they exhibit circulating malignant pDC, anemia, thrombocytopenia, and/or leukopenia due to extensive malignant pDC infiltrations in the bone marrow. A leukemic phase of the disease is a common feature of end stage and post-therapy relapsing BPDCN. Pathophysiology
There are three types of dendritic cells, plasmacytic dendritic cells (pDC) and two types of conventional dendritic 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 dendritic cells that further promote immune responses by, e.g. functioning as antigen-presenting cells. The malignant pDC in BPDCN have the appearance of immature plasmacytoid dendritic cells. They are distinguished from other dendritic, myeloid, lymphoid and NK cell types by exhibiting at least several of the following properties: 1) plasmacytoid morphology; 2) production of large amounts of type I interferons when properly stimulated; 3) ability to differentiate into conventional dendritic cells when properly stimulated; 4) the expression of key marker proteins such as granzyme B, TCF4,  interleukin-3 receptor (i.e.
However, this is partially explained by the fact that the indication itself, that is, complete DiGeorge syndrome, increases the risk of autoimmune disease. Thymoma-associated multiorgan autoimmunity (TAMA)
A GvHD-like disease called thymoma-associated multiorgan autoimmunity (TAMA) can occur in patients with thymoma. In these patients rather than a donor being a source of pathogenic T cells, the patients own malignant thymus produces self-directed T cells. This is because the malignant thymus is incapable of appropriately educating developing thymocytes to eliminate self-reactive T cells. The result is a disease virtually indistinguishable from GvHD. Mechanism
The pathophysiology of GvHD includes three phases:
The afferent phase: activation of APC (antigen presenting cells)
The efferent phase: activation, proliferation, differentiation and migration of effector cells
The effector phase: target tissue destructionActivation of APC occurs in the first stage of GvHD. Prior to haematopoietic stem cell transplantation, radiation or chemotherapy results in damage and activation of host tissues, especially intestinal mucosa. This allows the microbial products to enter and stimulate pro-inflammatory cytokines such as IL-1 and TNF-α. These proinflammatory cytokines increase the expression of MHC and adhesion molecules on APCs, thereby increasing the ability of APC to present antigen. The second phase is characterized by the activation of effector cells. Activation of donor T-cells further enhances the expression of MHC and adhesion molecules, chemokines and the expansion of CD8 + and CD4 + T-cells and guest B-cells. In the final phase, these effector cells migrate to target organs and mediate tissue damage, resulting in multiorgan failure.