Dermatoscopy of nodular/plaque-type primary cutaneous T- and B-cell lymphomas: A retrospective comparative study with pseudolymphomas and tumoral/inflammatory mimickers by the International Dermoscopy Society.

BACKGROUND: Limited data on dermatoscopy of nodular/plaque-type T-/B-cell primary cutaneous lymphomas (PCLs) is available. OBJECTIVE: To describe dermatoscopic features of nodular/plaque-type PCLs, comparing them with those of clinical mimickers (pseudolymphomas, tumors, and inflammatory lesions) and investigating possible differences according to histologic subtypes. METHODS: Participants were invited to join this retrospective, multicenter case-control study by submitting histologically/immunohistochemically confirmed instances of nodular/plaque-type PCLs and controls. Standardized assessments of the dermatoscopic images and comparative analyses were performed. RESULTS: A total of 261 lesions were included (121 PCLs and 140 controls). Orange structureless areas were the strongest PCL dermatoscopic predictor on multivariate analysis compared with tumors and noninfiltrative inflammatory dermatoses. On the other hand, a positive association was found between PCLs and either unfocused linear vessels with branches or focal white structureless areas compared with infiltrative inflammatory dermatoses, whereas white lines were predictive of PCLs over pseudolymphomas. Differences in the vascular pattern were also seen between B- and T-cell PCLs and among B-cell PCL subtypes. LIMITATIONS: Retrospective design and the lack of a dermatoscopic-pathologic correlation analysis. CONCLUSION: Nodular/plaque-type PCLs display dermatoscopic clues, which may partially vary according to histologic subtype and whose diagnostic relevance depends on the considered clinical differential diagnoses.

NONMELANOMA SKIN CANCER IN A HEART TRANSPLANT PATIENT: A CASE REPORT AND REVIEW OF THE LITERATURE.

Nonmelanoma skin cancers (NMSC) are the most common malignancies in solid organ transplant recipients. The most common types of skin cancer in these patients are squamous cell carcinoma (SCC), followed by basal cell carcinoma. In immunosuppressed patients, specifically patients after solid organ transplantation, these carcinomas tend to be more aggressive and have a much higher incidence of metastasizing compared to general population. We present a case of a patient who developed numerous SCCs after successful heart transplantation. SCCs which occurred in our patient were mostly treated surgically. However, the lesion on the scalp relapsed after it had been treated surgically three times and therefore superficial x-ray radiation therapy was administered due to its localization and extensive size. In the next year, five more new SCCs occurred throughout the patient's body and all of them were removed surgically. Soon afterwards, the patient died from adenocarcinoma of the colon which rapidly progressed and metastasized.

B regulatory cells and monocyte subpopulations in patients with chronic graft-vs-host disease.

AIM: To assess the correlations of B regulatory cells (Bregs) and monocyte subsets in peripheral blood with the National Institutes of Health (NIH)-consensus-defined clinical manifestations of chronic graft-vs-host disease (cGvHD), in an attempt to establish their role as cellular biomarkers. METHODS: This multidisciplinary prospective study enrolled adult cGVHD patients treated in the University Hospital Center Zagreb and University of Zagreb School of Medicine. Immunophenotypic subpopulations of CD24highCD38high Bregs (CD27-, CD27+, and total) and monocyte (classical, intermediate, and non-classical) counts were correlated with demographic, transplant, and cGVHD-related data. Bivariate correlation analysis was performed to evaluate the correlations between Bregs and monocytes subsets and cGVHD organ involvement, as well as cGVHD severity and immunosuppression intensity. RESULTS: Twenty-two adult patients (54.5% female) with cGVHD were enrolled. The median (range) age was 44.5 years (24-65). All patients were transplanted for hematologic malignancies and 40.9% had severe NIH cGVHD global score. The median time from cGVHD diagnosis to the analysis was 16.6 months (0-176). The organ most frequently affected with cGVHD were the eyes (68.2%), skin (45.5%), lungs (45.5%), and liver (40.9%). Lower total and CD27-Bregs counts were correlated with worse cGVHD severity, higher immunosuppression intensity, and lung cGVHD, in terms of cell count, but also with skin cGVHD, in terms of percentages. Patients with liver and joint/fascia cGVHD had a lower percentage of non-classical monocytes and patients with more severe global NIH score had a higher classical monocytes count. CONCLUSION: Different organs affected by cGVHD are differently associated with different subpopulations of Bregs and monocytes.

High frequency of cutaneous manifestations including vitiligo and alopecia areata in a prospective cohort of patients with chronic graft-vs-host disease.

AIM: To determine the frequency and the characteristics of cutaneous manifestations, especially vitiligo and alopecia areata, in patients with chronic graft-vs-host disease (cGVHD). METHODS: 50 patients with cGVHD were prospectively enrolled in the observational study protocol and evaluated by an experienced dermatologist. The evaluation was focused on the clinical spectrum of skin and adnexal involvement, and the cutaneous GVHD score was determined according to National Institutes of Health (NIH) Consensus criteria. The presence of vitiligo, alopecia, xerosis, nail changes, and dyspigmentation was also assessed. RESULTS: Out of 50 cGVHD patients, 28 (56%) had skin involvement, and 27 of them (96%) had hypo and/or hyperpigmentations. 11 patients (39%) had a mild cutaneous NIH cGVHD score, 22% moderate, and 39% severe. 15 (30%) patients had nail changes and 10 (20%) had vitiligo or alopecia areata. Univariate analysis showed that patients with vitiligo/alopecia areata received more lines of prior systemic immunosuppressive therapy (P=0.043), had lower Karnofsky performance status (P=0.028), and had a higher B-cell number (P=0.005), platelet count (P=0.022), and total protein (P=0.024). Vitiligo and alopecia areata were associated with higher NIH skin score (P=0.001), higher intensity of immunosuppressive treatment (P=0.020), and total body irradiation conditioning (P=0.040). Multivariate regression model showed that patients with higher NIH skin scoring were 3.67 times more likely to have alopecia and/or vitiligo (odds ratio 3.67; 95% confidence interval 1.26-10.73), controlled for all other factors in the model (age at study entry, number of B-cells, platelet count, and global NIH score). CONCLUSION: These data indicate that vitiligo and alopecia areata occur more frequently in cGVHD than previously reported.

[CROATIAN SOCIETY FOR MEDICAL ONCOLOGY CLINICAL GUIDELINES FOR DIAGNOSIS, TREATMENT AND FOLLOW-UP OF PATIENTS WITH MELANOMA]. / KLINICKE PREPORUKE HRVATSKOG DRUSTVA ZA INTERNISTICKU ONKOLOGIJU HLZ-A ZA DIJAGNOZU, LIJECENJE I PRACENJE BOLESNIKA/CA OBOLJELIH OD MELANOMA KOZE.

Melanoma in the Western world has an increasing incidence. One of the most important factor for the increase in incidence is sporadic, uncontrolled exposure to the sun. The basis for the treatment of primary melanoma is surgical treatment. Treatment of metastatic disease of melanoma in recent years experienced significant changes. BRAF and MEK inhibitors, immunotherapy with programmed cell-death immune checkpoint inhibitors (anti-PD-1-antibodies) are new options for the treatment of metastatic disease. A mulitidisiplinary team of Croatian Society for Medical Oncology provides recommendations for diagnosis, treatment and follow-up of melanoma primarily driven to the discovery of new drugs and therapeutic options, that change the prognosis of patients with metastatic melanoma.

The Prognostic Value of Histopathological Features in Early-Stage Mycosis Fungoides: Insights from a Retrospective-Prospective Cohort Study.

Primary cutaneous lymphomas (PCLs), especially mycosis fungoides (MF), pose significant diagnostic and therapeutic challenges. This study aims to correlate initial histological features with the disease course and survival in MF patients. A retrospective-prospective cohort study was conducted on 83 patients diagnosed with early-stage MF at the Departments of Dermatovenerology and Pathology, UHC Zagreb, from January 2003 to December 2012. The analyzed histopathological parameters included lichenoid dermal lymphocyte infiltrate, Pautrier microabscesses, and lymphocyte atypia. Patients with more than 30 guardian lymphocytes per 100 keratinocytes exhibited worse overall and progression-free survival. Furthermore, those with over 50% atypical lymphocytes demonstrated a faster progression rate. A dense lichenoid dermal infiltrate and a high count of lymphocyte "keepers" significantly increased the mortality risk within five years of diagnosis. This study did not fully confirm the hypothesis regarding the prognostic value of large Pautrier microabscesses but highlighted the importance of dense lichenoid infiltrates. The study identified new potential histopathological prognostic factors in early-stage MF, suggesting the need for larger studies to confirm these findings. The identification of such predictors could enhance the prognostic stratification and guide more tailored therapeutic approaches for MF patients.

Treatment of plaque-psoriasis in HIV-positive patients.

Psoriasis is a chronic inflammatory disease that can often accompany human immunodeficiency virus (HIV) epidemics. Development of psoriasis in HIV patients is correlated with a decrease in CD4+ count. Significant variability in the clinical presentation of psoriasis makes it a challenging disease to diagnose. Furthermore, associated immunodeficiency complicates standard treatment with immunosuppressive and biological therapy. Articles that match the terms psoriasis and HIV were searched in MEDLINE and Embase and selected based on their relevance. Highly active antiretroviral therapy (HAART) is a medication regimen used to manage and treat HIV infection. In treating mild psoriasis in HIV-positive patients, topical agents combined with HAART are considered first-line therapy, followed by phototherapy. Second-line therapy includes oral retinoids, alone or combined. In treating challenging cases, apremilast has been used due to its lack of immunosuppressive effect. In case of progressive and refractory disease, limited data from studies suggest that immunosuppressive or biological therapy may be effective. Treatment of psoriasis in HIV patients remains a challenge, which is largely attributable to its complicated etiopathology and lack of an approved therapy option. In treating severe psoriasis, close collaboration with an infectious disease specialist is highly recommended. Further research is needed, preferably with an aim toward developing individualized therapy.

The Role of Digital Dermoscopy and Follow-Up in the Detection of Amelanotic/Hypomelanotic Melanoma in a Group of High-Risk Patients-Is It Useful?

The prognosis, outcome, and overall survival of melanoma patients improve with early diagnosis which has been facilitated in the past few decades with the introduction of dermoscopy. Further advancements in dermoscopic research, coupled with skilled, educated dermatologists in dermoscopy, have contributed to timely diagnoses. However, detecting amelanotic and hypomelanotic melanoma remains a challenge even to the most skilled experts because these melanomas can mimic inflammatory diseases, numerous benign lesions, and non-melanoma skin cancers. The list of the possible differential diagnoses can be long. Melanoma prediction without the pigment relies only on vascular criteria, and all classic dermoscopic algorithms have failed to fulfill our expectations. In fact, the diagnosis of amelanotic and hypomelanotic melanomas is very challenging, which is why every tool in detecting these lesions is of significance. This review aims to explore the current knowledge and the literature on the possibility of detecting amelanotic/hypomelanotic melanomas using sequential monitoring with digital dermoscopy and total body skin photography.

[Guidelines for the diagnosis and treatment of psoriasis]. / Smjernice za dijagnostiku i lijecenje vulgarne psorijaze.

Croatian dermatovenerological society of the Croatian Medical Association formed the working group which consists of leading experts for psoriasis in Croatia. After a critical analysis of relevant scientific papers, the working group has developed guidelines for the diagnosis and treatment of psoriasis.

Merkel Cell Carcinoma of Unknown Primary Origin.

Merkel cell carcinoma (MCC) is a rare and highly aggressive primary cutaneous neuroendocrine carcinoma most often occurring in the elderly. Risk factors include chronic sun exposure and immunosuppression (1). MCC is associated with frequent recurrences and a high metastatic potential and mortality rate (1). It is the second most common cause of skin-cancer-related death after melanoma. At primary diagnosis with an apparent cutaneous tumor, loco-regional metastases are present in up to 30% of patients, and 6-12% have distant metastatic disease (2-3). Up to 5% of cases present with unknown primary origin (4). Five-year overall survival for patients with advanced or metastatic disease is 13-18% (4). We report two cases of MCC presenting without primary cutaneous involvement; first at an unusual location in the adipose tissue of the right breast, and the second one with only a clinically positive left inguinal lymph node. In October 2018, a 78-year-old woman presented with a 15-week history of a painless solitary mass in the upper outer quadrant (UOQ) of the right breast with no visible cutaneous involvement. Her medical history included hypertension, dyslipidemia, and plaque psoriasis. She underwent ultrasound guided biopsy, and histopathology confirmed the diagnosis of metastatic MCC (mMCC). Positron emission tomography/computed tomography (PET/CT) scans showed increased standardized uptake values in the mass in the UOQ and an additional mass in the lower inner quadrant (Figure 1A). The patient underwent mastectomy and lymph node dissection of the right axilla. Histopathology confirmed mMCC and negative axillary lymph nodes. Regular follow-up (clinical examination, PET/CT scan, ultrasound, mammography) every 6 months revealed no disease recurrence during this 4-year period (Figure 1B). In September 2021, a 66-year-old man was referred to our Clinic with clinically detectable painful left inguinal lymphadenopathy. Excisional biopsy was performed, and histopathology confirmed the diagnosis of mMCC (Figure 2). After an extensive clinical and imaging evaluation (PET/CT scan), which confirmed disseminated disease (Figure 3A), initial treatment with the programmed cell death ligand 1 inhibitor (anti PD-L1) avelumab was proposed. The first cycle consisting of seven intravenous applications, and was applied in October 2021. After one year and completion of the third cycle of therapy, imaging assessment (PET-CT scan) detected a solitary lesion in the pancreas. Fine needle aspiration biopsy confirmed a distant metastasis of MCC that was later treated with stereotactic radiosurgery. The fourth cycle of immunotherapy was completed in March 2023. No treatment-related adverse events were noted during these 18 months of follow-up. Recent PET/CT scans demonstrated scaring tissue in the pancreas with no signs of locoregional or distant metastatic disease (Figure 3B). Management of MCC should be individualized based on the specific pattern of disease presentation. The presence of nodal disease is one of the most powerful predictors of overall survival and risk for developing distant metastatic disease (3-4). Multidisciplinary tumor board discussions are mandatory for the management of advanced MCC. New emerging treatment options have once again returned focus to this rare and highly-aggressive entity. Until recent years, mMCC was managed with extensive surgery, radiotherapy, or chemotherapy, but responses were not durable (1). Based on new clinical trials, immunotherapy has now become a rational and promising treatment option and is considered as first-line treatment in patients with advanced MCC (5). The management of patients with MCC of unknown primary origin should adhere to that for patients with an identifiable primary tumour (6). Although cutaneous manifestations are the hallmark of MCC, only a minority of cases have been reported in the literature without any cutaneous involvement (7-10). Our cases highlight this unusual presentation of MCC that could be misleading and contribute to delayed diagnosis. We therefore emphasize the importance of considering rare forms of malignancies such as MCC even in the absence of a primary cutaneous lesion.

Mycosis fungoides with large cell transformation (CD30+) and B-cell chronic lymphocytic leukemia.

Mycosis fugnoides (MF) is an indolent cutaneous T-cell lymphoma (CTLC) and is the most common of all cutaneous lymphomas. An increased risk for developing a second primary malignancy in patients with CTCL has been described in several studies, with a range from 1.04 to 2.4 (1-4). Caucasian males are at higher risk for MF development. MF is often diagnosed at ages between 55 and 67 years, and second malignancy usually occurs 5 or 6 years after the diagnosis of MF was established (5). The most common second primary malignancies include non-Hodgkin lymphoma (NHL), Hodgkin lymphoma (HL), lung carcinoma, bladder carcinoma, and melanoma. Even though a higher incidence rate of all NHL was described in patients with MF (15/1000) in comparison with the general population (0.32/1000), there are still only a few cases of B-cell NHL following MF described in the literature (6,7). We describe a rare case of a patient with MF and simultaneous large cell transformation (LCT) and a small B-cell lymphocytic lymphoma/chronic lymphocytic leukemia (B-CLL). In 2017, an 82-year-old man previously treated for MF presented with two fast growing tumorous lesions with ulceration on the right tight (Figure 1). A biopsy was performed, and a diagnosis of MF with LCT was established (Figure 2). During hospitalization, mild leukocytosis (12.2 x109 L-1), lymphocytosis (64%, total count of 7.81 x109 L-1), and anemia were found. Bone marrow biopsy was not performed due to low pain threshold. Bone marrow aspirate showed 70% of atypical lymphocytes and few "smudged" cells. Immunophenotyping by flow cytometry detected 49% monoclonal kappa+ B-cells with phenotypic features typical for B-CLL (CD5+, CD23+, kappa +). Of overall bone marrow cells, the ratio of monoclonal kappa + B-cells with the B-CLL phenotype was 21%. Immunophenotyping of peripheral blood showed up to 50% monoclonal kappa+ B-cells with phenotypic features typical for B-CLL (CD5+, CD23+, kappa +). Of overall peripheral blood cells, the ratio of monoclonal kappa+ B-cells with the B-CLL phenotype was 28%. Multi-sliced computed tomography was within normal ranges. A flow cytometry showed lymphocytes with phenotypic findings for CD20+ B-CLL. A diagnosis of MF with LCT (CD30+) clinical grade IIB (T3, N0, M0) and B-CLL was established. The patient was treated with fractionated superficial irradiation that resulted in applanation and regression of the tumorous lesions. No hematologic treatment was indicated other than regular follow-up. On dermatologic follow up for 2 years, the patient was stable, with no active skin lesions and no progression of MF. The patient was subsequently lost to follow-up. This is a rare case of MF with LCT and B-CLL occurring simultaneously. Large cell transformation in patients with MF can occur in 20-55% of advanced MF, as in our case, and this something physicians must be aware of, so repeated biopsies are advised (8). We also should keep in mind that patients with MF are at higher risk of developing a second malignancy. Of those second malignancies, a coexistence of lymphoproliferative disorders in two lineages, T-cell and B-cell, such as CTCL and B-CLL, is very uncommon, and only a few cases have been published (6,7,10). In most of these cases, CTCL preceded B-CLL, and with the only established explanation being increased risk of second malignancy in patients with CTCL (3,5,10). Other explanatory hypotheses include neoplastic stem cells, a genetic predisposition to malignancy, the use of immunosuppressive agents for the treatment for a first neoplasm, viral agents, and modulation of the B-cell system by monoclonal T-cell proliferation (1,5,6,9,10). Regular follow-up is mandatory for all patients with CTCL as well as MF, in order to identify the disease progression but for the timely detection of second malignancies.

Apremilast Use in Severe Psoriasis: Real-World Data from Central and Eastern Europe.

INTRODUCTION: The broad and sustained efficacy of apremilast for psoriasis has been demonstrated in randomized and real-world observational studies. Data from Central and Eastern Europe (CEE) are lacking. Moreover, apremilast use in this region is limited by country-specific reimbursement criteria. This is the first study to report data on the real-world use of apremilast in the region. METHODS: APPRECIATE (NCT02740218) was an observational, retrospective, cross-sectional study assessing psoriasis patients 6 (± 1) months after apremilast treatment initiation. The study aimed to describe the characteristics of patients with psoriasis receiving apremilast, estimate treatment outcomes, including Psoriasis Area Severity Index (PASI), Body Surface Area (BSA), and Dermatology Life Quality Index (DLQI), and assess dermatologists' and patients' perspectives on treatment using questionnaires including the Patient Benefit Index (PBI). Adverse event reports were taken from the medical records. RESULTS: Fifty patients (Croatia: 25; Czech Republic: 20; Slovenia: 5) were enrolled. In patients continuing apremilast at 6 (± 1) months, mean (± SD) PASI score was reduced from 16.2 ± 8.7 points at treatment initiation to 3.1 ± 5.2 at 6 (± 1) months; BSA from 11.9% ± 10.3% to 0.8% ± 0.9%; DLQI from 13.7 ± 7.4 points to 1.6 ± 3.2. PASI 75 was reached by 81% of patients. Physicians reported that the overall treatment success fulfilled their expectations in more than two thirds of patients (68%). At least three-quarters of patients reported apremilast had a quite or very high benefit on the needs they identified as being most important. Apremilast was well tolerated; no serious or fatal adverse events were identified. CONCLUSION: Apremilast was effective in reducing skin involvement and improving quality of life in CEE patients having severe disease. Treatment satisfaction among physicians and patients was very high. These data add to the growing body of evidence showing consistent effectiveness of apremilast across the continuum of psoriasis disease severity and manifestations. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT02740218.

Photodynamic therapy in dermatology: current treatments and implications.

This article provides an update on photodynamic therapy by discussing each of the essential components in sequence: mechanisms of action, common photosensitizers, typical light sources, and indications. In dermatology, photodynamic therapy (PDT) is mainly used in the treatment of superficial skin cancers: actinic keratoses, Bowen's disease and superficial basal cell carcinomas. However the range of indications has been expanding continuously. PDT is also used for the treatment of other oncological indications and non-malignant conditions such as acne vulgaris and photoaged skin. The 5-aminolevulinic acid (ALA) or its methyl ester (MAL) is applied topically as photosensitizer before activation with visible light. The advantages of topical PDT are: ability to treat multiple lesions simultaneously, low invasiveness, good tolerance and excellent cosmetic results.

Current Knowledge on Psoriasis During the Covid-19 Pandemic.

Psoriasis is a chronic inflammatory disease associated with a defective epidermal barrier, in which the immune system is already activated in lesional sites of the skin, and it is thus possible that affected individuals can have different immunologic rates of viral response. This is especially important in the era of the novel coronavirus disease (COVID-19) that is affecting the entire world. Patients with psoriasis are often receiving systemic therapy which includes immunosuppressive and biologic therapy, so this new infectious disease has raised concerns among dermatologists regarding psoriasis treatment. Some of the risk factors of psoriasis are obesity, diabetes mellitus, and hypertension - all of which are diseases linked with negative outcomes and higher severity of COVID-19. Psoriasis is mediated by inflammatory cells and proinflammatory cytokines such as IL-17, IL-23, IFN-γ, and TNF-α, and patients with skin diseases have been shown to be more susceptible to COVID-19 infection, but with a less severe disease course. As an anti-inflammatory agent, vitamin D could play a significant role in the future as a possible treatment for reducing the risk and severity of psoriasis and COVID-19. It has been suggested that patients treated with biologic therapy should continue treatment, as it has not been shown to cause severe complications of the COVID-19 disease. Preventive measures, including vaccination, should be taken to minimize the risk of infection and severity of the clinical outcome.

Dermatologic Adverse Events in Oncologic Therapies.

During recent decades, the number of patients diagnosed with cancer has been increasing. Conventional treatments, which comprise chemotherapy, radiotherapy, surgery, and hormonal treatment, represent improvements in effectiveness and safety of administration and continue to be the standard model of treating malignancies. Advances in oncology have enabled the development of newer therapies such as immunotherapy and targeted therapy. However, numerous adverse events continue to emerge, including dermatologic adverse events, which significantly impact the course of treatment, treatment outcomes, and patient quality of life. Alopecia occurs most commonly, along with mucositis, xerosis, pruritus, hyperpigmentation, acral erythema, nail changes, and many others. The early detection, monitoring, and adequate treatment of these adverse events could prevent reduction, interruption, or permanent discontinuation of oncologic therapies. Herein we review various dermatologic adverse events that may occur due to the therapy applied, present their possible treatments, and emphasize the need to evaluate their impact on patient quality of life.

Noninvasive Imaging Techniques for the Diagnosis of Nonmelanoma Skin Cancers.

Nonmelanoma skin cancers (NMSC), basal cell carcinoma (BCC), and cutaneous squamous cell carcinoma (cSCC) are the most common neoplasms worldwide. Their incidence has been continually rising. This is due to several risk factors such as chronic sun exposure, longer life expectancy, sun-damaged skin, genetic predisposition, and immunosuppression. NMSCs are curable cancers if detected early and treated appropriately. Clinical examination is the first step towards their diagnosis, with accuracy depending on clinician expertise. Dermoscopy has become an irreplaceable diagnostic procedure for clinical examination and improving diagnostic accuracy of skin cancers. However, skin biopsy with histopathological analysis remains the gold standard in establishing a definite diagnosis. Repeated biopsies, however, are not acceptable in patients with multiple suspicious lesions and are often redundant in cases of lesions that are challenging to identify, as they are often benign. Several medical imaging technologies are available as additional tools for noninvasive examination of NMSCs and include reflectance confocal microscopy (RCM), high-frequency ultrasound (HFUS), optical coherence tomography (OCT), Raman spectroscopy, fluorescence polarization, and others. These methods enable clinicians to establish more rapid and accurate diagnoses without the need for invasive biopsies and to achieve optimal treatment for NMSC. RCM an HFUS are discussed along with their clinical applications.

Systemic Therapies for Advanced Basal Cell and Cutaneous Squamous Cell Carcinomas: Novel Targeted Therapies and Immunotherapies.

Nonmelanoma skin cancers (NMSC), basal cell carcinoma (BCC), and cutaneous squamous cell carcinoma (cSCC) are the most common malignancies worldwide with a prevalence of epidemic proportions and continually rising global incidence rates, associated with increased morbidity rates and significant economic burden of their management. Although treatable cancers with low rates of metastasis and mortality, NMSCs reach an incurable state in small proportion of patients, becoming advanced, unresectable, or metastatic. Until recent years, patients with these conditions were considered for palliative radiotherapy and/or classical chemotherapies, which offer modest clinical benefit. Based on better understanding of the pathogenesis of these cancers, novel targeted therapies have been developed. We review novel systemic approaches for the treatment of aggressive forms of BCCs and cSCCs, with special emphasis on approved targeted molecular therapies and immunotherapies.

The genetics of psoriasis--selected novelties in 2008.

The genetic background of psoriasis is clearly demonstrated by the familial occurrence, data from epidemiological studies, twin studies, and results of genome-wide scan investigations. In the last years, molecular genetics analyses have permitted new insights into psoriasis. A number of studies indicate the likely genomic location of psoriasis susceptibility genes and suggest their possible identity and function. According to current concepts, psoriasis is caused by the interplay of multiple genes and different trigger factors, and the disease is classified in the group of genetically "complex" diseases. The first associated locus (PSORS1) resides within the HLA region (6p21.3). Strong association of HLA-Cw6 allele at this locus was first reported in Finnish population over 26 years ago. However, the exact location of PSORS1 gene remains controversial due to extensive linkage disequilibrium across the region. Two genes lying within this interval have been intensively studied with respect to their role in psoriasis susceptibility: HCR and corneodesmosin (CDSN). The precise location of PSORS 1 is under intense screening. Other candidate loci identified by genetic linkage research include PSORS 2 (17q25), PSORS 3 (4q34), PSORS 4 (1q21), PSORS 5 (3q21), PSORS 6 (19p13), PSORS 7 (1p32), PSORS 8 (16q) and PSORS 9 (4q31). Despite a large body of new data, the extent of genetic heterogeneity and the role of environmental triggers and modifier genes have not yet been clarified. The isolation of novel susceptibility genes will provide an insight into the precise pathways that control the disease. Such pathways will also reveal additional candidate genes that can be tested for molecular alterations resulting in the disease.