TET2 mutations, myelodysplastic features, and a distinct immunoprofile characterize blastic plasmacytoid dendritic cell neoplasm in the bone marrow

Abstract

*Distinguishing blastic plasmacytoid dendritic cell neoplasm (BPDCN) from acute myeloid leukemia (AML) is gaining increased importance because of emerging differences in therapeutic approaches, and this distinction can be problematic in bone marrow specimens. We identified retrospectively 16 patients with bone marrow involvement by BPDCN: 11 men and 5 women with a median age of 62.5 years (range, 19-86 years). Myelodysplastic changes were observed in five patients. Immunophenotypic analysis showed that the neoplastic cells were positive for CD4, CD123, TCL-1, and HLA-DR and were negative for CD3, CD8, CD13, CD19, CD34, and myeloperoxidase. Other antigens expressed by subsets of BPDCN cases included the following: CD56 (13/15; 81%), CD33 (7/10; 70%), CD7 (11/14; 69%), TdT (5/15; 33%), CD2 (5/11; 31%), CD117 (2/ 9; 22%), and CD5 (2/13; 15%). Conventional cytogenetic analysis showed chromosomal abnormalities in 6 of 13 (46%) cases analyzed, of which 3 cases had 213/13q2. Targeted next-generation sequencing performed on five BPDCN cases identified TET2 (ten eleven translocation 2) mutations and no other AMLassociated mutations. In conclusion, BPDCN in the bone marrow has a characteristic immunoprofile (CD41, CD561, CD1231, and TCL-11) and appears to be commonly associated with myelodysplastic features and a high frequency of TET2 mutations in the absence of other mutations commonly observed in AML. Am.

Simultaneous deletion of 3′ETV6 and 5′EWSR1 genes in blastic plasmacytoid dendritic cell neoplasm: case report and literature review

“…Cell markers including CD2, CD4, CD5, CD7, CD13, CD14, CD15, CD19, CD22, CD33, CD34, CD36, CD38, CD45, CD56, CD64, CD117, CD123, HLA-DR (Becton-Dickinson Biosciences, San Jose, CA) were assessed by flow cytometry immunophenotyping [6, 10, 11]. No evidence of a CD123 positive, CD4 positive cell population was detected.…”

“…The BM sample was screened for somatic mutations using a clinically validated next-generation sequencing (NGS)-based 28-gene assay [6]. The genes in this panel included: ABL1 , ASXL1 , BRAF , DNMT3A , EGFR , EZH2 , FLT3 , GATA1 , GATA2 , HRAS , IDH1 , IDH2 , IKZF2 , JAK2 , KIT , KRAS , MDM2 , MLL , MPL , MYD88 , NOTCH1 , NPM1 , NRAS , PTPN11 , RUNX1 , TET2 , TP53 , and WT1 .…”

“…In Table 1, we have summarized a total of 46 BPDCN cases with abnormal karyotypes, 45 from previous literature reports [4, 6, 12–28] plus the case presented in this report. A minor modification has been made to some of the cases from previous literature reports in order to follow the ISCN 2013 nomenclature guidelines [8] as well as to integrate all findings derived by means other than conventional analysis (e.g., FISH and SKY) into the description of an abnormal karyotype.…”

“…A similar number of BPDCN cases with possible chromosomal abnormalities are not included in this table, mainly due to a lack of complete karyotype description in these literature [29–37]. In addition, our analysis has focused on cytogenetic alterations and does not include mutations in genes such as TET2 that have been shown to be present in a sizeable subset of BPDCN [6, 38]. The mutational landscape of BPDCN is beyond the scope of this review.…”

“…Based on literature reports of limited cases, over 50 % of BPDCN have chromosomal abnormalities, but no single chromosomal change has been shown to be diagnostic of this entity. The common chromosomal aberrations in BPDCN reported previously include abnormalities involving chromosomes 5q (72 %), 12p (64 %), 13q (64 %), 6q (50 %), 15q (43 %), and 9 (usually monosomy 9, 28 %) [4, 6]. Aberrations of 12p are among the most common findings in BPDCN.…”