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The International Journal of... 2022The epidermis is a stratified epithelium that forms the barrier between the organism and its environment. It is mainly composed of keratinocytes at various stages of...
The epidermis is a stratified epithelium that forms the barrier between the organism and its environment. It is mainly composed of keratinocytes at various stages of differentiation. The stratum corneum is the outermost layer of the epidermis and is formed of multiple layers of anucleated keratinocytes called corneocytes. We aim to highlight the roles of epidermal differentiation and proteolysis in skin diseases. Skin biopsies isolated from mice, the established model of Netherton syndrome (NS), and from patients with NS, seborrheic dermatitis (SD) and psoriasis, as well as healthy controls, were analyzed by histology and immunohistochemistry. Our results showed that NS, SD, and psoriasis are all characterized by abnormal epidermal differentiation, manifested by hyperplasia, hyperkeratosis, and parakeratosis. At the molecular level, abnormal differentiation is accompanied by increased expression of involucrin and decreased expression of loricrin in NS and psoriasis. Increased epidermal proteolysis associated with increased kallikrein-related peptidases (KLKs) expression is also observed in both NS and psoriatic epidermis. Furthermore, reduced expression of desmosomal proteins is observed in NS, but increased in psoriasis. Since desmosomal proteins are proteolytic substrates and control keratinocyte differentiation, their altered expression directly links epidermal proteolysis to differentiation. In conclusion, abnormal cellular differentiation and proteolysis are interconnected and underlie the pathology of NS, SD and psoriasis.
Topics: Animals; Cell Differentiation; Epidermis; Humans; Keratinocytes; Mice; Peptide Hydrolases; Proteolysis; Psoriasis
PubMed: 34881788
DOI: 10.1387/ijdb.210161gs -
Postepy Dermatologii I Alergologii Oct 2021Reflectance confocal microscopy (RCM) is abbreviated as skin three-dimensional computed tomography, which can help clearly observe the structure of the epidermis and... (Review)
Review
Reflectance confocal microscopy (RCM) is abbreviated as skin three-dimensional computed tomography, which can help clearly observe the structure of the epidermis and superficial dermis. It is a non-invasive skin disease examination method and provides fast access to real-time, dynamic skin micro-anatomical images. Therefore, RCM is widely used in the clinical diagnosis of skin diseases. For example, the RCM features of vitiligo are as follows: pigment loss or partial pigment loss in the lesion area, loss of the basal layer pigment ring. The RCM findings of Riehl melanosis are as follows: basal cell liquefaction and degeneration. The RCM results for verruca plana show: the Rose-like structure. The characteristics of psoriasis under RCM include: hyperkeratosis, parakeratosis, thickening of the spinous layer, capillary dilatation and hyperaemia, peripheral inflammatory cell infiltration. Epidermal brain-like structure was observed under RCM of seborrheic keratosis. With RCM, image acquisition and preservation of the skin is convenient, and the technique is convenient for comparing the development of lesions during long-term follow-up observation. Therefore, it helps to understand disease development in real time and dynamically and can be used to evaluate the curative effect. In this article, we briefly review the technical principles, diagnostic criteria for RCM application and RCM-related research progress in the diagnosis of pigmentary diseases, inflammatory diseases, skin tumours, and other common skin diseases.
PubMed: 34849113
DOI: 10.5114/ada.2021.110077 -
Gastroenterology Research Oct 2021Peroral endoscopic myotomy (POEM) has been increasingly used to treat achalasia. Previous studies have reported high frequency of muscular eosinophilic infiltration in...
BACKGROUND
Peroral endoscopic myotomy (POEM) has been increasingly used to treat achalasia. Previous studies have reported high frequency of muscular eosinophilic infiltration in achalasia. Esophageal mucosal changes in achalasia have only been studied in esophagectomy specimens. Cardia mucosal changes in achalasia have not been reported previously. We aimed to further characterize the esophageal, gastric cardia, and muscularis propria changes in achalasia.
METHODS
This was a pilot study. Patients with clinically and radiographically confirmed achalasia who underwent POEM were enrolled in the study. Mucosal biopsies were taken 1 cm proximal and 1 cm distal to the gastroesophageal junction, and muscularis propria biopsies were taken from the mid esophagus. Tissues were submitted for histological evaluation.
RESULTS
Eighteen patients (10 male and eight female, mean age: 60.7 (standard deviation (SD): 13) years) were enrolled in this pilot study. Nine patients had type II achalasia, two type III, one type I, five esophageal gastric outlet obstruction, and one unspecific type achalasia. The mean duration of symptoms prior to POEM was 79 (range 1 - 480) months. All patients had a dilated esophagus on examination, but no endoscopic evidence of Barrett's esophagus. Esophageal, gastric cardia, and muscular biopsies were performed in 17, 13, and 17 patients, respectively. Basal hyperplasia, spongiosis, ballooning, and parakeratosis were seen in 92.3%, 100%, 100%, and 76.5% of cases, respectively. Intraepithelial lymphocytosis was seen in 70.5% of cases, and active esophagitis was seen in 23.5% of case. Six (35.3%) cases had few intraepithelial eosinophils, but none of them had > 15 eosinophils per high power field. Histologic findings in gastric cardia mucosa included carditis (69.2%), gastritis (7.6%), and reactive gastropathy (15.4%). One case (7.6%) showed low-grade dysplasia arising from intestinal metaplasia in the cardia. Absence of ganglion cells in the muscular biopsies was noted in 88.2% of cases, and the remaining two showed rare residual ganglion cells with ganglionitis in one case (5.8%). Muscular atrophy and interstitial fibrosis were observed in 52.9% and 82.3% of the cases, respectively. Two cases (11.7%) had eosinophilic inflammation in the muscularis propria and one of them was accompanied by lymphocytic inflammation.
CONCLUSIONS
Muscular biopsies in our study revealed loss of ganglion cells, supporting the view that achalasia is a primary esophageal disease with ganglion cell depletion. Squamous mucosa in achalasia showed changes mimicking reflux and lymphocytic esophagitis. Cardia mucosa in achalasia patients often were inflamed and uncommonly showed intestinal metaplasia and glandular dysplasia.
PubMed: 34804272
DOI: 10.14740/gr1454 -
The British Journal of Dermatology Apr 2022For patients with early American Joint Committee on Cancer (AJCC)-stage melanoma the combined loss of the autophagy regulatory protein AMBRA1 and the terminal...
BACKGROUND
For patients with early American Joint Committee on Cancer (AJCC)-stage melanoma the combined loss of the autophagy regulatory protein AMBRA1 and the terminal differentiation marker loricrin in the peritumoral epidermis is associated with a significantly increased risk of metastasis.
OBJECTIVES
The aim of the present study was to evaluate the potential contribution of melanoma paracrine transforming growth factor (TGF)-β signalling to the loss of AMBRA1 in the epidermis overlying the primary tumour and disruption of epidermal integrity.
METHODS
Immunohistochemistry was used to analyse AMBRA1 and TGF-β2 in a cohort of 109 AJCC all-stage melanomas, and TGF-β2 and claudin-1 in a cohort of 30 or 42 AJCC stage I melanomas, respectively, with known AMBRA1 and loricrin (AMLo) expression. Evidence of pre-ulceration was analysed in a cohort of 42 melanomas, with TGF-β2 signalling evaluated in primary keratinocytes.
RESULTS
Increased tumoral TGF-β2 was significantly associated with loss of peritumoral AMBRA1 (P < 0·05), ulceration (P < 0·001), AMLo high-risk status (P < 0·05) and metastasis (P < 0·01). TGF-β2 treatment of keratinocytes resulted in downregulation of AMBRA1, loricrin and claudin-1, while knockdown of AMBRA1 was associated with decreased expression of claudin-1 and increased proliferation of keratinocytes (P < 0·05). Importantly, we show loss of AMBRA1 in the peritumoral epidermis was associated with decreased claudin-1 expression (P < 0·05), parakeratosis (P < 0·01) and cleft formation in the dermoepidermal junction (P < 0·05).
CONCLUSIONS
Collectively, these data suggest a paracrine mechanism whereby TGF-β2 causes loss of AMBRA1 overlying high-risk AJCC early-stage melanomas and reduced epidermal integrity, thereby facilitating erosion of the epidermis and tumour ulceration.
Topics: Adaptor Proteins, Signal Transducing; Epidermis; Humans; Melanoma; Skin Neoplasms; Transforming Growth Factor beta; Transforming Growth Factor beta2; Transforming Growth Factors
PubMed: 34773645
DOI: 10.1111/bjd.20889 -
Cancers Nov 2021Background-Actinic keratoses (AKs) are the most common sun-induced precancerous lesions that can progress to squamocellular carcinoma (SCC). Recently, the...
Background-Actinic keratoses (AKs) are the most common sun-induced precancerous lesions that can progress to squamocellular carcinoma (SCC). Recently, the grade-independent association between AKs and SCC has been suggested; however, the molecular bases of this potential association have not been investigated. This study has assessed the metabolomic fingerprint of AK I, AK II, AK III and SCC using high resolution magic angle spinning (HR-MAS) nuclear magnetic resonance (NMR) spectroscopy in order to evaluate the hypothesis of grade-independent association between AK and SCC. Association between AKs and SCCs has also been evaluated by histopathology. Methods-Metabolomic data were obtained through HR-MAS NMR spectroscopy. The whole spectral profiles were analyzed through multivariate statistical analysis using MetaboAnalyst 5.0. Histologic examination was performed on sections stained with hematoxylin and eosin; statistical analysis was performed using STATA software version 14. Results-A group of 35 patients affected by AKs and/or SCCs and 10 healthy controls were enrolled for metabolomics analysis. Histopathological analysis was conducted on 170 specimens of SCCs and AKs (including the ones that underwent metabolomic analysis). SCCs and AK I were found to be significantly associated in terms of the content of some metabolites. Moreover, in the logistic regression model, the presence of parakeratosis in AKs appeared to be less frequently associated with SCCs, while AKs with hypertrophy had a two-fold higher risk of being associated with SCC. Conclusions-Our findings, derived from metabolomics and histopathological data, support the notion that AK I are different from healthy skin and share some different features with SCCs. This may further support the expanding notion that all AKs should be treated independently from their clinical appearance or histological grade because they may be associated with SCC.
PubMed: 34771721
DOI: 10.3390/cancers13215560 -
Archive of Clinical Cases 2019Psoriasiform dermatoses represent a wide spectrum of inflammatory conditions, with several major forms represented by psoriasis, as the prototype of this category,... (Review)
Review
Psoriasiform dermatoses represent a wide spectrum of inflammatory conditions, with several major forms represented by psoriasis, as the prototype of this category, followed by pustular psoriasis, Reiter's syndrome, pityriasis rubra pilaris, lichen simplex chronicus and large-plaques parapsoriasis. They create a diagnostic challenge, both clinical and histopathological, because of their complexity and frequent overlapping of the microscopical features. The characteristic histopathological features of psoriasiform reaction comprise extensive hyperkeratosis, with horizontally confluent but vertically intermittent parakeratosis, which alternate with orthokeratosis, thin granular layer, with relative frequent mitoses, uniform elongated and fused rete ridges, edematous superficial papillary dermis, with dilated capillaries, perivascular lymphocytic infiltrate, Munro's microabscesses, and spongiform pustules of Kogoj. Our paper aims to review the histopathology of major form of psoriasiform dermatoses and to emphasize the characteristic microscopical differences between them, for a better approach of the diagnosis as an important key for clinical and therapeutical management. Using the clinicopathological correlations, a thoroughly evaluation of the microscopical features and compartments distribution or special stainings and techniques, the range of differential diagnosis can be decreased and a more accurate diagnostic can be usually achieved. The insights into the pathogenic mechanisms can lead to new therapeutic opportunities targeted to the specific type of inflammatory lesion.
PubMed: 34754910
DOI: 10.22551/2019.24.0603.10155 -
Clinical and Experimental Dermatology Mar 2022With the expansion of the COVID-19 vaccination drive, an increasing number of adverse effects are surfacing. A 74-year-old woman presented with multiple erythematous and...
With the expansion of the COVID-19 vaccination drive, an increasing number of adverse effects are surfacing. A 74-year-old woman presented with multiple erythematous and itchy patches on several sites. She had no relevant medical history, apart from the first AZD1222 vaccination 1 month previously. Microscopically, epidermal changes, including mild spongiosis and parakeratosis, were observed. Tight perivascular lymphocytic infiltration (coat-sleeve pattern) was also observed in the dermis. The final diagnosis was erythema annulare centrifugum (EAC) induced by SARS-CoV-2 vaccination. Based on this report, dermatologists should be aware of the possibility of EAC from the AZD1222 vaccination.
Topics: Aged; COVID-19 Vaccines; Erythema; Female; Humans; Skin Diseases, Genetic
PubMed: 34731529
DOI: 10.1111/ced.15002 -
Romanian Journal of Morphology and... 2021Turner syndrome (TS) is characterized by partial or complete loss of a sexual chromosome, resulting in an incomplete development of the body, gonadic failure, cardiac...
Turner syndrome (TS) is characterized by partial or complete loss of a sexual chromosome, resulting in an incomplete development of the body, gonadic failure, cardiac and renal abnormalities, oro-dental changes, etc. In our study, we proposed to perform a histological and immunohistochemical (IHC) study of the periodontium changes in patients with TS. The biological material under study was represented by fragments of gingival mucosa harvested from 18 patients with TS who presented advanced periodontal lesions and required dental extractions. The fragments of gingival mucosa were processed by the classical histological technique of paraffin inclusion, subsequently the obtained sections being stained by the Hematoxylin-Eosin (HE) and examined under the optical microscope. For the IHC study, there were performed serial sections incubated with anti-cluster of differentiation (CD) 3, anti-CD20 and anti-CD68 antibodies for highlighting immune cells, as well as with anti-matrix metalloproteinase (MMP) 2 and anti-MMP8 antibodies for highlighting MMPs (MMP2 and MMP8) involved in the periodontal tissue lesions. In the present study, during the histological examination, there were observed morphological changes, both in the epithelium and in the gingival mucosa chorion. Epithelial changes consisted in the onset of acanthosis processes, in the thickening of the epithelium due to the increase of the spinous layer, as well as in the parakeratosis phenomenon. In the chorion, there was observed the presence of inflammatory infiltrates in various stages, presence of fibrosis (extended in some cases) and the presence of an important vascularization in some cases, with a high number of immunocompetent cells involved in the inborn immune response, but also in the adaptive one, as well as a more or less intense immunoexpression of MMP2 and MMP8. Our study suggests that TS may contribute to the development of some inflammatory processes in the marginal periodontium.
Topics: Epithelium; Gingiva; Humans; Matrix Metalloproteinase 2; Periodontal Ligament; Periodontium; Turner Syndrome
PubMed: 34609427
DOI: 10.47162/RJME.62.1.24 -
American Journal of Clinical and... 2021Leishmaniasis is one of the most important infectious illnesses around the world. Given the high commonness of this disease, specifically its skin type in Iran and due...
BACKGROUND
Leishmaniasis is one of the most important infectious illnesses around the world. Given the high commonness of this disease, specifically its skin type in Iran and due to the role of the Leishman bodies in diagnosis, the aim of present study was evaluating the expression of two CD1a and CD68 markers in cutaneous leishmaniasis lesions with and without Leishman bodies.
METHODS
In this case-control study, 70 skin samples of patients with cutaneous leishmaniasis (35 patients with Leishman body as case group and 35 patients without Leishman boy as control group) were investigated during 2018-2019. The expression of CD1a and CD68 markers and immunohistochemistry staining (IHC) were investigated in this study.
RESULTS
The expression of CD1a in the group with Leishman body was significantly higher than group without Leishman body (P=0.01), but there was no significant difference between groups as expression of CD68 (P=0.40). The frequency of hyperkeratosis, parakeratosis, exocytosis, acanthosis, spongiosis, hydropic degeneration of basal cell layer, lichenoid reaction, pseudoepitheliomatous hyperplasia, ulcer, thinning of the epidermis, mononuclear cells, and extension of inflammation into lower dermis in the group with Leishman body was higher than group without Leishman body (P<0.05).
CONCLUSION
The expression of CD1a and other morphological findings help to diagnose the difference between leishmaniasis with and without Leishman body.
PubMed: 34584778
DOI: No ID Found -
Turkish Journal of Ophthalmology Aug 2021A 29-year-old woman presented with dark-colored raised lesions on both eyelids since early childhood. Ophthalmological examination revealed pigmented verrucous lesions...
A 29-year-old woman presented with dark-colored raised lesions on both eyelids since early childhood. Ophthalmological examination revealed pigmented verrucous lesions on her upper and lower eyelids bilaterally. The patient had a history of generalized tonic-clonic seizures. Dermatological examination revealed hyperpigmented verrucous plaques arranged along lines of Blaschko on the neck, trunk, and arms. On the basis of these findings, the diagnosis of epidermal nevus syndrome (ENS) was made. She had surgery for debulking of the lesions. Histological analysis revealed hyperkeratosis with foci of parakeratosis, acanthosis, and papillomatosis, consistent with linear verrucous epidermal nevus. Postoperative residual lesions did not respond to oral acitretin therapy (10 mg/kg/day for 2 months). Systematized ENS can rarely cause linear verrucous nevi on the upper and lower eyelids on both sides. These patients should be investigated for accompanying systemic anomalies and followed for potential malignant transformation of the skin lesions.
Topics: Adult; Child, Preschool; Eyelids; Female; Humans; Nevus; Nevus, Sebaceous of Jadassohn; Skin Neoplasms
PubMed: 34461711
DOI: 10.4274/tjo.galenos.2021.72662