Blastic plasmacytoid dendritic cell neoplasm (BPDCN) in leukaemic phase without skin lesions: a diagnostic and management challenge

Pathology ◽  
2019 ◽  
Vol 51 (4) ◽  
pp. 439-441 ◽  
Author(s):  
Nicholas Murphy ◽  
Daniel Owens ◽  
Emily Hinds ◽  
Niles Nelson
2020 ◽  
Vol 7 (4) ◽  
pp. 57-62
Author(s):  
Vlad Andrei Cianga ◽  
Cătălin Doru Dănăilă ◽  
Ion Antohe

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 immuno-histochemistry 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.


2018 ◽  
Vol 35 (2) ◽  
pp. e132-e135 ◽  
Author(s):  
Sean Dreyer ◽  
Suzanne Mednik ◽  
Allison Truong ◽  
Scott Worswick ◽  
Philip Scumpia ◽  
...  

2018 ◽  
Vol 93 (5) ◽  
pp. 487-491
Author(s):  
Hyun Ju Choi ◽  
Jongha Park ◽  
Jin Lee ◽  
Mi Young Kim ◽  
Heui Jeong Jeong ◽  
...  

2021 ◽  
Vol 20 (3) ◽  
pp. 60-67
Author(s):  
I. A. Demina ◽  
S. A. Kashpor ◽  
O. I. Illarionova ◽  
M. E. Dubrovina ◽  
A. A. Dudorova ◽  
...  

The diagnosis of rare hematological disorders requires a comprehensive clinical and laboratory investigation with careful interpretation of all test results. Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is one of such rare entities. We have performed a retrospective analysis of the results of immunophenotyping, cytomorphology and cytogenetics of bone marrow tumor cells from 5 patients with BPDCN aged from 8 to 51 years. The study was approved by the Independent Ethics Committee of the Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology. No specific characteristics of blasts were found. No correlation with the treatment and outcomes was noted as well: 3 patients died of progression or relapse (2 and 1, respectively). Bone marrow immunophenotyping is probably the most valuable laboratory test which allows physicians to establish the proper diagnosis in the absence of skin lesions. Flow cytometry immunophenotyping is the only technique used to determine the antigen profile that enables us to distinguish normal plasmacytoid dendritic cells from tumor ones by the presence (or absence) of the expression of CD2, CD7, CD38, CD56, CD303 etc. In the present paper, we provide a detailed description of five cases of BPDCN and main methods for flow cytometry data analysis. The parents of the patients agreed to use the information, including photos of children, in scientific research and publications.


Hematology ◽  
2016 ◽  
Vol 2016 (1) ◽  
pp. 16-23 ◽  
Author(s):  
Jill M. Sullivan ◽  
David A. Rizzieri

Abstract Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare myeloid malignancy with no defined standard of care. BPDCN presents most commonly with skin lesions with or without extramedullary organ involvement before leukemic dissemination. As a result of its clinical ambiguity, differentiating BPDCN from benign skin lesions or those of acute myeloid leukemia with leukemia cutis is challenging. BPDCN is most easily defined by the phenotype CD4+CD56+CD123+lineage–MPO–, although many patients will present with variable expression of CD4, CD56, or alternate plasmacytoid markers, which compounds the difficulty in differentiating BPDCN from other myeloid or lymphoid malignancies. Chromosomal aberrations are frequent, and the mutational landscape of BPDCN is being rapidly characterized although no obvious molecular target for chemoimmunotherapy has been identified. Chemotherapy regimens developed for acute myeloid leukemia, acute lymphoid leukemia, and myelodysplastic syndrome have all been used to treat BPDCN. Relapse is frequent, and overall survival is quite poor. Allogeneic transplantation offers a chance at prolonged remission and possible cure for those who are eligible; unfortunately, relapse remains high ranging from 30% to 40%. Novel therapies such as SL-401, a diphtheria toxin conjugated to interleukin-3 (IL-3) is commonly overexpressed in BPDCN and other aggressive myeloid malignancies and has shown considerable promise in ongoing clinical trials. Future work with SL-401 will define its place in treating relapsed or refractory disease as well as its role as a first-line therapy or bridge to transplantation.


2016 ◽  
Vol 23 (7) ◽  
pp. 552-556 ◽  
Author(s):  
Varinder Kaur ◽  
Arjun Swami ◽  
Atrash Shebli ◽  
Sara Shalin ◽  
Muthu Veeraputhiran ◽  
...  

Blastic plasmacytoid dendritic cell neoplasm is rare myeloid malignancy clinically characterized by non-pruritic, violaceous and papulo-nodular skin lesions, together with bone marrow and lymph node involvement. Histologically, there is infiltration of dermis by neoplastic mono-nuclear CD4, CD56, CD123 co-expressing cells with epidermal sparing. Most commonly blastic plasmacytoid dendritic cell neoplasm presents as a de-novo condition, and treatment-related blastic plasmacytoid dendritic cell neoplasm is a rare phenomenon. Due to rarity of the disease, there is no established standard of care treatment. Both acute myeloid leukemia and acute lymphoid leukemia type induction regimens have been used for treatment of blastic plasmacytoid dendritic cell neoplasm, with initial response rate of 50%–80%. We present a rare case of therapy-associated blastic plasmacytoid dendritic cell neoplasm in a patient with remote history alkylating agent systemic therapy. A lag period of five to seven years and presence of deletion 7q.31 seen in bone marrow biopsy specimen in our patient are consistent with a likely therapy-associated etiology of his blastic plasmacytoid dendritic cell neoplasm.


2013 ◽  
Vol 164 (6) ◽  
pp. 758-758 ◽  
Author(s):  
Ivan Dlouhy ◽  
Rodrigo Santacruz ◽  
Oscar Peña

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 4703-4703
Author(s):  
Paola Carluccio ◽  
Mario Delia ◽  
Anna Mestice ◽  
Domenico Pastore ◽  
Alessandra Ricco ◽  
...  

Abstract Abstract 4703 The World Health Organization (WHO) recently published a revised, updated edition of the WHO Classification of Tumours of the Haematopoietic and Lymphoid Tissues, including new criteria for the recognition of some previously described neoplasms as well as clarification and refinement of the defining criteria for others. It also adds entities – some defined mainly by genetic and immunophenotypic features – that have only recently been characterized. Particularly, the diagnosis and classification of acute leukemias of ambiguous lineage is debated; among these: “blastic NK-cell lymphoma” and “agranular CD4+/CD56+ hematodermic neoplasms”. Both of them are now known to be, in virtually all cases, a tumor derived from precursors of a specialized subset of dendritic cells, plasmacytoid dendritic cells, and so are myeloid-related neoplasms defined as blastic plasmacytoid dendritic cell neoplasm (BPDCN). This is a clinically aggressive neoplasm that is usually characterized at onset by solitary or multiple skin lesions, often with associated regional lymphadenopathy, and frequently by involvement of the PB and BM. Leukemic cells show submembranous cytoplasmic vacuoles and pseudopodia-like extensions of agranular cytoplasm. The blasts in such cases do not express myeloperoxidase or nonspecific esterase, and are characterized by the expression of CD4, CD43, CD56, CD123, BDCA-2/CD303, TCL1, and CLA; CD7 and CD33 are not uncommonly expressed as well, and TdT is expressed in about 30% of cases. There is no expression of CD34 or CD117. Here we report three cases with clinical data, cytological and immunophenotypic findings strongly suggesting the diagnosis of BPDCN. Case 1 An 80 year-old-man was admitted to our institution on December 2006. He referred the occurrence of skin lesions since January 2005, when a diagnosis of extranodal B-cell non-Hodgkin lymphoma was made and treatment with conventional chemotherapy was performed, but without achieving any response. At our evaluation he presented leukocytosis (144 × 109/L) associated with purplish, firm nodules on the trunk, arms and face. Peripheral blood and bone marrow aspirate showed the presence of blast cells with a lymphoid appearance, granular periodic acid-Schiff (PAS) positivity and a high expression of CD33, CD4, and CD56. He was treated with AML-like therapy, but died of disease progression. Case 2 A 79-year old woman was admitted in December 2006 with a 2-month history of anemia, splenomegaly, and weight loss of 10 kg in the last year. Laboratory tests were as follows: Hb, 41 g/L; leukocytes, 2.5 × 109/L (with 10% of blast cells); platelets, 43 × 109/L. No lymphadenopathy or skin lesions were present. Bone marrow examination revealed 41% of small to medium-sized blast cells without Auer rods or granula and negative reactivity to myeloperoxidase, esterase and PAS. She was treated with an AML-like protocol; she achieved partial response, but died after three months, of disease progression. Case 3 A 69-year-old man was admitted to our Institution for cytopenia in June 2009. He referred the occurrence of brownish-purple firm nodules on the trunk since April 2009. At our evaluation he presented pancytopenia; bone marrow aspiration was performed and revealed infiltration by 65% of blasts with reticulated chromatin, evident nucleoli, a vacuolated cytoplasm and pseudopodia-like expansions. The blasts were negative for myeloperoxidase, monocyte esterase and PAS staining. Skin biopsy revealed a dermal infiltration by the same blastic-cell BM population. He underwent AML-like therapy and, although the skin lesions disappeared, 30% blastic bone marrow infiltration persisted. Morphological revision of these cases, selected for their peculiar immunophenotype reported in the following Table, revealed the same cytological features and cytochemical reactivity in cases 2 and 3; case 1 had a lymphoblastic-like morphology and showed PAS positivity, but the lack of cCD3 was not consistent with the diagnosis of ALL. All the cases were FLT3-ITD+. We suggest that a correct modern panel of MoAb with a careful morphological examination could help to pose the diagnosis of BPDCN, which typically affects older patients and is characterized by poor prognosis. Disclosures: No relevant conflicts of interest to declare.


Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 3899-3899
Author(s):  
Hannah Beird ◽  
Maliha Khan ◽  
Feng Wang ◽  
Mansour Alfayez ◽  
Tianyu Cai ◽  
...  

Abstract Background: Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare hematologic neoplasm involving skin lesions and disseminated disease into bone marrow, peripheral blood, and lymph nodes, characterized by poor clinical outcomes and no standard therapeutic approaches. BPDCN is characterized by the malignant proliferation of precursor plasmacytoid dendritic cells (pDCs). It is now classified by WHO 2016 as a separate entity under myeloid malignancies owing to its unique clinico-pathologic nature, greater understanding of its distinct clinical course, but with some noted clinical, morphologic, and molecular similarities to AML and myelodysplastic syndrome (MDS). One of the most common molecular mutations observed by next-generation sequencing in the vast majority of patients with BPDCN has been the presence of TET2 mutations and variants. Notably, somatic missense and truncating mutations in TET2 have been reported in patients with both BPDCN and AML, yet their differential responses to similar therapeutic regimens in clinical trial testing indicates that there are likely key underlying etiologies that are yet to be determined. Aims: We sought to investigate and identify critical differences between patients with BPDCN and AML at the molecular level, utilizing a series of advanced analyses including transcriptome microarray, serum multiplex immunoassays and cytokine analysis. Methods: In order to discern these differences, we profiled bone marrow, peripheral blood and serum samples from primary patients samples with BPDCN (N = 16) and TET2-mutated AML (AMLTET2m) (N = 9) using 3 different assays. We first ascertained somatic point mutations and copy number alterations of 300 genes in our BPDCN specimens using an in-house hematologic malignancy panel ("T300" panel). Next, we confirmed the prevalence of compound truncating TET2 mutations in patients with BPDCN and few copy number alterations in the genes profiled. We then used the transcriptome microarray (ThermoFisher Scientific ClariomTM D Pico Assay, and serum multiplex immunoassays (Cytokine/Chemokine/Growth Factor 45-Plex Human ProcartaPlex™ Panel 1 (ThermoFisher Scientific, formerly Affymetrix) with the addition of IL-3 Human ProcartaPlex™ Simplex Kit, formerly Affymetrix) to compare BPDCN specimens against those from TET2-mutated AML patients. Results: With the microarray analysis, we found 920 genes to be up-regulated and 791 genes down-regulated in BPDCN specimens as compared to AMLTET2m. We corroborated known differentially expressed marker genes: higher levels of IL3Ra and TCL1A and lower levels of MPO in BPDCN as compared to AMLTET2m specimens. Genes specific to dendritic cells (PTPRS, LTK, LAMP5) were highly expressed in BPDCN than in AMLTET2m specimens. Of interest, two of these genes, PTPRS and LTK, provide possible links to the skin lesions as PTPRS is implicated in the progression of melanoma and LTK is involved in pigmentation of melanocytes. The serum cytokine profile analysis showed significantly elevated levels of eotaxin and RANTES in the BPDCN cohort as compared to the AMLTET2m cohort (Figure 1a,b). Both of these are implicated in allergic and autoimmune reactions by behaving as eosinophil chemo-attractants. Along with the higher levels of PTPRS and dendritic nature of the tumor cells, these findings suggest a possible autoimmune background which exists in the context of disease. Conclusions: In this novel analysis, we observed elevated levels of eotaxin and RANTES in patients with BPDCN as compared to AMLTET2m. These findings may represent an important aspect of pDC functioning even outside of BPDCN, as pDCs may contribute to the pathogenesis of systemic lupus erythematosus (SLE), an autoimmune disorder with hallmark cutaneous lesions. Moreover, autoimmune pathologies have been hypothesized to damage the bone marrow and induce destruction of myeloid precursor cells. This may incorporate some of the dendritic cell nature since in its natural context, as pDCs serve to recognize foreign particles such as viruses and synthetic oligonucleotides through Toll-like Receptors TLR7/9. These findings suggest that further study into these markers are warranted in patients with BPDCN. Figure 1. Differential serum cytokine levels between BPDCN and AMLTET2m (a) Eotaxin (pg/mL), Wilcox rank test P < 0.01 (b) RANTES (pg/mL), Wilcox rank test P < 0.05. Disclosures Konopleva: Stemline Therapeutics: Research Funding. Pemmaraju:stemline: Consultancy, Honoraria, Research Funding; plexxikon: Research Funding; SagerStrong Foundation: Research Funding; daiichi sankyo: Research Funding; celgene: Consultancy, Honoraria; Affymetrix: Research Funding; samus: Research Funding; cellectis: Research Funding; abbvie: Research Funding; novartis: Research Funding.


2020 ◽  
pp. 107815522095185
Author(s):  
Yazan Samhouri ◽  
Sorana Ursu ◽  
Nina Dutton ◽  
Verma Tanvi ◽  
Salman Fazal

Introduction Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare and aggressive hematologic malignancy that originates from plasmacytoid dendritic cells. It can involve skin, bone marrow, and/or lymph nodes. There is no consensus recommendation regarding treatment especially in the relapsed setting. Tagraxofusp, a CD123 directed agent, was recently approved by the Food and Drug Administration to treat BPDCN. We report a case of an elderly patient with diagnosis of BPDCN who was treated initially with tagraxofusp followed by azacitidine and venetoclax combination on relapse. Case report A 79 year old male presented with violaceous skin lesions. He had no other symptoms. Biopsy of these lesions was consistent with a diagnosis of BPDCN. Further testing showed no extracutaneous involvement. Management and outcome: Tagraxofusp was started at full dose (12 mcg/kg). This dose was not tolerated well. Patient could only tolerate the lowest dose (5 mcg/kg). Toxicities included elevated liver function tests, hyperglycemia, capillary leak syndrome, and pancreatitis. Dose escalation on progression was not possible due to side effects. Treatment was switched to venetoclax and azacitidine. Combination treatment was tolerated very well and patient showed major cutaneous response after 5 cycles and continues to do well. Discussion Tagraxofusp is a novel therapy that needs more real-world experience. This case describes the clinical course of an elderly patient on tagraxofusp. We also review the literature of azacytidine/venetoclax combination as a potential yet tolerable treatment option for this rare disease entity. This is the fourth case in literature to be treated with this combination.


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