Search

BACKGROUND The incidence of cutaneous melanoma has risen faster than almost any other type of cancer in the last 50 years. Ultraviolet (UV) radiation and genetic susceptibility are the most important risk factors. OBJECTIVE We aimed to determine the epidemiologic indicators of melanoma in Hungary, a country with an estimated population of 9.8 million and an area of 93 030 km2. METHODS Anonymized patient records from the National Health Insurance Fund Management covering the entire population were used to determine the incidence and prevalence of melanoma in the counties of Hungary from 2013 to 2017. Altogether 20 030 melanoma cases were identified for inclusion in this study. RESULTS The prevalence of melanoma increased over the investigated period and was significantly higher among women than men. The incidence of melanoma stagnated during this period and the incidence rate was the highest among the elderly. Interestingly, the incidence was higher in males in the elderly population, while the incidence was higher in females in the younger (

Összefoglaló. Két fiatal nőbetegnél a valproátról lamotriginre történő gyógyszerátállítás során a 3–4. héten influenzaszerű prodromalis tüneteket követően toxikus epidermalis necrolysis (TEN), más néven Lyell-szindróma alakult ki. Mindkét beteg 5 napja kezdődött bőr- és nyálkahártyatünetekkel, kiterjedt hámleválást okozó hámnekrózissal került felvételre a Debreceni Egyetem Bőrgyógyászati Klinikájának Égési Intenzív Osztályára. Multidiszciplináris szupportív terápia mellett nagy dózisú szteroid- és immunglobulin-terápiát alkalmaztunk. A 37 éves nőbetegnél 3 hét után a kórkép fatális kimenetellel végződött. A 19 éves nőbeteg tünetei 4 hét intenzív terápia után szövődményekkel gyógyultak. A TEN ritka, gyógyszer által okozott, életet veszélyeztető, késői hiperszenzitivitási reakció. Patogenezisében a gyógyszermolekula, a humán leukocytaantigén (HLA) I. osztályú molekula és a T-sejt-receptor kóros interakciója szerepel. Kezelésében a legfontosabb a kiváltó gyógyszer elhagyása, valamint az azonnal kezdett komplett szupportív terápia alkalmazása. A specifikus kezelést illetően nincsenek egységes szakmai irányelvek. A veszélyes gyógyszerek titrált bevezetése csökkentheti a kialakuló hiperszenzitivitás súlyosságát, ezenfelül a beteg szoros követése és az adverz tünetek korai felismerése javíthatja a TEN kimenetelét. Orv Hetil. 2020; 161(46): 1959–1965. Summary. After switching from valproate to lamotrigine, on the 3rd–4th weeks, two young female patients developed flu-like prodromal symptoms, followed by the development of toxic epidermal necrolysis (TEN), also known as Lyell syndrome. Both patients were admitted to the Burn Intensive Care Unit of the Department of Dermatology, University of Debrecen with skin and mucosa symptoms; extensive epithelial death and detachment started 5 days earlier. In addition to multidisciplinary supportive treatment, high-dose corticosteroid and immunoglobulin therapy were administered. In the case of the 37-year-old female patient, the disease resulted in a fatal outcome. The 19-year-old patient healed with some sequelae. TEN is a rare, life-threatening delayed-type hypersensitivity reaction caused by drugs. Its pathogenesis involves an interaction between small-molecule drug, human leukocyte antigen class I molecule and T-cell receptor. The most important treatment is immediate withdrawal of potentially causative drugs and prompt application of supportive therapy. There is no standard guidance on specific treatment. Slow dose escalation of dangerous drugs can be beneficial in avoiding severe reactions, furthermore, close patient follow-up and early detection of the possible adverse reactions contribute to a more favourable outcome of TEN. Orv Hetil. 2020; 161(46): 1959–1965.

IntroductionThe incidence of melanoma has been increasing in the last decades. A retrospective Hungarian epidemiological study provided real-world data on incidence and mortality rates. There have been changing trends in incidence in Hungary in the last decade and mortality decreased, shifting mortality-to-incidence rate ratios (MIR). MIR is an indicator of cancer management quality.ObjectivesOur aim is to show the changes of melanoma MIR in Hungary between 2011 and 2018 and to compare the real-world evidence-based results of our Hungarian nationwide retrospective study with other European countries.MethodsMIR is calculated from the age-specific standardized incidence and mortality rates from our study. Annual MIR values are presented for the total population and for both sexes between 2011 and 2018, along with 95% confidence intervals. Comparison with European countries are shown for 2012 and 2018 based on the GLOBOCAN database and Eurostat health care expenditure per capita data.ResultsMIR decreased by 0.035 during the study years. The decrease was same in both sexes (0.031). Male had higher MIRs in all study years. In both 2012 and 2018, Hungarian MIR in both sexes was lower than the European Union average (males: 0.192 vs. 0.212 and 0.148 vs. 0.174 respectively, women: 0.107 vs. 0.129 and 0.083 vs. 0.107 respectively).DiscussionHungarian mortality-to-incidence ratio is the lowest in Central and Eastern Europe and is close to the level of Western and Northern European countries. The results are driven by the high number of new diagnosed melanoma cases.

BackgroundThe incidence of malignant melanoma has continually increased during the past few decades, however, certain reports suggest a recent change in trends. The aim of our study was to examine the epidemiology of melanoma in Hungary.MethodsThis nationwide, retrospective, longitudinal study included melanoma patients diagnosed between 1 January 2009 and 31 December 2019 using the databases of the National Health Insurance Fund (NHIF) and Central Statistical Office (CSO) of Hungary. Age-standardized incidence and cause-specific mortality rates were calculated.ResultsWe identified 2,426 and 2,414 new melanoma cases in 2011 and in 2019. Age-standardized incidence rates were higher in males and varied between 28.28 and 34.57/100,000 person-years (PYs), and between 22.63 and 26.72/100,000 PYs in females. We found 16.14 and 18.82% increases in male and female incidence rates from 2011 to 2015 (p=0.067 and pConclusionsWe observed a significant trend change in melanoma incidence in the female and total melanoma population, and a significant decrease in mortality in the total melanoma population. These changes may be attributed to intensive melanoma awareness campaigns as well as to the increase in screening and access to modern therapies.

BackgroundThe clinical response to immune checkpoint inhibitors (ICIs) in only part of the treated patients, in conjunction with the potentially serious side effects associated with this type of therapy, has emphasized the need to identify biomarkers to select patients who may benefit from ICI treatment. The aim of our study was to test human leukocyte antigen (HLA) class I and II expression in melanoma metastases as potential biomarkers of response to ipilimumab and survival in patients with metastatic melanoma, since these molecules play a crucial role in the interactions of malignant cells with host’s immune system.Materials and methodsHLA class I and II antigen expression level in pretreatment surgical tissue samples (50 lymph node and 35 cutaneous or subcutaneous metastases) from 30 patients was analyzed by immunohistochemical staining with monoclonal antibodies. Expression levels were correlated to intratumoral density of lymphocytes expressing cluster of differentiation (CD)8, CD45RO, CD4, forkhead box P3 (FOXP3) and/or programmed cell death protein 1 (PD-1), to clinical response to treatment, and to patients’ survival.ResultsHLA class I antigen expression level in lymph node metastases, but not in cutaneous or subcutaneous metastases was significantly correlated to density of CD8+ and CD45RO+ T cells and of lymphocytes expressing PD-1, as well as to clinical response and to patients’ survival.ConclusionsOur results corroborate the role of HLA class I expression level (alone or in combination with T-cell density values) as a predictive biomarker of response to ipilimumab in patients with melanoma. In addition, our results show that this association is influenced by the anatomic site of the metastasis used to measure the HLA class I antigen expression level.

Background The role of sun exposure in the development of melanoma and nonmelanoma skin cancers is known; however, there are limited data on the contribution of pretransplantation total sun burden (TSB) to the increased skin cancer risk in organ transplant recipients (OTRs). The importance of patient education about sun-safe behaviors is understood, but educations are often unsuccessful in OTRs. Methods A questionnaire-based cross-sectional study was performed with kidney transplant patients at a single academic center to assess the pre- and post-transplant sun exposure, sun protection habits, and skin cancers. Results Two hundred and twenty-one patients participated in the study. 13.1% developed at least one skin cancer. High total sun burden before transplantation was reported by 58.4%, and 65.2% reported education about increased skin cancer risk at the time of transplantation. However, that education did not lead to less sun exposure or better sun protection methods after transplantation. Overall, OTR related but not sun protection-guided lifestyle changes affecting OTRs after transplantation led to reduction in sun exposure. Conclusion Our findings highlight the need for more tailored, population-specific education programmes, even for patients who expect to receive a transplant in the future, and suggest the importance of pretransplantation TSB in determining the post-transplant skin cancer risk.

Introduction: Ultraviolet light induced DNA damage, combined with immunosuppression and inflammation are involved in the pathogenesis of actinic keratosis. Photodynamic therapy not only destroys dysplastic cells via tissue destruction and vascular shutdown, but also induces an acute local inflammatory response and activates both the innate and adaptive immune system. In our current work we aimed to compare immunohistochemistry features of inflammatory infiltrate of actinic keratoses after 5-aminolevulinic acid photodynamic therapy with or without Er:YAG laser resurfacing. Methods: Eleven patients with multiple actinic keratosis on the scalp, face, hands or forearms were treated by conventional and Er:YAG laser assisted 5-aminolevulinic acid PDT in split-site manner. Biopsies of AKs were taken before, 48 h and 3 months after the treatment. CD3, CD4, CD8, CD1a, Ki67 and p53 expressions were analyzed by immunohistochemical methods. Results: The number of p53 and Ki67 positive cells decreased significantly 3 months after treatment, but the abnormal cells were not eliminated totally. The number of CD1a+ Langerhans cells significantly decreased 48 h after both treatments, while CD8+ T cell count was significantly lower 3 months after Er:YAG laser assisted photodynamic therapy. However, the number of CD3+ and CD4+ T cells were not changed significantly 48 h and 3 months later. Conclusions: One session of 5-aminolevulinic acid photodynamic therapy even with Er:YAG laser pretreatment could not terminate actinic damage totally. Photodynamic therapy induced immunological changes. However further investigations are needed to answer how the composition of actinic keratosis’ immune infiltrate influence the effect of photodynamic therapy.

The authors present the case of a 59-year-old male patient, whose first kidney transplantation was in 1983 and the second in 2000. The first squamous cell carcinoma appeared on the skin 2 years after the first transplantation. Since 2003, at least two precancerous lesions or non-melanoma skin tumors have been removed surgically yearly. These cancers appeared predominantly on the sun-exposed skin, and were multiple. As these tumors could behave aggressively and prone to recurrence, complex treatment was applied, which included a switch in immunosuppressive drugs and the application of field therapies. The authors give an overview of these treatment options in relation to the case presentation, emphasizing that not only early detection and active treatment of the precancerous lesions and skin cancers are essential, but education of proper sun-protection methods and dermatology care are also important in order to avoid the development of these tumors. Orv. Hetil., 2016, 157(24), 971–976.

The use of photodynamic therapy is extensive, due to its antitumoral, antibacterial and photorejuvenation effects. It destroys tumor via direct cell destruction and indirectly via vascular shutdown, induction of acute local inflammatory response and activation of the immune system. Both innate and adaptive immune cells are involved in the immunological effects of photodynamic therapy. In addition to UV-induced DNA damage, inflammation and immunosuppression are also essential elements in the pathogenesis of actinic keratosis. Both immunosuppression induced by UV and defective immune response to dysplastic keratinocytes may be the target of photodynamic therapy to eliminate actinic keratosis. These elements are discussed in the present review, highlighting the possible mechanism of photodynamic therapy to effectively treat actinic keratosis.

Inflammatory cytokines can impair the skin barrier, but the question as to whether barrier alterations affect keratinocyte immune responses remains unanswered. The aim of this study was to investigate whether immune-mediated skin inflammation differs between severe atopic dermatitis patients with or without filaggrin mutation. The levels of filaggrin, inflammatory T helper 2 polarizing cytokines (thymic stromal lymphopoietin (TSLP) and interleukin 33 (IL-33)) and chemokine (C-C motif) ligand 27 (CCL27), histological severity markers, T and dendritic cell counts in biopsies from lesional skin of severe atopic dermatitis patients with and without filaggrin mutation and healthy skin were quantified by immunohistochemistry. The results were confirmed by quantitative PCR analyses. No significant differences were found between the 2 patient groups. Expression of atopic dermatitis-specific cytokines showed significant correlation with histological severity. These findings suggest that the immune-mediated skin inflammation (represented by keratinocyte-derived factors, T cell and dendritic cell counts) is similar in the 2 patient groups with severe atopic dermatitis, and that immune activation is connected to the severity of the disease rather than to the origin of barrier alterations.

SummaryBackground The most important risk factors for malignant melanoma are skin type I or II, large number of atypical naevi and a history of sunburn in childhood and adolescence. Methods A cross-sectional study was performed to assess skin type, number of pigmented lesions and sun protection behaviour in 1157 12- to 19-year-old Hungarian students at 20 primary and secondary schools in Debrecen, Hungary. After receiving dermatological training, 18 school doctors examined the students' skin. A questionnaire was completed by the students with the assistance of their parents about sun protection, sunburns and the use of sunbed. Data from 612 questionnaires were evaluated. Results Based on the doctors' evaluation, most of the pupils were classified as having skin type II and majority of them had 5–20 naevi, particularly on the trunk. Based on the student's response, 5.2% purposely sunbathed daily, 10.1% did not use any form of sun protection, 32.2% wore sun-protective clothing and 65.7% applied sunscreen generally. 6.9% used sunbed, and 74.0% previously experienced serious sunburn at least once. Indoor tanning statistically correlated with the number of melanocytic naevi. Conclusion A high prevalence of sunburn was reported by the students and some of them did not apply any sun protection methods but used sunbed at a critical age for developing melanoma at a later time. These data highlight the importance of educating children and parents about appropriate sun protection.

Ultraviolet (UV) light is absorbed by nucleic acids, proteins or other endogenous chromophores, such as porphyrins, flavins and melanin, triggering biological processes in skin cells. Both UV-induced mutations in melanocytes and changes in the immune microenvironment are understood to play a role in the development of cutaneous melanoma. The degree of UV-induced stress and the protection against this stress are influenced by both intracellular and intercellular molecular interactions. The present review summarizes the known major molecular biological changes induced by UV light in the skin that play a role in melanoma initiation and promotion. Nevertheless, cutaneous melanoma is not a homogenous disease, and the interaction of variable environmental exposure and different genetic susceptibility and other host factors lead to the formation of melanomas with different biological behavior and clinical characteristics. This review highlights the challenges in the understanding of how UV radiation contributes to the formation of cutaneous melanoma, and reviews the new results of photobiology and their link to tumor genetics and tumor immunology with potential implications on melanoma prevention and therapeutic strategies. The information presented here is expected to add clarity to ongoing research efforts in this field to aid the development of novel strategies to prevent and treat melanoma.

Monoclonal antibodies targeting immune checkpoints are gaining ground in the treatment of melanoma and other cancers, and considerable effort is made to identify biomarkers predicting the efficacy of these therapies. Our retrospective study was performed on surgical tissue samples (52 lymph nodes and 34 cutaneous/subcutaneous metastases) from 30 patients with metastatic melanoma treated with ipilimumab. Using a panel of 11 antibodies against different immune cell types, intratumoral immune cell densities were determined and evaluated in relation to response to ipilimumab treatment and disease outcome. For most markers studied, median immune cell densities were at least two times higher in lymph node metastases compared to skin/subcutaneous ones; therefore, the prognostic and predictive associations of immune cell infiltration were evaluated separately in the two groups of metastases as well as in all samples as a whole. Higher prevalence of several immune cell types was seen in lymph node metastases of the responders compared to non-responders, particularly FOXP3+ cells and CD8+ T lymphocytes. In subcutaneous or cutaneous metastases, on the other hand, significant difference could be observed only in the case of CD16 and CD68. Associations of labeled cell densities with survival were also found for most cell types studied in nodal metastases, and for CD16+ and CD68+ cells in skin/s.c. metastatic cases. Our results corroborate the previous findings suggesting an association between an immunologically active tumor microenvironment and response to ipilimumab treatment, and propose new potential biomarkers for predicting treatment efficacy and disease outcome.

In a recent work, we have proposed a novel way to approximate point sets with grids using the LLL algorithm, which operates in polynomial time. Now, we show how this approach can be applied to pattern recognition purposes with interpreting the rate of approximation as a new feature for regularity measurement. Our practical problem is the characterization of pigment networks in skin lesions. For this task we also introduce a novel image processing method for the extraction of the pigment network. Then, we show how our grid approximation framework can be applied with specializing it for the recognition of hexagonal patterns. The classification performance of our approach for the pigment network characterization problem is measured on a database annotated by a clinical expert. Throughout the paper we address several practical issues that may help to apply our general framework to other practical tasks, as well.

Background The formation of metastases and the efficacy of systemic therapies in cutaneous malignant melanoma (CMM) depend on the characteristics of the tumour cells and the host immune response. Aberrant expression of metallothionein (MT) has been observed in several types of cancers with poor prognoses. Objective To perform an immunohistochemical study on primary CMM comparing the MT expression of tumours without metastases (n = 23) to that of samples with haematogenous metastases (n = 23) and to examine the correlation between MT staining and immunological markers relevant in CMM progression. Methods The immunohistochemical labelling of different tumour sections was analysed using tissue microarrays for the evaluation of the suitability of this method in future studies. Results Our results suggest that MT overexpression is significantly more frequent in primary CMM with haematogenous metastases (P = 0.018) and that the overexpression is independent of the Breslow tumour thickness (R = 0.102, P = 0.501). Interestingly, MT overexpression of the tumour cells was correlated with the presence of tumour-infiltrating CD68+ macrophages (P = 0.003), a known predictive factor for melanoma progression, thereby suggesting a role for MT in the development of a defective host immune response. Furthermore, the presence of CD163+ macrophages infiltrating the tumours correlated with metastasis formation (P

Recently, sunlight-induced damage of healthy human skin, including skin malignancies and a large scale of photodermatoses representing a diverse group of diseases, have increased in childhood as a result of unfavorable environmental changes. This article yields an overview of the diagnosis, the clinical features and the treatment of these conditions and disorders and also reveals perspectives. Some diseases are more frequent in the pediatric population than in adulthood, whereas others heal spontaneously during adolescence and vice versa. The majority of cases are idiopathic photodermatoses, mainly polymorphic light eruption. Photosensitivity may be an early symptom of genetic disorders, such as porphyria, or very rare genophotodermatoses. Photosensitivity, secondary to topical or systemic external agents as well as photoexacerbated dermatoses, is not so frequent in childhood. Effective photoprotection is crucial.

Aim: It is not clear whether the mutations in hemochromatosis (HFE) gene and hepatitis C virus (HCV) infection act independently in the pathogenesis of porphyria cutanea tarda (PCT). The prevalence of both risk factors varies greatly in different parts of the world. PCT patients from Hungary were evaluated to assess both factors. Methods: The prevalence of C282Y and H63D mutations in the HFE gene was determined in 50 PCT patients and compared with the reported control frequencies. Furthermore, the presence of HCV infection was determined and related to the patients' HFE gene status. Results: The C282Y mutation was found in 8/50 cases (three homozygotes and five heterozygotes), with an 11% allele frequency (vs. 3.8% control) (P

Background The precise role of total body 18F-fluorodeoxyglucose-positron emission tomography/computed tomography (PET/CT) in the clinical management of patients with cutaneous malignant melanoma (CMM) is not well established. Objective The purpose of this study was to investigate the diagnostic accuracy of PET/CT in early- and late-stage patients with high-risk CMM. Methods We retrospectively analysed various imaging, histopathological and clinical data from 97 patients also examined by PET/CT during a 5-year period (2007–2011). Three groups were assessed: stage I/II, resected stage III and unresectable stage III/stage IV. Results The median follow-up time of living patients was 43.48 ± 19.67 (15–142) months. We observed a high diagnostic accuracy in all stages (91.3%, 92.5% and 96.2% respectively). PET/CT appeared to be reliable diagnostic tool even for the detection of small lymph node metastases. PET/CT was informative in 14 of 19 cases wherein another imaging examination provided inconclusive results regarding lesion dignity. However, PET/CT was less suitable for properly evaluating the dignity of a lung lesion. A true positive scan was twice as likely in clinically negative patients with resected stage III disease than in patients with stage I/II disease (35.9% and 14.5%, P = 0.007). Conclusions These results confirm that PET/CT is an important diagnostic tool in the management of patients with high-risk CMM, but it cannot replace the standard of care examinations. More accurate clinicopathological and timing criteria must be defined to best utilize the advantages of this imaging method.

Photosensitivity in childhood is caused by a diverse group of diseases. It usually indicates idiopathic photodermatoses, first of all polymorphic light eruption. It may be an early symptom of genetic disorders such as porphyria or very rare genophotodermatoses. Photosensitivity secondary to topical or systemic external agents as well as photoexacerbated dermatoses is not so frequent in childhood. Here we present our experience with childhood photosensitivity skin diseases collected over a 40-year period.