Density and proportions of the epidermal T cell population in human sun-exposed skin differ from those in sun-protected skin: preliminary immunohistochemical study

Epidermal T cells, which are found in clinically normal human skin, show topographic differences in density and proportions; however, the mechanisms and the biological consequences of such differences are still unknown. In a previous work, we showed that epidermal T cells are altered in number and composition after a single exposure to solar-simulated radiation (SSR). The purposes of the present investigation were, first, to compare the density of epidermal T cells and the proportion of T cell subpopulations in habitually sun-exposed versus sun-protected sites; second, to determine the effects of repetitive exposures to SSR on the latter cell populations. Biopsies from habitually sun-exposed, sun-protected and solar-simulated-exposed skin of 28 healthy volunteers were taken and immunohistochemistry was performed on cryostat sections. Compared with sun-protected sites, epidermal CD3⁺ T cell numbers of habitually sun-exposed sites were significantly lower. Double staining showed that the number of CD3⁺CD8⁺ T cells was significantly lower in sun-exposed than in sun-protected skin, whereas the numbers of CD3⁺CD4⁺ T cells were similar in both sites. Therefore, the CD4/CD8 ratio was markedly higher in sun-exposed compared to sun-protected sites. Moreover, repeated exposures of sun-protected skin to SSR induced a significant reduction in number of epidermal CD3⁺ T cells. The mean number of epidermal CD3⁺CD8⁺ double stained cells significantly decreased after such exposures, while the epidermal CD3⁺CD4⁺ T cell subpopulation was not significantly changed. In conclusion, both chronically sun-exposed skin and repeatedly SSR-exposed skin show a decrease in density of epidermal CD3⁺ and CD3⁺CD8⁺ T cells. We hypothesize that such sun-induced changes may weaken the immunosurveillance capacity of the skin and therefore increase the occurrence of skin cancer.     

Telomere length of the skin in association with chronological aging and photoaging

BACKGROUND: Telomere shortening has been implicated in cellular senescence, which may cause certain aging phenotypes. OBJECTIVE: To reveal whether telomere shortening is associated with chronological aging and/or photoaging of the skin, we measured telomere length in the epidermis and in the dermis from sun-protected and from sun-exposed sites of the skin. METHODS: Seventy-six specimens of epidermis from sun-protected sites and 24 specimens of epidermis from sun-exposed sites were analyzed. Sixty specimens of the dermis were also analyzed. In six cases, epidermal specimens from sun-protected and from sun-exposed sites of the same individual were analyzed. RESULTS: Comparison of telomere lengths revealed that the epidermis has shorter telomeres than the dermis. Telomere length in the epidermis and in the dermis was reduced with age, and average telomere shortening rates in the epidermis and in the dermis were 9 and 11 bp/yr, respectively. Unexpectedly, telomere length was not significantly different between epidermis from sun-exposed sites and from sun-protected sites. CONCLUSION: We could not show the evidence that telomere shortening is associated with photoaging of the skin.     

Photoageing shows histological features of chronic skin inflammation without clinical and molecular abnormalities

BACKGROUND: Photodamage is characterized by degradation of collagen and accumulation of abnormal elastin in the superficial dermis. Mast cells and macrophages, which are found in higher numbers in photoaged skin, have been implicated in this process. OBJECTIVES: To analyse the phenotype of haematopoietic-derived infiltrating cells in photodamaged skin. METHODS: Chronically sun-exposed (preauricular) and control sun-protected (postauricular) skin was recovered from eight healthy subjects undergoing cosmetic surgery (facial lifting). RESULTS: Histological analysis showed that sun-exposed skin harboured more infiltrating mononuclear cells than sun-protected skin. Cellular infiltrates were found at the periphery of areas of elastolysis around hair follicles in sun-exposed sites, whereas they were found in the interfollicular dermis around blood vessels and around hair follicles in sun-protected samples. Immunohistochemical analysis revealed an increased number of mast cells, macrophages and CD4+ CD45RO+ T cells in sun-exposed dermis as well as a higher number of CD1a+ dendritic cells in sun-exposed epidermis, compared with the sun-protected samples. Thus photoageing displays histological features of chronic skin inflammation. However, no molecular sign of inflammation was observed and we even found a decreased expression of interleukin-1beta mRNA in sun-exposed compared with sun-protected sites. Furthermore, the patients' skin looked normal and did not display any clinical inflammation. CONCLUSIONS: Collectively, these data show that chronic ultraviolet irradiation induces alterations of innate immune cells which are recruited in sun-exposed skin without being activated.     

A Case of Axillary Adenoid Basal Cell Carcinoma

Basal cell carcinoma (BCC) is the most common skin cancer with a steadily increasing incidence. Ultraviolet radiation is considered the single most important risk factor for BCC, because the tumor occurs most frequently in sun-exposed areas of the body, with approximately four of five BCCs occurring on the face. BCC occurs infrequently in non-sun-exposed skin. The axilla is one of the most sun-protected areas of the body, and BCC arising at this site is very rare. We herein report a case of adenoid BCC which arose from the axilla in a 33-year-old woman.     

The incidence of both tandem duplications and the common deletion in mtDNA from three distinct categories of sun-exposed human skin and in prolonged culture of fibroblasts

The use of mtDNA damage as a biomarker of cumulative sunlight exposure in human skin is a relatively new field of research. Previous investigations have simply compared the frequency of occurrence of the mtDNA common deletion (CD), and to a much lesser extent that of tandem duplications (TDs), to distinguish between sun-protected and sun-exposed skin. This approach is limited because non-melanoma skin cancer is predominantly formed on body sites that are "usually" sun-exposed as opposed to sites that are "occasionally" sun-exposed and as such they differ in their cumulative UV exposure. This study addresses this limitation by investigating the frequency of occurrence of the CD and TDs in 116 age-matched human skin samples taken from three different sun-exposed body sites. There was a greater frequency of the mtDNA damage in "usually" sun-exposed compared to "occasionally" sun-exposed body sites for both the CD and the TDs (P < 0.0001 and P = 0.058, respectively). In addition, we identified a 260 bp triplication of the mtDNA D-loop for the first time in skin. No evidence of the CD or TDs was observed in sun-protected (ie rarely exposed) skin (n = 20). Comparatively little is known about mtDNA damage in prolonged skin cell culture. We have furthered this work by studying the level of the CD and the frequency of the TDs during continued culture of human fibroblasts derived from skin samples taken from usually sun-exposed sites (n = 7 patients). The level of the CD decreases with culture, whereas the frequency of TDs can be maintained.     

Exploratory Study of Epidermis,Basement Membrane Zone,Upper Dermis Alterations and Wnt Pathway Activation in Melasma Compared to Adjacent and Retroauricular Skin

BackgroundMelasma is a chronic acquired focal hypermelanosis which pathogenesis has not been fully elucidated. Classical pathophysiologic studies have analysed the affected and perilesional areas, but little is known about the status of sun-protected skin, which is subjected to the same endogenous and genetic factors.ObjectiveTo assess the histological characteristics of melasma compared to adjacent and retroauricular skin.MethodsSkin samples were collected from 10 female from: melasma, perilesional area and retroauricular. The samples were stained (haematoxylin-eosin, periodic acid-Schiff, Fontana-Masson, picrosirius red, toluidine blue and Verhoeff), immunolabelled for CD34 and Wnt1. The data from the skin sites were analysed simultaneously by a multivariate model.ResultsMelasma skin exhibited noteworthy stratum corneum compaction, greater collagen heterogeneity, solar elastosis, higher number of mast cells, basement membrane zone (BMZ) damage, Wnt1 expression, pendulum melanocytes, higher cellularity and vascular proliferation at the superficial dermis. Stratum corneum compaction, collagen heterogeneity and BMZ abnormalities were variables associated to melasma that not follow a continuum through retroauricular to adjacent skin. Mast cell count was the variable that disclosed correlation with the most other abnormalities as well as had the greater contribution in the multivariate model.ConclusionIn addition to melanocyte hyperactivity, melasma skin exhibits alterations in the epidermal barrier, upper dermis and BMZ, which differ from the adjacent sun-exposed skin and retroauricular skin, indicating a distinct phenotype, rather than a mere extension of photoageing or intrinsic ageing. Mast cells appear to play a central role in the physiopathology of melasma.     

Topographic variations in normal skin, as viewed by in vivo reflectance confocal microscopy.

Near-infrared confocal microscopy is a new tool that provides skin images in vivo, with high resolution and contrast at a specific depth. Regional variations in live human skin viewed by confocal microscope have not been studied so far. In vivo reflectance confocal microscopy was performed in 10 adults (eight males, two females) of various skin phototypes. Six topographic sites were studied in each subject: forehead, cheek, inner and outer forearm surfaces, lower back and leg. Epidermal thickness at suprapapillary epidermal plates and rete pegs was measured during real-time imaging and the number and diameter of epidermal keratinocytes in each epidermal cell layer as well as the characteristics of dermal papillae were defined from the grabbed images. Stratum corneum appeared brighter in sun-exposed than in sun-protected areas and particularly pronounced in heavily pigmented individuals. The epidermal thickness at rete pegs, but not the suprapapillary epidermal plate, was greater in sun-exposed areas than in sun-protected sites except forearm flexor surface. The en face numerical density of granular keratinocytes is greater on the face as compared with all other sites, whereas the surface density of spinous keratinocytes is greater on sun-protected sites. Additionally, the number of basal keratinocytes per millimeter length of dermoepidermal junction is greater in sun exposed areas. Interestingly, the dermal papillae shape varies and their sizes increase in circumference from sun-exposed to sun-protected sites, as observed at a specific depth below the stratum corneum. In summary, our results demonstrate that near infra-red reflectance confocal microscopy is a feasible tool for microscopic analysis of skin morphometry in vivo.     

p53 mutation in metastatic melanomas and primary melanomas from sun-exposed and sun-protected sites

Background p53 mutation has been observed in many human malignancies, including skin cancers. However, the data in melanoma has been conflicting. Material and methods We have examined, by immunohistochemistry, using the DO7 and CM1 antibodies, the frequency of p53 overexpression in 14 metastatic melanomas and 61 primary melanomas, of which 30 were from sun-protected sites and 31 from sun-exposed sites. Results Ten of 14 metastatic melanomas showed p53 overexpression compared to only eight of 61 primary melanomas (P < 0.004). No significant difference in p53 expression was found between primary melanomas from sun-protected (2/30) and sun-exposed sites (6/31). We have also examined p53 mutation by single-strand conformation polymorphism (SSCP) analysis of four melanoma cell lines. One cell line established from a primary melanoma from a sun-protected site showed evidence of an altered migration pattern in exon 7. Sequencing analysis of this region confirmed a point mutation in codon 244, showing a G to C transversion. This mutation is unlikely to be due to ultraviolet (UV) radiation since mutations caused by UV radiation are predominantly CC → TT or C → T transitions. Conclusions In summary, p53 mutation in primary melanoma is uncommon and does not appear to be related to UV radiation. p53 mutation is more common in metastatic melanomas suggesting that it may be involved as a late event in melanoma progression.     

Histological increase in inflammatory infiltrate in sun-exposed skin of female subjects: the possible involvement of matrix metalloproteinase-1 produced by inflammatory infiltrate on collagen degradation

To investigate morphological changes occurring during cutaneous photoageing, a correlation between the number of infiltrating cells in the dermis and the degree of collagen damage was examined using sections from clinically normal chronically sun-exposed and sun-protected skin of Japanese female subjects. Haematoxylin and eosin-stained sections from 134 sun-exposed (subjects aged 3-82 years) and 73 sun-protected (subjects aged 1-86 years) areas demonstrated a predominant lymphoid cell and to a lesser extent histiocyte infiltration. The mean +/- SD number of lymphoid cells and histiocytes in the sun-exposed skin sections (427.0+/-192.2 and 147.8+/-83.3 cells/mm2, respectively) was significantly higher than in the sun-protected skin sections (292.6+/-98.3 and 125.9+/-59.0 cells/mm2, respectively) (P < 0.001 and P < 0.05, respectively), and the number of lymphoid cells in the sun-exposed skin sections increased significantly with age up to 50 years (r = 0.400, P < 0.001). Sun-exposed skin sections with severe collagen degeneration had a significantly higher number of lymphoid cells than those with slightly degenerated collagen (mean 626.3 vs. 482.4 cells/mm2, P < 0.01). The mean count of mast cells in sun-exposed skin was 202.0 cells/mm2; this did not vary with the age of the subjects or the level of collagen damage. Immunohistochemical studies using 24 frozen sections identified most of the lymphoid cells infiltrating sun-exposed skin as memory T lymphocytes (CD3+, CD4+ and CD45RO+). The number of cells which displayed immunoreactivity to matrix metalloproteinase (MMP)-1 in the sun-exposed skin sections was significantly higher than in the sun-protected skin sections (mean 170.2 vs. 113.6 cells/mm2, P < 0.05). Among these cells were observed CD3 and MMP-1 double-stained T lymphocytes, and T lymphocytes contacting MMP-1-positive cells. These morphological observations suggest that T lymphocytes infiltrating photodamaged skin may play a part in the degeneration and reduction of collagen through MMP-1 activity.     

Acute exposure of human skin to ultraviolet or infrared radiation or heat stimuli increases mast cell numbers and tryptase expression in human skin in vivo

Background  Mast cells are key effector cells in diverse immunological and pathological processes. It is still unclear why there are more mast cells at peripheral and sun-exposed skin sites than at sun-protected sites.
Objectives  To investigate changes in mast cell numbers associated with natural ageing and photoageing, and to observe the effects of ultraviolet (UV) and infrared (IR) radiation and heat on the prevalence of mast cells and tryptase expression in human skin in vivo .
Methods  Sun-exposed and sun-protected skin samples were taken from individuals in four different age groups. UV, IR or heat-treated buttock skin of young volunteers was also obtained. Mast cells were quantified by immunohistochemical staining of mast cell-specific tryptase and chymase. The expression of tryptase was determined by Western blotting.
Results  Both sun-exposed and sun-protected skin showed a gradual decrease in total mast cells (MC_Total) number with ageing. The number of mast cells in sun-exposed skin was significantly higher than that in sun-protected skin. After UV irradiation (2 minimal erythema doses), MC_Total and mast cells expressing tryptase and chymase were significantly increased at 24 and 48 h postirradiation. After IR irradiation (3 minimal heating doses) and heat treatment (43 °C for 90 min), MC_Total reached peak induction at 8 and 48 h after stimulation, respectively. Tryptase expression was also clearly upregulated by UV, IR and heat.
Conclusions  Our data demonstrate that mast cell numbers decreased with ageing in human skin. Also, mast cells may be activated and recruited by UV, IR and heat. These findings should further our understanding of the reason for the high prevalence of mast cells at peripheral sun-exposed skin sites.     

Sensitivity and Usefulness of VE1 Immunohistochemical Staining in Acral Melanomas with BRAF Mutation

BackgroundAcral melanomas are known to have a low frequency of BRAF mutation, in contrary to higher KIT mutation. Recently, VE1 immunostaining was reported to have a good correlation with BRAF mutation status.ObjectiveWe aimed to evaluate the clinicopathological features of BRAF-mutated acral melanomas and validate the correlation of the VE1 immunohistochemical stains in those cases.MethodsThe clinical features (age, sex, anatomical site), and histopathological characteristics of 41 patients with acral melanoma were evaluated. We performed a next-generation sequencing to detect BRAF mutation status. We also determined the correlation of VE1 immunohistochemical staining with BRAF mutation status.ResultsAmong 19 acral melanomas with BRAF mutation, common histopathological subtype was acral lentiginous melanoma (8/19, 42%) and nodular melanoma (8/19, 42%) and superficial spreading melanoma (3/19, 16%) followed. VE1 immunostaining results were positive in all 15 cases with BRAF V600E mutation (sensitivity 100%), and negative in 4 cases of BRAF non-V600E mutation. However, VE1 immunostaining was negative in all 22 patients with BRAF wild-type.ConclusionVE1 immunostaining had a good correlation with BRAF V600E mutation status.     

表皮p63和CD44与年龄及曝光部位的相关性

目的 探讨p63与CD44在皮肤衰老过程中与年龄、紫外线的关系。方法 采用免疫组化方法检测121例正常全厚皮肤标本中p63与CD44的表达,光镜下观察并计算表皮基底层p63阳性细胞百分比,用图像分析软件image proplus 6.0测量表皮层p63与CD44表达的吸光度值。结果 ①表皮基底层p63阳性细胞百分比与年龄呈负相关（r = -0.218,P < 0.05）,51 ~ 79岁组最低;但在曝光部位、半曝光部位与非曝光部位间的差异无统计学意义。②表皮p63的表达强度与年龄在曝光部位呈负相关（r = -0.389,P = 0.010）,在半曝光部位无相关性,在非曝光部位呈正相关（r = 0.341,P < 0.05）;三个部位表达强度的差异在10 ~ 30岁组无统计学意义,在31 ~ 50岁组与51 ~ 79岁组由强至弱依次为非曝光部位、半曝光部位、曝光部位。③表皮CD44的表达强度与年龄之间呈微弱负相关（r = -0.083,P < 0.05）,10 ~ 30岁组最高;但在曝光部位、半曝光部位与非曝光部位间的差异无统计学意义。结论 表皮基底层p63阳性细胞百分比、表皮CD44的表达强度和年龄呈负相关,和紫外线照射量无关。表皮p63表达强度在31 ~ 50岁组与51 ~ 79岁组的表达强度依曝光多少而递减。     

Photoaging-associated changes in epidermal proliferative cell fractions in vivo

The epidermis is a dynamic epithelium with constant renewal throughout life. Epidermal homeostasis depends on two types of proliferative cells, keratinocyte stem cells (KSCs), and transit amplifying (TA) cells. In the case of chronologic aging, levels of KSCs tend to decrease and change functionally. However, little is known about the effect of photoaging on epidermal proliferative subtype populations. The aim of this study was to validate involucrin/β1-integrin ratio as a molecular marker of epidermal photoaging, and to investigate the effects of photoaging caused by chronic UV exposure on the proliferative subtype populations. A total of 15 male volunteers (age range 20–24 and 77–85 years, Fitzpatrick skin phototype III–IV) provided sun-exposed and sun-protected skin samples for real-time RT-PCR, Western blot analysis and immunostaining. Fractional changes in proliferative subtype populations in photoaged and chronologically aged skins were analyzed by flow cytometry. The expression of β1-integrin was found to be significantly reduced in photoaged skin and ratios of the expressions of involucrin to β1-integrin were increased 2.6-fold only in elderly subjects. Interestingly, immunostaining of the sun-exposed skins of elderly subjects showed aberrant β1-integrin expression over the basal layer and greater numbers of Ki-67-positive cells than in sun-protected buttock skin. Flow cytometric analysis revealed that the proportion of KSCs to TA cells was reversed in sun-exposed and sun-protected skins of elderly subjects. Our results suggest that KSC numbers may be lower in photoaged skin than in chronologically aged skin and could be applied to hyperplastic pattern of photoaging. These findings suggest that the epidermis of photoaged skin is impaired in terms of its proliferative potential by attempting to repair chronic UV exposure and that photoaging may be associated with alteration in the two proliferative cell fractions.     

DNA repair capacities of cutaneous fibroblasts: effect of sun exposure, age and smoking on response to an acute oxidative stress

BACKGROUND: Sun irradiation causes skin ageing and cancer through the accumulation of damage to cell components. Intrinsic ageing is also associated with accumulation of oxidized macromolecules. OBJECTIVES: In this study we investigated the effects of sun exposure on response to an acute in vitro oxidative stress (H(2)O(2)) using normal human fibroblasts prepared from biopsies from 10 volunteers taken from sun-protected and sun-exposed sites. METHODS: Time-course experiments measuring repair of DNA strand-breaks and formamidopyrimidine DNA N-glycosylase-sensitive sites were conducted using the single-cell gel electrophoresis (comet) assay. RESULTS: Our results demonstrated that repair of strand-breaks was slower in sun-exposed compared with sun-protected cells. Interestingly, ageing was also associated with decreased DNA repair capacities for single-strand breaks in both sun-exposed and sun-protected cells whereas for formamidopyrimidine glycosylase (Fpg)-sensitive sites, this feature was in evidence only in sun-protected cells. Smoking, associated with age, was shown to have a markedly negative impact on DNA repair. CONCLUSIONS: Taken together our data suggest that stresses like ageing, sun exposure and smoking might have an additive effect contributing to the overall heterogeneity and decrease of DNA repair capacities in human cells and so increase the danger of sun exposure for health. They also emphasize the importance of the quality of the biological samples when repair studies on skin cells are to be conducted.     

Seasonal variation in the proliferation fraction of Australian common nevi

Image cytometry was used to assess seasonal variation in the proliferation fraction of Australian common nevi. Twenty pairs of nevi were evaluated. One member of each pair had been excised during the Australian summer, and the other member of the pair had been excised during the winter. The nevi were matched for age, sex, and body site. From each nevus, 6-microns sections were Feulgen-stained and evaluated with a CAS 200 image analyzer, which was used to obtain DNA histograms. Proliferation fractions were calculated from the histograms. The proliferation fraction of the nevi removed during the winter was 1.65 +/- 0.32%, whereas the proliferation fraction of the nevi removed during the summer was 1.95 +/- 0.42% (p = 0.41). For nevi from sun-exposed sites only, the proliferation rate of nevi excised during the winter was 1.81 +/- 0.39%, and 2.58 +/- 0.39% for nevi excised during the summer (p = 0.11). For nevi from sun-protected sites, there was no difference between winter and summer. When nevi excised during the summer were compared by site, sun-exposed nevi had a proliferation rate of 2.60 +/- 0.48% (p = 0.04). For nevi excised during the winter, there was a much smaller difference between sun-exposed and sun-protected nevi.     

Comparison of basal cell carcinoma subtypes observed in preoperative biopsy and Mohs micrographic surgery

BackgroundThe treatment of basal cell carcinoma depends on its histological subtype. Therefore, a biopsy should be performed before definitive treatment. However, as the biopsy is only a sample of the tumor, it does not always shows every histological subtype present in the neoplasm. Few studies have compared the histological findings of biopsies with the findings of Mohs micrographic surgery. By evaluating the totality of the peripheral margins, in addition to sampling large tumor areas, this technique provides a more representative amount of tissue than preoperative biopsy.Objectivesa) Determine the agreement between the histological subtype of basal cell carcinoma from punch biopsy and the findings of Mohs surgery; b) To assess, among the discordant cases, the prevalence of non-aggressive tumors in the preoperative biopsy that were reclassified as aggressive by Mohs surgery.MethodsRetrospective analysis of 79 cases of basal cell carcinomas submitted to punch biopsy and subsequent Mohs surgery.ResultsThe agreement between the classification of the subtypes in the biopsy and in Mohs surgery was 40.5%. Punch biopsy was able to predict the most aggressive basal cell carcinoma growth pattern in 83% of cases.Study limitationsRetrospective nature, sample size, and biopsies performed by different professionals.ConclusionsThe agreement between the histopathological subtypes of basal cell carcinoma as seen in preoperative biopsy and Mohs surgery was low. However, preoperative biopsy presented good accuracy (83%) in detecting aggressive histopathological subtypes.     

The influence of sun exposure on the DNA methylation status of <Emphasis Type="Italic">MMP9</Emphasis>, <Emphasis Type="Italic">miR-137</Emphasis>, <Emphasis Type="Italic">KRT14</Emphasis> and <Emphasis Type="Italic">KRT19</Emphasis> genes in human skin

Background

Studies have shown that a variety of environmental factors and habits are associated with epigenetic changes. In addition, various genes are also found to respond to UV radiation.

Objectives

The aim of this study was to investigate the sun exposure influence on the DNA methylation profile on the matrix metalloprotease-9 (MMP9), microRNA 137 (miR-137), cytokeratin 14 (KRT14) and 19 (KRT19) genes of skin cells of subjects with no history of skin diseases.

Methods

Skin biopsies (5mm) were obtained using a punch technique on sun-exposed (outer forearm) and sun-protected areas (inner arm) from 30 corpses from the Brazilian Service of Death Investigation. Skin types were ranked according to Fitzpatrick’s criteria. Genomic DNA was extracted and a DNA methylation analysis was performed using Methylation Specific PCR (MSP) or Methylation-Sensitive Restriction Enzymes (MSRE) of sun-exposed and sun-protected skin areas.

Results

No differences were found among the areas (p>0.05; McNemar), with the partially methylated condition found to be a common event in skin for both MMP9 and miR-137 genes and the methylated condition for both KRT14 and KRT19 genes. Additional analysis showed no differences in the methylation status when age, gender and skin type were considered, however, the methylation status of miR-137 gene seems to be genderrelated.

Conclusions

We conclude that sun exposure does not induce changes in the DNA methylation status in MMP9, miR-137, KRT14 and KRT19 genes.

     

Elastophagocytosis: a non-specific reaction pattern associated with inflammatory processes in sun-protected skin

Four cases characterized by primary inflammatory processes localized to sun-shielded skin were observed to have associated phagocytosis of elastic fibers by multinucleate histiocytic giant cells. These findings support the idea that this reaction pattern may occur non-specifically, at least in some instances, in sun-protected areas, as well as in sun-exposed skin as previously reported.     

Keep it simple. A ten-year experience in reconstructions after Mohs micrographic surgery

BackgroundMohs micrographic surgery is worldwide used for treating skin cancers. After obtaining tumor-free margins, choosing the most appropriate type of closure can be challenging.ObjectivesOur aim was to associate type of surgical reconstructions after Mohs micrographic surgery with the characteristics of the tumors as histological subtype, anatomical localization and especially number of surgical stages to achieve complete excision of the tumour.MethodsTransversal, retrospective analyses of medical records. Compilation of data such as gender, age, tumor location, histological subtype, number of stages to achieve clear margins and type of repair used.ResultsA total of 975 of facial and extra-facial cases were analyzed. Linear closure was the most common repair by far (39%) and was associated with the smallest number of Mohs micrographic surgery stages. This type of closure was also more common in most histological subtypes and anatomical locations studied. Using Poisson regression model, nose defects presented 39% higher frequency of other closure types than the frequency of primary repairs, when compared to defects in other anatomic sites (p < 0.05). Tumors with two or more stages had a 28.6% higher frequency of other closure types than those operated in a single stage (p < 0.05).Study limitationsRetrospective study with limitations in obtaining information from medical records. The choice of closure type can be a personal choice.ConclusionsPrimary closure should not be forgotten especially in surgical defects with fewer stages and in non-aggressive histological subtypes in main anatomic sites where Mohs micrographic surgery is performed.     

Epiplakin accelerates the lateral organization of keratin filaments during wound healing

BackgroundParakeratosis, the persistent presence of nuclei in the stratum corneum (SC) is associated with serious disruption of skin barrier function. Squamous cell carcinoma antigen 1 (SCCA1) is strongly up-regulated in inflamed and parakeratotic skin.ObjectiveTo find a biochemical marker for the SC barrier disruption, especially the disruption associated with parakeratosis.MethodsAn ELISA assay system was established to quantify SCCA1 in the extract of tape-stripped cornified cells. Transepidermal water loss (TEWL) and other skin parameters were measured and compared with the amount of SCCA1. Localization of SCCA1 was investigated immunohistochemically in various skin diseases with parakeratosis. Nuclei and SCCA1 on the skin surface were detected by staining of corniocytes collected on an adhesive-coated slide glass.ResultsSCCA1 showed strong up-regulation in lesional skin with psoriasis (466-fold), hayfever skin caused by Japanese ceder pollen (232-fold) and sun-exposed skin of healthy individuals (90-fold) compared to their normal sun-protected skin. The increased levels of SCCA1 were well correlated with increased values of TEWL and the number of parakeratotic cells in the SC. Furthermore, subjects with high levels of SCCA1 in the epidermis were more susceptible to barrier disruption by external stimuli, and this was accompanied with a further increase of SCCA1. We confirmed that localization of SCCA1 was limited to parakeratotic areas by using the skin surface staining technique. Immunohistochemical study also demonstrated that SCCA1 was always present at high levels in parakeratotic epidermis.ConclusionAll of our findings indicate that SCCA1 plays an important role in the induction of epidermal barrier disruption. SCCA1 may be a critical determinant of barrier function in the epidermis.