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Meldola, Italy

Bazhin A.V.,University of Heidelberg | Bayry J.,INSER M Unite 872 | Umansky V.,Skin Cancer Unit | Werner J.,University of Heidelberg | Karakhanova S.,University of Heidelberg
OncoImmunology | Year: 2013

Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest types of malignancy. Via a broad stimulation of the immune system, PDAC activates both antitumor immune responses and immunosuppressive mechanisms. We propose that new immunotherapeutic strategies for the management of PDAC should be designed to specifically neutralize the immunosuppressive tumor microenvironment. © 2013 Landes Bioscience.

Losi A.,University of Modena and Reggio Emilia | Longo C.,Skin Cancer Unit | Cesinaro A.M.,University of Modena and Reggio Emilia | Benati E.,University of Modena and Reggio Emilia | And 3 more authors.
British Journal of Dermatology | Year: 2014

Background Amelanotic melanoma represents a diagnostic challenge both clinically and dermoscopically. Few studies based on case series have explored the possibility of using reflectance confocal microscopy (RCM) to diagnose amelanotic melanoma. Objectives To validate a new confocal feature, named hyporeflective pagetoid cells (HPCs), for the diagnosis of amelanotic melanoma. Methods A group of 20 amelanotic melanomas and a control population of nonpigmented melanocytic naevi (10), hypo/nonpigmented nonmelanocytic lesions (20) and pigmented melanomas (20), imaged by RCM, were retrospectively evaluated. The presence of HPCs and other diagnosis-specific confocal features was assessed and correlated with histopathology. Results HPCs were present, and usually abundant, in the majority of amelanotic melanomas (85%). As expected, they were also observed in Spitz naevi. On histopathology, they were correlated with pagetoid infiltration of hypomelanotic melanocytes in all melanocytic lesions. Few nonmelanocytic lesions (three squamous cell carcinomas, two seborrhoeic keratoses and one basal cell carcinoma) showed the presence of HPCs. In these cases, they corresponded to enlarged or dyskeratotic keratinocytes by histopathology. Conclusions The identification of HPCs in the epidermis is a new parameter that is frequently found in amelanotic melanoma. Possible confounders are represented by atypical keratinocytes that can be present in nonmelanocytic lesions. However, the whole architecture and the presence of additional diagnostic criteria should be considered in order to obtain a correct diagnosis. What's already known about this topic? Amelanotic and hypopigmented lesions can be readily evaluated by means of confocal microscopy. Few reports have explored the characteristic confocal aspects of amelanotic melanoma as seen by confocal microscopy. What does this study add? We define a new descriptor, named hypomelanotic pagetoid cells, as a clue for differentiating amelanotic melanoma from other benign and malignant nonpigmented lesions. © 2013 British Association of Dermatologists.

Ragazzi M.,Pathology Unit | Piana S.,Pathology Unit | Longo C.,Skin Cancer Unit | Castagnetti F.,Breast Surgery Unit | And 4 more authors.
Modern Pathology | Year: 2014

Confocal microscopy is a non-invasive method of optical imaging that may provide microscopic images of untreated tissue that correspond almost perfectly to hematoxylin- and eosin-stained slides. Nowadays, following two confocal imaging systems are available: (1) reflectance confocal microscopy, based on the natural differences in refractive indices of subcellular structures within the tissues; (2) fluorescence confocal microscopy, based on the use of fluorochromes, such as acridine orange, to increase the contrast epithelium-stroma. In clinical practice to date, confocal microscopy has been used with the goal of obviating the need for excision biopsies, thereby reducing the need for pathological examination. The aim of our study was to test fluorescence confocal microscopy on different types of surgical specimens, specifically breast, lymph node, thyroid, and colon. The confocal images were correlated to the corresponding histological sections in order to provide a morphologic parallel and to highlight current limitations and possible applications of this technology for surgical pathology practice. As a result, neoplastic tissues were easily distinguishable from normal structures and reactive processes such as fibrosis; the use of fluorescence enhanced contrast and image quality in confocal microscopy without compromising final histologic evaluation. Finally, the fluorescence confocal microscopy images of the adipose tissue were as accurate as those of conventional histology and were devoid of the frozen-section-related artefacts that can compromise intraoperative evaluation. Despite some limitations mainly related to black/white images, which require training in imaging interpretation, this study confirms that fluorescence confocal microscopy may represent an alternative to frozen sections in the assessment of margin status in selected settings or when the conservation of the specimen is crucial. This is the first study to employ fluorescent confocal microscopy on surgical specimens other than the skin and to evaluate the diagnostic capability of this technology from pathologists' viewpoint. © 2014 USCAP, Inc All rights reserved.

Zalaudek I.,Medical University of Graz | Argenziano G.,Skin Cancer Unit
Current Problems in Dermatology (Switzerland) | Year: 2015

In the realm of keratinocyte skin cancer, specific dermoscopic patterns that are associated with different stages of progression have been identified, which allows for an improved clinical diagnosis and differentiation actinic keratosis, intraepidermal carcinoma (also commonly named Bowen's disease, squamous cell carcinoma in situ or intraepidermal carcinoma) and invasive squamous cell carcinoma. Moreover, in times of increasing availability of topical treatment options for actinic keratoses, the knowledge of specific patterns associated with different grades and subtypes aids in the treatment choice and monitoring of the treatment response. © 2015 S. Karger AG, Basel.

Quintana R.M.,CIEMAT | Dupuy A.J.,University of Iowa | Bravo A.,University of Santiago de Compostela | Casanova M.L.,CIEMAT | And 6 more authors.
Journal of Investigative Dermatology | Year: 2013

Nonmelanoma skin cancer (NMSC) is by far the most frequent type of cancer in humans. NMSC includes several types of malignancies with different clinical outcomes, the most frequent being basal and squamous cell carcinomas. We have used the Sleeping Beauty transposon/transposase system to identify somatic mutations associated with NMSC. Transgenic mice bearing multiple copies of a mutagenic Sleeping Beauty transposon T2Onc2 and expressing the SB11 transposase under the transcriptional control of regulatory elements from the keratin K5 promoter were treated with TPA, either in wild-type or Ha-ras mutated backgrounds. After several weeks of treatment, mice with transposition developed more malignant tumors with decreased latency compared with control mice. Transposon/transposase animals also developed basal cell carcinomas. Genetic analysis of the transposon integration sites in the tumors identified several genes recurrently mutated in different tumor samples, which may represent novel candidate cancer genes. We observed alterations in the expression levels of some of these genes in human tumors. Our results show that inactivating mutations in Notch1 and Nsd1, among others, may have an important role in skin carcinogenesis. © 2013 The Society for Investigative Dermatology.

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