Mechanism of efficacy of trabectedin against myxoid liposarcoma entails detachment of the FUS-DDIT3 transcription factor from its DNA binding sites.

Background: The marine drug trabectedin has shown unusual effectiveness in the treatment of myxoid liposarcoma (MLPS), a liposarcoma characterized by the expression of the FUS-DDIT3 chimera. Trabectedin elicits a significant transcriptional response in MLPS resulting in cellular depletion and reactivation of adipogenesis. However, the role of the chimeric protein in the mechanism of action of the drug is not entirely understood.

True Mitotic Count Prediction in Gastrointestinal Stromal Tumors: Bayesian Network Model and PROMETheus (Preoperative Mitosis Estimator Tool) Application Development.

Background: Gastrointestinal stromal tumors (GISTs) present a complex clinical landscape, where precise preoperative risk assessment plays a pivotal role in guiding therapeutic decisions. Conventional methods for evaluating mitotic count, such as biopsy-based assessments, encounter challenges stemming from tumor heterogeneity and sampling biases, thereby underscoring the urgent need for innovative approaches to enhance prognostic accuracy.

Objective: The primary objective of this study was to develop a robust and reliable computational tool, PROMETheus (Preoperative Mitosis Estimator Tool), aimed at refining patient stratification through the precise estimation of mitotic count in GISTs.

Unveiling the risks of ChatGPT in diagnostic surgical pathology.

ChatGPT, an AI capable of processing and generating human-like language, has been studied in medical education and care, yet its potential in histopathological diagnosis remains unexplored. This study evaluates ChatGPT's reliability in addressing pathology-related diagnostic questions across ten subspecialties and its ability to provide scientific references. We crafted five clinico-pathological scenarios per subspecialty, simulating a pathologist using ChatGPT to refine differential diagnoses.

Hepatocellular Carcinoma Immune Microenvironment Analysis: A Comprehensive Assessment with Computational and Classical Pathology.

Purpose: The spatial variability and clinical relevance of the tumor immune microenvironment (TIME) are still poorly understood for hepatocellular carcinoma (HCC). In this study, we aim to develop a deep learning (DL)-based image analysis model for the spatial analysis of immune cell biomarkers and microscopically evaluate the distribution of immune infiltration.

Experimental Design: Ninety-two HCC surgical liver resections and 51 matched needle biopsies were histologically classified according to their immunophenotypes: inflamed, immune-excluded, and immune-desert.

Disruptions in antigen processing and presentation machinery on sarcoma.

Background: The antigen processing machinery (APM) plays a critical role in generating tumor-specific antigens that can be recognized and targeted by the immune system. Proper functioning of APM components is essential for presenting these antigens on the surface of tumor cells, enabling immune detection and destruction. In many cancers, defects in APM can lead to immune evasion, contributing to tumor progression and poor clinical outcomes.

How to measure your microscope's HPF. A critical guide for residents.

Counting stuff under the microscope is part of the duties of a surgical pathologist. Many textbooks and articles still report the surface area as the number of high-power fields (HPFs) counted. This is bad, since the area displayed by an HPF varies between two microscopes.

Prognostic value of mitotic count in leiomyosarcoma: A comprehensive monocentric retrospective study.

Background: Leiomyosarcomas (LMSs) include heterogeneous entities with different clinical courses not entirely predicted by known prognostic factors. In particular, the value of mitotic count as independent prognostic factor in LMS has been poorly investigated.

Methods: We retrospectively analyzed all patients with a diagnosis of LMS who accessed to our Institution from June 1999 to May 2022 for which mitotic count was numerically expressed within the pathology report.

Multidisciplinary management of adolescents and young adults (AYA) sarcoma: A successful effort of an adult high-volume cancer center.

Introduction: The aim of this retrospective study was to investigate the clinicopathological characteristics of AYA sarcomas and their clinical outcomes at a high-volume single center.

Methods: Demographic, clinicopathological data on the diagnosis, treatment and follow-up of all sarcoma patients aged 16-39 years (ys) observed at our Institute between January 2010 and December 2021 were retrospectively collected, including diagnostic (TTD) and treatment delay(TTT), clinical outcomes (OS and PFS), and late-treatment effects.

Results: We identified 228 AYA patients, median age 30 years, 29% ≤ 25 years, 57% males, 88% soft tissue sarcomas (STS), and 12% bone sarcomas (BS).

Case Report: Should Regorafenib be prescribed as a continuous schedule in gastrointestinal stromal tumors? Three case reports on Regorafenib personalized schedule.

Introduction: Regorafenib is a tyrosine kinase inhibitor (TKI) approved in metastatic gastrointestinal stromal tumor (GIST), colorectal cancer, and hepatocarcinoma. Anyway, the toxicity profile of Regorafenib standard schedule is associated with poor compliance and a high rate of discontinuation. For this reason, there is a growing need for a Regorafenib personalized schedule emerging from the scientific community.

Exploring the CXCR4/CXCR7/CXCL12 Axis in Primary Desmoid Tumors.

Background: Desmoid tumors have an extremely variable natural history. The uncertainty behind desmoid behavior reflects the complexity, which subtends its development and non-linear advancement. Apart from Wnt- βcatenin mutation, estrogen receptors, and COX-2 overexpression, little is known about the ability of desmoids to grow and recur while being unable to metastasize.

A clinical and pathological update on hepatocellular carcinoma.

It is estimated that more than 1 million individuals will be affected annually by hepatocellular carcinoma (HCC) by 2025. HCC can be broadly grouped into two major molecular subgroups, each of which is characterized by specific morphological and phenotypic features that mirror the genetic background. The use of these tissue biomarkers in the daily practice of pathologists promises to better allocate patients with HCC with adequate treatments.

Poorly-differentiated and undifferentiated sarcomas of the mediastinum: a bag of tricks.

Mediastinum is a Pandora's Box containing many different structures that can give origin to several cancer types. Our aims are to provide a general framework to make a diagnosis of an undifferentiated pleomorphic sarcoma and to highlight relevant immunohistochemical and molecular techniques that can help in the differential diagnosis. We, therefore, provide a simple three-step algorithmic approach to diagnose pleomorphic sarcoma, emphasizing the role of clinicopathological correlations and advocating for a "relative frequency" method, especially when the material for the diagnosis is scarce, as in small biopsies.

Hepatocellular carcinoma: a clinical and pathological overview.

HCC incidence rates have been rising in the past 3 decades and by 2025 > 1 million individuals will be affected annually. High-throughput sequencing technologies led to the identification of several molecular HCC subclasses that can be broadly grouped into 2 major subgroups, each characterized by specific morphological and phenotypical features. It is likely that this increasing knowledge and a more appropriate characterization of HCC at the pathological level will impact HCC patient management.

Myoid gonadal tumor. Case series, systematic review, and Bayesian analysis.

Myoid gonadal stromal tumor represents a rare testicular neoplasm displaying smooth muscular and gonadal stromal differentiation. This entity has very few cases reported in the literature that describe heterogeneous clinical and pathological characteristics. Bayesian statistics provides a useful framework to combine information from diverse sources.

Event-free survival in Desmoid-Type fibromatosis (DTF): A pre-post comparison of upfront surgery versus wait-and-see approach.

Background: Desmoid-Type Fibromatosis (DTF) is a rare mesenchymal neoplasm with a locally invasive pattern and high risk of local recurrence after surgery. Historically, the standard treatment for DTF was surgical resection. However, considering the difficulty of achieving surgical eradication, the possible unnecessary morbidity and the unpredictability of the natural history, a wait-and-see approach has been proposed for asymptomatic DTF.

Multimodality imaging of adult rhabdomyosarcoma: the added value of hybrid imaging.

Rhabdomyosarcoma (RMS) represents more than 50% of paediatric soft tissue tumours. Conversely, it is extremely rare among adults, where it shows peculiar biological and clinical features that are still poorly investigated. RMS patients should be referred to a Sarcoma Centre, where the contribution of experienced radiologists plays a relevant role in the diagnostic assessment of the disease, including precise localisation, staging, image-guided biopsy, response evaluation after treatment and follow-up.

Clinical Application of a Real-Time Telepathology System for Frozen Section Diagnosis in Comparison With Optical Microscope.

The imbalance between the increasing demand of highly specialized service and the reduction of specialists able to release this service is a global challenge for Pathology. This situation applies also to the setting of intra-operatory diagnostic: here the broad presence of Surgical divisions contrasts with the contraction of Pathology departments, progressively concentrated in few hospitals. The use of e-pathology device, such as remote-control microscopes, offers a possible solution to this imbalance.

Vessels Encapsulating Tumor Clusters (VETC) Is a Powerful Predictor of Aggressive Hepatocellular Carcinoma.

We investigated the clinical significance of a vascular growth pattern of hepatocellular carcinoma (HCC), the vessels that encapsulate tumor clusters (VETC), previously linked to HCC metastatic dissemination. VETC was assessed in a large multi-institutional cohort of 541 resected HCCs from Italy, Korea and Japan, and matched against a full spectrum of clinical and pathological variables. The VETC phenotype (defined as ≥ 55% tumor area by CD34 immunostaining) was easily reproducible and reliably detectable in whole sections and small-sized tissues of tissue microarray.

Cryoembedder, automatic processor/stainer, liquid nitrogen freezing, and manual staining for frozen section examination: A comparative study.

Frozen section examination (FSE) reshaped surgical pathology and is characterized by a high accuracy. Nonetheless pathologists can experience artefacts that can compromise or defer the diagnosis. We compared a commercial system, composed by a cryoembedder and a processor/stainer, to our FSE protocol.