Disease presentation and immunophenotype characteristics in 257 patients with blastic plasmacytoid dendritic cell neoplasm: A pethema/PALG study

Abstract Background Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare and aggressive hematologic malignancy characterized by a complex clinical presentation. Comprehensive characterization at diagnosis is essential for proper classification and therapeutic decisions. Immunophenotype and/or immunohistochemistry are currently mandatory diagnostic criteria for confirming this neoplasm. However, large series describing marker features at diagnosis are scarce. Material This multinational retrospective study performed by PALG and PETHEMA groups registered BPDCN patients from July 1999 to 2025 (EPI-BLAS project). Local data for clinical presentation, morphology, immunophenotype, and immunohistochemistry was collected from participating centers and reviewed centrally. BPDCN classification was made locally based on WHO criteria applicable at the time of diagnosis. Results A total of 257 patients diagnosed with BPDCN were included in the multinational PETHEMA and PALG registry. Most were male (78%), median age was 66 years old (range, 15-92), bone marrow involvement (>5% blasts) was documented in 75% (177/237, 20 data not available [NA]), and peripheral blood in 62% (103/165, 92 NA). Regarding extramedullary involvement, 197 (81%) out of 242 with available data had skin involvement, and 49% (131/237, 20 NA) had lymphadenopathy. A lumbar puncture was performed at diagnosis in 77% (168/217, 40 NA) patients and CNS infiltration was documented in 48 (29%) of them. Disease was restricted to the skin in (10%) 25 patients. Immunophenotypic and/or immunohistochemical information was available in 236 patients. Immunohistochemistry (IHQ) studies were conducted on 178 patients (115 skin biopsies, 47 bone marrow biopsies, 13 lymph nodes, 1 salivary gland, and 1 spleen specimen). Flow cytometry (FC) analyses were performed in 244 patients (179 bone marrow aspirates, 26 peripheral blood samples, 16 skin biopsies, 21 cerebrospinal fluid (CSF) samples, and 2 lymph nodes). In 6 additional patients, the specific technique used could not be determined due to insufficient documentation. Skin biopsies from IHQ showed in most cases positive expression of CD4 (94/96, 98%, 19 NA), CD56 (92/99, 93%, 16 NA), CD123 (66/66, 100%, 49 NA), CD304 (1/1, 100%, 114 NA), and TCL1 (6/7, 86%, 108 NA). CD303 and TCF4 expression were never assessed. Negative expression for CD3, CD14, CD19, CD34, lysozyme and myeloperoxidase (MPO) were found in 94% (79/84, 31 NA), 100% (6/6, 109 NA), 100% (2/2, 113 NA), 98% (55/56, 46 NA), 92% (11/12, 77 NA) and 98% (55/56, 45 NA), respectively. When performed, FC analysis of bone marrow detected BPDCN cells in 95% of cases (170/179), and the vast majority showed positivity for CD4 (132/141, 94%, 29 NA), CD56 (117/147, 80%, 23 NA), CD123 (143/147, 97%, 23 NA), CD304 (12/14, 86%, 156 NA), and TCL1 (22/22, 100%, 148 NA). CD303 was positive in 29% (2/7, 163 NA). TCF4 expression was never assessed. CD3, CD14, CD19, CD34, lysozyme, and MPO were consistently negative in 98% (89/91, 79 NA), 98% (96/98, 52 NA), 95% (112/118, 52 NA), 74% (100/135, 35 NA), 75% (3/4, 166 NA), and 93% (102/110, 60 NA), respectively. In 20% (30/149, 21 NA) of patients, more than one leukemic population was identified by FC in bone marrow, potentially representing different stages of plasmacytoid dendritic cells (pDC) differentiation. Among 23 BPDCN patients with ≤5% morphological blast cells in bone marrow and with available FC analyses, 18 patients (78%) showed BPDCN cells (median 1.95% blasts, range 0.01% to 20%), 2 (10%) showed pDC with normal immunophenotypic profile; and 5 (22%) showed no evidence of pDCs or BPDCN. Conclusion Our large registry study in this rare disease showed skin and bone marrow involvement in the vast majority of patients. Half of BPCN patients had lymph node involvement, and 29% CNS disease. IHQ and FC analyses showed positivity for CD123, CD4 and CD56 in almost all samples. CD304 and TCL1 were also positive in almost all cases, but these surface antigen markers were only tested in a minority of samples. FC analyses could detect BPDCN cells in most cases without bone marrow morphological infiltration, highlighting the role of FC assessment in this tissue. The consistent implementation of well-defined markers, particularly those outlined in the WHO 2022 classification, could further strengthen diagnostic precision of BPDCN. Disclosures The EPI-BLAS registry was partially funded by Menarini.

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Blood
Published
2025-11-03
DOI
https://doi.org/10.1182/blood-2025-218
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Cutaneous lymphoproliferative disorders research
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article

Disease presentation and immunophenotype characteristics in 257 patients with blastic plasmacytoid dendritic cell neoplasm: A pethema/PALG study

Pau Montesinos, Olga Salamero, Joana Brioso Infante, Leticia Rapan et al.
Blood
Cutaneous lymphoproliferative disorders research
article

Disease presentation and immunophenotype characteristics in 257 patients with blastic plasmacytoid dendritic cell neoplasm: A pethema/PALG study

Pau Montesinos, Olga Salamero, Joana Brioso Infante, Leticia Rapan, Amparo Sempere, Mar Tormo, Gabriela Rodríguez Macias, Irene Navarro Vicente, Nerea Caminos, Teresa Olavé, Jorge Labrador, Renata Guzicka‐Kazimierczak, Benjamín Herreros, Łukasz Targoński, Víctor Noriega Concepción, Juan Miguel Bergua Burgués, Manuel Pérez‐Encinas, Lorenzo Algarra, Anna Armatys, Marta Sobas, Cristina Gil, Delfim Duarte, Matxalen Olivares Salaverri, Tomás Rivero Equiza, Krzysztof Lewandowski, Tamara Castaño, Josefina Serrano, Ada Esteban-Figuerola, Pilar Lloret Madrid, Bruno Paiva, Eduardo Rodríguez‐Arbolí, Virginia Pradillo Fernández, Andrzej Szczepaniak, Teresa Bernal, Mercedes Colorado, Rolando Vallansot, Antonio Solana‐Altabella, Magdalena Karasek, Alberto Giménez Conca, María Teresa Cedena Romero, Joaquín Sánchez‐García, Manuel Barrios García, María García‐Fortes, Emilia Ulenberg, Santiago Cranco, Lisette Costilla-Barriga, Teresa Caballero‐Velázquez, Rafael Colmenares, Dunia de Miguel, Milena Sitkiewicz, Manuela Clavijo, Irene Rey, Fernanda Trigo, Małgorzata Sobczyk-Kruszelnicka, Isabel Simón-Pilo
article en

Abstract

Abstract Background Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare and aggressive hematologic malignancy characterized by a complex clinical presentation. Comprehensive characterization at diagnosis is essential for proper classification and therapeutic decisions. Immunophenotype and/or immunohistochemistry are currently mandatory diagnostic criteria for confirming this neoplasm. However, large series describing marker features at diagnosis are scarce. Material This multinational retrospective study performed by PALG and PETHEMA groups registered BPDCN patients from July 1999 to 2025 (EPI-BLAS project). Local data for clinical presentation, morphology, immunophenotype, and immunohistochemistry was collected from participating centers and reviewed centrally. BPDCN classification was made locally based on WHO criteria applicable at the time of diagnosis. Results A total of 257 patients diagnosed with BPDCN were included in the multinational PETHEMA and PALG registry. Most were male (78%), median age was 66 years old (range, 15-92), bone marrow involvement (>5% blasts) was documented in 75% (177/237, 20 data not available [NA]), and peripheral blood in 62% (103/165, 92 NA). Regarding extramedullary involvement, 197 (81%) out of 242 with available data had skin involvement, and 49% (131/237, 20 NA) had lymphadenopathy. A lumbar puncture was performed at diagnosis in 77% (168/217, 40 NA) patients and CNS infiltration was documented in 48 (29%) of them. Disease was restricted to the skin in (10%) 25 patients. Immunophenotypic and/or immunohistochemical information was available in 236 patients. Immunohistochemistry (IHQ) studies were conducted on 178 patients (115 skin biopsies, 47 bone marrow biopsies, 13 lymph nodes, 1 salivary gland, and 1 spleen specimen). Flow cytometry (FC) analyses were performed in 244 patients (179 bone marrow aspirates, 26 peripheral blood samples, 16 skin biopsies, 21 cerebrospinal fluid (CSF) samples, and 2 lymph nodes). In 6 additional patients, the specific technique used could not be determined due to insufficient documentation. Skin biopsies from IHQ showed in most cases positive expression of CD4 (94/96, 98%, 19 NA), CD56 (92/99, 93%, 16 NA), CD123 (66/66, 100%, 49 NA), CD304 (1/1, 100%, 114 NA), and TCL1 (6/7, 86%, 108 NA). CD303 and TCF4 expression were never assessed. Negative expression for CD3, CD14, CD19, CD34, lysozyme and myeloperoxidase (MPO) were found in 94% (79/84, 31 NA), 100% (6/6, 109 NA), 100% (2/2, 113 NA), 98% (55/56, 46 NA), 92% (11/12, 77 NA) and 98% (55/56, 45 NA), respectively. When performed, FC analysis of bone marrow detected BPDCN cells in 95% of cases (170/179), and the vast majority showed positivity for CD4 (132/141, 94%, 29 NA), CD56 (117/147, 80%, 23 NA), CD123 (143/147, 97%, 23 NA), CD304 (12/14, 86%, 156 NA), and TCL1 (22/22, 100%, 148 NA). CD303 was positive in 29% (2/7, 163 NA). TCF4 expression was never assessed. CD3, CD14, CD19, CD34, lysozyme, and MPO were consistently negative in 98% (89/91, 79 NA), 98% (96/98, 52 NA), 95% (112/118, 52 NA), 74% (100/135, 35 NA), 75% (3/4, 166 NA), and 93% (102/110, 60 NA), respectively. In 20% (30/149, 21 NA) of patients, more than one leukemic population was identified by FC in bone marrow, potentially representing different stages of plasmacytoid dendritic cells (pDC) differentiation. Among 23 BPDCN patients with ≤5% morphological blast cells in bone marrow and with available FC analyses, 18 patients (78%) showed BPDCN cells (median 1.95% blasts, range 0.01% to 20%), 2 (10%) showed pDC with normal immunophenotypic profile; and 5 (22%) showed no evidence of pDCs or BPDCN. Conclusion Our large registry study in this rare disease showed skin and bone marrow involvement in the vast majority of patients. Half of BPCN patients had lymph node involvement, and 29% CNS disease. IHQ and FC analyses showed positivity for CD123, CD4 and CD56 in almost all samples. CD304 and TCL1 were also positive in almost all cases, but these surface antigen markers were only tested in a minority of samples. FC analyses could detect BPDCN cells in most cases without bone marrow morphological infiltration, highlighting the role of FC assessment in this tissue. The consistent implementation of well-defined markers, particularly those outlined in the WHO 2022 classification, could further strengthen diagnostic precision of BPDCN. Disclosures The EPI-BLAS registry was partially funded by Menarini.

BloodVol. 146(Supplement 1)
University of Szczecin (PL), Poznan University of Medical Sciences (PL), Medical University of Silesia (PL), University of Economics in Katowice (PL), Universidade de Santiago de Compostela (ES), Hospital Italiano de Buenos Aires (AR), Hospital General Universitario Gregorio Marañón (ES), Hospital de São João (PT), Hospital Universitari i Politècnic La Fe (ES), Nicolaus Copernicus University (PL), Wroclaw Medical University (PL), University of Gdańsk (PL), Hospital Universitario de Guadalajara (ES), Hospital Quirónsalud Sagrado Corazón (ES), Complejo Hospitalario Universitario de Santiago (ES), Marqués de Valdecilla University Hospital (ES), Hospital Universitario 12 De Octubre (ES), Vall d'Hebron Institut de Recerca (ES), Instituto Português de Oncologia Francisco Gentil (PT), Hospital Ramos Mejía (AR), Hospital Regional Universitario de Málaga (ES), Hospital Universitario Quirónsalud Madrid (ES), IPO Porto (PT), Hospital San Pedro de Alcántara (ES), Centro Hospitalar Lisboa Norte (PT), Hospital Universitario de Burgos (ES), Hospital de Galdakao (ES), National Institute of Oncology (HU), Universidad San Jorge (ES), Hospital Universitario Reina Sofía (ES), Instituto Alexander Fleming (AR), Vall d'Hebron Hospital Universitari (ES), Hospital Universitario Fundación Jiménez Díaz (ES), Instituto de Biomedicina de Sevilla (ES), Clinica Universidad de Navarra (ES), Hospital Clínico Universitario Lozano Blesa (ES), Hospital General Universitario de Alicante Doctor Balmis (ES), Hospital San Pedro (ES), Donostiako Unibertsitate Ospitalea (ES), Hospital Alemán (AR), Complexo Hospitalario Universitario A Coruña (ES), Hospital General Universitario de Albacete (ES), Hospital Universitario de Valme (ES), Hospital de Santa Maria (PT), Łukasiewicz Research Network - Institute of Welding (PL), Hospital Universitari Joan XXIII de Tarragona (ES), Hospital Universitario Virgen del Rocío (ES), Hospital Universitari Germans Trias i Pujol (ES), Complejo Hospitalario Universitario de Albacete (ES), Hospital Clínico Universitario Virgen de la Victoria (ES), INCLIVA Health Research Institute (ES), Universidad Isabel I (ES), Instituto de Investigación Sanitaria La Fe (ES), Instituto de Investigación Sanitaria del Principado de Asturias (ES), Narodowy Instytut Leków (PL), Universidad de Burgos (ES), Poznań University of Technology (PL), Gdańsk Medical University (PL), University of Silesia in Katowice (PL)
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Cutaneous lymphoproliferative disorders research
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