Hematodermic Neoplasm Research Articles

Imaging blastic plasmacytoid dendritic cell neoplasm with 18FDG PET/CT: A rare paediatric case

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) previously called “CD4/CD56 hematodermic neoplasm” is a rare hematolymphoid neoplasm with a very poor prognosis. The disease has rarely been described in the paediatric population and is characterized by cutaneous involvement in most cases with hematological dissemination. Given the low number of cases described, the role of 18FDG PET/CT in this disease is very little known. We herein present a case of a 14-year-old girl with BPDCN to highlight the utility of 18FDG PET/CT for staging and treatment follow-up in this rare entity.

Analysis of First-Year Twitter Metrics of a Rare Disease Community for Blastic Plasmacytoid Dendritic Cell Neoplasm (BPDCN) on Social Media: #BPDCN.

The use of Twitter, one of the most commonly engaged social media platforms in the world, is increasing among the general public. Notably, this trend has also been observed among those involved in the healthcare field. With its ability to readily connect diverse groups of stakeholders in a given area of interest, Twitter has become a focal point for those involved in increasing awareness and information exchange in orphan disease fields. Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare, aggressive hematologic malignancy with generally poor long-term outcomes for adult patients and no standard therapeutic guidelines. Coupled with its low incidence rate, the disease has experienced a number of name changes over the past three decades (e.g., blastic NK cell lymphoma, CD4+CD56+ hematodermic tumor), thereby historically resulting in difficulties in its clinico-pathologic diagnosis and treatment approaches. All of these factors have led to a striking gap in terms of accurate information available to patients and the general public. Therefore, there is an urgent need for the development of more venues for the dissemination of information, particularly online, for this rare cancer. In this context, we began the Twitter medical community, #BPDCN, over a year ago, to help fill this information void. Now, completing its first year of existence, we aimed to analyze the metrics of Twitter use in order to better understand and to describe the characteristics and reach in of #BPDCN, and to determine the feasibility of starting and maintaining a disease-specific hashtag community in a particularly rare cancer.

Blastic plasmacytoid dendritic cell neoplasm: A case report

Blastic plasmacytoid dendritic cell neoplasm (BPDCN), formerly known as agranular cluster of differentiation (CD)4+/CD56+ hematodermic neoplasm, is a rare and aggressive type of lymphoma, with only ~100 cases reported worldwide. BPDCN is a hematological malignancy derived from precursors of plasmacytoid dendritic cells and is clinically characterized by cutaneous manifestations involving the lymph nodes and peripheral blood, a leukemia-like dissemination and a poor prognosis. The present study reports the case of a 54-year-old male who presented with symptoms characteristic of BPDCN. Pathological and immunohistochemical analysis of abdominal skin lesion biopsies were used to determine a diagnosis of stage IIIE BPDCN. Although cyclophosphamide, doxorubicin, vincristine and prednisolone chemotherapy was administered, the patient succumbed to BPDCN nine days after the discontinuation of chemotherapy. Thus, the period from BPDCN presentation to mortality was ≤3 months. The case reported in the present study was characterized by rapid development and poor prognosis, and displayed additional features of BPDCN, including systemic dissemination and a short survival period.

Gemcitabine in Blastic Plasmacytoid Dendritic Cell Neoplasm (CD4+CD56+ hematodermic neoplasm)

Once thought to be a natural killer cell lymphoma, blastic plasmacytoid dendritic cell neoplasm, also termed CD4+CD56+ hematodermic neoplasm, is a rare clinical entity which derives from plasmacytoid dendritic cells. Cutaneous predominant (with better prognosis) and non-cutaneous subtypes (often accompanied by mediastinal involvement and a poorer prognosis) have been described. Many patients are treated with CHOP-like regimens, but the prognosis remains poor. Patients presenting with only skin lesions (median survival 21 months) had a better prognosis than patients presenting with both cutaneous and extra-cutaneous disease.We describe an 86 yo female with a distant history of breast cancer. She noted rapid development of mildly itchy round pink cutaneous nodlues on the arms, buttock, and legs. She was treated with topical steroids without improvement. The CBC, calcium, and LDH were normal. ECOG 0. There was no adenopathy or organomegaly.Skin biopsy demonstrated a dense lymphoid infiltrate involving the upper and mid dermis, as well as adnexal structures, without epidermotropism. The infiltrate was composed predominantly of large to intermediate sized lymphoid cells having moderate amounts of cytoplasm and oval to cleaved nuclei having open chromatin and one or more small nucleoli. Mitotic figures were present. The neoplastic cells expressed CD4, CD56. Ki-67 was expressed by many of the cells. The cells were negative for CD1a, CD3, CD5, CD7, CD8, PAX-5, CD20, CD79a, CD10, CD23, CD30, CD163, bcl-2, bcl-6, myeloperoxidase, kappa/lambda light chains, p63, Tdt, tryptase, chromogranin, MART-1, mammoglobin, CAM 5.2, and AE1/3. The morphology and immunophenotype was consistent with a CD4+/CD56+ hematodermic neoplasm.The patient preferred no additional staging studies or therapy. Based on the available data, cutaneous-only disease was suggested. The disease was observed without intervention for a few weeks, but progressed on her skin. She then requested a gentle therapy that might provide palliative improvement and prevent progression.Gemcitabine (2′,2′-difluorodeoxycytidine) is a well tolerated pyrimidine antimetabolite that impairs DNA synthesis and promotes induction of apoptosis. In patients with relapsed or refractory aggressive non-Hodgkin lymphoma, gemcitabine led to a 20% response rate with median survival of 6 months.Therapy with Gemcitabine was administered at 1000 mg/M2 on days 1, 8, 15 every 28 days. There was rapid and marked improvement of the skin nodules. Treatment was very well tolerated with minimal bilateral leg edema. A 4 week chemotherapy holiday was associated with regrowth. Photographs document the disease progression before therapy and response of disease with ongoing therapy.Gemcitabine may provide palliative benefit in some patients with blastic plasmacytoid dendritic cell neoplasm.TablePre Therapy May 15 2014Day 1 Chemotherapy May 23 2014Day 22 Chemotherapy June 6 2014 [Display omitted] [Display omitted] [Display omitted] DisclosuresOff Label Use: Gemcitabine in blastic plasmacytoid dendritic cell neoplasm (CD4+CD56+ hematodermic neoplasm).

Long-Term Survival with High-Dose Chemotherapy Followed By Autologous Stem Cell Transplantation and Allogeneic Hematopoietic Stem Cell Transplantation for Patients with Blastic Plasmacytoid Dendritic Cell Neoplasm: A Retrospective Registry Study from the Japan Society for Hematopoietic Cell Transplantation

Background: Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare malignancy of plasmacytoid dendritic cells as classified by the World Health Organization (WHO), and is characterized by distinct clinical, pathological and genetic features. BPDCN used to be diagnosed as blastic NK-cell lymphoma or CD4+/CD56+ hematodermic neoplasm. Its prognosis is extremely poor with a median overall survival (OS) of about 1 year. Allogeneic hematopoietic stem cell transplantation (allo-HSCT) in remission has shown encouraging results for patients with BPDCN. However, the role of high-dose chemotherapy followed by autologous stem cell transplantation (HDT/ASCT) has not been reported.Methods: We surveyed the data of the Transplant Registry Unified Management Program of the Japan Society for Hematopoietic Cell Transplantation and identified 109 patients with an original diagnosis of BPDCN, blastic NK-cell or lymphoblastic lymphoma of NK-cell lineage. These diagnoses had been made by a pathologist at each institution in accordance with the WHO classification or previous lymphoma classification systems. Then, we sent out questionnaires to collect additional data on clinical presentation, prior therapies and update of follow-up, in addition to pathology and flow cytometry reports. The diagnosis of BPDCN was made with clinicopathological review by a consensus panel.Results: Of the 109 identified patients, additional data were obtained for 83. After central clinicopathological review, 58 patients were excluded from analysis due to disease other than BPDCN or the absence of important clinical data. Finally, the diagnosis of BPDCN was confirmed in 25 patients (allo-HSCT, N = 14; HDT/ASCT, N = 11).The median age at HSCT was 58 (range, 17-67) years and male patients were predominant (80%). Involvements of skin and bone marrow at diagnosis were observed in 88% and 68% of patients, respectively. The induction chemotherapy regimen was as follows: non-Hodgkin lymphoma (NHL)-like (e.g. cyclophosphamide, doxorubicin, vincristine, prednisone [CHOP]-like regimens; or ifosfamide/etoposide-based regimens) (N = 11), acute lymphoblastic leukemia (ALL)-like (N = 10) and acute myeloid leukemia (AML)-like (N = 4). The rate of initial response to induction chemotherapy was high, with a complete remission (CR) rate of 96%, except for one patient who experienced progressive disease in the central nervous system during induction therapy with an ALL-like regimen.The median time from diagnosis to HSCT was 6 months (range, 2-22). Among the patients who underwent allo-HSCT, myeloablative (MAC) and reduced-intensity (RIC) regimens were used in 8 (57%) and 6 (43%) patients, respectively. The donor of 1st allogeneic transplant was a relative in 7, unrelated bone marrow in 7 and cord blood in 1. Regarding the disease status at transplantation, all 11 patients underwent HDT/ASCT in CR1 whereas, among patients who underwent allo-HSCT, 12 were in CR1 (N=10)/CR2 (N =2) and two had disease.With a median follow-up of 53.5 months in surviving patients, OS and progression-free survival (PFS) at 4 years were 65% and 58%, respectively (Figure 1). The OS at 4 years for patients who received HDT/ASCT and allo-HSCT were 82% and 53%, respectively (P = 0.11, Figure 2). The PFS at 4 years for patients who received HDT/ASCT and allo-HSCT were 73% and 48%, respectively (P = 0.14, Figure 2). The three induction regimen groups (NHL-like, ALL-like and AML-like regimens) had similar OS rates: 62%, 70% and 67% at 4 years, respectively (P = 0.86). OS did not differ significantly between MAC and RIC groups (OS at 4 years: 45% vs. 60%, P = 0.31).There was no non-relapse mortality within 100 days after HSCT. Seven patients (28%) relapsed at a median of 10 months (range, 3-21) after HSCT (MAC allo-HSCT, N = 2; reduced-intensity conditioning allo-HSCT, N = 3; HDT/ASCT, N = 2). Notably, there was no relapse in patients without bone marrow (BM) infiltration at diagnosis in the HDT/ASCT treatment group. After allo-HSCT, grade 2-4 acute GVHD was observed in 5 patients (20%).Conclusions: As previous reports have shown, HSCT can achieve long-term survival in patients with BPDCN. In addition, the result of HDT/ASCT in CR1 seems to be promising and deserves further evaluation in the settings of prospective trials. Meanwhile, we need to clarify who could be cured by ASCT and need to improve outcome for high-risk patients, such as those with BM invasion. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Expression of CD123 (IL-3R-alpha), a Therapeutic Target of SL-401, on Myeloproliferative Neoplasms

Background: CD123 (alpha chain of the interleukin-3 receptor [IL-3RA]) heterodimerizes with CD131 (βc, common beta chain) to constitute the high-affinity receptor for IL-3. CD123 is not expressed on hematopoietic stem/progenitor cells from normal bone marrow (BM). In contrast, CD123 is highly expressed in CD34+/CD38- cells from acute myeloid leukemia (AML) patients, which recapitulate the leukemic phenotype in NOD/SCID mice; CD123, therefore, is a marker for leukemic stem cells in AML (Jordan CT et al., Leukemia 2000). CD123 is also highly expressed on CD4+/56+ leukemic cells in patients with blastic plasmacytoid dendritic cell neoplasm (BPDCN), an aggressive hematodermic neoplasm. The validity of CD123 as a rational therapeutic target was illustrated by clinical efficacy data for SL-401, a biologic target therapy directed to IL-3R, in patients with BPDCN and AML, respectively (Frankel AE et al., Blood 2014 andFrankel AE et al., J Clin Oncol 31, 2013 (suppl; abstr 7029)).Objectives: To study CD123 expression as a potential therapeutic target in myeloproliferative neoplasms (MPN).Methods: The study was approved by our institutional review board and patients provided written consent for sample collection. MPN diagnosis was based on WHO 2008 criteria. Surface antigen expression on hematopoietic cells of various lineages was interrogated using the 4-color multiparametric flow cytometer, FACSCaliber TM (BD Biosciences, San Jose, CA). Data analysis was performed using CellQuest Pro Software (BD Biosciences).Results: We studied a total of 21 MPN patients and 3 normal controls. Of the former, 14 patients had systemic mastocytosis (SM) (indolent SM=9, SM with associated myeloid neoplasm=4 and aggressive SM=1), 6 had primary myelofibrosis (PMF) and 1 had eosinophilic leukemia transformed to AML.Normal controls: Three normal BM samples were studied; the number of CD123 positive cells in the total population was <1%. Rare CD34+/CD38- cells were uniformly CD123-. Of the CD123+ cells, only a minor subset (<10%) coexpressed myeloid/granulocyte lineage (CD13+, CD15+ or CD16+) or monocyte/macrophage lineage (CD14+ or CD11b+) markers.Systemic mastocytosis: The data were informative for 6 patients (3 with peripheral blood [PB], 1 with BM, and 2 with paired PB and BM samples) for whom a sufficient number of mast cells (MC) were identified for immunophenotyping. Neoplastic MC were defined as CD117 hi/SSC hi/CD45 hi/CD34-/CD25+/FcεRI+. CD123 expression was seen in the majority of MC for 4 patients (#1-4, CD123 percentage positive, PB/BM): 91%/n.a. (#1), 75%/81% (#2), 84%/n.a. (#3), and 88%/n.a. (#4). In contrast, one patient (#5) had a minority of CD123+ MC (33%/28%).Clonal eosinophilia: PB was studied; the WBC differential count showed 41% leukemic blasts and 57% eosinophils (both confirmed to be clonally related based on FISH studies). Both cell populations were predominantly CD123+ (≥90%).Primary myelofibrosis: We studied PB samples from 6 PMF patients. Approximately 1-2% of circulating cells marked as CD123+; of these, expression was notable on CD34-/CD38+ cells (median 54%; range 41-74% positive). We found a larger proportion (30-50%) of CD123+ cells that coexpressed CD13+, CD16+ or CD11b+ representing monocytes, immature myeloid cells and granulocytes, as compared to normal BM controls. Studies on BM samples from PMF patients are ongoing.Conclusions: CD123 (IL-3RA) is expressed on relevant primary cells of interest in select MPNs, namely neoplastic mast cells in SM patients and eosinophils in clonal eosinophilia patients. In PMF, a minor population of circulating cells was CD123+ with a biased distribution on myeloid lineage cells as compared to normal BM samples. We are currently studying CD123 expression in additional MPN patients, and also analyzing CD123 expression on BM trephine biopsies by immunohistochemistry. In addition, the cytotoxicity assessment of SL-401 against MPN cell lines and primary cells is ongoing. Overall, the aforementioned data support the clinical development of SL-401 in patients with MPNs and clinical trials are currently being planned. DisclosuresBrooks:Stemline Therapeutics: Employment, Equity Ownership. Pardanani:Stemline Therapeutics Inc.: Research Funding.

Blastic plasmacytoid dendritic cell neoplasm presenting with a cutaneous tumor alone as the first symptom of onset: A case report and review of literature

Blastic plasmacytoid dendritic cell neoplasm (BPDCN), formerly named cluster of differentiation (CD)4+/CD56+ haematodermic neoplasm or blastic natural killer cell lymphoma, is a rare and highly aggressive haematopoietic malignancy. BPDCN typically occurs in the elderly, with a marked predilection for cutaneous involvement. The present study describes a case of BPDCN occurring in a 79-year-old male. The patient presented with skin lesions alone, with no evidence of extracutaneous involvement during the course of the disease. BPDCN was diagnosed based on histological and immunohistochemical observations and the patient was subsequently treated with local radiotherapy alone. However, rapid disease progression occurred and the patient succumbed five months after being diagnosed. The current result therefore demonstrated that BPDCN is highly aggressive even without systemic dissemination, and that radiotherapy appears to be ineffective in treating this tumor. The present study emphasizes the importance of pathologists and dermatologists being aware of this uncommon disease in order to avoid misdiagnosis.

Cytotoxic Variant of Mycosis Fungoides with CD8+ CD56+ Phenotype: A Case Report and Review of Literature.

Mycosis fungoides (MF) is the most common cutaneous Tcell lymphoma. Approximately 50% of all primary cutaneous lymphomas are MF[1]. These lymphomas are comprised of epidermotropic collections of small- to medium-sized T lymphocytes with cerebriform nuclei. The neoplastic cell shows a mature CD3+, CD4+, CD45RO+, CD8– memory T-cell phenotype. However, rarely, MF with a CD4–, CD8+ cytotoxic T-cell phenotype has been reported[2-5]. The World Health Organization (WHO)-European Organization for Research and Treatment of Cancer (EORTC) classification for cutaneous lymphomas describes three types of cutaneous lymphomas that express CD56: 1) subcutaneous panniculitis-like T-cell lymphoma, 2) extranodal natural killer (NK)/T-cell lymphoma, nasal type, and 3) CD4+/CD56+ hematodermic neoplasm (blastic NKcell lymphoma)[1]. However, the report does not mention, MF with CD56 expression. Earlier in 2003, a report by the EORTC cutaneous lymphoma task force workshop described cytotoxic/natural killer cell cutaneous lymphomas and divided them into eight categories[6]. One of these categories was the CD56+, cytotoxic variant of MF. This report presents a rare CD8+, CD56+ variant of MF having the cytotoxic phenotype.

Blastic Plasmacytoid Dendritic Cell Neoplasm: Update on Molecular Biology, Diagnosis, and Therapy

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare hematological malignancy with an aggressive clinical course. Most patients with BPDCN have skin lesions and simultaneous involvement of the peripheral blood, bone marrow, and lymph nodes. A search of PubMed and Medline was conducted for English-written articles relating to BPDCN, CD4(+)CD56(+) hematodermic neoplasm, and blastic natural killer cell lymphoma. Data regarding diagnosis, prognosis, and treatment were analyzed. BPDCN is derived from precursor plasmacytoid dendritic cells. The diagnosis of BPDCN is based on the characteristic cytology and immunophenotype of malignant cells coexpressing CD4, CD56, CD123, blood dendritic cell antigens 2 and 4, and CD2AP markers. Multiple chromosomal abnormalities and gene mutations previously reported in patients with myeloid and selected lymphoid neoplasms were identified in approximately 60% of patients with BPDCN. Prospectively controlled studies to guide treatment decisions are lacking. The overall response rate with aggressive acute lymphoblastic leukemia-type induction regimens was as high as 90%, but the durability of response was short. Median survival rates ranged between 12 and 16 months. Patients with relapsed disease may respond to L-asparaginase-containing regimens. Allogeneic hematopoietic stem cell transplantation, particularly when performed during the first remission, may produce durable remissions in selected adults. BPDCN is a rare aggressive disease that typically affects elderly patients. The most commonly affected nonhematopoietic organ is the skin. Although BPDCN is initially sensitive to conventional chemotherapy regimens, this response is relatively short and long-term prognosis is poor. In the near future, novel targeted therapies may improve outcomes for patients with BPDCN.

Sustained remission of blastic plasmacytoid dendritic cell neoplasm after unrelated allogeneic stem cell transplantation--a single center experience.

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare hematodermic neoplasm which typically presents with skin infiltrates with or without lymphadenopathy and bone marrow involvement. No standard of care exists for this aggressive disease and prognosis is particularly poor. Here, we present our experience with nine BPDCN patients diagnosed at our institution between 2005 and 2012. BPDCN patients were identified in the databases at the Department of Hematology and Oncology, the Department of Dermatology, and the Institute of Pathology at the Otto-von-Guericke-University Magdeburg. There were six male and three female patients with a median age at diagnosis of 66years. Sites involved were skin (five cases), lymph nodes (five cases), and bone marrow (five cases). Treatments varied from single agent chemotherapy to polychemotherapy and allogeneic stem cell transplantation for consolidation. The three patients that were treated with acute leukemia-type induction therapy followed by allogeneic stem cell transplantation (one after standard conditioning and two after reduced intensity conditioning using fludarabine in combination with thiotepa) achieved sustained remissions and are alive with a follow-up of 8, 35, and 41months. In contrast, median survival in the less intensively treated patients was only 9.5 (range 1 to 29) months.

A Rare Case of Acute Leukemic Presentation of Blastic Plasmacytoid Dendritic Cell Neoplasm without Cutaneous Lesions

A Rare Case of Acute Leukemic Presentation of Blastic Plasmacytoid Dendritic Cell Neoplasm without Cutaneous Lesions

Reduced Intensity Allogeneic Stem Cell Transplant for Treatment of Blastic Plasmacytoid Dendritic Cell Neoplasm

Blastic plasmacytoid dendritic cell neoplasm is a rare, aggressive tumor characterized by skin and/or marrow infiltration by CD4+ CD56+ cells. Historically, the tumor was variably thought to arise from either monocytes, T cells or NK cells giving rise to terms such as CD4+/CD56+ acute monoblastic leukemia, primary cutaneous CD4+/CD56+ hematodermic tumor and blastic NK-cell lymphoma. Whilst considerable progress has been made in understanding the histogenesis, the best modality of treatment remains to be defined. We are therefore reporting this case which was successfully treated with a T-deplete allogeneic transplant and the patient is currently alive and in remission 4 years post transplant.

Tumeur à cellules plasmocytoïdes dendritiques blastiques révélée par des lésions ecchymotiques du visage

Cutaneous CD4+CD56+ malignant tumor proliferation was previously called "CD4/CD56 hematodermic neoplasm". However, the most recent studies have shown that the disease develops from plasmacytoid dendritic cells and the tumor has been renamed "Blastic Plasmacytoid Dendritic Cell Neoplasm" (BPDCN). It is an aggressive disease with a poor prognosis and behaves like acute leukemia in the short to moderate term. A 65-year-old man with no particular history consulted for a left laterocervical lesion of ecchymotic aspect that had appeared one year earlier. Topical corticosteroid therapy had been unsuccessful. Examination of biopsies with lymphocyte typing enabled a diagnosis of BPDCN to be made. At the histopathological level, biopsy showed an infiltrate comprising medium to large cells. Immunohistochemical examination was remarkable for the absence of expression of markers of T- and B-cell lines. However, these tumor cells expressed CD4, CD56 and TCL1. Staging of the disease was normal. Treatment with chemotherapy was initiated in collaboration with a team of hematologists. Autologous bone marrow transplant was then performed. BPDCN is a rare malignant blood dyscrasia. It is distinguished by inaugural skin involvement, with systemic manifestations occurring much later. Histopathological examination of a skin biopsy with immunostaining establishes the diagnosis. In terms of phenotype, the tumor population is highly characteristic. The cells are negative for antigens of T- and B- cell lines. However, these cells express CD4, CD56 and TCL1, which are markers of plasmacytoid dendritic cells. The disease carries a poor prognosis and evolves in the short to middle term in the same way as acute leukemia. First-line treatment consists of the chemotherapy regimens used in aggressive lymphoma or acute leukemia. A bone marrow graft is sometimes performed at the time of initial relapse. Average survival is 12 months for chemotherapy alone and 30 months for transplant after first relapse. Early bone marrow transplantation has been shown to improve survival.

Loss-Of-Function Mutations In The Splicing Factor ZRSR2 Are Common In Blastic Plasmacytoid Dendritic Cell Neoplasm and Have Male Predominance

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is an aggressive malignancy previously known as blastic natural killer cell lymphoma, CD4+CD56+ hematodermic neoplasm, or agranular CD4+ NK cell leukemia. BPDCN has recently been classified as the malignant counterpart of plasmacytoid dendritic cells (pDCs), the most common dendritic cell subset in peripheral blood. Clinical outcomes in BPDCN are poor, with median survival of less than 12 months. The pathogenesis and genetic changes associated with pDC transformation are largely unknown, and the optimal treatment for this disease is unclear. Loss of the CDKN2A locus on 9p21 is the most common copy number alteration, and the sole targeted sequencing effort reported to date focused only on somatic mutations in TP53 and TET2 (Jardin et al. Br J Haem 2011). The goal of this study was to characterize the genetics of BPDCN by next-generation sequencing of all exons of 219 genes known to be recurrently mutated in hematologic malignancies. We sequenced a discovery cohort of seven adult patients with BPDCN, and confirmed the somatic status of single nucleotide variants (SNVs) and insertion-deletions (InDels) not present in dbSNP using paired germline tissue where available. All cases met World Health Organization criteria for pathological diagnosis of BPDCN. We confirmed the presence of TET2 (4 of 7 patients) and TP53 (1 of 7) mutations in BPDCN, and noted that the overall mutational spectrum was overlapping with previously sequenced hematologic neoplasms. Specifically, we observed mutations in ASXL1 (in 2 patients: K586* and an InDel causing a frameshift at S795), IDH2 (R140Q), KRAS (G13D), ABL1 (T315I), ARID1A (R1721*), GNA13 (E313*), U2AF1 (Q157L), and SRSF2 (P95L) that have been reported in myeloid and mature B cell neoplasms. Also of interest was an IRF8 R404W mutation; IRF8 is a transcription factor that drives pDC development and germline loss of IRF8 in humans is associated with dendritic cell deficiency. The most striking finding was the presence of premature stop, frame shift, and splice site mutations in the splicing factor ZRSR2 on chromosome Xp22.1 in 4 of 7 (57.1%) BPDCNs. ZRSR2 mutations were present in 71-84% of sequence reads at their respective locations, consistent with homo/hemizygous alterations in a dominant clone. Xenografting of one BPDCN that harbored a ZRSR2 premature stop mutation resulted in leukemia engraftment that retained the ZRSR2 mutation. From a validation cohort of 32 additional adult and pediatric BPDCNs, ZRSR2 mutations were present in 11 cases, for a total of 15 of 39 (38.5%) patients. Ten of 15 mutations were premature stop, frame shift, or splice site, while the remaining were missense variants. ZRSR2 is recurrently mutated in MDS and AML but at a much lower frequency (1-5%), and ZRSR2 mutations have not been described as characteristic of any other malignancy. Thus, ZRSR2 mutations are approximately 10-fold more prevalent among BPDCNs as compared to MDS or AML, indicating a unique association between BDPCN and ZRSR2 mutation. BPDCN is predominantly a disease of the male sex, both in previous studies and in our cohort (28 males among 36 patients, 77.8%). In a prior report (Yoshida et al. Nature 2012), 12 of 12 cases of MDS with ZRSR2 nonsense and frame shift mutations were male. All 10 cases of BPDCN with ZRSR2 nonsense, frame shift, and splice site mutations in our cohort were male (P=0.076 by two-sided Fisher's exact test). Thus, we hypothesize that BPDCN may be more common in males because of a gene dosage effect related to the chr.X location of ZRSR2. There was also a trend toward an association between ZRSR2 loss-of-function mutation and age ≥65 (P=0.068). There was no statistically significant difference in overall survival between patients with and without mutations in ZRSR2, although we were limited by the small cohort size and the heterogeneity of therapies received. We conclude that loss of ZRSR2 function is specifically associated with pDC transformation and leukemogenesis, as well as male sex and older age. Further studies to confirm these findings in additional cohorts and define the mechanism linking ZRSR2 mutation with BPDCN are underway. Disclosures:DeAngelo:Ariad, Novartis, BMS: Consultancy. Neuberg:Synta Pharmaceuticals: Trust owns stock; I am a Trustee Other.

Successful treatment of pediatric plasmacytoid dendritic cell tumors with a contemporary regimen for acute lymphoblastic leukemia

Dendritic cell leukemia (DCL) or hematodermic tumor is an uncommon subtype of acute leukemia. In contrast to adult cases, children tend to have a less aggressive course. The diagnosis of DCL should be considered when its characteristic morphologic features are present and leukemic cells co-express CD4 and CD56. Cases of DCL among pediatric patients have been reported to respond to therapeutic regimens for acute lymphoblastic leukemia, but details regarding the specifics of therapy are lacking.

Analysis of Outcomes of Patients with Blastic Plasmacytoid Dendritic Cell Neoplasm

AbstractAbstract ▪3554▪This icon denotes a clinically relevant abstract Background:Blastic plasmacytoid dendritic cell neoplasm (BPDCN), formerly known as CD4 + CD56 + hematodermic tumor or blastic NK cell lymphoma, is a rare and aggressive hematologic malignancy. Little is known about the outcome of patients (pts) with BPDCN. Methods:We performed a retrospective review of pts age ≥ 18 years of age with a pathological diagnosis of BPDCN. Results:19 pts, diagnosed and treated at our institution between October 1998-January 2011, were identified. There were 16 (84%) males and 3 females with a median age of 56 years (range 20–86 years). Bone marrow (BM) was involved in 13 (68%), skin in 13 (68%), lymph nodes in 5 (26%), and 1 (5%) pt each had disease involving the brain, CSF, uterus/ovary, elbow soft tissue, and pleural fluid. The tumor immunophenotype was: CD4+ (17/17), CD56+ (16/17), and TCL-1+ (9/9). Conventional cytogenetics in10 pts showed: diploid (5 pts), complex karyotype (4 pts), and del (12p13) (1pt). The median complete blood count was: WBC 6.7 × 109/L (1.7–76.5), Hb 13.3 g/dL (8.3–17.0), and platelet count 107 × 109/L (44–294). The median BM blast count was 40% (0–77). Therapy for these pts was: 13 (68%) first-line therapy with Hyper-CVAD alternating with high-dose methotrexate (MTX) and cytarabine (in 1 pt following one cycle of CHOP), 4 (21%) CHOP, 1 (5%) oral MTX (1), and 1 (5%) interferon-based therapy. 4 (21%) pts received radiation (XRT) as part of their therapy. The median follow-up time was 13 months (5–25 mo). The median number of chemotherapy regimens was 1 (1–6). Complete remission (CR) was achieved in 12 pts. The median CR1: 18 mo (4–39 mo). Median overall survival (OS) was 29 mo (1–44 mo). 14 (74%) pts died, with the most common cause of death being multi-organ failure (8 pts).For 6 (32%) pts without BM involvement at diagnosis; all 6 had skin involvement. Comparison of pts with BM involvement versus those with skin only showed no differences. For pts with BM disease, the median OS, and median CR1 were 23 mo (1–44 mo), 21 mo (4–39 mo), respectively. For pts with skin only disease, the median OS and median CR1 were 29 mo (8–31 mo), 18 mo (8–23 mo), respectively, p=0.82 (OS), p=0.78 (CR1).6 pts (32%) received stem cell transplant (SCT) (3 autologous, 2 allogeneic,1 cord blood). The median OS for pts receiving SCT (n=6) was 31 mo (10–40 mo) versus a median OS for non-SCT group (n=13) of 29 mo (1–44), p= 0.82.13 pts (68%) received HCVAD as part of first line therapy: the median OS was 29 mo (1–44 mo) and median CR1: 21 mo (4–39 mo). Eleven (92%) of 12 of these pts achieved CR1; 1 pt did not achieve CR1 (died, pneumonia, day 15). Conclusions:Despite intensive multi-agent chemotherapy and SCT, response rates are low and survival is short for pts with BPDCN. A better understanding of the biologic basis of this disease and novel treatment approaches are needed. Disclosures:No relevant conflicts of interest to declare.

Blastic Plasmacytoid Dendritic Cell Neoplasm With Leukemic Progression

Blastic plasmacytoid dendritic cell neoplasm (BPDN), previously described as blastic NK cell lymphoma and CD4 +/ CD56 + hematodermic neoplasm is an aggressive hematologic malignancy with poor prognosis. We report a patient with BPDN who developed multiple recurrences and eventually leukemic progression. The patient died of disease 31 months after initial diagnosis. Long term survival for BPDN is poor despite multiple regimens of chemotherapy and bone marrow stem cell transplant. doi: http://dx.doi.org/10.4021/jmc829w

Blastic Plasmacytoid Dendritic Cell Neoplasm: A Report of 2 Cases

Blastic plasmacytoid dendritic cell neoplasm is a recently classified aggressive hematodermic neoplasm derived from plasmacytoid dendritic cells. We describe two cases of this neoplasm, one a 15year old child and other a 65year male. The diagnosis was made by evaluating the detailed clinical history, morphology and flow cytometric findings. The diagnosis is rendered difficult owing to common morphological and flow cytometric overlaps. The neoplasms were characterized by skin and soft tissue involvement and strong CD4/CD56 positivity. These neoplasms are highly aggressive and have many diagnostic overlaps. Strong suspicion and detection will help in early therapeutic interventions.

Analysis of outcomes of patients (pts) with blastic plasmacytoid dendritic cell neoplasm (BPDCN).

6578 Background: BPDCN, formerly known as CD4 + CD56 + hematodermic tumor or blastic NK cell lymphoma, is a rare and aggressive hematologic malignancy. Little is known about outcomes of pts with BPDCN. Methods: We conducted a retrospective review of pts meeting following criteria: pathological diagnosis of BPDCN confirmed by an experienced hematopathologist and age ≥ 18. Results: 13 pts, diagnosed October 1998-July 2011, were identified. Median (med) age: 62 years (range 20-86 years), 12 (92%) were male. Bone marrow (BM) involved in 9 (69%), skin 8 (62%), lymph nodes 5 (38%), brain 1 and uterine/ovarian 1 pt. Immunophenotype by flow cytometry: CD4+ (11/11 pts), CD56+ (10/11 pts), TCL-1+ (4/4 pts). Karyotype (8 pts): del(12) (1pt), complex (2), and diploid (5). Med CBC: WBC 5.8 x 109/L (1.7-76.5), Hb 12.3 g/dL (8.3-17.0), platelet 107 x 109/L (44-255). Med BM blasts: 22% (0-77). 10 pts received first-line therapy with Hyper-CVAD alternating with high-dose methotrexate(MTX) and cytarabine (HCVAD) (in 1 pt following one cycle of CHOP), CHOP (2), oral MTX (1). Med follow-up time: 9 months (mo) (2-14 mo). Med number chemotherapy regimens: 1 (1-5). Complete remission (CR) in 10 pts. Med CR1: 19 mo (4-39 mo). Med overall survival (OS) 29 mo (1-44 mo). 9 pts have died, unknown cause (3), multi-organ failure (6). 10 pts received HCVAD as part of first line therapy: med OS: 29 mo (1-44 mo), med CR1: 21 mo (4-39 mo), 9/10 (90%) pts achieved CR1; 1 pt did not achieve CR1 (died, pneumonia, day 15). 9 pts (69%) had BM involvement (7 with other organs involved besides BM). 4 (31%) pts had no BM involvement; all 4 of these pts had skin involvement only. Med OS, med CR1 of pts with BM involvement: 23 mo (1-44mo), 22 mo (4-39mo), respectively. Med OS, med CR1 of skin only pts: 29 mo (2-31 mo), 7 mo (6-19 mo), respectively, p=not significant. 4 pts received stem cell transplant (SCT) (2 allogeneic ,2 autologous). Med OS for pts receiving SCT (n=4) was 31 mo(8-31 mo) versus med OS for non-SCT group (n=9) of 29 mo (1-44), p=not significant. Conclusions: Despite intensive multi-agent chemotherapy and SCT, response rates are low and survival is short. Better understanding of the biologic basis of this disease and novel treatment approaches for treatment of BPCDN are crucial.

Blastic plasmacytoid dendritic cell neoplasm: a report of four cases and review of the literature

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. 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. A collaborative work between dermatologists and onco-haematologists is essential to give patients the best chance of complete and long-term response.