Cutaneous Amelanotic Melanoma Metastasis and Dermatofibromas Showing a Dotted Vascular Pattern

Sir, Dermoscopic patterns specific for hypopigmented and amelanotic cutaneous lesions have not yet been thoroughly characterized, which makes dermoscopic diagnosis of these lesions difficult. Among hypopigmented malignant cutaneous neoplasia, differential diagnoses may include primary melanoma, local recurrent melanoma and cutaneous melanoma metastases from a primary pigmented melanoma. In most cases of poorly pigmented primary melanoma, dermoscopic analysis can detect the presence of pigmented structures such as atypical pigment network and/or irregular dots/globules. True ''amelanotic'' melanoma, lacking any pigmented structures, are rare, and the presence of an atypical vascular pattern characterized by linear irregular and/or dotted vessels may support the diagnosis of melanoma (1, 2). Only a few reports describe dermoscopic findings of pigmented, hypopigmented and amelanotic melanoma metastases (3 – 6). In rare cases, dermatofibroma may clinically simulate melanoma, but can be differentiated by the presence of a central white scar-like patch surrounded by a delicate pigment network or a diffuse, light-brown pigmentation (7). We report here dermoscopic features of three hypopigmented lesions. A dotted vascular pattern was observed in the absence of any pigmented structure in a cutaneous amelanotic local recurrent melanoma and in two dermatofibromas

Immunopathogenesis of psoriasis: a possible role of TGFβ/Smads pathway

Psoriasis is a chronic immune-mediated inflammatory skin disease with both genetic and environmental factors contributing to its pathogenesis. Transforming Growth Factor beta (TGFβ) is a member of a large family of pleiotropic cytokines with three different isoforms (TGFβ1,2,3). Smads are a family of eight-related proteins that function as intracellular signaling intermediates for TGFβ once the latter is bound to its receptors (TGFbRI, II and III). The involvement of Smads in TGFβ signaling has been studied intensively in the skin in the process of wound healing. Few studies, and with controversial results, have investigated at the immunohistochemical and molecular level the role of TGFβ/Smads signaling in psoriasis

Contribution of Common Genetic Variants to Familial Aggregation of Disease and Implications for Sequencing Studies

Despite genetics being accepted as the primary cause of familial aggregation for most diseases, it is still unclear whether afflicted families are likely to share a single highly penetrant rare variant, many minimally penetrant common variants, or a combination of the two types of variants. We therefore use recent estimates of SNP heritability and the liability threshold model to estimate the proportion of afflicted families likely to carry a rare, causal variant. We then show that Polygenic Risk Scores (PRS) may be useful for identifying families likely to carry such a rare variant and therefore for prioritizing families to include in sequencing studies with that aim. Specifically, we introduce a new statistic that estimates the proportion of individuals carrying causal rare variants based on the family structure, disease pattern, and PRS of genotyped individuals. Finally, we consider data from the MelaNostrum consortium and show that, despite an estimated PRS heritability of only 0.05 for melanoma, families carrying putative causal variants had a statistically significantly lower PRS, supporting the idea that PRS prioritization may be a useful future tool. However, it will be important to evaluate whether the presence of rare mendelian variants are generally associated with the proposed test statistic or lower PRS in future and larger studies

Patient satisfaction with calcipotriol/betamethasone dipropionate cutaneous foam for the treatment of plaque psoriasis: The LION real-life multicenter prospective observational cohort study

Topical treatment is the mainstay for mild or moderate psoriasis, but patients are generally little satisfied. Calcipotriol/betamethasone dipropionate (Cal/BD) cutaneous foam has shown to improve signs and symptoms in plaque psoriasis patients. This study assessed patient's satisfaction with Cal/BD foam in a real-life Italian dermatological clinical practice. A multicenter, 4-week observational prospective cohort study enrolled, in 17 Italian dermatology clinics, adult patients with plaque psoriasis on the body and/or scalp. Treatment satisfaction was assessed by 9-item Treatment Satisfaction Questionnaire for Medication (TSQM-9), preference over previous treatments by Patient Preference Questionnaire (PPQ), and change in disease state by Psoriasis Area Severity Index (PASI). Overall 256 patients were eligible, with a mean (SD) age of 55.6 (15.4) years, 59.4% were males. Psoriasis severity was mild in 52.0% of patients, moderate in 43.3%, and severe in 4.7%. Scalp involvement was present in 36.7% of patients. Previous antipsoriatic treatments had been received by 80.5% of patients. TSQM-9 median (25th-75th percentile) scores were 83.3 (66.7-88.9) for effectiveness, 77.8 (66.7-88.9) for convenience, and 78.6 (64.3-92.9) for global satisfaction. Mean (SD) PASI value decreased from 7.3 (4.8) to 2.1 (2.7) after 4 weeks. More than 90% of patients previously treated for psoriasis evaluated the Cal/BD foam more effective, easier to use and better tolerated compared to previous topical treatments at PPQ. This observational study provides real-life evidence of a high level of satisfaction with effectiveness and convenience of the Cal/BD foam in a cohort of plaque psoriasis patients, with an objective improvement in PASI

Contribution of Common Genetic Variants to Familial Aggregation of Disease and Implications for Sequencing Studies

Despite genetics being accepted as the primary cause of familial aggregation for most diseases, it is still unclear whether afflicted families are likely to share a single highly penetrant rare variant, many minimally penetrant common variants, or a combination of the two types of variants. We therefore use recent estimates of SNP heritability and the liability threshold model to estimate the proportion of afflicted families likely to carry a rare, causal variant. We then show that Polygenic Risk Scores (PRS) may be useful for identifying families likely to carry such a rare variant and therefore for prioritizing families to include in sequencing studies with that aim. Specifically, we introduce a new statistic that estimates the proportion of individuals carrying causal rare variants based on the family structure, disease pattern, and PRS of genotyped individuals. Finally, we consider data from the MelaNostrum consortium and show that, despite an estimated PRS heritability of only 0.05 for melanoma, families carrying putative causal variants had a statistically significantly lower PRS, supporting the idea that PRS prioritization may be a useful future tool. However, it will be important to evaluate whether the presence of rare mendelian variants are generally associated with the proposed test statistic or lower PRS in future and larger studies

Clinical Features and Response to Treatment in Elderly Subjects Affected by Hidradenitis Suppurativa: A Cohort Study

hidradenitis suppurativa (HS) is a chronic-relapsing inflammatory skin disease. It usually appears in the second and third decades, but a smaller proportion of patients develop late-onset HS. geriatric HS, defined as the persistence or the development of HS after the age of 65 years, has been poorly explored. this study aimed to investigate the clinical features, treatment management and response to therapies of HS elderly subjects (>= 65 years old). we designed a multicentric observational study, gathering data from seven Italian university hospitals. demographic and clinical data of HS patients aged over 65 years were collected at baseline, week 12 and week 24. overall, 57 elderly subjects suffering from HS were enrolled. at baseline, disease severity was predominantly moderate-to-severe, with 45.6% of patients classified as hurley III. the gluteal phenotype was the most frequently observed; it also appeared to affect patients' quality of life more than other phenotypes. gluteal involvement was detected in about half (49.1%) of cases and associated with severe stages of the disease. In terms of therapeutic response, hurley III patients showed the persistency of higher values of mean IHS4, DLQI, itch- and pain-NRS scores compared to hurley I/II. In conclusion, disease severity in this subpopulation appears high and treatment is often challenging

Family history of cancer as surrogate predictor for immunotherapy with anti-PD1/PD-L1 agents: preliminary report of the FAMI-L1 study.

Aim: Tumors related to hereditary susceptibility seem to have an immunosensitive phenotype. Materials & methods: We conducted a multicenter retrospective study, to investigate if family history of cancer, multiple neoplasms and early onset of cancer could be related to clinical outcomes of anti-PD-1/PD-L1 therapy. Activity and efficacy data of 211 advanced cancer patients (kidney, non-small-cell lung cancer, melanoma, urothelium, colorectal and HeN), treated at seven Italian centers with anti-PD-1/PD-L1 agents, were analyzed. Results: In this preliminary report at multivariate analyses, positive family history of cancer showed a statistically significant relationship with a better objective response rate (p = 0.0024), disease control rate (p = 0.0161), median time to treatment failure (p = 0.0203) and median overall survival (p = 0.0221). Diagnosis of multiple neoplasms significantly correlates only to a better disease control rate, while interestingly non-early onset of cancer and sex (in favor of female patients) showed significant correlation with a better median overall survival (p = 0.0268 and p = 0.0272, respectively). Conclusion: This pilot study seems to individuate easily available patient's features as possible predictive surrogates of clinical benefit for anti-PD-1/PD-L1 treatments. These preliminary results need to be confirmed with a greater sample size, in prospective trials with immunotherapy

On the Interplay of Telomeres, Nevi and the Risk of Melanoma

The relationship between telomeres, nevi and melanoma is complex. Shorter telomeres have been found to be associated with many cancers and with number of nevi, a known risk factor for melanoma. However, shorter telomeres have also been found to decrease melanoma risk. We performed a systematic analysis of telomere-related genes and tagSNPs within these genes, in relation to the risk of melanoma, dysplastic nevi, and nevus count combining data from four studies conducted in Italy. In addition, we examined whether telomere length measured in peripheral blood leukocytes is related to the risk of melanoma, dysplastic nevi, number of nevi, or telomere-related SNPs. A total of 796 cases and 770 controls were genotyped for 517 SNPs in 39 telomere-related genes genotyped with a custom-made array. Replication of the top SNPs was conducted in two American populations consisting of 488 subjects from 53 melanoma-prone families and 1,086 cases and 1,024 controls from a case-control study. We estimated odds ratios for associations with SNPs and combined SNP P-values to compute gene region-specific, functional group-specific, and overall P-value using an adaptive rank-truncated product algorithm. In the Mediterranean population, we found suggestive evidence that RECQL4, a gene involved in genome stability, RTEL1, a gene regulating telomere elongation, and TERF2, a gene implicated in the protection of telomeres, were associated with melanoma, the presence of dysplastic nevi and number of nevi, respectively. However, these associations were not found in the American samples, suggesting variable melanoma susceptibility for these genes across populations or chance findings in our discovery sample. Larger studies across different populations are necessary to clarify these associations