scholarly journals Pathology Quiz Case: Plasmacytoid Dendritic Cell Neoplasm

2014 ◽  
Vol 5 (1) ◽  
pp. ar.2014.5.0085 ◽  
Author(s):  
Quinn A. Dunlap ◽  
Kristine E. Day ◽  
Samuel G. Borak ◽  
Bradford A. Woodworth
Keyword(s):  
Dendritic Cell ◽  
Early Diagnosis ◽  
Hematologic Malignancy ◽  
Plasmacytoid Dendritic Cell ◽  
Current Case ◽  
Systemic Involvement ◽  
Cell Neoplasm ◽  
Putative Origin ◽  
Diagnostic Modalities ◽  
Paranasal Sinus Tumor

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare hematologic malignancy that possesses a heterogenous clinical and immunophenotypic presentation. The current case report describes an interesting and unique presentation of BPDCN as a primary paranasal sinus tumor without evidence of cutaneous or systemic involvement. As such, the report further contributes to the ongoing debate regarding the true putative origin of the neoplasm, as well as highlights the optimal diagnostic modalities, paramount importance of early diagnosis, and vast heterogeneity exhibited by this fascinating malignancy. The atypical presentation described here indicates the manifestations of BPDCN are more heterogenous than previously documented and thus can not be definitively ruled out in the absence of bone marrow, peripheral blood, or cutaneous involvement. Furthermore, atypical neoplastic presentations mandate flow cytometry and adjunctive immunohistochemistry for the definitive diagnosis of BPDCN, and early diagnosis of such neoplasms are critical for rapid initiation of treatment and improved outcomes.

scholarly journals A Case of Blastic Plasmacytoid Dendritic Cell Neoplasm Extensively Studied by Flow Cytometry and Immunohistochemistry

2017 ◽  
Vol 2017 ◽  
pp. 1-6
Author(s):  
Martina Pennisi ◽  
Clara Cesana ◽  
Micol Giulia Cittone ◽  
Laura Bandiera ◽  
Barbara Scarpati ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
Dendritic Cell ◽  
Hematologic Malignancy ◽  
Lymphoblastic Leukemia ◽  
Plasmacytoid Dendritic Cell ◽  
Bone Marrow Involvement ◽  
Hematopoietic Stem ◽  
Cell Neoplasm ◽  
Specific Antigens ◽  
Aggressive Clinical Course

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare hematologic malignancy with aggressive clinical course and poor prognosis. Diagnosis is based on detection of CD4+CD56+,CD123high, TCL-1+, and blood dendritic cell antigen-2/CD303+blasts, together with the absence of lineage specific antigens on tumour cells. In this report we present a case of BPDCN presenting with extramedullary and bone marrow involvement, extensively studied by flow cytometry and immunohistochemistry, who achieved complete remission after acute lymphoblastic leukemia like chemotherapy and allogeneic hematopoietic stem cell transplantation.

scholarly journals Approval of tagraxofusp-erzs for blastic plasmacytoid dendritic cell neoplasm

2020 ◽  
Vol 4 (16) ◽  
pp. 4020-4027 ◽  
Author(s):  
Naveen Pemmaraju ◽  
Marina Konopleva
Keyword(s):  
Dendritic Cell ◽  
Hematologic Malignancy ◽  
Phase 1 ◽  
Plasmacytoid Dendritic Cell ◽  
Package Insert ◽  
Drug Approval ◽  
Clinical Aspects ◽  
Patients Âgés ◽  
Cell Neoplasm ◽  
Surface Receptor

Abstract Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare and clinically challenging hematologic malignancy with dismal outcomes. With a median age of ∼70 years, the majority of patients with BPDCN have experienced historically suboptimal responses with intensive chemotherapy regimens. The major scientific breakthrough in this field was the recognition of overexpression of a surface receptor, CD123/interleukin 3 (IL-3) receptor α, in all patients. Importantly, a novel therapeutic agent consisting of a truncated diphtheria toxin (DT) payload fused to recombinant human IL-3 was being developed, one that targeted CD123, initially known as DT-IL-3 (later known as SL401; tagraxofusp; tagraxofusp-erzs [Elzonris]). The identification of this agent, and subsequent clinical trials specifically dedicated to patients with BPDCN (including a pilot study, followed by a larger phase 1/2 multicenter study [90% overall response rate [ORR] in frontline and 67% ORR in relapsed/refractory setting]), in part led to approval of tagraxofusp-erzs on 21 December 2018. Tagraxofusp-erzs was the first agent approved for BPDCN (for patients ages 2 years and older), and importantly, established this drug as the first CD123-targeted agent ever approved. The most notable toxicity of tagraxofusp-erzs is occurrence of the capillary leak syndrome, which occurs frequently at all grades, and has also been observed to be life-threatening, appropriately leading to a US Food and Drug Administration “black box” warning in the package insert. The preclinical and clinical aspects of drug development of tagraxofusp-erzs as monotherapy leading to drug approval are reviewed herein, with discussion of future directions of this novel agent, including consideration for rational combinations in BPDCN and beyond.

scholarly journals Features of non-activation dendritic state and immune deficiency in blastic plasmacytoid dendritic cell neoplasm (BPDCN)

2019 ◽  
Vol 9 (12) ◽  
Author(s):  
Hannah C. Beird ◽  
Maliha Khan ◽  
Feng Wang ◽  
Mansour Alfayez ◽  
Tianyu Cai ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Dendritic Cell ◽  
Peripheral Blood ◽  
Profile Analysis ◽  
Hematologic Malignancy ◽  
Plasmacytoid Dendritic Cell ◽  
Serum Samples ◽  
Molecular Features ◽  
Cell Neoplasm ◽  
Poor Outcomes

AbstractBlastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare, male-predominant hematologic malignancy with poor outcomes and with just one recently approved agent (tagraxofusp). It is characterized by the abnormal proliferation of precursor plasmacytoid dendritic cells (pDCs) with morphologic and molecular similarities to acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS)/chronic myelomonocytic leukemia (CMML) in its presentation within the bone marrow and peripheral blood. To identify disease-specific molecular features of BPDCN, we profiled the bone marrow, peripheral blood, and serum samples from primary patient samples using an in-house hematologic malignancy panel (“T300” panel), transcriptome microarray, and serum multiplex immunoassays. TET2 mutations (5/8, 63%) were the most prevalent in our cohort. Using the transcriptome microarray, genes specific to pDCs (LAMP5, CCDC50) were more highly expressed in BPDCN than in AML specimens. Finally, the serum cytokine profile analysis showed significantly elevated levels of eosinophil chemoattractants eotaxin and RANTES in BPDCN as compared with AML. Along with the high levels of PTPRS and dendritic nature of the tumor cells, these findings suggest a possible pre-inflammatory context of this disease, in which BPDCN features nonactivated pDCs.

scholarly journals An Unusual Manifestation of Blastic Plasmacytoid Dendritic Cell Neoplasm as a Testicular Tumor

2019 ◽  
Vol 2019 ◽  
pp. 1-4
Author(s):  
Daniel M. Pak ◽  
Maria S. Tretiakova
Keyword(s):  
Dendritic Cell ◽  
Hematologic Malignancy ◽  
Plasmacytoid Dendritic Cell ◽  
Testicular Tumor ◽  
Integrated Approach ◽  
Significant Heterogeneity ◽  
Tumor Pathology ◽  
First Case ◽  
Cell Neoplasm ◽  
Immunohistochemical Studies

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a clinically aggressive hematologic malignancy arising from precursors of plasmacytoid dendritic cells that represent less than 1% of hematological malignancies. BPDCN initially presents with cutaneous involvement and a characteristic immunophenotype of CD4, CD56, and CD123 co-expression. Upon disease progression, BPDCN shows a strong predilection for bone marrow, peripheral blood, and lymph nodes, whereas manifestations in visceral organs are rare. Significant heterogeneity in clinical presentation and immunophenotypic profile makes BPDCN challenging to diagnose without an integrated approach based on patient history, clinical features, tumor pathology, and comprehensive immunohistochemical studies. Herein we report the first case of relapsed BPDCN manifesting as a unilateral testicular tumor.

scholarly journals Multicenter analysis of outcomes in blastic plasmacytoid dendritic cell neoplasm offers a pretargeted therapy benchmark

Blood ◽  
2019 ◽  
Vol 134 (8) ◽  
pp. 678-687 ◽  
Author(s):  
Justin Taylor ◽  
Michael Haddadin ◽  
Vivek A. Upadhyay ◽  
Erwin Grussie ◽  
Neha Mehta-Shah ◽  
...  
Keyword(s):  
Dendritic Cell ◽  
Clinical Characteristics ◽  
Treatment Guidelines ◽  
Hematologic Malignancy ◽  
Systemic Disease ◽  
Plasmacytoid Dendritic Cell ◽  
New Drugs ◽  
Cell Neoplasm ◽  
Poor Outcomes ◽  
Modern Era

Abstract Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is an uncommon hematologic malignancy with poor outcomes. Existing data on the clinical behavior of BPDCN are limited because reported outcomes are from small retrospective series, and standardized treatment guidelines are lacking. The interleukin-3 cytotoxin conjugate tagraxofusp was recently tested in phase 1/2 trials that led to US Food and Drug Administration approval, the first ever for BPDCN. However, because there was no matched internal comparator in this or any clinical study to date, results of BPDCN trials testing new drugs are difficult to compare with alternative therapies. We therefore sought to define the clinical characteristics and outcomes of a group of patients with BPDCN treated at 3 US cancer centers in the modern era but before tagraxofusp was available. In 59 studied patients with BPDCN, the median overall survival from diagnosis was 24 months, and outcomes were similar in patients with “skin only” or with systemic disease at presentation. Intensive first-line therapy and “lymphoid-type” chemotherapy regimens were associated with better outcomes. Only 55% of patients received intensive chemotherapy, and 42% of patients underwent stem cell transplantation. Clinical characteristics at diagnosis associated with poorer outcomes included age >60 years, abnormal karyotype, and terminal deoxynucleotidyltransferase (TdT) negativity in the BPDCN cells. We also identified disease responses to pralatrexate and enasidenib in some patients. This study highlights poor outcomes for patients with BPDCN in the modern era and the need for new treatments. Outcomes from ongoing clinical trials for BPDCN can be evaluated relative to this contemporary cohort.

scholarly journals Newly-Discovered Neural Features Expand the Pathobiological Knowledge of Blastic Plasmacytoid Dendritic Cell Neoplasm

Cancers ◽  
2021 ◽  
Vol 13 (18) ◽  
pp. 4680
Author(s):  
Maria Rosaria Sapienza ◽  
Giuseppe Benvenuto ◽  
Manuela Ferracin ◽  
Saveria Mazzara ◽  
Fabio Fuligni ◽  
...  
Keyword(s):  
Dendritic Cell ◽  
Chromatin Immunoprecipitation ◽  
Hematologic Malignancy ◽  
Plasmacytoid Dendritic Cell ◽  
Neuronal Progenitor ◽  
Neural Genes ◽  
Tumor Dissemination ◽  
Cell Neoplasm ◽  
Chromatin Immunoprecipitation Sequencing ◽  
The Impact

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare and highly aggressive hematologic malignancy originating from plasmacytoid dendritic cells (pDCs). The microRNA expression profile of BPDCN was compared to that of normal pDCs and the impact of miRNA dysregulation on the BPDCN transcriptional program was assessed. MiRNA and gene expression profiling data were integrated to obtain the BPDCN miRNA-regulatory network. The biological process mainly dysregulated by this network was predicted to be neurogenesis, a phenomenon raising growing interest in solid tumors. Neurogenesis was explored in BPDCN by querying different molecular sources (RNA sequencing, Chromatin immunoprecipitation-sequencing, and immunohistochemistry). It was shown that BPDCN cells upregulated neural mitogen genes possibly critical for tumor dissemination, expressed neuronal progenitor markers involved in cell migration, exchanged acetylcholine neurotransmitter, and overexpressed multiple neural receptors that may stimulate tumor proliferation, migration and cross-talk with the nervous system. Most neural genes upregulated in BPDCN are currently investigated as therapeutic targets.

scholarly journals Comprehensive metagenomic analysis of blastic plasmacytoid dendritic cell neoplasm

2020 ◽  
Vol 4 (6) ◽  
pp. 1006-1011
Author(s):  
Jason Nomburg ◽  
Susan Bullman ◽  
Sun Sook Chung ◽  
Katsuhiro Togami ◽  
Mark A. Walker ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Dendritic Cell ◽  
Cell Carcinoma ◽  
Kaposi's Sarcoma ◽  
Hematologic Malignancy ◽  
Normal Skin ◽  
Plasmacytoid Dendritic Cell ◽  
Kaposi’S Sarcoma ◽  
Merkel Cell ◽  
Cell Neoplasm

Abstract Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a hematologic malignancy believed to originate from plasmacytoid dendritic cells (pDCs), the immune cells responsible for producing type 1 interferons during infection. Nearly all patients with BPDCN have prominent skin involvement, with cutaneous infiltration occupying the dermis and subcutis. One half of patients present with BPDCN cells only in the skin, with no evidence of disease elsewhere. Because normal pDCs are rare or absent in cutaneous sites, and they only traffic to the skin after activation by pathogen or inflammation, our aim was to determine if a microorganism is associated with BPDCN. We performed RNA sequencing in BPDCN skin and bone marrow, with cutaneous T-cell lymphoma (CTCL) and normal skin as controls. GATK-PathSeq was used to identify known microbial sequences. Bacterial reads in BPDCN skin were components of normal flora and did not distinguish BPDCN from controls. We then developed a new computational tool, virID (Viral Identification and Discovery; https://github.com/jnoms/virID), for identification of microbial-associated reads remaining unassigned after GATK-PathSeq. We found no evidence for a known or novel virus in BPDCN skin or bone marrow, despite confirming that virID could identify Merkel cell polyomavirus in Merkel cell carcinoma, human papillomavirus in head and neck squamous cell carcinoma, and Kaposi’s sarcoma herpesvirus in Kaposi’s sarcoma in a blinded fashion. Thus, at the level of sensitivity used here, we found no clear pathogen linked to BPDCN.

Myeloid Lineage-Associated Mutations Are Detected in Blastic Plasmacytoid Dendritic Cell Neoplasm

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 5123-5123
Author(s):  
Yongbao Wang ◽  
Justin Windham ◽  
Shere Billouin-Frazier ◽  
Dan Jones
Keyword(s):  
Lymph Node ◽  
Dendritic Cell ◽  
Dna Sequencing ◽  
Hematologic Malignancy ◽  
Plasmacytoid Dendritic Cell ◽  
Poor Quality ◽  
Sequencing Data ◽  
Double Mutation ◽  
Cell Neoplasm ◽  
Close Relationship

Abstract Abstract 5123 Background/Purpose: Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare but highly aggressive hematologic malignancy that frequently presents with skin, lymph node, and leukemic disease. Since BPDCN can evolve into acute myelomonocytic leukemia (AMML) with other cases associated with monocytosis, a close relationship of BPDCN to the myelomonocytic lineage is suspected. Here we investigate the frequency of myeloid-associated DNA mutations in BPDCN using a targeted exon sequencing panel. Methods: Nine cases of BPDCN (5 skin, 1 lymph node, 3 bone marrow clot sections) were studied. All showed blastic cytomorphology; characteristic expression of CD56 and CD123; CD4 and/or TCL1 expression; and absence of definitive lymphoid, myeloid, and monocytic marker expression. AMML recurrence at 18 months, seen in 1 patient, was also assessed. Genomic DNA was extracted from formalin-fixed paraffin-embedded sections and subjected to a 161-amplicon PCR-based DNA sequencing assay that includes the commonly mutated areas of KRAS, NRAS, IDH1, IDH2, TET2, EZH2, JAK2, and ASXL1. Limited multiplex PCR and product harvesting was performed on an Access Array chip (Fluidigm). Ion adaptors were added and DNA sequencing was performed on a PGM sequencer using the 316 chip with 200 base-pair sequencing chemistry (Life Technologies). Sensitivity of mutation detection varied between 5–10%. Sequencing data were analyzed by SeqNext software (JSI MedSystems). Detected mutations were confirmed using conventional Sanger sequencing, with an approximate sensitivity of 15%, or pyrosequencing (5%). Results: Mutations in one or more of the tested genes were found in 6 of 9 patients, with unconfirmed mutations in 2 additional cases due to low-level mutations in samples with poor quality DNA. One patient with a typical BPDCN showed an IDH2 mutation (R140Q) with recurrence as AMML showing this mutation as well as a double mutation in KRAS (G12R, Q61R). Other mutations identified included 3 in ASXL1 including W608C, NRAS G12D, EZH2 C-terminal truncation, and 2 TET2indels. Conclusions: The presence of myeloid-associated mutations particularly in IDH2, TET2 and ASXL1 in cases of BPDCN is support for a relationship to the myelomonocytic lineage. The presence of shared and new mutations in the AMML recurrence in 1 patient with BPDCN further indicates a pathogenetic relationship between the two entities. Disclosures: Wang: Quest Diagnostics: Employment. Windham:Quest Diagnostics: Employment. Billouin-Frazier:Quest Diagnostics: Employment. Jones:Quest Diagnostics: Employment.

scholarly journals Recent developments in the treatment of blastic plasmacytoid dendritic cell neoplasm

2019 ◽  
Vol 10 ◽  
pp. 204062071987473 ◽  
Author(s):  
Minas P. Economides ◽  
Marina Konopleva ◽  
Naveen Pemmaraju
Keyword(s):  
Dendritic Cell ◽  
Hematologic Malignancy ◽  
Plasmacytoid Dendritic Cell ◽  
Standard Of Care ◽  
Specific Tumor ◽  
Cell Neoplasm ◽  
Rational Combination ◽  
United States Food ◽  
Recent Developments ◽  
States Food

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a clinically aggressive hematologic malignancy derived from precursors of dendritic cells and involves most frequently the skin, bone marrow and lymph nodes. Diagnosis depends upon identification of specific tumor markers including CD4, CD56 and CD123. Historically, the median survival has been less than 2 years in most reported series. While for many years, conventional chemotherapy followed by stem cell transplantation was the standard of care, recently tagraxofusp, a cytotoxin directed against CD123, received United States Food and Drug Administration approval specifically for patients with BPDCN. In this review, we will discuss the markers used for diagnosis of BPDCN and focus on the new targeted treatments available. Specifically in BPDCN, tagraxofusp was highly effective with a safety profile found to be acceptable overall, with the noted occurrence of capillary leak syndrome. Future directions in therapy approaches for patients with BPDCN will include the development of other CD123-targeted agents, agents targeting beyond CD123 and investigation of rational combination approaches of CD123-directed therapy with other therapies.

Tagraxofusp followed by combined azacitidine and venetoclax in blastic plasmacytoid dendritic cell neoplasm: A case report and literature review

2020 ◽  
pp. 107815522095185
Author(s):  
Yazan Samhouri ◽  
Sorana Ursu ◽  
Nina Dutton ◽  
Verma Tanvi ◽  
Salman Fazal
Keyword(s):  
Elderly Patient ◽  
Case Report ◽  
Dendritic Cell ◽  
Hematologic Malignancy ◽  
Plasmacytoid Dendritic Cell ◽  
Liver Function Tests ◽  
Skin Lesions ◽  
Consensus Recommendation ◽  
Novel Therapy ◽  
Cell Neoplasm

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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