Invasion Of Skin Research Articles

Invasive Micropapillary Carcinoma of the Breast: Comparison of Clinical, Epidemiological, Anatomopathological and Therapeutic Features with Infiltrating Carcinoma of Non-Specific Type

Invasive micropapillary carcinoma (IMCC) is a rare histological subtype of invasive breast cancer, its frequency ranges from 1.0 to 8.4% of all breast cancer cases. It is identified as a particularly aggressive tumor since frequent invasion of vessels, skin and lymph nodes is often reported. The aim of the work is to describe and compare the epidemiological, clinical, anatomopathological and molecular aspects of CMPI compared to CINS. Compare the overall survival of the two groups in order to identify the prognostic factors for CMPI. This is a retrospective, descriptive and analytical study spread over 6 years from January 2015 to December 2020, involving all cases of CMPI and CINS of the breast collected at the Obstetrics and Gynecology department of the Maternity and Neonatology Center of Monastir. The frequency found was 5.5% for CMPI and 72.69% for CINS. In our series we found the average age to be more advanced in CINS compared to CMPI without having a statistically significant difference (p=0.49). CMPI tends to be slightly larger than CINS with an average size of 3.7 compared to 3 for CINS. The right breast was the predominant tumor site for the 2 types of cancer p=0.71. CMPI presents a higher frequency of locoregional ADP and vascular emboli with p=0.001. Distant metastases were more frequent in CINS but without having a statistically significant difference. The overall survival of CMPI is 76% versus 86.4%. % of CINS. CMPI represents a particular variety of breast carcinomas; in this study we tried to dissect its different epidemiological, clinical, radiological and therapeutic characteristics which were largely in agreement with the literature.

The Oxylipin Dependent Quorum Sensing System enhances Pseudomonas aeruginosa dissemination during burn-associated infection.

Following severe burn injury, Pseudomonas aeruginosa is the leading cause of life-threatening infection. Herein, we unveil how P. aeruginosa strategically employs host-derived oleic acid, released as consequence of burn-injury, to induce a hypervirulent phenotype via its Oxylipin Dependent Quorum Sensing system (ODS). ODS activation enhanced P. aeruginosa invasion of burned skin and promoted its dissemination to distant organs in vivo . ODS regulation of P. aeruginosa virulence involved the control of nitic oxide levels, a key signaling molecule in bacteria, through upregulation of the nitric oxide reductases NorCB. Immunization with OdsA, one of the enzymes involved in oxylipin generation, or treatment with a pharmacological inhibitor of OdsA, protected mice against lethal P. aeruginosa infection following burn-injury. Our findings reveal a new mechanism underlying P. aeruginosa hypervirulence in burn wounds and identifies OdsA as a promising target for preventing disseminated infections following burns.

Bacterial isolates and their antimicrobial susceptibility profile of superficial and deep-seated skin and soft tissue infections.

Skin and soft tissue infections (SSTIs) are caused by microbial invasion of healthy or damaged skin. SSTIs are difficult to manage and contribute to chronicity and emergence of antimicrobial resistance. To ascertain the prevalence of bacteria causing SSTIs and their antimicrobial susceptibility patterns. A prospective study between November 2020 and May 2021. A total of 447 samples from SSTIs were analyzed. A total of 347 samples revealed mono-bacterial growth, of which 67% were male. SSTIs are common among patients aged 21-50 years with the dominance (78%) of gram-negative rods (GNRs). Escherichia coli (36%), Klebsiella spp. (22%), Staphylococcus aureus (16%), and Pseudomonas aeruginosa (11%) were predominant organisms. GNRs were highly resistant (>65%) to ciprofloxacin and trimethoprim-sulfamethoxazole. For injectable antibiotics, the highest resistance was determined against ceftriaxone, and the least resistance was determined against amikacin. Resistance against carbapenem was the highest among P. aeruginosa (53%) and Klebsiella spp. (32%). S. aureus showed the highest resistance against ciprofloxacin, and the least resistance was determined against clindamycin. Of 57 S. aureus isolates, 86% isolates were methicillin-resistant Staphylococcus aureus (MRSA). All isolates of P. aeruginosa and S. aureus were sensitive to polymyxin B and vancomycin, respectively. The prevalence of multidrug-resistant E. coli and Klebsiella spp. was higher among deep-seated SSTIs (dSSTIs). The predominant etiology of SSTIs is GNR. Currently, there is very high resistance against oral antibiotics. Antimicrobial resistance against carbapenem has also increased. Moreover, there is a high frequency of MRSA. MDR E. coli and Klebsiella spp. isolates are frequently involved in dSSTIs.

A review of 14 cases of perianal Paget’s disease: characteristics of anorectal cancer with pagetoid spread

BackgroundPerianal Paget’s disease (PPD) is an intraepithelial invasion of the perianal skin and is frequently associated with underlying anorectal carcinoma. The relatively rare nature of this disease has made it difficult to develop treatment recommendations. This study aims to analyze the clinical and pathological features of perianal Paget’s disease (PPD) and to explore rational treatment options and follow-up for this disease.MethodsThe National Cancer Center Hospital database was searched for all cases of perianal Paget’s disease diagnosed between 2006 and 2021. In the 14 patients identified, we reviewed the diagnosis, management, and outcomes of adenocarcinoma with pagetoid spread, including suspected or recurrent cases.ResultsAll 14 cases met the inclusion criteria. The median follow-up period after diagnosis was 4.5 (range, 0.1–13.0) years. Pagetoid spread before initial treatment was suspected in 12 cases (85.7%). Underlying rectal cancer was identified in 6 cases, and no primary tumor was detected in the other 6 cases. Seven patients had recurrent disease, with the median time to recurrence of 34.6 (range, 19.2–81.7) months. The time to the first relapse was 3 months, and that to the second relapse was 6 months. The overall 5-year survival rate was 90.0%.ConclusionsEndoscopic and radiologic evaluation, as well as immunohistologic examination, should be performed. is to differentiate PPD with and without underlying anorectal carcinoma. The time to first recurrence varies widely, and long-term and regular follow-up for more than 5 years is considered necessary for local recurrence and distant metastasis.

S2.4a Pythiosis: An emerging disease in Hong Kong

S2.4 Veterinary mycology research, September 21, 2022, 3:00 PM - 4:30 PMOomycosis is an emerging disease of humans and animals caused by oomycetes in the Stramenopiles-Alveolata-Rhizaria super group, mainly Pythium insidiosum and occasionally Lagenidium giganteum or Paralagenidum species. In surface freshwater, oomycetes produce motile biflagellate asexual zoospores with marked chemotactic attraction to epithelial surfaces of vertebrate hosts. Infection is the result of encystation and invasion of damaged skin or gastrointestinal mucosa.Of ∼ 4200 cases of pythiosis reported globally between 1980 and 2021 only ∼ 20% involved humans while 80% involved animals, mainly horses, dogs, and cattle. Most human cases occur in India and Thailand, whereas most animal infections were reported in the United States and Brazil. Pythiosis has been reported in mainland China, but the burden of the disease is low and comprises <1% of overall cases in humans.Neither pythiosis nor lagenidiosis has been previously reported in humans or animals in Hong Kong. From January 2018 to January 2022, the Veterinary Diagnostic Laboratory of City University of Hong Kong diagnosed 10 cases of oomycosis (5 canine, 5 feline) after identification of non-parallel walled, irregularly branching, and poorly septate hyphae in the center of necrotic regions of histological sections of formalin-fixed paraffin-embedded tissues (FFPET). Species identity was confirmed by PCR and sequencing of 28S rDNA from DNA extracts of FFPET. There were 8 cases of P. insidiosum and 2 of L. giganteum infection. Serum ELISA was positive for Pythium antibodies in 5/6 cases tested and negative for Pythium/Lagenidium/Paralagenidum antibodies in a German shepherd dog (GSD) with disseminated disease caused by L. giganteum.Affected dogs were young to middle-aged at presentation (9 months to 5 years old). Two dogs had focal cutaneous infections, two had extensive gastrointestinal involvement, and the GSD had disseminated disease with cutaneous, mediastinal, and abdominal involvement.Affected cats were young (8 weeks to 18 months) and presented with subcutaneous/cutaneous disease. Three cats had a distinctive perianal ring of bulging subcutaneous granulation tissue, including one that also had an ulcerated, proliferative and necrotic lesion involving two adjacent hind-limb digits. One cat had facial subcutaneous swelling with mandibular lymph node enlargement and the remaining cat presented with extensive circumferential swelling of one hind limb from the distal paw to the mid-stifle.All cats tested negative for the Feline leukemia virus and Feline immunodeficiency virus. Traumatic or surgical wounds preceding infection were identified in a kitten caught in a rodent glue-trap with skin wounds, in a cat with facial involvement that had an injured globe surgically enucleated, and in a dog with cutaneous pythiosis that had chronic dermatitis.Treatment data were available for one canine case. The GSD with lagenidiosis was treated with combination antimicrobial therapy including voriconazole, terbinafine, minocycline, and azithromycin. The dog responded poorly. Mefenoxam was substituted for voriconazole and hyperbaric oxygen therapy was administered. After initial response, the dog succumbed 4 months from diagnosis. We have had success with the treatment of four feline cases using combination therapy including surgical debridement, immunotherapy with a Pythium vaccine, and combinations of antifungal drugs (posaconazole and terbinafine), and/or antimicrobials (doxycycline/minocycline and azithromycin).

Bacteriologic Profile Along With Antimicrobial Susceptibility Pattern of Pediatric Pyoderma in Eastern India.

BackgroundPyogenic skin infection (pyoderma) is a bacterial infection of the skin and its appendages. Primary pyoderma is caused by the direct invasion of healthy skin, whereas secondary pyoderma originates in diseased skin as superimposed conditions, such as scabies, pediculosis, wounds, insect bites, and eczema. This study aimed to identify the clinical patterns and risk factors of pyoderma in a pediatric population and to isolate various causative bacteria and determine their susceptibility patterns.MethodologyA prospective study was performed at the Medical College and Hospital, Kolkata, India, for one year (from August 2016 to July 2017), which included all children younger than 12 years with pyoderma attending the outpatient dermatology department (as the study was conducted among the pediatric population, only children below 12 years of age were included). Sterile cotton swabs were used to aseptically collect exudates or pus from lesions and anterior nares, which were used for culture, identification, and antibiotic susceptibility testing of the causative organisms.ResultsDuring the study period, a total of 182 patients were included, 121 (66.48%) of whom had primary pyoderma and 61 (33.52%) of whom had secondary pyoderma. Of the 182 patients, 161 showed bacterial growth on culture: 126 (78.26%) were Staphylococcus aureus, 18 (11.18%) were coagulase-negative staphylococci, 16 (9.94%) were Streptococcus pyogenes, and 1 (0.62%) was Pseudomonas aeruginosa. All staphylococci were susceptible to vancomycin and linezolid.ConclusionsThe most common cause of pyoderma in the pediatric age group is S. aureus, although the prevalence of methicillin-resistant S. aureus was low in this hospital. Proper identification and antibiogram are required for managing these cases.

The clinical features and long-term surgical outcomes of different types of abdominal wall endometriosis.

To classify abdominal wall endometriosis (AWE) according to the invasive levels of tissue mass, and to compare the differences in clinical characteristics between different types of AWE. In this study, we retrospectively analyzed the clinical data of 367 patients who had undergone resection of abdominal-wall endometriotic lesions at the Peking Union Medical College Hospital from January 2008 to December 2018, and we divided the patients into three types according to their deepest level of lesion invasion. Type I designated invasion of skin and subcutaneous tissue; type II, of fascia and rectus abdominis; and type III, of peritoneum. We classified, compared, and analyzed the general conditions, clinical manifestations, auxiliary examinations, surgical conditions, postoperative conditions, and recurrence status of patients. Of the 367 patients, type I patients accounted for 13.62%, type II patients for 56.68%, and type III for 29.7%. With respect to group comparisons, we observed that as the location of the mass deepened, the rate of concurrent pelvic endometriosis increased (P = 0.007), recurrent AWE was augmented (P = 0.02), the size of the mass increased (P < 0.001), the rate of multiple lesions became elevated (P < 0.001), the rate of mesh implantation increased (P < 0.001), the length of postoperative hospital stay (P < 0.001) was lengthened, the number of postoperative fever cases (P = 0.006) increased, and the risk of drainage placement (P < 0.001) was enhanced. The 5-year cumulative recurrence rate was 3.3%, and there was no significant difference in the recurrence rate among various types of AWE. Type III AWE carries more severe clinical manifestations, larger lesion size, longer operative time, greater intraoperative surgical difficulty, higher necessity of mesh implantation, and longer postoperative recovery process. Complete resection of AWE lesion is the main therapeutically approach and shows relatively low long-term recurrency rate.

Tea Tree Oil and Terpinen-4-Ol Induce Cytoskeletal Reorganization of Human Melanoma Cells

AbstractTea tree oil is an essential oil distilled from the leaves of Melaleuca alternifolia, a plant native to Australia. It has been used in traditional medicine for its antiseptic and anti-inflammatory properties to treat various skin conditions and infections. It has also been incorporated into many topical formulations to treat cutaneous infections and speed wound healing. In vivo and in vitro studies report antiproliferative effects in skin disorders but the molecular mechanisms underlying this effect remain to be still elucidated. In this study MTT assay, scanning electron microscopy-field emission gun, flow cytometry, cell cycle assays, and laser scanning confocal microscopy were utilized to investigate a novel mechanism underlying the antiproliferative effects of tea tree oil and terpinen-4-ol on transformed skin (melanoma) M14 cells. The analysis of the actin cytoskeleton by laser scanning confocal microscopy evidenced a clear action of both essential oil and its main active component on F-actin, which interfered with bundling of actin microfilaments in stress fibers. As for the microtubular network, both tea tree oil and terpinen-4-ol induced a disorganization of the perinuclear cage with the rupture and collapse of microtubules. Finally, they noticeably changed the intermediate filaments architecture by inducing the formation of large vimentin cables. Results obtained in the present study point to the cytoskeleton as a further target of tea tree oil and terpinen-4-ol and could account for the inhibition of proliferation and invasion of skin transformed M14 cells. In our experimental conditions, vimentin intermediate filaments appear to be the cytoskeletal element more affected by the treatments. Moreover, the role of cross-linker proteins in the mechanism of action of tea tree oil has been discussed.

Multifunctional Synthetic Amphiphile for Niche Therapeutic Applications: Mitigation of MRSA Biofilms and Potential in Wound Healing.

The relentless menace of implant- and skin wound-associated infections caused by methicillin-resistant Staphylococcus aureus (MRSA) biofilms demands the design of therapeutics that have an edge over conventional antibiotics. The present study reports the potential of pluri-active amphiphiles having a 12-carbon alkyl chain and a salicaldehyde head group (C1) or a napthaldehyde head group (C2) in mitigating wound site- and implant-associated MRSA biofilms and as a topical wound healing agent. The amphiphiles impeded S. aureus MRSA 100 biofilm formation on collagen both on extraneous addition and on impregnation into collagen and inflicted damage to MRSA cells embedded in collagen matrix infused with simulated wound fluid, with C1 being more potent than C2. Adhesion of the MRSA biofilm was hampered on C1-coated orthopedic stainless-steel wire, while eluates from C1-coated wires were non-toxic to HEK 293 cells, highlighting the prospect of C1 as an implant-associated antibacterial coating. Upon treatment with C1, expression of the adhesin fnbA gene was low in the MRSA biofilm and downregulated in non-adherent MRSA cells, while δ-toxin (hld) gene expression in the MRSA biofilm increased, implying that C1 hindered cell-cell adhesion and planktonic-biofilm transition and also reduced biofilm adhesion. Oral administration of C1 (300 and 1000 mg/kg) was non-toxic to BALB/c mice as evidenced in stable hematological parameters and normal histopathological features of vital organs. Topical application of C1 (50 and 100 mg/kg) on a skin excision wound in female BALB/c mice resulted in effective wound closure, fibrous tissue proliferation, and tissue reorganization. Confocal microscopy revealed that topical application of C1 in an ex vivo murine skin explant could alleviate invasion of skin by MRSA, while solution-based studies indicated subdued MRSA adhesion onto the skin explants. The pluri-active synthetic amphiphile C1 provides a framework for developing antibacterials that hold translational potential as a therapeutic for implant- and skin wound-associated MRSA infections.

Schistosoma japonicum cathepsin B2 (SjCB2) facilitates parasite invasion through the skin.

Cercariae invasion of the human skin is the first step in schistosome infection. Proteases play key roles in this process. However, little is known about the related hydrolytic enzymes in Schistosoma japonicum. Here, we investigated the biochemical features, tissue distribution and biological roles of a cathepsin B cysteine protease, SjCB2, in the invasion process of S. japonicum cercariae. Enzyme activity analysis revealed that recombinant SjCB2 is a typical cysteine protease with optimum temperature and pH for activity at 37°C and 4.0, respectively, and can be totally inhibited by the cysteine protease inhibitor E-64. Immunoblotting showed that both the zymogen (50 kDa) and mature enzyme (30.5 kDa) forms of SjCB2 are expressed in the cercariae. It was observed that SjCB2 localized predominantly in the acetabular glands and their ducts of cercariae, suggesting that the protease could be released during the invasion process. The protease degraded collagen, elastin, keratin, fibronectin, immunoglobulin (A, G and M) and complement C3, protein components of the dermis and immune system. In addition, proteomic analysis demonstrated that SjCB2 can degrade the human epidermis. Furthermore, it was showed that anti-rSjCB2 IgG significantly reduced (22.94%) the ability of the cercariae to invade the skin. The cysteine protease, SjCB2, located in the acetabular glands and their ducts of S. japonicum cercariae. We propose that SjCB2 facilitates skin invasion by degrading the major proteins of the epidermis and dermis. However, this cysteine protease may play additional roles in host-parasite interaction by degrading immunoglobins and complement protein.

Genetics and epigenetics of melanoma.

[This retracts the article DOI: 10.3892/ol.2016.5093.].

Effectiveness of the immidacloprid/ivermectin combination for external application (“MEGA STOP” for cats)

Diseases of the skin, inflammation, complications of suppurative processes can be caused by invasion of akariformes and lead to the deterioration of animal health, slimming and intoxication. The aim of this work was to investigate the efficacy of the drug “MEGA STOP” by analyzing the clinical status of the animals and the dynamics of hematological parameters. It was used 15 animals aged from 8 months to 5 years, of both sexes. Examined the General condition of the animals (behavior, reaction to external stimuli, presence of appetite, skin and coat, the color of the mucous membranes and the like). It was performed microscopic examination of scrapings from the affected skin and ears, as well as clinical analysis of blood. The drugs were applied according to the instructions and the invasion of intact skin. In all animals with a flea in a single treatment was effective. The blood counts were normal (the upper and lower lime), except for erythrocytes (below normal from 4.72 % to 2.26 %). It was established, that all animals treated with the drug MEGA STOP at 0 day was deviation in the norm of the indicator red blood cells to decrease from 0.4 of 7.36 %. In the following days of the study (10 and 20 day), indicators are normalized and the condition of the animals improved. The maximum deviation of the blood parameters from the norm were detected in an animal with double invasion (otodectosis and fleas). The study of the animals before treatment were violations of the skin in the affected areas of agents, anemia, leukocytosis and eosinophilia. These changes of the blood, characteristic of allergic and intoxication metabolites acariformes. After the first treatment the condition of the ears and skin, according to the results of clinical examination and microscopy, have improved as the blood counts. After the second treatment the animals of both groups a swab from the ears clean and no clinical manifestations. The high efficacy of the drug “MEGA STOP” for the prevention and treatment of flea infestations and acarosan (notoedres, otodectosis in, demodicosis) in single/double skin applied depending on the degree of infestation.

Knockdown of fibronectin extra domain B suppresses TGF-β1-mediated cell proliferation and collagen deposition in keloid fibroblasts via AKT/ERK signaling pathway

Keloids represent a dermal fibrotic disease characterized by excess collagen deposition and invasion of normal skin beyond the wound boundary, similar to malignant tumor features. Fibronectin extra domain B (EDB) is highly expressed in many tumors but has not been studied in keloids. The present study aimed to investigate the expression and the influence of EDB on keloid and elucidate the putative signaling pathway. We examined expression of EDB and the effects of EDB on fibroblast proliferation, apoptosis and the expression of the related proteins and genes. The level of phosphorylation of Smad, ERK, and AKT was estimated to elucidate the signaling pathways. The results showed that EDB in human keloid tissues and fibroblasts was overexpressed. EDB knockdown suppressed the cell proliferation of keloid fibroblasts (KFs) treated by transforming growth factor-β1 (TGF-β1). Also, the phosphorylation of Smad, ERK, and AKT in TGF-β1-induced KFs was inhibited In addition, the low expression of pro-collagen-I (Col-I) and Col-III protein and mRNA level was observed in the siEDB group. EDB knockdown inhibited cell proliferation and suppressed collagen deposition in TGF-1-induced KFs. The underlying mechanism is the activation of TGF-β1/Smad, ERK, and AKT signaling pathways. Together, the results suggested that EDB is a promising therapeutic target for keloid clinical treatment.

Mode of presentation and skin thickening on ultrasound may predict nodal burden in breast cancer patients with a positive axillary core biopsy

A number of pre-operative factors predicting nodal burden in females with breast cancer have recently been identified. The aim of this study is to assess if these factors independently influence nodal burden in females with a positive axillary core biopsy. All node positive patients detected on axillary core biopsy were identified in our cancer audit database. Mode of presentation, age, core tumour grade, core tumour type, ER and HER2 status were evaluated. Tumours were assessed for ultrasound size, distance of tumour-to-skin, presence of invasion of skin and diffuse skin thickening. Axillary lymph nodes were assessed for cortical thickness and presence of ultrasound replaced nodes. Statistical significance was ascertained using univariate logistic regression. A predictive model was produced following a multiple logistic regression model incorporating cross-validation and assessed using receiving operating characteristic curve. 115 patients' data were analysed. Patients referred because of symptoms (70% vs 38%, p = 0.005), and those with ultrasound skin thickening (87% vs 59%, p = 0.055) have higher nodal burden than those referred from screening or without skin thickening. These factors were significant after multivariate analysis. The final predictive model included mode of presentation, ultrasound tumour size, cortical thickness and presence of ultrasound skin thickening. The area under curve is 0.77. We have shown that mode of presentation and ultrasound skin thickening are independent predictors of high nodal burden at surgery. A model has been developed to predict nodal burden pre-operatively, which may lead to avoidance of axillary node clearance in patients with lower nodal burden. Method of presentation and skin involvement/proximity to skin by the primary tumour are known to influence outcome and nodal involvement respectively but have not been studied with regard to nodal burden. We have shown that mode of presentation and skin thickening at ultrasound are independent predictors of high nodal burden at surgery.

Reference genes for accurate evaluation of expression levels in Trichophyton interdigitale grown under different carbon sources, pH levels and phosphate levels

Tinea pedis is a type of dermatophytosis caused by anthropophilic keratinolytic fungi such as Trichophyton interdigitale. Quantitative reverse transcription PCR (RT-qPCR) is a reliable and reproducible technique for measuring changes in target gene expression across various biological conditions. A crucial aspect of accurate normalization is the choice of appropriate internal controls. To identify reference genes for accurate evaluation of expression levels in T. interdigitale, the transcription levels of eight candidate reference genes (adp-rf, β-act, ef1-α, gapdh, psm1, sdha, rpl2 and ubc) and one target gene (Tri m4) were analysed by RT-qPCR after growing the dermatophyte under different environmental conditions. The results obtained from expression stability evaluations with NormFinder, geNorm, BestKeeper, and RefFinder software demonstrated that adp-rf and psm1 were the most stable internal control genes across all experimental conditions. The present study constitutes the first report of the identification and validation of reference genes for RT-qPCR normalization for T. interdigitale grown under different environmental conditions resembling the conditions encountered by fungi during invasion of skin.

A pleiotropic effect of the APOE gene: association of APOE polymorphisms with multibacillary leprosy in Han Chinese from Southwest China

Summary This is a study by investigators from the Chinese Academy of Sciences and Dermatology departments based in Yunnan province in China. Basing their research on a previous observation that patients with leprosy have a lower frequency of dementia due to Alzheimer's Disease than patients without, they investigated whether there was any link between the occurrence of leprosy and the human genes involved in the formation and breakdown of different lipids or fats, processes that are key steps in the development of both Alzheimer's disease as well as the invasion of skin and nerves in leprosy. They searched for a link between a gene called Apolipoprotein E (APOE) which is known to be involved in Alzheimer's and found that certain mutations in the gene were more common in patients with leprosy. They suggested that this might lead to an increase in a lipid binding protein found in blood plasma and that this in turn would aid the survival of the bacteria that cause leprosy, Mycobacterium leprae, thus allowing it to spread and the disease to develop.

Genetics and epigenetics of melanoma.

Cancer affects multiple organs in the body Malignant melanoma involves the invasion of skin and occasionally mucosal membrane or eye choroidal tissues. The incidence of cutaneous malignant melanoma is on the increase worldwide and is a major concern in current research. The increase is associated with UV irradiation-induced genetic aberrations that stimulate skin melanocytes to develop unlimited growth. This eventually leads to cell immortality, which in turn causes metastases. The present review examines the genetics and epigenetics of this pathological state together with recent perspectives of the therapeutic management of disease.

Tumors Involving Skin, Soft Tissue and Skeletal Muscle: Benign, Primary Malignant or Metastatic?

Metastatic cancer with invasion of skin, soft tissue and skeletal muscle is not common. Examples presenting as soft tissue masses could sometimes lead to misdiagnosis with delayed or inappropriate management. The purpose of current study was to investigate clinical characteristics in the involvement of metastatic cancer. A total of 1,097 patients complaining of skin or soft tissue masses and/or lesions were retrospectively reviewed from January 2012 to June 2013. Tumors involving skin, soft tissue and skeletal muscle of head and neck, chest wall, abdominal wall, pelvic region, back, upper and lower extremities were included in the study. Fifty-seven (5.2%) patients were recognized as having malignancies on histopathological examination. The most common involvement of malignancy was basal cell carcinoma, followed by cutaneous squamous cell carcinoma, sarcoma and melanoma. The most common anatomical location in skin and soft tissue malignancies was head and neck (52.6% of the malignancies). Four (0.36%) of the malignant group were identified as metastatic cancer with the primary cancer source from lung, liver and tonsil and the most common site was upper extremities. One of them unexpectedly expired during the operation of metastatic tumor excision at the scalp. Discrimination between benign and malignant soft tissue tumors is crucial. Performance of imaging study could assist in the differential diagnosis and the pre-operative risk evaluation of metastatic tumors involving skin, soft tissue and skeletal muscle.

Entry Mechanisms of Herpes Simplex Virus 1 into Murine Epidermis: Involvement of Nectin-1 and Herpesvirus Entry Mediator as Cellular Receptors

Skin keratinocytes represent a primary entry site for herpes simplex virus 1 (HSV-1) in vivo. The cellular proteins nectin-1 and herpesvirus entry mediator (HVEM) act as efficient receptors for both serotypes of HSV and are sufficient for disease development mediated by HSV-2 in mice. How HSV-1 enters skin and whether both nectin-1 and HVEM are involved are not known. We addressed the impact of nectin-1 during entry of HSV-1 into murine epidermis and investigated the putative contribution of HVEM. Using ex vivo infection of murine epidermis, we showed that HSV-1 entered the basal keratinocytes of the epidermis very efficiently. In nectin-1-deficient epidermis, entry was strongly reduced. Almost no entry was observed, however, in nectin-1-deficient keratinocytes grown in culture. This observation correlated with the presence of HVEM on the keratinocyte surface in epidermis and with the lack of HVEM expression in nectin-1-deficient primary keratinocytes. Our results suggest that nectin-1 is the primary receptor in epidermis, while HVEM has a more limited role. For primary murine keratinocytes, on which nectin-1 acts as a single receptor, electron microscopy suggested that HSV-1 can enter both by direct fusion with the plasma membrane and via endocytic vesicles. Thus, we concluded that nectin-1 directs internalization into keratinocytes via alternative pathways. In summary, HSV-1 entry into epidermis was shown to strongly depend on the presence of nectin-1, but the restricted presence of HVEM can potentially replace nectin-1 as a receptor, illustrating the flexibility employed by HSV-1 to efficiently invade tissue in vivo. Herpes simplex virus (HSV) can cause a range of diseases in humans, from uncomplicated mucocutaneous lesions to life-threatening infections. The skin is one target tissue of HSV, and the question of how the virus overcomes the protective skin barrier and penetrates into the tissue to reach its receptors is still open. Previous studies analyzing entry into cells grown in vitro revealed nectin-1 and HVEM as HSV receptors. To explore the contributions of nectin-1 and HVEM to entry into a natural target tissue, we established an ex vivo infection model. Using nectin-1- or HVEM-deficient mice, we demonstrated the distinct involvement of nectin-1 and HVEM for HSV-1 entry into epidermis and characterized the internalization pathways. Such advances in understanding the involvement of receptors in tissue are essential preconditions for unraveling HSV invasion of skin, which in turn will allow the development of antiviral reagents.

Comparison of Malignant Skin Tumor Thickness and Relative Depth of Invasion Estimates from Preoperative MR-Microscopy and Pathological Evaluation

Tumor thickness and relative depth of invasion are prognostic parameters considered when developing treatment plans for malignant skin tumors. Although conventional magnetic resonance (MR) imaging techniques cannot identify small tumors, use of microscopy coils considerably improves spatial resolution. Some studies have shown that this technique is efficacious in preoperative assessment of relative depth of invasion; however, its ability to provide accurate measurements of tumor thickness remains unconfirmed. The purpose of this pilot study was to evaluate the usefulness of preoperative MR-microscopy in determining tumor thickness and relative depth of invasion of malignant skin tumors. Magnetic resonance images of malignant skin tumors in seven female patients (six with basal cell carcinoma and one with malignant melanoma) were obtained using a 1.5 T system and a 47-mm or 23-mm microscopy coil. Tumors were then excised, fixed, dehydrated, embedded, and stained with hematoxylin and eosin. We then compared MR-microscopy and pathology values for thickness and relative depth of invasion of each tumor. Both techniques produced similar measurements of tumor thickness and relative depth of invasion. MR-microscopy is very useful for accurate preoperative estimation of not only relative depth of invasion, but also thickness of malignant skin tumors.