Plump endothelial cells integrated into pre-existing venules contribute to the formation of 'mother' and 'daughter' vessels in pyogenic granuloma: possible role of galectin-1, -3 and -8.

INTRODUCTION: Pyogenic granuloma (PG) is a reactive inflammatory vascular lesion of the skin and mucous membranes, characterised by the presence of enlarged venules and seamed and seamless capillaries with plump endothelial cells (EC), and numerous macrophages. EC activation upregulates the synthesis of galectins and induces their translocation to the EC surface promoting angiogenesis and lymphangiogenesis, particularly galectin-1 (Gal-1), Gal-3 and Gal-8. However, the presence and distribution of Gal-1, -3 and -8, as well as their implications in the pathogenesis of PG, has not been considered. MATERIALS AND METHODS: Eight biopsies from patients diagnosed with PG were selected. The presence of PECAM-1/CD31, IL-1ß, VEGF-C, VEGFR-2, VEGFR-3, integrin ß1, CD44, fibronectin and Gal-1, -3 and -8 was assessed by immunofluorescence staining using confocal laser scanning microscopy. RESULTS AND DISCUSSION: Immunostaining revealed that these molecules were present in the enlarged venules with plump ECs, in some macrophages and other immune cells. We propose that macrophages release VEGF-A and VEGF-C inducing VEGFR-2/VEGFR-3 expression and activation, leading macrophages to transdifferentiate into plump ECs that might integrate into pre-existing venules, contributing to the formation of enlarged venules with transluminal bridges and capillaries. EC activation, induced by certain cytokines, has been shown to stimulate galectin expression and changes in the cellular localisation through association and activation of specific EC surface glycoproteins. Therefore, it is plausible that Gal-1, -3 and -8, acting in a concerted manner, could be mediating the transdifferentiation of macrophages into plump ECs and facilitating their migration and incorporation into the new vessels. LAY SUMMARY: In this study, immunostaining of pyogenic granuloma (PG) tissue sections showed immunoreactivity for PECAM-1/CD31, IL-1ß, VEGF-C, VEGFR-2 and VEGFR-3, and galectin-1, -3 and -8 in enlarged venules with plump endothelial cells (EC), as well as in some macrophages and other immune cells. Interestingly, enlarged and thin-walled transient vessels lined by PECAM-1/CD31 and VEGFR-2 immunopositive ECs that form from pre-existing normal venules in response to VEGF-A (called 'mother' vessels [MV]) and that undergo intraluminal bridging evolving into various types of capillaries (called 'daughter' vessels [DV]) have been observed in benign and malignant tumours, in physiological and pathological angiogenesis as well as in vascular malformations, suggesting an important role for VEGF-A and VEGFR-2 in such a process. However, it is not only the mechanisms by which the MVs evolve in different types of DVs that remains to be elucidated, but also whether the cells that form intraluminal bridges proceed from locally activated ECs or whether they are derived from bone marrow precursors or from resident macrophages.Given that the formation of homodimers by Gal-1 and Gal-8 and pentamers by Gal-3 to generate gal-glycan lattices at the cell surface and in the extracellular space has been shown, it is possible that in PG tissue Gal-1, -3 and -8, through their binding partners, form a supramolecular structure at the surface of ECs and plump ECs, macrophages and in the extracellular space that might be mediating the transdifferentiation of macrophages into plump ECs and facilitating the migration and incorporation of these cells into the pre-existing venules, thus contributing to the formation of MVs and DVs.

Galectin-1 and Galectin-3 and Their Potential Binding Partners in the Dermal Thickening of Keloid Tissues.

Keloids are defined histopathologically as an inflammatory disorder characterized by exhibiting numerous fibroblasts, abnormal vascularization, increased number of proinflammatory immune cells as well as uncontrolled cell proliferation, and exacerbated and disorganized deposition of extracellular matrix (ECM) molecules. Importantly, many of these ECM molecules display N- and O-linked glycan residues and are considered as potential targets for galectin-1 (Gal-1) and galectin-3 (Gal-3). Nevertheless, the presence and localization of Gal-1 and Gal-3 as well as the interactions with some of their binding partners in keloid tissues have not been considered. Here, we show that in the dermal thickening of keloids, versican, syndecan-1, fibronectin, thrombospondin-1, tenascin C, CD44, integrin ß1, and N-cadherin were immunolocalized in the elongated fibroblasts that were close to the immune cell infiltrate, attached to collagen bundles, and around the microvasculature and in some immune cells. We also show that Gal-1 and Gal-3 were present in the cytoplasm and along the cell membrane of some fibroblasts and immune and endothelial cells of the dermal thickening. We suggest that Gal-1 and Gal-3, in concert with some of the ECM molecules produced by fibroblasts and by immune cells, counteract the inflammatory response in keloids. We also proposed that Gal-1 and Gal-3 through their binding partners may form a supramolecular structure at the cell surface of fibroblasts, immune cells, endothelial cells, and in the extracellular space that might influence the fibroblast morphology, adhesion, proliferation, migration, and survival as well as the inflammatory responses.

Presence of MUC1 in the epidermal thickening of psoriatic plaques.

Mucin 1 (MUC1) is a transmembrane glycoprotein that protects epithelial cells from injury caused by external stimuli. In addition to this role, MUC1 is involved in cell-cell adhesion, proliferation, motility, invasion and survival. In epithelial cells, MUC1 expression is regulated by binding of TNFα to TNFR1 and activation of the NFκB pathway. In human skin, MUC1 is not expressed in normal epidermis but rather in pre-malignant and malignant conditions. Nevertheless, the expression of MUC1 and its implication in psoriasis vulgaris has not been considered. Here, we show that MUC1 was present in the epidermis of psoriatic plaques observed in 11 biopsies from patients diagnosed with psoriasis vulgaris which were compared with 5 normal human skin. Interestingly, MUC1 in addition to being localized at the apical surface of some suprabasal keratinocytes, was also localized over the entire cell surface of some of these cells and some basal keratinocytes. Conversely, no MUC1 immunoreactivity was detected in the epidermis of normal skin. Additionally, we demonstrated that activated TNFR1, c-Src, IKKα/ß and p50/p65 were present in the epidermal thickening. This study demonstrates the presence of MUC1 in psoriatic plaque and suggests a possible role for MUC1 during the motility, migration and survival of human keratinocytes, where activated TNFR1, c-Src and NFκB seem to be required.

Mycobacterium cosmeticum sp. nov., a novel rapidly growing species isolated from a cosmetic infection and from a nail salon.

Four isolates of a rapidly growing Mycobacterium species had a mycolic acid pattern similar to that of Mycobacterium smegmatis, as determined by HPLC analyses. Three of the isolates were from footbath drains and a sink at a nail salon located in Atlanta, GA, USA; the fourth was obtained from a granulomatous subdermal lesion of a female patient in Venezuela who was undergoing mesotherapy. By random amplified polymorphic DNA electrophoresis and PFGE of large restriction fragments, the three isolates from the nail salon were shown to be the same strain but different from the strain from the patient in Venezuela. Polymorphisms in regions of the rpoB, hsp65 and 16S rRNA genes that were shown to be useful for species identification matched for the two strains but were different from those of other Mycobacterium species. The 16S rRNA gene sequence placed the strains in a taxonomic group along with Mycobacterium frederiksbergense, Mycobacterium hodleri, Mycobacterium diernhoferi and Mycobacterium neoaurum. The strains produced a pale-yellow pigment when grown in the dark at the optimal temperature of 35 degrees C. Biochemical testing showed that the strains were positive for iron uptake, nitrate reduction and utilization of d-mannitol, d-xylose, iso-myo-inositol, l-arabinose, citrate and d-trehalose. The strains were negative for d-sorbitol utilization and production of niacin and 3-day arylsulfatase, although arylsulfatase activity was observed after 14 days. The isolates grew on MacConkey agar without crystal violet but not on media containing 5 % (w/v) NaCl or at 45 degrees C. They were susceptible to ciprofloxacin, amikacin, tobramycin, cefoxitin, clarithromycin, doxycycline, sulfamethoxazole and imipenem. The name Mycobacterium cosmeticum sp. nov. is proposed for this novel species; two strains, LTA-388(T) (=ATCC BAA-878(T)=CIP 108170(T)) (the type strain) and 2003-11-06 (=ATCC BAA-879=CIP 108169) have been designated, respectively, for the strains of the patient in Venezuela and from the nail salon in Atlanta, GA, USA.

Características clínicas e histológicas del carcinoma basocelular / Clinical characteristics and histological of the basal cell carcinoma

El Carcinoma Basocelular (CBC) es el tumor maligno más común en los seres humanos y afecta sobre todo a la población caucásica. Determinar la frecuencia de CBC y su distribución según sexo, edad, fototipo de piel y localización anatómica. Se realizó un estudio epidemiológico descriptivo donde se incluyeron todas las biopsias con el diagnóstico de CBC durante el lapso comprendido entre Mayo 2001 y Agosto 2002 realizadas en el Laboratorio de dermopatología del Instituto de Biomedicina, Hospital Vargas. Se recolectaron datos referentes a edad, sexo, fototipo de piel, localización anatómica y subtipo histológico. Resultados. En el periodo estudiado fueron diagnosticados 203 CBC, lo cual representa un 5 por ciento del total de biopsias procesadas. 45 por ciento de los pacientes eran del sexo femenino y 55 por ciento del masculino con edades promedio de 57 y 59 años, respectivamente. El sitio de localización mas frecuente fue la región de la cabeza, especialmente la nariz. La presencia de un patrón histológico único fue encontrado en 80 por ciento de las biopsias, siendo el CBC nodular el subtipo histológico más frecuente (68 por ciento) seguido por el CBC basoescamoso (18 por ciento). Nuestros hallazgos son similares a aquellos reportados en la literatura mundial con respecto al sexo, localización anatómica y subtipo histológico mas frecuente

Carcinoma adenoideo-quístico primario de piel: presentación de un caso / Primary skin adenoided cystic carcinoma: presentation of a case

El carcinoma adenoideo-quístico primario de piel es una neoplasia infrecuente y constituye sólo el 2 por ciento de los tumores malignos de las glándulas sudoríparas. Hasta la actualidad se han reportado sólo 25 casos en la literatura. Desde el punto de vista clínico se presenta como un tumor de crecimiento lento, indolente, pero progresivo con recurrencias locales de 50 por ciento. La metástasis a distancia representan un evento raro y tardío en el curso de la enfermedad. Desde el punto de vista histológico es indistinguible de su contraparte en las glándulas salivales y presentan un perfil similar de antígenos tales como CEA, EMA, y citoqueratinas de bajo peso molecular. Debe ser diferenciado principalmente del carcinoma basocelular con patrón adenoideo y de otros carcinomas ecrinos como el acrospiroma ecrino maligno. En este trabajo se presenta un nuevo caso de carcinoma adenoideo-quístico cutáneo, revisando sus características y comparándolas con las descritas en la literatura

El uso inadecuado de los materiales de implante dérmico es la causa más probable de complicación en los pacientes / Inadequate technique in dermal implants is the most probable cause of complications

Los materiales de relleno dérmico son herramientas de dermatólogos o cirujanos plásticos en el manejo de problemas estéticos. Las lesiones que pueden producirse como consecuencia de su uso son inquietantes. Se realiza un estudio descriptivo de las características clínicas e histopatológicas de las lesiones ocasionadas por materiales de relleno dérmico estudiadas en la Sección de Dermatología del Instituto de BIomedicina. Se obtuvieron un total de nueve biopsias procedentes de seis pacientes. Ocho provenían del sitio de implante de material de relleno y una de ellas del lugar donde migró. Cinco pacientes eran de sexo femenino y uno masculino con una edad promedio de 50,8 años. Cinco biopsias provenían del surco nasogeniano. Cinco de los pacientes referían haber recibido implantes con silicona líquida y uno de ellos con una sustancia denominada "cartílago". Siete biopsias presentaban características típicas de infiltración por la forma líquida de silicona. Siete biopsias presentaban vacuolas desde la dermis papilar o media. Se concluye que el material más empleado fue la silicona liquída. Se describen tres patrones histopatológicos en estas lesiones: xantomatoso, en queso suizo e inflamatorio. La causa más probable de la lesión fue inadecuada técnica en más de la mitad de los casos. Se sugiere buscar mecanismos de control para evitar la realización de este procedimiento por personas no autorizadas y sin la adecuada formación

Enfermedad de kimura e hiperplasia angiolinfoide con eosinofilia: diferencias clinicas e histopatológicas presentación de dos casos / Kimura's disease and angiolymphoid hiperplasia with eosinophilia: clinicals and histopathologic differences: presentation of two cases

Existe considerable controversia acerca de la relación entre la enfermedad de Kimura y la Hiperplasia angiolinfoide eosinofílica (HALE). Los autores presentan y revisan los hallazgos clínicos e hispatológicos de dos casos con estos diagnósticos. La enfermedad de Kimura se presenta en una paciente (adulto joven) de 44 años como un nódulo subcutáneo profundo, la piel que lo recubre es normal, de curso crónico y recidivante posterior a su intervención quirúrgica, sin tendencia al sangrado. El estudio histológico muestra folículos linfoides típicos con proliferación vascular periférica y eosinofilia periférica. La HALE se observó en un paciente de 72 años con nódulo exofítico en cuero cabelludo, la piel que lo recubre es eritematosa, de meses de evolución y fácil tendencia a ulcerarse y sangrar. El estudio histológico permitió observar acentuada proliferación vascular cuyas células endoteliales de tipo epitelioide se proyectan hacia la luz con un citoplasma vacuolado rodeados por un estroma con acentuada fibrosis. Se realiza la revisión de la literatura y se concluye que son entidades separadas diferenciables tanto desde el punto de vista clínico como histológico

Hemangiopericitoma / Hemangiopericytoma

Se presentan dos casos, el primer caso, es un paciente masculino, de 17 años de edad, quien resultó por presentar lesión tumoral en ala nasal izquierda, asintomática, de dos años de evolución, de 1,5 x 1,2 cms. de diámetro, color piel, sólido y recidivante ya que había sido extirpado quirúrgicamente un año antes. El segundo caso corresponde a una paciente femenina, de 29 años de edad, quien consultó con una lesión tumoral en labio inferior, asintomática, de un mes de evolución, de 1 cm. de diámetro, eritematosa y de consistencia blanda. En ambos casos, el diagnóstico de hemangiopericitoma se realizó a traves del estudio histopatológico. La presentación de estos casos confirma una vez más que el diagnóstico de hemangiopericitoma es histopatológico, que es un tumor de localización variable, en algunos casos recidivante y no siempre de comportamiento maligno