Desmoplastic melanoma: a challenge for the oncologist

To evaluate clinical, pathologic and genetic features of desmoplastic melanoma (DM).MATERIALS & METHODS: Analysis of all DM records from 1991 to 2015. RESULTS: The most common location of DMs was the head and neck (69%); median age and follow-up were 60.5 and 7.3 years, respectively. A familial predisposition for DMs and others malignancies was analyzed. Thin Breslow thickness (<4.5 mm) was associated with an intraepidermal component or a previous lentigo maligna, whereas high Breslow thickness (>4.5 mm) was observed in 'pure' DM. CONCLUSION: DM could progress from an early phase, characterized by an intraepidermal component, to late phase, characterized by a dermal nodule. This hypothesis correlates with melanoma genetic and NF1 mutation, which could be an early event in the progression of DM

BRAFV600E mutated and wild type melanomas: dermoscopy and reflectance confocal microscopy characterization

The advent of modern molecular approaches was of crucial importance for the identification of melanoma genetic signatures, opening new horizons in the treatment of metastatic disease with molecular targeted therapies. Similarly the melanoma diagnosis is aided by reflectance confocal microscopy (RCM): a promising technique that allows non-invasive imaging from the skin surface to the upper dermis with quasi-histologic resolution. The most common melanoma mutation involves the gene BRAF and it is represented by the BRAFV600E, however, V600K, V600R and V600D mutations are also known. Because different genetic aberrations categorize melanoma subtypes with distinct clinical characteristics, it is reasonable to hypothesize that a distinctive molecular signature corresponds to specific morphologic patterns. A comparison between the dermoscopic patterns of BRAF p.V600E, BRAF p.V600K and wild-type BRAF primary melanomas was assessed from a collection of 12 lesions (4 primary melanomas per each BRAFV600 mutated status and 4 wt). In 9 cases the RCM images were available and the frequency of the RCM descriptors was examined. The RCM analysis showed that the presence of plump bright cells, collagen bundles and inflammatory cells in the dermis were frequently observed even when dermoscopy showed no regression features. Our study showed that regression phenomena and the associated dermoscopic and RCM descriptors could help the clinician to discriminate between the different BRAF mutated status, providing key information for patient screening, management and follow-up

BRAFp.V600E, p.V600K, and p.V600R Mutations in Malignant Melanoma: Do They Also Differ in Immunohistochemical Assessment and Clinical Features?

Although the detection of BRAF p.V600E mutation by immunohistochemistry was clearly described in melanoma, discordant evidences were reported for the detection of p.V600K and p.V600R mutations. The aim of the study was to evaluate the efficacy of BRAFp.V600E, p.V600K, and p.V600R detection by immunohistochemistry in melanoma

Quick assessment of cell-free DNA in seminal fluid and fragment size for early non-invasive prostate cancer diagnosis

Liquid biopsy consists in the quantification and qualification of circulating cell-free DNA (cfDNA) and tumor-derived DNA (ctDNA) for cancer recognition. Recently, the characterization of seminal cfDNA (scfDNA) has been reported as a possible biomarker for prostate cancer (PCa) diagnosis

NF1 truncating mutations associated to aggressive clinical phenotype with elephantiasis neuromatosa and solid malignancies

Background/aim: Von Recklinghausen disease is a syndrome characterized by a wide phenotypic variability giving rise to both, cutaneous and visceral benign and malignant neoplasms. The first include cutaneous neurofibromas, subcutaneous and plexiform neurofibromas. The latter can undergo malignant transformation and/or determine elephantiasis neuromatosa. Visceral tumors may include malignant peripheral nerve sheet tumors, gastrointestinal stromal tumors, cerebral gliomas and abdominal neurofibromas. In the present study, the authors discuss the clinical and biomolecular characterization of a cohort of 20 families with a diagnosis of type 1 neurofibromatosis. Patients and methods: Clinically, the cohort includes three probands with elephantiasis neuromatosa and a peculiarly high incidence of breast and gastrointestinal cancer. Results: Among the 14 NF1 mutations documented, 10 encoding for a truncated protein have been associated to particularly aggressive clinical phenotypes including elephantiasis neuromatosa, malignant peripheral nerve sheet tumors, breast cancer, gastrointestinal stromal tumors. Conclusion: This effect on protein synthesis, rather than the type of NF1 mutation, is the key to the explanation of the genotype-phenotype correlations in the context of neurofibromatosis type 1

A VLBI experiment using a remote atomic clock via a coherent fibre link

We describe a VLBI experiment in which, for the first time, the clock reference is delivered from a National Metrology Institute to a radio telescope using a coherent fibre link 550 km long. The experiment consisted of a 24-hours long geodetic campaign, performed by a network of European telescopes; in one of those (Medicina, Italy) the local clock was alternated with a signal generated from an optical comb slaved to a fibre-disseminated optical signal. The quality of the results obtained with this facility and with the local clock is similar: interferometric fringes were detected throughout the whole 24-hours period and it was possible to obtain a solution whose residuals are comparable to those obtained with the local clock. These results encourage further investigation of the ultimate VLBI performances achievable using fibre dissemination at the highest precision of state-of-the-art atomic clocks

Comparing Remote Atomic Clocks via VLBI Networks and Fiber Optic Links: the LIFT/MetGeSp Perspective

Very Long Baseline Interferometry experiments require an extremely precise synchronization between the atomic clocks keeping the time and frequency standards at radiotelescope observatories. Recently the availability of fiber optic links from a few radio observatories and their national metrological institutes has made the streaming of extremely stable frequency standards via optical atomic clocks possible (even two orders of magnitudes better than Rubidium or Hydrogen maser standards). Firstly, we present the infrastructure of the Italian Link for Frequency and Time (LIFT) and results of the MetGeSp project aimed at finally creating a common clock between two of the antennas of the VLBI Italian Network. Secondly, the results are shown from VLBI experiments in which the rms phase noise was used to accurately compare the synchronicity of atomic clocks located at a few European stations (Medicina, Noto, Yebes, Torun, and Matera). VLBI clock timing proves a valid alternative to satellite-based techniques such as the Global Navigation Satellite System or the Two-Way Satellite Time and Frequency Transfer

The First Geodetic VLBI Field Test of LIFT: a 550-km-long Optical Fiber Link for Remote Antenna Synchronization

We present the first field test of the implementation of a coherent optical fiber link for remote antenna synchronization realized in Italy between the Italian Metrological Institute (INRIM) and the Medicina radio observatory of the National Institute for Astrophysics (INAF). The Medicina VLBI antenna participated in the EUR137 experiment carried out in September 2015 using, as reference systems, both the local H-maser and a remote H-maser hosted at the INRIM labs in Turin, separated by about 550 km. In order to assess the quality of the remote clock, the observed radio sources were split into two sets, using either the local or the remote H-maser. A system to switch automatically between the two references was integrated into the antenna field system. The observations were correlated in Bonn and preliminary results are encouraging since fringes were detected with both time references along the full 24 hours of the session. The experimental set-up, the results, and the perspectives for future radio astronomical and geodetic experiments are presented

Optical Fiber Links Used in VLBI Networks and Remote Clock Comparisons: the LIFT/MetGesp Project

The synchronization between atomic clocks plays an important part in both radio astronomical and geodetic Very Long Baseline Interferometry, as the clocks are responsible for providing time and frequency reference at radio stations. The availability of highly stable optical fiber links from a few radio observatories and their national metrological institutes has recently allowed the streaming of frequencies from optical clocks based on the Sr/Yb lattice technology (even two order of magnitudes more stable than H-maser clocks). We will present the current status of the Italian Link for Frequency and Time (LIFT) and the ongoing e orts to realize a geodetic experiment utilizing the radio stations in Medicina and Matera connected in common clock via the optical fiber link. We will then show the results from the latest VLBI clock timing experiments also making use of the LIFT link to compare atomic clocks of the three italian radio VLBI antennas (Mc, Sr and Nt) using the rms noise in the interferometric phase. VLBI clock timing proves more e ective than Global Navigation Satellite System and less expensive than Two-Way Satellite Frequency and Time Transfer in synchronizing remote clocks