Blastic Plasmacytoid Dendritic Cell Neoplasm Developed in Chronic Myeloid Leukemia in Molecular Remission During a Four-Year Treatment-Free Interval After Six Years of Dasatinib Treatment.

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare hematological malignancy affecting multiple sites, most commonly the skin. About 10-20% of BPDCN cases are accompanied by hematological neoplasms. A 71-year-old male was diagnosed with chronic myeloid leukemia in the chronic phase (CML-CP) 11 years prior (at 60 years of age), and dasatinib treatment was initiated. A major molecular response (MMR) was achieved 18 months after diagnosis, and the molecular response (MR)4.0 lasted beyond 36 months. Due to pancytopenia, dasatinib was discontinued at 74 months, but the CML-CP remained undetectable. One hundred and twenty-two months after the diagnosis, the patient presented with cutaneous lesions on the forehead and abdomen. Immunological and histological analyses of the skin biopsy showed infiltration of atypical cells from the deep epidermis to the entire dermis, expressing clusters of differentiation (CD) 4, CD56, and CD123 without any other markers. The same cells were observed in bone marrow samples. BPDCN was diagnosed, followed by chemotherapy and possibly autologous or allogeneic hematopoietic stem cell transplantation (HSCT). To the best of our knowledge, this is the first case report of the development of BPDCN in a patient with CML in molecular remission. Further studies are required to clarify the pathogenesis of BPDCN in patients with hematological malignancies in remission.

Flow Cytometry Profiling of Plasmacytoid Dendritic Cell Neoplasms.

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.

A rare case of Blastic plasmacytoid dendritic cell neoplasm with gynecologic presentation.

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare hematological malignancy characterized by the proliferation of plasmacytoid dendritic cells with a blast-like appearance. It usually presents in elderly people, and clinical manifestations include nodular blue-violet skin lesions, bone marrow infiltration and, less frequently, extramedullary involvement. Gynecological manifestation (breast mass and exocervical lesion) is an unusual and rare presentation. Herein, we report the case of a 51-year-old woman patient who presented with a history of a rapidly growing and bleeding breast mass, along with a decline in general health. Notably, the disease had multifocal involvement, affecting the breast, uterine cervix, and cervical lymphadenopathy. Biopsies were performed on the breast mass and cervical lesion. Histopathological examination showed a diffuse lymphoid proliferation. The neoplastic cells show immunoreactivity for CD45 and CD56. The myelogram showed a 50 % excess of blasts with a heterogeneous appearance with the presence of cells that could suggest dendritic plasmacytoid cells. Bone marrow immunophenotyping showed the presence of blast-like cells that were positive for CD4, CD56, CD123, which supported the diagnosis of BPDCN. Despite initiating chemotherapy, the patient's condition rapidly deteriorated, highlighting the aggressive nature of BDCP. This case underscores the importance of early detection and the need for further research to improve outcomes for this rare condition.

A systematic literature review of 74 Chinese blastic plasmacytoid dendritic cell neoplasm patients.

Background: Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare and aggressive hematological cancer. Due to its low incidence, researchers struggle to gather sufficient prospective data to inform clinical treatment. Objectives: We sought to summarize the clinical characteristics and current treatment methods of BPDCN and provide more specific guidance on treatment options. Design: A systematic literature review using data from 74 Chinese BPDCN patients. Date resources and methods: We retrospectively analyzed the clinical manifestations, treatment response, survival outcomes, and prognostic factors of six BPDCN patients treated at the First Affiliated Hospital of Zhengzhou University and 68 patients described in 28 articles published in the China Knowledge Network database since 2019. Results: In Chinese patients, the disease occurred with a male-to-female ratio of 2.52 and a median age of onset of 50 years in adults and 10 years in pediatric patients. Immunohistochemical analysis revealed distinctive immune phenotypes of BPDCN cells, characterized by high expression levels of CD4, CD56, CD123, and HLA-DR, while showing minimal to no expression of myeloperoxidase (MPO), CD20, and CD79a. There was no significant difference in the initial complete remission (CR) rate, relapse rate, and the overall survival (OS) time of patients receiving acute myeloid leukemia-like, acute lymphocytic leukemia-like, or non-Hodgkin's lymphoma-like chemotherapy regimens. Univariate analysis identified CD3 expression, male gender, and central nervous system infiltration as hazardous factors. In multivariate analysis, age proved to be an independent prognostic indicator, indicating better prognosis and longer OS time in younger patients. Notably, hematopoietic stem cell transplantation (HSCT) emerged as a significant factor in improving the survival outcomes for individuals diagnosed with BPDCN. However, further investigation is needed to explore the role of HSCT and the best timing for its implementation in pediatric BPDCN patients. Conclusion: Administering HSCT during the initial CR state following inductive chemotherapy might extend the OS and improve the prognosis of patients with BPDCN.

Systematic literature review of 74 BPDCN patients Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare, aggressive neoplasm that derives from the precursors of plasmacytoid dendritic cell (pDC), accounting for 0.44% of hematological malignancy. Although CD123 targeted therapy has been implemented in the treatment of BPDCN, but a unique complication, capillary leak syndrome presents a therapeutic challenge, and retrospective analysis of conventional chemotherapy regimens is of irreplaceable importance for patients cannot tolerate CD123 targeted therapy. For the first time, we conduced retrospective analysis of large-scale clinical cases based on Chinese patients, and found that age and hematopoietic stem cell transplantation (HSCT) were two independent prognostic factors of BPDCN. In conclusion, younger patients had longer overall survival (OS) time and better prognosis. Combining HSCT in the initial complete remission state significantly prolonged the OS time and improved survival outcomes of BPDCN patients.

Blastic plasmacytoid dendritic cell neoplasm: a single-center experience. Clinical characterization, mutational landscape, and clinical outcome of patients undergoing hematopoietic stem cell transplantation intensive therapy.

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare and aggressive hematodermic neoplasm usually involving the skin. In this retrospective case series, 10 cases of BPDCN were identified, 90% of which had skin involvement and exhibited predominantly violaceous nodules and/or bruise-like plaques. Skin lesions showed diffuse or nodular dermal-based infiltrates of intermediate sized blasts with a grenz zone. Tumor immunophenotyping was CD4(+), CD56(+), CD123(+) and CD303(+). The most frequently mutated genes according to targeted next-generation sequencing were TET2 (3/7) and NRAS (2/7). Multiagent chemotherapy (CT) was administered as first-line therapy, and a total of 5 patients underwent allogenic hematopoietic stem cell transplantation (allo-HSCT). Better outcomes were observed in younger patients and those treated with acute lymphoblastic leukemia (ALL)-like CT followed by allo-HSCT. This study shows the clinical range of cutaneous lesions of BPDCN. Despite the absence of a gold standard therapy, patients treated with myeloablative intensive regimens and allo-HSCT seem to have a more favorable prognosis.

Spontaneous Remission of Blastic Plasmacytoid Dendritic Cell Neoplasm: A Case Report.

Spontaneous remissions (SRs) in blastic plasmacytoid dendritic cell neoplasms (BPDCNs) are infrequent, poorly documented, and transient. We report a 40-year-old man presenting with bycitopenia and soft tissue infection. The bone marrow exhibited 3% abnormal cells. Immunophenotyping of these cells revealed the antigens CD45+ (dim), CD34+, CD117+, CD123+ (bright), HLA-DR+ (bimodal), CD56+ (bright), CD33+, CD13+, CD2+, and CD22+ (dim) and the partial expression of the CD10+, CD36+, and CD7+ antigens. All other myeloid, monocytic, and lymphoid antigens were negative. Genetic studies showed a complex karyotype and mutations in the TP53R337C and KRASG12D genes. On hospital admission, the patient showed a subcutaneous nodule on the right hand and left lower limb. Flow cytometry multiparameter (FCM) analysis showed the presence of 29% abnormal cells with the previously described immunophenotype. The patient was diagnosed with BPDCN. The patient was treated with broad-spectrum antibiotics for soft tissue infection, which delayed therapy for BPDCN. No steroids or chemotherapeutic or hypomethylating agents were administered. His blood cell counts improved and skin lesions disappeared, until the patient relapsed five months after achieving spontaneous remission. About 60% of abnormal cells were identified. No changes in immunophenotype or the results of genetic studies were observed. The patient underwent a HyperCVAD chemotherapy regimen for six cycles. Consolidation therapy was performed via allogeneic bone marrow transplantation with an HLA-unrelated donor. One year after the bone marrow transplant, the patient died due to the progression of his underlying disease, coinciding with a respiratory infection caused by SARS-CoV-2. In the available literature, SRs are often linked to infections or other stimulators of the immune system, suggesting that powerful immune activation could play a role in controlling the leukemic clone. Nevertheless, the underlying mechanism of this phenomenon is not clearly understood. We hypothesize that the immune system would force the leukemic stem cell (LSC) to undergo a state of quiescence. This loss of replication causes the LSC progeny to die off, resulting in the SR of BPDCN.

Thiotepa-busulfan-fludarabine-based conditioning as a promising approach prior to allogeneic hematopoietic stem cell transplantation in patients with blastic plasmacytoid dendritic cell neoplasm.

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare and aggressive myeloid malignancy associated with a poor prognosis. Although allogeneic hematopoietic stem cell transplantation (allo-HSCT) has emerged as a potential treatment strategy for BPDCN, standardized conditioning regimens remain lacking. In this manuscript, we present two cases of BPDCN that were treated with a thiotepa-busulfan-fludarabine (TBF)-based conditioning regimen prior to allo-HSCT. Both cases demonstrated complete remission post-transplantation, sustained donor chimerism, and remission maintenance, suggesting the potential efficacy of the TBF conditioning regimen for BPDCN transplantation. Given the small sample size in our study, we emphasize caution and advocate for larger studies to confirm the efficacy of TBF in the treatment of BPDCN.

[Clinical Characteristics of CD4-CD56+ Blastic Plasmacytoid Dendritic Cell Neoplasm].

OBJECTIVE: To explore the clinical manifestations, pathological features, immunophenotype, as well as diagnosis, treatment and prognosis of patients with CD4-CD56+ blastic plasmacytoid dendritic cell neoplasm (BPDCN), in order to further understand the rare disease. METHODS: The clinical data, laboratory examinations and treatment regimens of two patients with CD4-CD56+ BPDCN in the First Affiliated Hospital of Wannan Medical College were retrospectively analyzed. RESULTS: The two patients were both elderly males with tumor involved in skin, bone marrow, lymph nodes, etc. Immunohistochemical results of skin lesions showed that both CD56 and CD123 were positive, while CD4, CD34, TdT, CD3, CD20, MPO and EBER were negative. Flow cytometry of bone marrow demonstrated that CD56, CD123, and CD304 were all positive, while specific immune markers of myeloid and lymphoid were negative. Two patients were initially very sensitive to acute lymphoblastic leukemia or lymphomatoid chemotherapy regimens, but prone to rapid relapse. The overall survival of both patients was 36 months and 4 months, respectively. CONCLUSION: CD4-CD56+ BPDCN is very rare and easily misdiagnosed as other hematological tumors with poor prognosis. Acute lymphoblastic leukemia or lymphomatoid therapy should be used first to improve the poor prognosis.

Simultaneous blastic plasmacytoid dendritic cell neoplasm and myelofibrosis: A case report.

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is an extremely rare and aggressive tumor with an unknown pathogenesis. Myelofibrosis (MF) is a type of myeloproliferative neoplasm. MF can be secondary to several hematological malignancies, including chronic myeloid leukemia, myelodysplastic syndrome and hairy cell leukemia. In the present report, a rare case of BPDCN secondary to MF is described. A 70-year-old male patient developed a large purplish-red rash with recurrent symptoms. BPDCN was confirmed by immunohistochemistry of a biopsy specimen and flow cytometry of bone marrow cells. Bone marrow histopathology revealed MF. Next-generation sequencing of peripheral blood revealed mutations in the Tet methylcytosine dioxygenase 2 and NRAS proto-oncogene GTPase genes. The patient underwent one cycle of chemoimmunotherapy, but the condition progressed, an infection developed and the patient eventually died. The present case suggests that BPDCN can occur in conjunction with MF and that the prognosis of such patients is poor. Pathological examination and genetic testing aided in the diagnosis and treatment. This case emphasizes the need to raise awareness of BPDCN among clinicians and to be alert to the potential for fatal infection in patients with BPDCN combined with MF following myelosuppression triggered during chemotherapy.

Tagraxofusp, a first-in-class CD123-targeted agent: Five-year postapproval comprehensive review of the literature.

Tagraxofusp is a first-in-class CD123-directed conjugate of an amended diphtheria toxin platform and recombinant interleukin 3. Binding and subsequent internalization of the drug result in cell death via disruption of intracellular protein synthesis. CD123 is a surface marker that is expressed in several hematological malignancies, especially blastic plasmacytoid dendritic cell neoplasm (BPDCN), where its expression is ubiquitous. A pivotal study of tagraxofusp in BPDCN resulted in its approval for the treatment of BPDCN, the first treatment approved for this indication. Since the introduction of tagraxofusp, research has focused on the management of adverse effects, combination therapy to improve outcomes in fit patients, and dosing and combination strategies to mitigate toxicities while preserving efficacy, especially among older patients. The successful targeting of CD123 in BPDCN has also encouraged research into a variety of other CD123-positive hematological neoplasms, including acute myeloid leukemia (AML), and informed the development of other novel agents targeting CD123. This review examines the clinical data leading to the development and approval of tagraxofusp in BPDCN, how it is being used in combination to improve outcomes in BPDCN and AML, and its developing role in other hematological malignancies.

Diagnóstico clínico-patológico de la neoplasia de células dendríticas plasmocitoides blásticas: reporte de 3 casos / Clinicopathological diagnosis of blastic plasmacytoid dendritic cell neoplasm: Report of three cases

La neoplasia de células dendríticas plasmocitoides blásticas (NCDPB) es una enfermedad de baja incidencia y muy mal pronóstico, que con gran frecuencia afecta a la piel, pudiendo ser el primer signo clínico de la enfermedad. Se presentan 3 casos en los que la primera manifestación de la enfermedad fueron lesiones cutáneas. Se describe el cuadro clínico, los hallazgos histopatológicos e inmunohistoquímicos, así como los estudios de extensión y las características moleculares de las 3 neoplasias. Uno de los pacientes permanece en un ensayo clínico con IMGN632, una molécula dirigida contra CD123, mientras que los otros 2 pacientes fallecieron tras distintos regímenes terapéuticos. La NCDPB es una entidad de diagnóstico complejo. Esto, unido a su mal pronóstico, obligan a una comunicación clínico-patológica estrecha que acelere su diagnóstico y ofrezca alternativas terapéuticas precoces con fármacos dirigidos contra dianas moleculares específicas de esta entidad. (AU)

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare disease with a poor prognosis. It frequently affects the skin; indeed, dermal lesions may be the first clinical manifestation. We report three cases of BPDCN where the patients presented with skin lesions and describe the clinical, histopathological and immunohistochemical findings, its molecular characteristics and metastatic work-up. One of the patients remains in a clinical trial with IMGN632, a molecule directed against CD123, while the other two patients died after different therapeutic regimens. BPDCN is a complex diagnostic challenge which, together with its poor prognosis, requires close clinical-pathological cooperation in order to accelerate its diagnosis and offer early therapeutic alternatives with drugs directed against specific molecular targets. (AU)

Diagnóstico clínico-patológico de la neoplasia de células dendríticas plasmocitoides blásticas: reporte de 3 casos / Clinicopathological diagnosis of blastic plasmacytoid dendritic cell neoplasm: Report of three cases

La neoplasia de células dendríticas plasmocitoides blásticas (NCDPB) es una enfermedad de baja incidencia y muy mal pronóstico, que con gran frecuencia afecta a la piel, pudiendo ser el primer signo clínico de la enfermedad. Se presentan 3 casos en los que la primera manifestación de la enfermedad fueron lesiones cutáneas. Se describe el cuadro clínico, los hallazgos histopatológicos e inmunohistoquímicos, así como los estudios de extensión y las características moleculares de las 3 neoplasias. Uno de los pacientes permanece en un ensayo clínico con IMGN632, una molécula dirigida contra CD123, mientras que los otros 2 pacientes fallecieron tras distintos regímenes terapéuticos. La NCDPB es una entidad de diagnóstico complejo. Esto, unido a su mal pronóstico, obligan a una comunicación clínico-patológica estrecha que acelere su diagnóstico y ofrezca alternativas terapéuticas precoces con fármacos dirigidos contra dianas moleculares específicas de esta entidad. (AU)

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare disease with a poor prognosis. It frequently affects the skin; indeed, dermal lesions may be the first clinical manifestation. We report three cases of BPDCN where the patients presented with skin lesions and describe the clinical, histopathological and immunohistochemical findings, its molecular characteristics and metastatic work-up. One of the patients remains in a clinical trial with IMGN632, a molecule directed against CD123, while the other two patients died after different therapeutic regimens. BPDCN is a complex diagnostic challenge which, together with its poor prognosis, requires close clinical-pathological cooperation in order to accelerate its diagnosis and offer early therapeutic alternatives with drugs directed against specific molecular targets. (AU)

Treatment of patients with blastic plasmacytoid dendritic cell neoplasm (BPDCN): focus on the use of tagraxofusp and clinical considerations.

BPDCN is an aggressive myeloid malignancy with a poor prognosis. It derives from the precursors of plasmacytoid dendritic cells and is characterized by CD123 overexpression, which is seen in all patients with BPDCN. The CD123-directed therapy tagraxofusp is the only approved treatment for BPDCN; it was approved in the US as monotherapy for the treatment of patients aged ≥2 years with treatment-naive or relapsed/refractory BPDCN. Herein, we review the available data supporting the utility of tagraxofusp in treating patients with BPDCN. In addition, we present best practices and real-world insights from clinicians in academic and community settings in the US on how they use tagraxofusp to treat BPDCN. Several case studies illustrate the efficacy of tagraxofusp and discuss its safety profile, as well as the prevention, mitigation, and management of anticipated adverse events.

Azacitidine maintenance therapy for blastic plasmacytoid dendritic cell neoplasm allograft: A case report.

BACKGROUND: Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare, highly invasive malignant neoplasm. There is no universally accepted standard of care because of its rarity and the dearth of prospective research. It is still challenging for some patients to achieve persistent clinical remission or cure, despite the success of allogeneic hematopoietic stem cell transplantation (allo-HSCT), indicating that there is still a significant recurrence rate. We report a case of prevention of BPDCN allograft recurrence by azacitidine maintenance therapy and review the relevant literature. CASE SUMMARY: We report a 41-year-old man with BPDCN who was admitted to hospital due to skin sclerosis for > 5 mo' duration. BPDCN was diagnosed by combined clinical assessment and laboratory examinations. Following diagnosis, the patients underwent induction consolidation chemotherapy to achieve the first complete remission, followed by bridging allo-HSCT. Post-transplantation, azacitidine (75 mg/m2 for 7 d) was administered as maintenance therapy, with repeat administration every 4-6 wk and appropriate extension of the chemotherapy cycle. After 10 cycles, the patient has been disease free for 26 mo after transplantation. Regular assessments of bone marrow morphology, minimal residual disease, full donor chimerism, Epstein-Barr virus, and cytomegalovirus all yielded normal results with no abnormalities detected. CONCLUSION: Azacitidine may be a safe and effective maintenance treatment for BPDCN following transplantation because there were no overt adverse events during the course of treatment.

Low-dose venetoclax combined with azacitidine for blastic plasmacytoid dendritic cell neoplasm: a case report and literature review.

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare hematologic malignancy that is highly aggressive with a poor prognosis. There is no standard treatment for BPDCN. Although conventional chemotherapies are usually sensitive in the initial therapy, relapse and drug resistance are inevitable within a short duration. Targeted therapies have enlightened new prospects for the treatment of BPDCN, especially for those in a frail state and intolerable to standard chemotherapies or hematopoietic stem cell transplantation. Here, we report an 82-year-old man diagnosed with cutaneous-limited BPDCN. Considering the old age and limited involvement of the tumor, we reduced the dosage of venetoclax. His skin lesions subsided significantly after 1 cycle of azacytidine (100 mg d1-7) combined with reduced doses of venetoclax (200 mg d1-14). The reduction in the dose of venetoclax avoided severe myelosuppression while achieving satisfactory outcomes. The patient received 2 cycles of therapy with no skin lesions re-occurred for 7 months before relapsing.

[Clinicopathological diagnosis of blastic plasmacytoid dendritic cell neoplasm: Report of three cases]. / Diagnóstico clínico-patológico de la neoplasia de células dendríticas plasmocitoides blásticas: reporte de 3 casos.

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare disease with a poor prognosis. It frequently affects the skin; indeed, dermal lesions may be the first clinical manifestation. We report three cases of BPDCN where the patients presented with skin lesions and describe the clinical, histopathological and immunohistochemical findings, its molecular characteristics and metastatic work-up. One of the patients remains in a clinical trial with IMGN632, a molecule directed against CD123, while the other two patients died after different therapeutic regimens. BPDCN is a complex diagnostic challenge which, together with its poor prognosis, requires close clinical-pathological cooperation in order to accelerate its diagnosis and offer early therapeutic alternatives with drugs directed against specific molecular targets.

A blastic plasmacytoid dendritic cell neoplasm-like immunophenotype is negatively associated with CEBPA bZIP mutation and predicts unfavorable prognosis in acute myeloid leukemia.

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare and aggressive myeloid malignancy which characteristically expresses an atypical phenotype including CD123+, CD56+, and CD4+. We are aimed to investigate the clinical and prognostic characteristics of AML patients exhibiting BPDCN-like immunophenotype and provide additional insights for risk stratification of AML. A total of 241 newly diagnosed AML patients were enrolled in this retrospective study and categorized into BPDCN-like positive (n = 125)/negative (n = 116) groups, determined by the present with CD123+ along with either CD56+ or CD4+, or both. Subsequently, an analysis was conducted to examine the general clinical characteristics, genetic profiles, and prognosis of the two respective groups. Patients with BPDCN-like immunophenotype manifested higher frequencies of acute myelomonocytic leukemia and acute monoblastic leukemia. Surprisingly, the presence of the BPDCN-like immunophenotype exhibited an inverse relationship with CEBPA bZIP mutation. Notably, patients with BPDCN-like phenotype had both worse OS and EFS compared to those without BPDCN-like phenotype. In the CN-AML subgroups, the BPDCN-like phenotype was associated with worse EFS. Similarly, a statistically significant disparity was observed in both OS and EFS within the favorable-risk subgroup, while only OS was significant within the adverse-risk subgrouMoreover, patients possessing favorable-risk genetics without BPDCN-like phenotype had the longest survival, whereas those who had both adverse-risk genetics and BPDCN-like phenotype exhibited the worst survival. Our study indicated that BPDCN-like phenotype negatively associated with CEBPA bZIP mutation and revealed a significantly poor prognosis in AML. Moreover, the 2022 ELN classification, in combination with the BPDCN-like phenotype, may better distinguish between different risk groups.

Ulcerating skin lesions from blastic plasmacytoid dendritic cell neoplasm responding to low-dose radiotherapy-a case report and literature review.

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare hematologic malignancy that can manifest with skin nodules and erythematous plaques. In most cases BPDCN progresses rapidly, causing multiple skin lesions and also affecting internal organs and bone marrow, warranting initiation of systemic therapies or hematopoietic stem cell transplantation (HCT). Although not curative, radiotherapy for isolated lesions might be indicated in case of (imminent) ulceration and large or symptomatic lesions. To this end, doses of 27.0-51.0 Gy have been reported. Here, we present the case of an 80-year-old male with BPDCN with multiple large, nodular, and ulcerating lesions of the thorax, abdomen, and face. Low-dose radiotherapy of 2â€¯× 4.0 Gy was administered to several lesions, which resolved completely within 1 week with only light residual hyperpigmentation of the skin in affected areas and reliably prevented further ulceration. Radiotoxicity was not reported. Therefore, low-dose radiotherapy can be an effective and low-key treatment in selected cases of BPDCN, especially in a palliative setting, with a favorable toxicity profile.

Diagnostic management of blastic plasmacytoid dendritic cell neoplasm (BPDCN) in close interaction with therapeutic considerations.

Blastic plasmacytoid dendritic cell neoplasm (BPDCN), a rare malignancy derived from plasmacytoid dendritic cells, can mimic both acute leukemia and aggressive T-cell lymphoma. Therapy of this highly aggressive hematological disease should be initiated as soon as possible, especially in light of novel targeted therapies that have become available. However, differential diagnosis of BPDCN remains challenging. This retrospective study aimed to highlight the challenges to timely diagnoses of BPDCN. We documented the diagnostic and clinical features of 43 BPDCN patients diagnosed at five academic hospitals from 2001-2022. The frequency of BPDCN diagnosis compared to AML was 1:197 cases. The median interval from the first documented clinical manifestation to diagnosis of BPDCN was 3 months. Skin (65%) followed by bone marrow (51%) and blood (45%) involvement represented the most common sites. Immunophenotyping revealed CD4 + , CD45 + , CD56 + , CD123 + , HLA-DR + , and TCL-1 + as the most common surface markers. Overall, 86% (e.g. CD33) and 83% (e.g., CD7) showed co-expression of myeloid and T-cell markers, respectively. In the median, we detected five genomic alterations per case including mutational subtypes typically involved in AML: DNA methylation (70%), signal transduction (46%), splicing factors (38%), chromatin modification (32%), transcription factors (32%), and RAS pathway (30%), respectively. The contribution of patients (30%) proceeding to any form of upfront stem cell transplantation (SCT; autologous or allogeneic) was almost equal resulting in beneficial overall survival rates in those undergoing allogeneic SCT (p = 0.0001). BPDCN is a rare and challenging entity sharing various typical characteristics of other hematological diseases. Comprehensive diagnostics should be initiated timely to ensure appropriate treatment strategies.

A CD56- immunoblastoid variant of blastic plasmacytoid dendritic cell neoplasm.

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is an aggressive malignant hematologic neoplasm arising from plasmacytoid dendritic cells. It is a very rare tumor that constitutes less than 0.1% of all hematologic malignancies. Most patients with BPDCN present clinically with cutaneous lesions as the first sign of disease. Immunophenotypic variability with aberrant marker profiles has been reported. We report a case of a transcription factor 4 (TCF-4) + BPDCN, with negative CD56 expression in an 85-year-old woman with multiple skin nodules. A punch biopsy revealed a diffuse, monomorphous, and non-epidermotropic cell infiltrate involving the entire dermis. The infiltrate was composed of intermediate-sized cells with immunoblastoid morphology, which is an unusual morphologic variant. The neoplastic cells were strongly positive for CD45 and co-expressed CD4, CD123, TCF-4, BCL-2, and CD10. The Ki-67 proliferative rate was very high (90%). Negative immunostains included CD56, an unusual finding in BPDCN. This case illustrates the challenges encountered in the diagnosis of this entity, particularly in unusual morphologic variants and phenotypes. The elucidation of molecular signatures and development of targeted therapies for its management have been recently introduced and differ from acute myeloid leukemias. Hence, accurate diagnosis of BPDCN is critical for dermatopathologists.