Ossifying fasciitis of the nose

A case of ossifying fasciitis in a 22-year-old woman is described. The lesion, which appeared suddenly, was located on the tip of the nose. Histologically the lesion contained spindle-shaped myofibroblastic cells, trabeculae of woven bone rimmed by plump osteoblasts within a myxoid stroma

Evaluation of Hedgehog Pathway Inhibition on Nevoid Basal Cell Carcinoma Syndrome Fibroblasts and Basal Cell Carcinoma-Associated Fibroblasts: Are Vismodegib and Sonidegib Useful to Target Cancer-Prone Fibroblasts?

Activating mutations in the Hh pathway underlies the development of sporadic and familial skin BCC. For these oncogenic proliferations displaying ligand-independent activation of the intracellular pathway, two molecules have been approved for therapeutic purposes: vismodegib and sonidegib. Improper Hh signalling occurs in many human tumours also via a paracrine mechanism (ligand-dependent) in which the secretion of Hh ligands by stromal cells support tumour growth. On the other hand, the mobilization of neoplastic stroma by cancer cells is sustained by the activation of Hh signalling in surrounding fibroblasts suggesting a central role of this bidirectional crosstalk in carcinogenesis. Additionally, loss-of-function mutations in the PTCH1 gene in the context of NBCCS, an autosomal dominant disorder predisposing to multiple BCCs, determine tumour permissive phenotypes in dermal fibroblasts. Here, profiling syndromic and BCC-associated fibroblasts unveiled an extraordinary similarity characterized by overexpression of several Hh target genes and a marked pro-inflammatory outline. Both cell types exposed to Hh inhibitors displayed reversion of the tumour-prone phenotype. Under vismodegib and sonidegib treatment, the Wnt/β-catenin pathway, frequently over-active in tumour stroma, resulted down-regulated by pAKT-GSK3β axis and consequent increase of β-catenin turnover. Overall, this study demonstrated that vismodegib and sonidegib impacting on fibroblast tumour supportive functions might be considered in therapy for BCC independently to the mutation status of Hh components in neoplastic cells

Human Papillomaviruses, p16^INK4aand Akt expression in basal cell carcinoma

Abstract Background The pathogenic role of beta-HPVs in non melanoma skin cancer (NMSC), is not still completely understood, and literature data indicate that they might be at least cofactors in the development of certain cutaneous squamous cell carcinomas. However, only few reports contain data on basal cell carcinoma (BCC). The HPVs interact with many cellular proteins altering their function or the expression levels, like the p16INK4a and Akt. Our study aimed to determine the presence of different beta -HPV types and the expression of p16INK4a and Akt in BCC, the commonest NMSC, in the normal appearing perilesional skin and in forehead swab of 37 immunocompetent patients. Methods The expression of p16INK4a and Akt, by immunohistochemistry, and the HPV DNA, by nested PCR, were investigated in each sample. Results No correspondence of HPV types between BCC and swab samples was found, whereas a correspondence between perilesional skin and BCC was ascertained in the 16,7% of the patients. In BCC, 16 different types of beta HPV were found and the most frequent types were HPV107 (15,4%), HPV100 (11,5%) and HPV15 (11,5%) all belonging to the beta HPV species 2. Immunohistochemistry detected significant p16INK4a expression in almost all tumor samples (94,3%) with the highest percentages (> 30%) of positive cells detected in 8 cases. A statistically significant (p = 0,012) increase of beta HPV presence was detected in p16INK4a strongly positive samples, in particular of species 2. pAkt expression was detected in all tumor samples with only 2 cases showing rare positive cells, whereas Akt2 expression was found in 14 out of 35 BCC (40%); in particular in HPV positive samples over-expressing p16INK4a. Conclusions Our data show that p16INK4a and pAkt are over-expressed in BCC and that the high expression of p16INK4a and of Akt2 isoform is often associated with the presence of beta-HPV species 2 (i.e. HPV 15). The association of these viruses with the up-regulation of p16INK4a and Akt/PI3K pathway suggests that in a subtype of BCC these viruses may exert a role in the carcinogenesis or in other, still undefined, biological property of these tumors. If this particular type of BCC reflects a different biology it will remain undisclosed until further studies on a larger number of samples will be performed.</p

Lentigo maligna of the face: A quantitative simple method to identify individual patient risk probability on dermoscopy

Background/Objectives: The clinical and dermoscopic differential diagnosis of flat pigmented facial lesions represents a great challenge for the clinicians. Our aim was to report a quantitative method based on dermoscopic features to better classify pigmented facial lesions. Methods: This is a retrospective case-series study that analysed the dermoscopic features of 582 pigmented facial lesions. Results: The individual patient probability of lentigo maligna (LM) was predicted by a multivariate model, with an accuracy of 0.72. According to the odds ratio at the multivariate analysis, an individual scoring index was assigned to each criterion, and a value of 4.56 was identified as optimal cut-off point. Up to a score of 2.5, the probability that a lesion is an LM is 0. The probability increases from 10 to 50% for a score ranging between 4.5 and 6. It is about 90% for a score of 7. Conclusion: The optimal cut-off point obtained and the curve that identifies the probability of a patient having a LM could improve the classification and the management strategies of equivocal pigmented facial lesions

Lentigo maligna of the face: A quantitative simple method to identify individual patient risk probability on dermoscopy

Fil: Iucci, Matías José. Universidad Nacional de La Plata. Facultad de Humanidades y Ciencias de la Educación; Argentina

Clinical features predicting identification of CDKN2A mutations in Italian patients with familial cutaneous melanoma

CDKN2A is the most common, most penetrant gene whom germline mutations predisposing to cutaneous familial melanoma (FAM). Multiple primary melanoma (MPM), early age at onset, >2 affected members and pancreatic cancer are consistent features predicting positive test. However, the impact that cumulative clinical features have on the likelihood of molecular testing is unknown. In this work, genotype-phenotype correlations focused on selected clinical features were performed in 100 Italian FAM unrelated patients. Molecular studies of CDKN2A mutations were performed by direct sequencing. Statistical study included multiple correspondence analysis, uni- and multivariate analyses, and individual patient's probability calculation. MPM, >2 affected family members, Breslow thickness >0.4 mm, and age at onset <= 41 years were the unique independent features predicting positive CDKN2A screening. The rate of positive testing ranged from 93.2% in the presence of all of them, to 0.4% in their absence. The contribution of each of them was quantified accordingly, with MPM being the most significant. These findings confirm previous data and add novel insights for the role of accurate patients' selection in CDKN2A screening. (C) 2011 Elsevier Ltd. All rights reserved