Blastic plasmacytoid dendritic cell neoplasm with leukemic manifestation and ETV6 gene rearrangement: A case report

Abstract

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare malignant tumor of the hemopoietic system that arises from plasmacytoid dendritic cell precursors with a highly aggressive course. BPDCN frequently involves the skin, lymph nodes, peripheral blood and bone marrow. BPDCN is known to develop leukemic dissemination as a feature of myelomonocytic leukemia in the late phase of the disease, which leads to a poorer prognosis. In the present study, a case of BPDCN with leukemic manifestation without cutaneous involvement was reported. In addition, ETS variant gene 6 (ETV6) gene rearrangement was detected in the patient. The patient relapsed soon after complete remisson and had no response to further treatment. To the best of our knowledge, this is the first reported case of BPDCN with ETV6 rearrangement. Following chemotherapy treatment, the patient suffered from severe headache in the complete remission stage; however, brain CT scans showed no significant abnormalities. Several lumbar punctures and intrathecal chemotherapy were performed, and the patient recovered gradually. Therefore, the patient was considered to suffer from central nervous system leukemia. In conclusion, implementation of lumbar punctures and preventive intrathecal chemotherapy are required in BPDCN patients with leukemic manifestation during the remission stage.

E-Cadherin Expression in Blastic Plasmacytoid Dendritic Cell Neoplasms: An Unrecognized Finding and Potential Diagnostic Pitfall

“…BPCDN transformation following primary myelofibrosis is rare. [5][6][7][8][9] BPDCN is characterized by a diffuse monomorphic infiltrate of medium-sized blasts with scant cytoplasm, slightly irregular nuclei, and multiple small nucleoli which on morphology alone can be indistinguishable from other lymphoid and myeloid/monocytic proliferations. The diagnosis requires the expression of CD4 and/or CD56 together with one or more markers of plasmacytoid dendritic cell-associated antigen (CD123, TCL-1, CD303, CD2AP), in the absence of lineage-specific myeloid, monocytic, or lymphoid markers (lysozyme, myeloperoxidase, CD11c, CD34, CD163, CD3, CD20).…”

Blastic Plasmacytoid Dendritic Cell Neoplasm: From Origin of the Cell to Targeted Therapies

“…Gao et al [53] reported a case of BPDCN with an ETS variant 6 (ETV6) gene rearrangement shown by FISH. ETV6, which maps to 12p13, encodes an ETS family transcription factor, essential for the hematopoietic process.…”

Whole‐genome analysis uncovers recurrent IKZF1 inactivation and aberrant cell adhesion in blastic plasmacytoid dendritic cell neoplasm

“…Single nucleotide variants (SNVs) and indels presumed as pathogenic have been observed predominantly in genes involved in cell cycle control (eg, ATM , TP53 ), chromatin regulation (eg, ASXL1 , IDH2 , NPM1 , TET2 ), signal transduction (eg, KRAS , NRAS ), splicing (eg, ZRSR2 ) and transcriptional regulation (eg, IKZF1/2/3 , ZEB2 ) . Additionally, cytogenetic studies, most of them performed in the context of case reports, have revealed chromosomal rearrangements involving ALK , ETV6 , EWSR1 , KMT2A ( MLL ), MYB , MYC , and SUPT3H in a handful of cases …”

“…Recurrent copy number alterations (CNAs) in BPDCN include broad deletions within chromosomes 7,9,12,13, and 15, particularly the regions containing tumor suppressors CDKN2A/B, CDKN1B, and RB1. [3][4][5][6] Overexpressed genes with pathogenic relevance include BCL2 and CCND1.…”

“…[8][9][10][11] Additionally, cytogenetic studies, most of them performed in the context of case reports, have revealed chromosomal rearrangements involving ALK, ETV6, EWSR1, KMT2A (MLL), MYB, MYC, and SUPT3H in a handful of cases. [12][13][14][15][16][17][18] Even though these studies have uncovered a variety of genetic abnormalities in BPDCN, none of the reported alterations has provided a clear biological rationale behind neither the genesis of the disease nor its clinical behavior. Furthermore, as yet no study has characterized the landscape of genomic rearrangements and CNAs of BPDCN using high resolution NGS.…”