Dermatoscopic patterns of cutaneous metastases: A multicentre cross-sectional study of the International Dermoscopy Society.

BACKGROUND: The detection of cutaneous metastases (CMs) from various primary tumours represents a diagnostic challenge. OBJECTIVES: Our aim was to evaluate the general characteristics and dermatoscopic features of CMs from different primary tumours. METHODS: Retrospective, multicentre, descriptive, cross-sectional study of biopsy-proven CMs. RESULTS: We included 583 patients (247 females, median age: 64 years, 25%-75% percentiles: 54-74 years) with 632 CMs, of which 52.2% (n = 330) were local, and 26.7% (n = 169) were distant. The most common primary tumours were melanomas (n = 474) and breast cancer (n = 59). Most non-melanoma CMs were non-pigmented (n = 151, 95.6%). Of 169 distant metastases, 54 (32.0%) appeared on the head and neck region. On dermatoscopy, pigmented melanoma metastases were frequently structureless blue (63.6%, n = 201), while amelanotic metastases were typified by linear serpentine vessels and a white structureless pattern. No significant difference was found between amelanotic melanoma metastases and CMs of other primary tumours. CONCLUSIONS: The head and neck area is a common site for distant CMs. Our study confirms that most pigmented melanoma metastasis are structureless blue on dermatoscopy and may mimic blue nevi. Amelanotic metastases are typified by linear serpentine vessels and a white structureless pattern, regardless of the primary tumour.

Prognostic Value of Lactate Dehydrogenase in Patients with Melanoma Treated with Pembrolizumab.

INTRODUCTION: Elevated LDH levels have been extensively reported as a biomarker of poorer outcome in patients with melanoma during the chemotherapeutic era. The role of LDH level as a prognostic factor for treatment outcomes in patients with metastatic melanoma treated with immunooncological therapy has also been reported but requires further analysis. OBJECTIVES: In this study, we aimed to evaluate the prognostic value of lactate dehydrogenase (LDH) among patients with metastatic and unresectable melanoma treated with pembrolizumab in terms of progression-free survival (PFS). METHODS: The study included 59 patients with unresectable and metastatic melanoma treated with pembrolizumab. A comparison was performed between patients with normal and elevated levels of LDH in terms of PFS, with subgroup analysis. RESULTS: There was a significant reduction in PFS among patients with elevated levels of LDH compared with patients with normal levels of LDH (NR vs. 5 months; P=0.02). Patients with elevated LDH levels were older (P=0.01), with liver metastasis (P=0.004), and with less frequent CNS deposits (P=0.028). CONCLUSION: Although novel agents improved outcomes in patients with melanoma, high levels of LDH persist as an independent prognostic biomarker of poor prognosis.

Unusual Clinical Presentation of Giant Extragenital Condyloma.

Dear editor, Condylomata accuminatum (CA) is a human papillomavirus (HPV) related sexually transmitted infection (STI), clinically characterized by solitary or even clustered dark red or pink lesions solely affecting the anogenital area (1). CA involving the extragenital, non-mucosal skin has been sporadically reported (2-4). Diagnosis of CA is usually straightforward when the lesions are located on the anogenital area. However, involvement of extragenital skin may pose a diagnostic challenge. Herein, we report a rare case of giant linear extragenital CA without coexisting genital lesions, diagnosed with a synergic intervention of dermatoscopy and clinics. A 70-year-old Caucasian man was referred to our department for an atypical asymptomatic seborrheic keratosis presenting as a linear verrucous plaque (20 × 2 cm) with few solitary reddish satellite papules on the abdomen (Figure 1, a). No similar lesions were present in both cutaneous and mucosal districts. Medical history was unremarkable, and the patient denied having recent sexual intercourse or any history of condylomas. Remarkably, the patient underwent a diet in the last 8 months that resulted in a loss of 30 kg. We employed dermatoscopy to further assess the lesions, highlighting a finger-like pattern on the main lesion (Figure 1, c), while satellite lesions presented a mosaic pattern (Figure 1, b). The clinical appearance and these dermatoscopic findings were suggestive of condyloma acuminatum (CA), but due to its extraordinary presentation we also performed an incisional biopsy. Histopathological examination reviled features compatible with the diagnosis of CA (Figure 1, d, e). To better characterized the HPV genotype (high-risk and low-risk HPV) a polymerase chain reaction (PCR) from lesional tissue sample was performed and found HPV type 6 positivity. The lesions were successfully removed by electrosurgery. Regular follow-up was scheduled. Sexually transmitted infections (STIs) were also screened, namely syphilis, gonorrhea, chlamydia trachomatis, and HIV status. In addition, laboratory tests and imaging examinations (radiography of the chest and ultrasound examination of the abdomen) revealed no pathological findings. CA involving the extragenital skin has been reported within intertriginous areas, including the inframammary fold, the groin, and the axillary vault, as well as mucosal surface such as intraoral and conjunctival mucosa (1-5). In most cases, extragenital CA coexisted with genital lesions. Staples et al. reported three obese patients with extragenital CA on the skin of the abdominal pannus (3). However, all of the patients had involvement of the inguinal folds, from where the CA had extended. Generally, CA is acquired by genital, oral, or anal sexual contact. Among the wide spectrum of HPV genotypes, types 6 and 11 are responsible of 90% of CA (1). Our paradigmatic case allows us reflect on the concept of transitory immune dysregulation due to a significant amount of weight loss, and the position of the lesions in particular seems to suggest that frictional triggers may disrupt the barrier integrity, leading to higher probability of infection. Dermoscopy is a noninvasive diagnostic tool with a significant role in the assessment of melanocytic and non-melanocytic skin tumors. Furthermore, the utility of dermatoscopy has expanded to the field of inflammatory and infectious skin disease, where dermoscopy enhances the differential diagnosis between them. Seborrheic keratosis, as the most common benign epithelial tumor, can occur anywhere in the skin excluding the palms, soles, and mucosa (6). In the anogenital area, seborrheic keratosis usually resembles CA. However, dermatoscopically, seborrheic keratosis can be immediately identified by the presence of milia-like cysts, comedo-like openings, fissures, finger-print structures, and sharply demarcated borders (6). In contrast, reports of CA dermoscopy suggested four different dermoscopic patterns: fingerlike, mosaic, knoblike, and the most commonly, an unspecific pattern (7). Our case showed that dermoscopy of extragenital CA presented a mosaic pattern in an early stage of CA, while fully developed lesions revealed a fingerlike pattern, as has previously been reported by Dong et al. (7), where two different stages of clinical development of CA exhibit distinctive dermoscopic patterns, which correlates with our case. We did not observe the typical dermoscopic features of seborrheic keratosis. CA arising in an extragenital area is very rare and perhaps also underestimated. Thus, dermatologists should be aware of this unusual presentation even in the absence of genital HPV involvement. Moreover, dermoscopy may facilitate CA recognition in a such uncommon location. To our knowledge, this is the first report of extragenital condyloma acuminatum documented dermoscopically.

Anthocyanins Protect Hepatocytes against CCl4-Induced Acute Liver Injury in Rats by Inhibiting Pro-inflammatory mediators, Polyamine Catabolism, Lipocalin-2, and Excessive Proliferation of Kupffer Cells.

: This study examined the hepatoprotective and anti-inflammatory effects of anthocyanins from Vaccinim myrtillus (bilberry) fruit extract on the acute liver failure caused by carbon tetrachloride-CCl4 (3 mL/kg, i.p.). The preventive treatment of the bilberry extract (200 mg anthocyanins/kg, orally, 7 days) prior to the exposure to the CCl4 resulted in an evident decrease in markers of liver damage (glutamate dehydrogenase, sorbitol dehydrogenase, malate dehydrogenase), and reduced pro-oxidative (conjugated dienes, lipid hydroperoxide, thiobarbituric acid reactive substances, advanced oxidation protein products, NADPH oxidase, hydrogen peroxide, oxidized glutathione), and pro-inflammatory markers (tumor necrosis factor-alpha, interleukin-6, nitrite, myeloperoxidase, inducible nitric oxide synthase, cyclooxygenase-2, CD68, lipocalin-2), and also caused a significant decrease in the dissipation of the liver antioxidative defence capacities (reduced glutathione, glutathione S-transferase, and quinone reductase) in comparison to the results detected in the animals treated with CCl4 exclusively. The administration of the anthocyanins prevented the arginine metabolism's diversion towards the citrulline, decreased the catabolism of polyamines (the activity of putrescine oxidase and spermine oxidase), and significantly reduced the excessive activation and hyperplasia of the Kupffer cells. There was also an absence of necrosis, in regard to the toxic effect of CCl4 alone. The hepatoprotective mechanisms of bilberry extract are based on the inhibition of pro-oxidative mediators, strong anti-inflammatory properties, inducing of hepatic phase II antioxidant enzymes (glutathione S-transferase, quinone reductase) and reduced glutathione, hypoplasia of Kupffer cells, and a decrease in the catabolism of polyamines.

Dietary compounds as potential modulators of microRNA expression in psoriasis.

Nutrigenomic DNA reprogramming in different chronic diseases and cancer has been assessed through the stimulation of gene expression and mRNA synthesis versus DNA silencing by CpG DNA modification (methylation); histone modification (acetylation, methylation) and expression of small noncoding RNAs, known as microRNAs (miRNAs). With regard to the specific nutrigenomic effects in psoriasis, the influence of specific diets on inflammatory cell signaling transcriptional factors such as nuclear factor (NF)-κB and Wnt signaling pathways, on disease-related specific cytokine expression, pro/antioxidant balance, keratinocyte proliferation/apoptosis and on proliferation/differentiation ratio have been documented; however, the influence of dietary compounds on the balance between 'good and bad' miRNA expression has not been considered. This review aims to summarize knowledge about aberrant microRNAs expression in psoriasis and to emphasize the potential impact of some dietary compounds on endogenous miRNA synthesis in experimental conditions in vivo and in vitro. Among the aberrantly expressed miRNAs in psoriasis, one of the most prominently upregulated seems to be miR-21. The beneficial effects of phenolic compounds (curcumin and resveratrol), vitamin D, methyl donors, and omega-3 fatty acids (eicosapentaenoic acid and docosahexaenoic acid) are discussed. Highly expressed miR-155 has been downregulated by flavonoids (through a quercetin-rich diet) and by vitamin D. Quercetin has been effective in modulating miR-146a. On the other hand, downregulated miR-125b expression was restored by vitamin D, Coenzyme Q10 and by microelement selenium. In conclusion, the miRNA profile, together with other 'omics', may constitute a multifaceted approach to explore the impact of diet on psoriasis prevention and treatment.