Histopathological Landscape of Precursor Lesions of Gastro-Entero-Pancreatic Neuroendocrine Neoplasms.

Background: Despite the important advances in research on neuroendocrine neoplasms of the gastro-entero-pancreatic tract, their precursor lesions are much less well known.

Summary: This review analyzes the preneoplastic neuroendocrine lesions of the gastro-entero-pancreatic tract, by adopting a coherent anatomical benchmark. In particular, the settings in which neuroendocrine precursor lesions represent well-recognized pathophysiological and morphological entities (with eventual molecular correlates) have been distinguished from the ones in which the nature of preneoplastic changes is still obscure.

The Morpho-Molecular Landscape of Spitz Neoplasms.

Spitz neoplasms are a heterogeneous group of melanocytic proliferations with a great variability in the histological characteristics and in the biological behavior. Thanks to recent discoveries, the morpho-molecular landscape of Spitz lineage is becoming clearer, with the identification of subtypes with recurrent features thus providing the basis for a more solid and precise tumor classification. Indeed, specific mutually exclusive driver molecular events, namely or mutations, copy number gains of 11p, and fusions involving and genes, correlate with distinctive histological features.

mTOR pathway and somatostatin receptors expression intratumor-heterogeneity in ileal NETs.

The knowledge of the molecular landscape of ileal neuroendocrine tumors (NETs) is affected by the lack of systematic studies investigating intra-tumoral heterogeneity. In this study, intra-tumoral heterogeneity was investigated in 27 primary ileal G1-NETs and their matched nodal and liver metastases in order to assess the tumor grading, the expression status of two somatostatin receptor isoforms (i.e.

Histopathological landscape of rare oesophageal neoplasms.

The landscape of neoplastic pathology of the oesophagus is dominated by malignancies of epithelial origin, in particular by oesophageal adenocarcinoma and oesophageal squamous cell carcinoma. However, several other histopathological variants can be distinguished, some associated with peculiar histopathological profiles and prognostic behaviours and frequently underrecognized in clinical practice. The aim of this review is to provide a comprehensive characterization of the main morphological and clinical features of these rare variants of oesophageal neoplastic lesions.

The heterogeneous clinical and pathological landscapes of metastatic -mutated colorectal cancer.

Colorectal cancer (CRC) is a complex and molecularly heterogeneous disease representing one of the most frequent causes of cancer-related death worldwide. About 8-15% of CRCs harbor a mutation in gene, a proto-oncogene involved in cell proliferation, differentiation and survival through the MAPK signaling cascade. The acquisition of mutation is an early event in the "serrated" CRC carcinogenetic pathway and is associated with specific and aggressive clinico-pathological and molecular features.

Tumor mutation burden: from comprehensive mutational screening to the clinic.

The recent advent of immunomodulatory therapies into the clinic has demanded the identification of innovative predictive biomarkers to identify patients most likely to respond to immunotherapy and support the design of tailored clinical trials. Current molecular testing for selection of patients with gastrointestinal or pulmonary carcinomas relies on the prevalence of PD-L1 expression in tumor as well as immune cells by immunohistochemistry and/or on the evaluation of the microsatellite status. Tumor Mutational Burden (TMB) has emerged as a promising novel biomarker in this setting to further aid in patient selection.