CASE REPORT: Diagnostic Challenge in a 43-Year-Old Female - Acute Monocytic Leukemia (AML-M5) Presenting as Blastic Plasmacytoid Dendritic Cell Neoplasm

CASE REPORT: Diagnostic Challenge in a 43-Year-Old Female - Acute Monocytic Leukemia (AML-M5) Presenting as Blastic Plasmacytoid Dendritic Cell Neoplasm | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Case Report CASE REPORT: Diagnostic Challenge in a 43-Year-Old Female - Acute Monocytic Leukemia (AML-M5) Presenting as Blastic Plasmacytoid Dendritic Cell Neoplasm Alhejairi Rehab, Kaixin Li, Ruaa Ahmed Alnour, Yongfeng Chen, and 1 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7327413/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 12 You are reading this latest preprint version Abstract Statement of the Problem Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare and aggressive hematologic malignancy that originates from plasmacytoid dendritic cells (pDCs). BPDCN typically presents with skin lesions, which can appear as bruise-like patches, nodules, or plaques. These lesions are often violaceous and can be found on the face, trunk, and extremities. The disease can also involve the bone marrow, blood, lymph nodes, and other organs, including the central nervous system. BPDCN has a poor prognosis, with a median overall survival of less than two years in many cases. The purpose of this study We present a comprehensive case of BPDCN in a 43-year-old female patient. The patient presented with facial swelling, chest papules and nodules. She experienced skin tightness for two months. We performed detailed histopathological examinations including H&E staining. We analyzed bone marrow findings and immunophenotyping results. This case highlights the diagnostic challenges and aggressive nature of BPDCN. Conclusion This case demonstrates that AML-M5 can closely mimic BPDCN clinically and histologically, emphasizing the critical role of comprehensive immunophenotyping in reaching the correct diagnosis. Blastic plasmacytoid dendritic cell neoplasm BPDCN Myeloid sarcoma Histopathology H&E staining Figures Figure 1 Figure 2 Figure 3 Introduction Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a distinct hematologic malignancy. It shows components of both myeloid and lymphoid cancers. BPDCN presents an aggressive clinical course. It creates a challenging therapeutic trajectory for patients [ 1 ] . BPDCN affects four principal organ systems. These include cutaneous locations, bone marrow/blood, lymph nodes, and the central nervous system. Cerebrospinal fluid (CSF) involvement occurs frequently [ 2 ] . The diagnostic triad consists of specific markers. These include IL-3Rα surface marker (CD123+), CD4+, and CD56+. This combination represents the most recognized diagnostic criterion for BPDCN. Additional markers enhance diagnostic accuracy. TCL1, TCF4, and CD303 help achieve 100% specificity in detecting this rare cancer [ 3 ] . BPDCN shares molecular features with myeloid malignancies. These include myelodysplastic syndrome (MDS), chronic myelomonocytic leukemia (CMML), and acute myeloid leukemia (AML). Common mutations include TET2, ASXL1, RAS, and splicing factor mutations like ZRSR2 [ 4 ] . Risk factors for BPDCN include several elements. Male sex increases risk. Ultraviolet light exposure contributes to development. Smoking is another risk factor. Genetic alterations like TET2 and RAS mutations occur more frequently in elderly patients [ 5 ] . Case presentation A 43-year-old female patient presented to our department. She had no known medical illnesses. No allergies were documented. The patient complained of facial edema persisting for two months. She noticed papules and nodules on her chest. She experienced a constricted sensation in affected areas. No prior history of hypertension existed. She had no cardiovascular disease. Physical examination revealed significant findings. Facial edema was prominent. The skin showed rigidity. Multiple papules and nodules were visible. Numerous nodules were located on the chest. The lesions appeared violaceous. They were firm to palpation. Physical examination findings are shown in Fig. 1 . Laboratory Findings Basic laboratory work revealed several abnormalities. Monocyte levels were elevated. The patient showed moderate anemia. Erythrocyte sedimentation rate (ESR) was increased. Blood Smear Analysis Giant and late-stage erythroblasts were present. White blood cell count was elevated. Immature monocytes accounted for 53% of cells. Immature granulocytes showed morphological characteristics consistent with bone marrow findings. Mature red cells exhibited similar morphology to bone marrow smear. Platelets showed scattered distribution. They were relatively easy to identify. Complete Blood Count Results (October 2024): WBC: 36.13 × 10⁹/L (elevated) RBC: 1.88 × 10¹²/L (decreased) Hemoglobin: 64 g/L (decreased) Platelets: 109 × 10⁹/L (normal) Neutrophils: 12.44 × 10⁹/L (elevated) Lymphocytes: 7.12 × 10⁹/L Monocytes: 16.49 × 10⁹/L (markedly elevated) Neutrophil percentage: 34.4% Lymphocyte percentage: 19.7% Monocyte percentage: 45.6% (elevated) Eosinophil percentage: 0.2% Nucleated RBC: 0.25 × 10⁹/L (elevated) NRBC percentage: 0.7% Cytochemical Staining Results AKP (Alkaline Phosphatase) : Variable positivity was observed. Results showed: ++12%, ++11%, +++4% (granular positive), +++3% and +++2% (focal positive). PAS (Periodic Acid-Schiff) : Positive in 95% of cells. Total score was 240. Staining showed coarse and fine granular positivity. Particles were diffusely distributed. Some areas showed finely dispersed granules. Differential Diagnosis Several conditions were considered initially: Epstein-Barr virus-related mononucleosis Cutaneous lymphoma Leprosy Connective tissue disease Skin infection Cutaneous mucinosis Histopathological Examination Skin Biopsies: Skin biopsies were performed from face and neck regions. They were subjected to comprehensive histopathological examination. Gross Findings: Face: Formalin-fixed skin biopsy specimen included skin and subcutaneous tissue. It measured approximately 0.7 cm × 0.4 cm × 0.4 cm. Surface color corresponded to skin tone. Neck: Formalin-fixed skin biopsy specimen included skin and subcutaneous tissue. It measured approximately 1 cm × 0.7 cm × 0.5 cm. Surface color corresponded to skin tone. Microscopic Findings : The subepidermal area showed no distinct infiltration zone. Dermis demonstrated extensive diffuse infiltration by lymphoid-like cells. Nuclear fragmentation was evident. Vesicular nuclei were visible. Special stains were performed: Face biopsy showed PAS negative and Acid-fast stain negative results. Neck biopsy also showed PAS negative and Acid-fast stain negative results. H&E Staining Analysis Hematoxylin and eosin staining revealed characteristic features. The sections demonstrated diffuse infiltration of medium-sized cells throughout the dermis. No grenz zone was observed between epidermis and tumor infiltrate. This finding is typical of aggressive lymphoid malignancies. The tumor cells showed distinct morphology. Nuclei were round to oval with fine chromatin patterns. The cytoplasm appeared moderately abundant with pale eosinophilic quality. Cell borders were indistinct. Mitotic figures were scattered throughout the infiltrate. The infiltrative pattern extended through all dermal layers. It reached the dermal-subcutaneous junction. The overlying epidermis remained intact. No epidermotropism was noted. The surrounding stroma showed minimal inflammatory response. Vascular structures were preserved but compressed by tumor cells. These histopathological features are illustrated in Fig. 2 . Pathological Diagnosis Lymphoproliferative disorder was considered. The findings suggested a process related to the lymphoid or hematopoietic system. Bone Marrow Examination Bone Marrow Smear Findings Bone marrow showed hyperplasia with active cellular proliferation. Granulocyte to erythrocyte ratio was 3.17. Cell Lineage Analysis: Granulocyte Lineage : Comprised 19.0% with reduced proliferation. Myeloblasts constituted 5%. Cells showed varying sizes with mostly round or oval nuclei. Cytoplasm was moderately abundant and blue with occasional purple granules. Mature granulocytes showed nuclear segmentation abnormalities. Erythroid Lineage : Constituted 6% with reduced proliferation. Predominantly intermediate and late-stage erythroblasts were seen. Some showed megaloblastic changes and nuclear abnormalities. Maturing red cells varied in size with morphological irregularities. Megakaryocyte Lineage : 52 megakaryocytes were observed. This included 20 pro-platelet-forming cells. Platelets were scattered. Morphological abnormalities were evident. Monocyte Lineage : Monocyte population was 66.5%. The majority (65.5%) were immature forms. Cells showed variable size, often round or oval. They had pseudopod projections or fine hair-like projections. Cytoplasm was moderately blue-gray with small purple granules. Auer rods were occasionally observed. Nuclei were round or oval with occasional distortion, folding, or indentations. Nuclear chromatin appeared fine. Nucleoli were visible (0–3 per cell). Other Cell Populations : Lymphocytes comprised 8.5%. No significant morphological abnormalities were observed. Bone Marrow Biopsy Two gray-white tissue strips were examined. Each measured approximately 1.2 cm in length and 0.3 cm in diameter. Microscopic Findings The bone marrow biopsy showed diffuse proliferation of immature cells. These cells filled the bone trabeculae. Cells were medium in size with abundant eosinophilic cytoplasm. Nuclei were medium-sized, round or polygonal. Chromatin was fine and granular. Nucleoli were inconspicuous. Other hematopoietic cells were markedly reduced. Special Stains Reticulin stain showed Grade 0 (no significant fibrosis). Pathological Diagnosis Diffuse proliferation of immature cells within bone trabeculae was noted. Findings were consistent with acute leukemia. Immunophenotyping Results Flow cytometry and immunohistochemistry revealed a specific immunophenotype: CD3: Negative CD20: Negative CD123: Negative (unusual for BPDCN) CD4: Positive (focal, moderate intensity) CD79a: Negative ALK (D5F3): Negative Ki-67: 80% positive MPO: Approximately 5% positive CD56: Positive CD30: Negative TIA-1: Negative CD5: Negative CD7: Negative CD8: Negative CD10: Negative CD117: Negative BCL-6: Negative BCL-2: Approximately 60% positive PD1: Negative TCL1: Negative CD11c: Positive CD14: Focal positive CD33: Positive CD34: Negative CD68: Positive CD163: Positive Lysozyme: Positive EBER in situ hybridization: Negative Immunocytochemical Staining Patterns Immunohistochemical analysis revealed a distinct expression profile that supported the diagnosis of acute monocytic leukemia (Fig. 3 ). The monocytic markers CD68, CD163, and lysozyme all showed positive staining in the tumor cells. CD14 demonstrated focal positivity, while CD33 showed diffuse expression. Additional markers included BCL-2 positivity and a high Ki-67 proliferative index. CD4 and CD56 were also positive, while MPO showed minimal expression. Final Diagnosis Based on comprehensive analysis, the diagnosis was acute monocytic leukemia (AML-M5). The initial suspicion of BPDCN was not confirmed due to CD123 negativity and the predominant monocytic features. Discussion BPDCN is a rare hematologic malignancy recently recognized as a distinct entity. It was initially thought to derive from natural killer cells due to CD56 positivity [ 6 ] . The discovery of its origin from plasmacytoid dendritic cell precursors led to current nomenclature. BPDCN was established as a distinct neoplastic entity in the 2008 WHO classification [ 7 ] . The characteristic immunophenotype includes co-expression of specific markers. CD4, CD56, and plasmacytoid dendritic cell markers are essential. These include CD123, BDCA2, TCL1, CD138, CD68, and BCL2. The absence of T-cell, B-cell, myeloid, and NK-cell markers helps confirm diagnosis [ 8 ] . Our case presented diagnostic challenges. The patient showed typical clinical features of BPDCN. Skin involvement with violaceous nodules is characteristic. The aggressive clinical course matched BPDCN behavior. However, immunophenotyping revealed unexpected findings. The H&E staining showed features compatible with hematologic malignancy. Diffuse dermal infiltration without grenz zone is typical. The medium-sized cells with fine chromatin supported this diagnosis. The minimal inflammatory response suggested rapid progression. These findings correlated with the two-month symptom duration. The absence of CD123 expression was unusual for BPDCN. CD123 is considered a hallmark marker. Its negativity, combined with strong monocytic features, redirected the diagnosis. The high percentage of immature monocytes (65.5%) supported AML-M5. The immunophenotype with CD68+, CD163+, and lysozyme positivity confirmed monocytic lineage. The immunohistochemical findings were crucial in establishing the correct diagnosis. The positivity for monocytic markers CD68, CD163, and lysozyme confirmed monocytic differentiation. The focal CD14 expression is typical for acute monocytic leukemia, as this marker can show variable expressions. The presence of CD33 confirmed myeloid lineage, while the minimal MPO expression (approximately 5% as noted in the flow cytometry) is consistent with monocytic rather than granulocytic differentiation. The high Ki-67 index correlated with the aggressive clinical course observed in this patient. BPDCN commonly presents with cutaneous lesions initially [ 9 ] . Patients often receive empirical treatments before diagnosis. Antibiotics or steroids may cause partial regression. This leads to diagnostic delays [ 10 ] . Early skin biopsy is crucial for timely diagnosis. The bone marrow findings in our case were significant. The hypercellular marrow with monocytic predominance was striking. The presence of Auer rods, though occasional, supported AML diagnosis. The cytochemical staining pattern with PAS positivity is typical for monocytic leukemia. Treatment approaches differ significantly between BPDCN and AML-M5. BPDCN often requires lymphoma-type regimens. These include hyper-CVAD, VPDL, or CHOP protocols [ 11 ] . Some groups report improved survival with high-dose chemotherapy and stem cell transplant [ 12 ] . However, median survival remains 12–14 months [ 13 ] . Our case emphasizes the importance of comprehensive evaluation. Clinical presentation alone cannot distinguish BPDCN from other hematologic malignancies. Detailed immunophenotyping is essential. The integration of morphology, immunohistochemistry, and flow cytometry ensures accurate diagnosis. Conclusion We present a case initially suspected as BPDCN based on clinical features. Comprehensive analysis revealed acute monocytic leukemia instead. This case highlights diagnostic challenges in aggressive hematologic malignancies with skin involvement. The absence of CD123 and predominant monocytic features were key diagnostic clues. Early biopsy and complete immunophenotyping are essential for accurate diagnosis and appropriate treatment selection. Declarations Funding This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors. Conflicts of Interest/Competing Interests The authors declare that they have no conflicts of interest or competing interests related to this work. Ethics Approval This case report was conducted in accordance with the Declaration of Helsinki. Ethics approval was obtained from the Ethics Committee of Dermatology Hospital, Southern Medical University, Guangzhou, China. The study was performed in accordance with relevant guidelines and regulations. Consent to Participate / for Publication Ethics Written informed consent for publication of their clinical details and/or clinical images was obtained from the patient. A copy of the consent form is available for review by the Editor of this journal. Availability of Data and Material All data generated or analyzed during this study are included in this published article. Additional data is available from the corresponding author upon reasonable request. Code Availability Not applicable. Authors’ Contributions Alhejairi Rehab and Kaixin Li conceived and designed the study. Alhejairi Rehab performed the clinical examination and collected patient data. Kaixin Li conducted the histopathological examination and H&E staining analysis. Ruaa Ahmed Alnour performed the immunohistochemical staining and flow cytometry analysis. Alhejairi Rehab and Kaixin Li analyzed and interpreted the data. Alhejairi Rehab wrote the initial draft of the manuscript. Yongfeng Chen and Rongyi Chen supervised the study, provided critical revisions to the manuscript, and gave final approval for submission. All authors reviewed and approved the final version of the manuscript. All authors read and approved the final manuscript. References Khoury JD. Blastic plasmacytoid dendritic cell neoplasm. Current hematologic malignancy reports. 2018;13:477–83. 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. 2019;11(5):595. Adimora IJ, Wilson NR, Pemmaraju N. Blastic plasmacytoid dendritic cell neoplasm (BPDCN): A promising future in the era of targeted therapeutics. Cancer. 2022;128(16):3019–26. Ohgami RS, Aung PP, Gru AA, Hussaini M, Singh K, Querfeld C, Yao K, Small C, Gollapudi S, Jaye D, Wang SA. An analysis of the pathologic features of blastic plasmacytoid dendritic cell neoplasm based on a comprehensive literature database of cases. Archives of Pathology & Laboratory Medicine. 2023;147(7):837–46. Di Raimondo C, Lozzi F, Di Domenico PP, Paganini C, Campione E, Galluzzo M, Bianchi L. Blastic plasmacytoid dendritic cell neoplasm, from a dermatological point of view. International Journal of Molecular Sciences. 2024;25(13):7099. Cazzato G, Capuzzolo M, Bellitti E, De Biasi G, Colagrande A, Mangialardi K, Gaudio F, Ingravallo G. Blastic Plasmocytoid Dendritic Cell Neoplasm (BPDCN): Clinical Features and Histopathology with a Therapeutic Overview. Hematology Reports. 2023;15(4):696–706. Pemmaraju N. BPDCN: state of the art. Hematology. 2024;2024(1):279–86. Koerber RM, Held SA, Vonnahme M, Feldmann G, Wenzel J, Gütgemann I, Brossart P, Heine A. Blastic plasmacytoid dendritic-cell neoplasia: a challenging case report. Journal of Cancer Research and Clinical Oncology. 2022;148(3):743–8. Silveira SO, Fernandes CM, Pinto ÉB, Einecke YS, Palheta CD, Brito CV, Dias Júnior LB, Carneiro FR. Blastic plasmacytoid dendritic cell neoplasm: an early presentation. Dermatology Online Journal. 2019;25(2). Roussel X, Garnache Ottou F, Renosi F. Plasmacytoid dendritic cells, a novel target in myeloid neoplasms. Cancers. 2022;14(14):3545. Lee HJ, Park HM, Ki SY, Choi YD, Yun SJ, Lim HS. Blastic plasmacytoid dendritic cell neoplasm of the breast: a case report and review of the literature. Medicine. 2021;100(19):e25699. Reimer, P., Rüdiger, T., Kraemer, D., Kunzmann, V., Weissinger, F., Zettl, A., … Wilhelm, M. (2003). What is CD4 + CD56 + malignancy and how should it be treated?. Bone marrow transplantation , 32 (7), 637–646. Pagano L, Valentini CG, Grammatico S, Pulsoni A. Blastic plasmacytoid dendritic cell neoplasm: diagnostic criteria and therapeutical approaches. British journal of haematology. 2016;174(2):188–202. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Under Review Version 1 posted Editorial decision: Revision requested 29 Aug, 2025 Reviews received at journal 29 Aug, 2025 Reviews received at journal 26 Aug, 2025 Reviewers agreed at journal 20 Aug, 2025 Reviewers agreed at journal 20 Aug, 2025 Reviewers agreed at journal 18 Aug, 2025 Reviewers agreed at journal 17 Aug, 2025 Reviewers agreed at journal 17 Aug, 2025 Reviewers invited by journal 15 Aug, 2025 Editor assigned by journal 15 Aug, 2025 Submission checks completed at journal 14 Aug, 2025 First submitted to journal 08 Aug, 2025 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-7327413","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Case Report","associatedPublications":[],"authors":[{"id":503114128,"identity":"51da2f93-3471-4daa-88ef-80dd6c030acb","order_by":0,"name":"Alhejairi Rehab","email":"","orcid":"","institution":"Southern Medical University","correspondingAuthor":false,"prefix":"","firstName":"Alhejairi","middleName":"","lastName":"Rehab","suffix":""},{"id":503114129,"identity":"e3343f80-c5e0-4e44-bf0d-b3a8543c261e","order_by":1,"name":"Kaixin Li","email":"","orcid":"","institution":"Southern Medical 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edema and (B) violaceous nodules on the chest.\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-7327413/v1/2736c9e25060a5496e653ad1.png"},{"id":89862740,"identity":"1248d7e8-108d-448b-843b-38bbe141c882","added_by":"auto","created_at":"2025-08-25 21:31:43","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":553547,"visible":true,"origin":"","legend":"\u003cp\u003eHematoxylin and eosin staining of skin biopsy specimens.\u003c/p\u003e\n\u003cp\u003e(A) Face biopsy showing diffuse dermal infiltration without grenz zone (magnification ×0.89).\u003c/p\u003e\n\u003cp\u003e(B) Neck biopsy with similar infiltrative pattern (×0.77).\u003c/p\u003e\n\u003cp\u003e(C) Another section demonstrating sheet-like infiltration of tumor cells (×0.77).\u003c/p\u003e\n\u003cp\u003e(D) Low power view showing the extent of dermal involvement (×0.6).\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-7327413/v1/ea438caeea9eb49392771d9b.png"},{"id":89862746,"identity":"376d4012-f7eb-4a99-a5b4-98d6dc2729dd","added_by":"auto","created_at":"2025-08-25 21:31:43","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":1305957,"visible":true,"origin":"","legend":"\u003cp\u003eImmunohistochemical staining panel of the skin biopsy\u003c/p\u003e\n\u003cp\u003eAll positive markers show appropriate staining patterns supporting the diagnosis of acute monocytic leukemia.\u003c/p\u003e","description":"","filename":"3.png","url":"https://assets-eu.researchsquare.com/files/rs-7327413/v1/f39c18e367168c0a834bc415.png"},{"id":89863106,"identity":"4f0938ad-b348-451d-9a95-1643e46c836e","added_by":"auto","created_at":"2025-08-25 21:39:44","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":3963037,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7327413/v1/6a3c79f9-bbba-4008-8d6e-9d016e4ee933.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"CASE REPORT: Diagnostic Challenge in a 43-Year-Old Female - Acute Monocytic Leukemia (AML-M5) Presenting as Blastic Plasmacytoid Dendritic Cell Neoplasm","fulltext":[{"header":"Introduction","content":"\u003cp\u003eBlastic plasmacytoid dendritic cell neoplasm (BPDCN) is a distinct hematologic malignancy. It shows components of both myeloid and lymphoid cancers. BPDCN presents an aggressive clinical course. It creates a challenging therapeutic trajectory for patients \u003csup\u003e[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]\u003c/sup\u003e.\u003c/p\u003e\u003cp\u003eBPDCN affects four principal organ systems. These include cutaneous locations, bone marrow/blood, lymph nodes, and the central nervous system. Cerebrospinal fluid (CSF) involvement occurs frequently \u003csup\u003e[\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]\u003c/sup\u003e.\u003c/p\u003e\u003cp\u003eThe diagnostic triad consists of specific markers. These include IL-3Rα surface marker (CD123+), CD4+, and CD56+. This combination represents the most recognized diagnostic criterion for BPDCN. Additional markers enhance diagnostic accuracy. TCL1, TCF4, and CD303 help achieve 100% specificity in detecting this rare cancer \u003csup\u003e[\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]\u003c/sup\u003e.\u003c/p\u003e\u003cp\u003eBPDCN shares molecular features with myeloid malignancies. These include myelodysplastic syndrome (MDS), chronic myelomonocytic leukemia (CMML), and acute myeloid leukemia (AML). Common mutations include TET2, ASXL1, RAS, and splicing factor mutations like ZRSR2 \u003csup\u003e[\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]\u003c/sup\u003e.\u003c/p\u003e\u003cp\u003eRisk factors for BPDCN include several elements. Male sex increases risk. Ultraviolet light exposure contributes to development. Smoking is another risk factor. Genetic alterations like TET2 and RAS mutations occur more frequently in elderly patients \u003csup\u003e[\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]\u003c/sup\u003e.\u003c/p\u003e"},{"header":"Case presentation","content":"\u003cp\u003eA 43-year-old female patient presented to our department. She had no known medical illnesses. No allergies were documented. The patient complained of facial edema persisting for two months. She noticed papules and nodules on her chest. She experienced a constricted sensation in affected areas. No prior history of hypertension existed. She had no cardiovascular disease.\u003c/p\u003e\u003cp\u003ePhysical examination revealed significant findings. Facial edema was prominent. The skin showed rigidity. Multiple papules and nodules were visible. Numerous nodules were located on the chest. The lesions appeared violaceous. They were firm to palpation. Physical examination findings are shown in Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e.\u003c/p\u003e\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e\u003ch2\u003eLaboratory Findings\u003c/h2\u003e\u003cp\u003eBasic laboratory work revealed several abnormalities. Monocyte levels were elevated. The patient showed moderate anemia. Erythrocyte sedimentation rate (ESR) was increased.\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eBlood Smear Analysis\u003c/strong\u003e\u003cp\u003eGiant and late-stage erythroblasts were present. White blood cell count was elevated. Immature monocytes accounted for 53% of cells. Immature granulocytes showed morphological characteristics consistent with bone marrow findings. Mature red cells exhibited similar morphology to bone marrow smear. Platelets showed scattered distribution. They were relatively easy to identify.\u003c/p\u003e\u003c/p\u003e\u003c/div\u003e\n\u003ch3\u003eComplete Blood Count Results (October 2024):\u003c/h3\u003e\n\u003cp\u003e\u003cul\u003e\u003cli\u003e\u003cp\u003eWBC: 36.13 \u0026times; 10⁹/L (elevated)\u003c/p\u003e\u003c/li\u003e\u003cli\u003e\u003cp\u003eRBC: 1.88 \u0026times; 10\u0026sup1;\u0026sup2;/L (decreased)\u003c/p\u003e\u003c/li\u003e\u003cli\u003e\u003cp\u003eHemoglobin: 64 g/L (decreased)\u003c/p\u003e\u003c/li\u003e\u003cli\u003e\u003cp\u003ePlatelets: 109 \u0026times; 10⁹/L (normal)\u003c/p\u003e\u003c/li\u003e\u003cli\u003e\u003cp\u003eNeutrophils: 12.44 \u0026times; 10⁹/L (elevated)\u003c/p\u003e\u003c/li\u003e\u003cli\u003e\u003cp\u003eLymphocytes: 7.12 \u0026times; 10⁹/L\u003c/p\u003e\u003c/li\u003e\u003cli\u003e\u003cp\u003eMonocytes: 16.49 \u0026times; 10⁹/L (markedly elevated)\u003c/p\u003e\u003c/li\u003e\u003cli\u003e\u003cp\u003eNeutrophil percentage: 34.4%\u003c/p\u003e\u003c/li\u003e\u003cli\u003e\u003cp\u003eLymphocyte percentage: 19.7%\u003c/p\u003e\u003c/li\u003e\u003cli\u003e\u003cp\u003eMonocyte percentage: 45.6% (elevated)\u003c/p\u003e\u003c/li\u003e\u003cli\u003e\u003cp\u003eEosinophil percentage: 0.2%\u003c/p\u003e\u003c/li\u003e\u003cli\u003e\u003cp\u003eNucleated RBC: 0.25 \u0026times; 10⁹/L (elevated)\u003c/p\u003e\u003c/li\u003e\u003cli\u003e\u003cp\u003eNRBC percentage: 0.7%\u003c/p\u003e\u003c/li\u003e\u003c/ul\u003e\u003c/p\u003e\u003cp\u003e\u003cb\u003eCytochemical Staining Results\u003c/b\u003e\u003c/p\u003e\u003cp\u003e\u003col\u003e\u003cspan\u003e\u003cli\u003e\u003cp\u003e\u003cb\u003eAKP (Alkaline Phosphatase)\u003c/b\u003e: Variable positivity was observed. Results showed: ++12%, ++11%, +++4% (granular positive), +++3% and +++2% (focal positive).\u003c/p\u003e\u003c/li\u003e\u003c/span\u003e\u003cspan\u003e\u003cli\u003e\u003cp\u003e\u003cb\u003ePAS (Periodic Acid-Schiff)\u003c/b\u003e: Positive in 95% of cells. Total score was 240. Staining showed coarse and fine granular positivity. Particles were diffusely distributed. Some areas showed finely dispersed granules.\u003c/p\u003e\u003c/li\u003e\u003c/span\u003e\u003c/ol\u003e\u003c/p\u003e\n\u003ch3\u003eDifferential Diagnosis\u003c/h3\u003e\n\u003cp\u003eSeveral conditions were considered initially:\u003c/p\u003e\u003cp\u003e\u003cul\u003e\u003cli\u003e\u003cp\u003eEpstein-Barr virus-related mononucleosis\u003c/p\u003e\u003c/li\u003e\u003cli\u003e\u003cp\u003eCutaneous lymphoma\u003c/p\u003e\u003c/li\u003e\u003cli\u003e\u003cp\u003eLeprosy\u003c/p\u003e\u003c/li\u003e\u003cli\u003e\u003cp\u003eConnective tissue disease\u003c/p\u003e\u003c/li\u003e\u003cli\u003e\u003cp\u003eSkin infection\u003c/p\u003e\u003c/li\u003e\u003cli\u003e\u003cp\u003eCutaneous mucinosis\u003c/p\u003e\u003c/li\u003e\u003c/ul\u003e\u003c/p\u003e\n\u003ch3\u003eHistopathological Examination\u003c/h3\u003e\n\u003cdiv id=\"Sec7\" class=\"Section2\"\u003e\u003ch2\u003eSkin Biopsies:\u003c/h2\u003e\u003cp\u003eSkin biopsies were performed from face and neck regions. They were subjected to comprehensive histopathological examination.\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec8\" class=\"Section2\"\u003e\u003ch2\u003eGross Findings:\u003c/h2\u003e\u003cp\u003e\u003cul\u003e\u003cli\u003e\u003cp\u003eFace: Formalin-fixed skin biopsy specimen included skin and subcutaneous tissue. It measured approximately 0.7 cm \u0026times; 0.4 cm \u0026times; 0.4 cm. Surface color corresponded to skin tone.\u003c/p\u003e\u003c/li\u003e\u003cli\u003e\u003cp\u003eNeck: Formalin-fixed skin biopsy specimen included skin and subcutaneous tissue. It measured approximately 1 cm \u0026times; 0.7 cm \u0026times; 0.5 cm. Surface color corresponded to skin tone.\u003c/p\u003e\u003c/li\u003e\u003c/ul\u003e\u003c/p\u003e\u003cp\u003e\u003cb\u003eMicroscopic Findings\u003c/b\u003e: The subepidermal area showed no distinct infiltration zone. Dermis demonstrated extensive diffuse infiltration by lymphoid-like cells. Nuclear fragmentation was evident. Vesicular nuclei were visible. Special stains were performed: Face biopsy showed PAS negative and Acid-fast stain negative results. Neck biopsy also showed PAS negative and Acid-fast stain negative results.\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eH\u0026amp;E Staining Analysis\u003c/strong\u003e\u003cp\u003eHematoxylin and eosin staining revealed characteristic features. The sections demonstrated diffuse infiltration of medium-sized cells throughout the dermis. No grenz zone was observed between epidermis and tumor infiltrate. This finding is typical of aggressive lymphoid malignancies.\u003c/p\u003e\u003c/p\u003e\u003cp\u003eThe tumor cells showed distinct morphology. Nuclei were round to oval with fine chromatin patterns. The cytoplasm appeared moderately abundant with pale eosinophilic quality. Cell borders were indistinct. Mitotic figures were scattered throughout the infiltrate.\u003c/p\u003e\u003cp\u003eThe infiltrative pattern extended through all dermal layers. It reached the dermal-subcutaneous junction. The overlying epidermis remained intact. No epidermotropism was noted. The surrounding stroma showed minimal inflammatory response. Vascular structures were preserved but compressed by tumor cells. These histopathological features are illustrated in Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e.\u003c/p\u003e\u003cp\u003e\u003cstrong\u003ePathological Diagnosis\u003c/strong\u003e\u003cp\u003eLymphoproliferative disorder was considered. The findings suggested a process related to the lymphoid or hematopoietic system.\u003c/p\u003e\u003c/p\u003e\u003c/div\u003e\n\u003ch3\u003eBone Marrow Examination\u003c/h3\u003e\n\u003cp\u003e\u003cstrong\u003eBone Marrow Smear Findings\u003c/strong\u003e\u003cp\u003eBone marrow showed hyperplasia with active cellular proliferation. Granulocyte to erythrocyte ratio was 3.17.\u003c/p\u003e\u003c/p\u003e\n\u003ch3\u003eCell Lineage Analysis:\u003c/h3\u003e\n\u003cp\u003e\u003cul\u003e\u003cli\u003e\u003cp\u003e\u003cb\u003eGranulocyte Lineage\u003c/b\u003e: Comprised 19.0% with reduced proliferation. Myeloblasts constituted 5%. Cells showed varying sizes with mostly round or oval nuclei. Cytoplasm was moderately abundant and blue with occasional purple granules. Mature granulocytes showed nuclear segmentation abnormalities.\u003c/p\u003e\u003c/li\u003e\u003cli\u003e\u003cp\u003e\u003cb\u003eErythroid Lineage\u003c/b\u003e: Constituted 6% with reduced proliferation. Predominantly intermediate and late-stage erythroblasts were seen. Some showed megaloblastic changes and nuclear abnormalities. Maturing red cells varied in size with morphological irregularities.\u003c/p\u003e\u003c/li\u003e\u003cli\u003e\u003cp\u003e\u003cb\u003eMegakaryocyte Lineage\u003c/b\u003e: 52 megakaryocytes were observed. This included 20 pro-platelet-forming cells. Platelets were scattered. Morphological abnormalities were evident.\u003c/p\u003e\u003c/li\u003e\u003cli\u003e\u003cp\u003e\u003cb\u003eMonocyte Lineage\u003c/b\u003e: Monocyte population was 66.5%. The majority (65.5%) were immature forms. Cells showed variable size, often round or oval. They had pseudopod projections or fine hair-like projections. Cytoplasm was moderately blue-gray with small purple granules. Auer rods were occasionally observed. Nuclei were round or oval with occasional distortion, folding, or indentations. Nuclear chromatin appeared fine. Nucleoli were visible (0\u0026ndash;3 per cell).\u003c/p\u003e\u003c/li\u003e\u003cli\u003e\u003cp\u003e\u003cb\u003eOther Cell Populations\u003c/b\u003e: Lymphocytes comprised 8.5%. No significant morphological abnormalities were observed.\u003c/p\u003e\u003c/li\u003e\u003c/ul\u003e\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eBone Marrow Biopsy\u003c/strong\u003e\u003cp\u003eTwo gray-white tissue strips were examined. Each measured approximately 1.2 cm in length and 0.3 cm in diameter.\u003c/p\u003e\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eMicroscopic Findings\u003c/strong\u003e\u003cp\u003eThe bone marrow biopsy showed diffuse proliferation of immature cells. These cells filled the bone trabeculae. Cells were medium in size with abundant eosinophilic cytoplasm. Nuclei were medium-sized, round or polygonal. Chromatin was fine and granular. Nucleoli were inconspicuous. Other hematopoietic cells were markedly reduced.\u003c/p\u003e\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eSpecial Stains\u003c/strong\u003e\u003cp\u003eReticulin stain showed Grade 0 (no significant fibrosis).\u003c/p\u003e\u003c/p\u003e\u003cp\u003e\u003cstrong\u003ePathological Diagnosis\u003c/strong\u003e\u003cp\u003eDiffuse proliferation of immature cells within bone trabeculae was noted. Findings were consistent with acute leukemia.\u003c/p\u003e\u003c/p\u003e\u003cdiv id=\"Sec11\" class=\"Section2\"\u003e\u003ch2\u003eImmunophenotyping Results\u003c/h2\u003e\u003cp\u003eFlow cytometry and immunohistochemistry revealed a specific immunophenotype:\u003c/p\u003e\u003cp\u003e\u003cul\u003e\u003cli\u003e\u003cp\u003eCD3: Negative\u003c/p\u003e\u003c/li\u003e\u003cli\u003e\u003cp\u003eCD20: Negative\u003c/p\u003e\u003c/li\u003e\u003cli\u003e\u003cp\u003eCD123: Negative (unusual for BPDCN)\u003c/p\u003e\u003c/li\u003e\u003cli\u003e\u003cp\u003eCD4: Positive (focal, moderate intensity)\u003c/p\u003e\u003c/li\u003e\u003cli\u003e\u003cp\u003eCD79a: Negative\u003c/p\u003e\u003c/li\u003e\u003cli\u003e\u003cp\u003eALK (D5F3): Negative\u003c/p\u003e\u003c/li\u003e\u003cli\u003e\u003cp\u003eKi-67: 80% positive\u003c/p\u003e\u003c/li\u003e\u003cli\u003e\u003cp\u003eMPO: Approximately 5% positive\u003c/p\u003e\u003c/li\u003e\u003cli\u003e\u003cp\u003eCD56: Positive\u003c/p\u003e\u003c/li\u003e\u003cli\u003e\u003cp\u003eCD30: Negative\u003c/p\u003e\u003c/li\u003e\u003cli\u003e\u003cp\u003eTIA-1: Negative\u003c/p\u003e\u003c/li\u003e\u003cli\u003e\u003cp\u003eCD5: Negative\u003c/p\u003e\u003c/li\u003e\u003cli\u003e\u003cp\u003eCD7: Negative\u003c/p\u003e\u003c/li\u003e\u003cli\u003e\u003cp\u003eCD8: Negative\u003c/p\u003e\u003c/li\u003e\u003cli\u003e\u003cp\u003eCD10: Negative\u003c/p\u003e\u003c/li\u003e\u003cli\u003e\u003cp\u003eCD117: Negative\u003c/p\u003e\u003c/li\u003e\u003cli\u003e\u003cp\u003eBCL-6: Negative\u003c/p\u003e\u003c/li\u003e\u003cli\u003e\u003cp\u003eBCL-2: Approximately 60% positive\u003c/p\u003e\u003c/li\u003e\u003cli\u003e\u003cp\u003ePD1: Negative\u003c/p\u003e\u003c/li\u003e\u003cli\u003e\u003cp\u003eTCL1: Negative\u003c/p\u003e\u003c/li\u003e\u003cli\u003e\u003cp\u003eCD11c: Positive\u003c/p\u003e\u003c/li\u003e\u003cli\u003e\u003cp\u003eCD14: Focal positive\u003c/p\u003e\u003c/li\u003e\u003cli\u003e\u003cp\u003eCD33: Positive\u003c/p\u003e\u003c/li\u003e\u003cli\u003e\u003cp\u003eCD34: Negative\u003c/p\u003e\u003c/li\u003e\u003cli\u003e\u003cp\u003eCD68: Positive\u003c/p\u003e\u003c/li\u003e\u003cli\u003e\u003cp\u003eCD163: Positive\u003c/p\u003e\u003c/li\u003e\u003cli\u003e\u003cp\u003eLysozyme: Positive\u003c/p\u003e\u003c/li\u003e\u003cli\u003e\u003cp\u003eEBER in situ hybridization: Negative\u003c/p\u003e\u003c/li\u003e\u003c/ul\u003e\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec12\" class=\"Section2\"\u003e\u003ch2\u003eImmunocytochemical Staining Patterns\u003c/h2\u003e\u003cp\u003eImmunohistochemical analysis revealed a distinct expression profile that supported the diagnosis of acute monocytic leukemia (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e). The monocytic markers CD68, CD163, and lysozyme all showed positive staining in the tumor cells. CD14 demonstrated focal positivity, while CD33 showed diffuse expression. Additional markers included BCL-2 positivity and a high Ki-67 proliferative index. CD4 and CD56 were also positive, while MPO showed minimal expression.\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec13\" class=\"Section2\"\u003e\u003ch2\u003eFinal Diagnosis\u003c/h2\u003e\u003cp\u003eBased on comprehensive analysis, the diagnosis was acute monocytic leukemia (AML-M5). The initial suspicion of BPDCN was not confirmed due to CD123 negativity and the predominant monocytic features.\u003c/p\u003e\u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eBPDCN is a rare hematologic malignancy recently recognized as a distinct entity. It was initially thought to derive from natural killer cells due to CD56 positivity \u003csup\u003e[\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]\u003c/sup\u003e. The discovery of its origin from plasmacytoid dendritic cell precursors led to current nomenclature. BPDCN was established as a distinct neoplastic entity in the 2008 WHO classification \u003csup\u003e[\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]\u003c/sup\u003e.\u003c/p\u003e\u003cp\u003eThe characteristic immunophenotype includes co-expression of specific markers. CD4, CD56, and plasmacytoid dendritic cell markers are essential. These include CD123, BDCA2, TCL1, CD138, CD68, and BCL2. The absence of T-cell, B-cell, myeloid, and NK-cell markers helps confirm diagnosis \u003csup\u003e[\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]\u003c/sup\u003e.\u003c/p\u003e\u003cp\u003eOur case presented diagnostic challenges. The patient showed typical clinical features of BPDCN. Skin involvement with violaceous nodules is characteristic. The aggressive clinical course matched BPDCN behavior. However, immunophenotyping revealed unexpected findings.\u003c/p\u003e\u003cp\u003eThe H\u0026amp;E staining showed features compatible with hematologic malignancy. Diffuse dermal infiltration without grenz zone is typical. The medium-sized cells with fine chromatin supported this diagnosis. The minimal inflammatory response suggested rapid progression. These findings correlated with the two-month symptom duration.\u003c/p\u003e\u003cp\u003eThe absence of CD123 expression was unusual for BPDCN. CD123 is considered a hallmark marker. Its negativity, combined with strong monocytic features, redirected the diagnosis. The high percentage of immature monocytes (65.5%) supported AML-M5. The immunophenotype with CD68+, CD163+, and lysozyme positivity confirmed monocytic lineage.\u003c/p\u003e\u003cp\u003eThe immunohistochemical findings were crucial in establishing the correct diagnosis. The positivity for monocytic markers CD68, CD163, and lysozyme confirmed monocytic differentiation. The focal CD14 expression is typical for acute monocytic leukemia, as this marker can show variable expressions. The presence of CD33 confirmed myeloid lineage, while the minimal MPO expression (approximately 5% as noted in the flow cytometry) is consistent with monocytic rather than granulocytic differentiation. The high Ki-67 index correlated with the aggressive clinical course observed in this patient.\u003c/p\u003e\u003cp\u003eBPDCN commonly presents with cutaneous lesions initially \u003csup\u003e[\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]\u003c/sup\u003e. Patients often receive empirical treatments before diagnosis. Antibiotics or steroids may cause partial regression. This leads to diagnostic delays \u003csup\u003e[\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]\u003c/sup\u003e. Early skin biopsy is crucial for timely diagnosis.\u003c/p\u003e\u003cp\u003eThe bone marrow findings in our case were significant. The hypercellular marrow with monocytic predominance was striking. The presence of Auer rods, though occasional, supported AML diagnosis. The cytochemical staining pattern with PAS positivity is typical for monocytic leukemia.\u003c/p\u003e\u003cp\u003eTreatment approaches differ significantly between BPDCN and AML-M5. BPDCN often requires lymphoma-type regimens. These include hyper-CVAD, VPDL, or CHOP protocols \u003csup\u003e[\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]\u003c/sup\u003e. Some groups report improved survival with high-dose chemotherapy and stem cell transplant \u003csup\u003e[\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]\u003c/sup\u003e. However, median survival remains 12\u0026ndash;14 months \u003csup\u003e[\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]\u003c/sup\u003e.\u003c/p\u003e\u003cp\u003eOur case emphasizes the importance of comprehensive evaluation. Clinical presentation alone cannot distinguish BPDCN from other hematologic malignancies. Detailed immunophenotyping is essential. The integration of morphology, immunohistochemistry, and flow cytometry ensures accurate diagnosis.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eWe present a case initially suspected as BPDCN based on clinical features. Comprehensive analysis revealed acute monocytic leukemia instead. This case highlights diagnostic challenges in aggressive hematologic malignancies with skin involvement. The absence of CD123 and predominant monocytic features were key diagnostic clues. Early biopsy and complete immunophenotyping are essential for accurate diagnosis and appropriate treatment selection.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConflicts of Interest/Competing Interests\u003c/strong\u003e The authors declare that they have no conflicts of interest or competing interests related to this work.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics Approval\u003c/strong\u003e This case report was conducted in accordance with the Declaration of Helsinki. Ethics approval was obtained from the Ethics Committee of Dermatology Hospital, Southern Medical University, Guangzhou, China. The study was performed in accordance with relevant guidelines and regulations.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent to Participate / for Publication\u003c/strong\u003e Ethics Written informed consent for publication of their clinical details and/or clinical images was obtained from the patient. A copy of the consent form is available for review by the Editor of this journal.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of Data and Material\u003c/strong\u003e All data generated or analyzed during this study are included in this published article. Additional data is available from the corresponding author upon reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCode Availability\u003c/strong\u003e Not applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026rsquo; Contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAlhejairi Rehab and Kaixin Li conceived and designed the study. Alhejairi Rehab performed the clinical examination and collected patient data. Kaixin Li conducted the histopathological examination and H\u0026amp;E staining analysis. Ruaa Ahmed Alnour performed the immunohistochemical staining and flow cytometry analysis. Alhejairi Rehab and Kaixin Li analyzed and interpreted the data. Alhejairi Rehab wrote the initial draft of the manuscript. Yongfeng Chen and Rongyi Chen supervised the study, provided critical revisions to the manuscript, and gave final approval for submission. All authors reviewed and approved the final version of the manuscript. All authors read and approved the final manuscript.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eKhoury JD. Blastic plasmacytoid dendritic cell neoplasm. Current hematologic malignancy reports. 2018;13:477\u0026ndash;83.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eSapienza 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. 2019;11(5):595.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eAdimora IJ, Wilson NR, Pemmaraju N. Blastic plasmacytoid dendritic cell neoplasm (BPDCN): A promising future in the era of targeted therapeutics. Cancer. 2022;128(16):3019\u0026ndash;26.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eOhgami RS, Aung PP, Gru AA, Hussaini M, Singh K, Querfeld C, Yao K, Small C, Gollapudi S, Jaye D, Wang SA. An analysis of the pathologic features of blastic plasmacytoid dendritic cell neoplasm based on a comprehensive literature database of cases. Archives of Pathology \u0026amp; Laboratory Medicine. 2023;147(7):837\u0026ndash;46.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eDi Raimondo C, Lozzi F, Di Domenico PP, Paganini C, Campione E, Galluzzo M, Bianchi L. Blastic plasmacytoid dendritic cell neoplasm, from a dermatological point of view. International Journal of Molecular Sciences. 2024;25(13):7099.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eCazzato G, Capuzzolo M, Bellitti E, De Biasi G, Colagrande A, Mangialardi K, Gaudio F, Ingravallo G. Blastic Plasmocytoid Dendritic Cell Neoplasm (BPDCN): Clinical Features and Histopathology with a Therapeutic Overview. Hematology Reports. 2023;15(4):696\u0026ndash;706.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003ePemmaraju N. BPDCN: state of the art. Hematology. 2024;2024(1):279\u0026ndash;86.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eKoerber RM, Held SA, Vonnahme M, Feldmann G, Wenzel J, G\u0026uuml;tgemann I, Brossart P, Heine A. Blastic plasmacytoid dendritic-cell neoplasia: a challenging case report. Journal of Cancer Research and Clinical Oncology. 2022;148(3):743\u0026ndash;8.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eSilveira SO, Fernandes CM, Pinto \u0026Eacute;B, Einecke YS, Palheta CD, Brito CV, Dias J\u0026uacute;nior LB, Carneiro FR. Blastic plasmacytoid dendritic cell neoplasm: an early presentation. Dermatology Online Journal. 2019;25(2).\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eRoussel X, Garnache Ottou F, Renosi F. Plasmacytoid dendritic cells, a novel target in myeloid neoplasms. Cancers. 2022;14(14):3545.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eLee HJ, Park HM, Ki SY, Choi YD, Yun SJ, Lim HS. Blastic plasmacytoid dendritic cell neoplasm of the breast: a case report and review of the literature. Medicine. 2021;100(19):e25699.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eReimer, P., R\u0026uuml;diger, T., Kraemer, D., Kunzmann, V., Weissinger, F., Zettl, A., \u0026hellip; Wilhelm, M. (2003). What is CD4\u0026thinsp;+\u0026thinsp;CD56\u0026thinsp;+\u0026thinsp;malignancy and how should it be treated?. \u003cem\u003eBone marrow transplantation\u003c/em\u003e, \u003cem\u003e32\u003c/em\u003e(7), 637\u0026ndash;646.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003ePagano L, Valentini CG, Grammatico S, Pulsoni A. Blastic plasmacytoid dendritic cell neoplasm: diagnostic criteria and therapeutical approaches. British journal of haematology. 2016;174(2):188\u0026ndash;202.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"sn-comprehensive-clinical-medicine","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"sncm","sideBox":"Learn more about [SN Comprehensive Clinical Medicine](https://www.springer.com/journal/42399)","snPcode":"42399","submissionUrl":"https://submission.nature.com/new-submission/42399/3","title":"SN Comprehensive Clinical Medicine","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"Blastic plasmacytoid dendritic cell neoplasm, BPDCN, Myeloid sarcoma, Histopathology, H\u0026E staining","lastPublishedDoi":"10.21203/rs.3.rs-7327413/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7327413/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eStatement of the Problem\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eBlastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare and aggressive hematologic malignancy that originates from plasmacytoid dendritic cells (pDCs). BPDCN typically presents with skin lesions, which can appear as bruise-like patches, nodules, or plaques. These lesions are often violaceous and can be found on the face, trunk, and extremities. The disease can also involve the bone marrow, blood, lymph nodes, and other organs, including the central nervous system. BPDCN has a poor prognosis, with a median overall survival of less than two years in many cases.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eThe purpose of this study\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe present a comprehensive case of BPDCN in a 43-year-old female patient. The patient presented with facial swelling, chest papules and nodules. She experienced skin tightness for two months. We performed detailed histopathological examinations including H\u0026amp;E staining. We analyzed bone marrow findings and immunophenotyping results. This case highlights the diagnostic challenges and aggressive nature of BPDCN.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusion\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis case demonstrates that AML-M5 can closely mimic BPDCN clinically and histologically, emphasizing the critical role of comprehensive immunophenotyping in reaching the correct diagnosis.\u003c/p\u003e","manuscriptTitle":"CASE REPORT: Diagnostic Challenge in a 43-Year-Old Female - Acute Monocytic Leukemia (AML-M5) Presenting as Blastic Plasmacytoid Dendritic Cell Neoplasm","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-08-25 21:31:38","doi":"10.21203/rs.3.rs-7327413/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2025-08-29T19:08:11+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-08-29T10:45:26+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-08-26T14:53:08+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"111752299523286018009577770079040685157","date":"2025-08-20T12:10:31+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"85130172389939060807048047743259991049","date":"2025-08-20T11:56:43+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"176769508146471297015180539438799265256","date":"2025-08-18T08:04:13+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"38837489510580486205501535117827546692","date":"2025-08-17T12:04:49+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"232337513464281233580195153116981533264","date":"2025-08-17T11:48:15+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-08-15T11:45:20+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-08-15T07:37:32+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-08-15T03:43:17+00:00","index":"","fulltext":""},{"type":"submitted","content":"SN Comprehensive Clinical Medicine","date":"2025-08-08T12:43:50+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"sn-comprehensive-clinical-medicine","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"sncm","sideBox":"Learn more about [SN Comprehensive Clinical Medicine](https://www.springer.com/journal/42399)","snPcode":"42399","submissionUrl":"https://submission.nature.com/new-submission/42399/3","title":"SN Comprehensive Clinical Medicine","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"8d84fdac-7a6b-49c8-b26b-9301ec88e7dc","owner":[],"postedDate":"August 25th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2025-09-10T08:23:57+00:00","versionOfRecord":[],"versionCreatedAt":"2025-08-25 21:31:38","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-7327413","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7327413","identity":"rs-7327413","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}