Broadening the List of Basal Cell Carcinoma Mimickers: Dermoscopic Features of Trichoadenoma

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Negative Pigment Network Identifies a Peculiar Melanoma Subtype and Represents a Clue to Melanoma Diagnosis: A Dermoscopic Study of 401 Melanomas

The dermoscopic descriptor "negative pigment network" (NPN) has been reported in several types of melanocytic and non-melanocytic lesions, although it has a higher frequency of association with melanoma and Spitz naevus. In a study of 401 consecutive melanomas, excluding facial, acral and mucosal locations, the frequency and variability of NPN were investigated, and the results of NPN correlated with clinical and histopathological data. NPN of any extension was found in 27% of melanomas, most frequently invasive and arising from a naevus on the trunk of young subjects. Seven percent of melanomas in the study population showed presence of NPN in more than half of the lesion area; most of these did not show typical dermoscopic melanoma features. The authors propose a new melanoma subtype, in which extensive NPN should be considered as a diagnostic indicator

Dermoscopy and Reflectance Confocal Microscopy for Monitoring the Treatment of Actinic Keratosis with Ingenol Mebutate Gel: Report of Two Cases

Introduction: A relatively novel application for dermoscopy and reflectance confocal microscopy (RCM) is their use in the monitoring of topical treatment response for non-melanoma skin cancer. Actinic keratosis (AK) is the early phase of a multistep biologic continuum leading to invasive squamous cell carcinoma. A number of topical therapies are now available for the treatment of AK but their disadvantages include long treatment duration and prolonged local reactions. Ingenol mebutate is a newer therapy for AK which is only applied for 2 or 3 days. Case Report: Dermoscopy and RCM findings in two patients with AK treated with ingenol mebutate confirm that it induces rapid lesion necrosis and specific neutrophil-mediated, antibody-dependent cellular cytotoxicity. Necrosis occurs via mitochondrial membrane disruption, with subsequent eradication of residual tumor cells via transient inflammation. Local skin reactions to ingenol mebutate should be considered part of the drug’s mechanism of action rather than an adverse effect. Conclusion: Ingenol mebutate is a valuable therapy for the treatment of AK. This case report adds further evidence to the usefulness of dermoscopy and RCM in the assessment and monitoring of treatment outcome

Are the neck malignant melanomas different from the ones affecting the head? Clinicopathologic, dermoscopic and prognostic findings

Background: Malignant melanomas of the head and neck are usually considered as a unique entity in comparison to other body sites. However, no characterization of neck melanoma has been performed so far, despite the clear anatomic and histological differences. Aim: We investigated clinical, demographic, histological and dermoscopic differences between face, scalp and neck melanoma. Materials and methods: A retrospective analysis of medical and histologic records from 116 melanomas of the head and neck area collected between January 2003 and January 2008 was performed. Body site, gender, age, number of lesions, age at first melanoma diagnosis, size, Clark level, association with nevi, presence or absence of mitoses and/or ulceration, presence of synchronous and/or metachronous melanoma were recorded. Moreover, digital dermoscopy images of 92 melanomas of the head and neck area were analyzed for main dermoscopic patterns and lesion diameter. Results: Significant differences in Breslow thickness, ex-naevo origin and tumor size among neck and face-scalp melanomas were observed. Neck MM patients were younger than those with MM of face and scalp. In contrast to scalp and face, no patient died from neck melanoma. Dermoscopic patterns were similar to those of trunk-limbs MM, and no lesion showed a lentigo maligna pattern which was observed in most lesions of the face. Conclusion: Melanomas of the neck must be distinguished from face and scalp melanomas because of younger age, different dermoscopic patterns and ex-naevo origin and better prognosis. These data should be taken into account both from an epidemiological and clinical point of view

A solitary pink lesion: dermoscopy and RCM features of lichen planus

We present an unusual onset of cutaneous lichen planus (LP) in a middle-aged patient. The initial presentation as solitary, indolent pink lesion required further investigations to rule out malignancy, especially amelanotic melanoma. Dermoscopy and reflectance confocal microscopy findings were found to be helpful in our case in addressing the correct diagnosis

Quantitative evaluation of healthy epidermis by means of multiphoton microscopy and fluorescence lifetime imaging microscopy

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Development and characterization of a novel human 3D model of bone metastasis from breast carcinoma in vitro cultured

Breast cancer frequently metastasizes to the skeleton causing significant morbidity. Here, we set-up a novel and advanced ex vivo model by using fresh tissue from human vertebral bone metastasis from breast carcinoma patients able to retain the tumor microenvironment and tumor cells heterogeneity

Mutazioni somatiche di BRAF in pazienti affetti da melanoma maligno metastatico ed efficacia clinica degli approcci terapeutici a bersaglio molecolare con inibitori di BRAF

L’introduzione di terapie a bersaglio molecolare ha rivoluzionato la prognosi dei pazienti affetti da melanoma in stadio avanzato. Attualmente è possibile determinare lo status molecolare del melanoma analizzando geni quali C-KIT, BRAF ed N-RAS per la scelta di strategie terapeutiche mirate. Mutazioni di BRAF si riscontrano in circa il 50% dei melanomi: tra queste la V600E e la V600K sono maggiormente frequenti e ben studiate nei pregressi protocolli di sperimentazione fase II/III con inibitori di BRAF. Questi ultimi (Dabrafenib e Vemurafenib) hanno dimostrato chiara efficacia nell’indurre risposte obiettive nel melanoma avanzato. Con il presente lavoro presentiamo le preliminari valutazioni delle correlazioni tra tipologie di mutazioni somatiche del gene BRAF riscontrate in una coorte di melanomi in stadio IV e le risposte cliniche a tale inibitori selettivi. A partire dal giugno 2011, 19 pazienti (10 M; 9F; età media 55 anni) affetti da melanoma stage IV BRAF+ sono stati arruolati in protocolli terapeutici con Dabrafenib (150 mg 2 volte/die) o Vemurafenib (960 mg 2volte/die) presso l’Università di Modena. Il restaging strumentale della malattia veniva eseguito a 8 settimane dall’inizio della terapia. Sono state riscontrate mutazione hot spot V600E (c.1799T>A) in 18 pazienti, in due differenti pazienti sono state individuate le rare mutazioni V600M (c.1798G>A) e V600R (c.1790T>G). In un melanoma è stata evidenziata una doppia mutazione (V600E; V600M) ed il relativo paziente, trattato con Dabrafenib, ha presentato una rapida regressione delle importati lesioni metastatiche. In due casi la ricerca mutazionale in BRAF, risultata inizialmente negativa, è stata poi riscontrata in una successiva analisi. I dati clinici preliminari evidenziano una risposta obiettiva già nelle primissime settimane di terapia, buona tolleranza con scarsi effetti collaterali sia nei pazienti con mutazioni V600E che in quelli con le rare mutazioni V600 M e V600R. Il periodo di sopravvivenza medio libero da progressione dei 15 pazienti con follow-up di almeno 8 settimane è stato di 7 mesi. In 9 pazienti persiste la risposta terapeutica ad oggi. La doppia mutazione di BRAF potrebbe costituire un fattore prognostico positivo per la risposta agli inibitori di BRAF. Nei casi negativi alla ricerca mutazionale, dovrebbe essere routinariamente impiegate indagini più approfondite atte ad evidenziare non solo la presenza della comune V600E ma anche delle varianti meno comuni degli esoni 11 e 15

Chroman-4-One Derivatives Targeting Pteridine Reductase 1 and Showing Anti-Parasitic Activity

Flavonoids have previously been identified as antiparasitic agents and pteridine reductase 1 (PTR1) inhibitors. Herein, we focus our attention on the chroman-4-one scaffold. Three chroman-4-one analogues (1-3) of previously published chromen-4-one derivatives were synthesized and biologically evaluated against parasitic enzymes (Trypanosoma brucei PTR1-TbPTR1 and Leishmania major-LmPTR1) and parasites (Trypanosoma brucei and Leishmania infantum). A crystal structure of TbPTR1 in complex with compound 1 and the first crystal structures of LmPTR1-flavanone complexes (compounds 1 and 3) were solved. The inhibitory activity of the chroman-4-one and chromen-4-one derivatives was explained by comparison of observed and predicted binding modes of the compounds. Compound 1 showed activity both against the targeted enzymes and the parasites with a selectivity index greater than 7 and a low toxicity. Our results provide a basis for further scaffold optimization and structure-based drug design aimed at the identification of potent anti-trypanosomatidic compounds targeting multiple PTR1 variants