br Discussion BPDCN is an

Discussion BPDCN is an aggressive, rare hematologic neoplasm that mainly affects elderly individuals 60 to 70 years of age, with a male predominance and a median survival of 12–16 months. Most patients present with multiple nonpruritic cutaneous lesions followed by involvement of the lymph nodes, bone marrow, and peripheral blood. The clinical appearances of skin lesions are variable. They have been described as papules, patches, plaques, or tumor nodules with erythematous to bruise-like discoloration. Julia et al reported that 74.2% of patients presented initially with one to two isolated cutaneous nodules only, but 35% of patients developed disseminated lesions as the disease progressed. Mucosal lesions have rarely been described. When the lymph node and bone marrow are involved, generalized lymphadenopathy, hepatosplenomegaly, and cytopenia occur. Two clinical patterns of the disease course exist. More than 90% of patients have an indolent onset dominated by skin lesions and followed by tumor dissemination. In fewer cases, the leukemic variant occurs as acute leukemia with systemic involvement from the beginning. Rare cases of BPDCN have been associated with another myeloid neoplasm, that might precede, occur with, or follow BPDCN. The reported incidence of this type of tumor is 6%. The etiology of BPDCN is unknown, but complex chromosomal aberrations often occur. The diagnosis of BPDCN is based on histopathological and immunohistochemical studies. Cutaneous BPDCN is characterized by diffuse dermal monotonous infiltrates of blast-like secreted frizzled related protein without epidermotropism or adnexal involvement. Angioinvasion and tumor necrosis are absent. The differential diagnosis includes AML, lymphoblastic lymphoma, and other small cell neoplasms. An immunohistochemical study is needed to establish the diagnosis. The essential immunophenotype for the diagnosis of BPDCN includes immunopositivity for CD4, CD56, CD123, and TCL-1, with negative granzyme B expression. Immunopositivity of CD123 indicates that the tumor cells are of plasmacytoid dendritic cell origin. However, mature plasmacytoid dendritic cell proliferation in myeloid neoplasms should be distinguished. Mature plasmacytoid dendritic cells express CD4, CD123, TCL1, and also granzyme B, but CD56 is negative. Reactive plasmacytoid dendritic cells can also be seen in Kikuchi’s lymphadenitis, Castleman disease, and lupus erythematosus, but they can be distinguished by CD56 negativity. Although BPDCN frequently expresses myeloid marker CD33, lysozyme and myeloperoxidase negativity and CD123 and TCL-1 positivity can differentiate this disease from AML or related diseases. In addition to BPDCN, cutaneous extranodal NK/T cell lymphoma and gamma/delta T-cell lymphoma also express CD56. The present case was misdiagnosed elsewhere as extranodal NK/T-cell lymphoma because CD4+/CD56+ expression was detected without an adequate panel of antibodies in the immunohistochemical study. The absence of angioinvasion and necrosis, negative cytotoxic protein, and the absence of Epstein–Barr virus by EBER in situ hybridization distinguish BPDCN from NK/T-cell lymphoma. Additionally, CD123 and TCL-1 positivity with the absence of cytotoxic proteins also distinguish BPDCN from CD56-positive gamma/delta T cell lymphoma. Patients with BPDCN have poor outcomes. Owing to its rarity and recent recognition as a distinct entity, no standardized therapeutic strategy exists for BPDCN. For patients with skin-limited disease, with poor performance status because of underlying comorbidities, and who are unable to tolerate systemic intensive chemotherapy, skin-directed therapies with focal radiation therapy, systemic glucocorticosteroids, or nonintensive chemotherapy regimens could be considered as initial therapy and may lead to complete resolution; however, nearly all patients relapse. Vassallo et al reported that an 83-year-old man diagnosed with cutaneous BPDCN with cervical lymphadenopathy and splenomegaly was treated palliatively with prednisolone (25 mg/d), and achieved complete remission 8 months later, but the disease quickly relapsed 1 month later after discontinuation of oral prednisolone. Regarding the induction regimen, retrospective studies have shown that treatment with regimens for more common hematological malignancies, such as non-Hodgkin lymphoma, acute lymphoblastic leukemia, and AML, yielded a complete remission rate of 80–90%, but responses were typically short-lived, and approximately 35% of patients relapsed within 8.6 months. Pagano et al suggested treatment with regimens used in acute lymphoblastic leukemia, and also with central nervous system prophylaxis, to obtain a better outcome. Allogeneic hematopoietic stem cell transplantation (HSCT) has been utilized as consolidative therapy in adult patients with BPDCN who achieved complete remission. Autologous HSCT may be reserved for patients who are not eligible for allogeneic procedures or if a suitable donor is not available. For older patients or those who are not eligible for HSCT, monochemotherapy, such as pralatrexate or etoposide, can be considered as palliative therapy. Promising data were recently reported using the immunotoxin SL-401 to target the interleukin (IL)-3 receptor α subunit (CD123). This treatment consists of a recombinant human IL-3α protein conjugated with truncated diphtheria α-toxin, a potent inhibitor of protein synthesis. The long-term prognosis for BPDCN patients is still poor because of the aggressive behavior of the disease, the advanced age of most patients, and an absence of an effective targeted therapy.