Blastic Plasmacytoid Dendritic Cell Neoplasm With De Novo TET2 and KDM6A Mutations

J Cutan Pathol. 2026 Apr;53(4):377-382. doi: 10.1111/cup.70050. Epub 2026 Jan 2.

Abstract

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare, highly aggressive hematologic malignancy characterized by cutaneous involvement with potential dissemination to peripheral blood, bone marrow, lymph nodes, or extranodal sites. We present the first documented case of BPDCN exhibiting complex epigenetic dysregulation in a 54-year-old female who developed rapidly progressive purpuric lesions on the trunk, diagnosed via skin biopsy and immunohistochemistry. Cytogenetic analysis revealed triple molecular aberrations including a t(1;6) (p31;q25) translocation, a TET2 frameshift deletion (44.1% VAF), and a KDM6A missense mutation (c.262G>A, 46.6% VAF). The patient died within 6 months post-diagnosis, suggesting that this aggressive clinical course may be associated with a novel clinicogenetic subtype of BPDCN.

Keywords: KDM6A mutation; TET2 mutation; aggressive malignancy; blastic plasmacytoid dendritic cell neoplasm; chromosomal translocation.

Publication types

  • Case Reports

MeSH terms

  • Blastic Plasmacytoid Dendritic Cell Neoplasm
  • DNA-Binding Proteins* / genetics
  • DNA-Binding Proteins* / metabolism
  • Dendritic Cells* / metabolism
  • Dendritic Cells* / pathology
  • Dioxygenases
  • Fatal Outcome
  • Female
  • Hematologic Neoplasms* / genetics
  • Hematologic Neoplasms* / pathology
  • Histone Demethylases* / genetics
  • Histone Demethylases* / metabolism
  • Humans
  • Middle Aged
  • Mutation
  • Mutation, Missense
  • Nuclear Proteins* / genetics
  • Nuclear Proteins* / metabolism
  • Proto-Oncogene Proteins* / genetics
  • Proto-Oncogene Proteins* / metabolism
  • Skin Neoplasms* / genetics
  • Skin Neoplasms* / pathology
  • Translocation, Genetic

Substances

  • TET2 protein, human
  • Dioxygenases
  • DNA-Binding Proteins
  • Proto-Oncogene Proteins
  • KDM6A protein, human
  • Histone Demethylases
  • Nuclear Proteins