Actinic Cheilitis - From Risk Factors to Therapy.

Actinic cheilitis or solar cheilosis is considered a precursor of malignancy or even an in situ squamous cell carcinoma (SCC) of the lip, located most frequently on the lower lip. Actinic cheilitis (AC) has a higher likelihood of developing into invasive SCC of the lip, which is one of the deadliest non-melanoma skin cancers. Risk factors include chronic UV exposure, increasing age, male gender, fair phototypes, chronic scarring, immunosuppressive therapy, and tobacco use. From a clinical point of view, AC is characterized by dryness, scaling, atrophy, indistinct borders, and erosions. Ulceration and the appearance of a nodule often suggest the progression to invasive SCC. Dermoscopic examination reveals white structureless areas, scales, erosions, and white halos of the vermilion. Reflectance confocal microscopy shows disruption of the stratum corneum, parakeratosis, an atypical honeycomb pattern, solar elastosis, and dilated and tortuous blood vessels with increased blood flow. The rate of malignant transformation ranges from 10 to 30% and early diagnoses and treatment are essential in preventing the development of invasive SCC. Optimal treatment has not been established yet, but invasive and topical treatments can be tried. The present paper aims to review the existing data regarding epidemiology, risk factors, clinical picture, non-invasive imaging, diagnosis, and therapy in AC.

Role of dynamic contrast enhanced magnetic resonance imaging in the diagnosis and management of vascular lesions of the head and neck.

Vascular anomalies comprise a wide and heterogeneous group of lesions that may be found in all parts of the body, with most of the cases of vascular malformations involving the head and neck region. Ultrasound (US) is the reliable first-line imaging technique to assess flow parameters. However, in some cases, US fails to depict the real extent of the lesions. On the other hand, magnetic resonance imaging (MRI) allows the evaluation of the full extension and anatomic relationship of the vascular anomalies with the neighboring structures and provides hemodynamic characterization using dynamic contrast enhanced MRI (DCE-MRI), avoiding unnecessary invasive catheter-based procedures. DCE-MRI angiography can make a distinction between low and high flow vascular anomalies and it is useful for selecting adequate therapy and appreciating prognosis. The aim of this paper is to review the role of DCE -MRI in the evaluation of flow characteristics and lesion extent in vascular anomalies of the head and neck region.

Complete regression of primary melanoma associated with nevi involution under BRAF inhibitors: A case report and review of the literature.

Melanoma is one of the most immunogenic tumors among human neoplasms, with numerous clinical observations of partial or completely regressed tumors. It is an aggressive tumor, with the greatest reported number of somatic mutations, BRAF mutation being the most common one. BRAF mutation is also present in a higher percentage in benign nevi. Complete regression of primary tumor and involution of nevi are, however, rare phenomenon in melanoma that can appear in relation with UV exposure, surgical trauma, target therapy in melanoma, pregnancy or host immune response to an evolving melanoma tumor. We present the case of a 58-year-old man with a completely regressed metastatic melanoma who developed a second melanoma with concomitant involution of papillomatous nevi under BRAF inhibitors treatment. In reviewed literature we have found 53 cases of completely regressed primary melanomas, neither of them reporting nevi involution. Complete regression of primary tumor can occur as an immune response to tumor progression. Nevi can involute under BRAF inhibitor therapy, but development of new malignant lesions under BRAF inhibitors is linked to BRAF wild-type. Documentation of primary tumor and dynamic changes in nevi highlight the need of a good clinical skin examination and increase the utility of baseline and sequential dermoscopy in melanoma.

Progesterone hypersensitivity: Case report with favorable evolution.

Progesterone hypersensitivity or autoimmune progesterone dermatitis is characterized by heterogeneous skin eruptions that cyclically aggravate during the second half of the menstrual cycle, corresponding to a rise in the progesterone level. Clinical presentation is highly variable and includes all urticaria manifestations with or without angioedema, vesiculobullous, eczematous, purpuric or target-like lesions on the skin and mucous membrane. Both endogenous progesterone as well as exogenous progestogens may represent an initial trigger. We report a case of progesterone hypersensitivity in a 27-year old woman with favorable evolution only on topical therapy, the positive clinical outcome being maintained during a subsequent pregnancy and postpartum period.

Sexual Behaviors, Attitudes, and Knowledge about Sexually Transmitted Infections: A Cross-sectional Study in Romania.

Sexually transmitted infections (STIs) are serious public health problems. Little is known about sex knowledge, attitudes, and sexual behaviors among young adults in Romania; an effective preventive campaigns should be based on an appropriate understanding of these factors. The aim of the present study was to obtain data about sexual behavior, attitudes, and knowledge about STIs among university students aged 18-25 in Romania. 3872 persons completed an internet-based questionnaire, advertised on Facebook, regarding sexual behavior, attitudes, and knowledge about STIs from January 28 to February 28, 2016. 6.01% of the respondents had no sexual experience; of the remaining (N=3639, 945 men and 2694 women) 94% were heterosexual, 1.5% homosexual, and 4.6% bisexual. 53.7% of the respondents started their sexual activity between 14 and 18 years of age; only 2.3% become sexually active before 14 years of age. 30% of both sexes reported multiple sexual partners during the previous year. 25.9% of men and 23.3% of women used no contraception at sexual onset, the proportion being higher among those with an early sexual debut. 98% of the respondents knew that HIV could be contracted sexually, 75.8% knew that gonorrhea and 61.1% that Chlamydia trachomatis were sexually transmitted, and approximately one third knew that trichomoniasis and hepatitis B or C were STIs. We found a relatively high proportion of students engaged in risky sexual behaviors and insufficient knowledge about STIs. The results are important in planning future sexual education campaigns and they call for new preventive strategies.

Regression and Sentinel Lymph Node Status in Melanoma Progression.

BACKGROUND The purpose of this study was to assess the role of regression and other clinical and histological features for the prognosis and the progression of cutaneous melanoma. MATERIAL AND METHODS Between 2005 and 2016, 403 patients with melanoma were treated and followed at our Department of Dermatology. Of the 403 patients, 173 patients had cutaneous melanoma and underwent sentinel lymph node (SLN) biopsy and thus were included in this study. RESULTS Histological regression was found in 37 cases of melanoma (21.3%). It was significantly associated with marked and moderate tumor-infiltrating lymphocyte (TIL) and with negative SLN. Progression of the disease occurred in 42 patients (24.2%). On multivariate analysis, we found that a positive lymph node and a Breslow index higher than 2 mm were independent variables associated with disease free survival (DFS). These variables together with a mild TIL were significantly correlated with overall survival (OS). The presence of regression was not associated with DFS or OS. CONCLUSIONS We could not demonstrate an association between regression and the outcome of patients with cutaneous melanoma. Tumor thickness greater than 2 mm and a positive SLN were associated with recurrence. Survival was influenced by a Breslow thickness >2 mm, the presence of a mild TIL and a positive SLN status.

Pyoderma gangrenosum with spleen involvement. Review of the literature and case report.

BACKGROUND: Pyoderma gangrenosum is a rare, ulcerative, destructive, non-infectious dermatologic disease and it is one clinical entity within the spectrum of neutrophilic dermatoses. Visceral involvement, manifesting as sterile neutrophilic infiltrates in sites other than skin and, is infrequent. Splenic involvement is very rare. MAIN OBSERVATIONS: We present a case of a 58-year-old woman with pyoderma gangrenosum with spleen involvement and review all reports of similar cases.We have found nine reported cases, our case being the tenth. CONCLUSION: Our review showed that spleen involvement in the course of pyoderma gangrenosum can occur at any age. It is slightly more frequent in men. An underlying or associated neutrophilic disorder is present in almost half of the patients. Skin manifestations were usually present before splenic involvement. In most cases the disese responds well to glucocorticosteroids.

Assessment of Cutaneous Melanoma by Use of Very- High-Frequency Ultrasound and Real-Time Elastography.

OBJECTIVE: The primary objective of this study was to evaluate the usefulness of very-high-frequency ultrasound as tool for assessment of skin melanoma by investigation of the correlation between the ultrasound measurement of the thickness of a melanoma and the histopathologically measured Breslow index. The secondary objective was to assess the potential role of real-time elastography in the preoperative evaluation of skin melanoma. SUBJECTS AND METHODS: The study included 42 cutaneous melanoma lesions in 39 adult subjects examined in the division of ultrasound of a department of radiology between September 2011 and January 2015. Gray-scale sonographic features at 40 MHz (thickness, echogenicity, contour) and real-time strain elastographic (qualitative and semiquantitative, strain ratio) characteristics were evaluated and compared with the pathologic results. RESULTS: The melanoma lesions had a homogeneous hypoechoic appearance with a regular contour and stiff or medium consistency. The mean difference between Breslow index and ultrasound thickness was -0.05 mm (95% CI, -0.24 to 0.13 mm), sustaining the absence of significant differences between these two measurements. A strong relation was identified between real-time elastographic appearance and strain ratio for the relations between lesion and hypodermis and between lesion and neighboring dermis (p < 0.002) or hypodermis. CONCLUSION: Our study showed that very-high-frequency ultrasound and real-time elastography can be useful examinations for comprehensive preoperative evaluation of cutaneous melanoma.

Doppler ultrasound and strain elastography in the assessment of cutaneous melanoma: preliminary results.

AIM: To study the usefulness of color or power Doppler ultrasound (US) in the pre-surgical evaluation of skin melanoma, and to correlate the Doppler characteristics with the appearance on high frequency ultrasound strain elastography (SE) in the preoperative evaluation of cutaneous melanoma. MATERIALS AND METHOD: The study included 42 cutaneous melanoma lesions in 39 adult subjects examined between September 2011 and January 2015. Doppler US features (the presence and aspect of vascularization, and the number of vascular pedicles) and elasticity by strain elastography were evaluated together with the pathological results. RESULTS: The melanoma lesions presented hyper-vascularization, with multiple vascular pedicles and stiff appearance. Significant correlations between the thickness of the tumor, measured histopathologically by the Breslow index, and the degree of vascularization (p=0.0167), and number of vascular pedicles (p=0.0065) were identified. Strong correlations between the SE appearance and vascularization on one hand, and SE and the number of vascular pedicles were also identified (p<0.001). CONCLUSION: Our study demonstrates that Doppler US and SE offer useful information for THE preoperative evaluation of cutaneous melanoma and may contribute to better defining the long term prognosis.

Intravenous methylprednisolone pulse therapy in severe alopecia areata.

BACKGROUND: Severe, extensive, therapy resistant alopecia areata represents a clinical challenge. Systemic corticosteroids are a therapeutic tool that still needs to be evaluated. AIM: The purpose of this study was to assess the efficacy and safety of methylprednisolone pulse therapy in alopecia areata and to find prognostic factors for a favourable outcome. METHODS: A total of 32 patients with severe multifocal alopecia areata (more than 40% scalp hair loss), alopecia totalis, and alopecia universalis were treated with infusions of 500 mg methylprednisolone for 3 days every month for 3 consecutive months. The end point of the study was 12 months. RESULTS: Of 32 patients, 26 (81.3%) reported a clinical response. Four patients (12.5%) showed complete hair regrowth, 6 patients (18.8%) showed >50% hair regrowth, ten (31.3%) had <50% hair regrowth, 6 (18.75%) were non responders, and another 6 patients (18.8%) had relapse after an initial regrowth. Multivariate analysis revealed that patients reporting at the first episode and those with multifocal disease had the best results. CONCLUSION: Methylprednisolone infusions represent a possible therapeutic option for patients with multifocal alopecia areata and those presenting with the first episode of the disease.

Active and inactive forms of matrix metalloproteinases 2 and 9 in cutaneous melanoma.

BACKGROUND: Cutaneous melanoma is the most aggressive type of skin cancer, with high implications on the morbidity and mortality of patients. Matrix metalloproteinases (MMP) 2 and 9 have been involved in melanoma progression because they degrade important components of the basement membrane. We studied the relationship between the levels of active and inactive MMP 2, MMP 9, and clinicopathological parameters. MATERIALS AND METHODS: Expression of both active and latent forms of MMP 2 and MMP 9 was evaluated by zymography in 21 melanoma tissue samples and 19 benign melanocytic nevi samples. RESULTS: In the melanoma group, inactive MMP 2 was detected in 100% of samples and active MMP 2 in 95%. Inactive MMP 9 was detected in 85% of samples and active MMP 9 in 38%. In the nevi group, 78.9% of samples expressed inactive MMP 2, 5.26% active MMP 2, 21% inactive MMP 9, and 0% active MMP 9. Both forms of MMP 2 and MMP 9 were found to be correlated with skin tumor malignancy. Expression of active and latent MMP 9 was higher in tumors >2 mm thick (P = 0.03, P = 0.014). A correlation was also found between positive lymph node metastasis, inactive MMP 9, and active MMP 9 expression (r = 0.59 P < 0.01, r = 0.668, P < 0.01). The amount of active and latent form of MMP 2 did not have an impact on lymph node metastasis. CONCLUSIONS: Our study demonstrates that active and latent MMP 2 and MMP 9 correlate with melanoma, and both forms of MMP 9 correlate with positive lymph node metastasis.

Correlation of dermatoscopy with the histopathological changes in the diagnosis of thin melanoma.

UNLABELLED: Dermatoscopy is a non-invasive technique that enables the early diagnosis of melanoma. The purpose of the present study is to identify the dermatoscopic structures or changes that can indicate the presence of thin melanoma and their correlation with the histopathological aspect. MATERIALS AND METHODS: Twenty-four thin melanomas diagnosed at the Department of Dermatology in Cluj-Napoca, Romania, have been assessed from the point of view of the presence of dermatoscopic structures likely to indicate malignancy. The lesions have been excised and serially sectioned to identify the histopathological correspondent of the various dermatoscopic structures. RESULTS: The dermatoscopic analysis has indicated the following characteristics that suggest the presence of thin melanoma: irregular dots or globules, small white or grey-blue areas, some peripheral pseudopods or radial streaming, red dots at the level of the lesion or the presence of an atypical vascular pattern. As far as lesions under dermatoscopic follow-up are concerned, the following may be signs of malignant transformation: changes of the pigment network, newly appeared small white or red-blue areas or irregularly distributed dots or globules. All these structures are correlated with the histopathological changes that characterize thin melanoma. CONCLUSIONS: Slight dermatoscopic changes are extremely important in diagnosing thin melanomas as they correlate with the histopathological aspect.

Dystrophic epidermolysis bullosa: two case reports.

We identified the mutations in two patients with different phenotypes of dystrophic epidermolysis bullosa (DEB). We performed molecular diagnosis to a patient aged 45 years who showed the typical severe generalized autosomal recessive DEB signs when admitted to the hospital. The other patient is a 4-month-old boy who showed a moderate clinical aspect of DEB, dominated by nail dystrophy. The molecular diagnosis disclosed in the first patient the presence of a heterozygous mutation consisting of a nucleotide substitution that lead to a splice site mutation, namely 425-2 A>G, associated to a premature termination codon, in exon 5, namely c.553 C>T, p.R185X and in the second patient a heterozygous substitution at nucleotide position 6100 that converts a glycine amino acid to arginine (6100G>A). The mutation is designated G2034R. We conclude that molecular diagnosis is the conclusive EBD investigation, maps the phenotype of a patient with his genotype and thus allows a better understanding of the disease mechanism and the development of gene therapy. Molecular diagnosis also enables genetic counseling and prenatal diagnosis.

Photodamaging effects of porphyrins and chitosan on primary human keratinocytes and carcinoma cell cultures.

BACKGROUND: Photodynamic therapy (PDT) is a non-surgical method for treating non-melanoma skin cancer and precancerous lesions which involves the activation of a photosensitizer by visible light to produce activated oxygen species within target cells, resulting in the destruction of the latter. The present study evaluates the effect of PDT on primary normal and basal cell carcinoma cultures in vitro. METHODS: Primary human keratinocytes and carcinoma cell cultures were exposed to various concentrations of 5,10,15,20-tetra-(para-methoxyphenyl) porphyrin (TMP) and its zinc compound (Zn-TMP) for 24 hours, with or without chitosan, and then irradiated using a PDT lamp (630 nm, 6 J/cm(2)). The effects of PDT were assessed using a 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium inner salt (MTS) assay and an immunocytochemical method with Annexin V-FITC for detecting apoptosis. RESULTS: Both tested substances, TMP and Zn-TMP, had a phototoxic effect on primary human carcinoma cell cultures in concentrations of 1-100 µg/ml, which positively correlated with the concentration of the photosensitizer. There was no phototoxic effect on primary keratinocytes, probably because of the preferential accumulation of photosensitizing substances in tumoral cells. Administration of chitosan in association with photosensitizing substances increased cell viability compared with photosensitizers alone, exerting a cytoprotective effect. CONCLUSIONS: The study demonstrates that the photodynamic activity of TMP and its metalloporphyrin derivative is limited to primary human carcinoma cells and suggests that these porphyrins could be efficiently used in PDT in vivo.