Molecular diagnostics are increasingly performed routinely in the diagnosis and management of patients with melanoma due to the development of novel therapies that target specific genetic mutations. ...The development of next-generation sequencing (NGS) technologies has enabled to sequence multiple cancer-driving genes in a single assay, with improved sensitivity in mutation detection. The main objective of this study was the design and implementation of a melanoma-specific sequencing panel, and the identification of the spectrum of somatic mutations in a series of primary melanoma samples. A custom panel was designed to cover the coding regions of 35 melanoma-related genes. Panel average coverage was 2,575.5 reads per amplicon, with 92,8% of targeted bases covered ≥500×. Deep coverage enabled sensitive discovery of mutations in as low as 0.5% mutant allele frequency. Eighty-five percent (85/100) of the melanomas had at least one somatic mutation. The most prevalent mutated genes were BRAF (50%;50/199), NRAS (15%;15/100), PREX2 (14%;14/100), GRIN2A (13%;13/100), and ERBB4 (12%;12/100). Turn-around-time and costs for NGS-based analysis was reduced in comparison to conventional molecular approaches. The results of this study demonstrate the cost-effectiveness and feasibility of a custom-designed targeted NGS panel, and suggest the implementation of targeted NGS into daily routine practice.
Epidermal necrolysis (EN) compromises a spectrum of life‐threatening dermatoses (Stevens–Johnson Syndrome SJS, overlap syndrome and toxic epidermal necrolysis TEN). Currently, no active therapeutic ...regimen with unequivocal benefit exists for SJS/TEN. SCORTEN is the widely‐used prognostic scale specific for SJS/TEN. Nevertheless, a new prognostic scale, the ABCD‐10, has been recently proposed. In this context, acute renal failure (ARF) seems to be an important comorbidity that could influence prognosis in SJS/TEN patients more than it is assumed by these two scales. Our objectives were to compare the accuracy of the SCORTEN and ABCD‐10 scales in predicting the mortality in SJS/TEN, and to investigate the influence of renal failure on prognosis. The prognostic results of 18 patients with EN treated in two referral centers between 2013 and 2018 are presented. SCORTEN, ABCD‐10 and renal function values were retrospectively collected for all patients. Out of the 18 patients who were analyzed, nine (50%) received only supportive therapy, four were treated with etanercept 50 mg in a single dose (22.2%) and five with corticosteroids (27.8%). Five patients developed ARF. Predicted mortality was 3.48 for SCORTEN and 2.33 for ABCD‐10. Eventually, four patients died (22.2%), all had ARF and none of them received active treatment. Despite study limitations and in the absence of active treatment of choice, SCORTEN behaved as a reliable predictor of mortality in patients with EN, outperforming the newer ABCD‐10. ARF was an early event associated with a poor prognosis, which could represent a prognostic marker to consider in the future.
Abstract Background Consensus is lacking on adequate deep histological margins in cutaneous squamous cell carcinoma (cSCC). Deep clearance for tumours located on the scalp is limited by anatomic ...constraints. Objective To determine whether clear but close deep histological margins (<1 mm) confer a higher risk of recurrence in cSCCs of the scalp treated by wide local excision, compared to deep histological margins ≥1 mm. Methods Multicentre retrospective observational cohort study and multivariate competing risk analysis to evaluate risk factors for recurrence. Results In total, 295 patients with 338 cSCCs were included. Close deep histological margins were not associated with an increased cumulative incidence of recurrence (subhazard ratio SHR 1.96 95% CI 0.87–4.41). However, an increased risk of recurrence was observed for those tumours that presented concurrent invasion of the galea aponeurotica and close deep margins, as opposed to patients without these factors (SHR 3.52 1.24–10.01). Tumours with clear but close peripheral margins (<1 mm) also had higher risk of recurrence (SHR 5.01 1.68–14.97). Limitations Retrospective observational study based on pathology reports. Conclusion Deep histological margins <1 mm do not confer a greater risk of recurrence as long as the tumour is completely excised and the galea aponeurotica is not involved. Surgical excision of cSCC on the scalp should include the galea to ensure proper assessment of deep margins.
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