Basal cell carcinoma accounts for 75% of skin cancers worldwide and is the most common malignancy in Caucasians. Since chronic ultraviolet exposure is the major risk factor for its development, ...sun‐exposed areas such as the face are frequently affected. The gold‐standard treatment is surgical excision. Radiotherapy may be considered in selected cases such as unresectable primary tumors. In some patients, when the risk of a significant functional/cosmetic deficit advises against both surgery and radiotherapy, target therapy (hedgehog pathway inhibitors) can be administered alone or in a neoadjuvant setting, to reduce the tumor size and make it eligible for surgery. Vismodegib as a neoadjuvant treatment before surgery has been investigated in a single, multicentre, open‐label, phase II trial (VISMONEO); however, sonidegib has not yet been evaluated in this setting. We report the cases of two patients with locally advanced basal cell carcinoma of the face who achieved complete remission with sonidegib followed by a more limited surgical excision than would have been needed without target therapy.
Background
Cutaneous vascular lesions (VLs) are benign or malignant processes involving blood and/or lymphatic vessels, usually readily diagnosed with dermoscopy. However, cases showing unclear ...clinical/dermoscopic findings may require further investigations. Line‐field confocal optical coherence tomography (LC‐OCT) is a new, non‐invasive imaging technique displaying high resolution and deep penetration. The aim of this study was to describe the LC‐OCT features of the most common benign and malignant VLs and to correlate them with histopathological substrates.
Methods
Clinical, dermoscopic, LC‐OCT and histopathological images of VLs were retrospectively collected. Detailed LC‐OCT description and histopathological correlations were produced for different types of VLs.
Results
The study included 71 VLs belonging to 50 caucasian patients 31 (62%) females; median age 56.8 (30–83) years study lesions included 25 cherry haemangiomas, 15 angiokeratomas, 10 thrombosed haemangiomas, six pyogenic granulomas, five venous lakes, four targetoid haemosiderotic haemangiomas, four Kaposi's sarcomas and two extraungual glomus tumours. LC‐OCT detected increased dermal vascularity, assuming different size and shape according to the particular type of VLs. LC‐OCT criteria correlated well to established histopathologic findings.
Conclusion
The results of our preliminary observations indicate that in vivo evaluation with LC‐OCT may provide practical clues for the identification of the vascular nature of a lesion and its differential diagnosis.
Summary
Background
The parallel ridge pattern (PRP) is considered the dermoscopic hallmark of acral melanoma (AM). However, it was recently shown that approximately one‐third of AMs do not display a ...PRP dermoscopically, rendering their detection more troublesome.
Objectives
To investigate the diagnostic accuracy of dermoscopic criteria for the diagnosis of AM.
Methods
Dermoscopic images of consecutive cases of histopathologically diagnosed AMs and acral naevi with histopathological diagnosis or with at least 1 year of follow‐up were evaluated by three independent investigators for the presence of predefined criteria. Crude and adjusted odds ratios and their corresponding 95% confidence intervals were calculated by univariate and multivariate logistic regression, respectively. Receiver operating characteristic curves were used to choose among competing classification schemes.
Results
In total 603 lesions (472 naevi and 131 AMs) were included in the study. A scoring system (named BRAAFF) composed of six variables was associated with optimal area under the curve and sensitivity for the diagnosis of AM. This method includes four positive (irregular blotches, ridge pattern, asymmetry of structures and asymmetry of colours) and two negative predictors (furrow pattern and fibrillar pattern).
Conclusions
The BRAAFF checklist significantly improves the diagnostic accuracy of dermoscopy for the diagnosis of AM.
What's already known about this topic?
Approximately one‐third of acral melanomas (AMs) lack a dermoscopic parallel ridge pattern, rendering their detection more troublesome.
What does this study add?
A scoring system composed of six variables achieves the highest diagnostic accuracy for AM.
Application of this diagnostic scheme minimizes the possibility of missing AMs that are not dermoscopically characterized by a parallel ridge pattern.
Linked Comment: Rao and Giambrone, Br J Dermatol 2015; 173: 893–894.
Cutaneous squamous cell carcinoma (cSCC) represents 20% of all skin cancers. Although primary cSCCs can be successfully treated with surgery, a subset of highly aggressive lesions may progress to ...advanced disease, representing a public healthcare problem with significant cancer‐related morbidity and mortality. A complex network of genes (TP53, CDKN2A, NOTCH1 and NOTCH2, EGFR and TERT) and molecular pathways (RAS/RAF/MEK/ERK and PI3K/AKT/mTOR) have been shown to play an important role in the pathogenesis of cSCC. The epigenetic regulation of TP53 and CDKN2A is an attractive therapeutic target for the treatment of cSCC, as well as NOTCH‐activating agents capable to restore its tumour‐suppressor function. EGFR inhibitors including both monoclonal antibodies (cetuximab and panitumumab) and tyrosine kinase inhibitors (erlotinib, gefitinib and dasatinib) have been used in clinical trials for the treatment of advanced cSCC, achieving only partial clinical benefit. Recently, an immune‐modulatory drug (cemiplimab) has been introduced for the treatment of advanced cSCC with good clinical results and a favourable safety profile, while other PD1/PD‐L1 inhibitors, either as monotherapy or in combination with targeted therapies, are currently under investigation. This review focuses on molecular findings involved in the pathogenesis of cSCC and their implications for the future development of new treatment strategies. In addition, current and ongoing treatments on targeted therapies and/or immunotherapy are illustrated.
: Real-life data often highlight the side effects of certain drugs not previously reported in randomized controlled trials (RCTs).
To describe cutaneous inflammatory eruptions in psoriatic patients ...treated with an anti IL-17A agent (secukinumab or ixekizumab).
: Retrospective analysis of a cohort of patients with chronic plaque psoriasis who started an anti IL-17A agent between September 2016-February 2019 and who developed cutaneous inflammatory eruptions during treatment. A systematic review of similar events reported in the literature was performed.
: Data of 468 patients were reviewed and 27 cutaneous inflammatory eruptions of 27 (5.8%) patients were collected. The eruptions appeared after a mean of 16.9 ± 17.0 weeks of therapy showing a classical acute eczema in 11 patients (40.7%), an atopic dermatitis-like rash in 11 patients (40.7%) and a psoriasiform eruption in 5 patients (18.5%). Histopathology of 12/27 cases showed epidermal spongiosis in all these variants.
: We described the clinic-pathologic features of some eczematous eruptions occurring in psoriatic patients, 3-4 months after treatment initiation with an anti IL-17A agent. Further investigations are needed to explain this phenomenon, that might be defined a paradoxical adverse event, based upon the role of IL17 in eczema pathogenesis.
Common primary cutaneous squamous cell carcinoma (CSCC) accounts for 20% of keratinocyte cancers that is usually successfully treated with surgery or radiotherapy. In a minority of cases, CSCC ...lesions may progress to locally advanced or metastatic disease that may be difficult to be treated causing significant morbidity and mortality. Chemotherapies and targeted therapy with anti‐epidermal growth factor receptor antibodies have been used off‐label in small studies and case reports of advanced CSCC, but data are scarce and response short‐lived. Recently, two PD‐1 immune checkpoint inhibitors, cemiplimab and pembrolizumab, have been approved for the treatment of advanced CSCC; specifically the former can be administered in patients with locally advanced and metastatic tumours, while the latter in case of recurrent metastatic CSCC. The introduction of immune checkpoint inhibitors represents a breakthrough in the treatment of CSCC, since numerous clinical trials showed that these agents may provide remarkable clinical benefit with an acceptable safety profile, in a high‐need population who had no standard of care. In addition, real‐world studies are needed to validate the results observed in clinical trials and numerous clinical trials in the neoadjuvant or adjuvant setting are ongoing. Finally, further studies should investigate predictive biomarkers useful to better select patients to maximize the treatment efficacy.
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Chemical modifications of quinoline moiety have been recognized as a useful strategy to development of new drugs. Here, the cytotoxicity of a set of twenty-four 4-substituted ...quinolines (named HTI) was screened for their antitumor and antileishmanial potential in vitro, and the underlying mechanisms investigated. HTI 21 and HTI 22 exhibited the highest cytotoxicity, being selected to the subsequent studies. Both derivatives induced caspase-dependent apoptosis associated to the dissipation of the mitochondrial transmembrane potential (ΔΨ) and ROS generation. HTI-induced cell death was calcium dependent, associated to thiol oxidation and cysteine proteases activation. In isolated mitochondria, HTI derivatives promoted mitochondrial permeabilization by different mechanisms. The inhibition of BCL-2 by venetoclax enhanced the HTI-induced cytotoxicity. Regarding the inhibition of cysteine proteases type B of Leishmania mexicana, HTI 15 exhibited the most potent inhibitory activity through a linear non-competitive mechanism. These data highlight the therapeutic potential of 4-substituted quinolines as antitumor and antileishmanial drugs.
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