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

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B, Lesions on all fingernails." ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "J. Sánchez-Bernal, M. Álvarez-Salafranca, M. Ara-Martín" "autores" => array:3 [ 0 => array:2 [ "nombre" => "J." "apellidos" => "Sánchez-Bernal" ] 1 => array:2 [ "nombre" => "M." "apellidos" => "Álvarez-Salafranca" ] 2 => array:2 [ "nombre" => "M." 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Caracterización de la población de una clínica ambulatoria especializada en urticaria" ] ] "contieneResumen" => array:2 [ "en" => true "es" => true ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:8 [ "identificador" => "fig0015" "etiqueta" => "Figure 3" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr3.jpeg" "Alto" => 2404 "Ancho" => 2167 "Tamanyo" => 221934 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0015" "detalle" => "Figure " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "CTT and CsTT according to H1-antihistamines treatment regimens (H1-antiH/day). A and B—patients were divided in two groups: ≤1 representing patients treated on-demand or 1/day and ≥2 representing those needing 2 or more antihistamines to control the disease. C and D: Y represents daily dosage of antihistamines (OD-on demand). Only one patient was treated with 3/day dosage and had negative CST." ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "M. Paulino, C. Costa, M. Neto, E. Pedro" "autores" => array:4 [ 0 => array:2 [ "nombre" => "M." "apellidos" => "Paulino" ] 1 => array:2 [ "nombre" => "C." "apellidos" => "Costa" ] 2 => array:2 [ "nombre" => "M." "apellidos" => "Neto" ] 3 => array:2 [ "nombre" => "E." "apellidos" => "Pedro" ] ] ] ] ] "idiomaDefecto" => "en" "Traduccion" => array:1 [ "es" => array:9 [ "pii" => "S0001731021001435" "doi" => "10.1016/j.ad.2021.04.003" "estado" => "S300" "subdocumento" => "" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:1 [ "total" => 0 ] "idiomaDefecto" => "es" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0001731021001435?idApp=UINPBA000044" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S1578219021001827?idApp=UINPBA000044" "url" => "/15782190/0000011200000008/v2_202110201006/S1578219021001827/v2_202110201006/en/main.assets" ] "en" => array:20 [ "idiomaDefecto" => true "cabecera" => "Original Article" "titulo" => "Immunohistological Analysis of CD34-Positive Dermal Dendritic Cells and Microvessel Density in the Genital and Extragenital Lichen Sclerosus" "tieneTextoCompleto" => true "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "747" "paginaFinal" => "754" ] ] "autores" => array:1 [ 0 => array:3 [ "autoresLista" => "M.R.A. Hussein" "autores" => array:1 [ 0 => array:3 [ "nombre" => "M.R.A." "apellidos" => "Hussein" "email" => array:1 [ 0 => "frcpath17@gmail.com" ] ] ] "afiliaciones" => array:1 [ 0 => array:2 [ "entidad" => "Servicio de Anatomía Patológica, Hospital Universitario de Assuit Assuit, Egypt" "identificador" => "aff0005" ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Análisis inmunohistológico de las células dendríticas dérmicas positivas para CD34 y de la densidad de microvasos en el liquen escleroso genital y extragenital" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:8 [ "identificador" => "fig0015" "etiqueta" => "Figure 3" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr3.jpeg" "Alto" => 1900 "Ancho" => 2508 "Tamanyo" => 938022 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0015" "detalle" => "Figure " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "Genital (penile) lichen sclerosus (Balanitis xerotica obliterans of the foreskin, prepuce). A: The features of the penile LiS include the thinning of the epidermis with loss of the normal rete ridge pattern, broad condensation of the homogenously, and massively hyalinized papillary dermal collagen (arrowhead), and the dense patchy dermal lymphocytic infiltrate (arrow). B: Edema, condensation, and curling of the elastic fibers (Verhoeff-van Gieson stain for elastic fibers, arrow) at the base of the homogenized collagen (star). C-D: CD34 staining shows loss of CD34 dermal dendritic cells and an increased microvessel density (star). (Original magnifications. A: ×20, B: ×200, C:×20, and D: ×100)." ] ] ] "textoCompleto" => "IntroductionLichen sclerosus (LiS) is an insidious, chronic scleroatrophic inflammatory disease of unknown etiology. It affects the anogenital area such as the vulva (vulvar LiS), the male genitalia (LiS of the male genitalia or balanitis xerotica obliterans), and occasionally some extragenital sites such as buttocks, inner thigh, and under the breasts (extragenital LiS). LiS of the male genitalia usually affects the glans penis, foreskin (prepuce), the anterior urethra, and meatus, usually of uncircumcised males, resulting in phimosis and meatal stenosis<a class="elsevierStyleCrossRef" href="#bib0005">1</a>. Squamous cell carcinoma is the most common malignancy of the vulva. Its precursor lesions include the usual and the differentiated types of vulvar intraepithelial neoplasia (VIN). The differentiated VIN is associated with chronic dermatoses such as LiS and can progress to invasive squamous cell carcinoma. Human papillomavirus (HPV) DNA is always absent in these lesions. The usual type VIN affects is associated with high-risk HPV infection<a class="elsevierStyleCrossRef" href="#bib0010">2</a>.In 1984, CD34 antigen was first discovered on hematopoietic stem and progenitor cells. It is a transmembrane phosphoglycoprotein that consists of a heavily sialylated, O-linked glycosylated extracellular domain, a single transmembrane helix, and a cytoplasmic tail. Dendritic cells (DCs) are professional antigen-presenting cells. In the skin, there are CD34-positive dendritic cells (DDCs) in the dermis. CD34 is also expressed by vascular endothelial progenitors, and clusters of newly formed endothelial cells (microvessels), and therefore CD34 expression is an indicator of microvessel density (MVD) and tissue vascularization<a class="elsevierStyleCrossRefs" href="#bib0015">3,4</a>.LiS is closely related to other scleroatrophic conditions such as morphea and scleroderma. Some authorities consider LiS as a superficial or subepidermal morphea, or as scleroderma of the papillary dermis<a class="elsevierStyleCrossRefs" href="#bib0025">5,6</a>. These viewpoints are supported by several observations including the coexistence of morphea and LiS in some patients, the overlapping clinicopathological features, and their common possible underlying etiologies (Borrelia infection and autoimmunity)<a class="elsevierStyleCrossRefs" href="#bib0025">5,7</a> in both of them. Histologically, both morphea and LiS are characterized by the attenuation of the epidermis, which is reasoned to the aftermath of the dermal stromal changes including dermal hyalinization, sclerosis with decreased vascularization, and impaired tissue perfusion<a class="elsevierStyleCrossRefs" href="#bib0025">5–7</a>.Although to date the exact role and origin of DDCs are largely unknown, some investigations have suggested that DDCs are important for maintaining the dermal microarchitecture and the modulation of the immune response, and as such, they contribute to the development of scleroatrophic conditions such as LiS, morphea, and scleroderma<a class="elsevierStyleCrossRefs" href="#bib0040">8–11</a>. In morphea and scleroderma, previous studies have shown a decreased quantity of CD34-positive DDCs in the dermis<a class="elsevierStyleCrossRefs" href="#bib0040">8–12</a>. Aiba et al. examined the skin biopsies from lesions of 27 cases with scleroderma and also biopsies from normal skin of 17 individuals using antibodies against CD34. CD34-positive DDCs were either few or completely absent in the lesional skin of scleroderma. The authors suggested that CD34-positive cells may represent primary target cells in the autoreactive phenomenon in scleroderma<a class="elsevierStyleCrossRef" href="#bib0040">8</a>. Similarly, Gilmour et al. examined the number of CD34-positive DDCs in 33 skin biopsies of morphea and found a progressive decline in the numbers of these cells with the progression from the inflammatory to the sclerotic stages of morphea<a class="elsevierStyleCrossRef" href="#bib0055">11</a>. Moreover, there was an increased MVD both in both morphea and scleroderma<a class="elsevierStyleCrossRefs" href="#bib0065">13,14</a>. Taken together, CD34-positive DDCs seem to contribute to the development of scleroderma and morphea. To date, similar studies in LiS are limited<a class="elsevierStyleCrossRefs" href="#bib0065">13,14</a>.The tumor suppressor p53 gene encodes for a 53 KD nuclear protein that plays important roles in the regulation of cell cycle, and apoptosis<a class="elsevierStyleCrossRef" href="#bib0075">15</a>. In most benign cells, including the keratinocytes of the penile foreskin and vulvar skin<a class="elsevierStyleCrossRefs" href="#bib0080">16,17</a>, the expression of p53 protein is either absent or weak. Overexpression of p53 protein is frequent in the dysplastic and malignant squamous epithelial cells<a class="elsevierStyleCrossRef" href="#bib0090">18</a>. In LiS, p53 protein expression is weak to moderate nuclear, discontinuous, and localized to the basal cell keratinocytes (Pattern 0)<a class="elsevierStyleCrossRefs" href="#bib0085">17,19</a>.To date, we have limited knowledge about the profiles of CD34-positive DDCs, MVD, and p53 protein expression in LiS. This study used immunohistochemical techniques to address these issues.Materials and methodsThis is a retrospective case series in which the archival formalin-fixed paraffin-embedded tissues of 19 cases of LiS (sclerotic stage), from the Pathology Department, Assuit University Hospitals, and consultation files of this author, were used. All the materials (paraffin-embedded tissue blocks, slides, and pathology reports) were coded. The information obtained was analyzed and reported in such a way that the identities of the participants cannot be ascertained. The study did not include any interaction or intervention with human subjects or included any access to any identifiable private information. Therefore the study did not require institutional review board review<a class="elsevierStyleCrossRef" href="#bib0100">20</a>. The study was performed in accordance with the principles of the Declaration of Helsinki. The materials represented vulvar (11 cases), extragenital LiS (two cases), and LiS of the male genitalia (6 cases). The control group (normal skin) included ten healthy age and sex-matched individuals who underwent skin excisions for benign skin lesions. Paraffin-embedded tissues were sectioned for routine histological (Hematoxylin and Eosin stains) and special stains (elastic fibers, Verhoeff-van Gieson stain, VVG). The histologic sections were examined for the features of the usual and differentiated types of VIN. The tissue sections were prepared for immunostaining following other groups<a class="elsevierStyleCrossRefs" href="#bib0015">3,18</a>. Heat-induced epitope antigen retrieval technique was used (Dako Target Retrieval Solution, S1699; Dako, Carpinteria, California, USA) for 30 min at 95 °C followed by a 20-minute cooldown. The endogenous peroxidase activity was blocked with 10% hydrogen peroxide. Anti-CD34 primary antibody (DakoCytomation (Glostrup, Denmark; anti-human CD34 antibody), diluted in phosphate-buffered saline (PBS) was applied to each section. Antibodies against p53 (at a dilution of 1:200 dilution, Thermo scientific, Lab Vision Corporation, Fermont, Clone SP5, RM-9105-S1, USA) were applied to each section. Sections were incubated with primary antibodies at 4 °C overnight. Then sections were treated using the labeled polymer peroxidase method (DAKO EnVision™ + Peroxidase Kit, Dako, Carpinteria, CA) for 60 min following the manufacturer's instructions. Proteins were visualized using a liquid diaminobenzidine substrate kit (Zymed Laboratories, San Francisco, CA). Sections were counterstained in Mayer's Hematoxylin. Sections from hemangioma and squamous cell carcinoma were used as positive controls for the anti-CD34 and anti-p53 antibodies, respectively. Sections with PBS replacing the primary antibody were used as negative controls<a class="elsevierStyleCrossRef" href="#bib0015">3</a>. All slides were coded and evaluated by two observers blinded for clinical details and identity of the patients<a class="elsevierStyleCrossRef" href="#bib0105">21</a>.Immunohistochemical evaluation of the MVD, CD34-positive DDCs, and p53 protein expression: The immunostained sections were examined. In normal and lesional skins, CD34 immunostaining was absent from the epidermis. CD34-positive dermal dendritic cells in the dermis were counted in three randomly chosen square fields (1 mm2) following other groups<a class="elsevierStyleCrossRef" href="#bib0105">21</a>. Evaluation of MVD was performed following other groups. The sections were examined at low power magnification (×40) to identify the hot spots of microvessels in the dermis. Single endothelial cells or a cluster of endothelial cells reactive (membrane/cytoplasm staining) for CD34 in the membrane/cytoplasm was regarded as a distinct single countable microvessel. The number of microvessels was counted at higher magnification (×400). Vessel lumen and red cells, though often present, were not required to define a microvessel<a class="elsevierStyleCrossRefs" href="#bib0015">3,22</a>. p53 protein expression values were scored and reported following other groups<a class="elsevierStyleCrossRef" href="#bib0090">18</a>. Only nuclear staining was considered positive. Initially, the distribution of p53 positive cells was categorized into basal versus suprabasal. The staining intensity was scored as follows: weak 1+, moderate 2+, or strong 3+. The percentage of positive cells was calculated as the number of positive cells per 100 consecutive cells (0–25, 26–50, 51–75%, or >75%)<a class="elsevierStyleCrossRefs" href="#bib0085">17,18</a>. p53 staining profiles included three patterns. Pattern 0 indicates the presence of a nuclear, discontinuous; weak to moderate p53 staining that is localized to the basal cell keratinocytes (no suprabasal extension). Pattern 1 indicates the presence of a significantly increased p53 moderate to strong nuclear staining in the basal cell layer but without prominent suprabasal extension. Pattern 2 indicates the presence of a significantly increased p53moderate to strong nuclear reactivity in the basal cell layer, which is associated with prominent suprabasal extension<a class="elsevierStyleCrossRef" href="#bib0115">23</a>.Statistical analysis: Differences between the groups (normal skin versus LiS) were determined using the non-parametric Wilcoxon-Mann-Whitney following other groups<a class="elsevierStyleCrossRefs" href="#bib0060">12,24</a>. p values of less than 0.05 were treated as statistically significant. The results were presented as the Mean and standard error of the mean (SEM). Statistical tests were performed using SPSS version 23 (IBM Corp, New York, U.S.A.).ResultsClinicopathologic findings: The study included 19 cases with LiS with a mean age of 60.6 ± 4.5 years. The study included 11 cases of vulvar LiS (mean ± standard error of the mean of age: 64.3 ± 3.2 years). The sites of the vulvar lesions were labia minor (9 cases), perineum, and the posterior fourchette (one case, each). The study also included 6 cases of LiS of male genitalia involving the foreskin (mean ± standard error of the mean of age: 53.7 ± 13.1 years), and two cases of extragenital LiS (right breast and paraumbilical region, one case each, mean ± standard error of the mean of age: 60.0 ± 1.0 years). The histological sections were examined to obtain the diagnosis of LiS and to rule out squamous neoplasia. Features diagnostic of early differentiated type VIN/differentiated squamous cell carcinoma was seen in one case of LiS. Histologically, sections from both genital and extragenital LiS showed attenuation of the epidermis with the loss of the regular rete ridge pattern. A granular layer was present. There was no basal nuclear atypia. There was no acanthosis. There was papillary dermal edema and homogenization of the dermal collagen, fragmentation, and haphazard arrangement (horizontal, vertical, and random orientation) of the dermal elastic fibers (VVG stain). There were condensation and curling of the elastic fibers in the surrounding dermis. No fungal elements were detected (periodic acid–Schiff with and without diastase). Few, scattered lymphocytes were seen in the dermis. No evidence of squamous neoplasia could be identified in 18 cases. A summary of these findings was shown in <a class="elsevierStyleCrossRefs" href="#fig0005">Figs. 1–4</a>.<elsevierMultimedia ident="fig0005"></elsevierMultimedia><elsevierMultimedia ident="fig0010"></elsevierMultimedia><elsevierMultimedia ident="fig0015"></elsevierMultimedia><elsevierMultimedia ident="fig0020"></elsevierMultimedia>A markedly decreased number or complete loss of CD34-positive DDCs in LiS against their presence in the normal skin: The CD34-positive DDCs show brownish cytoplasmic staining. The dermis from the lesional skin (LiS) showed either complete loss of CD34-positive DDCs or rare CD34-positive DDCs as compared to the normal skin group. The mean expression values of DDCs counts were 1.7 ± 0.5/mm2 versus 23.4 ± 2.1/mm2 for LiS (both genital and extragenital cases) versus normal skin, respectively. The mean values of CD34-positive DDCs counts were 2.0 ± 0.7/mm2 (vulvar LiS), 1.8 ± 0.7/mm2 (LiS of the male genitalia), and 0.0 ± 0.0/mm2 (extragenital LiS). The differences between the lesional (LiS) and normal skins were statistically significant (p < 0.000). A summary of these findings was shown in <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a> and <a class="elsevierStyleCrossRefs" href="#fig0005">Figs. 1–4</a>.<elsevierMultimedia ident="tbl0005"></elsevierMultimedia>A markedly increased MVD in the dermis of LiS as compared to the normal skin: CD34 marker reactivity in the microvessels appeared as brown cytoplasmic reactivity with or without membrane staining. Areas with vessels having caliber larger than eight red blood cells were excluded. Large and medium-sized blood vessels with thick muscular walls or vessels with a luminal diameter of greater than 50 mM were excluded from the final count. The MVD values in the lesional skin of both genital and extragenital LiS (20.47 ± 0.63, p = 0.000) were statistically significantly high (p < 0.000) as compared to the normal skin (5.50 ± 0.2). The mean values of MVD were 19.45 ± 0.82 (vulvar LiS), 23 ± 0.44 (LiS of the male genitalia), and 18.50 ± 0.50 (extragenital LiS). A summary of these findings is shown in <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a> and <a class="elsevierStyleCrossRefs" href="#fig0005">Figs. 1–4</a>.p53 protein staining patterns in the normal skin, and LiS: The lesional and normal skins showed nearly similar p53 protein staining values and patterns. The reactivity was in the form of discontinuous individual single-cell p53+ nuclear staining (weak to moderate staining intensity) in the basal cell keratinocytes of the epidermis (in less than 10 % of basal keratinocytes). A suprabasal or continuous linear basal staining was not evident in all LiS cases. The expression values of p53 protein were summarized in <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a> and <a class="elsevierStyleCrossRefs" href="#fig0005">Figs. 1–4</a>. Ki67 staining was localized to the basal cell keratinocytes both in LiS and normal skin.DiscussionTo date, our knowledge about the counts of CD34-positive DDCs, MVD, and expression patterns of p53 in LiS is limited. This study aims to get insights into these issues. I revealed the following observations: i) a markedly decreased number or complete loss of CD34-positive DDCs in LiS skin against their presence in normal skin, ii) a markedly increased MVD in the dermis of LiS as compared to normal skin and iii) lack of p53 protein accumulation in these lesions.A markedly decreased number or complete loss of CD34-positive DDCs in LiS against their presence in normal skin: CD34-positive DDCs are present in the dermis of normal skin. They play roles in the development of the surrounding epithelial and mesenchymal cells and the modulation of the immune response<a class="elsevierStyleCrossRef" href="#bib0105">21</a>. In accordance with previous investigations in morphoeic skin<a class="elsevierStyleCrossRefs" href="#bib0040">8–12</a>, and dermal scars<a class="elsevierStyleCrossRef" href="#bib0105">21</a>, the current study showed a markedly decreased number of CD34-positive DDCs or their complete loss or in the dermis of LiS lesions. Skobieranda et al. examined the expression of CD34-positive progenitor cells in 26 lesional skin biopsies from cases with morphea side by side with an additional 11 biopsies from normal skin. They found a decreased quantity of CD34-expressing cells in the lesional skin as compared to the normal skins. The authors proposed regulatory roles for CD34-positive DDCs in collagen synthesis and hence, the development of morphea<a class="elsevierStyleCrossRef" href="#bib0045">9</a>. Lee et al. examined the distribution of CD34-positive DDCs and smooth muscle actin (SMA-positive) myofibroblasts in punch skin biopsies from patients with morphea and healthy individuals (normal skin).CD34-positive DDCs were markedly reduced or absent in morphoeic skin as compared to the normal skin. SMA-positive myofibroblasts increased mostly in the dermal locations where CD34-positive DDCs declined or disappeared<a class="elsevierStyleCrossRef" href="#bib0060">12</a>. The authors proposed that the lack of CD34-positive DDCs in morphea was compatible with similar findings in the wound-healing process<a class="elsevierStyleCrossRefs" href="#bib0060">12,25</a>, both are associated with phenotypic differentiation of CD34-positive DDCs into SMA-positive myofibroblasts. Taken together, these findings suggest that the DDCs contribute to the regulation of collagen production in the skin.The myofibroblasts are smooth muscle actin positive cells that can play an important role in the pathogenesis of fibrosis. These cells can arise from the CD34-positive fibrocytes under the stimulation with fibrogenic cytokines<a class="elsevierStyleCrossRefs" href="#bib0130">26,27</a>. Lee et al. used immunohistochemical staining methods to examine the expression profile of CD34, factor XIIIa, smooth muscle actin, CD31, and vascular cell adhesion molecule-1 in morphea. They found a reduced CD34 stromal stain in these lesions whereas factor XIIIa, smooth muscle actin, and vascular cell adhesion molecule-1 protein expression was high as compared to the normal skin. There was an inverse correlation between CD34 stromal stain and the spatial expression pattern with smooth muscle actin stain. The authors indicated that the mutually exclusive staining patterns of CD34 stromal and SMA stains suggest a phenotypic change of CD34+ DDCs into smooth muscle actin-positive myofibroblasts in morphea<a class="elsevierStyleCrossRef" href="#bib0060">12</a>. It is tempting for future studies to compare the expression pattern of these proteins in LiS.A markedly increased MVD in the dermis of LiS as compared to normal skin: In this investigation, the findings of increased MVD in LiS support previous findings in morphoeic and sclerodermic skin<a class="elsevierStyleCrossRefs" href="#bib0065">13,14,28</a>. Olejek et al. examined MVD (using CD34 antibodies) in punch skin biopsies from vulvarLiS in 28 women<a class="elsevierStyleCrossRef" href="#bib0065">13</a> and 100 cases of anogenital LiS and they found a significant increase of MVD after photodynamic therapy<a class="elsevierStyleCrossRef" href="#bib0070">14</a>. In 2009, Dziankowska-Bartkowiak examined the vascular endothelial changes in scleroderma (systemic sclerosis and morphea). They analyzed the serum vascular endothelial growth factor (VEGF) and its soluble receptor 2 (sVEGFR2) using the ELISA method as well as the immunohistochemical expression of CD34 antigen in the lesional skin. There was a higher mean serum VEGF/sVEGFR2 ratio in systemic sclerosis patients as compared to the control group. Also, there were variations in the CD34 expression in the vascular endothelial cells<a class="elsevierStyleCrossRef" href="#bib0140">28</a>. Taken collectively, the increased MVD in LiS may be due to the release of angiogenic factors that enhance neoangiogenesis<a class="elsevierStyleCrossRef" href="#bib0140">28</a>.CD34-positive cells can also differentiate into progenitor cells that further incorporate into newly formed blood vessels<a class="elsevierStyleCrossRef" href="#bib0145">29</a>.p53 protein expression in LiS: In agreement with other investigators, the current study reported that p53 staining in LiS was weak to moderate nuclear, discontinuous, and localized to the basal cell keratinocytes indicative of lack of p53 protein accumulaiton<a class="elsevierStyleCrossRefs" href="#bib0085">17,19</a>. This pattern of p53 nuclear staining reflects a stress-related response secondary to dermal inflammation and ischemia rather than underlying p53 gene mutations<a class="elsevierStyleCrossRef" href="#bib0095">19</a>. Yang et al., examined the expression profile of p53 in 12 cases of differentiated VIN using immunohistochemical staining methods<a class="elsevierStyleCrossRef" href="#bib0095">19</a>. In differentiated VIN, p53 protein expression was seen in the basal cell keratinocytes with suprabasal extension. In contrast, suprabasilar p53 staining was not seen in LiS cases<a class="elsevierStyleCrossRef" href="#bib0095">19</a>. Hantschmann et al., examined p53 protein expression in patients with squamous cell carcinoma, VIN, LiS, and squamous hyperplasia. In LiS and the normal vulval skin, p53 protein expression was localized to the basal cell keratinocytes. The usual and differentiated types of VIN showed basal and suprabasal p53 nuclear reactivity. Most of the squamous cell carcinomas showed moderate to strong diffuse nuclear p53 staining<a class="elsevierStyleCrossRef" href="#bib0085">17</a>.To conclude, to the best of this author's knowledge, this is the first study analyzing DDCs, MVD, and p53 profiles together in LiS. This study showed that the counts of CD34-positive DDCs were significantly lower in LiS than normal skin (controls), while MVD was significantly higher in patients than controls. These findings suggest that alterations of DDCs and MVD have possible roles in the pathogenesis of fibrosis in these lesions. Future investigations are needed to comprehend the mechanisms underlying these alterations. Moreover, the examination of the correlations among the expression of CD34, factor XIIIa, smooth muscle actin, CD31, and vascular cell adhesion molecule-1 in morphea is open for future investigations." "textoCompletoSecciones" => array:1 [ "secciones" => array:9 [ 0 => array:3 [ "identificador" => "xres1591558" "titulo" => "Abstract" "secciones" => array:5 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Background" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Objectives" ] 2 => array:2 [ "identificador" => "abst0015" "titulo" => "Materials and methods" ] 3 => array:2 [ "identificador" => "abst0020" "titulo" => "Results" ] 4 => array:2 [ "identificador" => "abst0025" "titulo" => "Conclusions" ] ] ] 1 => array:2 [ "identificador" => "xpalclavsec1430029" "titulo" => "Keywords" ] 2 => array:3 [ "identificador" => "xres1591559" "titulo" => "Resumen" "secciones" => array:5 [ 0 => array:2 [ "identificador" => "abst0030" "titulo" => "Introducción" ] 1 => array:2 [ "identificador" => "abst0035" "titulo" => "Objetivos" ] 2 => array:2 [ "identificador" => "abst0040" "titulo" => "Materiales y métodos" ] 3 => array:2 [ "identificador" => "abst0045" "titulo" => "Resultados" ] 4 => array:2 [ "identificador" => "abst0050" "titulo" => "Conclusiones" ] ] ] 3 => array:2 [ "identificador" => "xpalclavsec1430030" "titulo" => "Palabras clave" ] 4 => array:2 [ "identificador" => "sec0005" "titulo" => "Introduction" ] 5 => array:2 [ "identificador" => "sec0010" "titulo" => "Materials and methods" ] 6 => array:2 [ "identificador" => "sec0015" "titulo" => "Results" ] 7 => array:2 [ "identificador" => "sec0020" "titulo" => "Discussion" ] 8 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2020-11-10" "fechaAceptado" => "2021-02-10" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec1430029" "palabras" => array:5 [ 0 => "CD34" 1 => "Dendritic cells" 2 => "Lichen" 3 => "Microvessel" 4 => "Sclerosus" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec1430030" "palabras" => array:5 [ 0 => "CD34" 1 => "Células dendríticas" 2 => "Liquen" 3 => "Microvasos" 4 => "Esclerosis" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:3 [ "titulo" => "Abstract" "resumen" => "BackgroundLichen 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. ObjectivesTo examine the profile of CD34-positive DDCs, microvessel density (MVD), and p53 protein in LiS. Materials and methodsThe 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. ResultsThere 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. ConclusionsTo 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." "secciones" => array:5 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Background" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Objectives" ] 2 => array:2 [ "identificador" => "abst0015" "titulo" => "Materials and methods" ] 3 => array:2 [ "identificador" => "abst0020" "titulo" => "Results" ] 4 => array:2 [ "identificador" => "abst0025" "titulo" => "Conclusions" ] ] ] "es" => array:3 [ "titulo" => "Resumen" "resumen" => "IntroducciónEl 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. ObjetivosExaminar el perfil de las DDC positivas para el CD34, la densidad de microvasos (MVD) y la proteína p53 en el LiE. Materiales y métodosSe 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. ResultadosHubo 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. ConclusionesHasta 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." "secciones" => array:5 [ 0 => array:2 [ "identificador" => "abst0030" "titulo" => "Introducción" ] 1 => array:2 [ "identificador" => "abst0035" "titulo" => "Objetivos" ] 2 => array:2 [ "identificador" => "abst0040" "titulo" => "Materiales y métodos" ] 3 => array:2 [ "identificador" => "abst0045" "titulo" => "Resultados" ] 4 => array:2 [ "identificador" => "abst0050" "titulo" => "Conclusiones" ] ] ] ] "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "Please cite this article as: Hussein MRA. Análisis inmunohistológico de las células dendríticas dérmicas positivas para CD34 y de la densidad de microvasos en el liquen escleroso genital y extragenital. Actas Dermosifiliogr. 2021. https://doi.org/10.1016/j.ad.2021.02.009" ] ] "multimedia" => array:5 [ 0 => array:8 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 935 "Ancho" => 2508 "Tamanyo" => 437422 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0005" "detalle" => "Figure " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "CD34 immunostaining in normal skin. A: variable-sized dermal blood vessels lined by CD34-positive endothelial cells (arrowhead). B: CD34-positive dermal dendrocytes (arrow). (Original magnifications. A: ×200, B: ×400)." ] ] 1 => array:8 [ "identificador" => "fig0010" "etiqueta" => "Figure 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 1898 "Ancho" => 2508 "Tamanyo" => 859279 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0010" "detalle" => "Figure " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "Genital (vulvar) lichen sclerosus. A–B: The features of LiS include the markedly attenuated epidermis with a transition from the edematous papillary dermis (star) to the hyalinized homogenized dermal collagen (arrow), and subtle inflammatory cell infiltrate (arrowhead). C-D: CD34 staining shows loss of CD34-labeled dermal dendritic cells and an increased microvessel density (arrowheads). (Original magnifications. A: ×40, B: ×100, C: ×40, and D: ×100)." ] ] 2 => array:8 [ "identificador" => "fig0015" "etiqueta" => "Figure 3" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr3.jpeg" "Alto" => 1900 "Ancho" => 2508 "Tamanyo" => 938022 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0015" "detalle" => "Figure " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "Genital (penile) lichen sclerosus (Balanitis xerotica obliterans of the foreskin, prepuce). A: The features of the penile LiS include the thinning of the epidermis with loss of the normal rete ridge pattern, broad condensation of the homogenously, and massively hyalinized papillary dermal collagen (arrowhead), and the dense patchy dermal lymphocytic infiltrate (arrow). B: Edema, condensation, and curling of the elastic fibers (Verhoeff-van Gieson stain for elastic fibers, arrow) at the base of the homogenized collagen (star). C-D: CD34 staining shows loss of CD34 dermal dendritic cells and an increased microvessel density (star). (Original magnifications. A: ×20, B: ×200, C:×20, and D: ×100)." ] ] 3 => array:8 [ "identificador" => "fig0020" "etiqueta" => "Figure 4" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr4.jpeg" "Alto" => 1884 "Ancho" => 2508 "Tamanyo" => 1309146 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0020" "detalle" => "Figure " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "Extragenital lichen sclerosus (breast lesions). A: The features of LiS include the presence of focal hyperkeratosis, thinning of the epidermis, hyalinization of the papillary dermal collagen (star), and edema. B: Fragmentation and haphazard arrangement (horizontal, vertical, and random orientation) of the dermal elastic fibers (Verhoeff-van Gieson stain for elastic fibers, arrow). C–D: CD34 staining shows loss of CD34-dermal dendritic cells and an increased microvessel density (arrowheads). (Original magnifications. A: ×20, B: ×40, C: ×20, and D: ×40)." ] ] 4 => array:8 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0025" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:2 [ "leyenda" => "LiS: lichen sclerosus, VLiS: vulvar lichen sclerosus, Penile LiS, CD34 + DDCs: CD34-positive dermal dendritic cells, and MVD: microvessel density. SI: staining intensity, PP%: percentage of positive cells, and SEM: standard error of mean. NS: not statistically significant." "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col">Aspects \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " colspan="4" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Patient group (19 cases)</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col">Normal skin (10 cases) \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col">p Value (LiS versus control groups) \t\t\t\t\t\t\n \t\t\t\t\t\t</th></tr><tr title="table-row"><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Vulvar LiS \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Penile LiS \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">ExtragenitalLiS \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">LiS (all cases) \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">(Control) \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Age (years) (mean ± SEM) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">64.3 ± 5.0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">53.7 ± 13.1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">61.0 ± 1.0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">60.6 ± 4.5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">56.20 ± 2.66 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.111 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Sex \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Females \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Males \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Females \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Females and males \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">3 males and 7 females \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.000 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">DDCs (mean ± SEM) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2.0 ± 0.7 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1.8 ± 0.7 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.0 ± 0.0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1.7 ± 0.5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">23.4 ± 2.1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.000 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">MVD \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">19.45 ± 0.82 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">23 ± 0.44 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">18.5 ± 0.5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">20.47 ± 0.63 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">5.50 ± 0.16 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.000 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">P53 staining values \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">SI (mean ± SEM) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1.36 ± 0.15 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1.66 ± 0.16 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1.5 ± 0.5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1.31 ± 0.1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1.1 ± 0.10 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">NS \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">PP% (mean ± SEM) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">4.36 ± 0.5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">4.33 ± 0.55 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">4.5 ± 0.5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">4.36 ± 0.33 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">3.5 ± 0.44 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">NS \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Pattern \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">NS \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab2723527.png" ] ] ] ] "descripcion" => array:1 [ "en" => "The clinical and immunohistochemical findings in patients with lichen sclerosus." ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:29 [ 0 => array:3 [ "identificador" => "bib0005" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Lichen sclerosus. 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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

M.R.A. Hussein

Servicio de Anatomía Patológica, Hospital Universitario de Assuit Assuit, Egypt

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            "en" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">CTT and CsTT according to H1-antihistamines treatment regimens &#40;H1-antiH&#47;day&#41;&#46; A and B&#8212;patients were divided in two groups&#58; &#8804;1 representing patients treated on-demand or 1&#47;day and &#8805;2 representing those needing 2 or more antihistamines to control the disease&#46; C and D&#58; Y represents daily dosage of antihistamines &#40;OD-on demand&#41;&#46; Only one patient was treated with 3&#47;day dosage and had negative CST&#46;</p>"
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          "en" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Genital &#40;penile&#41; lichen sclerosus &#40;Balanitis xerotica obliterans of the foreskin&#44; prepuce&#41;&#46;</p> <p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">A&#58; The features of the penile LiS include the thinning of the epidermis with loss of the normal rete ridge pattern&#44; broad condensation of the homogenously&#44; and massively hyalinized papillary dermal collagen &#40;arrowhead&#41;&#44; and the dense patchy dermal lymphocytic infiltrate &#40;arrow&#41;&#46; B&#58; Edema&#44; condensation&#44; and curling of the elastic fibers &#40;Verhoeff-van Gieson stain for elastic fibers&#44; arrow&#41; at the base of the homogenized collagen &#40;star&#41;&#46; C-D&#58; CD34 staining shows loss of CD34 dermal dendritic cells and an increased microvessel density &#40;star&#41;&#46; &#40;Original magnifications&#46; A&#58; &#215;20&#44; B&#58; &#215;200&#44; C&#58;&#215;20&#44; and D&#58; &#215;100&#41;&#46;</p>"
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    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">Lichen sclerosus &#40;LiS&#41; is an insidious&#44; chronic scleroatrophic inflammatory disease of unknown etiology&#46; It affects the anogenital area such as the vulva &#40;vulvar LiS&#41;&#44; the male genitalia &#40;LiS of the male genitalia or balanitis xerotica obliterans&#41;&#44; and occasionally some extragenital sites such as buttocks&#44; inner thigh&#44; and under the breasts &#40;extragenital LiS&#41;&#46; LiS of the male genitalia usually affects the glans penis&#44; foreskin &#40;prepuce&#41;&#44; the anterior urethra&#44; and meatus&#44; usually of uncircumcised males&#44; resulting in phimosis and meatal stenosis<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a>&#46; Squamous cell carcinoma is the most common malignancy of the vulva&#46; Its precursor lesions include the usual and the differentiated types of vulvar intraepithelial neoplasia &#40;VIN&#41;&#46; The differentiated VIN is associated with chronic dermatoses such as LiS and can progress to invasive squamous cell carcinoma&#46; Human papillomavirus &#40;HPV&#41; DNA is always absent in these lesions&#46; The usual type VIN affects is associated with high-risk HPV infection<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a>&#46;</p><p id="par0010" class="elsevierStylePara elsevierViewall">In 1984&#44; CD34 antigen was first discovered on hematopoietic stem and progenitor cells&#46; It is a transmembrane phosphoglycoprotein that consists of a heavily sialylated&#44; O-linked glycosylated extracellular domain&#44; a single transmembrane helix&#44; and a cytoplasmic tail&#46; Dendritic cells &#40;DCs&#41; are professional antigen-presenting cells&#46; In the skin&#44; there are CD34-positive dendritic cells &#40;DDCs&#41; in the dermis&#46; CD34 is also expressed by vascular endothelial progenitors&#44; and clusters of newly formed endothelial cells &#40;microvessels&#41;&#44; and therefore CD34 expression is an indicator of microvessel density &#40;MVD&#41; and tissue vascularization<a class="elsevierStyleCrossRefs" href="#bib0015"><span class="elsevierStyleSup">3&#44;4</span></a>&#46;</p><p id="par0015" class="elsevierStylePara elsevierViewall">LiS is closely related to other scleroatrophic conditions such as morphea and scleroderma&#46; Some authorities consider LiS as a superficial or subepidermal morphea&#44; or as scleroderma of the papillary dermis<a class="elsevierStyleCrossRefs" href="#bib0025"><span class="elsevierStyleSup">5&#44;6</span></a>&#46; These viewpoints are supported by several observations including the coexistence of morphea and LiS in some patients&#44; the overlapping clinicopathological features&#44; and their common possible underlying etiologies &#40;Borrelia infection and autoimmunity&#41;<a class="elsevierStyleCrossRefs" href="#bib0025"><span class="elsevierStyleSup">5&#44;7</span></a> in both of them&#46; Histologically&#44; both morphea and LiS are characterized by the attenuation of the epidermis&#44; which is reasoned to the aftermath of the dermal stromal changes including dermal hyalinization&#44; sclerosis with decreased vascularization&#44; and impaired tissue perfusion<a class="elsevierStyleCrossRefs" href="#bib0025"><span class="elsevierStyleSup">5&#8211;7</span></a>&#46;</p><p id="par0020" class="elsevierStylePara elsevierViewall">Although to date the exact role and origin of DDCs are largely unknown&#44; some investigations have suggested that DDCs are important for maintaining the dermal microarchitecture and the modulation of the immune response&#44; and as such&#44; they contribute to the development of scleroatrophic conditions such as LiS&#44; morphea&#44; and scleroderma<a class="elsevierStyleCrossRefs" href="#bib0040"><span class="elsevierStyleSup">8&#8211;11</span></a>&#46; In morphea and scleroderma&#44; previous studies have shown a decreased quantity of CD34-positive DDCs in the dermis<a class="elsevierStyleCrossRefs" href="#bib0040"><span class="elsevierStyleSup">8&#8211;12</span></a>&#46; Aiba et al&#46; examined the skin biopsies from lesions of 27 cases with scleroderma and also biopsies from normal skin of 17 individuals using antibodies against CD34&#46; CD34-positive DDCs were either few or completely absent in the lesional skin of scleroderma&#46; The authors suggested that CD34-positive cells may represent primary target cells in the autoreactive phenomenon in scleroderma<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a>&#46; Similarly&#44; Gilmour et al&#46; examined the number of CD34-positive DDCs in 33 skin biopsies of morphea and found a progressive decline in the numbers of these cells with the progression from the inflammatory to the sclerotic stages of morphea<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">11</span></a>&#46; Moreover&#44; there was an increased MVD both in both morphea and scleroderma<a class="elsevierStyleCrossRefs" href="#bib0065"><span class="elsevierStyleSup">13&#44;14</span></a>&#46; Taken together&#44; CD34-positive DDCs seem to contribute to the development of scleroderma and morphea&#46; To date&#44; similar studies in LiS are limited<a class="elsevierStyleCrossRefs" href="#bib0065"><span class="elsevierStyleSup">13&#44;14</span></a>&#46;</p><p id="par0025" class="elsevierStylePara elsevierViewall">The tumor suppressor p53 gene encodes for a 53 KD nuclear protein that plays important roles in the regulation of cell cycle&#44; and apoptosis<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">15</span></a>&#46; In most benign cells&#44; including the keratinocytes of the penile foreskin and vulvar skin<a class="elsevierStyleCrossRefs" href="#bib0080"><span class="elsevierStyleSup">16&#44;17</span></a>&#44; the expression of p53 protein is either absent or weak&#46; Overexpression of p53 protein is frequent in the dysplastic and malignant squamous epithelial cells<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">18</span></a>&#46; In LiS&#44; p53 protein expression is weak to moderate nuclear&#44; discontinuous&#44; and localized to the basal cell keratinocytes &#40;Pattern 0&#41;<a class="elsevierStyleCrossRefs" href="#bib0085"><span class="elsevierStyleSup">17&#44;19</span></a>&#46;</p><p id="par0030" class="elsevierStylePara elsevierViewall">To date&#44; we have limited knowledge about the profiles of CD34-positive DDCs&#44; MVD&#44; and p53 protein expression in LiS&#46; This study used immunohistochemical techniques to address these issues&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Materials and methods</span><p id="par0035" class="elsevierStylePara elsevierViewall">This is a retrospective case series in which the archival formalin-fixed paraffin-embedded tissues of 19 cases of LiS &#40;sclerotic stage&#41;&#44; from the Pathology Department&#44; Assuit University Hospitals&#44; and consultation files of this author&#44; were used&#46; All the materials &#40;paraffin-embedded tissue blocks&#44; slides&#44; and pathology reports&#41; were coded&#46; The information obtained was analyzed and reported in such a way that the identities of the participants cannot be ascertained&#46; The study did not include any interaction or intervention with human subjects or included any access to any identifiable private information&#46; Therefore the study did not require institutional review board review<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">20</span></a>&#46; The study was performed in accordance with the principles of the Declaration of Helsinki&#46; The materials represented vulvar &#40;11 cases&#41;&#44; extragenital LiS &#40;two cases&#41;&#44; and LiS of the male genitalia &#40;6 cases&#41;&#46; The control group &#40;normal skin&#41; included ten healthy age and sex-matched individuals who underwent skin excisions for benign skin lesions&#46; Paraffin-embedded tissues were sectioned for routine histological &#40;Hematoxylin and Eosin stains&#41; and special stains &#40;elastic fibers&#44; Verhoeff-van Gieson stain&#44; VVG&#41;&#46; The histologic sections were examined for the features of the usual and differentiated types of VIN&#46; The tissue sections were prepared for immunostaining following other groups<a class="elsevierStyleCrossRefs" href="#bib0015"><span class="elsevierStyleSup">3&#44;18</span></a>&#46; Heat-induced epitope antigen retrieval technique was used &#40;Dako Target Retrieval Solution&#44; S1699&#59; Dako&#44; Carpinteria&#44; California&#44; USA&#41; for 30&#160;min at 95&#160;&#176;C followed by a 20-minute cooldown&#46; The endogenous peroxidase activity was blocked with 10&#37; hydrogen peroxide&#46; Anti-CD34 primary antibody &#40;DakoCytomation &#40;Glostrup&#44; Denmark&#59; anti-human CD34 antibody&#41;&#44; diluted in phosphate-buffered saline &#40;PBS&#41; was applied to each section&#46; Antibodies against p53 &#40;at a dilution of 1&#58;200 dilution&#44; Thermo scientific&#44; Lab Vision Corporation&#44; Fermont&#44; Clone SP5&#44; RM-9105-S1&#44; USA&#41; were applied to each section&#46; Sections were incubated with primary antibodies at 4&#160;&#176;C overnight&#46; Then sections were treated using the labeled polymer peroxidase method &#40;DAKO EnVision&#8482;&#160;&#43;&#160;Peroxidase Kit&#44; Dako&#44; Carpinteria&#44; CA&#41; for 60&#160;min following the manufacturer&#39;s instructions&#46; Proteins were visualized using a liquid diaminobenzidine substrate kit &#40;Zymed Laboratories&#44; San Francisco&#44; CA&#41;&#46; Sections were counterstained in Mayer&#39;s Hematoxylin&#46; Sections from hemangioma and squamous cell carcinoma were used as positive controls for the anti-CD34 and anti-p53 antibodies&#44; respectively&#46; Sections with PBS replacing the primary antibody were used as negative controls<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a>&#46; All slides were coded and evaluated by two observers blinded for clinical details and identity of the patients<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">21</span></a>&#46;</p><p id="par0040" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleBold">Immunohistochemical evaluation of the MVD&#44; CD34-positive DDCs&#44; and p53 protein expression&#58;</span> The immunostained sections were examined&#46; In normal and lesional skins&#44; CD34 immunostaining was absent from the epidermis&#46; CD34-positive dermal dendritic cells in the dermis were counted in three randomly chosen square fields &#40;1&#160;mm<span class="elsevierStyleSup">2</span>&#41; following other groups<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">21</span></a>&#46; Evaluation of MVD was performed following other groups&#46; The sections were examined at low power magnification &#40;&#215;40&#41; to identify the hot spots of microvessels in the dermis&#46; Single endothelial cells or a cluster of endothelial cells reactive &#40;membrane&#47;cytoplasm staining&#41; for CD34 in the membrane&#47;cytoplasm was regarded as a distinct single countable microvessel&#46; The number of microvessels was counted at higher magnification &#40;&#215;400&#41;&#46; Vessel lumen and red cells&#44; though often present&#44; were not required to define a microvessel<a class="elsevierStyleCrossRefs" href="#bib0015"><span class="elsevierStyleSup">3&#44;22</span></a>&#46; p53 protein expression values were scored and reported following other groups<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">18</span></a>&#46; Only nuclear staining was considered positive&#46; Initially&#44; the distribution of p53 positive cells was categorized into basal versus suprabasal&#46; The staining intensity was scored as follows&#58; weak 1&#43;&#44; moderate 2&#43;&#44; or strong 3&#43;&#46; The percentage of positive cells was calculated as the number of positive cells per 100 consecutive cells &#40;0&#8211;25&#44; 26&#8211;50&#44; 51&#8211;75&#37;&#44; or &#62;75&#37;&#41;<a class="elsevierStyleCrossRefs" href="#bib0085"><span class="elsevierStyleSup">17&#44;18</span></a>&#46; p53 staining profiles included three patterns&#46; Pattern 0 indicates the presence of a nuclear&#44; discontinuous&#59; weak to moderate p53 staining that is localized to the basal cell keratinocytes &#40;no suprabasal extension&#41;&#46; Pattern 1 indicates the presence of a significantly increased p53 moderate to strong nuclear staining in the basal cell layer but without prominent suprabasal extension&#46; Pattern 2 indicates the presence of a significantly increased p53moderate to strong nuclear reactivity in the basal cell layer&#44; which is associated with prominent suprabasal extension<a class="elsevierStyleCrossRef" href="#bib0115"><span class="elsevierStyleSup">23</span></a>&#46;</p><p id="par0045" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleBold">Statistical analysis&#58;</span> Differences between the groups &#40;normal skin versus LiS&#41; were determined using the non-parametric Wilcoxon-Mann-Whitney following other groups<a class="elsevierStyleCrossRefs" href="#bib0060"><span class="elsevierStyleSup">12&#44;24</span></a>&#46; <span class="elsevierStyleItalic">p</span> values of less than 0&#46;05 were treated as statistically significant&#46; The results were presented as the Mean and standard error of the mean &#40;SEM&#41;&#46; Statistical tests were performed using SPSS version 23 &#40;IBM Corp&#44; New York&#44; U&#46;S&#46;A&#46;&#41;&#46;</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Results</span><p id="par0050" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleBold">Clinicopathologic findings&#58;</span> The study included 19 cases with LiS with a mean age of 60&#46;6&#160;&#177;&#160;4&#46;5 years&#46; The study included 11 cases of vulvar LiS &#40;mean&#160;&#177;&#160;standard error of the mean of age&#58; 64&#46;3&#160;&#177;&#160;3&#46;2 years&#41;&#46; The sites of the vulvar lesions were labia minor &#40;9 cases&#41;&#44; perineum&#44; and the posterior fourchette &#40;one case&#44; each&#41;&#46; The study also included 6 cases of LiS of male genitalia involving the foreskin &#40;mean&#160;&#177;&#160;standard error of the mean of age&#58; 53&#46;7&#160;&#177;&#160;13&#46;1 years&#41;&#44; and two cases of extragenital LiS &#40;right breast and paraumbilical region&#44; one case each&#44; mean&#160;&#177;&#160;standard error of the mean of age&#58; 60&#46;0&#160;&#177;&#160;1&#46;0 years&#41;&#46; The histological sections were examined to obtain the diagnosis of LiS and to rule out squamous neoplasia&#46; Features diagnostic of early differentiated type VIN&#47;differentiated squamous cell carcinoma was seen in one case of LiS&#46; Histologically&#44; sections from both genital and extragenital LiS showed attenuation of the epidermis with the loss of the regular rete ridge pattern&#46; A granular layer was present&#46; There was no basal nuclear atypia&#46; There was no acanthosis&#46; There was papillary dermal edema and homogenization of the dermal collagen&#44; fragmentation&#44; and haphazard arrangement &#40;horizontal&#44; vertical&#44; and random orientation&#41; of the dermal elastic fibers &#40;VVG stain&#41;&#46; There were condensation and curling of the elastic fibers in the surrounding dermis&#46; No fungal elements were detected &#40;periodic acid&#8211;Schiff with and without diastase&#41;&#46; Few&#44; scattered lymphocytes were seen in the dermis&#46; No evidence of squamous neoplasia could be identified in 18 cases&#46; A summary of these findings was shown in <a class="elsevierStyleCrossRefs" href="#fig0005">Figs&#46; 1&#8211;4</a>&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><elsevierMultimedia ident="fig0010"></elsevierMultimedia><elsevierMultimedia ident="fig0015"></elsevierMultimedia><elsevierMultimedia ident="fig0020"></elsevierMultimedia><p id="par0055" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleBold">A markedly decreased number or complete loss of CD34-positive DDCs in LiS against their presence in the normal skin&#58;</span> The CD34-positive DDCs show brownish cytoplasmic staining&#46; The dermis from the lesional skin &#40;LiS&#41; showed either complete loss of CD34-positive DDCs or rare CD34-positive DDCs as compared to the normal skin group&#46; The mean expression values of DDCs counts were 1&#46;7&#160;&#177;&#160;0&#46;5&#47;mm<span class="elsevierStyleSup">2</span> versus 23&#46;4&#160;&#177;&#160;2&#46;1&#47;mm<span class="elsevierStyleSup">2</span> for LiS &#40;both genital and extragenital cases&#41; versus normal skin&#44; respectively&#46; The mean values of CD34-positive DDCs counts were 2&#46;0&#160;&#177;&#160;0&#46;7&#47;mm<span class="elsevierStyleSup">2</span> &#40;vulvar LiS&#41;&#44; 1&#46;8&#160;&#177;&#160;0&#46;7&#47;mm<span class="elsevierStyleSup">2</span> &#40;LiS of the male genitalia&#41;&#44; and 0&#46;0&#160;&#177;&#160;0&#46;0&#47;mm<span class="elsevierStyleSup">2</span> &#40;extragenital LiS&#41;&#46; The differences between the lesional &#40;LiS&#41; and normal skins were statistically significant &#40;<span class="elsevierStyleItalic">p</span>&#160;&#60;&#160;0&#46;000&#41;&#46; A summary of these findings was shown in <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a> and <a class="elsevierStyleCrossRefs" href="#fig0005">Figs&#46; 1&#8211;4</a>&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0060" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleBold">A markedly increased MVD in the dermis of LiS as compared to the normal skin</span>&#58; CD34 marker reactivity in the microvessels appeared as brown cytoplasmic reactivity with or without membrane staining&#46; Areas with vessels having caliber larger than eight red blood cells were excluded&#46; Large and medium-sized blood vessels with thick muscular walls or vessels with a luminal diameter of greater than 50&#160;mM were excluded from the final count&#46; The MVD values in the lesional skin of both genital and extragenital LiS &#40;20&#46;47&#160;&#177;&#160;0&#46;63&#44; p&#160;&#61;&#160;0&#46;000&#41; were statistically significantly high &#40;<span class="elsevierStyleItalic">p</span>&#160;&#60;&#160;0&#46;000&#41; as compared to the normal skin &#40;5&#46;50&#160;&#177;&#160;0&#46;2&#41;&#46; The mean values of MVD were 19&#46;45&#160;&#177;&#160;0&#46;82 &#40;vulvar LiS&#41;&#44; 23&#160;&#177;&#160;0&#46;44 &#40;LiS of the male genitalia&#41;&#44; and 18&#46;50&#160;&#177;&#160;0&#46;50 &#40;extragenital LiS&#41;&#46; A summary of these findings is shown in <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a> and <a class="elsevierStyleCrossRefs" href="#fig0005">Figs&#46; 1&#8211;4</a>&#46;</p><p id="par0065" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleBold">p53 protein staining patterns in the normal skin&#44; and LiS&#58;</span> The lesional and normal skins showed nearly similar p53 protein staining values and patterns&#46; The reactivity was in the form of discontinuous individual single-cell p53&#43; nuclear staining &#40;weak to moderate staining intensity&#41; in the basal cell keratinocytes of the epidermis &#40;in less than 10 &#37; of basal keratinocytes&#41;&#46; A suprabasal or continuous linear basal staining was not evident in all LiS cases&#46; The expression values of p53 protein were summarized in <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a> and <a class="elsevierStyleCrossRefs" href="#fig0005">Figs&#46; 1&#8211;4</a>&#46; Ki67 staining was localized to the basal cell keratinocytes both in LiS and normal skin&#46;</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Discussion</span><p id="par0070" class="elsevierStylePara elsevierViewall">To date&#44; our knowledge about the counts of CD34-positive DDCs&#44; MVD&#44; and expression patterns of p53 in LiS is limited&#46; This study aims to get insights into these issues&#46; I revealed the following observations&#58; i&#41; a markedly decreased number or complete loss of CD34-positive DDCs in LiS skin against their presence in normal skin&#44; ii&#41; a markedly increased MVD in the dermis of LiS as compared to normal skin and iii&#41; lack of p53 protein accumulation in these lesions&#46;</p><p id="par0075" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleBold">A markedly decreased number or complete loss of CD34-positive DDCs in LiS against their presence in normal skin&#58;</span> CD34-positive DDCs are present in the dermis of normal skin&#46; They play roles in the development of the surrounding epithelial and mesenchymal cells and the modulation of the immune response<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">21</span></a>&#46; In accordance with previous investigations in morphoeic skin<a class="elsevierStyleCrossRefs" href="#bib0040"><span class="elsevierStyleSup">8&#8211;12</span></a>&#44; and dermal scars<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">21</span></a>&#44; the current study showed a markedly decreased number of CD34-positive DDCs or their complete loss or in the dermis of LiS lesions&#46; Skobieranda et al&#46; examined the expression of CD34-positive progenitor cells in 26 lesional skin biopsies from cases with morphea side by side with an additional 11 biopsies from normal skin&#46; They found a decreased quantity of CD34-expressing cells in the lesional skin as compared to the normal skins&#46; The authors proposed regulatory roles for CD34-positive DDCs in collagen synthesis and hence&#44; the development of morphea<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">9</span></a>&#46; Lee et al&#46; examined the distribution of CD34-positive DDCs and smooth muscle actin &#40;SMA-positive&#41; myofibroblasts in punch skin biopsies from patients with morphea and healthy individuals &#40;normal skin&#41;&#46;CD34-positive DDCs were markedly reduced or absent in morphoeic skin as compared to the normal skin&#46; SMA-positive myofibroblasts increased mostly in the dermal locations where CD34-positive DDCs declined or disappeared<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">12</span></a>&#46; The authors proposed that the lack of CD34-positive DDCs in morphea was compatible with similar findings in the wound-healing process<a class="elsevierStyleCrossRefs" href="#bib0060"><span class="elsevierStyleSup">12&#44;25</span></a>&#44; both are associated with phenotypic differentiation of CD34-positive DDCs into SMA-positive myofibroblasts&#46; Taken together&#44; these findings suggest that the DDCs contribute to the regulation of collagen production in the skin&#46;</p><p id="par0080" class="elsevierStylePara elsevierViewall">The myofibroblasts are smooth muscle actin positive cells that can play an important role in the pathogenesis of fibrosis&#46; These cells can arise from the CD34-positive fibrocytes under the stimulation with fibrogenic cytokines<a class="elsevierStyleCrossRefs" href="#bib0130"><span class="elsevierStyleSup">26&#44;27</span></a>&#46; Lee et al&#46; used immunohistochemical staining methods to examine the expression profile of CD34&#44; factor XIIIa&#44; smooth muscle actin&#44; CD31&#44; and vascular cell adhesion molecule-1 in morphea&#46; They found a reduced CD34 stromal stain in these lesions whereas factor XIIIa&#44; smooth muscle actin&#44; and vascular cell adhesion molecule-1 protein expression was high as compared to the normal skin&#46; There was an inverse correlation between CD34 stromal stain and the spatial expression pattern with smooth muscle actin stain&#46; The authors indicated that the mutually exclusive staining patterns of CD34 stromal and SMA stains suggest a phenotypic change of CD34&#43; DDCs into smooth muscle actin-positive myofibroblasts in morphea<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">12</span></a>&#46; It is tempting for future studies to compare the expression pattern of these proteins in LiS&#46;</p><p id="par0085" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleBold">A markedly increased MVD in the dermis of LiS as compared to normal skin</span>&#58; In this investigation&#44; the findings of increased MVD in LiS support previous findings in morphoeic and sclerodermic skin<a class="elsevierStyleCrossRefs" href="#bib0065"><span class="elsevierStyleSup">13&#44;14&#44;28</span></a>&#46; Olejek et al&#46; examined MVD &#40;using CD34 antibodies&#41; in punch skin biopsies from vulvarLiS in 28 women<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">13</span></a> and 100 cases of anogenital LiS and they found a significant increase of MVD after photodynamic therapy<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">14</span></a>&#46; In 2009&#44; Dziankowska-Bartkowiak examined the vascular endothelial changes in scleroderma &#40;systemic sclerosis and morphea&#41;&#46; They analyzed the serum vascular endothelial growth factor &#40;VEGF&#41; and its soluble receptor 2 &#40;sVEGFR2&#41; using the ELISA method as well as the immunohistochemical expression of CD34 antigen in the lesional skin&#46; There was a higher mean serum VEGF&#47;sVEGFR2 ratio in systemic sclerosis patients as compared to the control group&#46; Also&#44; there were variations in the CD34 expression in the vascular endothelial cells<a class="elsevierStyleCrossRef" href="#bib0140"><span class="elsevierStyleSup">28</span></a>&#46; Taken collectively&#44; the increased MVD in LiS may be due to the release of angiogenic factors that enhance neoangiogenesis<a class="elsevierStyleCrossRef" href="#bib0140"><span class="elsevierStyleSup">28</span></a>&#46;CD34-positive cells can also differentiate into progenitor cells that further incorporate into newly formed blood vessels<a class="elsevierStyleCrossRef" href="#bib0145"><span class="elsevierStyleSup">29</span></a>&#46;</p><p id="par0090" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleBold">p53 protein expression in LiS&#58;</span> In agreement with other investigators&#44; the current study reported that p53 staining in LiS was weak to moderate nuclear&#44; discontinuous&#44; and localized to the basal cell keratinocytes indicative of lack of p53 protein accumulaiton<a class="elsevierStyleCrossRefs" href="#bib0085"><span class="elsevierStyleSup">17&#44;19</span></a>&#46; This pattern of p53 nuclear staining reflects a stress-related response secondary to dermal inflammation and ischemia rather than underlying p53 gene mutations<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">19</span></a>&#46; Yang et al&#46;&#44; examined the expression profile of p53 in 12 cases of differentiated VIN using immunohistochemical staining methods<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">19</span></a>&#46; In differentiated VIN&#44; p53 protein expression was seen in the basal cell keratinocytes with suprabasal extension&#46; In contrast&#44; suprabasilar p53 staining was not seen in LiS cases<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">19</span></a>&#46; Hantschmann et al&#46;&#44; examined p53 protein expression in patients with squamous cell carcinoma&#44; VIN&#44; LiS&#44; and squamous hyperplasia&#46; In LiS and the normal vulval skin&#44; p53 protein expression was localized to the basal cell keratinocytes&#46; The usual and differentiated types of VIN showed basal and suprabasal p53 nuclear reactivity&#46; Most of the squamous cell carcinomas showed moderate to strong diffuse nuclear p53 staining<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">17</span></a>&#46;</p><p id="par0095" class="elsevierStylePara elsevierViewall">To conclude&#44; to the best of this author&#39;s knowledge&#44; this is the first study analyzing DDCs&#44; MVD&#44; and p53 profiles together in LiS&#46; This study showed that the counts of CD34-positive DDCs were significantly lower in LiS than normal skin &#40;controls&#41;&#44; while MVD was significantly higher in patients than controls&#46; These findings suggest that alterations of DDCs and MVD have possible roles in the pathogenesis of fibrosis in these lesions&#46; Future investigations are needed to comprehend the mechanisms underlying these alterations&#46; Moreover&#44; the examination of the correlations among the expression of CD34&#44; factor XIIIa&#44; smooth muscle actin&#44; CD31&#44; and vascular cell adhesion molecule-1 in morphea is open for future investigations&#46;</p></span></span>"
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            0 => "CD34"
            1 => "Dendritic cells"
            2 => "Lichen"
            3 => "Microvessel"
            4 => "Sclerosus"
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            0 => "CD34"
            1 => "C&#233;lulas dendr&#237;ticas"
            2 => "Liquen"
            3 => "Microvasos"
            4 => "Esclerosis"
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        "titulo" => "Abstract"
        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Background</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">Lichen sclerosus &#40;LiS&#41; is a chronic scleroatrophic condition that usually affects the anogenital area and occasionally the extragenital sites&#46; CD34-positive dermal dendritic cells &#40;DDCs&#41; contribute to the maintenance of the dermal microarchitecture and modulation of the immune response&#46; p53 is a tumor suppressor gene important for the regulation of the cell cycle and apoptosis&#46; Similar to morphea &#40;a LiS-closely related scleroatrophic condition&#41;&#44; dermal sclerosis&#44; alterations of DDCs&#44; and dermal microvasculature may be important underlying pathogenetic mechanisms in LiS&#46;</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Objectives</span><p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">To examine the profile of CD34-positive DDCs&#44; microvessel density &#40;MVD&#41;&#44; and p53 protein in LiS&#46;</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Materials and methods</span><p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">The immunohistological profiles of DDCs&#44; MVD&#44; and p53 were examined in 19 cases of LiS and their age- and sex-matched normal skin &#40;10 specimens&#41;&#44; using antibodies against CD34 and p53&#46;</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Results</span><p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">There was a markedly decreased counts &#40;1&#46;7&#160;&#177;&#160;0&#46;5&#47;mm<span class="elsevierStyleSup">2</span>&#41; or complete loss of CD34-positive DDCs in LiS against their abundance in the normal skin &#40;23&#46;4&#160;&#177;&#160;2&#46;1&#47;mm<span class="elsevierStyleSup">2</span>&#44; p&#160;&#61;&#160;0&#46;000&#41;&#46; MVD was markedly increased in LiS lesions &#40;20&#160;&#177;&#160;0&#46;47&#41; as compared to normal skin &#40;5&#46;50&#160;&#177;&#160;0&#46;20&#44; p&#160;&#61;&#160;0&#46;000&#41;&#46; Discontinuous single-cell p53 weakly positive nuclear staining was seen in the epidermal basal cell keratinocytes in normal skin and LiS lesions&#46;</p></span> <span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Conclusions</span><p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">To the best of this author&#39;s knowledge&#44; this is the first study analyzing DDCs&#44; MVD&#44; and p53 profiles together in LiS&#46; The findings suggest that alterations of DDCs and MVD have roles in the pathogenesis of LiS&#46;</p></span>"
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            "titulo" => "Background"
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            "titulo" => "Objectives"
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          2 => array:2 [
            "identificador" => "abst0015"
            "titulo" => "Materials and methods"
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        "resumen" => "<span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Introducci&#243;n</span><p id="spar0065" class="elsevierStyleSimplePara elsevierViewall">El liquen escleroso &#40;LiE&#41; es una enfermedad cr&#243;nica escleroatr&#243;fica que afectar&#225; generalmente el &#225;rea anogenital y ocasionalmente a localizaciones extragenitales&#46; Las c&#233;lulas dendr&#237;ticas d&#233;rmicas CD34 positivas &#40;DDC&#41; contribuyen al mantenimiento de la microarquitectura d&#233;rmica y a la modulaci&#243;n de la respuesta inmunitaria&#46; El p53 es un gen supresor de tumores importante para la regulaci&#243;n del ciclo celular y de la apoptosis&#46; De manera similar a lo que ocurre en la morfea &#40;una condici&#243;n escleroatr&#243;fica estrechamente relacionada con el LiE&#41;&#44; la esclerosis d&#233;rmica&#44; las alteraciones de las DDC y de la microvasculatura d&#233;rmica pueden ser mecanismos patog&#233;nicos subyacentes importantes en el LiE&#46;</p></span> <span id="abst0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Objetivos</span><p id="spar0070" class="elsevierStyleSimplePara elsevierViewall">Examinar el perfil de las DDC positivas para el CD34&#44; la densidad de microvasos &#40;MVD&#41; y la prote&#237;na p53 en el LiE&#46;</p></span> <span id="abst0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Materiales y m&#233;todos</span><p id="spar0075" class="elsevierStyleSimplePara elsevierViewall">Se evaluaron los perfiles inmunohistol&#243;gicos de las DDC&#44; de la MVD y del p53 en 19 casos de LiE y en la piel normal de pacientes emparejados por edad y sexo &#40;10 muestras&#41;&#44; utilizando los anticuerpos contra el CD34 y el p53&#46;</p></span> <span id="abst0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Resultados</span><p id="spar0080" class="elsevierStyleSimplePara elsevierViewall">Hubo una marcada disminuci&#243;n de los recuentos &#40;1&#44;7&#160;&#177;&#160;0&#44;5&#47;mm<span class="elsevierStyleSup">2</span>&#41; o p&#233;rdida completa de DDC CD34&#160;&#43;&#160;en el LiE en comparaci&#243;n con su elevada expresi&#243;n en la piel normal &#40;23&#44;4&#160;&#177;&#160;2&#44;1&#47;mm<span class="elsevierStyleSup">2</span>&#44; p&#160;&#61;&#160;0&#44;000&#41;&#46; La MVD estaba notablemente aumentada en las lesiones de LiE &#40;20&#160;&#177;&#160;0&#44;47&#41; en comparaci&#243;n con la de la piel normal &#40;5&#44;50&#160;&#177;&#160;0&#44;20&#44; p&#160;&#61;&#160;0&#44;000&#41;&#46; Se observ&#243; una tinci&#243;n nuclear discontinua&#44; de c&#233;lulas aisladas&#44; d&#233;bilmente positiva para el p53&#44; localizada en los queratinocitos de las capas basales epid&#233;rmicas de la piel sana y de la piel afectada por el LiE&#46;</p></span> <span id="abst0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0060">Conclusiones</span><p id="spar0085" class="elsevierStyleSimplePara elsevierViewall">Hasta donde tenemos conocimiento&#44; este es el primer estudio que analiza los perfiles de las DDC&#44; de la MVD y del p53 de manera simult&#225;nea en el LiE&#46; Los hallazgos sugirieron que las alteraciones de las DDC y de la MVD tienen papeles en la patog&#233;nesis del LiE&#46;</p></span>"
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        "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as&#58; Hussein MRA&#46; An&#225;lisis inmunohistol&#243;gico de las c&#233;lulas dendr&#237;ticas d&#233;rmicas positivas para CD34 y de la densidad de microvasos en el liquen escleroso genital y extragenital&#46; Actas Dermosifiliogr&#46; 2021&#46; <span class="elsevierStyleInterRef" id="intr0005" href="https://doi.org/10.1016/j.ad.2021.02.009">https&#58;&#47;&#47;doi&#46;org&#47;10&#46;1016&#47;j&#46;ad&#46;2021&#46;02&#46;009</span></p>"
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          "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">CD34 immunostaining in normal skin&#46; A&#58; variable-sized dermal blood vessels lined by CD34-positive endothelial cells &#40;arrowhead&#41;&#46; B&#58; CD34-positive dermal dendrocytes &#40;arrow&#41;&#46; &#40;Original magnifications&#46; A&#58; &#215;200&#44; B&#58; &#215;400&#41;&#46;</p>"
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          "en" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Genital &#40;vulvar&#41; lichen sclerosus&#46; A&#8211;B&#58; The features of LiS include the markedly attenuated epidermis with a transition from the edematous papillary dermis &#40;star&#41; to the hyalinized homogenized dermal collagen &#40;arrow&#41;&#44; and subtle inflammatory cell infiltrate &#40;arrowhead&#41;&#46; C-D&#58; CD34 staining shows loss of CD34-labeled dermal dendritic cells and an increased microvessel density &#40;arrowheads&#41;&#46; &#40;Original magnifications&#46; A&#58; &#215;40&#44; B&#58; &#215;100&#44; C&#58; &#215;40&#44; and D&#58; &#215;100&#41;&#46;</p>"
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          "en" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Genital &#40;penile&#41; lichen sclerosus &#40;Balanitis xerotica obliterans of the foreskin&#44; prepuce&#41;&#46;</p> <p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">A&#58; The features of the penile LiS include the thinning of the epidermis with loss of the normal rete ridge pattern&#44; broad condensation of the homogenously&#44; and massively hyalinized papillary dermal collagen &#40;arrowhead&#41;&#44; and the dense patchy dermal lymphocytic infiltrate &#40;arrow&#41;&#46; B&#58; Edema&#44; condensation&#44; and curling of the elastic fibers &#40;Verhoeff-van Gieson stain for elastic fibers&#44; arrow&#41; at the base of the homogenized collagen &#40;star&#41;&#46; C-D&#58; CD34 staining shows loss of CD34 dermal dendritic cells and an increased microvessel density &#40;star&#41;&#46; &#40;Original magnifications&#46; A&#58; &#215;20&#44; B&#58; &#215;200&#44; C&#58;&#215;20&#44; and D&#58; &#215;100&#41;&#46;</p>"
        ]
      ]
      3 => array:8 [
        "identificador" => "fig0020"
        "etiqueta" => "Figure 4"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
          0 => array:4 [
            "imagen" => "gr4.jpeg"
            "Alto" => 1884
            "Ancho" => 2508
            "Tamanyo" => 1309146
          ]
        ]
        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "at0020"
            "detalle" => "Figure "
            "rol" => "short"
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Extragenital lichen sclerosus &#40;breast lesions&#41;&#46; A&#58; The features of LiS include the presence of focal hyperkeratosis&#44; thinning of the epidermis&#44; hyalinization of the papillary dermal collagen &#40;star&#41;&#44; and edema&#46; B&#58; Fragmentation and haphazard arrangement &#40;horizontal&#44; vertical&#44; and random orientation&#41; of the dermal elastic fibers &#40;Verhoeff-van Gieson stain for elastic fibers&#44; arrow&#41;&#46; C&#8211;D&#58; CD34 staining shows loss of CD34-dermal dendritic cells and an increased microvessel density &#40;arrowheads&#41;&#46; &#40;Original magnifications&#46; A&#58; &#215;20&#44; B&#58; &#215;40&#44; C&#58; &#215;20&#44; and D&#58; &#215;40&#41;&#46;</p>"
        ]
      ]
      4 => array:8 [
        "identificador" => "tbl0005"
        "etiqueta" => "Table 1"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "at0025"
            "detalle" => "Table "
            "rol" => "short"
          ]
        ]
        "tabla" => array:2 [
          "leyenda" => "<p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">LiS&#58; lichen sclerosus&#44; VLiS&#58; vulvar lichen sclerosus&#44; Penile LiS&#44; CD34&#160;&#43;&#160;DDCs&#58; CD34-positive dermal dendritic cells&#44; and MVD&#58; microvessel density&#46; SI&#58; staining intensity&#44; PP&#37;&#58; percentage of positive cells&#44; and SEM&#58; standard error of mean&#46; NS&#58; not statistically significant&#46;</p>"
          "tablatextoimagen" => array:1 [
            0 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col">Aspects&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " colspan="4" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Patient group &#40;19 cases&#41;</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col">Normal skin &#40;10 cases&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col"><span class="elsevierStyleItalic">p</span> Value &#40;LiS versus control groups&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr><tr title="table-row"><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Vulvar LiS&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Penile LiS&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">ExtragenitalLiS&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">LiS &#40;all cases&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">&#40;Control&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Age &#40;years&#41; &#40;mean&#160;&#177;&#160;SEM&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">64&#46;3&#160;&#177;&#160;5&#46;0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">53&#46;7&#160;&#177;&#160;13&#46;1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">61&#46;0&#160;&#177;&#160;1&#46;0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">60&#46;6&#160;&#177;&#160;4&#46;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">56&#46;20&#160;&#177;&#160;2&#46;66&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;111&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Sex&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Females&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Males&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Females&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Females and males&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">3 males and 7 females&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;000&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">DDCs &#40;mean&#160;&#177;&#160;SEM&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2&#46;0&#160;&#177;&#160;0&#46;7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#46;8&#160;&#177;&#160;0&#46;7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;0&#160;&#177;&#160;0&#46;0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#46;7&#160;&#177;&#160;0&#46;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">23&#46;4&#160;&#177;&#160;2&#46;1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;000&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">MVD&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">19&#46;45&#160;&#177;&#160;0&#46;82&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">23&#160;&#177;&#160;0&#46;44&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">18&#46;5&#160;&#177;&#160;0&#46;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">20&#46;47&#160;&#177;&#160;0&#46;63&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">5&#46;50&#160;&#177;&#160;0&#46;16&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;000&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">P53 staining values&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">SI &#40;mean&#160;&#177;&#160;SEM&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#46;36&#160;&#177;&#160;0&#46;15&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#46;66&#160;&#177;&#160;0&#46;16&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#46;5&#160;&#177;&#160;0&#46;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#46;31&#160;&#177;&#160;0&#46;1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#46;1&#160;&#177;&#160;0&#46;10&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">NS&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">PP&#37; &#40;mean&#160;&#177;&#160;SEM&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">4&#46;36&#160;&#177;&#160;0&#46;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">4&#46;33&#160;&#177;&#160;0&#46;55&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">4&#46;5&#160;&#177;&#160;0&#46;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">4&#46;36&#160;&#177;&#160;0&#46;33&nbsp;\t\t\t\t\t\t\n
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Article information

ISSN: 15782190
Original language: English

DOI:10.1016/j.adengl.2021.05.013

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Year/Month	Html	Pdf	Total

2024 November	5	6	11
2024 October	95	31	126
2024 September	87	31	118
2024 August	125	57	182
2024 July	135	35	170
2024 June	96	43	139
2024 May	95	50	145
2024 April	75	34	109
2024 March	88	33	121
2024 February	74	36	110
2024 January	61	52	113
2023 December	62	30	92
2023 November	86	24	110
2023 October	85	42	127
2023 September	69	34	103
2023 August	38	21	59
2023 July	59	41	100
2023 June	65	30	95
2023 May	59	38	97
2023 April	44	26	70
2023 March	66	33	99
2023 February	34	25	59
2023 January	31	31	62
2022 December	47	56	103
2022 November	28	31	59
2022 October	26	29	55
2022 September	23	39	62
2022 August	32	32	64
2022 July	27	38	65
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2022 May	55	41	96
2022 April	78	47	125
2022 March	55	67	122
2022 February	75	36	111
2022 January	88	63	151
2021 December	52	45	97
2021 November	75	70	145
2021 October	79	75	154
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