Precision medicine translates through molecular assays and in minimally invasive diagnosis, evident in analyses of effusions that serve therapeutic and diagnostic purposes. This cost-effective and low-risk approach provides advantages, playing a pivotal role in late-stage oncology and frequently standing as the primary resource for cancer diagnosis and treatment pathways. This article outlines the workflow for managing serous fluid and explores how cytology effusion analysis extends beyond immunocytological diagnosis. Combined with current molecular tests it showcases the potential to be a skillful tool in precision cytopathology.

Osteosarcoma, a rare primary bone cancer, presents diverse molecular aberrations that underscore its complexity. Despite the persistent endeavors by researchers, the limited amelioration in the five-year survival rate indicates that current therapeutic strategies prove inadequate in addressing the clinical necessities. Advancements in molecular profiling have facilitated an enhanced comprehension of the biology of osteosarcoma, offering a promising outlook for treatment. There is an urgent need to develop innovative approaches to address the complex challenges of osteosarcoma, ultimately contributing to enhanced patient outcomes. This review explores the nexus between osteosarcoma and cancer predisposition syndromes, intricacies in its somatic genome, and clinically actionable alterations. This review covers treatment strategies, including surgery, chemotherapy, immune checkpoint inhibitors (ICIs), and tyrosine kinase inhibitors (TKIs). Innovative treatment modalities targeting diverse pathways, including multi-target tyrosine kinases, cell cycle, PI3K/mTOR pathway, and DNA damage repair (DDR), offer promising interventions. This review also covers promising avenues, including antibody-drug conjugates (ADCs) and immunotherapy strategies, such as cytokines, adoptive cellular therapy (ACT), ICIs, and cancer vaccines. This comprehensive exploration contributes to a holistic understanding, offering guidance for clinical applications to advance the management of osteosarcoma.

The increasing availability of genomic sequencing of tumor tissue in oncology provided valuable insights into tumor evolution and offered clinicians the unprecedented opportunity to tailor therapies on each individual patient, according to the treatment-impacting alterations identified in the tumor cells. In addition to the characterization of somatic alterations in tumor samples, the identification of germline (i.e., constitutional) pathogenic variants can provide additional information to guide informed and personalized therapeutic planning for patients and to enable risk-based screening protocols for at-risk relatives. In genitourinary malignancies, only a few associations between germline mutations and cancer risk and behavior have been thoroughly investigated (e.g., alterations in DNA repair genes in prostate cancer or mutations in Lynch syndrome genes in upper tract urothelial carcinoma). To achieve a wider use of both tumor genomic and germline genetic testing, an integrative approach led by scientific societies is necessary to involve physicians, patients and advocacy groups, to develop a shared strategy to advance the field and provide value-based and reproducible standards of care for patients and their families.

Mesothelioma (MM) is an aggressive and lethal disease with few therapeutic opportunities. Platinum-pemetrexed chemotherapy is the backbone of first-line treatment for MM. The introduction of immunotherapy (IO) has been the only novelty of the last decades, allowing an increase in survival compared to standard chemotherapy (CT). However, IO is not approved for epithelioid histology in many countries. Therefore, therapy for relapsed MM remains an unmet clinical need, and the prognosis of MM remains poor, with an average survival of only 18 months. Increasing evidence reveals MM complexity and heterogeneity, of which histological classification fails to explain. Thus, scientific focus on possibly new molecular markers or cellular targets is increasing, together with the search for target therapies directed towards them. The molecular landscape of MM is characterized by inactivating tumor suppressor alterations, the most common of which is found in CDKN2A, BAP1, MTAP, and NF2. In addition, cellular targets such as mesothelin or metabolic enzymes such as ASS1 could be potentially amenable to specific therapies. This review examines the major targets and relative attempts of therapeutic approaches to provide an overview of the potential prospects for treating this rare neoplasm.

Aging refers to complete deterioration of physiological integrity and function. By midcentury, adults over 60 years of age and children under 15 years will begin to outnumber people in working age. This shift will bring multiple global challenges for economy, health, and society. Eventually, aging is a natural process playing a vital function in growth and development during pediatric stage, maturation during adult stage, and functional depletion. Tissues experience negative consequences with enhanced genomic instability, deregulated nutrient sensing, mitochondrial dysfunction, and decline in performance on cognitive tasks. As brain ages, its volume decreases, neurons & glia get inflamed, vasculature becomes less developed, blood pressure increases with a risk of stroke, ischemia, and cognitive deficits. Diminished cellular functions leads to progressive reduction in functional and emotional capacity with higher possibility of disease and finally death. This review overviews cellular as well as molecular aspects of aging, biological pathway related to accelerated brain aging, and strategies minimizing cognitive aging. Age-related changes include altered bioenergetics, decreased neuroplasticity and flexibility, aberrant neural activity, deregulated Ca2+ homeostasis in neurons, buildup of reactive oxygen species, and neuro-inflammation. Unprecedented progress has been achieved in recent studies, particularly in terms of how herbal or natural substances affect genetic pathways and biological functions that have been preserved through evolution. Herein, the present work provides an overview of ageing and age-related disorders and explore the molecular mechanisms that underlie therapeutic effects of herbal and natural chemicals on neuropathological signs of brain aging.

Cannabis is the most used illicit substance for recreational purposes around the world. However, it has become increasingly common to witness the use of approved cannabis preparations for symptoms management in various diseases. The aim of this study was to investigate the effects of cannabis nano emulsion in the liver of Wistar rats, with different proportions of delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD). For this, a total of 40 male Wistar rats were distributed into 5 groups, as follows (n = 8 per group): Control: G1, Experimental group (G2): treated with cannabis nano emulsion (THC and CBD) at a dose of 2.5 mg/kg, Experimental group (G3): treated with cannabis nano emulsion (THC and CBD) at a dose of 5 mg/kg, Experimental group (G4): treated with cannabis nano emulsion (CBD) at a dose of 2.5 mg/kg; Experimental group (G5): treated with cannabis nano emulsion (CBD) at a dose of 5 mg/kg. Exposure to the nano emulsion was carried out for 21 days, once a day, orally (gavage). Our results showed that cannabis nano emulsions at higher doses (5 mg/kg), regardless of the composition, induced histopathologic changes in the liver (G3 and G5) in comparison with the control group. In line with that, placental glutathione S-transferase (GST-P) positive foci increased in both G3 and G5 (p < 0.05), as well as the immune expression of Ki-67, vascular endothelial growth factor (VEGF) and p53 (p < 0.05). Also, the nano emulsion intake induced an increase in the number of micronucleated hepatocytes in G5 (p < 0.05) whereas G3 showed an increase in binucleated cells (p < 0.05). As for metanuclear alterations, karyolysis and pyknosis had an increased frequency in G3 (p < 0.05). Taken together, the results show that intake of cannabis nano emulsion may induce degenerative changes and genotoxicity in the liver in higher doses, demonstrating a clear dose-response relationship.

Pancreatic ductal adenocarcinoma (PDAC) is one of the leading causes of cancer-related death worldwide. It is commonly diagnosed in advanced stages and therapeutic interventions are typically constrained to systemic chemotherapy, which yields only modest clinical outcomes. In this review, we examine recent developments in targeted therapy tailored to address distinct molecular pathway alteration required for PDAC. Our review delineates the principal signaling pathways and molecular mechanisms implicated in the initiation and progression of PDAC. Subsequently, we provide an overview of prevailing guidelines, ongoing investigations, and prospective research trajectories related to targeted therapeutic interventions, drawing insights from randomized clinical trials and other pertinent studies. This review focus on a comprehensive examination of preclinical and clinical data substantiating the efficacy of these therapeutic modalities, emphasizing the potential of combinatorial regimens and novel therapies to enhance the quality of life for individuals afflicted with PDAC. Lastly, the review delves into the contemporary application and ongoing research endeavors concerning targeted therapy for PDAC. This synthesis serves to bridge the molecular elucidation of PDAC with its clinical implications, the evolution of innovative therapeutic strategies, and the changing landscape of treatment approaches.

BACKGROUND: Poorly differentiated primary sarcomatoid parotid malignancies are extremely rare. These tumors have not been consistently studied by morphology, immunohistochemistry, or molecular techniques.
METHODS: We report three unusual cases of parotid gland poorly-differentiated sarcomatoid malignancy investigated by fine-needle aspiration and studied histologically, by immunohistochemistry and molecular investigations. Aspirates showed poorly specific polymorphous sarcomatoid malignancy in all cases. Histologically, all cases were polymorphous high-grade malignancies, and additionally, one case showed epithelial structures and was finally classified as salivary carcinosarcoma. Immunohistochemistry showed classical melanocytic markers negativity but positivity for PRAME, CD10, and WT1 in all three tumors and for CD56 in two tumors, which can potentially be supportive of melanocytic origin. Although not entirely specific, molecular characterization also suggested the melanocytic lineage of these tumors.
CONCLUSIONS: Although rare, primary malignant melanoma of salivary gland was already described, but undifferentiated/dedifferentiated amelanotic forms are unknown in this localization up today. Further case reports of similar presentations are required to confirm the unequivocal primary origin of these obscure neoplasms in the parotid gland.

Acute myeloid leukemia (AML) is an aging-related and heterogeneous hematopoietic malignancy. In this study, a total of 1,474 newly diagnosed AML patients with RNA sequencing data were enrolled, and targeted or whole exome sequencing data were obtained in 94% cases. The correlation of aging-related factors including age and clonal hematopoiesis (CH), gender, and genomic/transcriptomic profiles (gene fusions, genetic mutations, and gene expression networks or pathways) was systematically analyzed. Overall, AML patients aged 60 y and older showed an apparently dismal prognosis. Alongside age, the frequency of gene fusions defined in the World Health Organization classification decreased, while the positive rate of gene mutations, especially CH-related ones, increased. Additionally, the number of genetic mutations was higher in gene fusion-negative (GF-) patients than those with GF. Based on the status of CH- and myelodysplastic syndromes (MDS)-related mutations, three mutant subgroups were identified among the GF- AML cohort, namely, CH-AML, CH-MDS-AML, and other GF- AML. Notably, CH-MDS-AML demonstrated a predominance of elderly and male cases, cytopenia, and significantly adverse clinical outcomes. Besides, gene expression networks including HOXA/B, platelet factors, and inflammatory responses were most striking features associated with aging and poor prognosis in AML. Our work has thus unraveled the intricate regulatory circuitry of interactions among different age, gender, and molecular groups of AML.

Gastrointestinal stromal tumors (GISTs), although rare, are the most common mesenchymal neoplasms of the gastrointestinal tract. Their potential for malignancy underscores the significance of identifying them through cytomorphologic findings and pertinent immunohistochemical markers. GISTs can emerge anywhere along the gastrointestinal tract with a predilection for the stomach. The clinical manifestations vary from nonspecific abdominal symptoms to incidental discovery during diagnostic interventions for unrelated signs and symptoms. Cytologically, GIST aspirates contain spindle or epithelioid cells with immunoreactivity for CD117/c-KIT, DOG-1, and CD34. Molecularly, KIT or PDGFRA mutations are prevalent, guiding targeted therapy with tyrosine kinase inhibitors. Distinct subtypes like succinate dehydrogenase-deficient GISTs pose challenges, often affecting younger individuals and displaying unique features. Histologically, GISTs are graded by mitotic rates, aiding prognostication. Distinguishing GISTs from similar entities is pivotal, necessitating attention to their immunostaining patterns for making an accurate diagnosis and molecular alterations for effectively planning treatment. Common differential diagnoses include leiomyoma, schwannoma, and solitary fibrous tumor. This article presents a classic GIST case and showcases relatively simple diagnostic clues for identifying similar lesions that may occur in diverse locations.