"Pathologists in Venice - Real World Cases for an Immersive Training Experience": Education, Gaming, and Show.

An international meeting entitled "Pathologists in Venice: Real World Cases for an Immersive Training Experience" took place on December 12 and 13, 2024 in Venice, Italy. More than 100 pathologists from all over the world were brought together to join four opinion leaders in different pathology fields. By matching real-time whole slide imaging-based navigation exposure with a technologically cutting-edge gaming format, the meeting engaged and provided the attendees with an innovative and immersive educational approach to real-world compelling scenarios they are likely to encounter in their daily practice.

MYC ecDNA promotes intratumour heterogeneity and plasticity in PDAC.

Intratumour heterogeneity and phenotypic plasticity drive tumour progression and therapy resistance. Oncogene dosage variation contributes to cell-state transitions and phenotypic heterogeneity, thereby providing a substrate for somatic evolution. Nonetheless, the genetic mechanisms underlying phenotypic heterogeneity are still poorly understood.

Oncocytic and spindle cell typical carcinoids of lung: different immunophenotype and biological behavior.

Pulmonary typical carcinoids (TCs) are uncommon, well-differentiated neuroendocrine tumors of the lung that do not exhibit necrosis and have fewer than two mitoses per 2 mm, as defined by the current World Health Organization classifications. Despite their low-grade status and favorable prognostic impact, the protein expression profile and morphological characteristics associated with tumor progression and metastatic spread remain largely unidentified. Oncocytic and spindle cell histological variants are acknowledged for their role in differential diagnosis, though their clinical significance remains a topic of debate.

Real-World Impact of Olaparib Exposure in Advanced Pancreatic Cancer Patients Harboring Germline BRCA1-2 Pathogenic Variants.

Introduction: Pancreatic cancer arising in the context of BRCA predisposition may benefit from poly(ADP-ribose) polymerase inhibitors. We analyzed real-world data on the impact of olaparib on survival in metastatic pancreatic cancer patients harboring germline BRCA mutations in Italy, where olaparib is not reimbursed for this indication.

Methods: Clinico/pathological data of pancreatic cancer patients with documented BRCA1-2 germline pathogenic variants who had received first-line chemotherapy for metastatic disease were collected from 23 Italian oncology departments and the impact of olaparib exposure on overall survival (OS) was analyzed.

iForensic, multicentric validation of digital whole slide images (WSI) in forensic histopathology setting according to the College of American Pathologists guidelines.

Pathology has benefited from the rapid progress of image-digitizing technology during the last decade. However, the application of digital whole slide images (WSI) in forensic pathology still needs to be improved. WSI validation is crucial to ensure diagnostic performance, at least equivalent to glass slides and light microscopy.

Challenges in developing response evaluation criteria for peptide receptor radionuclide therapy: A consensus report from the European Neuroendocrine Tumor Society Advisory Board Meeting 2022 and the ENETS Theranostics Task Force.

Assessing the response to systemic therapy in neuroendocrine tumors (NET) is challenging since morphological imaging response is often delayed and not necessarily reflective of clinical benefit. Peptide receptor radionuclide therapy (PRRT) has a complex mechanism of action, further complicating response assessment. In response to these challenges, the European Neuroendocrine Tumor Society (ENETS) Theranostics Task Force conducted a statement-based survey among experts to identify the current landscape and unmet needs in PRRT response assessment.

Local ablation disrupts immune evasion in pancreatic cancer.

Background: Pancreatic cancer (PC) is characterised by late diagnosis, tumour heterogeneity, and a peculiar immunosuppressive microenvironment, leading to poor clinical outcomes. Local ablative techniques have been proposed to treat unresectable PC patients, although their impact on activating the host immune system and overcoming resistance to immunotherapy remains elusive.

Methods: We dissected the immune-modulatory abilities triggered by local ablation in mouse and human PC models and human specimens, integrating phenotypic and molecular technologies with functional assays.

Combined analysis of a serum mRNA/miRNA marker signature and CA 19-9 for timely and accurate diagnosis of recurrence after resection of pancreatic ductal adenocarcinoma: A prospective multicenter cohort study.

Background And Aims: Timely and accurate detection of tumor recurrence in pancreatic ductal adenocarcinoma (PDAC) patients is an urgent and unmet medical need. This study aimed to develop a noninvasive molecular diagnostic procedure for the detection of recurrence after PDAC resection based on quantification of circulating mRNA and miRNA biomarkers in serum samples.

Methods: In a multicentric study, serum samples from a total of 146 patients were prospectively collected after resection.

Morphologic Characterization of Pancreatic Ductal Adenocarcinoma following Post-neoadjuvant Pancreatectomy and Clinical value of Intratumor Heterogeneity.

Objective: To evaluate the morphologic landscape of pancreatic ductal adenocarcinoma (PDAC), intratumor spatial heterogeneity, and the resulting clinical impact following post-neoadjuvant pancreatectomy.

Summary Background Data: The clinical value of PDAC morphologic subtypes and intratumor spatial heterogeneity post-treatment remains an open issue.

Materials And Methods: The study cohort included patients who underwent post-neoadjuvant pancreatectomy for PDAC at the University of Verona Hospital Trust between 2013 and 2019.

Long-Term Survivor of Intrahepatic Cholangiocarcinoma for over 18 Years: Case Study with Longitudinal Histo-molecular and Tumor Immune Microenvironment Characterization and Systematic Review of the Literature.

Background: Intrahepatic cholangiocarcinoma is a biliary neoplasm usually showing a dismal prognosis. In early stages, surgical resection is the best treatment option, significantly increasing the overall survival. This approach is also recommended in the case of relapsing disease.

The Exon Junction Complex component EIF4A3 plays a splicing-linked oncogenic role in pancreatic ductal adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal cancers, underscoring the urgent need for in-depth biological research. The phenomenon of alternative RNA splicing dysregulation is a common hallmark in cancer, including PDAC, presenting new avenues for understanding and developing diagnostic and therapeutic tools. Our research focuses on EIF4A3, a core component of the Exon Junction Complex intimately linked to RNA splicing, and its role in PDAC.

Tackling challenges in rare diseases: The ISGACA approach on non-pancreatic cancers in the periampullary region.

Objective: Rare but aggressive cancer types like non-pancreatic periampullary cancers pose unique challenges for cancer research due to their low incidence rates and lack of consensus on optimal treatment strategies, therefore necessitating a collaborative approach. The International Study Group on non-pancreatic peri-Ampullary CAncer (ISGACA) aimed to build a collaborative initiative to pool expertise, funding opportunities, and data from over 60 medical centers, in order to improve outcomes for underrepresented patients with rare cancers.

Methods: The ISGACA approach predefined a stepwise approach including a research scope, establishing a dedicated steering committee, creating a recognizable brand, identifying research gaps, following a well-defined timeline, ensuring robust data collection, addressing legal and ethical considerations, securing financial resources, investing in research ethics training and statistical expertise, raising awareness, creating uniformity, and initiating prospective studies.

SWI/SNF Complex-Deficient Undifferentiated Carcinoma of the Pancreas: Clinicopathologic and Genomic Analysis.

Inactivating alterations in the SWItch/Sucrose NonFermentable (SWI/SNF) Chromatin Remodeling Complex subunits have been described in multiple tumor types. Recent studies focused on SMARC subunits of this complex to understand their relationship with tumor characteristics and therapeutic opportunities. To date, pancreatic cancer with these alterations has not been well studied, although isolated cases of undifferentiated carcinomas have been reported.

Subgrading of G2 Pancreatic Neuroendocrine Tumors as 2A (Ki67 3% to < 10%) Versus 2B (10% to ≤ 20%) Identifies Behaviorally Distinct Subsets in Keeping with the Evolving Management Protocols.

Background: Grade 1/2 PanNETs are mostly managed similarly, typically without any adjunct treatment with the belief that their overall metastasis rate is low. In oncology literature, Ki67-index of 10% is increasingly being used as the cutoff in stratifying patients to different protocols, although there are no systematic pathology-based studies supporting this approach.

Methods: Ki67-index was correlated with clinicopathologic parameters in 190 resected PanNETs.

Comprehensive Characterization of Intraductal Oncocytic Papillary Neoplasm of the Pancreas: A Systematic and Critical Review.

Intraductal oncocytic papillary neoplasm (IOPN) of the pancreas is a recently recognized pancreatic tumor. Here, we aimed to determine its most essential features with the systematic review tool. PubMed, Scopus, and Embase were searched for studies reporting data on pancreatic IOPN.

Treatment of Locally Advanced Rectal Cancer in the Era of Total Neoadjuvant Therapy: A Systematic Review and Network Meta-Analysis.

Importance: Treatment of locally advanced rectal cancer (LARC) involves neoadjuvant chemoradiotherapy plus total mesorectal excision and adjuvant chemotherapy. However, total neoadjuvant therapy (TNT) protocols (ie, preoperative chemotherapy in addition to radiotherapy) may allow better adherence and early treatment of distant micrometastases and may increase pathological complete response (pCR) rates.

Objective: To assess the efficacy and tolerability of TNT protocols for LARC.

Expression of the membrane tetraspanin claudin 18 on cancer cells promotes T lymphocyte infiltration and antitumor immunity in pancreatic cancer.

Tumors weakly infiltrated by T lymphocytes poorly respond to immunotherapy. We aimed to unveil malignancy-associated programs regulating T cell entrance, arrest, and activation in the tumor environment. Differential expression of cell adhesion and tissue architecture programs, particularly the presence of the membrane tetraspanin claudin (CLDN)18 as a signature gene, demarcated immune-infiltrated from immune-depleted mouse pancreatic tumors.