A very rare case of FLT3-D835 positive blastic plasmacytoid dendritic cell neoplasm

Vlad Andrei Cianga, Cătălin Doru Dănăilă, Ion Antohe, Raluca Oană, Mihaela Mențel, Iuliu Ivanov, Loredana Dragoș, Angela Smaranda Dăscălescu


Blastic plasmacytoid dendritic cell neoplasms (BPDCNs) are extremely rare and aggressive hematological malignancies that derive from precursors of plasmacytoid dendritic cells (pDC) and frequently involve skin lesions and bone marrow infiltration. They mostly affect the elderly population and the prognosis is poor with the therapeutic choices currently available. Diagnosis is made with the help of tools such as immunohistochemistry and flow cytometry. Here, we present a particular case of BPDCN with a positive FLT3-D835 mutation and we discuss the possible impact this may have on the evolution of the disease and response to treatment.


blastic plasmacytoid dendritic cell neoplasm; aggressive hematopoietic neoplasm; acute leukemia; flow cytometry; FLT3-D835

Full Text:



Faccheti F, Petrella T, Pileri SA, Blastic Plasmacytoid dendritic cell neoplasm. In: Swerdlow SH (Ed.) WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues (Revised 4th edition). IARC: Lyon 2017; 9:174-177.

O’Keeffe M, Mok WH, Radford KJ. Human dendritic cell subsets and function in health and disease. Cell Mol Life Sci 2015; 72(22):1–17. doi: 10.1007/s00018-015-2005-0.

Hermans IF, Silk JD, Gileadi U, et al. NKT cells enhance CD4+ and CD8+ T cell responses to soluble antigen in vivo through direct interaction with dendritic cells. J Immunol 2003; 171(10):5140–5147. doi: 10.4049/jimmunol.171.10.5140.

Reizis B, Bunin A, Ghosh HS, Lewis KL, Sisirak V. Plasmacytoid dendritic cells: recent progress and open questions. Annu Rev Immunol 2011; 29:163–183. doi: 10.1146/annurev-immunol-031210-101345.

Venugopal S, Zhou S, El Jamal SM, Lane AA, Mascarenhas J. Blastic Plasmacytoid Dendritic Cell Neoplasm-Current Insights. Clin Lymphoma Myeloma Leuk 2019; 19(9):545-554. doi:10.1016/j.clml.2019.06.002.

Guru Murthy GS, Pemmaraju N, Atallah E. Epidemiology and survival of blastic plasmacytoid dendritic cell neoplasm. Leuk. Res 2018; 73:21-23.

Julia F, Dalle S, Duru G, et al. Blastic plasmacytoid dendritic cell neoplasms: clinico-immunohistochemical correlations in a series of 91 patients. Am J Surg Pathol 2014; 38(5):673-680.

Kameoka J, Ichinohasama R, Tanaka M, et al. A cutaneous agranular CD2- CD4+ CD56+ ‘lymphoma’: Report of two cases and review of the literature. Am J Clin Pathol 1998; 110(4):478–488.

Khoury JD, Medeiros LJ, Manning JT, Sulak LE, Bueso-Ramos C, Jones D. CD56(+) TdT(+) blastic natural killer cell tumor of the skin: a primitive systemic malignancy related to myelomonocytic leukemia. Cancer 2002; 94(9):2401–2408.

Petrella T, Comeau MR, Maynadié M, et al. Agranular CD4+ CD56+ hematodermic neoplasm' (blastic NK-cell lymphoma) originates from a population of CD56+ precursor cells related to plasmacytoid monocytes. Am J Surg Pathol 2002; 26(7):852-862. doi:10.1097/00000478-200207000-00003.

Chaperot L, Bendriss N, Manches O, et al. Identification of a leukemic counterpart of the plasmacytoid dendritic cells. Blood 2001; 97(10):3210-3217.

Jacob MC, Chaperot L, Mossuz P, et al. CD4+ CD56+ lineage negative malignancies: a new entity developed from malignant early plasma- cytoid dendritic cells. Haematologica 2003; 88(8):941-955.

Vardiman JW, Thiele J, Arber DA, et al. The 2008 revision of the World Health Organization (WHO) classification of myeloid neoplasms and acute leukemia: rationale and important changes. Blood 2009; 114(5):937–951. doi: https://doi.org/10.1182/blood-2009-03-209262.

Arber DA, Orazi A, Hasserjian R, et al. The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia. Blood 2016; 127(20):2391–2405.

Lim MS, Lemmert K, Enjeti A. Blastic plasmacytoid dendritic cell neoplasm (BPDCN): a rare entity. BMJ Case Rep 2016; Published 2016 Jan 20. doi:10.1136/bcr-2015-214093

Herling M, Jones D. CD4+/CD56+ hematodermic tumor: the features of an evolving entity and its relationship to dendritic cells. Am J Clin Pathol 2007; 127(5):687-700. doi:10.1309/FY6PK436NBK0RYD4.

Leroux D, Mugneret F, Callanan M, et al. CD4(+), CD56(+)DC2 acute leukemia is characterized by recurrent clonal chromosomal changes affecting 6 major targets: a study of 21 cases by the Groupe Français de Cytogénétique Heνmatologique. Blood 2002; 99(11):4154–4159.

Magro CM, Porcu P, Schaefer J, et al. Cutaneous CD4+ CD56+ hematologic malignancies. J Am Acad Dermatol 2010; 63(2):292-308. doi:10.1016/j.jaad.2009.08.044.

Garnache-Ottou F, Feuillard J, Ferrand C, et al. Extended diagnostic criteria for plasmacytoid dendritic cell leukaemia. Br J Haematol 2009; 145(5):624-636. doi:10.1111/j.1365-2141.2009.07679.x.

Petrovici K, Graf M, Hecht K, Reif S, Pfister K, Schmetzer H. Use of NG2 (7.1) in AML as a tumor marker and its association with a poor prognosis. Cancer Genomics Proteomics 2010; 7(4):173-180.

Prieto C, López-Millán B, Roca-Ho H, et al. NG2 antigen is involved in leukemia invasiveness and central nervous system infiltration in MLL-rearranged infant B-ALL [published correction appears in Leukemia. 2018 Oct; 32(10): 2306]. Leukemia 2018; 32(3):633-644. doi:10.1038/leu.2017.294.

Jardin F, Callanan M, Penther D, et al. Recurrent genomic aberrations combined with deletions of various tumour suppressor genes may deregulate the G1/S transition in CD4+CD56+ haematodermic neoplasms and contribute to the aggressiveness of the disease. Leukemia 2009; 23(4):698-707.

Sakamoto K, Katayama R, Asaka R, et al. Recurrent 8q24 rearrangement in blastic plasmacytoid dendritic cell neoplasm: association with immunoblastoid cytomor- phology, MYC expression, and drug response. Leukemia 2018; 32(12):2590-2603.

Chang TC, Yu D, Lee YS, et al. Widespread microRNA repression by Myc contributes to tumorigenesis. Nat Genet 2008; 40(1):43-50.

Sapienza MR, Fuligni F, Agostinelli C, et al. Molecular profiling of blastic plasmacytoid dendritic cell neoplasm reveals a unique pattern and suggests selective sensitivity to NF-kB pathway inhibition. Leukemia 2014; 28(8):1606–1616.

Menezes J, Acquadro F, Wiseman M, et al. Exome sequencing reveals novel and recurrent mutations with clinical impact in blastic plasmacytoid dendritic cell neoplasm. Leukemia 2014; 28(4):823–829.

Sheikhha MH, Awan A, Tobal K, Liu Yin JA. Prognostic significance of FLT3 ITD and D835 mutations in AML patients. Hematol J 2003; 4(1):41-46. doi:10.1038/sj.thj.6200224.

Dohner H, Estey EH, Amadori S, et al. Diagnosis and management of acute myeloid leukemia in adults: recommendations from an international expert panel, on behalf of the European Leukemia Net. Blood 2010; 115(3):453‐474.

Bacher U, Haferlach C, Kern W, Haferlach T, Schnittger S. Prognostic relevance of FLT3-TKD mutations in AML: the combination matters--an analysis of 3082 patients. Blood 2008; 111(5):2527-2537. doi:10.1182/blood-2007-05-091215.

Sullivan JM, Rizzieri DA. Treatment of blastic plasmacytoid dendritic cell neoplasm. Hematology Am Soc Hematol Educ Program 2016; 2016(1):16-23. doi:10.1182/asheducation-2016.1.16.

Dalle S, Beylot-Barry M, Bagot M, et al. Blastic plasmacytoid dendritic cell neoplasm: is transplantation the treatment of choice? Br J Dermatol 2010; 162(1):74–79.

DOI: http://dx.doi.org/10.22551/2020.29.0704.10174

Copyright (c) 2021 Vlad Andrei Cianga, Cătălin Doru Dănăilă, Ion Antohe, Raluca Oană, Mihaela Mențel, Iuliu Ivanov, Loredana Dragoș, Angela Smaranda Dăscălescu

Creative Commons License
Archive of Clinical Cases is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.


ISSN: 2360-6975