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Luo Y, Wang LJ, Wang CL. Advancing the understanding and management of blastic plasmacytoid dendritic cell neoplasm: Insights from recent case studies. World J Clin Cases 2024; 12:6441-6446. [PMID: 39507120 PMCID: PMC11438698 DOI: 10.12998/wjcc.v12.i31.6441] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/15/2024] [Revised: 07/15/2024] [Accepted: 07/26/2024] [Indexed: 09/11/2024] Open
Abstract
We specifically discuss the mechanisms of the pathogenesis, diagnosis, and management of blastic plasmacytoid dendritic cell neoplasm (BPDCN), a rare but aggressive haematologic malignancy characterized by frequent skin manifestations and systemic dissemination. The article enriches our understanding of BPDCN through detailed case reports showing the clinical, immunophenotypic, and histopathological features that are critical for diagnosing this disease. These cases highlight the essential role of pathologists in employing advanced immunophenotyping techniques to accurately identify the disease early in its course and guide treatment decisions. Furthermore, we explore the implications of these findings for management strategies, emphasizing the use of targeted therapies such as tagraxofusp and the potential of allogeneic haematopoietic stem cell transplantation in achieving remission. The editorial underscores the importance of interdisciplinary approaches in managing BPDCN, pointing towards a future where precision medicine could significantly improve patient outcomes.
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Affiliation(s)
- Yan Luo
- Department of Stomatology, The People's Hospital of Dadukou District, Chongqing 400084, China
| | - Li-Juan Wang
- Department of Pathology, The Chongqing Hospital of Traditional Chinese Medicine, Chongqing 400021, China
| | - Cheng-Long Wang
- Department of Pathology, The Chongqing Hospital of Traditional Chinese Medicine, Chongqing 400021, China
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2
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Cai JW, Li MY, Wang WH, Shi HQ, Yang YH, Chen JJ. Blastic plasmacytoid dendritic cell neoplasm in Jinhua, China: Two case reports. World J Clin Cases 2024; 12:5263-5270. [DOI: 10.12998/wjcc.v12.i22.5263] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/29/2024] [Revised: 05/31/2024] [Accepted: 06/20/2024] [Indexed: 06/30/2024] Open
Abstract
BACKGROUND Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare and clinically aggressive hematologic malignancy originating from the precursors of plasmacytoid dendritic cells. BPDCN often involves the skin, lymph nodes, and bone marrow, with rapid clinical progression and a poor prognosis. The BPDCN diagnosis is mainly based on the immunophenotype.
CASE SUMMARY In this paper, we retrospectively analyzed 2 cases of BPDCN. Both patients were elderly males. The lesions manifested as skin masses. Morphological manifestations included diffuse and dense tumor cell infiltration of the dermis and subcutaneous tissues. Immunohistochemistry staining showed that cluster of differentiation CD4, CD56, CD43, and CD123 were positive.
CONCLUSION In this paper, we retrospectively analyzed 2 cases of BPDCN. Both patients were elderly males. The lesions manifested as skin masses. Morphological manifestations included diffuse and dense tumor cell infiltration of the dermis and subcutaneous tissues. Immunohistochemistry staining showed that cluster of differentiation CD4, CD56, CD43, and CD123 were positive.
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Affiliation(s)
- Jia-Wei Cai
- Department of Pathology, Jinhua Hospital, Jinhua 321000, Zhejiang Province, China
| | - Meng-Yao Li
- Department of Pathology, Shaoxing People’s Hospital, Shaoxing 312000, Zhejiang Province, China
| | - Wei-Hao Wang
- Department of Urology, Shaoxing People's Hospital, Shaoxing 312000, Zhejiang Province, China
| | - Hong-Qi Shi
- Department of Pathology, Jinhua Hospital, Jinhua 321000, Zhejiang Province, China
| | - Yi-Hui Yang
- Department of Pathology, Jinhua Hospital, Jinhua 321000, Zhejiang Province, China
| | - Jia-Jun Chen
- Department of Urology, Shaoxing People's Hospital, Shaoxing 312000, Zhejiang Province, China
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El Hussein S, Wang W. Flow Cytometry Profiling of Plasmacytoid Dendritic Cell Neoplasms. Cancers (Basel) 2024; 16:2118. [PMID: 38893237 PMCID: PMC11171351 DOI: 10.3390/cancers16112118] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/01/2024] [Revised: 05/26/2024] [Accepted: 05/28/2024] [Indexed: 06/21/2024] Open
Abstract
In this review, we aim to provide a summary of the diverse immunophenotypic presentations of distinct entities associated with plasmacytoid dendritic cell (pDC) proliferation. These entities include the following: (1) blastic plasmacytoid dendritic cell neoplasm (BPDCN); (2) mature pDC proliferation (MPDCP), most commonly seen in chronic myelomonocytic leukemia (CMML); and (3) myeloid neoplasms with pDC differentiation, in which pDCs show a spectrum of maturation from early immature pDCs to mature forms, most commonly seen in acute myeloid leukemia (pDC-AML). Our aim is to provide a flow cytometry diagnostic approach to these distinct and sometimes challenging entities and to clarify the immunophenotypic spectrum of neoplastic pDCs in different disease presentations. In this review, we also cover the strategies in the evaluation of residual disease, as well as the challenges and pitfalls we face in the setting of immune and targeted therapy. The differential diagnosis will also be discussed, as blasts in some AML cases can have a pDC-like immunophenotype, mimicking pDCs.
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Affiliation(s)
- Siba El Hussein
- Department of Pathology, University of Vermont Larner College of Medicine, 111 Colchester Avenue, Burlington, VT 05401, USA
| | - Wei Wang
- Department of Hematopathology, University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX 77030, USA
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El Hussein S, Wang W. Plasmacytoid dendritic cells in the setting of myeloid neoplasms: Diagnostic guide to challenging pathologic presentations. Br J Haematol 2023; 200:545-555. [PMID: 36606610 DOI: 10.1111/bjh.18632] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/20/2022] [Revised: 12/14/2022] [Accepted: 12/19/2022] [Indexed: 01/07/2023]
Abstract
In this article, we describe three broad pathologic presentations of plasmacytoid dendritic cells (pDCs) that may be encountered in clinical practice, in which an association between pDCs and myeloid neoplasms is identified: (1) myeloid neoplasms with mature pDC expansion, most commonly seen in chronic myelomonocytic leukaemia (CMML); (2) myeloid neoplasms with pDC differentiation, in which pDCs show a spectrum of maturation from early immature pDCs to mature forms, most commonly seen in acute myeloid leukaemia (AML); (3) myeloid neoplasms associated with blastic plasmacytoid dendritic cell neoplasm (BPDCN), either stemming from the same precursor or representing an independent clonal process. Additionally, we also discuss AML with pDC-like phenotype, in which myeloblasts show immunophenotypic features that may mimic those seen in pDCs. Using these presentations, we provide a diagnostic algorithm for appropriate pathologic classification, while attempting to clarify and homogenize nomenclatures pertaining to different biologic states of pDCs.
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Affiliation(s)
- Siba El Hussein
- Department of Pathology, University of Rochester Medical Center, Rochester, New York, USA
| | - Wei Wang
- Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
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5
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Wang Y, Xiao L, Yin L, Zhou L, Deng Y, Deng H. Diagnosis, treatment, and genetic characteristics of blastic plasmacytoid dendritic cell neoplasm: A review. Medicine (Baltimore) 2023; 102:e32904. [PMID: 36800625 PMCID: PMC9936012 DOI: 10.1097/md.0000000000032904] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/19/2023] Open
Abstract
Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a highly aggressive and extremely rare hematologic disease with a poor prognosis, involving mainly the skin and bone marrow. The immunophenotype of these tumor cells is characterized by the expression of CD4, CD56, CD123, TCL-1, and CD303. To date, no consensus has been reached on the standard of care for BPDCN. Currently, clinical treatment is mainly based on high-dose chemotherapy combined with hematopoietic stem cell transplantation. However, this treatment method has limitations for elderly, frail, and relapsed/refractory patients. In recent years, breakthroughs in molecular biology and genetics have not only provided new ideas for the diagnosis of BPDCN but also helped develop targeted treatment strategies for this disease. The emergence of targeted drugs has filled the gap left by traditional therapies and shown great clinical promise. This article focuses on the latest advances in genetics and targeted therapies for BPDCN, especially the emerging therapies that may provide new ideas for the clinical treatment of BPDCN.
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Affiliation(s)
- Yemin Wang
- Department of Pathology, Fourth Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China
| | - Li Xiao
- Department of Pathology, Fourth Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China
| | - Lili Yin
- Department of Pathology, Fourth Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China
| | - Lv Zhou
- Department of Pathology, Fourth Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China
| | - Yanjuan Deng
- Department of Pathology, Fourth Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China
- Mol. Med. & Genet. Center, Fourth Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China
| | - Huan Deng
- Department of Pathology, Fourth Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China
- Mol. Med. & Genet. Center, Fourth Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China
- * Correspondence: Huan Deng, Department of Pathology, Fourth Affiliated Hospital of Nanchang University, 133 South Guangchang Road, Nanchang, Jiangxi 330003, China (e-mail: )
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6
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Sherstnev AA, Kovrigina AM, Solovyova TI, Moiseeva TN. Pathomorphological and clinical characteristics of blastic plasmocytoid dendritic cell neoplasm. Case report. TERAPEVT ARKH 2022; 94:891-896. [DOI: 10.26442/00403660.2022.07.201734] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/11/2022] [Accepted: 08/11/2022] [Indexed: 11/22/2022]
Abstract
The paper reveals the 5 cases date about blastic plasmacytoid dendritic cell neoplasm. The presented information demonstrates morphological, immunohistochemical data and clinical manifestations.
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Valentini CG, Piciocchi A, Facchetti F, Guolo F, Pulsoni A, Vignetti M, Pagano L. Blastic plasmocitoid dendritic cell neoplasm with leukemic spread: a GIMEMA survey. Blood Adv 2021; 5:5608-5611. [PMID: 34644376 PMCID: PMC8714711 DOI: 10.1182/bloodadvances.2021005802] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/21/2021] [Accepted: 09/22/2021] [Indexed: 11/20/2022] Open
Affiliation(s)
- Caterina Giovanna Valentini
- Dipartimento di Diagnostica per Immagini, Radioterapia Oncologica ed Ematologia, Fondazione Policlinico Universitario A. Gemelli, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Rome, Italy
| | - Alfonso Piciocchi
- GIMEMA Foundation, Roma Italian Group for Adult Hematologic Diseases (GIMEMA), Data Center and Health Outcomes Research Unit, Rome, Italy
| | - Fabio Facchetti
- Pathology Section, Department of Molecular and Translational Medicine, University of Brescia, Brescia, Italy
| | - Fabio Guolo
- IRCCS Ospedale Policlinico San Martino, Genova, Switzerland
- Clinic of Hematology, Department of Internal Medicine, University of Genoa, Genova, Italy
| | - Alessandro Pulsoni
- Ematologia, Dipartimento di Medicina Traslazionale e di Precisione, Sapienza Università di Roma, Rome, Italy; and
| | - Marco Vignetti
- GIMEMA Foundation, Roma Italian Group for Adult Hematologic Diseases (GIMEMA), Data Center and Health Outcomes Research Unit, Rome, Italy
| | - Livio Pagano
- Dipartimento di Diagnostica per Immagini, Radioterapia Oncologica ed Ematologia, Fondazione Policlinico Universitario A. Gemelli, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Rome, Italy
- Sezione di Ematologia, Dipartimento di Scienze Radiologiche ed Ematologiche, Università Cattolica del Sacro Cuore, Rome, Italy
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8
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Cheng W, Yu TT, Tang AP, He Young K, Yu L. Blastic Plasmacytoid Dendritic Cell Neoplasm: Progress in Cell Origin, Molecular Biology, Diagnostic Criteria and Therapeutic Approaches. Curr Med Sci 2021; 41:405-419. [PMID: 34218354 DOI: 10.1007/s11596-021-2393-3] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/03/2021] [Accepted: 06/23/2021] [Indexed: 12/13/2022]
Abstract
Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare hematological malignancy characterized by recurrent skin nodules, an aggressive clinical course with rapid involvement of hematological organs, and a poor prognosis with poor overall survival. BPDCN is derived from plasmacytoid dendritic cells (pDCs) and its pathogenesis is unclear. The tumor cells show aberrant expression of CD4, CD56, interleukin-3 receptor alpha chain (CD123), blood dendritic cell antigen 2 (BDCA 2/CD303), blood dendritic cell antigen 4 (BDCA4) and transcription factor (E protein) E2-2 (TCF4). The best treatment drugs are based on experience by adopting those used for either leukemia or lymphoma. Relapse with drug resistance generally occurs quickly. Stem cell transplantation after the first complete remission is recommended and tagraxofusp is the first targeted therapy. In this review, we summarize the differentiation of BPDCN from its cell origin, its connection with normal pDCs, clinical characteristics, genetic mutations and advances in treatment of BPDCN. This review provides insights into the mechanisms of and new therapeutic approaches for BPDCN.
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Affiliation(s)
- Wei Cheng
- Department of Hematology, the Second Affiliate Hospital of Nanchang University, Nanchang, 330006, China
| | - Tian-Tian Yu
- Department of Hematology, the Second Affiliate Hospital of Nanchang University, Nanchang, 330006, China
| | - Ai-Ping Tang
- Department of Hematology, the Second Affiliate Hospital of Nanchang University, Nanchang, 330006, China
| | - Ken He Young
- Division of Hematopathology and Department of Pathology, Duke University Medical Center, Durham, 27710, USA
| | - Li Yu
- Department of Hematology, the Second Affiliate Hospital of Nanchang University, Nanchang, 330006, China.
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Deconinck E, Petrella T, Garnache Ottou F. Blastic Plasmacytoid Dendritic Cell Neoplasm: Clinical Presentation and Diagnosis. Hematol Oncol Clin North Am 2020; 34:491-500. [PMID: 32336414 DOI: 10.1016/j.hoc.2020.01.010] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Abstract
Clinical and biological presentation of patients with blastic plasmacytoid dendritic cell neoplasm (BPDCN) is depicted to highlight criteria that might alert physicians. Diagnosis of BPDCN is still challenging and requires (1) immunophenotyping of blood or bone marrow aspiration using several markers (CD4, CD56, HLA-DR, myeloid and lymphoid lineage markers) and should include pDC markers such as CD123, cTCL1, CD303, and CD304, and/or (2) pathologic analysis of cutaneous lesions, also with immunohistochemistry using markers specific to BPDCN.
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Affiliation(s)
- Eric Deconinck
- Service Hématologie, Université de Bourgogne Franche-Comté, INSERM Unite Mixte de Recherche (UMR) 1098, RIGHT Interactions Greffon-Hôte-Tumeur/Ingénierie Cellulaire et Génique, Centre Hospitalier Universitaire de Besançon, 3 Boulevard Alexandre Fleming, Besançon Cedex 25030, France
| | - Tony Petrella
- Department of Pathology, University of Montréal, Hôpital Maisonneuve-Rosemont, 2900 Boulevard Edouard-Montpetit, Montréal QC H3T 1J4, Quebec, Canada
| | - Francine Garnache Ottou
- Université de Bourgogne Franche-Comté, INSERM Unite Mixte de Recherche (UMR) 1098, RIGHT Interactions Greffon-Hôte-Tumeur/Ingénierie Cellulaire et Génique, Etablissement Français du sang Bourgogne Franche-Comté, 8 rue du Dr JFX Girod, Besançon 25000, France.
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10
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Hirner JP, O'Malley JT, LeBoeuf NR. Blastic Plasmacytoid Dendritic Cell Neoplasm: The Dermatologist's Perspective. Hematol Oncol Clin North Am 2020; 34:501-509. [PMID: 32336415 DOI: 10.1016/j.hoc.2020.01.001] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]
Abstract
Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare, aggressive malignancy derived from the plasmacytoid dendritic cell that commonly involves the skin. Cutaneous involvement is often the initial presentation, with deep purple or red-brown macules, plaques, or tumors. As such, dermatologists may be the first to see these patients and, in addition to oncologists, should be familiar with its presentation to facilitate early diagnosis, helping to distinguish it from acute myelogenous leukemia cutis.
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Affiliation(s)
- Jesse P Hirner
- Department of Dermatology, The Center For Cutaneous Oncology, Dana-Farber Cancer Institute, Brigham and Women's Hospital, Harvard Medical School, 375 Longwood Avenue, Boston, MA 02115, USA
| | - John T O'Malley
- Department of Dermatology, The Center For Cutaneous Oncology, Dana-Farber Cancer Institute, Brigham and Women's Hospital, Harvard Medical School, 375 Longwood Avenue, Boston, MA 02115, USA
| | - Nicole R LeBoeuf
- Department of Dermatology, The Center For Cutaneous Oncology, Dana-Farber Cancer Institute, Brigham and Women's Hospital, Harvard Medical School, 375 Longwood Avenue, Boston, MA 02115, USA.
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Abstract
BPDCN is ultimately a bone marrow disease requiring induction-type eradication therapy followed by hematopoietic stem cell transplant (HSCT) to achieve long-lasting remissions or cure. Various regimens have been applied to this disease with varying success. A cumulative review of the literature suggests more intense regimens have greater efficacy with acute lymphoblastic leukemia regimens preferred to acute myeloid leukemia regimens. This approach benefits fit patients who are eligible for HSCT; however, most BPDCN patients require other treatment options. The recent FDA approval of the CD123-targeted agent tagraxofusp provides a novel therapeutic alternative to traditional chemotherapy but with potential toxicities.
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12
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Zhang X, Sun J, Yang M, Wang L, Jin J. New perspectives in genetics and targeted therapy for blastic plasmacytoid dendritic cell neoplasm. Crit Rev Oncol Hematol 2020; 149:102928. [PMID: 32234682 DOI: 10.1016/j.critrevonc.2020.102928] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/16/2018] [Revised: 12/26/2019] [Accepted: 03/02/2020] [Indexed: 01/12/2023] Open
Abstract
Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is one rare but clinically aggressive hematological malignancy, and it is typically characterized by skin lesion and bone marrow involvement. Diagnosis of BPDCN relies on the immunophenotype positive for four of CD4, CD56, CD123, TCL1 and BDCA-2, and commonly without the expression of MPO, cytoplasmic CD3, CD13, CD64, cytoplasmic CD79a, CD19 and CD20. Commonly, BPDCN is characterized by high CD123 expression, aberrant NF-κB activation, dependence on TCF4-/BRD4-network, and deregulated cholesterol metabolism. Under conventional therapy, the survival duration is only improved in a small number of BPDCN patients. Therefore, targeted therapy should be developed. Up to now, tagraxofusp is the leading edge and has been approved for BPDCN treatment. However, most of other targeted therapy agents were still not pushed to clinical trials for BPDCN. In this review, we emphatically discuss recent perspectives on BPDCN genetic features and developments of its targeted therapy.
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Affiliation(s)
- Xiang Zhang
- Department of Hematology, The First Affiliated Hospital, Zhejiang University College of Medicine, Hangzhou, Zhejiang, China; Key Laboratory of Hematologic Malignancies, Diagnosis and Treatment, Zhejiang, Hangzhou, Zhejiang, China; Institute of Hematology, Zhejiang University, Hangzhou, Zhejiang, China.
| | - Jiewen Sun
- Center Laboratory, Affiliated Secondary Hospital, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China.
| | - Min Yang
- Department of Hematology, The First Affiliated Hospital, Zhejiang University College of Medicine, Hangzhou, Zhejiang, China; Key Laboratory of Hematologic Malignancies, Diagnosis and Treatment, Zhejiang, Hangzhou, Zhejiang, China; Institute of Hematology, Zhejiang University, Hangzhou, Zhejiang, China.
| | - Lei Wang
- Department of Hematology, The First Affiliated Hospital, Zhejiang University College of Medicine, Hangzhou, Zhejiang, China; Key Laboratory of Hematologic Malignancies, Diagnosis and Treatment, Zhejiang, Hangzhou, Zhejiang, China; Institute of Hematology, Zhejiang University, Hangzhou, Zhejiang, China.
| | - Jie Jin
- Department of Hematology, The First Affiliated Hospital, Zhejiang University College of Medicine, Hangzhou, Zhejiang, China; Key Laboratory of Hematologic Malignancies, Diagnosis and Treatment, Zhejiang, Hangzhou, Zhejiang, China; Institute of Hematology, Zhejiang University, Hangzhou, Zhejiang, China.
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Sapienza MR, Pileri A, Derenzini E, Melle F, Motta G, Fiori S, Calleri A, Pimpinelli N, Tabanelli V, Pileri S. Blastic Plasmacytoid Dendritic Cell Neoplasm: State of the Art and Prospects. Cancers (Basel) 2019; 11:cancers11050595. [PMID: 31035408 PMCID: PMC6562663 DOI: 10.3390/cancers11050595] [Citation(s) in RCA: 61] [Impact Index Per Article: 10.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/20/2019] [Revised: 04/16/2019] [Accepted: 04/25/2019] [Indexed: 12/13/2022] Open
Abstract
Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is an extremely rare tumour, which usually affects elderly males and presents in the skin with frequent involvement of the bone-marrow, peripheral blood and lymph nodes. It has a dismal prognosis, with most patients dying within one year when treated by conventional chemotherapies. The diagnosis is challenging, since neoplastic cells can resemble lymphoblasts or small immunoblasts, and require the use of a large panel of antibodies, including those against CD4, CD56, CD123, CD303, TCL1, and TCF4. The morphologic and in part phenotypic ambiguity explains the uncertainties as to the histogenesis of the neoplasm that led to the use of various denominations. Recently, a series of molecular studies based on karyotyping, gene expression profiling, and next generation sequencing, have largely unveiled the pathobiology of the tumour and proposed the potentially beneficial use of new drugs. The latter include SL-401, anti-CD123 immunotherapies, venetoclax, BET-inhibitors, and demethylating agents. The epidemiologic, clinical, diagnostic, molecular, and therapeutic features of BPDCN are thoroughly revised in order to contribute to an up-to-date approach to this tumour that has remained an orphan disease for too long.
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Affiliation(s)
- Maria Rosaria Sapienza
- Division of Diagnostic Haematopathology, European Institute of Oncology, IRCCS, Via Ripamonti 435, 20141 Milano, Italy.
| | - Alessandro Pileri
- Unit of Dermatology, Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna, School of Medicine, Via Massarenti 1, 40138 Bologna, Italy.
| | - Enrico Derenzini
- Division of Haematology, European Institute of Oncology, Via Ripamonti 435, 20141 Milano, Italy.
| | - Federica Melle
- Division of Diagnostic Haematopathology, European Institute of Oncology, IRCCS, Via Ripamonti 435, 20141 Milano, Italy.
| | - Giovanna Motta
- Division of Diagnostic Haematopathology, European Institute of Oncology, IRCCS, Via Ripamonti 435, 20141 Milano, Italy.
| | - Stefano Fiori
- Division of Diagnostic Haematopathology, European Institute of Oncology, IRCCS, Via Ripamonti 435, 20141 Milano, Italy.
| | - Angelica Calleri
- Division of Diagnostic Haematopathology, European Institute of Oncology, IRCCS, Via Ripamonti 435, 20141 Milano, Italy.
| | - Nicola Pimpinelli
- Dermatology Unit, Department of Health and Science, University of Florence, School of Medicine, Viale Michelangiolo 104, 50100 Firenze, Italy.
| | - Valentina Tabanelli
- Division of Diagnostic Haematopathology, European Institute of Oncology, IRCCS, Via Ripamonti 435, 20141 Milano, Italy.
| | - Stefano Pileri
- Division of Diagnostic Haematopathology, European Institute of Oncology, IRCCS, Via Ripamonti 435, 20141 Milano, Italy.
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Sullivan JM, Rizzieri DA. Treatment of blastic plasmacytoid dendritic cell neoplasm. HEMATOLOGY. AMERICAN SOCIETY OF HEMATOLOGY. EDUCATION PROGRAM 2016; 2016:16-23. [PMID: 27913457 PMCID: PMC6142460 DOI: 10.1182/asheducation-2016.1.16] [Citation(s) in RCA: 48] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/13/2023]
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.
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15
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Pagano L, Valentini CG, Grammatico S, Pulsoni A. Blastic plasmacytoid dendritic cell neoplasm: diagnostic criteria and therapeutical approaches. Br J Haematol 2016; 174:188-202. [PMID: 27264021 DOI: 10.1111/bjh.14146] [Citation(s) in RCA: 126] [Impact Index Per Article: 14.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare haematological malignancy derived from the precursors of plamacytoid dendritic cells, with an aggressive clinical course and high frequency of cutaneous and bone marrow involvement. Neoplastic cells express CD4, CD43 (also termed SPN), CD45RA and CD56 (also termed NCAM1), as well as the plasmacytoid dendritic cell-associated antigens CD123 (also termed IL3RA), BDCA-2 (also termed CD303, CLEC4E) TCL1 and CTLA1 (also termed GZMB). The median survival is only a few months as the tumour exhibits a progressive course despite initial response to chemotherapy. The best modality of treatment remains to be defined. Generally, patients receive acute leukaemia-like induction, according to acute myeloid leukaemia (AML)-type or acute lymphoid leukaemia (ALL)-type regimens. The frequent neuromeningeal involvement indicates systematic pre-emptive intrathecal chemotherapy in addition to intensive chemotherapy. Allogeneic haematopoietic stem cell transplantation (HSCT), particularly when performed in first remission, may improve the survival. Preliminary data suggest a potential role for immunomodulatory agents and novel targeted drugs. Herein epidemiology, clinical manifestations, diagnosis and management of BPDCN will be presented. In detail, this review focuses on the therapeutic aspects of BPDCN, proposing a treatment algorithm for the management of the disease, including induction chemotherapy, allogeneic HSCT and intrathecal prophylaxis at different steps of treatment, according to compliance, biological and clinical characteristics of patients.
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Affiliation(s)
- Livio Pagano
- Institute of Haematology, Catholic University, Rome, Italy
| | | | - Sara Grammatico
- Division of Haematology, Department of Cellular Biotechnologies and Haematology, "Sapienza University", Rome, Italy
| | - Alessandro Pulsoni
- Division of Haematology, Department of Cellular Biotechnologies and Haematology, "Sapienza University", Rome, Italy
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Lim MS, Lemmert K, Enjeti A. Blastic plasmacytoid dendritic cell neoplasm (BPDCN): a rare entity. BMJ Case Rep 2016; 2016:bcr-2015-214093. [PMID: 26791132 DOI: 10.1136/bcr-2015-214093] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022] Open
Abstract
Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare and aggressive haematological malignancy in the elderly, with a high frequency of cutaneous and bone marrow involvement and poor prognosis. We report a case of BPDCN with classic presentation and discuss its treatment and the value of different investigation tools used in diagnosis and response assessment.
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Affiliation(s)
- Ming Sheng Lim
- Department of Haematology, Calvary Mater Newcastle, Waratah, New South Wales, Australia
| | - Karla Lemmert
- Department of Flow Cytometry, Pathology North Hunter, NSW Pathology, Newcastle, New South Wales, Australia
| | - Anoop Enjeti
- Department of Haematology, Calvary Mater Newcastle, Waratah, New South Wales, Australia
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Paluri R, Nabell L, Borak S, Peker D. Unique presentation of blastic plasmacytoid dendritic cell neoplasm: a single-center experience and literature review. Hematol Oncol 2015; 33:206-211. [DOI: 10.1002/hon.2147] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 08/30/2023]
Affiliation(s)
- Ravi Paluri
- Hematology & Oncology; University of Alabama at Birmingham; AL USA
| | - Lisle Nabell
- Hematology & Oncology; University of Alabama at Birmingham; AL USA
| | - Samuel Borak
- Department of Pathology; University of Alabama at Birmingham; AL USA
| | - Deniz Peker
- Department of Pathology; University of Alabama at Birmingham; AL USA
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Liegeon AL, Fougerousse AC, Carassou P, Valois A, Veran Y. Manifestations cutanées révélatrices d’une leucémie aiguë dendritique plasmocytoïde (LADP) : deux observations. Presse Med 2015; 44:681-4. [DOI: 10.1016/j.lpm.2015.01.009] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/05/2014] [Revised: 01/11/2015] [Accepted: 01/27/2015] [Indexed: 12/01/2022] Open
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Parkins GJ, Jackson R, Wylie GR. Purple skin nodules - what lies beneath? J Eur Acad Dermatol Venereol 2015; 30:857-9. [PMID: 25690331 DOI: 10.1111/jdv.13026] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Affiliation(s)
- G J Parkins
- The Alan Lyell Centre for Dermatology, Southern General Hospital Glasgow, Glasgow, UK
| | - R Jackson
- Department of Pathology, Southern General Hospital Glasgow, Glasgow, UK
| | - G R Wylie
- The Alan Lyell Centre for Dermatology, Southern General Hospital Glasgow, Glasgow, UK
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Atalay F, Demirci GT, Bayramgürler D, Ateşoğlu EB, Yıldız S. Blastic plasmacytoid dendritic cell neoplasm: skin and bone marrow infiltration of three cases and the review of the literature. Indian J Hematol Blood Transfus 2014; 31:302-6. [PMID: 25825579 DOI: 10.1007/s12288-014-0464-3] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/24/2014] [Accepted: 10/03/2014] [Indexed: 11/30/2022] Open
Abstract
Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a distinct and rare neoplastic entity and was classified as a subgroup of acute myeloblastic leukemia by the WHO in 2008. The median survival of patients was 15.2 months in a large case series. Allogeneic or autologous bone marrow transplantation has been recommended by some reports because of the disease's poor prognosis. We present three patients who presented with both skin and bone marrow infiltration. A 57-year-old man, a 62-year-old woman, a 64-year-old man were admitted to our outpatient clinic because of skin lesions. All of the patient's had bone marrow infiltration with positivity of the CD4, CD56, and CD123 staining. Survival of the patient's were 42, 6 and 12 months, respectively. Two of the patients who presented as blastic form didn't respond to any chemotherapy. BPDCN is a difficult disease to diagnosis and manage. CD4, CD56, CD123, CD303, and T cell leukemia/lymphoma 1. Cutaneous lesions can present as isolated nodules, macules, and disseminated macules and nodules. Positivities are crucial to the diagnosis of the disease in histological examination. Bone marrow infiltration or disease relapse at presentation were related to poor prognosis. Complete immunocytochemical staining must be performed for all patients who have cutaneous lesions with or without blood count abnormalities. Bone marrow (allogeneic or autologous) transplantation should be considered at the first remission.
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Affiliation(s)
- Figen Atalay
- Department of Hematology, Başkent University School of Medicine, Oymaci Sok, No: 7, Altunizade, Istanbul, Turkey
| | | | - Dilek Bayramgürler
- Department of Dermatology, Kocaeli University School of Medicine, Kocaeli, Turkey
| | - Elif Birtaş Ateşoğlu
- Department of Hematology, Kocaeli University School of Medicine, Kocaeli, Turkey
| | - Semsi Yıldız
- Department of Pathology, School of Medicine, Baskent University, Istanbul, Turkey
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Dunlap QA, Day KE, Borak SG, Woodworth BA. Pathology quiz case: Plasmacytoid dendritic cell neoplasm. ALLERGY & RHINOLOGY 2014; 5:50-2. [PMID: 25199145 PMCID: PMC4019746 DOI: 10.2500/ar.2014.5.0085] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 11/20/2022]
Abstract
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.
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Affiliation(s)
- Quinn A Dunlap
- Department of Surgery, Division of Otolaryngology, University of Alabama at Birmingham, Birmingham, Alabama, USA
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Shi Y, Wang E. Blastic plasmacytoid dendritic cell neoplasm: a clinicopathologic review. Arch Pathol Lab Med 2014; 138:564-9. [PMID: 24678689 DOI: 10.5858/arpa.2013-0101-rs] [Citation(s) in RCA: 45] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/06/2022]
Abstract
Blastic plasmacytoid dendritic cell neoplasm is a rare entity grouped with the acute myeloid leukemia-related precursor neoplasms in the 2008 World Health Organization classification. It was previously postulated to originate from natural killer cells, T cells, or monocytes but is now believed to arise from the plasmacytoid dendritic cell. The pathogenesis of blastic plasmacytoid dendritic cell neoplasm is not well understood, although the neoplasm demonstrates frequent deletion of tumor suppressor genes, including RB1, CDKN1B, CDKN2A, and TP53. Blastic plasmacytoid dendritic cell neoplasm is a clinically aggressive tumor that often initially presents as cutaneous lesions and subsequently progresses to bone marrow involvement and leukemic dissemination. It is characterized by enhanced expression of CD56, CD4, and CD123, which can be detected by flow cytometry/immunohistochemistry. The differential diagnoses include myeloid sarcoma/acute myeloid leukemia, T-cell lymphoblastic leukemia/lymphoma, NK-cell lymphoma/leukemia, and some mature T-cell lymphomas/leukemias. Patients usually respond to initial chemotherapy but often relapse. Stem cell transplant may improve survival.
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Affiliation(s)
- Yang Shi
- From the Department of Pathology, Duke University Medical Center, Durham, North Carolina
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Yu S, Kwon MJ, Kim K, Koo DH, Woo HY, Park H. A rare case of acute leukemic presentation of blastic plasmacytoid dendritic cell neoplasm without cutaneous lesions. Ann Lab Med 2014; 34:148-51. [PMID: 24624352 PMCID: PMC3948829 DOI: 10.3343/alm.2014.34.2.148] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/12/2013] [Revised: 07/17/2013] [Accepted: 08/20/2013] [Indexed: 11/19/2022] Open
Affiliation(s)
- Shinae Yu
- Department of Laboratory Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Min-Jung Kwon
- Department of Laboratory Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Kyungeun Kim
- Department of Pathology, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Dong-Hoe Koo
- Department of Internal Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Hee-Yeon Woo
- Department of Laboratory Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Hyosoon Park
- Department of Laboratory Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea
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Pagano L, Valentini CG, Pulsoni A, Fisogni S, Carluccio P, Mannelli F, Lunghi M, Pica G, Onida F, Cattaneo C, Piccaluga PP, Di Bona E, Todisco E, Musto P, Spadea A, D'Arco A, Pileri S, Leone G, Amadori S, Facchetti F. Blastic plasmacytoid dendritic cell neoplasm with leukemic presentation: an Italian multicenter study. Haematologica 2013; 98:239-246. [PMID: 23065521 PMCID: PMC3561431 DOI: 10.3324/haematol.2012.072645] [Citation(s) in RCA: 246] [Impact Index Per Article: 20.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/21/2012] [Accepted: 09/26/2012] [Indexed: 12/24/2022] Open
Abstract
The objective of this study was to evaluate the clinical features, prognostic factors, and efficacy of treatments in patients with blastic plasmacytoid dendritic cell neoplasm with a leukemic presentation at onset of the disease. In order to do this, a retrospective multicenter study was performed from 2005-2011 in 28 Italian hematology divisions in which 43 cases were collected. Forty-one patients received an induction therapy, consisting of an acute myeloid leukemia-type regimen in 26 patients (60%) and acute lymphoid leukemia/lymphoma-type regimen in 15 patients (35%). Six patients (14%) underwent allogeneic hematopoietic stem cell transplantation. Seventeen patients (41%) achieved a complete remission: seven after acute myeloid leukemia-type treatment and 10 after an acute lymphoid leukemia/lymphoma-type regimen, with a significant advantage for acute lymphoid leukemia/lymphoma-type chemotherapy (P=0.02). Relapse occurred in six of the 17 patients (35%) who achieved complete remission, more frequently after acute lymphoid leukemia/lymphoma-type chemotherapy. The median overall survival was 8.7 months (range, 0.2-32.9). The patients treated with an acute myeloid leukemia-type regimen had an overall survival of 7.1 months (range, 0.2-19.5), whereas that of the patients receiving acute lymphoid leukemia/lymphoma-type chemotherapy was 12.3 months (range, 1-32.9) (P=0.02). The median overall survival of the allogeneic hematopoietic stem cell transplant recipients was 22.7 months (range, 12-32.9), and these patients had a significant survival advantage compared to the non-transplanted patients (median 7.1 months, 0.2-21.3; P=0.03). In conclusion, blastic plasmacytoid dendritic cell neoplasm with bone-marrow involvement is an aggressive subtype of high-risk acute leukemia. The rarity of this disease does not enable prospective clinical trials to identify the better therapeutic strategy, which, at present, is based on clinicians' experience.
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Affiliation(s)
- Livio Pagano
- Institute of Hematology, Catholic University, Rome, Italy.
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Lung involvement at initial presentation in blastic plasmacytoid dendritic cell neoplasm lacking cutaneous lesion. Ann Hematol 2012; 92:269-70. [DOI: 10.1007/s00277-012-1557-4] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/06/2012] [Accepted: 08/14/2012] [Indexed: 10/27/2022]
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Borchiellini D, Ghibaudo N, Mounier N, Del Giudice P, Quinsat D, Ticchioni M, Perrin C, Cardot Leccia N, Lacour JP. Blastic plasmacytoid dendritic cell neoplasm: a report of four cases and review of the literature. J Eur Acad Dermatol Venereol 2012; 27:1176-81. [PMID: 22455538 DOI: 10.1111/j.1468-3083.2012.04503.x] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/29/2022]
Abstract
BACKGROUND Blastic plasmacytoid dendritic cell neoplasm (BPDCN), formerly known as agranular CD4(+) /CD56(+) haematodermic neoplasm (CD4/CD56 HN), is a rare distinct form of lymphoma-like entity known of dermatologists because of its marked predilection for cutaneous involvement, and its aggressive behaviour. Moreover, the association or the evolution to an acute leukaemia entity that still expresses CD4 and CD56 markers is almost systematic. This new described entity of 'CD4(+) /CD56(+) leukaemia' or 'leukaemia of plasmacytoid dendritic cell lineage' has a poor prognostic and may lead to include haematopoietic stem cell transplantation in the treatment strategy as early as possible. REPORT OF CASES We report here four cases presenting with skin lesions and haematological signs. One of the patients underwent allogeneic stem cell transplantation, with a relapse-free survival of 40 months. We discuss the diagnosis features as well as the treatment options. CONCLUSION A collaborative work between dermatologists and onco-haematologists is essential to give patients the best chance of complete and long-term response.
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Affiliation(s)
- D Borchiellini
- Department of Haematology, Archet Hospital, University of Nice, France
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