New driver alterations in non-small cell lung cancer. A narrative review

Objective: This review aims to provide an up-to-date snapshot on the state of development of novel biomarker-driven treatments in non-small cell lung cancer (NSCLC). Background: The introduction of immune checkpoint inhibitors and target therapies has revolutionized the natural history of many NSCLCs, allowing for lasting and profound responses. In particular, mutations in the epidermal growth factor receptor (EGFR), rearrangements of the anaplastic lymphoma kinase (ALK), or oncogene c-Ros 1 (ROS1) have marked a paradigm shift in the treatment of NSCLC. Furthermore, new inhibitors for B-Raf proto-oncogene (BRAF), rearranged during transfection (RET), mesenchymal-to-epithelial transition factor (MET), or neurotrophic tyrosine kinase (NTRK) 1–3 have revealed fascinating data, obtaining accelerated approvals from the Food and Drug Administration (FDA) and European Medicines Agency (EMA). Today, the extensive use of next-generation sequencing (NGS) techniques has shown a broad molecular heterogeneity of NSCLC. Many of the mutations identified are considered potential therapeutic targets, and numerous studies are currently evaluating the efficacy of selective inhibitors. Methods: We carried out an extensive review of the literature on PubMed, Web of Science, and Scopus databases and the congress abstracts presented at the American Society of Clinical Oncology (ASCO), European Society for Medical Oncology (ESMO), and World Conference on Lung Cancer (WCLC) in the last 5 years. Our analysis considered works regarding new inhibitors for alterations of Kirsten rat sarcoma viral oncogene homolog (KRAS), PIK3CA, neuregulin-1 (NRG-1), human epidermal growth factor receptor 2 (HER2), fibroblast growth factor receptor (FGFR), genes that have recently become no longer undruggable. Conclusions: Precision oncology is revolutionizing the natural history of NSCLC. Several alterations have been identified as possible treatment targets, and numerous inhibitors show promising results in ongoing clinical trials

A Challenging Nodular Lesion of the Ear

Skin nodular lesion are really frequent, but rapidly growing ones needs to be quickly removed since they can hide really aggressive skin tumor. Among malignant lesion Merkel cell carcinoma arise. It is a rare neuroendocrine skin tumor highly aggressive, not easy to diagnose at first stage, since at first diagnosis it is already widespreading all over the body. In order to renew interest in this letal skin tumori is mandatory to remind high risk population which include elderly people, white skin, chronically exposed to UV immunocompromised. Our unhappy case was described to increase awareness on this kind of skin tumor, since new drug appeared in the market can give an hope to these patients

Deep Sequencing of Immunoglobulin Genes Identifies a Very Low Percentage of Monoclonal B Cells in Primary Cutaneous Marginal Zone Lymphomas with CD30-Positive Hodgkin/Reed–Sternberg-like Cells

The spectrum of cutaneous CD30-positive lymphoproliferative disorders encompasses both inflammatory and neoplastic conditions. CD30+ Hodgkin and Reed–Sternberg-like cells have been occasionally reported in primary cutaneous marginal zone lymphoma, where they are thought to represent a side neoplastic component within a dominant background of lymphomatous small B cells. Herein, we describe the histological and molecular findings of three cases of primary cutaneous marginal zone lymphomas with CD30+ H/RS cells, in which next-generation sequencing analysis revealed the clonal population to consist in less than 5% of the cutaneous B-cell infiltrate, providing a thought-provoking focus on a possible main role for CD30+ cells in primary cutaneous marginal zone lymphoproliferations

Rna sequencing of primary cutaneous and breast-implant associated anaplastic large cell lymphomas reveals infrequent fusion transcripts and upregulation of PI3K/AKT signaling via neurotrophin pathway genes

Cutaneous and breast implant-associated anaplastic large-cell lymphomas (cALCLs and BI-ALCLs) are two localized forms of peripheral T-cell lymphomas (PTCLs) that are recognized as distinct entities within the family of ALCL. JAK-STAT signaling is a common feature of all ALCL subtypes, whereas DUSP22/IRF4, TP63 and TYK gene rearrangements have been reported in a proportion of ALK-negative sALCLs and cALCLs. Both cALCLs and BI-ALCLs differ in their gene expression profiles compared to PTCLs; however, a direct comparison of the genomic alterations and transcriptomes of these two entities is lacking. By performing RNA sequencing of 1385 genes (TruSight RNA Pan-Cancer, Illumina) in 12 cALCLs, 10 BI-ALCLs and two anaplastic lymphoma kinase (ALK)-positive sALCLs, we identified the previously reported TYK2-NPM1 fusion in 1 cALCL (1/12, 8%), and four new intrachromosomal gene fusions in 2 BI-ALCLs (2/10, 20%) involving genes on chromosome 1 (EPS15-GNG12 and ARNT-GOLPH3L) and on chromosome 17 (MYO18A-GIT1 and NF1-GOSR1). One of the two BI-ALCL samples showed a complex karyotype, raising the possibility that genomic instability may be responsible for intra-chromosomal fusions in BI-ALCL. Moreover, transcriptional analysis revealed similar upregulation of the PI3K/Akt pathway, associated with enrichment in the expression of neurotrophin signaling genes, which was more conspicuous in BI-ALCL, as well as differences, i.e., over-expression of genes involved in the RNA polymerase II transcription program in BI-ALCL and of the RNA splicing/processing program in cALCL