Collision Lesions: Genuine Collision (Conflict) or not?

By definition, the term "collision lesion" refers to two or more tumors coinciding in the same anatomic position or visceral organ. Collision lesions coexisting on the same skin location are defined as collision skin lesions (CSLs). Although this term implies a conflict between the tumors, this is not the case. CSLs appear to be rare, but still pose a significant diagnostic problem in everyday clinical practice and clinicians should be aware of their existence. The aim of this study was to elucidate the problem of CSLs in clinical practice, with an emphasis on classification of CSLs according to position dependence, tumor histogenesis, etiology, and possible lesion combinations in CSLs, as well as diagnostic possibilities. According to our results, accurate clinical diagnosis could be only rarely reached, requiring lesion excision and pathohistological confirmation of CSLs. Considering the fact that tumors in CSLs can be partially or completely overlying or can even be positioned one within the other, the existence of two or more tumors is extremely difficult to detect.

Melanoma Controls the Metastatic Process only in Terms of Metastatic Cell Dissemination - What Is Responsible for Metastatic Cell Proliferation?

The process of melanoma metastasis can be divided into two stages of metastatic cell dissemination and proliferation. The whole process should be observed and distinguished through the variable or prism of time. The fact that melanoma metastases are detected in visceral organs at the stage when they are macroscopically visible does not imply that their onset has occurred much earlier. Additionally, it is quite obvious that the entire process is not driven by melanoma but rather only the initial stage of metastatic cell dissemination, whereas the later stage of metastatic cell proliferation is driven by other factors, firstly by mutated genes in the presence of melanoma or without it. Dissemination of metastatic cells occurs at approximately the same time in all melanomas, at MIS transition to MM, but is not immediately followed by metastatic cell proliferation; instead, some time has to elapse for a particular gene mutation to occur, and this timing varies among melanomas. Following dissemination of metastatic cells to visceral organs, they remain inactive, and in this period the presence of melanoma is not necessary anymore for metastatic cell proliferation, as they are waiting for a signal to start multiplying. This is clearly discernible from the fact that melanoma is today detected and removed frequently and early, but visible metastases then develop in the absence of melanoma, which may also regress spontaneously. Accordingly, MM is no longer necessary for metastasis later on. Finally, let me rephrase the title: melanoma is only responsible for initial dissemination of metastatic cells, whereas subsequent proliferation of metastatic cells is driven by other factors, most probably mutated genes.

Inequalities in the patterns of dermoscopy use and training across Europe: conclusions of the Eurodermoscopy pan-European survey.

BACKGROUND: Dermoscopy is a widely used technique, recommended in clinical practice guidelines worldwide for the early diagnosis of skin cancers. Intra-European disparities are reported for early detection and prognosis of skin cancers, however, no information exists about regional variation in patterns of dermoscopy use across Europe. OBJECTIVE: To evaluate the regional differences in patterns of dermoscopy use and training among European dermatologists. MATERIALS & METHODS: An online survey of European-registered dermatologists regarding dermoscopy training, practice and attitudes was established. Answers from Eastern (EE) versus Western European (WE) countries were compared and their correlation with their respective countries' gross domestic product/capita (GDPc) and total and government health expenditure/capita (THEc and GHEc) was analysed. RESULTS: We received 4,049 responses from 14 WE countries and 3,431 from 18 EE countries. A higher proportion of WE respondents reported dermoscopy use (98% vs. 77%, p<0.001) and training during residency (43% vs. 32%) or anytime (96.5% vs. 87.6%) (p<0.001) compared to EE respondents. The main obstacles in dermoscopy use were poor access to dermoscopy equipment in EE and a lack of confidence in one's skills in WE. GDPc, THEc and GHEc correlated with rate of dermoscopy use and dermoscopy training during residency (Spearman rho: 0.5-0.7, p<0.05), and inversely with availability of dermoscopy equipment. CONCLUSION: The rates and patterns of dermoscopy use vary significantly between Western and Eastern Europe, on a background of economic inequality. Regionally adapted interventions to increase access to dermoscopy equipment and training might enhance the use of this technique towards improving the early detection of skin cancers.

Evaluation of the glycemic effect of methotrexate in psoriatic arthritis patients with metabolic syndrome: A pilot study.

Methotrexate (MTX) is a systemic immunosuppressant drug used for the treatment of psoriasis and psoriatic arthritis. Previous studies demonstrated a potential association between psoriasis and diabetes mellitus, obesity, atherosclerosis, hypertension, eventuating into metabolic syndrome. This study aimed at exploring the glycemic effects of MTX in psoriatic arthritis (PsA) patients. In this prospective cross-sectional study, 27 patients with PsA were evaluated. The status of PsA and presence of accompanying metabolic syndrome was determined by standard criteria and indices. Blood indicators including HbA1c, erythrocyte sedimentation rate, fasting blood sugar, total cholesterol, high-density lipoprotein, triglycerides, and C-reactive protein were examined before and 12 weeks after MTX therapy. There were no significant changes between HbA1c levels before and after MTX therapy in both genders (men: P=0.131, women: P=0.803). In addition, HbA1c levels in PsA patients with metabolic syndrome were not different before and after treatment (P=0.250). Finally, HbA1c levels did not change in PsA patients without metabolic syndrome before and after therapy (P=0.506). MTX in PsA patients does not appear to have hyperglycaemic effects in the short-term and can be safely used in patients with metabolic syndrome and diabetes.

Dermatomycosis in Cutaneous Tumors is a Predictor for Non-malignancy: A Cross-sectional Study.

The aim of this study was to evaluate the presence of spores and/or hyphae in benign cutaneous tumors (CT) and compare their presence in malignant cutaneous tumors. In this cross-sectional study we evaluated 328 CTs positive for spores and/or hyphae. The results show that the greatest number of involved CTs which contained spores and/or hyphae were found in compound nevi 181 (55.18%) and seborrheic warts 61 (18.60%). No spores and/or hyphae were observed in the melanoma samples, and a very low prevalence was found in squamous cell carcinomas (SCCs) (2; 0.61%) and basal cell carcinoma (BCC) (1; 0.30%). The presence of spores and/or hyphae could be a good indicator for non-malignancy, allowing differential diagnosis between benign CTs and SCCs or BCCs as well as between melanoma and nevi.

Man against machine: diagnostic performance of a deep learning convolutional neural network for dermoscopic melanoma recognition in comparison to 58 dermatologists.

Background: Deep learning convolutional neural networks (CNN) may facilitate melanoma detection, but data comparing a CNN's diagnostic performance to larger groups of dermatologists are lacking. Methods: Google's Inception v4 CNN architecture was trained and validated using dermoscopic images and corresponding diagnoses. In a comparative cross-sectional reader study a 100-image test-set was used (level-I: dermoscopy only; level-II: dermoscopy plus clinical information and images). Main outcome measures were sensitivity, specificity and area under the curve (AUC) of receiver operating characteristics (ROC) for diagnostic classification (dichotomous) of lesions by the CNN versus an international group of 58 dermatologists during level-I or -II of the reader study. Secondary end points included the dermatologists' diagnostic performance in their management decisions and differences in the diagnostic performance of dermatologists during level-I and -II of the reader study. Additionally, the CNN's performance was compared with the top-five algorithms of the 2016 International Symposium on Biomedical Imaging (ISBI) challenge. Results: In level-I dermatologists achieved a mean (±standard deviation) sensitivity and specificity for lesion classification of 86.6% (±9.3%) and 71.3% (±11.2%), respectively. More clinical information (level-II) improved the sensitivity to 88.9% (±9.6%, P = 0.19) and specificity to 75.7% (±11.7%, P < 0.05). The CNN ROC curve revealed a higher specificity of 82.5% when compared with dermatologists in level-I (71.3%, P < 0.01) and level-II (75.7%, P < 0.01) at their sensitivities of 86.6% and 88.9%, respectively. The CNN ROC AUC was greater than the mean ROC area of dermatologists (0.86 versus 0.79, P < 0.01). The CNN scored results close to the top three algorithms of the ISBI 2016 challenge. Conclusions: For the first time we compared a CNN's diagnostic performance with a large international group of 58 dermatologists, including 30 experts. Most dermatologists were outperformed by the CNN. Irrespective of any physicians' experience, they may benefit from assistance by a CNN's image classification. Clinical trial number: This study was registered at the German Clinical Trial Register (DRKS-Study-ID: DRKS00013570; https://www.drks.de/drks_web/).

Melanoma can control development of metastasis--Fact or myth?

The malignant melanoma spreading process cannot explain occurrence of metastases several years following local surgical therapy of primary malignancy. But, this complex process of delayed metastases is still challenging and not completely understood. We hypotheses that melanoma metastases occur early in disease, probably at the same time with the occurrence of the primary melanoma. We suggest that dissemination of metastatic "seed cells" occur at an early stage of the disease together with the development of primary melanoma and cannot be detected by standard diagnostic methods. These cells are masked between healthy cells and have the potential to proceed in true metastasis following the activation triggered by signal from primary tumor or other source. Other possibility includes the existence of two different genes, one responsible for development of primary melanoma, and the other with a roll in development of metastases. We believe that future investigation should be directed toward better understanding of mechanisms involved in metastases development keeping in mind that melanoma behavior is irrational and defies logical thinking.

[ASSOCIATION OF PSORIASIS WITH OTHER DISEASES]. / UDRUZENOST PSORIJAZE S DRUGIM BOLESTIMA.

Psoriasis is a chronic relapsing autoimmune disease with a multigenetic predisposition, which occurs in about 2% of patients in Croatia and shows variable occurrence in the world. Psoriasis can be associated with various diseases, including autoimmune diseases (pemphigus, pemphigoid, vitiligo), and slightly less with allergic diseases (atopic dermatitis, asthma, urticaria, allergic contact dermatitis). According to clinical manifestations, psoriasis appears as plaque psoriasis, erythrodermic form and pustular psoriasis. Provocative factors that encourage psoriasis are infections, endogenous factors, hypocalcemia, psychogenic factors and medications. Psoriasis may worsen other dermatoses such as contact dermatitis, inflammatory dermatoses and skin cancer, and the association of psoriasis with internal diseases is quite common (HIV, Crohn's disease, liver lesions, vascular diseases, amyloidosis and gout). Today, psoriasis is considered as a systemic inflammatory disease that can also affect the joints. Atypical localization of psoriasis, as well as resistant cases of psoriasis and other papulosquamous and eczematoid dermatoses require detailed work-up and confirming of diagnosis because of the possibility of the existence of other diseases. This paper discusses the association of psoriasis with rheumatic and other internal diseases.

Differences between keratoacanthoma and squamous cell carcinoma using TGF-alpha.

Squamous cell carcinoma (SCC) and keratoacanthoma (KA) are skin neoplasms of epithelial origin. In contrast to clearly malignant skin neoplasm SCC, KA is an unusual cutaneous neoplasm with a tendency to regression. The distinction between these two neoplasms, on histological grounds only, is still a challenge. In order to investigate further and to assess the possible differences in transforming growth factor-alpha (TGF-alpha) expression between SCC and KA, 40 of skin tumor specimens, 20 cases of each SCC and KA were analyzed immunohystochemicaly. We have found a significant difference in staining patterns between KA and SCC. In KAs we have detected TGF-alpha staining mainly diffusely (90% of cases) and without peripheral staining of cells in 1-2 layers (60% of cases). Contrary, there was a mostly patchy staining (55% of cases) with peripheral staining of cells in 1-2 layers (100% of cases) in SCCs. Generally, differentiation between KA and SCC can be based on clinical and histological ground, but the distinction between these two skin tumors could sometimes be difficult. We have shown that these skin neoplasms could be differentiated based on staining patterns of TGF-alpha expression, thus this method could aid in differentiation between these two closely related entities in clinical practice.

Negative and positive life experiences in patients with psoriatic arthritis.

Recent data suggest that childhood and adulthood stressors may play a significant role in the development of an autoimmune disease. The present study explores the relationship between psoriatic arthritis (PsA) and positive and negative life events during childhood and adulthood in psoriatic patients. Forty-five patients with psoriatic arthritis and 101 controls (patients with skin conditions considered to be "non-psychosomatic") were enrolled in the study. All participants completed a specific questionnaire measuring traumatic life experiences [Traumatic Antecedents Questionnaire (TAQ)]. The TAQ assesses positive personal experiences (competence and safety) and negative personal experiences (neglect, separation, secrets, emotional, physical and sexual abuse, trauma witnessing, other traumas and exposure to alcohol/drugs) from early childhood to adulthood. The patients with psoriatic arthritis exhibited lower mean scores of total positive experiences during late childhood (latency) as compared to the control group. Negative experiences during four developmental periods appeared more frequently in patients with psoriatic arthritis than in the controls. The most frequently reported negative experiences were neglect, emotional abuse, physical abuse, sexual abuse, alcohol/drug abuse and other traumas. The present findings add evidence to the relationship between retrospectively reported childhood experiences and psoriatic arthritis. Furthermore, a high amount of reported emotional and physical abuse occurs in patients with psoriatic arthritis during latency and adolescence.

Psoriasis vulgaris - an inflammatory skin disease and/or benign epidermal hyperplasia.

Psoriasis vulgaris (PV) is a systemic inflammatory disease in which immune and genetic factors are involved in the pathogenesis. Some treatment approaches in PV patients have been similar to therapy of some tumors. This fact has led to a new scientific approach to PV not only as an inflammatory disease, but also as a benign epidermal hyperplasia or a benign tumor. In this article, we hypothesize that there has been a parallel between some benign tumors and neoplasms and PV. The aim of this article is to present the approach to PV as an inflammatory disease as well as benign epidermal hyperplasia or tumor, and to introduce a new meaning.

Adhesion molecules in keratinocytes.

Adhesion molecules are proteins on the cell surface that are involved in the interactions between lymphocytes and antigen-presenting cells, especially in inflammatory skin diseases and autoimmune bullous disorders. Adhesion molecules include cadherins (subgroups E, N, P, M), integrins, selectins, and the immunoglobulin gene family. Cadherins E in the epidermis including desmocollin 1 and 2 and desmoglein 1 and 3 are essential transmembrane components of desmosome glycoproteins, which play a major role in bullous diseases, pemphigus in particular. Also important are integrin beta 1 alpha 1 and other integrins, which connect ligands of the collagen, laminin, and fibronectin. Selectins (E, P) are important for leukocyte migration on endothelial cells. Adhesion molecules from the immunoglobulin superfamily (intercellular adhesion molecule-1, 3 [ICAM-1,3]; vascular adhesion molecule-1 [VCAM-1]) have significant roles in the immune and inflammatory mechanisms.

Effect of progesterone and pregnancy on the development of varicose veins.

The aim of this study was to investigate the contribution of progesterone in the development of primary varicose veins on lower limbs during pregnancy. In 50 primiparae with varicose veins, serum progesterone level was quantitatively determined in the 14th week of pregnancy and results were compared with those obtained in a control group of 25 primiparae without visible varicose veins. The mean serum progesterone concentration recorded in pregnant women with dilated veins (159.9+/-15.8 nmol/L) was significantly higher as compared with the control group (159.9+/-15.8 nmol/L vs. 40.4+/-1.6 nmol/L; P<0.0001). These findings supported the role of hormonal factor in the development of varicose veins in women.

The role of CD4 and CD8 lymphocytes and macrophages in psoriasis vulgaris.

Current knowledge of the immunopathogenesis of psoriasis vulgaris is based on the crucial role of CD4 and CD8 lymphocytes. Also, the connection of activated lymphocytes with macrophages, especially dendritic cells and plasmacytoid dendritic cells, is considered to be significant. In the present study, the expression of CD4+ lymphocytes as well as CD8+ lymphocytes (P < 0.001) and macrophages (P < 0.001) was found to be significantly increased in lesional skin epidermis and dermis in psoriasis vulgaris patients as compared with healthy skin. These findings suggested a cascade or chain reaction with cells and cytokines playing an important role to be involved in the immunopathogenesis of psoriasis vulgaris.

The incidence of basal cell carcinoma in Croatia: an epidemiological study.

The aim of the study was to investigate the basal cell carcinoma (BCC) incidence in Croatia in the 2003-2005 period. Data were collected from University Department of Dermatology and Venereology, Zagreb University Hospital Center and National Cancer Registry. The age-specific incidence rate and age-standardized incidence rate were calculated per 100,000 inhabitants according to the latest population census in Croatia from 2001. In the study period, there were 7,244 BCC cases (3,519 men and 3,725 women) in Croatia. The crude incidence rate for the Croatian population of 100,000 was 54.9 for men and 53.9 for women. The age-standardized incidence rate (adjusted for the world standard population) was 33.6 for men and 24.5 for women. The head and neck were almost exclusive localizations of BCC. The highest BCC incidence was recorded in Zadar County. The incidence of BCC was high in both littoral and inland counties of Croatia. Study results will serve as reference figures on studying the trend of BCC incidence in Croatia and Europe in the forthcoming years.

The distinction between lesional and non-lesional skin in psoriasis vulgaris through expression of adhesion molecules ICAM-1 and VCAM-1.

Psoriasis vulgaris [pv] is a systemic inflammatory skin disease affecting 2-4% population. It is well known that pv affects some parts of the skin and also whole skin as in erythrodermic form. We still do not know why in pv some parts of the skin are affected and others are not. In our hypothesis we assumed that the whole skin is in <> position and non-lesional skin could become in every moment lesional. According to our hypothesis and also other author's research, high expression of adhesion molecules ICAM-1 and VCAM-1 in lesional as well as non-lesional skin in pv, supports this hypothesis, suggesting a significance of these molecules in pathogenesis of pv. Our hypothesis could be proved by immunohistochemical stain of ICAM-1 and VCAM-1 in lesional and non-lesional skin of pv patient in comparison with healthy skin.

Influence of PUVA and UVB radiation on expression of ICAM-1 and VCAM-1 molecules in psoriasis vulgaris.

The expression of adhesion molecules Intercellular adhesion molecule-1 (ICAM-1) and Vascular cell adhesion molecule-1 (VCAM-1) is increased in lesional and in non-lesional skin of psoriatic patients, and play role in pathogenesis of the disease. PUVA and UVB therapy are important treatments of psoriasis vulgaris. It has been demonstrated that UVA and UVB therapies reduce expression of these molecules. In this investigation, phototherapy was used to treat psoriatic patients. The expression of these molecules was examined by immunohistochemical method in lesional and non-lesional skin of 10 patients with psoriasis vulgaris before and after treatment. Results showed increased expression of ICAM-1 molecules in keratinocytes, in perivascular infiltrate--lymphocytes, and in endothelial cells. The expression of VCAM-1 molecules was also increased, although with less intensity then ICAM-1. After therapy, the expression of the adhesion molecules decreased together with a marked improvement of the disease. In conclusion, study demonstrated that phototherapy improves psoriasis vulgaris probably through mechanisms acting on the adhesions molecules. Adverse reactions due to intense or long lasting UVA (PUVA) and UVB therapies are immunosuppression and damage of DNA which can lead to development of non-melanocytic skin tumors like basal cell carcinoma and squamous cell carcinoma, as well as melanoma.

Molecular and genetic mechanisms in melanoma.

Recent studies have indicated an increasing incidence of melanoma worldwide. Although UV signature mutations are found rarely in melanoma cells, there is some evidence that intense intermittent exposure to sunlight can induce melanocyte tumorigenesis, and this is also observed after UV irradiation in some animals. The purpose of this paper is to review some of the most important mechanisms involved in the pathogenesis of this tumor. Genetic studies showed the familiar melanoma is linked to the mutation or deletion of the suppressor gene CDKN2A, and perhaps to CDK4. Studies showed that BRAF mutation is frequent in primary and metastatic melanoma cells but also in naevocytic nevi. This mutation activates the RAF/MEK pathway. Exposure to UV radiation induces immunosuppression. Recent investigations showed that chemokines, angiogenesis, metalloproteinases can play a role in the mechanism of metastasis. In spite of these advances the initiating events are still not completely understood. In conclusion, the pathogenesis of melanoma is very complex because numerous genetic and epigenetic factors are implicated in its development and progression, but some of the showed mechanisms can be targets for new therapies.

Phytophotodermatitis in Rijeka region, Croatia.

Contact with plants can cause phototoxic or rarely photoallergic reactions. Phototoxic dermatitis (photophytodermatitis) occurs after contact or ingestion of plants containing furocumarins i.e. psoralens and followed by sun exposure. Skin lesions develop usually after 24-48 hours with erythema, bulla formation, itch or pain, followed by a long lasting hyperpigmentation. Furocumarins can be linear i.e. psoralens (5-MOP, 8-MOP), or angular like angelicin and pimpinellin. Their binding to DNA causes cellular damage. This can happen in florists, gardeners, farmers, horticulturists, food handlers, and botanists. The plants causing phototoxic reaction can vary with the local flora but are commonly a member of the family apiaceae (formerly umbelliferae), family rutaceae, leguminosae and moraceae. The authors give special consideration to the phytophotodermatitis that appeared in their region in spring and summer during a three year period.