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.

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)

Sarcoma folicular de células dendríticas mediastinal: primer reporte de caso en Costa Rica / Mediastinal Follicular Dendritic Cell Sarcoma: First Case Report in Costa Rica

El sarcoma folicular de células dendríticas (SFCD) es una neoplasia maligna rara derivada de las células dendríticas foliculares. Ha sido clasificado, dadas sus características inmunohistoquímicas, como parte del grupo de los sarcomas, donde representa un porcentaje menor al 1%. Actualmente, existen menos de 1.000 reportes en la literatura a nivel mundial, lo cual plantea una dificultad no sólo diagnóstica, siendo confundido frecuentemente con neoplasias de tipo linfoide; sino también terapéutica al no existir un claro consenso sobre su manejo definitivo. Esta revisión de caso clínico describe el primer caso reportado de SFCD en Costa Rica.

Follicular dendritic cell sarcoma (SFCD) is a rare malignant neoplasm derived from follicular dendritic cells, which has been classified, given its immunohistochemical characteristics, as part of the group of sarcomas, where it represents less than 1%. Currently, there are less than 1000 reports in the literature worldwide, which generates a difficulty not only in diagnosis, being frequently confused with lymphoid type neoplasms; but also, as therapeutic as there is no clear consensus on its definitive management. This clinical case review describes the first reported case of SFCD in Costa Rica.

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)

[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.

Diacerein mitigates renal ischemia/reperfusion injury via inhibition of renal inflammation, dendritic cells maturation and apoptosis: the role of TLR4/NF-kB/NLRP3/IL-1beta signaling pathway / La diacereína mitiga la lesión por isquemia/reperfusión renal a través de la inhibición de la inflamación renal, la maduración de las células dendríticas y la apoptosis: el papel de la vía de señalización TLR4/NF-kB/NLRP3/IL-1beta

SUMMARY: One of the reasons for acute kidney damage is renal ischemia. Nevertheless, there are limited protective and therapeutic approaches for this problem. Diacerein is an anti-inflammatory drug characterized by numerous biological activities. We aimed to determine the ameliorative impact of diacerein on renal ischemia/reperfusion injury (I/R) condition, exploring the underlying mechanisms. Twenty-four male rats were allotted into four groups (n= 6): sham group; Diacerein (DIA) group; I/R group, in which a non-crushing clamp occluded the left renal pedicle for 45 min, and the right kidney was nephrectomized for 5 min before the reperfusion process; I/R + diacerein group, injected intraperitoneally with 50 mg diacerein/kg i.m 30 minutes prior to I/R operation. Ischemia/ reperfusion was found to affect renal function and induce histopathological alterations. The flow cytometry analysis demonstrated an elevated expression of innate and mature dendritic cells in I/R renal tissues. Moreover, upregulation in the expression of the inflammatory genes (TLR4, Myd88, and NLRP3), and overexpression of the pro-inflammatory cytokines (IL-1β), apoptotic (caspase-3) and pyroptotic (caspase-1) markers were observed in I/R-experienced animals. The aforementioned deteriorations were mitigated by pre-I/R diacerein treatment. Diacerein alleviated I/R-induced inflammation and apoptosis. Thus, it could be a promising protective agent against I/R.

La isquemia renal es una de los motivos del daño renal agudo. Sin embargo, los enfoques protectores y terapéuticos para este problema son limitados. La diacereína es un fármaco antiinflamatorio caracterizado por numerosas actividades biológicas. Nuestro objetivo fue determinar el impacto de mejora de la diacereína en la condición de lesión por isquemia/ reperfusión renal (I/R), explorando los mecanismos subyacentes. Veinticuatro ratas macho se distribuyeron en cuatro grupos (n= 6): grupo simulado; grupo de diacereína (DIA); grupo I/R, en el que una pinza no aplastante ocluyó el pedículo renal izquierdo durante 45 min, y el riñón derecho fue nefrectomizado durante 5 min antes del proceso de reperfusión; Grupo I/R + diacereína, inyectado por vía intraperitoneal con 50 mg de diacereína/kg i.m. 30 min antes de la operación I/R. Se encontró que la isquemia/ reperfusión afecta la función renal e induce alteraciones histopatológicas. El análisis de citometría de flujo demostró una expresión elevada de células dendríticas innatas y maduras en tejidos renales I/R. Además, se observó una regulación positiva en la expresión de los genes inflamatorios (TLR4, Myd88 y NLRP3) y una sobreexpresión de las citoquinas proinflamatorias (IL-1β), marcadores apoptóticos (caspasa-3) y piroptóticos (caspasa-1) en animales con experiencia en I/R. Los deterioros antes mencionados fueron mitigados por el tratamiento previo a la diacereína I/R. La diacereína alivió la inflamación y la apoptosis inducidas por I/R. Por lo tanto, podría ser un agente protector prometedor contra I/R.

Novas perspectivas em imunoterapia: a importância das células dendríticas na imunoterapia alérgeno-específica / New perspectives in immunotherapy: the importance of dendritic cells in allergen-specific immunotherapy

A imunoterapia alérgeno-específica é o único tratamento capaz de alterar o curso natural da doença alérgica. Ensaios clínicos mostram que a imunoterapia é segura e eficaz para muitos pacientes. No entanto, ainda enfrenta problemas relacionados à eficácia, segurança, longa duração do tratamento e baixa adesão dos pacientes. Neste contexto, tem havido intensa pesquisa no desenvolvimento de adjuvantes com objetivo de aumentar a segurança, otimizar os esquemas de tratamento e melhorar a adesão dos pacientes. Alérgenos foram modificados (glicoconjugados) com carboidratos derivados de Saccharomyces cerevisae para aumentar sua captação e apresentação através dos receptores de carboidratos presentes nas células dendríticas, beneficiando-se da capacidade de atuarem na indução de tolerância para iniciar respostas imunes. À luz de novas evidências, essas células constituem alvo terapêutico chave para se obter uma resposta adequada à imunoterapia alérgeno-específica, com potencial de contribuição na inovação do campo da Imunoterapia.

Allergen-specific immunotherapy is the only treatment capable of altering the natural course of allergic disease. Clinical trials have shown that immunotherapy is safe and effective for many patients. However, it still faces problems related to efficacy, safety, long treatment duration and poor patient compliance. In this context, there has been intense research into the development of adjuvant treatments that increase safety, optimize treatment regimens, and improve patient compliance. Allergens were modified (glycoconjugated) with carbohydrates derived from Saccharomyces cerevisae to increase their uptake and presentation through carbohydrate receptors in dendritic cells, benefiting from their ability to induce tolerance and initiate immune response. In light of the new evidence, these cells are a key therapeutic target for adequate response to allergenspecific immunotherapy and can drive innovation in the field of immunotherapy.

Mecanismo de células dendríticas derivadas de sangre periférica humana en la regulación de la autofagia en células de carcinoma / Mechanism of human peripheral blood-derived dendritic cells in the regulation of autophagy in carcinoma cells

Resumen Introducción: Las células dendríticas (CD) están involucradas en el reconocimiento, respuesta y modulación inmunológicos relacionados con la aparición del cáncer. Objetivo: Explorar el mecanismo de las CD en la inhibición de la autofagia de las células del hepatoma. Métodos: Células mononucleares de sangre periférica humana se aislaron mediante centrifugación en gradiente de densidad de Ficoll y se indujeron en CD, las cuales fueron cocultivadas con células HepG2 por ensayo de migración Transwell. La actividad de las células HepG2 se determinó mediante ensayo CCK8. La expresión del índice de autofagia LC3 se midió con análisis de transferencia Western y la expresión y secreción de citocinas mediante qRT-PCR y ELISA. Resultados: En el sistema de cocultivo, las CD redujeron la viabilidad de HepG2; la expresión de IL-2, IL-12, IL-10 e IFN-γ en CD también se inhibió significativamente, si bien IL-2 e IFN-γ aún se expresaron 0.6 y 0.53 más que en el grupo de control. Conclusión: Las CD pueden regular la autofagia de las células del carcinoma hepatocelular. El mecanismo puede estar relacionado con la síntesis y liberación de citocinas como IL-2, IL-12 e IFN-γ por parte de las CD.

Abstract Introduction: Dendritic cells (DC) are involved in immune recognition, response and immunomodulation mechanisms related to the onset of cancer. Objective: To explore DCs mechanism in the inhibition of autophagy in hepatoma cells. Methods: Human peripheral blood mononuclear cells were isolated by Ficoll density gradient centrifugation and induced into DCs, which were co-cultured with HepG2 cells by Transwell migration assay. HepG2 cell activity was determined using the CCK8 assay. LC3 autophagy index expression was measured with Western blot analysis, and the expression and secretion of cytokines, with qRT-PCR and ELISA. Results: In the co-culture system, DCs were able to reduce HepG2 cells viability; IL-2, IL-12, IL-10 and IFN-γ expression in DCs was also significantly inhibited, although IL-2 and IFN-γ were still expressed 0.6 and 0.53 more than in the control group. Conclusion: DCs can regulate autophagy in hepatocellular carcinoma cells. The mechanism may be related to the synthesis and release of cytokines such as IL-2, IL-12 and IFN-γ by DCs.

Mechanism of human peripheral blood-derived dendritic cells in the regulation of autophagy in carcinoma cells.

INTRODUCTION: Dendritic cells (DC) are involved in immune recognition, response and immunomodulation mechanisms related to the onset of cancer. OBJECTIVE: To explore DCs mechanism in the inhibition of autophagy in hepatoma cells. METHODS: Human peripheral blood mononuclear cells were isolated by Ficoll density gradient centrifugation and induced into DCs, which were co-cultured with HepG2 cells by Transwell migration assay. HepG2 cell activity was determined using the CCK8 assay. LC3 autophagy index expression was measured with Western blot analysis, and the expression and secretion of cytokines, with qRT-PCR and ELISA. RESULTS: In the co-culture system, DCs were able to reduce HepG2 cells viability; IL-2, IL-12, IL-10 and IFN-γ expression in DCs was also significantly inhibited, although IL-2 and IFN-γ were still expressed 0.6 and 0.53 more than in the control group. CONCLUSION: DCs can regulate autophagy in hepatocellular carcinoma cells. The mechanism may be related to the synthesis and release of cytokines such as IL-2, IL-12 and IFN-γ by DCs.

INTRODUCCIÓN: Las células dendríticas (CD) están involucradas en el reconocimiento, respuesta y modulación inmunológicos relacionados con la aparición del cáncer. OBJETIVO: Explorar el mecanismo de las CD en la inhibición de la autofagia de las células del hepatoma. MÉTODOS: Células mononucleares de sangre periférica humana se aislaron mediante centrifugación en gradiente de densidad de Ficoll y se indujeron en CD, las cuales fueron cocultivadas con células HepG2 por ensayo de migración Transwell. La actividad de las células HepG2 se determinó mediante ensayo CCK8. La expresión del índice de autofagia LC3 se midió con análisis de transferencia Western y la expresión y secreción de citocinas mediante qRT-PCR y ELISA. RESULTADOS: En el sistema de cocultivo, las CD redujeron la viabilidad de HepG2; la expresión de IL-2, IL-12, IL-10 e IFN-γ en CD también se inhibió significativamente, si bien IL-2 e IFN-γ aún se expresaron 0.6 y 0.53 más que en el grupo de control. CONCLUSIÓN: Las CD pueden regular la autofagia de las células del carcinoma hepatocelular. El mecanismo puede estar relacionado con la síntesis y liberación de citocinas como IL-2, IL-12 e IFN-γ por parte de las CD.

Análisis inmunohistológico de las células dendríticas dérmicas positivas para CD34 y de la densidad de microvasos en el liquen escleroso genital y extragenital / Immunohistological Analysis of CD34-Positive Dermal Dendritic Cells and Microvessel Density in the Genital and Extragenital Lichen Sclerosus

Introducción El liquen escleroso (LiE) es una enfermedad crónica escleroatrófica que afectará generalmente el área anogenital y ocasionalmente a localizaciones extragenitales. Las células dendríticas dérmicas CD34 positivas (DDC) contribuyen al mantenimiento de la microarquitectura dérmica y a la modulación de la respuesta inmunitaria. El p53 es un gen supresor de tumores importante para la regulación del ciclo celular y de la apoptosis. De manera similar a lo que ocurre en la morfea (una condición escleroatrófica estrechamente relacionada con el LiE), la esclerosis dérmica, las alteraciones de las DDC y de la microvasculatura dérmica pueden ser mecanismos patogénicos subyacentes importantes en el LiE. Objetivos Examinar el perfil de las DDC positivas para el CD34, la densidad de microvasos (MVD) y la proteína p53 en el LiE. Materiales y métodos Se evaluaron los perfiles inmunohistológicos de las DDC, de la MVD y del p53 en 19 casos de LiE y en la piel normal de pacientes emparejados por edad y sexo (10 muestras), utilizando los anticuerpos contra el CD34 y el p53. Resultados Hubo una marcada disminución de los recuentos (1,7±0,5/mm2) o pérdida completa de DDC CD34+en el LiE en comparación con su elevada expresión en la piel normal (23,4±2,1/mm2, p =0,000). La MVD estaba notablemente aumentada en las lesiones de LiE (20±0,47) en comparación con la de la piel normal (5,50±0,20, p =0,000). Se observó una tinción nuclear discontinua, de células aisladas, débilmente positiva para el p53, localizada en los queratinocitos de las capas basales epidérmicas de la piel sana y de la piel afectada por el LiE. Conclusiones Hasta donde tenemos conocimiento, este es el primer estudio que analiza los perfiles de las DDC, de la MVD y del p53 de manera simultánea en el LiE. Los hallazgos sugirieron que las alteraciones de las DDC y de la MVD tienen papeles en la patogénesis del LiE (AU)

Background Lichen sclerosus (LiS) is a chronic scleroatrophic condition that usually affects the anogenital area and occasionally the extragenital sites. CD34-positive dermal dendritic cells (DDCs) contribute to the maintenance of the dermal microarchitecture and modulation of the immune response. p53 is a tumor suppressor gene important for the regulation of the cell cycle and apoptosis. Similar to morphea (a LiS-closely related scleroatrophic condition), dermal sclerosis, alterations of DDCs, and dermal microvasculature may be important underlying pathogenetic mechanisms in LiS. Objectives To examine the profile of CD34-positive DDCs, microvessel density (MVD), and p53 protein in LiS. Materials and methods The immunohistological profiles of DDCs, MVD, and p53 were examined in 19 cases of LiS and their age- and sex-matched normal skin (10 specimens), using antibodies against CD34 and p53. Results There was a markedly decreased counts (1.7±0.5/mm2) or complete loss of CD34-positive DDCs in LiS against their abundance in the normal skin (23.4±2.1/mm2, p=0.000). MVD was markedly increased in LiS lesions (20±0.47) as compared to normal skin (5.50±0.20, p=0.000). Discontinuous single-cell p53 weakly positive nuclear staining was seen in the epidermal basal cell keratinocytes in normal skin and LiS lesions. Conclusions To the best of this author's knowledge, this is the first study analyzing DDCs, MVD, and p53 profiles together in LiS. The findings suggest that alterations of DDCs and MVD have roles in the pathogenesis of LiS (AU)

Sarcoma de células dendríticas foliculares. Informe de un caso.

ANTECEDENTES: El sarcoma de células dendríticas foliculares es una enfermedad rara, caracterizada principalmente en sitios nodales como la cabeza, el cuello y la orofaringe, aunque puede ser extranodal, como en el bazo y el hígado. En la mayoría de los casos cursa asintomática, pero puede presentar síntomas generales, dolor abdominal o fiebre. La inmunohistoquímica es indispensable para llegar a un diagnóstico definitivo. PRESENTACIÓN DEL CASO: Mujer de 40 años, con abultamiento submaxilar en el cuello, región frontoparietooccipital derecha, y sequedad de mucosa oral. Se manejó inicialmente como un síndrome de Sjögren, que fue descartado por el resultado histopatológico de la biopsia de glándula salival. Posteriormente se realizó biopsia de ganglio del cuello, que reportó sarcoma de células dendríticas foliculares con expresión inmunohistoquímica positiva para CD23 y negativa para CD21 y ACL. Se manejó con samario y tuvo una sobrevida de 3 meses desde el diagnóstico. CONCLUSIONES: el sarcoma de células dendríticas foliculares es raro y la sobrevida es corta. BACKGROUND: Follicular dendritic cell sarcoma is a rare pathology, it occurs mainly in nodal sites such as head, neck, oropharynx, although extranodal presentation such as spleen and liver may occur. In most cases it is asymptomatic but may present general symptoms, abdominal pain or fever. Immunohistochemistry is essential to make a definitive diagnosis. CASE PRESENTATION: Forty year-old woman, with submaxillary lesion, in the neck, right fronto-parieto-occipital region with dry oral mucosa. It was initially managed as a Sjögren's syndrome ruled out by the histopathological result of salivary gland biopsy. Subsequently, a neck ganglion biopsy was performed that reported follicular dendritic cell sarcoma, with positive immunohistochemical expression for CD23 and negative for CD21 and LCA. It was managed with samarium with a survival of 3 months from the time of its diagnosis. CONCLUSIONS: Follicular dendritic cell sarcoma is rare and its global survival is short.

Immunohistological Analysis of CD34-Positive Dermal Dendritic Cells and Microvessel Density in the Genital and Extragenital Lichen Sclerosus.

BACKGROUND: Lichen sclerosus (LiS) is a chronic scleroatrophic condition that usually affects the anogenital area and occasionally the extragenital sites. CD34-positive dermal dendritic cells (DDCs) contribute to the maintenance of the dermal microarchitecture and modulation of the immune response. p53 is a tumor suppressor gene important for the regulation of the cell cycle and apoptosis. Similar to morphea (a LiS-closely related scleroatrophic condition), dermal sclerosis, alterations of DDCs, and dermal microvasculature may be important underlying pathogenetic mechanisms in LiS. OBJECTIVES: To examine the profile of CD34-positive DDCs, microvessel density (MVD), and p53 protein in LiS. MATERIALS AND METHODS: The immunohistological profiles of DDCs, MVD, and p53 were examined in 19 cases of LiS and their age- and sex-matched normal skin (10 specimens), using antibodies against CD34 and p53. RESULTS: There was a markedly decreased counts (1.7 ± 0.5/mm2) or complete loss of CD34-positive DDCs in LiS against their abundance in the normal skin (23.4 ± 2.1/mm2, p = 0.000). MVD was markedly increased in LiS lesions (20 ± 0.47) as compared to normal skin (5.50 ± 0.20, p = 0.000). Discontinuous single-cell p53 weakly positive nuclear staining was seen in the epidermal basal cell keratinocytes in normal skin and LiS lesions. CONCLUSIONS: To the best of this author's knowledge, this is the first study analyzing DDCs, MVD, and p53 profiles together in LiS. The findings suggest that alterations of DDCs and MVD have roles in the pathogenesis of LiS.

Immunohistological Analysis of CD34-Positive Dermal Dendritic Cells and Microvessel Density in the Genital and Extragenital Lichen Sclerosus. / Análisis inmunohistológico de las células dendríticas dérmicas positivas para CD34 y de la densidad de microvasos en el liquen escleroso genital y extragenital.

BACKGROUND: Lichen sclerosus (LiS) is a chronic scleroatrophic condition that usually affects the anogenital area and occasionally the extragenital sites. CD34-positive dermal dendritic cells (DDCs) contribute to the maintenance of the dermal microarchitecture and modulation of the immune response. p53 is a tumor suppressor gene important for the regulation of the cell cycle and apoptosis. Similar to morphea (a LiS-closely related scleroatrophic condition), dermal sclerosis, alterations of DDCs, and dermal microvasculature may be important underlying pathogenetic mechanisms in LiS. OBJECTIVES: To examine the profile of CD34-positive DDCs, microvessel density (MVD), and p53 protein in LiS. MATERIALS AND METHODS: The immunohistological profiles of DDCs, MVD, and p53 were examined in 19 cases of LiS and their age- and sex-matched normal skin (10 specimens), using antibodies against CD34 and p53. RESULTS: There was a markedly decreased counts (1.7±0.5/mm2) or complete loss of CD34-positive DDCs in LiS against their abundance in the normal skin (23.4±2.1/mm2, p=0.000). MVD was markedly increased in LiS lesions (20±0.47) as compared to normal skin (5.50±0.20, p=0.000). Discontinuous single-cell p53 weakly positive nuclear staining was seen in the epidermal basal cell keratinocytes in normal skin and LiS lesions. CONCLUSIONS: To the best of this author's knowledge, this is the first study analyzing DDCs, MVD, and p53 profiles together in LiS. The findings suggest that alterations of DDCs and MVD have roles in the pathogenesis of LiS.

Estudo da dinâmica celular da pele após tratamento epicutâneo com 7,12- Dimetilbenzantraceno em modelo murino de inflamação aguda / Study of skin cellular dynamic under 7,12 dimethylbenzantracene (DMBA) treatment in murine model of acute inflammatory response: the role of Ahr gene

The skin immune system is composed of different cell types of the innate immunity, among them the classic dendritic cells, Langerhans cells and Tγδ lymphocytes that are part of a set of cells which play a fundamental role in protecting against external infectious agents or carcinogenesis control. Found mainly in the epidermis, these cells constitute the cellular group of skin immunity and, therefore, are important for the study of cutaneous carcinogenesis. Polycyclic aromatic hydrocarbons (PAH) such as 7,12-dimethylbenzanthracene (DMBA), a synthetic prototype, present toxic action when coming in contact with skin. DMBA binds to the Aryl hydrocarbon receptor (AHR) in the cytoplasm to act as a Transcription Factor within the nucleus by inducing different genes transcription, including CYPs enzymes (P450) important in the PAH metabolism. Here, we analyzed the tumorigenic action of DMBA when applied on the skin of phenotypically selected mice for maximum (AIRmax) or minimum (AIRmin) acute inflammatory response. These mice, due the AHR genetic polymorphism, the DMBA action on the skin induces papillomas appearance and a particular cell dynamic in each lines of mice. Thus, we treated groups of 6 mice of each group, Acetone (control), and DMBA (5 consecutive applications). A second approach was carried out with the association of TPA (12-O-tetradecanoylphorbol- 13-acetate) and DMBA. In both approaches we evaluated the number of cutaneous lesions, skin histology and cell populations in the epidermis and dermis. We found that, for the two protocols used, AIRmin mice showed greater sensitivity to DMBA concerning the multiplicity and incidence of papillomas, the skin architecture and the presence of two Tγδ lymphocyte populations and dendritic cells. These characteristics observed mainly in AIRmin mice depend on their particular sensitivity to DMBA and open a field to identify the cellular mechanisms operating in the sensitivity to HPA carcinogens. Studies focusing on the two populations of Tγδ lymphocytes and dendritic cells may be promising in the sense of the therapeutic studies aiming to control the non-melanoma skin carcinogenesis development.

O sistema imunológico da pele é composto por diversas células que compõem a imunidade inata, dentre elas destacam-se as células dendríticas clássicas, de Langerhans e linfócitos Tγδ que fazem parte de um conjunto de células que possuem um papel fundamental na proteção contra agentes externos infecciosos e com funções importantes na carcinogênese. Localizadas principalmente na epiderme, essas células constituem o grupo celular da imunidade inata de proteção da pele e, por isso, são importantes para o estudo de carcinogênese cutânea. Tratando-se de agentes cancerígenos, podem-se destacar os hidrocarbonetos policíclicos aromáticos como, por exemplo, o 7,2-dimethylbenzanthraceno (DMBA) um protótipo sintético que possui ação tóxica quando em contato com a pele. O DMBA liga-se ao receptor Aril hidrocarboneto (AHR) localizado no citoplasma das células para exercer suas funções de Fator de Transcrição, induzindo a transcrição de diferentes genes, incluindo as enzimas CYPs importantes na metabolização dos compostos HPA. No presente estudo, analisamos a ação tumorigênica do DMBA quando aplicado na pele de camundongos fenotipicamente selecionados para resposta inflamatória aguda máxima (AIRmax) ou mínima (AIRmin). Esses animais, por apresentarem polimorfismo genético no gene codificador do AHR, a ação do DMBA na pele induz o aparecimento de papilomas em número diferente e provavelmente propicia uma dinâmica celular particular em cada uma dessas linhagens. Assim, tratamos grupos de 6 animais de cada linhagem com Acetona (controle), DMBA (cinco aplicações) e avaliamos o aparecimento de lesões durante 62 dias. Um segundo protocolo com a associação de TPA (12-O- Tetradecanoylphorbol-13-acetate) e DMBA foi realizado com 3 animais de cada grupo e avaliados aos 78 dias após os tratamentos. Em ambos os experimentos avaliamos as características histopatológicas e a presença de populações celulares na epiderme e derme. Verificamos que, para os dois protocolos utilizados, os animais AIRmin apresentaram maior sensibilidade ao DMBA quando avaliamos a multiplicidade e a incidência de papilomas, as estruturas internas da pele e a presença principalmente de duas populações de linfócitos Tγδ e populações de células dendríticas. Essas características observadas nos camundongos AIRmin refletem sua maior sensibilidade ao DMBA e abre campo de estudo para identificar mecanismos celulares operantes na sensibilidade a carcinógenos do tipo HPA. Estudos focando as duas populações de linfócitos Tγδ e as populações de células dendríticas pode ser promissor no sentido de indicar essas células como alvos terapêuticos para o controle da carcinogênese de pele não melanoma.

Ausencia de expresión de la proteína Core del virus de la hepatitis C en células dendríticas derivadas de monocitos humanos utilizando virus del Bosque de Semliki recombinante / Lack of expression of hepatitis c virus core protein in human monocyte-derived dendritic cells using recombinant semliki forest virus

ABSTRACT Hepatitis C Virus belongs to the Flaviviridae family. One proposed mechanism of HCV persistence in the ability to infect hematopoietic cells, including Dendritic cells (DCs). HCV infection of DCs could impair their functions that represent one of the mechanisms, thus hampering viral clearance by the host immune system. Among HCV-encoded proteins, the highly conserved Core protein has been suggested to be responsible for the immunomodulatory properties of this Hepacivirus. Recombinant viral vectors expressing the HCV Core protein and allowing its transduction and therefore the expression of the protein into DCs could be useful tools for the analysis of the properties of the Core protein. Vaccinia Virus and retrovirus have been used to transduce human DCs. Likewise, gene transfer into DCs using Semliki Forest Virus has been reported. This study aimed to express the HCV Core protein in human monocyte-derived DCs using an SFV vector, in which the subgenomic RNA encoding the structural proteins was replaced by the HCV Core sequence and then analyze the effects of its expression on DCs functions.

RESUMEN El virus de la Hepatitis C (VHC) pertenece a la familia Flaviviridae. Uno de los mecanismos propuestos de la persistencia del VHC es la capacidad de infectar células hematopoyéticas, incluidas las células dendríticas (DCs). La infección por VHC de DCs podría alterar sus funciones y corresponde a uno de los mecanismos que impiden el aclaramiento de la infección por VHC por el sistema inmunitario del hospedero. Entre las proteínas codificadas por el VHC, se ha sugerido que la proteína Core, altamente conservada, es responsable de las propiedades inmunomoduladoras de este Hepacivirus. Los vectores virales recombinantes que expresan la proteína Core y permiten su transducción a DCs podrían ser herramientas útiles para el análisis de las propiedades de esta proteína. El virus Vaccinia y el retrovirus se han utilizado para la transducción de DCs humanas. Del mismo modo, la transducción de DCs usando el virus del bosque de Semliki ha sido reportada. El objetivo de este estudio fue expresar la proteína Core de VHC en DCs derivadas de monocitos humanos utilizando un vector de SFV, en el que el ARN subgenómico que codifica las proteínas estructurales fue reemplazado por la secuencia Core del VHC y evaluar los efectos de su expresión en las funciones de DCs.

Las células dendríticas plasmacitoides evocan la respuesta efectora de los linfocitos T citotóxicos específicos para Salmonella / The plasmacytoid dendritic cells evoke Salmonella-specific CTL effector response

Resumen Introducción. La función inmunológica de las células dendríticas plasmacitoides durante las infecciones bacterianas, como la de Salmonella spp., es poco conocida. En ese contexto, se analizó su función efectora para presentar antígenos de Salmonella Typhimurium ante linfocitos T citotóxicos. Objetivo. Analizar la respuesta de los linfocitos T citotóxicos específicos para Salmonella evocada por las células dendríticas plasmacitoides. Materiales y métodos. Se usaron células dendríticas plasmacitoides marcadas con éster de succinimidil-carboxifluoresceína, pulsadas con el epítopo de Salmonella OmpC73 Kb- restringido o infectadas con S. Typhimurium como blanco en ensayos de citotoxicidad. Resultados. La lisis específica tuvo significación estadística usando células dendríticas plasmacitoides positivas pulsadas con OmpC73 en todas las relaciones de células efectoras y blanco (E:B) (p≤0,05); en cuanto a las células dendríticas plasmacitoides positivas para S. Typhimurium, solo se observó significación estadística en la relación de 1:100 (p≤0,05) usando las células efectoras OmpC73. Conclusión. Las células dendríticas plasmacitoides pueden evocar la respuesta de los linfocitos T citotóxicos durante la infección con S. Typhimurium.

Abstract Introduction: The immunological role of plasmacytoid dendritic cells (pDC) in bacterial infections such as Salmonella has been poorly documented. Therefore, we analyzed the effector function of these cells by presenting cytotoxic T lymphocytes (CTL) with Salmonella Typhimurium antigens. Objective: To analyze the Salmonella-specific CTL response evoked by pDCs. Materials and methods: We used plasmacytoid dendritic cells stained with carboxyfluorescein succinimidyl ester (CFSE) and pulsed with OmpC73, Salmonella Kb- restricted epitopes or S. Typhimurium as targets for cytotoxicity assays. Results: Specific lysis was shown to be statistically significant in pDC + OmpC73 for all effector:target ratios (p≤0.05). For pDC + S. Typhimurium, statistical significance was only observed at a 1:100 ratio (p≤0.05) using OmpC73. Conclusion: Plasmacytoid dendritic cells evoke CTL response during S. Typhimurium infection.

Neoplasia blástica de células dendríticas plasmocitoides variante leucemia aguda: reporte de un caso / Blastic plasmacytoid dendritic cell neoplasm variant acute leukemia: case report

RESUMEN La neoplasia blástica de células dendríticas plasmocitoides (NBCDP) es una malignidad hematológica poco frecuente y generalmente agresiva, por lo cual se requiere su reconocimiento precoz. A continuación, se describe el curso clínico prolongado de un paciente masculino de 60 años con NBCDP procedente de Venezuela, en cuyos hallazgos más relevantes destacó la presencia de lesiones cutáneas, organomegalias, infiltración de la médula ósea y del sistema nervioso central. Posterior al diagnóstico se indicó quimioterapia sistémica, no obstante, el paciente falleció por complicaciones respiratorias durante la fase de inducción del tratamiento. En esta enfermedad es necesario establecer el diagnóstico diferencial con trastornos linfoproliferativos, leucemias linfoides y mieloides agudas, constituyendo el análisis morfológico de las células neoplásicas un aspecto importante para una adecuada orientación diagnóstica.

ABSTRACT Blastic plasmacytoid dendritic cell blast neoplasm (BPDCN) is a rare and generally aggressive hematologic malignancy, requiring early recognition. Below is a description of the prolonged clinical course of a 60-year-old male patient with BPDCN from Venezuela, whose most relevant findings highlighted the presence of skin lesions, organomegaly, infiltration of the bone marrow and central nervous system. Systemic chemotherapy was prescribed after diagnosis; however, the patient died of respiratory complications during the induction phase of treatment. In this disease, it is necessary to establish the differential diagnosis with lymphoproliferative disorders, acute lymphoid and myeloid leukemias. The morphological analysis of neoplastic cells is, thus, an important aspect toward proper diagnostic guidance.

[Histiocytic and dendritic cell neoplasms: Review of the literature]. / Neoplasias de células histiocitarias y dendríticas: revisión de la literatura.

Histiocytic and dendritic cell neoplasms (HDN) are rare and their biology, prognosis, treatment and terminology are still under discussion. They are composed of macrophage and dendritic-derived cells and show a wide range of clinical, morphological and prognostic features. Clinicopathological correlation and a broad immunohistochemical panel are required to establish a correct diagnosis. After the detection of BRAF mutations in Langerhans cell histiocytosis, the potential role of other molecular alterations is being studied. We have reviewed the literature published in the last 10 years to provide an overview of NHD, with particular emphasis their molecular features.

Role of altered immune cells in liver diseases: a review.

Immune cells play an important role in controlling liver tumorigenesis, viral hepatitis, liver fibrosis and contribute to pathogenesis of liver inflammation and injury. Accumulating evidence suggests the effectiveness of natural killer (NK) cells and Kupffer cells (KCs) against viral hepatitis, hepatocellular damage, liver fibrosis, and carcinogenesis. Activation of natural killer cells provides a novel therapeutic strategy to cure liver related diseases. This review discusses the emerging roles of immune cells in liver disorders and it will provide baseline data to scientists to design better therapies for treatment.

Sarcoma de células dendríticas foliculares: una entidad poco frecuente / Follicular dendritic cell sarcoma: an unsual entity

Los sarcomas de células dendríticas foliculares son neoplasias linfoides extremadamente raras. Afectan primordialmente a ganglios linfáticos con compromiso extranodal ocasional. El diagnóstico defini-tivo requiere inmunohistoquímica. Su comportamiento clínico, el tratamiento, así como su evolución resultan poco conocidos. Presentamos el caso de un paciente al que se le diagnosticó un sarcoma dendrítico folicular con afectación axilar.

Folicular dendritic cell sarcoma is an extremelly rare lymphoid neoplasm. Lymph nodes are predominantly afected, but occasionallu extranodal compromise is seen. Definitive diagnosis requires confirmaton by inmunohistochemistry. The clinical features and management are not well know. We present the case follicular dendritic cell sarcoma with axilary afectaton.