compared to two other histiocytoses (Langerhans cell histiocytosis (LCH, N=15) and Erdheim-Chester disease (ECD, N=4), which are most often considered in the clinicopathologic differential diagnosis of RDD. We found that gene expression levels by RNA sequencing correlated well with known immunohistochemistry results for diagnostic markers for all three diseases, highlighting the ability to use RNA-based approaches for diagnosis of these tumors. RDD samples showed enrichment of gene sets related to B cells and the IL27 pathway. In contrast, LCH showed enrichment of gene sets related to resting dendritic cells and the HNF3A pathway. We found significant differences in the composition of the microenvironment with an enrichment of memory B cells, plasma cells and CD8 T cells in the RDD microenvironment and enrichment of dendritic cells in the LCH microenvironment. In summary, our study demonstrates unique gene expression signatures in RDD that show overlap as well as distinctive patterns from LCH or ECD. These novel gene expression signatures encompass pathways that could potentially contribute to the pathogenesis and targeted treatment of this rare histiocytic entity.