Classification and clinical behavior of blastic plasmacytoid dendritic cell neoplasms according to their maturation-associated immunophenotypic profile

Abstract

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare subtype of leukemia/lymphoma, whose diagnosis can be difficult to achieve due to its clinical and biological heterogeneity, as well as its overlapping features with other hematologic malignancies. In this study we investigated whether the association between the maturational stage of tumor cells and the clinico-biological and prognostic features of the disease, based on the analysis of 46 BPDCN cases classified into three maturation-associated subgroups on immunophenotypic grounds. Our results show that blasts from cases with an immature plasmacytoid dendritic cell (pDC) phenotype exhibit an uncommon CD56− phenotype, coexisting with CD34+ non-pDC tumor cells, typically in the absence of extramedullary (e.g. skin) disease at presentation. Conversely, patients with a more mature blast cell phenotype more frequently displayed skin/extramedullary involvement and spread into secondary lymphoid tissues. Despite the dismal outcome, acute lymphoblastic leukemia-type therapy (with central nervous system prophylaxis) and/or allogeneic stem cell transplantation appeared to be the only effective therapies. Overall, our findings indicate that the maturational profile of pDC blasts in BPDCN is highly heterogeneous and translates into a wide clinical spectrum -from acute leukemia to mature lymphoma-like behavior-, which may also lead to variable diagnosis and treatment.

Blastic plasmacytoid dendritic cell neoplasm with leukemic presentation: 10‐Color flow cytometry diagnosis and HyperCVAD therapy

“…The survival of this patient was not different from the others. In some patients, the blastic tumor cells showed aberrant expressions of other antigens not characteristically expressed by BPDCN (e.g., CD2, CD7, and CD79a) [1,2,6]. Similar to other groups, our study showed that BPDCN with leukemic presentation is an aggressive neoplasm despite mature blastic pDCs phenotype.…”

“…immature BPDCN (Group 1); showed CD34 expression in a fraction of pDCs blasts, and an uncommon CD56-phenotype coexisting with CD341 non-pDC tumor cells, with confinement to the bone marrow and some peripheral blood, but not extramedullary involvement. This group would be classified as AL of ambiguous or minimally differentiated myeloid lineage, by WHO 2008 criteria, due to a lack of clear differentiation markers for cell lineages other than pDC; b. intermediate BPDCN (Group 2); displayed partial positivity for CD117 in the absence of CD34 expression with extramedullary clinical features between that of the immature and mature groups of patients; and c. mature BPDCN (Group 3); demonstrated CD34-, CD117-, tumor pDC immunophenotype with frequent involvement of the skin or extramedullary sites and spread to lymphoid tissues [6]. Despite the clearly different clinical behaviors of BPDCN at presentation, no significant differences were observed in the outcomes between the three groups; median OS was only 11 months.…”

“…Diagnosis relies on strict immunophenotypic criteria by immunochemistry (IHC) and/or flow cytometry (FCM) [1][2][3][4][5][6]. The minimum requirement for diagnosis is a CD41, CD561, and CD1231 phenotype associated with negativity for lineage specific (Lin 2 ) markers; the diagnosis is further supported by expression of BDCA2/CD303 and other plasmacytoid dendritic cell-associated antigens (e.g., TCL1 and CD2AP).…”

Treatment of blastic plasmacytoid dendritic cell neoplasm

“…A statistically significant difference in OS was also observed, with median OS of 7.1 months in those treated with AML regimens vs 12.3 months in those treated with an ALL or lymphoma regimen. To complement these findings Martín-Martín et al 41 recently presented a study of 46 patients (9% children) treated with ALL, AML, or lymphoma regimens. CRs were obtained in the majority of patients (92%), despite the induction regimen, with a poor OS of 11 months; however, subanalysis demonstrated that patients treated with ALL-like regimens had better OS, confounded by the inclusion of children in this cohort, who can have prolonged survival to ALL regimens alone.…”

A Challenging Blastic Plasmacytoid Dendritic Cell Neoplasm Case: Tough Decisions to Make

“…There was a significant difference in the percentage of patients who achieved a CR (0.67 vs. 0.27 respectively, P = 0.02) and a higher median overall survival (12.3 months versus 7.1 months, P = 0.02) with an ALL based protocol [8]. A more recent retrospective study compared ALL versus AML versus lymphoma-type therapy and found that ALL-type therapy had the lowest rates of relapse and overall mortality [9]. However, these results may be potentially confounded by the inclusion of children in the cohort.…”