RESUMO
Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare hematological malignancy characterized by recurrent skin nodules, an aggressive clinical course with rapid involvement of hematological organs, and a poor prognosis with poor overall survival. BPDCN is derived from plasmacytoid dendritic cells (pDCs) and its pathogenesis is unclear. The tumor cells show aberrant expression of CD4, CD56, interleukin-3 receptor alpha chain (CD123), blood dendritic cell antigen 2 (BDCA 2/CD303), blood dendritic cell antigen 4 (BDCA4) and transcription factor (E protein) E2-2 (TCF4). The best treatment drugs are based on experience by adopting those used for either leukemia or lymphoma. Relapse with drug resistance generally occurs quickly. Stem cell transplantation after the first complete remission is recommended and tagraxofusp is the first targeted therapy. In this review, we summarize the differentiation of BPDCN from its cell origin, its connection with normal pDCs, clinical characteristics, genetic mutations and advances in treatment of BPDCN. This review provides insights into the mechanisms of and new therapeutic approaches for BPDCN.
Assuntos
Células Dendríticas/patologia , Neoplasias Hematológicas/genética , Neoplasias Cutâneas/genética , Doença Aguda/epidemiologia , Antígenos de Superfície/genética , Antígenos CD4/genética , Antígeno CD56/genética , Diferenciação Celular/genética , Células Dendríticas/metabolismo , Progressão da Doença , Neoplasias Hematológicas/patologia , Humanos , Subunidade alfa de Receptor de Interleucina-3/genética , Lectinas Tipo C/genética , Glicoproteínas de Membrana/genética , Receptores Imunológicos/genética , Neoplasias Cutâneas/diagnóstico , Neoplasias Cutâneas/patologia , Neoplasias Cutâneas/terapia , Fator de Transcrição 4/genéticaRESUMO
Despite advances in treatment and surveillance, melanoma continues to claim approximately 9,000 lives in the US annually (SEER 2013). The National Comprehensive Cancer Network currently recommends ipilumumab, vemurafenib, dabrafenib, and high-dose IL-2 as first line agents for Stage IV melanoma. Little data exists to guide management of cutaneous and subcutaneous metastases despite the fact that they are relatively common. Existing options include intralesional Bacillus Calmette-Guérin, isolated limb perfusion/infusion, interferon-α, topical imiquimod, cryotherapy, radiation therapy, interferon therapy, and intratumoral interleukin-2 injections. Newly emerging treatments include the anti-programmed cell death 1 receptor agents (nivolumab and pembrolizumab), anti-programmed death-ligand 1 agents, and oncolytic vaccines (talimogene laherparepevec). Available treatments for select sites include adoptive T cell therapies and dendritic cell vaccines. In addition to reviewing the above agents and their mechanisms of action, this review will also focus on combination therapy as these strategies have shown promising results in clinical trials for metastatic melanoma treatment.