There are three types of<unk>  cells, plasmacytic<unk>  cells (pDC) and two types of conventional<unk>  cells (cDC), myeloid cDC1 and myeloid cDC2. pDC circulate in the blood, representing <0.4% of all nucleated blood cells, and are present in various hematological tissues such as lymph nodes and spleen. Their major function is to detect and then initiate immune responses to intracellular pathogens, particularly viruses such as the cold sore-causing Herpes simplex viruses, HIV, and hepatitis viruses but also bacteria such as the tuberculosis-causing Mycobacterium tuberculosis, fungi such as the aspergillosis-causing Aspergillus fumigatus and parasites such as malaria-causing Plasmodium falciparum. Following detection of these intracellular pathogens, pCD initiate immune responses by producing massive amounts of type I and type III interferons as well as by differentiating (i.e. maturing) into conventional<unk>  cells that further promote immune responses by, e.g. functioning as antigen-presenting cells. The malignant pDC in BPDCN have the appearance of immature<unk><unk>  cells. They are distinguished from other<unk> , myeloid, lymphoid and NK cell types by exhibiting at least several of the following properties: 1)<unk>  morphology; 2) production of large amounts of type I interferons when properly stimulated; 3) ability to differentiate into conventional<unk>  cells when properly stimulated; 4) the expression of key marker proteins such as granzyme B, TCF4, interleukin-3 receptor (i.e. CD123), CLEC4C, and Neuropilin, and 5) failure to express certain marker proteins that are commonly expressed by myeloid, lymphoid, and NK cell lineages.<unk>  typically arises after the serial acquisition of multiple genetic abnormalities in pDC or their precursor cells. Inactivating mutations (i.e. mutations which cause the gene to make no or a less active product) in the TET2 gene are the most common genetic abnormality in the disease, occurring in 32-67% of all BPDCN cases and often accompanied by mutations in either the NPM1 or SRSF2 gene. Numerous other genetic abnormalities are associated with the disease: 1) mutations in NRAS, ASXL1, and TP53; 2) deletions of the CDKN2A-ARF-CDKN2B locus on the short arm of chromosome 9, CDKN1B locus on the short arm of chromosome 12, RB1 locus on the long arm of chromosome 13, or NRC1 locus on the long arm of chromosome 5; 3) fusions of KMT2A on the long arm of chromosome 11 with MLLT1 on the short arm of chromosome 10, SUPT3H on the short arm of chromosome with MYC on the long arm of chromosome 8, or KMT2A on the long arm of chromosome 11 with MLLT1 on the long arm of chromosome 19; and 4) duplication or loss of entire chromosomes, particularly chromosomes 9, 13, or 15. Laboratory studies indicate that malignant pDC have a pathologically overactive NF-κB pathway that promotes their survival and production of various cytokines) that stimulate their own proliferation. Presumably, these genetic abnormalities lead to the activation of the NF-κB pathway and/or other cellular activation pathways which promote the survival, proliferation, and/or other malignant phenotypic traits in pDC and thereby cause BPDCN.
Blastic plasmacytoid dendritic cell neoplasm
Congenital self-healing reticulohistiocytosis
Nodal marginal zone B cell lymphoma
Angioimmunoblastic T-cell lymphoma
Mature T-cell lymphoma
Peripheral T-cell lymphoma
Precursor T-lymphoblastic lymphoma
Pleomorphic T-cell lymphoma