Primary Ewing sarcoma of the lung: A systematic review of the recent literature.

Primary pulmonary Ewing sarcoma (PES) is a rare malignancy with only sporadic cases reported in the scientific literature. We performed a systematic review of the cases published in the last decade on PubMed, with the aim to describe the clinical, pathological, therapeutic, and prognostic data of PES. Forty-two articles reporting on 50 cases have been reviewed. Globally, 60 % of the patients were males, and the mean age at diagnosis was 30.5 years, with only a few cases diagnosed after 50 years of age. The most common clinical manifestations at diagnosis were dyspnea, cough and chest pain. The most common immunohistochemistry findings were staining for CD99 and (less frequently) for vimentin, and no staining for TTF-1, cytokeratin, desmin and S-100. ESWR1-FL1 translocation was tested in less than half of the cases. The disease was often locally advanced, treated generally with multidisciplinary treatment combining surgery, chemotherapy and radiation therapy. Among patients with follow-up data, approximately 40 % were dead at the time of publication, with the median survival being 11.5 months. Among those who were alive, only 8.3 % was free from disease at 48 months from diagnosis.

Mutational Profiles of Cutaneous Squamous Cell Carcinomas with Different Patterns of Clinical Aggression from Head and Neck Regions.

Cutaneous squamous cell carcinoma is a prevalent malignancy with a rising incidence and a notably high mutational load. Exploring the genetic nuances of cSCC and investigating molecular approaches stands as a potential avenue for improving outcomes in high-risk patients. This retrospective case-control study involved two cohorts, one of 14 patients (the "discovery cohort") and the other of 12 patients (the "validation cohort"), with cSCC located in the head/neck anatomical region and diagnosed at the pT2 stage. Overall, cases developed early local relapses of the disease, whereas controls never relapsed during the entire follow-up period. A next-generation sequencing (NGS) approach conducted on histological samples revealed that TP53 and CDKN2A were the most frequently mutated genes in our series. No specific mutations were identified as potential prognostic or therapeutic targets. Controls exhibited a tendency toward a higher mutational rate compared to cases. It is possible that an increased number of mutations could prompt the cSCC to expose more antigens, becoming more immunogenic and facilitating recognition by the immune system. This could enhance and sustain the immunological response, potentially preventing future recurrences.

Whole-exome Sequencing of Prostate Cancer in Sardinian Identify Recurrent UDP-glucuronosyltransferase Amplifications.

Globally, prostate cancer is the third most common cancer in the world, and the second most common cancer in men. However, rates for incidence and mortality vary considerably with race, ethnicity, and geography. Over 97 significantly mutated genes that have been identified in prostate cancer; however, a lack of genomic prostate cancer studies focusing on different racial and ethnic groups and racial mixing pose a serious challenge to universalize these findings. The Sardinian population is an isolated Mediterranean population that has a high frequency of centenarians and a much lower incidence of prostate cancer than found in males in mainland Europe. Here, we conducted a genomic prostate cancer study on a Sardinian cohort diagnosed with local prostate cancer. Our data reveals a low rate of ERG fusion in Sardinian prostate cancer. Interestingly, we identified a novel BTBD7-SLC2A5 fusion that occurred in 13% of the patients. We also found that the UGT2B4 on 4q13.2 was amplified in 20% of the Sardinian patients but rarely amplified in patients of other population. These observations underscore the importance of the inter-population molecular heterogeneity of prostate cancer. In addition, we examined the expression of UGT2B4 in 497 prostate cancer patients derived from The Cancer Genome Atlas database. We found that high expression of UGT2B4 was associated with low-grade prostate cancer and upregulation of UGT2B4 in tumors was associated with upregulation of metabolism pathways such as 'de novo' IMP biosynthetic process, glutamine and monocarboxylic acid metabolism. These data provide insight into clinical relevance and functional mechanism of UGT2B4. Further understanding functional mechanism of UGT2B4 amplification and BTBD7-SLC2A5 fusion will aid in developing drugs to benefit the prostate cancer patients.

Comparison of BRAF Mutation Screening Strategies in a Large Real-Life Series of Advanced Melanoma Patients.

Malignant melanoma (MM) is one of the deadliest skin cancers. BRAF mutation status plays a predominant role in the management of MM patients. The aim of this study was to compare BRAF mutational testing performed by conventional nucleotide sequencing approaches with either real-time polymerase chain reaction (rtPCR) or next-generation sequencing (NGS) assays in a real-life, hospital-based series of advanced MM patients. Consecutive patients with AJCC (American Joint Committee on Cancer) stage IIIC and IV MM from Sardinia, Italy, who were referred for molecular testing, were enrolled into the study. Initial screening was performed to assess the mutational status of the BRAF and NRAS genes, using the conventional methodologies recognized by the nationwide guidelines, at the time of the molecular classification, required by clinicians: at the beginning, Sanger-based sequencing (SS) and, after, pyrosequencing. The present study was then focused on BRAF mutation detecting approaches only. BRAF wild-type cases with available tissue and adequate DNA were further tested with rtPCR (Idylla™) and NGS assays. Globally, 319 patients were included in the study; pathogenic BRAF mutations were found in 144 (45.1%) cases examined with initial screening. The rtPCR detected 11 (16.2%) and 3 (4.8%) additional BRAF mutations after SS and pyrosequencing, respectively. NGS detected one additional BRAF-mutated case (2.1%) among 48 wild-type cases previously tested with pyrosequencing and rtPCR. Our study evidenced that rtPCR and NGS were able to detect additional BRAF mutant cases in comparison with conventional sequencing methods; therefore, we argue for the preferential utilization of the aforementioned assays (NGS and rtPCR) in clinical practice, to eradicate false-negative cases and improve the accuracy of BRAF detection.

Primary extranodal vaginal non-hodgkin lymphoma: Diagnostic pitfalls and therapeutic challenges.

INTRODUCTION: Primary extranodal non-hodgkin vaginal lymphoma (PeNHVL) represents a rare entity, with few data published until now. We present here a series of patients with PeNHVL, analyzing our data as part of a detailed review of the available literature. METHODS: The study included a consecutive series of 6 patients with final diagnosis of PeNHVL admitted at our Institution between January 2000 and December 2017. The systematic review was conducted according to PRISMA guidelines. A literature search of the PubMed, MEDLINE and EMBASE electronic databases was performed using the following terms: 'vaginal lymphoma'. Relevant data were collected and analyzed for the purposes of this study, reporting results through a narrative approach. RESULTS: In our series discomfort and vaginal pain, refractory to medical treatments represent the symptoms of disease presentation, and the presence of localized/diffused anelastic area in the vaginal wall with tactile sensation of cork emerges as diagnostic sign (Cork Wall sign). The literature revision included 41 studies, with an overall population of 74 patients. The vast majority of women were diagnosed as early stage disease (93.6%) and received chemotherapy (74.6%) with a very high response rate (96%). Death from disease occurred in 5 women (6.7%). CONCLUSIONS: Localized or diffused hard-ligneous vaginal areas with Cork Wall sign represent the typical sign of disease presentation. PeNHVL is characterized by a very high sensitivity to chemotherapy and very favourable prognosis; therefore, radical surgery is not indicated. Histotype characterization is crucial to identify those uncommon variants associated with a less favorable clinical outcome.

BRAF Mutations and Dysregulation of the MAP Kinase Pathway Associated to Sinonasal Mucosal Melanomas.

Sinonasal mucosal melanoma (SNM) is a rare and aggressive type of melanoma, and because of this, we currently have a limited understanding of its genetic and molecular constitution. The incidence among SNMs of somatic mutations in the genes involved in the main molecular pathways, which have been largely associated with cutaneous melanoma, is not yet fully understood. Through a next-generation sequencing (NGS) approach using a panel of 25 genes involved in melanoma pathogenesis customized by our group, we performed a mutation analysis in a cohort of 25 SNM patients. Results showed that pathogenic mutations were found in more than 60% of SNM cases at a somatic level, with strikingly 32% of them carrying deleterious mutations in the BRAF gene. The identified mutations mostly lack the typical UV signature associated with cutaneous melanomas and showed no significant association with any histopathological parameter. Oncogenic activation of the BRAF-depending pathway, which may induce immune tolerance into the tumour microenvironment (i.e., by increasing the VEGF production) was poorly associated with mutations in genes that have been related to diminished clinical benefit of the treatment with BRAF inhibitors. Screening for mutations in BRAF and other MAPK genes should be included in the routine diagnostic test for a better classification of SNM patients.