LAUSR

A 63-year old man presented in May 2019; for 3 weeks, he complained of a slowly enlarging asymptomatic lesion on his left chest. On examination, he was found to have a single 12 9 8 cm large bruise-like, slightly infiltrated macule/ plaque on his left chest (Fig. 1a). Physical examination did not reveal any other, particularly enlarged lymph nodes or splenomegaly. He was otherwise healthy, and denied taking any drug; he did not report night sweating, fever or weight loss. Laboratory tests disclosed only a slight leukocytosis (9.59 9 10^9/L) with lymphocytosis (3.68 9 10^9/ L). A skin biopsy showed a diffuse non-epidermotropic lymphoid infiltrate in the superficial and deep dermis with involvement of the subcutaneous fat, separated from the epidermis by a clear-cut grenz zone. The infiltrate was composed of medium-sized pleomorphic atypical cells with also medium-sized blasts with prominent nucleoli. Immunophenotype results were positive for CD4, CD56, CD68, CD123 and negative for CD3, CD5, CD8, CD20, MPO and EBER-1 (Fig. 2). A diagnosis of blastic plasmacytoid dendritic cell neoplasm (BPDCN) was made, and multidisciplinary discussion with the haemato-oncologist occurred. Total body computed tomography (CT) scan and positron emission tomography (PET) revealed only a paratracheal lesion consistent with BPNCD. Bone marrow examination revealed a neoplastic infiltrate of 70% consistent with BPDCN. Three cycles of tagraxofusp (dose: 12 μg/kg body weight) every 21 days were administrated. After the first cycle, a complete resolution of the skin lesion was achieved (Fig. 1b); he developed a grade III capillary leak syndrome that resolved over seven days after treatment with systemic steroids, furosemide and high doses albumin. Bone marrow biopsy, CT and PET scan performed after the third cycle confirmed complete remission. The patient went on for an haploidentical haematopoietic stem cell transplantation (HSCT) after a myeloablative conditioning regimen (busulfan, thiotepa, fludarabine). As graftversus-host prophylaxis, the patient received high doses of cyclophosphamide, ciclosporin and mycophenolate mofetile. Transplantation was substantially uneventful. At 9month post-transplant follow-up, the patient is in remission without graft-versus-host disease. BPDCN is a rare haematological aggressive neoplasm presenting with violaceous or erythematous haemorrhagic infiltrated macules, plaques or tumours, frequently concomitant involvement of bone marrow, lymph nodes and a poor prognosis due to limited response to conventional chemotherapy followed by allogeneic HSCT. Difficulties in treating BPDCN are enhanced by its rarity and recognition in already advanced stages with diffuse disease at diagnosis. Plasmacytoid dendritic cells are the precursors of the neoplastic cells that usually express CD4, CD56 and CD123. In 2018, the FDA approved as first treatment for BPDCN tagraxofusp (anti-CD123 fusion protein), as a bridge to HSCT. (10 allogeneic SCTs, 3 autologous SCTs, with an overall survival of 59% at 18 months and 52% at 24 months). Haploidentical allogeneic HSCT has been reported in only few cases.