Caucasians with acral lentiginous melanoma have the same outcome as patients with stage- and limb-matched superficial spreading melanoma

$\bf Purpose$ Acral lentiginous melanoma (ALM), a relatively rare subtype of cutaneous melanoma, has been reported to have a worse prognosis than other melanomas. We aimed to assess clinical findings in Caucasian ALM patients and compare the data with a matched cohort of superficial spreading melanoma (SSM) patients. $\bf Methods$ We studied 63 patients with ALM and 63 randomly stage- and limb-matched patients with SSM (non-ALM). In both cohorts, guideline-adjusted diagnosis, treatment and follow-up were performed. $\bf Results$ We did not observe differences in prognostic factors (e.g., tumor thickness, ulceration) between the two cohorts. Both in ALM and non-ALM patients positive sentinel lymph node was a significant independent predictor for disease relapse and melanoma-specific death. However, disease relapse and melanoma-specific death rates did not significantly differ between ALM and non-ALM patients. An overall 5-year melanoma-specific survival of 82.5% and 81% was observed in ALM and non-ALM patients, respectively. $\bf Conclusions$ Our data confirm that patients with ALM have no worse outcome than non-ALM patients when correcting for significant prognostic factors. Hence, the reportedly high rates of fatal ALM cases should not be ascribed to pathobiological differences between ALM and non-ALM but are most likely are a consequence of a delay in diagnosis and thus advanced stage of ALM

Model for end-stage liver disease correlates with disease relapse and death of patients with Merkel cell carcinoma

Merkel cell carcinoma (MCC) is a highly malignant skin tumor that occurs mainly in elderly and/or immunosuppressed patients. MCC prognosis has been significantly improved by the introduction of immune checkpoint inhibitor treatment. Recently, blood-based biomarkers have been investigated that can potentially predict the outcome of MCC patients. In this context, parameters of liver scores have not yet been investigated. We retrospectively recruited 47 MCC patients with available relevant laboratory data at primary diagnosis. At this time, we investigated blood-based scores as follows: model for end-stage liver disease (MELD), aspartate aminotransferase/platelet count ratio index (APRI), and the alanine transaminase/aspartate aminotransferase ratio (De Ritis ratio). MCC relapse was negatively correlated with the De Ritis score (r = −0.3, $\it p$ = 0.024) and positively correlated with the MELD score (r = 0.3, $\it p$ = 0.035). Moreover, MCC-specific death positively correlated with CCI score (r = 0.4, $\it p$ = 0.01) and MELD score (r = 0.4, $\it p$ = 0.003). In multivariable analysis, the MELD score remained in the regression model as significant independent predictor for MCC relapse (hazard ratio: 1.16 (95% CI 1.04 to 1.29; $\it p$ = 0.008) and MCC-specific death (hazard ratio: 1.2 (95% CI 1.04 to 1.3; $\it p$ = 0.009). We observed for the first time that the MELD score appears to independently predict both MCC relapse and MCC-specific death. These results should be further investigated in larger prospective studies

Multivariate analysis of prognostic factors in patients with nodular melanoma

$\bf Purpose$ Nodular melanoma (NM) is associated with worse disease outcome when compared to superficial spreading melanoma (SSM). We aimed to perform a single-center analysis of prognostic factors in patients with NM and compare the data with SSM patients. $\bf Methods$ We studied 228 patients with NN and 396 patients with SSM. Patients with in situ melanomas or stage IV at diagnosis were not included in the study. Data were analyzed using the Mann–Whitney test, Chi-square test, Kaplan–Meier curves including the log-rank test, and logistic regression model. $\bf Results$ When compared to patients with SSM, patients with NM had less likely lower Clark level, higher tumor thickness, less likely tumor regression, more often ulcerated tumors, and less likely a history of precursor lesions such as a nevus. Within a 5-year follow-up we observed significantly more disease relapses and deaths in NM patients than in SSM patients. On multivariate analysis, disease relapse in NM patients was independently predicted by tumor thickness and positive SLNB, whereas melanoma-specific death of NM patients was independently predicted by male sex and tumor thickness. Histologic regression also remained in the logistic regression model as a significant independent negative predictor of NM death. $\bf Conclusions$ We did not observe that NM subtype was per se a significant independent predictor for disease relapse or melanoma-specific death. Among the well-known prognostic factors such as tumor thickness and male sex, NM is also associated with other unfavorable factors such as absence of regression

Waiving subsequent complete lymph node dissection in melanoma patients with positive sentinel lymph node does not result in worse outcome on 20-year analysis

The aim of the present study was to investigate long-term outcomes of melanoma patients who had micrometastasis on sentinel lymph node (SLN) biopsy. We focused on the comparison between melanoma patients with and without complete lymph node dissection (CLND) following a positive SLN biopsy result. Patients without CLND did not significantly differ from patients with CLND in regard to age, gender, tumor thickness, tumor ulceration, capsule infiltration of SLN, and invasion level of SLN. On 10-year analysis, we did not observe a significantly increased risk for melanoma relapse or melanoma-specific death in patients who did not undergo CLND after the detection of micrometastases on SLN biopsy. On 20-year analysis, again, the patients without CLND had no significantly increased risk of melanoma relapse and worse melanoma-specific survival. Hence, our 10-year survival data confirm the current notion that waiving CLND in SLN-positive patients does not result in clinical disadvantages with respect to melanoma-specific survival. For the first time, we demonstrate on 20-year survival analysis that relapse rates and melanoma-specific survival does not significantly differ between patients with or without CLND on long-term follow-up

Diclofenac Sodium 3% in hyaluronic acid 2.5% gel significantly diminishes the actinic keratosis area and severity index

$\textbf {Background/Aims:}$ Actinic keratosis area and severity index (AKASI) is a new assessment tool to quantify the severity of actinic damage on the head. Thus far, it has not been evaluated in monitoring the efficacy of field-directed topical treatments in actinic keratosis (AK) in routine clinical practice. Thus, the aim of this study was to determine treatment outcomes by using AKASI 3 months after the initiation of topical application of diclofenac sodium 3% in hyaluronic acid 2.5% gel (DFS) in patients with AKs on the head. $\textbf {Methods:}$ We performed a retrospective analysis of patients with AKs who had AKASI scores prior to and after treatment with DFS. $\textbf {Results:}$ Of the 24 patients included, 20 (83.3%) showed an improvement in AKASI, 2 (8.3%) a stable AKASI, and 2 (8.3%) a worsening of AKASI after a median (interquartile range) follow-up period of 91.5 days (89.8–104.3). The median AKASI reduction was 31.4% (16.7–59.1). The Wilcoxon test showed significant differences ($\it p$ = 0.0008) between baseline and posttreatment AKASI values. $\textbf {Conclusions:}$ AKASI is an easy-to-use quantitative tool for assessing the treatment outcome of field-directed therapies. Field-directed therapies of AK should no longer be monitored by assessments based on lesion counts alone

The role of hormones in hidradenitis suppurativa

Hidradenitis suppurativa (HS) is a chronic inflammatory disease manifesting in inverse body regions. In a systematic review, the role of hormones in HS will be presented to better understand the pathomechanisms of HS. The review is based on the PRISMA criteria. Systematic research was carried out using keywords. Subsequently, the data were analyzed based on the clinical response and other relevant information. The main focus of our systematic review was on HS manifestation, exacerbation, sex hormones, antiandrogen therapy, thyroid function, polycystic ovary syndrome, insulin resistance, and adipokines. In HS, there appears to be a dysregulated adipokine release that is shifted towards pro-inflammatory adipokines. Insulin resistance is significantly more common in HS than in healthy patients regardless of BMI, age, and gender. Insulin resistance in HS patients leads to further cardiovascular disease. The mechanism of insulin resistance and role of adipokines should be investigated in future studies to better provide the pathomechanisms of HS. The role of androgens seems to be important in a certain subgroup of female patients. Anti-androgenic therapy can be useful and helpful in some patients. However, further studies are needed to better understand the hormonal relationship in HS

The antineoplastic effect of dimethyl fumarate on virus-negative Merkel cell carcinoma cell lines

Merkel cell carcinoma (MCC) is a rare, difficult-to-treat skin cancer once immunotherapy has failed. MCC is associated either with the clonal integration of the Merkel cell polyomavirus (MCPyV) or mutagenic UV-radiation. Fumaric acid esters, including dimethyl fumarate (DMF), have been shown to inhibit cell growth in cutaneous melanoma and lymphoma. We aimed to explore the effects of DMF on MCPyV-negative MCC cell lines. Three MCC cell lines (MCC13, MCC14.2, and MCC26) were treated with different doses of DMF. The cytotoxic effects and cell proliferation were assessed by the MTT cytotoxicity assay and BrdU proliferation assay at different time points. A significant reduction in cell viability and proliferation were demonstrated for all the cell lines used, with DMF proving to be effective

Primary thyroid dysfunction is prevalent in hidradenitis suppurativa and marked by a signature of Hhypothyroid graves’ disease

Hidradenitis suppurativa (HS) is a chronic skin disease that can have an association with endocrine disorders. There is conflicting information in the literature regarding the role of the thyroid gland in HS. This study aimed to close this knowledge gap and investigate how thyroid disease is involved in patients with HS. We carried out a case–control study with a total of 160 patients, of whom 108 were patients with HS and 52 were controls matched for age and sex. Parametric and non-parametric methods were used to analyze the results. We calculated structural parameters of thyroid homeostasis to detect subclinical thyroid disease, non-thyroid disease syndrome and other forms. The severity of HS was not associated with thyroid hormone levels and antibodies ($\it p$ > 0.05). HS patients with or without hypothyroidism had decreased FT4 levels and a decreased thyroid secretory capacity (SPINA-GT). Titers of TSH receptor autoantibodies (TRAb) were significantly higher in smoking HS patients compared to non-smokers (median: 1.18 vs. 1.08; $\it p$ = 0.042). The rate of subclinical hypothyroidism was significantly higher in HS patients; thus, subclinical hypothyroidism is an important comorbidity of HS ($\it p$ < 0.05). Further studies are needed to investigate whether the chronic inflammation of HS is a cause of increased rates of (subclinical) hypothyroidism

Cancer and immune checkpoint inhibitor treatment in the era of SARS-CoV-2 infection

Whether cancer patients receiving immune checkpoint inhibitors (ICI) are at an increased risk of severe infection and mortality during the corona pandemic is a hotly debated topic that will continue to evolve. Here, we summarize and discuss current studies regarding COVID-19 and anti-cancer treatment with an emphasis on ICI. Importantly, several lines of evidence suggest that patients currently treated with ICI do not display an increased vulnerability to infection with SARS-CoV-2. Data regarding morbidity and mortality associated with COVID-19 in cancer patients receiving ICI are less clear and often conflicting. Although mostly based on experimental data, it is possible that ICI can promote the exacerbated immune response associated with adverse outcome in COVID-19 patients. On the other hand, mounting evidence suggests that ICI might even be useful in the treatment of viral infections by preventing or ameliorating T cell exhaustion. In this context, the right timing of treatment might be essential. Nevertheless, some cancer patients treated with ICI experience autoimmune-related side effects that require the use of immunosuppressive therapies, which in turn may promote a severe course of infection with SARS-CoV-2. Although there is clear evidence that withholding ICI will have more serious consequences, further studies are urgently needed in to better evaluate the effects of ICI in patients with COVID-19 and the use of ICI during the corona pandemic in general

Increased expression profile of NCSTN, Notch and PI3K/AKT3 in hidradenitis suppurativa

$\bf Background$ In a small number of kindreds with familial hidradenitis suppurativa (HS) different mutations of NCSTN (nicastrin) have been identified. Blocking of NCSTN leads to impairment of the Notch and PI3K/AKT signalling pathway, which is assumed to play a pathogenic role in HS. However, very limited data are available concerning expression levels of these pathway components in HS skin. $\bf Objectives$ To analyse the mRNA and protein expression of NCSTN, Notch1–3, PIK3R3 and AKT3 in HS. $\bf Methods$ Skin samples from healthy controls, lesional and perilesional skin of HS patients with and without a positive family history were analysed by quantitative real-time RT-PCR and immunohistochemistry. Univariate statistical analyses were conducted regarding association between expression levels and patient's characteristics. $\bf Results$ Expression levels of all investigated genes showed significantly higher levels in lesional HS skin compared with healthy controls. Univariate analysis showed no association between a positive family history and mRNA expression levels. Perilesional HS skin of patients with mild disease severity (Hurley I) showed significant higher mRNA expression levels of the investigated pathway components compared to moderate (Hurley II) and severe disease (Hurley III). $\bf Conclusion$ We found no evidence for diminished expression levels of the Notch signalling. In contrast, the NCSTN, Notch and PI3K/AKT signalling components are overexpressed in HS. Future research is needed to investigate a possible pathogenetic role or to reveal a coactivation of these overexpressed components during inflammatory response in HS