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.

Association of Oral-Health Related Quality of Life and General Health Assessment in Patients with Rheumatoid Arthritis.

PURPOSE: To determine the impact of oral health related quality of life (OHRQoL) on general health in patients suffering from rheumatoid arthritis (RA). MATERIALS AND METHODS: Ninety-one patients with RA (mean age 52.82 ± 11 years, 75.82% female, 20.87% smokers) and 30 systemically healthy patients (control) were evaluated for their OHRQoL by means of the Geriatric Oral Health Assessment Index (GOHAI) and the Oral Health Impact Profile (OHIP)-14 questionnaires. Self-perceived RA status was assessed using the Routine Assessment of Patient Index Data 3 (RAPID3). RESULTS: The mean SC-GOHAI score was 3.69 ± 2.47 for RA subjects and 1.36 ± 2.69 in the control group. Statistically significant differences were seen between RA and control groups (p < 0.05). RA patients with and without periodontitis (PA) exhibited similar SC-GOHAI (Simple Count GOHAI) scores (p = 0.980). No statistically significant differences were observed between any of the groups, either for the OHIP 14-extent or for the OHIP 14-prevalence. RAPID3 scores showed that the majority of the RA patients (65.93%) had high disease severity (RAPID3 >12, mean RAPID3 score 14.39 ± 5.14). Statistically significantly higher values were recorded for general health assessment (PTGE, p = 0.009) and fatigue (FT, p = 0.004) in RA with PA as compared to those without. SC-GOHAI with values between 5 and 8 was statistically significantly associated with high severity health impairment (RAPID3 >12, p = 0.014, OR: 8.64). CONCLUSION: Within their limits, the present findings indicate that: a) moderate OHRQoL as assessed by GOHAI may contribute to high severity impairment of health in RA patients, and b) the GOHAI questionnaire may represent a more adequate tool than OHIP-14 for assessing OHRQoL in patients suffering from RA.

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.

Desmoplakin mutations with palmoplantar keratoderma, woolly hair and cardiomyopathy.

Mutations in genes encoding for desmosomal components are associated with a broad spectrum of phenotypes comprising skin and hair abnormalities and account for 45-50% of cases of arrhythmogenic right ventricular cardiomyopathy. Today, more than 120 dominant and recessive desmoplakin (DSP) gene mutations have been reported to be associated with skin, hair and/or heart defects. Here we report on 3 cases with yet unreported DSP mutations, c.7566_7567delAAinsC, p.R2522Sfs*39, c.7756C>T, p.R2586*, c.2131_2132delAG and c.1067C>A, p.T356K, that were associated with variable woolly hair or hypotrichosis, palmoplantar keratoderma, and cardiac manifestations. In addition, we review and summarise the clinical features and DSP mutations of the patients described in the literature, which illustrates the complexity of this group of disorders and of their genotype-phenotype correlations, which cannot be easily predicted. Early diagnosis is crucial and cardiac examinations have to be performed on a regular basis.

Multiple primary melanomas: Our experience.

Patients with melanoma have an increased risk of having other neoplasms, and particularly other melanomas and non-melanoma skin cancers. The study aimed to describe multiple primary melanomas in a large medical university centre from Romania (Cluj-Napoca) from 2004 to 2020. Out of 699 patients with melanoma included in the study, 26 (3.71%) developed multiple tumours. The 26 patients developed a total of 59 melanomas, corresponding to a mean of 2.3 melanomas per patient. The site and histological subtype of the first and second melanomas were not consistent. The proportion of subsequent melanomas that were in situ (51.5%) or thin melanomas (<1 mm, 24.2%) was higher compared with first melanomas (7.7%, respectively 11.5%). The median and mean time to diagnosis was 2.75 months, respectively, 28.09 months. In total, 76.92% of second melanomas were detected within three years, but we were able to document a subsequent melanoma more than ten years after the first diagnosis. The study highlights the importance of follow-up in patients diagnosed with melanoma, not only in the first years after the primary diagnoses but for the entire life.

A Recurrent Case of Targetoid Hemosiderotic Hemangioma: A Case Report and a Comprehensive Review of the Literature.

Targetoid hemosiderotic hemangioma is an acquired vascular malformation of unknown origin. We report the case of a 31-year-old man with a recurrent and spontaneous regressive targetoid hemosiderotic hemangioma. Diagnosis relied on clinical and histological findings. Physical examination revealed presence of an approximately 2 cm targetoid lesion located on the left arm, and associated with pain after pressure. No trigger agent (trauma, insect sting) was reported. Dermoscopy showed a group of red lacunae centrally, encircled by an intermediate yellow circular homogenous area and a red violaceous homogenous ring in the periphery. The histopathological examination and the immunohistochemical staining of the lesion were characteristic for a hemangioma-like proliferation of vessels in the upper part of the dermis, similar to a targetoid hemosiderotic angioma. We also review epidemiological, clinical, and histopathological findings in 6 similar cases presented in the literature. Spontaneous regression and recurrence have rarely been described in this type of skin lesion.

Assessment of sun-related behavior and serum vitamin D in basal cell carcinoma: Preliminary results.

Ultraviolet radiation (UV), mainly from sunlight, is the main risk factor of the most common human skin cancer, basal cell carcinoma (BCC). A positive effect of UV on the skin is its contribution to the synthesis of vitamin D, which is important in sustaining general health, but having high levels of vitamin D is considered a risk factor for BCC. However, vitamin D receptor has antagonistic effects to UV radiation in regulating Sonic Hedgehog pathway. This is a pilot study aimed at characterizing the sun-related behavior and vitamin D status of 52 BCC patients and 59 controls from our geographical area. Patients were included in 4 subgroups: Single, multiple, recurrent, and both multiple and recurrent BCCs. Patients, more than controls, had at least one sunburn in childhood and lentigines (P<0.001). Also, they spent daily, on average, more time in the sun than controls (P<0.001) (3.00-8.00 and 1.50-4.00 h respectively). Outdoor work was similar in both groups. Participants had lower vitamin D serum levels than expected. Due to the small number of cases, no statistically significant differences were found between the subgroups but some tendencies were noted. Patients with only one recurrent BCC had less sunburns than the ones who also developed tumors at multiple sites (P=0.2). Patients with multiple and recurrent tumors had slightly lower vitamin D levels compared with single BCC patients (P=0.1) although they used more vitamin D supplements after the BCC diagnosis (P=0.2). Having a diagnosis of BCC, made patients more compliant to the use of sunscreen cream, but even so, half of them still did not use it. In conclusion, more effort should be invested in sun-related education and public health actions should focus on vitamin D deficiencies.

Cutaneous manifestations in inflammatory bowel disease (Review).

Inflammatory bowel disease (IBD) is defined as a chronic condition characterized by unpredictable relapsing episodes of gastrointestinal inflammation. IBD is not limited to the gastrointestinal tract and should be considered a systemic disease which can involve any organ. Cutaneous manifestations in IBD are frequent and comprise a broad spectrum of diseases, ranging from mild to severe and sometimes debilitating lesions. Some of the cutaneous manifestations can present signs of an underlying intestinal disease, leading to the screening for non-detected IBD even in the absence of symptoms. Cutaneous EIMs are divided into 4 categories: i) Disease-specific lesions that show the same histopathologic findings as the underlying gastrointestinal disease, ii) reactive lesions which are inflammatory lesions that share a common pathogenetic mechanism but do not share the same pathology with the gastrointestinal disease, iii) associated conditions are more frequently observed in the context of IBD, without sharing the pathogenetic mechanism or the histopathological findings with the underlying disease and iv) drug-related skin reactions.

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.

Pemphigoid nodularis - rare presentation of bullous pemphigoid: A case report and literature review.

Pemphigoid nodularis (PN) is a rare clinical variant of bullous pemphigoid characterized by the presence of nodular prurigo-like lesions and pemphigoid blisters. The diagnosis is confirmed by direct immunofluorescence (DIF)/ indirect immunofluorescence (IIF) and immunoserology tests. For some patients, with long mean duration of symptoms, the correct diagnosis of PN is delayed because the disease is not recognized. We present a case and summarize the reported characteristics of PN. The search in MEDLINE database, after selection, resulted in 36 articles presenting 47 cases of PN. Between published cases a female predominance was noted (female to male ratio of 1.8:1), almost half of the reported patients were non-Caucasian, and the mean age at presentation was 66.2 years. The mean duration until the diagnosis was almost 2 years. Sixteen patients also had other autoimmune diseases. Twenty-two patients developed vesicles/bullae/urticarial plaques before or after the diagnosis. Peripheral eosinophilia and high levels of serum total IgE were reported in 10.6 and 27.2% of patients, respectively. ELISA for either BP180, BP230 or both were positive in all tested cases. DIF and IIF microscopy were positive overall in 100 and 92.3% of cases, respectively. Corticosteroids, either topical or systemic, were the most efficient therapeutic option, although many others were used. PN remains a diagnostic and therapeutic challenge in elderly patients with unexplained refractory chronic pruritus associated with papulo-nodular lesions.

Risk factors for melanoma and skin health behaviour: An analysis on Romanian melanoma patients.

In contrast to Western Europe, in Central and Eastern Europe reports show higher rates of advanced melanoma and lower survival. Our aim was to document and compare melanoma risk factors and skin health behaviour in patients diagnosed with melanoma and people not affected by this disease in a large medical university centre from Romania (Cluj-Napoca). Two hundred and forty-seven melanoma patients followed-up in the Department of Dermatology at the Cluj-Napoca Emergency County Hospital and 956 people not affected by melanoma completed a paper-based questionnaire regarding melanoma risk factors, risk behaviour and self-protecting measures, after giving informed consent. People with melanoma had significantly higher personal risk and protective behaviour, and lower risk behaviour than those not affected. Although our data suggest that melanoma patients are better educated about how to avoid a second primary melanoma, our results are concerning when compared with studies from other countries. The low incidence of self and clinical skin-examination together with the relatively low percentage of participants which would consult a doctor in the case of new/changing mole could be one of the explanations for the late diagnosis of melanoma in the studied population. According to our findings, there is an urgent need for population health campaigns regarding not only primary but also secondary melanoma prevention.

Vitamin D receptor polymorphisms and melanoma.

Melanoma represents the most aggressive skin cancer, with an unpredictable and often treatment resistant behavior. The etiology of melanoma is multifactorial and includes both environmental and genetic factors. Recent evidence indicates that vitamin D has a role in the development and progression of melanoma. The biologically active form of vitamin D/1,25-dihydroxyvitamin D3 acts by binding to a intranuclear receptor; vitamin D receptor (VDR). Single nucleotide polymorphisms (SNPs) in the vitamin D receptor gene may alter the expression or the function of the VDR protein leading to various diseases, including melanoma. More than 600 SNPs have been identified in the VDR gene, but only a few have been analyzed in relation to melanoma risk: FokI, TaqI, BsmI, ApaI, Cdx2, EcoRV, and BglI. Individual studies carried on small cohorts of patients reported controversial results. In an attempt to clarify the available data in the literature on this subject, we elaborated a systematic review in which we analyzed the relationship between VDR gene polymorphisms and melanoma risk and progression. We concluded that vitamin D pathway is important for the pathogenesis and the progression of cutaneous melanoma, illustrating the gene-environment interactions, but well-designed prospective studies that include data on both genotypes and phenotypes of vitamin D metabolism are essential in order to understand the mechanisms underlying the association between vitamin D and melanoma.

[Lisch nodules. Markers for a non-invasive diagnosis in Recklinghausen neurofibromatosis]. / Nodulii LISCH. Markeri de diagnostic noninvaziv in neurofibromatoza Recklinghausen.

INTRODUCTION: Von Recklinghausen's neurofibromatosis is an autosomal dominant disorder that affects both sexes at the same rate. The diagnosis is suggested by the family history, the presence of multiple neurofibromas and cutaneous pigmentary macules but is only confirmed by the presence of the Lisch nodules at the iris level and by histological exam. The disease is associated with different nervous system, bone, endocrine, blood vascular abnormalities. PURPOSE: Evaluation of Lisch nodules in patients with Recklinghausen disease or immediate relatives, that do not present characteristic cutaneous lesions. MATERIAL AND METHOD: The study involves three cases of Recklinghausen neurofibromatosis and also a part of their immediate relatives. The diagnosis of NF1 was based on clinical aspects, family pedigree analysis and ophthalmological exam. The histological exam was only performed for complicated cutaneous lesions. RESULTS AND DISCUSSIONS: The clinical exam revealed characteristic cutaneous lesions but also Lisch nodules in all three studied cases. According to the pedigrees, Recklinghausen disease is inherited as an autosomal dominant trait (in 2 patients), but it may also arise as de novo mutations (1 patient). The ophthalmological exam performed for the patients' relatives, identified Lisch nodules in all subjects presenting cutaneous lesions (neurofibromas), and also in children without characteristic cutaneous features. Both pedigree analysis and ophthalmological examination are compulsory, noninvasive methods for precocious diagnosis of the disease and the identification of high-risk patients. CONCLUSIONS: Lisch nodules are ophthalmological and pathognomonic markers of Recklinghausen neurofibromatosis. Lisch nodules facilitate a precocious, noninvasive diagnosis inclusively in children without cutaneous features (neurofibromas) but positive antecedents. Ophthalmological examination and pedigree analysis are compulsory both in patients and their immediate relatives.

Junctional Epidermolysis Bullosa: Allelic Heterogeneity and Mutation Stratification for Precision Medicine.

Junctional epidermolysis bullosa (JEB) is a hereditary blistering disease caused by reduced dermal-epidermal adhesion due to deficiencies of one of the proteins, laminin-332, type XVII collagen, integrin α6ß4 or integrin α3. Significant progress has been achieved in the development of therapies for EB, such as bone-marrow transplantation, local or systemic injections with fibroblasts or mesenchymal stromal cells, readthrough of premature termination codons, or exon skipping. These were tailored in particular for dystrophic EB, which is caused by type VII collagen deficiency and have not yet reached broad clinical practice. Recently, pioneering combined gene and stem cell therapy was successful in treating one boy with junctional EB. Beside these exclusive approaches, no specific therapy to amend the major clinical features, skin and mucosal blistering and non-healing wounds is available to date. Here we extend the mutational spectrum of junctional EB, provide a stratification of COL17A1 mutations and discuss potential molecular therapeutic approaches.

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.

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.

The role of lymph node ultrasound evaluation in melanoma - review of the literature.

Melanoma is an aggressive tumour, resistant to treatment, derived from melanocytes, with an increasing incidence in the last years in the majority of countries. The most important prognostic factor in the initial stages (I/II) is the presence of metastases at the level of lymph nodes. Ultrasound (US) is a non-invasive method, used in the pre- and post-operative node evaluation due to its high availability, the reduced cost and easy reproducibility. The US accuracy is however dependent on operator expertise. The present article proposes a presentation of the US role in the evaluation of lymph nodes in melanoma patients.

Clinico-pathologic, dermoscopic and ultrasound examination of a rare acral tumour involving the nail - case report and review of the literature.

There is a large spectrum of tumors presenting as nodular lesions that may affect the subungual space. We report the case of a 62-year-old woman presenting with a rapidly growing nodular lesion under the nail of the first left toe. Non-invasive examinations using dermoscopy, ultrasonography and elastography were performed for the preoperative assessment of the lesion. The biopsy of the lesion revealed superficial acral fibromyxoma, a benign tumor with predisposition for acral sites. The patient underwent radical surgery with wide resection margins. This is the first case report of a superficial acral fibromyxoma affecting the subungual region characterized by dermoscopic, ultrasonographic and elastographic features. We also performed a short review of the literature.