1,721,286 research outputs found
The importance of tumor microenvironment modulations in the progression of pancreatic intraductal papillary mucinous neoplasms†
No full textIntraductal papillary mucinous neoplasms (IPMNs) of the pancreas have attracted substantial attention since they represent the most prevalent macroscopic precursor of pancreatic cancer. Most lesions show an epithelium with low-grade dysplasia and will remain indolent and unknown to the patient. Notably, a subgroup of IPMNs will progress to invasive cancer through a stepwise process characterized by the accumulation of specific genomic alterations and concomitant modifications of the tumor microenvironment (TME). The manuscript of Jamouss et al, recently published in The Journal of Pathology, expands the current knowledge on TME dynamics in IPMNs. The neoplastic progression of IPMNs is paralleled by a shift toward an immunosuppressive TME, with depletion of cytotoxic T cells, elevated expression of immune checkpoint molecules, including PD-L1 and VISTA, and increased density of macrophages. Overall, TME modifications are crucial in the progression of pancreatic IPMNs, calling for potential therapeutic strategies focused on TME modulations for cancer interception. (c) 2025 The Author(s). The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland
Diagnostic Pearls and Pitfalls in the Evaluation of Biopsies of the Pancreas
No full textContext: The examination of small pancreatic biopsies is a difficult task for pathologists. This is due to the scant and fragmented material often obtained from diagnostic procedures as well as the significant overlap between different neoplastic and nonneoplastic entities. In the upcoming neoadjuvant era, biopsies could become even more important, representing the only possibility to look at the real histomorphology of tumors before chemotherapy-induced modifications. Objectives: To summarize and discuss the state-of-the-art diagnostic workflow for small pancreatic biopsies, including the most important morphologic and immunohistochemical features and molecular alterations. The main diagnostic pearls and pitfalls of this challenging scenario are also discussed. The most important topics of this review are represented by: (1) pancreatic ductal adenocarcinoma, along with its main differential diagnoses, including autoimmune pancreatitis; (2) solid hypercellular neoplasms, including neuroendocrine neoplasms, acinar cell carcinoma, pancreatoblastoma, and solid pseudopapillary neoplasms; and (3) cystic lesions. Real-world considerations will be also presented and discussed. Data sources: Sources included a literature review of published studies and the author's own work. Conclusions: The correct diagnosis of pancreatic lesions is a crucial step in the therapeutic journey of patients. It should be based on robust, standardized, and reliable hallmarks. As presented and discussed here, the integration of morphology with immunohistochemistry, and in selected cases, with molecular analysis, represents a decisive step in this complex scenario
Undifferentiated carcinoma of the pancreas with osteoclast-like giant cells: a challenging cancer with new horizons?
No full textNo abstract availabl
The Roles of Chromatin Remodeling Genes in Pancreatic-Biliary Malignancies
No full textRecent studies have definitively established that chromatin remodeling is a crucial epigenetic mechanism not only in physiological conditions but also in influencing cancer biology. It is a dynamic process in which the chromatin, the functional entity of DNA, can undergo specific modifications by obtaining transcriptional activation or transcriptional silencing. One of the most important recent discoveries in cancer genetics and genomics is that the genes involved in the establishment of chromatin structure, the so called chromatin remodelers, are frequently mutated in different types of human cancer. This review aims to summarize the main novelties related to this topic, describing also the contribution of such genes during oncogenesis. Particularly, we focus on the switch/sucrose non-fermentable complexes and on three of the most important chromatin remodeling genes in biliary and pancreatic cancer: ARID1A, PBRM1, and BAP1
Genomic determinants of biological aggressiveness and poor prognosis of pancreatic cancers: KRAS and beyond
No full textIntroduction: A marked histomolecular heterogeneity characterizes pancreatic cancer. Thus, different tumor histologies with divergent genomic profiles exist within the same category. Areas covered: Using data from PubMed, SCOPUS, and Embase (last search date: 04/04/2024), this expert-based, narrative review presents and discusses the essential molecular determinants of biological aggressiveness and poor prognosis in pancreatic cancer. First, KRAS mutation still represents one of the most critical difficulties in treating pancreatic cancers. In this district, it is mutated in > 90% of malignant tumors. Notably, actionable alterations for molecular-based therapies are typically lacking in KRAS-mutated pancreatic cancer. Furthermore, transcriptome-based studies clarified that the squamous phenotype is characterized by poorer prognosis and response to standard chemotherapy. We also discuss molecular biomarkers related to dismal prognosis in specific subsets of pancreatic cancer, such as SMAD4 in signet-ring cell carcinoma and TP53 in invasive cancers derived from intraductal tubulopapillary neoplasms. Expert opinion: The identification of the subgroups of pancreatic cancer with particularly unfavorable prognoses is a critical step for addressing specific research efforts. In addition to implementing and strengthening current precision oncology strategies, the decisive step for improving the survival of patients affected by pancreatic cancer must pass through targeting the KRAS gene
Microsatellite instability in pancreatic and ampullary carcinomas: histology, molecular pathology and clinical implications
No full textMicrosatellite instability (MSI) / defective DNA mismatch repair (dMMR) represent an important molecular alteration with diagnostic, prognostic and predictive value. The increasing interest towards this genetic alteration is given to the high response rate of MSI/dMMR tumors to immunotherapy. There are different cancers in the periampullary region that can harbor MSI/dMMR, and significant morphological-molecular correlates should be acknowledged in this district: 1) Pancreatic ductal adenocarcinoma (PDAC): in this tumor category, the prevalence of MSI/dMMR is about 1-2%, and medullary and colloid variants are the most typically involved; 2) Ampullary adenocarcinoma: here the prevalence of MSI/dMMR is up to 18%. In this neoplastic group, MSI/dMMR is more commonly found in the intestinal subtype; 3) Pancreatic acinar cell carcinoma: here the prevalence of MSI/dMMR is up to 14%; 4) pancreatic and ampullary neuroendocrine carcinoma: in this tumor category, the prevalence of MSI/dMMR is up to 5-8%, and this molecular alteration should be assessed also in cases of mixed neuroendocrine-non neuroendocrine neoplasms. Given the clinical importance of MSI/dMMR and its not-negligible prevalence among the different carcinomas arising in this district, its assessment should become part of the routine diagnostic workflow at least for the most typical histotypes. The test of choice is represented by immunohistochemistry for PDAC and ampullary carcinomas, and by direct molecular analyses including MSI-based polymerase chain reaction and next-generation sequencing for acinar cell and neuroendocrine carcinomas
Benign Tumors and Tumor-Like Conditions of Ampulla and Small Intestine: The PathologyOutlines.com Review
No full text: Small intestine and ampulla can be involved in a heterogeneous group of benign tumors and tumor-like diseases, potentially mimicking malignant neoplasms. In-depth knowledge of them is critical for practicing pathologists since they represent potential pitfalls in routine diagnostic activity. Such conditions include the following: (1) Brunner gland lesions, including Brunner gland hyperplasia and hamartoma; (2) polyps, such as adenoma, hyperplastic, hamartomatous, and inflammatory; (3) mesenchymal proliferations encompassing inflammatory fibroid polyp, inflammatory myofibroblastic tumor, leiomyomas, lipomas, and lipomatosis of the ileocecal valve; (4) fibrosis-associated diseases, such as idiopathic retroperitoneal fibrosis, reactive nodular fibrous pseudotumor, and sclerosing peritonitis; (5) disorders of lymphatic vessels, including lymphangiectasia and lymphangiomas; and (6) other rare conditions/miscellanea, such as enteritis cystica profunda, intussusception, ischemia, and pneumatosis cystoides intestinalis. This review, inspired by the content of the PathologyOutlines website (https://www.pathologyoutlines.com), aims to provide a reference point in this complex scenario, summarizing the essential histopathological features of all these entities for better addressing routine practice and differential diagnoses
Neoplastic Progression in Neuroendocrine Neoplasms of the Pancreas
No full textContext: Pancreatic neuroendocrine neoplasms (PanNENs) represent a heterogeneous group of epithelial tumors of the pancreas showing neuroendocrine differentiation. These neoplasms are classified into well-differentiated pancreatic neuroendocrine tumors (PanNETs), which include G1, G2, and G3 tumors, and poorly differentiated pancreatic neuroendocrine carcinomas (PanNECs), which are G3 by definition. This classification mirrors clinical, histologic, and behavioral differences and is also supported by robust molecular evidence. Objective: To summarize and discuss the state of the art regarding neoplastic progression of PanNENs. A better comprehension of the mechanisms underpinning neoplastic evolution and progression of these neoplasms may open new horizons for expanding the biologic knowledge and ultimately for addressing new therapeutic strategies for patients with PanNEN. Data sources: Literature review of published studies and the authors' own work. Conclusions: PanNETs can be seen as a unique category, where G1-G2 tumors may progress to G3 tumors mainly driven by DAXX/ATRX mutations and alternative lengthening of telomeres. Conversely, PanNECs display totally different histomolecular features more closely related to pancreatic ductal adenocarcinoma, including TP53 and Rb alterations. They seem to derive from a nonneuroendocrine cell of origin. Even the study of PanNEN precursor lesions corroborates the rationale of considering PanNETs and PanNECs as separate and distinct entities. Improving the knowledge regarding this dichotomous distinction, which guides tumor evolution and progression, will represent a critical basis for PanNEN precision oncology
Biliary adenofibroma: is it truly a benign neoplasm or benign-looking cholangiocarcinoma?
No full textNo abstract availabl
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