Mesenchymal tumours of the gastrointestinal tract

Mesenchymal tumours represent a heterogenous group of neoplasms encopassing benign, intermediate malignancy, and malignant entities. Sarcomas account for approximately 1% of human malignancies. In consideration of their rarity as well as of intrinsic complexity, diagnostic accuracy represents a major challenge. Traditionally, mesenchymal tumours are regarded as lesions the occurrence of which is mostly limited to somatic soft tissues. However, the occurrence of soft tissue tumours at visceral sites represent a well recognized event, and the GI-tract ranks among the most frequently involved visceral location. There exist entities such as gastrointestinal stromal tumours (GIST) and malignant gastointestinal neuroectodermal tumors that exhibit exquisite tropism for the GI-tract. This review will focus also on other relevant clinico-pathologic entities in which occurrence at visceral location is not at all negligible

Current molecular biomarkers evaluation in gastric/gastroesophageal junction adenocarcinoma: pathologist does matter

The comprehensive molecular characterization of gastric and gastroesophageal junction adenocarcinomas has led to the improvement of targeted and more effective treatments. As a result, several biomarkers have been introduced into clinical practice and the implementation of innovative diagnostic tools is under study. Such assessments are mainly based on the evaluation of limited biopsy material in clinical practice. In this setting, the pathologist represents a key player in the selection of patients facilitating precision medicine approaches

Colorectal adenosquamous carcinoma: Peculiar morphologic features and distinct immunoprofiles in squamous and glandular components

Colorectal adenosquamous carcinoma (ASC) is exceedingly rare, comprising less than 0.1% of all colorectal malignancies, and is characterized by the admixture of glandular and squamous components. Due to its rarity, immunohistochemical and biological profiles have not been well investigated. The clinico-pathologic features of 29 cases of primary colorectal adenosquamous carcinomas, including four synchronous metastases, as well as the immunohistochemical expression of keratin 20, CDX2, keratin 34 beta E12, keratin 5/6, p63, p40, beta-Catenin, Cyclin D1 and mismatch repair protein (MMR) expression in both squamous and glandular components are described. All ASCs showed aggressive clinico-pathologic features; all cases showed at least one aggressive pathologic characteristic (poorly differentiated, vascular invasion, infiltrative growth pattern) and 69% of cases were either stage III or IV. The squamous component was keratin 34 beta E12 positive in all cases and keratin 5/6 positive in 27 cases, while only 7 cases showed p63 and/or p40 expression. beta-Catenin and Cyclin D1 showed different expression, with nuclear staining of Cyclin D1 in the squamous component of all cases (both primary and metastatic lesions) and nuclear staining of beta-Catenin predominantly in the glandular component. All but one case showed proficient MMR profile. Sixteen patients (64%) died of their disease with median survival of 10 months. ASC show aggressive clinical outcome and aggressive pathologic characteristics. A peculiar keratin 34 beta E12 positive profile in the squamous component is seen differing from squamous cell carcinoma and non-intestinal ASC. The staining patterns for beta-Catenin and Cyclin D1 between components, supports a possible divergent clonal evolution of the neoplasm

The Pathologic and Molecular Landscape of Esophageal Squamous Cell Carcinogenesis

Esophageal squamous cell carcinoma represents the most common histotype of epithelial neoplasm occurring within esophageal mucosa worldwide. Despite the comprehensive molecular characterization of this entity, to date no significant targeted therapy has been introduced into clinical practice. In this review, we describe the molecular landscape of esophageal squamous cell carcinoma based on the most recent literature. Moreover, we focus on other rare variants and on the relationship with head and neck squamous cell carcinomas

The Immunopathological and Histological Landscape of COVID-19-Mediated Lung Injury

A complete understanding of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) physiopathology and related histopathologic lesions is necessary to improve treatment and outcome of coronavirus disease 2019 (COVID-19) patients. Many studies have focused on autopsy findings in COVID-19-related deaths to try and define any possible specific pattern. Histopathologic alterations are principally found within lungs and blood vessels, and these abnormalities also seem to have the highest clinical impact. Nevertheless, many of the morphological data collected so far are non-specific, fickle, and possibly associated with other co-existing factors. The aim of this minireview is to describe the main histopathological features related to COVID-19 and the mechanism known as "cytokine storm"

MicroRNAs as Predictive Biomarkers of Resistance to Targeted Therapies in Gastrointestinal Tumors

The advent of precision therapies against specific gene alterations characterizing different neoplasms is revolutionizing the oncology field, opening novel treatment scenarios. However, the onset of resistance mechanisms put in place by the tumor is increasingly emerging, making the use of these drugs ineffective over time. Therefore, the search for indicators that can monitor the development of resistance mechanisms and above all ways to overcome it, is increasingly important. In this scenario, microRNAs are ideal candidate biomarkers, being crucial post-transcriptional regulators of gene expression with a well-known role in mediating mechanisms of drug resistance. Moreover, as microRNAs are stable molecules, easily detectable in tissues and biofluids, they are the ideal candidate biomarker to identify patients with primary resistance to a specific targeted therapy and those who have developed acquired resistance. The aim of this review is to summarize the major studies that have investigated the role of microRNAs as mediators of resistance to targeted therapies currently in use in gastro-intestinal neoplasms, namely anti-EGFR, anti-HER2 and anti-VEGF antibodies, small-molecule tyrosine kinase inhibitors and immune checkpoint inhibitors. For every microRNA and microRNA signature analyzed, the putative mechanisms underlying drug resistance were outlined and the potential to be translated in clinical practice was evaluated

Molecular Landscapes of Gastric Pre-Neoplastic and Pre-Invasive Lesions

none14: Gastric carcinoma (GC) represents one of the most common and most lethal malignancies worldwide. The histopathological characterization of GC precursor lesions has provided great knowledge about gastric carcinogenesis, with the consequent introduction of effective strategies of primary and secondary prevention. In recent years, a large amount of data about the molecular events in GC development is emerging, flanking the histomorphological descriptions. In this review, we describe the landscape of molecular alterations in gastric pre-invasive lesions with a glance at their potential use in the diagnostic and therapeutic decision-making process.openBusinello, Gianluca; Angerilli, Valentina; Parente, Paola; Realdon, Stefano; Savarino, Edoardo; Farinati, Fabio; Grillo, Federica; Vanoli, Alessandro; Galuppini, Francesca; Paccagnella, Silvia; Pennelli, Gianmaria; Mastracci, Luca; Saragoni, Luca; Fassan, MatteoBusinello, Gianluca; Angerilli, Valentina; Parente, Paola; Realdon, Stefano; Savarino, Edoardo; Farinati, Fabio; Grillo, Federica; Vanoli, Alessandro; Galuppini, Francesca; Paccagnella, Silvia; Pennelli, Gianmaria; Mastracci, Luca; Saragoni, Luca; Fassan, Matte

Colorectal adenosquamous carcinoma: genomic profiling of a rare histotype of colorectal cancer

Colorectal adenosquamous carcinoma (ASC) is exceedingly rare, comprising less than 0.1% of all colorectal malignancies, and is characterized by an aggressive disease course, with a higher metastatic rate and worse outcome than conventional colorectal adenocarcinoma. A comprehensive molecular profile of this group of neoplasms is still lacking. A total of 22 cases of colorectal ASCs (with 22 primary lesions and 7 metastases matched with 4 primaries) were subject to NGS targeting 67 cancer-related genes (VariantPlex solid tumor; Archer). Mismatch repair (MMR), p53, and (V600E)BRAF status were also investigated by immunohistochemistry. In 28 of 29 (96.6%) ASC samples, at least one single-nucleotide variant (SNV) or copy number variation (CNV) was detected. Among the 22 primary tumors, the most frequently mutated genes were TP53 (59.1%), APC (40.9%), KRAS (27.3%), BRAF (13.6%), and GNAS (9.1%). Only 1/22 (4.5%) primary ASC was MMR-deficient (MMRd) and harbored a BRAF mutation. Limited differences in SNVs were observed between primary and metastatic diseases. This study sheds light on the molecular landscape of colorectal ASCs. According to our data, the genomic profile of colorectal ASC is similar to that of conventional colorectal carcinoma, with significant druggable genetic alterations. Further studies are required to understand the more aggressive clinical behavior of this neoplasm