Blastic plasmacytoid dendritic cell neoplasm

Clinical features

• Skin involvement in ~90% at presentation — frequently the first manifestation that prompts a haematology referral.
• Characteristic bruise-like (purpuric / violaceous), red-brown patches, plaques or nodules; occasionally ulcerated.
• Truncal and head/neck predilection; lower limbs less common.
• Bone marrow involvement (~75–90% at presentation): cytopenias.
• Lymph node and splenic involvement common.
• Leukaemic blood involvement frequent.
• CNS involvement at presentation in ~10%; develops in ~25% during the disease course.
• Median age 60–70; M:F ~3:1.
• Differential: leukaemia cutis (AML, CLL); cutaneous lymphoma (PCDLBCL-LT, PCBCL, MF tumour stage); cutaneous metastasis; vasculitis; Kaposi sarcoma.

Histology & immunophenotype

• Dense, monomorphic dermal infiltrate of medium-sized blasts with fine "blastic" chromatin and indistinct nucleoli.
• Sparing of the epidermis (Grenz zone).
• Angiocentric / angiodestructive growth common.
• Diagnostic immunophenotype:
  • CD4+, CD56+ — the original diagnostic doublet.
  • CD123+ (IL-3Rα) — strong, the therapeutic target for tagraxofusp.
  • TCL1+, BDCA-2 (CD303)+, BDCA-4+, TCF4+ — plasmacytoid dendritic cell markers; specific.
  • HLA-DR+
  • TdT positive in ~30–50% (do not mistake for B-/T-lymphoblastic leukaemia); CD68 often shows a characteristic punctate cytoplasmic dot pattern.
  • Negative for lineage-defining markers — CD3, CD20, CD19, CD79a, MPO, lysozyme, CD117 — distinguishing from AML and B-/T-cell lymphomas.
  • EBV negative.
• Cytogenetics — complex karyotype with multiple deletions; recurrent NPM1, TET2, ASXL1, IKZF1 mutations.

Staging

• FBC, peripheral blood film and flow cytometry.
• Bone marrow aspirate and trephine.
• CT chest/abdomen/pelvis ± PET-CT.
• Lumbar puncture for CSF cytology and flow cytometry.
• HLA typing and donor work-up if allogeneic transplantation contemplated.
• Refer urgently to a specialist haematology service.

Management

• Multidisciplinary management through a specialist leukaemia / lymphoma service.
• First-line — tagraxofusp (Elzonris):
  • CD123-directed cytotoxin (anti-CD123 + diphtheria toxin) for first-line treatment of adults.
  • The NICE appraisal (TA782) was terminated — not NICE-recommended. Any UK use should be confirmed through the local specialist haematology service and current local / specialist funding, IFR, clinical-trial or compassionate-use route before initiating.
  • Response rate ~90%; complete response ~57% in first-line.
  • Toxicities: capillary leak syndrome (potentially severe), hepatic transaminitis, thrombocytopenia.
  • Used as a bridge to allogeneic transplantation in fit patients.
• Intensive chemotherapy regimens (HyperCVAD, ALL-style, AML-style) — historical first-line; now reserved for patients ineligible for tagraxofusp.
• Allogeneic haematopoietic stem-cell transplantation in first remission — the only curative modality; substantially improves long-term survival.
• CNS prophylaxis (intrathecal methotrexate / cytarabine) given high CNS relapse risk.
• Relapsed / refractory disease — clinical trials (CD123 CAR-T cells, BCL2 inhibitor venetoclax, BET inhibitors).

Prognosis

Historically grim — median overall survival 12–14 months without targeted therapy or transplantation. With tagraxofusp followed by allogeneic transplantation in remission, 2-year overall survival approaches 50% in fit younger patients. CNS relapse remains a major cause of treatment failure. Long-term surveillance (clinical, marrow, imaging, CSF) is essential.