CD1a-positive Langerhans Cells Research Articles

Pathological and clinical relevance of selective recruitment of Langerhans cells in the respiratory bronchioles of smokers

Smoking causes an influx of inflammatory cells including Langerhans cells (LCs) into the airways and lung parenchyma, thus inducing histological changes, such as emphysema and fibrosis. We examined the distribution and quantity of Langerhans cells in relation to clinical and pathological findings and explored the association between smoking and accumulation of Langerhans cells in the respiratory bronchioles. Fifty-three patients who underwent lung resection for primary diseases, including lung cancer, were recruited. Histological and immunohistochemistry analyses were utilized to identify CD1a-positive Langerhans cells in peripheral lung specimens separated from primary lesions. Clinical characteristics, pathological changes, and distribution of CD1a-positive Langerhans cells distribution were assessed. Of the 53 patients, 35 were smokers and 18 were non-smokers. The number of Langerhans cells in the respiratory bronchioles was significantly increased in smokers as compared to that in non-smokers (p<0.001). The number of Langerhans cells in smokers was significantly higher in patients with mild emphysema than in those without emphysema (p<0.01). The high-LC group showed more frequent smoking-related histological changes, such as respiratory bronchiolitis, parenchymal fibrosis, accumulation of macrophages, and smoking-related interstitial fibrosis, than the low-LC group. However, there were no differences in the smoking indices and pulmonary functions of the groups. Selective accumulation of Langerhans cells in the respiratory bronchioles of smokers may lead to the development of smoking-related pathological changes.

Expression of Cluster of Differentiation 1a-Positive Langerhans Cells in Oral Lichen Planus.

Background/Purpose:Lichen planus is a T-cell-mediated mucocutaneous disorder characterized histopathologically by a band of chronic inflammatory cells in the subepithelial zone and degeneration of basal layer. The present study was aimed to evaluate the distribution and quantitative assessment of cluster of differentiation 1a (CD1a)-positive Langerhans cells (LCs) in oral lichen planus (OLP), thus to determine the role of LCs pertaining to the changes occurring in OLP.Materials and Methods:Five cases of normal oral mucosa and 20 cases of OLP were immunostained with CD1a antibody; the positive cells were counted manually in the photomicrographs and statistically analyzed using t-test, Mann–Whitney test, and Wilcoxon signed-rank test.Results:The average percentage of CD1a-positive LCs in normal subjects was 0.9%, and in the OLP cases higher percentage was observed (3.93%). The statistical comparison of these two parameters was significant (P=0.018). The degree of basal cell degeneration and density of subepithelial infiltrate on statistical comparison with the concentration of CD1a-positive LCs showed significant results.Conclusion:LCs play a pivotal role in the recruitment of CD4+ and CD8+ cells to the subepithelial region and basal keratinocytes apoptosis. A small number of study subjects, assessment of only CD1a molecule and LCs in the epidermis only were a few of the drawbacks of the study.

Distribution of Dendritic Cells and Langerhans Cells in Peri-implant Mucosa.

Background:Peri-implant diseases leading to the failure of dental implants is concern in the field of dentistry. Difference in immune response around peri-implant tissues with healthy tissue might be responsible for the hidden cause of peri-implant diseases. Hence, in the current study, the dispersion of the dendritic cell (DC) subpopulations and Langerhans cells (LCs) was evaluated in healthy peri-implant mucosa (HPIM) and healthy mucosa (HM) to know the imbalance in immune homeostasis.Subjects and Methods:A total of 15 nonsmoker participants were selected for the study. First sample of the HM was obtained before the implant placement (Group I) and second sample of peri-implant mucosa was obtained at the time of placement of the gingival former (Group II). Immunochemistry was used to quantify DCs and LCs in the samples.Statistical Analysis Used:To analyze the distribution of cells in the epithelium and lamina propria, Wilcoxon matched pairs test was used.Results:Mean numbers of CD1a (LCs) in the epithelium and lamina propria of Group I and Group II were 25.2 ± 6.41 and 27.47 ± 10.26 and 19.27 ± 7.27 and 12.46 ± 3.04, respectively. Mean numbers of factor XIIIa (DCs) in the epithelium and lamina propria in Group I and Group II were 30.37 ± 5.42 and 86.93 ± 13.99 and 50.47 ± 7.27 and 124.33 ± 10.27, respectively. Statistically significant differences in the number of cells in the epithelium and lamina propria of Group I and Group II were noted (P = 0.001 and P = 0.001).Conclusions:CD1a-positive LCs were more in the epithelium rather than lamina propria in Group II. Higher numbers of factor XIIIa-positive DCs were observed in the lamina propria than epithelium in Group I and II.

Significant association of high-grade inflammation and thick lining epithelium with the increased number of Langerhans cells in dentigerous cysts.

Langerhans cells (LCs) are antigen-presenting cells. This study assessed the LC counts in 80 dentigerous cysts (DCs). The CD1a-positive LC numbers in the lining epithelia and subepithelial connective tissues were counted at 80 DC sites without inflammation, 33 DC sites with mild/moderate inflammation, and 9 DC sites with severe inflammation from 80 DC specimens. The mean LC counts in the lining epithelia and subepithelial connective tissues increased significantly from no inflammation (0.5±0.5 and 0.2±0.3cell/high-power field or HPF, respectively) through mild/moderate inflammation (6.8±1.8 and 2.4±2.0cells/HPF, respectively) to severe inflammation DC sites (18.9±7.0 and 6.7±5.8cells/HPF, respectively; all P-values<0.001). DC sites with inflammation had thicker lining epithelia than those without inflammation. Moreover, the mean LC counts in the lining epithelia and subepithelial connective tissues of DCs were significantly higher in the thicker lining epithelium (>50μm) group (7.4±6.5 and 2.6±3.4cells/HPF, respectively) than in the thinner lining epithelium (≦ 50μm) group (0.5±0.5 and 0.2±0.3cells/HPF, respectively; both P-values<0.001). A significant association of high-grade inflammation and thick lining epithelium with the increased LC number in DCs is found. The finding of few LCs in the lining epithelia of DCs without inflammation indicates the reduced immunosurveillance ability against DC lining epithelial cells in DC patients. It needs further studies to confirm the role of reduced immunosurveillance in the enlargement of the DC.

The morphology and distribution of CD1a positive Langerhans cells in normal and squamous cell carcinoma of cervix

IntroductionLangerhans cells (LCs), a type of dendritic cells are the professional antigen presenting cells present in the mucosa surfaces. They play an important role in antitumor immune response. The present study aims to find out the morphology and distribution of CD1a positive LCs in normal and squamous cell carcinoma of cervix. MethodsTwenty two normal and eleven ectocervical specimens with squamous cell carcinoma were processed for immunohistochemistry and stained with monoclonal mouse anti-human CD1a (Dako, USA). The morphology of CD1a positive LCs was studied using Olympus BX43 microscope. Morphometric analysis was done using Cellsens imaging analysing software. ResultsThere was a statistically significant difference in the number of LCs between normal (8±2.76) and squamous cell carcinoma of cervix (5.36±2.88). In the region of lymphatic infiltration both in epithelium and lamina propria, there were more number of LCs and most of the cells lost their dendritic processes in squamous cell carcinoma. 31.77% of the cells had no dendritic processes. The difference in the mean diameters of LCs was statistically significant (p=0.005) between normal and squamous cell carcinoma of cervix. DiscussionFewer number of CD1a positive LCs and their loss of dendritic processes in the squamous cell carcinoma of cervix compared to normal cervix indicate that immune responses are suppressed in patients with cancer.

Expression of indoleamine 2, 3-dioxygenase in condyloma acuminatum lesions

Objective To measure the expression of indoleamine 2, 3-dioxygenase (IDO) in condy-loma acuminatum (CA) lesions, and to evaluate its ability to locally metabolize tryptophan. Methods Immunohistochemical study was performed to observe the protein expression of IDO in skin lesions of patients with CA, and count the number of IDO-positive cells. Immunofluorescence assay was conducted to estimate the relationship between IDO-positive cells and dendritic cells. Epidermal cells and keratinocytes were isolated from warts of 30 patients with CA and prepuces of 11 healthy controls respectively, and both in vitro incubated with tryptophan solution for 4 hours. Then, high-performance liquid chromatography (HPLC) was performed to detect the level of tryptophan metabolite, kynurenine, in the culture supernatant of the above cells, which could reflect the ability of epidermal cells to metabolize tryptophan. Results Rare IDO-positive cells were found in the normal skin, but a lot of IDO-positive cells gathered in the epidermis of the wart tissues. The IDO-positive cell/total cell ratio was significantly higher in the wart tissues than in the normal skin (48.3% ± 15.4% vs. 5.2% ± 2.4%, P < 0.05) . The fluorescence signals of IDO-positive cells and CD1a-positive Langerhans cells were not overlapped with each other, suggesting that IDO-positive cells were derived from epidermal cells of the wart tissues. Compared with the keratinocytes from the healthy skin, the epidermal cells from warts had a stronger ability to metabolize tryptophan in vitro. Conclusion A large number of IDO-positive cells exist in CA warts, and may be involved in occurrence of CA. Key words: Condylomata acuminata; Indoleamine-pyrrole 2,3,-dioxygenase; Langerhans cells; Immunohistochemistry; Fluoroimmunoassay

Drug delivery across intact and disrupted skin barrier: Identification of cell populations interacting with penetrated thermoresponsive nanogels

Nanoscaled soft particles, such as nanogels, can be designed to incorporate different types of compounds and release them in a controlled and triggered manner. Thermoresponsive nanogels (tNG), releasing their cargo above a defined temperature, are promising carrier systems for inflammatory skin diseases, where the temperature of diseased skin differs from that of healthy skin areas. In this study a polyglycerol-based tNG with diameter of 156nm was investigated for penetration and release properties upon topical application on ex vivo human skin with intact or disrupted barrier. Furthermore, temperature-triggered effects and the internalization of tNG by skin cells upon translocation to the viable skin layers were analyzed. The investigated tNG were tagged with indodicarbocyanine and loaded with fluorescein, so that fluorescent microscopy and flow cytometry could be used to evaluate simultaneously particle penetration and release of the fluorochrome. Topically applied tNG penetrated into the SC of both intact and disrupted skin explants. Only in barrier-disrupted skin significant amounts of released fluorochrome and tNG penetrated in the epidermis and dermis 2h after topical application. When a thermal trigger was applied by infrared radiation (30s, 3.9mJ/cm2), a significantly higher penetration of tNG in the SC and release of the dye in the epidermis were detected with respect to non-triggered samples. Penetrated tNG particles were internalized by skin cells in both epidermis and dermis. Only few CD1a-positive Langerhans cells associated with tNG were found in the epidermis. However, in the dermis a significant percentage of cells associated with tNG were identified to be antigen presenting cells, i.e. HLA-DR+and CD206+cells. Thus, tNG represent promising carrier systems for the treatment of inflammatory skin diseases, not only because of their improved penetration and controlled release properties, but also because of their ability to effectively reach dermal dendritic cells in barrier-disrupted skin.

Langerhans cell number is a strong and independent prognostic factor for head and neck squamous cell carcinomas

ObjectivesHead and neck squamous cell carcinomas (HNSCCs) exhibit great biological heterogeneity and relatively poor prognosis. Tobacco and alcohol consumption is involved in the cause of the majority of these cancers, but over the last several years, Human Papilloma Virus (HPV) infection has increased specifically in oropharyngeal cancers and become an additional risk factor. Here, we evaluated the number of Langerhans cells (LCs) in HNSCC and reporting its prognostic power in comparison to other risk factors. Materials and methodsOur clinical series was composed of 25 tumor-free peritumoral epithelium, 64 low-grade dysplasia, 54 high-grade dysplasia and 125 carcinoma samples. HPV was detected by E6/E7 qPCR and p16 immunohistochemistry. CD1a-positive LCs were counted in intra-tumoral and stromal compartments as well as lymph nodes. MIP-3α was assessed in carcinomas using immunohistochemistry. ResultsUnivariate Cox regression analyses demonstrated that high LC number is associated with longer recurrence-free survival in both intra-tumoral and stromal compartments and longer overall survival in stromal compartment. Tobacco and alcohol habits, but not HPV status, are also correlated with poor prognoses in terms of recurrence. Multivariate analyses reported stromal LC number as a strong prognostic factor independent of tobacco, alcohol and HPV status. Moreover, LC number is higher in tumors and invaded lymph nodes than dysplastic lesions but it decreases in HPV-positive cancer patients. Further, LC number correlates with MIP-3α expression. ConclusionThese findings suggest that LC number is a significant and independent prognostic factor for HNSCC. LC infiltration is increased in cancer lesions but decrease with HPV infection.

The morphology and distribution of CD1a positive Langerhans cells in normal and squamous cell carcinoma of cervix

Power consumed in metal cutting is typically converted into heat near the cutting tool edge. Cutting fluids are then provided to a cutting zone in order to improve the tribological characteristics of machining processes and to dissipate the generated heat. The use of conventional cutting fluids however has lately been questioned due to the adverse impact on the environment and human health. Therefore, trends are directed to various alternatives such as vegetable oils (VOs). VOs offer a combination of good biodegradability and high lubricity, eco-friendly and compatibility with additives, low toxicity and volatility, high flash points and high viscosity indices. This paper details preliminary experimental results when turning Ti-6Al-4 V. The impact of VO-based cutting fluids, cutting tool materials and working conditions were investigated. Two sets of experimental plans were designed comprising 25 and 27 tests with analysis of variance (ANOVA) employed to evaluate the effect of process variables on Ra and tool flank wear. In general, surface roughness Ra ranged between 0.56 μm and 1.81 μm and statistical analysis showed that the main contributing factor for Ra is feed rate having a high Percentage Contribution Ratio (PCR) of 94.4%. Noticeable increase in tool tip flank wear was recorded when higher cutting speeds were used.

Regional differences in the density of Langerhans cells, CD8-positive T lymphocytes and CD68-positive macrophages: a preliminary study using elderly donated cadavers.

To provide a better understanding of the local immune system in the face and external genitalia, i.e., the oral floor, lower lip, palpebral conjunctiva, anus and penis, we examined the distribution and density of CD1a-positve Langerhans cells, CD8-positive suppressor T lymphocytes and CD68-positive macrophages using specimens from 8 male elderly cadavers. The density of Langerhans cells showed an individual difference of more than (or almost) 10-fold in the lip (oral floor). In the oral floor, Langerhans cells were often spherical. Submucosal or subcutaneous suppressor lymphocytes, especially rich in the oral floor and penile skin, migrated into the epithelium at 4 sites, except for the anus. In the conjunctiva, macrophage migration into the epithelium was seen in all 8 specimens. The density of suppressor lymphocytes showed a significant correlation between the oral floor and the lip (r=0.78). In contrast, the anal and penile skins showed no positive correlation in the density of all three types of immunoreactive cells examined. Overall, irrespective of the wide individual differences, the oral floor and conjunctiva seemed to be characterized by a rich content of all three cell types, whereas the penile skin was characterized by an abundance of suppressor lymphocytes. Based on the tables, as mean value, the relative abundance of three different cell types were as follows; CD1a-positive Langerhans cells (anus), CD8-positive lymphocytes (penis), and CD68-positive macrophages (lip). The present observations suggest that the local immune response is highly site-dependent, with a tendency for tolerance rather than rejection.

SKIN CHANGES AND PECULIARITIES IN PATIENTS WITH METABOLIC SYNDROME

Approximately 20-25 % of the World’s adult population aged 40 - 75 years have metabolic syndrome (MS). MS is one of the most widespread risk factors for: diabetes mellitus, cardiovascular disorders and skin disorders MS, due to the oxidative stress, supports a chronic inflammatory reaction in the skin and in the other parts of the body. During oxidative stress the net amount of reactive oxygen species (ROS) exceeds the antioxidant capacity of the body causing lipid peroxidation, protein oxidation and oxidative DNA damage. The role of oxidative stress in pathogenesis of early skin changes in patients with MS is not clearly defined. The aim of our study was to compare visual skin changes between patients with MS and without it, and to reveal early histological manifestations of MS in the skin. The study was conducted at the Clinic of Aesthetic Dermatology, Riga, Latvia. 50 patients aged 45-55 were enrolled. The research consisted of a clinical examination, biochemical testing and Punch biopsies. Tissue samples were stained with haematoxylin-eosin, Masson’s Trichrome and also immunohistochemically stainining with antibodies to CD34, CD117, CD20, CD8 and bcl-2. CD1a positive Langerhans cells were evaluated in 3 fields of vision. Data was analyzed with Microsoft Excel 2010 software. Gender ratio was women: men= 1.6:1. Histological changes in the skin of patients with MS were: hyperkeratosis, acanthosis, dermal fibrosis, elastosis and mild thickening of the stratum spinosum. Infiltrates around blood vessels were composed of T lymphocytes (CD3+). More significant expression and accumulation of apoptotic protein Bcl2 in skin of patients with MS in comparison to patients without MS was noted. Initial skin histological changes in MS are dermal elastosis, thickening of stratum spinosum and acanthosis. Mild T lymphocytic infiltration around capillaries possibly reflects the inflammatory component of MS. Increased accumulation of bcl2 anti-apoptotic protein in epidermis was more significantly expressed in patients with MS.

Changes in distribution and ultrastructure of Langerhans cells in condyloma acuminatum tissues, and analysis of the underlying mechanism

To determine the changes in distribution and function of Langerhans cells (LCs) in condyloma acuminatum (CA) tissues, as well as the possible underlying mechanism. The expression of CD1a and E-cadherin in 26 CA lesions and 10 normal prepuce tissues was determined using the streptavidin peroxidase method. The mRNA expression of CD1a and E-cadherin was determined using reverse transcriptase polymerase chain reaction. The ultrastructure of LCs was observed under a transmission electronic microscope (TEM). In the CA tissues, the number of CD1a-positive LCs was significantly decreased (10.66 ± 11.71) compared with the number in normal prepuce tissues ( p < 0.05). The LCs in the CA tissues had smaller cell bodies with fewer and shortened cytodendrites. The CD1a mRNA expression in the CA tissues significantly decreased compared with that in the normal tissues (0.4066 ± 0.2671 vs. 0.7444 ± 0.3667; p < 0.01). The average E-cadherin staining score in the CA tissues was significantly lower than that in the normal tissues (2.36 ± 1.41 vs. 7.67 ± 1.64; p < 0.01). The E-cadherin mRNA expression in the CA tissues was also significantly lower than that in the normal tissues (0.1737 ± 0.1083 vs. 0.3786 ± 0.1460; p < 0.01). A positive correlation was observed between the LC number and E-cadherin expression density ( r = 0.8381, p < 0.05), as well as between the mRNA expression of CD1a and E-cadherin ( r = 0.8381, p < 0.05). TEM observation revealed changes in the morphology and quantity of subcellular organelles (Birbeck granules) in the CA tissues. CA lesions are characterized by a decreased number of LCs and antigen presentation dysfunction. The decrease in the number of LCs may be correlated with reduced E-cadherin expression, which hinders intraepidermal LC retention.

CD1a‐positive Langerhans cells and their relationship with E‐cadherin in ameloblastomas and keratocystic odontogenic tumors

Ameloblastomas and keratocystic odontogenic tumors (KOTs) are lesions that are characterized by locally invasive growth and cause extensive bone destruction. In addition, it is known that E-cadherin influences the adhesion of Langerhans cells (LCs) to keratinocytes. The aim of this study was to investigate, using immunohistochemistry, the distribution of CD1a-positive cells in ameloblastomas and KOTs and their relationship with E-cadherin, in comparison to calcifying cystic odontogenic tumor (CCOT). The CD1a-positive LCs were observed in 11 ameloblastomas and KOTs. All of the cases of CCOT showed CD1a-positive LCs and a significant difference was found when this tumor was compared with ameloblastomas (P < 0.05, Mann-Whitney test). A statistically significant difference was also noted when comparing CD1a-positive LCs between CCOTs and KOTs (P < 0.05, Mann-Whitney test). Lower expression of E-cadherin in ameloblastomas (AMs) in relation to KOTs and CCOTs (P < 0.05, Fisher test) was observed. There was no correlation between E-cadherin and CD1a-positive LCs between all odontogenic tumors that were studied (P > 0.05, Spearman test). A quantitative difference of CD1a-positive cells between AMs and KOTs in comparison to CCOTs was observed. This permits to speculate that a depletion of CD1a-positive LCs might influence the local invasiveness of ameloblastomas and KOTs. Furthermore, it is suggested that E-cadherin mediates cell adhesion in these tumors.

Immunohistochemical localization of CD1a and S100 in gingival tissues of healthy and chronic periodontitis subjects

The aim of this study was to evaluate the presence and distribution of CD1a and S100 protein markers in states of gingival health and chronic periodontitis in human subjects. Gingival tissue samples were derived from 10 healthy and 10 chronic periodontitis-affected human subjects. The presence and distribution of CD1a and S100 protein was assessed using immunohistochemistry, and the cell types involved in their expression was determined. The presence and distribution of CD1a was confined only to the gingival epithelium, whereas S100 was seen in the epithelium and connective tissue. However, increased expression of both CD1a and S100 protein was seen in periodontitis-affected gingival tissues compared with healthy gingiva. Immunohistochemistry demonstrated that CD1a- and S100-positive cells in the epithelium are Langerhans cells (LCs) and S100 positive cells in the connective tissue are dendritic cells (DCs). Our findings suggest the transition of CD1a-positive LCs to S100-positive DCs from epithelium to connective tissue in response to an antigenic challenge. Demonstration of increased number of S100-positive DCs in the gingival connective tissue in chronic periodontitis possibly suggests their involvement in bone resorption in addition to their antigen presentation property.

Demonstration of Langerhans Cells (Lcs) in the Intra-Follicular and Inter-Follicular Regions of the Human Palatine Tonsil Ultrastructural and Immunohistochemical Study

Dendritic cells (DCs) and macrophages function to capture and process antigen and present it to T lymphocytes, a critical step in early immune response. The dendritic Langerhans cells (LCs) belong to the system of antigen presenting cells and play a role in cutaneous immune responses. In our previous studies, we have ultrastructurally demonstrated the presence of LCs in the crypt epithelium and surface epithelium of the human palatine tonsil. In the present study our aim was to demonstrate the LCs in the intra-follicular and inter-follicular area of human palatine tonsil by conventional electron microscopy and immunocytochemistry. Here we report the presence of CD1a positive Langerhans Cells (LCs) in the intra-follicular and inter-follicular areas of the human palatine tonsil and confirm their presence ultrastructurally by demonstrating typical Birbeck granules (BGs) in their cytoplasm. Identification of LCs in the intra-follicular and inter-follicular areas of the palatine tonsil supports the migratory nature of the LCs. Apposition between the Langerhans cells and lymphocytes in the intra-follicular area further strengthens the function of Langerhans cells as antigen presenting cells in initiating immune responses in human palatine tonsil.

Evaluation of Langerhans Cell Infiltrate by CD1a Immunostain in Liver Biopsy for the Diagnosis of Primary Biliary Cirrhosis

Primary biliary cirrhosis (PBC) is characterized by chronic nonsuppurative destructive cholangitis, which is considered to be a cell-mediated immune reaction. Antigen-presenting cells, including Langerhans cells and dendritic cells, have been found in portal tracts and in bile duct epithelium and may play a role in the pathogenesis of PBC, but the importance of identifying these cells for diagnosing PBC has not been studied yet. In this study, we sought to evaluate the importance of identifying Langerhans cells using a CD1a immunostain in the diagnosis of PBC. Liver biopsies from adult patients diagnosed with PBC (n=60), primary sclerosing cholangitis (n=29), obstructive cholangitis (n=13), chronic viral hepatitis B or C (n=19), autoimmune hepatitis (AIH, n=15), acute cellular rejection (n=11), and chronic rejection (n=10) at our institution were retrospectively reviewed. An immunohistochemical stain for CD1a was used to detect Langerhans cells, and the distribution of CD1a-positive Langerhans cell infiltrate was recorded as lobular, portal with bile duct sparing, and intraepithelial. Intraepithelial Langerhans cells were identified in 58% of PBC including antimitochondrial antibody-negative PBC and PBC-AIH overlap cases, 14% of primary sclerosing cholangitis, 15% of obstructive cholangitis, 9% of acute cellular rejection, 6% of AIH, and no cases of chronic viral hepatitis or chronic rejection. The number of intraepithelial Langerhans cells was significantly higher in PBC than in other conditions, with the mean number of CD1a-positive intraepithelial Langerhans cells per bile duct in PBC calculated as 2.2 compared with <1 per duct for the other control cases. Thirty-three of 60 (55%) PBC cases showed at least one bile duct containing ≥2 CD1a-positive Langerhans cells. This was statistically significant (P<0.01) when compared with control groups. The overall sensitivity and specificity of using ≥2 CD1a-positive Langerhans cells per bile duct as the diagnostic criteria for PBC were 55% and 96%. Given the heterogenous nature of liver involvement by PBC, a review of cases with morphologic features of duct damage yielded an increased sensitivity (79%) with no reduction in specificity. In conclusion, the detection of a Langerhans cell infiltrate of ≥2 cells by CD1a in a given bile duct on needle biopsy may be a valuable tool in the diagnosis of PBC.

Clinicopathologic and Immunohistochemical Features of Pigmented Basal Cell Carcinomas of the Eyelids

To describe the clinical and microscopic features of pigmented basal cell carcinomas (pBCC) of the eyelid. Retrospective observational case series collected at one institution. An analysis of clinical records, photographs, and histopathologic characteristics of 257 BCCs with a review of the literature. The frequencies of clinically pigmented, and of microscopically pigmented but clinically nonpigmented, BCCs were determined. Cytochemical stains (Fontana-Masson, Prussian blue) and immunohistochemical probes (S-100, microphthalmia-associated transcription factor [MiTF], HMB-45, MART-1, CK20, synaptophysin, chromogranin, CD1a, Ki-67) were then employed and the findings correlated with the degree of clinical pigmentation. Histopathologically, 13 of 257 cases (5.06%) were found to have pigment; of these 13, 6 (all white patients) had clinically apparent pigmentation (2.33%), either focal or diffuse. Eight of 13 lesions developed on the lower eyelids. All stained positively for melanin but negatively for iron. MiTF highlighted numerous melanocytic nuclei in the tumor lobules, while MART-1 and HMB-45 revealed the dendritic shapes of the entrapped melanocytes. There was a subtotal blockage of melanin transfer to the surrounding basaloid cells. Intralobular S-100-positive cells included CD1a-positive Langerhans cells, while CK20 did not identify any Merkel cells. Only 1 of 6 lesions was uniformly clinically pigmented, whereas the other 5 were only focally brown-black. The clinical pigmentation was imparted by varying densities and distributions of melanocytes with arborizing dendrites, which were present in all BCCs. Melanophages within the stroma and basaloid cell melanization also contributed to pigmentation. No behavioral or biologic differences in pBCC were documented compared with clinically nonpigmented lesions.

Immunohistochemical assessment of CD1a‐positive Langerhans cells and their relationship with E‐cadherin in minor salivary gland tumors

The aim of this study was to investigate the presence of CD1a-positive Langerhans cells and their relationship with E-cadherin in minor salivary gland tumors. Twenty-seven minor salivary gland tumors were investigated using immunohistochemistry for CD1a and E-cadherin. A significant difference regarding the mean density of CD1a-positive Langerhans cells was observed between pleomorphic adenomas and malignant tumors studied (P = 0.001). No CD1a-positive cells were detected in most cases (n = 5) of cystic adenoid carcinomas. CD1a-positive cells were detected in one mucoepidermoid carcinoma case, and six low-grade polymorphous adenocarcinomas cases. Comparison of the mean density of CD1a-positive cells between the three malignant tumors showed no significant difference (P = 0.127). No significant difference was observed in the presence of E-cadherin between tumors (P = 0.73), but it was detected in 24 cases. The lack of CD1a-positive in malignant salivary gland tumors facilitates the neoplastic development and suggests that these cells might be useful as auxiliary diagnostic and prognostic tool in minor salivary gland tumors. Furthermore, it is suggested that E-cadherin mediates cell adhesion in these tumors although we did not demonstrate significance.

Antioxidants add protection to a broad-spectrum sunscreen

Exposure of human skin to ultraviolet radiation (UVR) results in erythema, pigment darkening, skin cancer and photoageing. In addition to conventional organochemical and the physical-mineral type sunscreens (SS), other non-SS protective strategies have been investigated, including antioxidants (AOx) and topical DNA repair enzymes. To investigate whether AOx could improve the protection provided by a broad-spectrum sunscreen (SS) preparation. Volunteers were exposed to repetitive solar-simulated (ss)UVR at 1.5 times minimal erythema dose for four consecutive days. Thirty minutes before each exposure and 6, 24 and 48 h after the last exposure, the test materials [vehicle, SS (sun protection factor 25) alone, AOx alone and SS plus AOx] were applied to four different sites. Another two sites received ssUVR only, or SS plus AOx only, and a third site was left untreated (neither ssUVR or product). Erythema and pigmentation were measured using a Mexameter. Biopsy specimens were taken 72 h after the last irradiation. The thickness of the stratum corneum and epidermis were measured by microscopy. Expression of cytokeratins (CKs), matrix metalloproteinases (MMPs) and CD1a-positive Langerhans cells (LCs) analysed by immunohistochemical staining, and relative expression levels were compared between all seven sites. AOx alone did not reduce erythema. There was a significant reduction in pigmentation, and the product almost completely protected against LC depletion. AOx plus SS gave better protection against pigment formation and CK5/6 induction than SS alone. AOx alone protected against ssUVR-induced hyperproliferation, as shown by epidermal thickness and CK16 biomarkers, and was better than SS alone. Interestingly, although protection against induction of MMP-9, a marker of photoageing, did not reach significance when either SS or AOx were applied separately, there was complete protection against MMP-9 induction when these were combined. Non-SS materials such as AOx can contribute significantly to sun protection when added to a broad-spectrum SS and applied topically to human skin in vivo.

Accumulation of CD1a-positive Langerhans cells and mast cells in actinic cheilitis

LCs and MCs are known to be directly influenced by UV radiation. This study investigated the presence of Langerhans cells (LCs) and mast cells (MCs) in actinic cheilitis (AC) exhibiting epithelial dysplasia (ED). Using immunohistochemistry for CD1a and mast cell tryptase, LCs and MCs density was assessed in 35 cases of AC with different degrees of ED. LCs were found in 32 cases of AC whereas MCs were found in all cases. There was an increase in LCs density irrespective of degree of ED when the cases were compared to normal lip mucosa (P=0.04343). No statistical difference in LCs density was observed regarding the different degrees of dysplasia (P>0.05). Significant difference in MCs density between mild and moderate dysplasia and normal lip mucosa was found (P<0.05). No significant correlation between LCs and MCs was seen (P=0.1258). Although no correlation could be established between LCs and MCs and the different degrees of ED; it is possible that the accumulation of LCs plays an immunostimulatory and protective role in the defense against progression of dysplasia. Further studies are necessary to determine the role of MCs in the development of AC.