Comprehensive Metagenomic Analysis of Blastic Plasmacytoid Dendritic Cell Neoplasm

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a hematologic malignancy thought to originate from plasmacytoid dendritic cells (pDCs), the immune cell responsible for producing type 1 interferons during infection. Nearly all patients with BPDCN have prominent skin involvement, with cutaneous tumors occupying the dermis. Half of patients present with BPDCN cells only in the skin, without evidence of disease elsewhere. As normal pDCs are rare or absent in cutaneous sites, and only traffic to skin after activation by pathogen or inflammation, we asked if a microorganism is associated with BPDCN. We performed RNA sequencing in BPDCN skin and bone marrow, with cutaneous T-cell lymphoma and normal skin as controls. We employed GATK-PathSeq to identify known microbial sequences. Bacterial reads in BPDCN skin were components of normal flora and did not distinguish BPDCN from controls. We then developed a new computational tool, virID, for identification of microbial-associated reads remaining unassigned after GATK-PathSeq. We found no evidence for a known or novel virus in BPDCN skin or bone marrow, despite confirming that virID could identify Merkel cell polyomavirus in Merkel cell carcinoma in a blinded fashion. Thus, at the level of sensitivity employed here, we find no clear pathogen linked to BPDCN.