N-acetylcysteine (NAC) is a mucolytic agent with antioxidant and anti-inflammatory properties. The respiratory syncytial virus (RSV) is one of the most important etiological factors of lower respiratory tract infections, and exposure to air pollution appears to be additionally associated with higher RSV incidence and disease severity. We aimed to systematically review the existing literature to determine which molecular mechanisms mediate the effects of NAC in an RSV infection and air pollution, and to identify the knowledge gaps in this field. A search for original studies was carried out in three databases and a calibrated extraction grid was used to extract data on the NAC treatment (dose, timing), the air pollutant type, and the most significant mechanisms. We identified only 28 studies conducted in human cellular models (n = 18), animal models (n = 7), and mixed models (n = 3). NAC treatment improves the barrier function of the epithelium damaged by RSV and air pollution, and reduces the epithelial permeability, protecting against viral entry. NAC may also block RSV-activated phosphorylation of the epidermal growth factor receptor (EGFR), which promotes endocytosis and facilitates cell entry. EGFR also enhances the release of a mucin gene, MUC5AC, which increases mucus viscosity and causes goblet cell metaplasia; the effects are abrogated by NAC. NAC blocks virus release from the infected cells, attenuates the cigarette smoke-induced shift from necrosis to apoptosis, and reverses the block in IFN-γ-induced antiviral gene expression caused by the inhibited Stat1 phosphorylation. Increased synthesis of pro-inflammatory cytokines and chemokines is induced by both RSV and air pollutants and is mediated by the nuclear factor kappa-B (NF-κB) and mitogen-activated protein kinase (MAPK) signaling pathways that are activated in response to oxidative stress. MCP-1 (monocyte chemoattractant protein-1) and RANTES (regulated upon activation, expressed and secreted by normal T cells) partially mediate airway hyperresponsiveness (AHR), and therapeutic (but not preventive) NAC administration reduces the inflammatory response and has been shown to reduce ozone-induced AHR. Oxidative stress-induced DNA damage and cellular senescence, observed during RSV infection and exposure to air pollution, can be partially reversed by NAC administration, while data on the emphysema formation are disputed. The review identified potential common molecular mechanisms of interest that are affected by NAC and may alleviate both the RSV infection and the effects of air pollution. Data are limited and gaps in knowledge include the optimal timing or dosage of NAC administration, therefore future studies should clarify these uncertainties and verify its practical use.

Myelodysplastic neoplasms (MDS) with ring sideroblasts (RS) are diagnosed via bone marrow aspiration in the presence of either (i) ≥15% RS or (ii) 5-14% RS and an SF3B1 mutation. In the MEDALIST trial and in an interim analysis of the COMMANDS trial, lower-risk MDS-RS patients had decreased transfusion dependency with luspatercept treatment. A total of 6817 patients with suspected hematologic malignancies underwent molecular testing using a next-generation-sequencing-based genetic assay and 395 MDS patients, seen at our centre from 1 January 2018 to 31 May 2023, were reviewed. Of these, we identified 39 evaluable patients as having lower-risk MDS with SF3B1 mutations: there were 20 (51.3%) males and 19 (48.7%) females, with a median age of 77 years (range of 57 to 92). Nineteen (48.7%) patients had an isolated SF3B1 mutation with a mean variant allele frequency of 35.2% +/- 8.1%, ranging from 7.4% to 46.0%. There were 29 (74.4%) patients with ≥15% RS, 6 (15.4%) with 5 to 14% RS, one (2.6%) with 1% RS, and 3 (7.7%) with no RS. Our study suggests that a quarter of patients would be missed based on the morphologic criterion of only using RS greater than 15% and supports the revised 2022 definitions of the World Health Organization (WHO) and International Consensus Classification (ICC), which shift toward molecularly defined subtypes of MDS and appropriate testing.

This case report details a rare instance of a perforated jejunal gastrointestinal stromal tumor (GIST) in a 76-year-old female patient. The patient presented with acute abdominal pain and distension without any changes in bowel habits or episodes of nausea and vomiting. Initial diagnostics, including abdominal plain radiography and ultrasonography, were inconclusive; however, a computed tomography (CT) scan revealed pneumoperitoneum and an irregular fluid collection suggestive of small intestine perforations. Surgical intervention uncovered a 35 mm jejunal GIST with a 10 mm perforation. Histopathological examination confirmed a mixed cell type GIST with high malignancy potential, further substantiated by immunohistochemistry markers CD117, DOG1, and vimentin. Molecular analysis illuminated the role of key oncogenes, primarily KIT and PDGFRA mutations, emphasizing the importance of molecular diagnostics in GIST management. Despite the severity of the presentation, the patient\'s postoperative recovery was favorable, highlighting the effectiveness of prompt surgical and multidisciplinary approaches in managing complex GIST cases.

Wilms tumor (WT), or nephroblastoma, is an uncommon malignant neoplasm occurring in the kidney of pediatric patients. Its extrarenal location is extremely rare and has been reported in various sites, including the female genital tract, with only 9 cases arising in the uterine corpus. We present the case of an adult woman who underwent total abdominal hysterectomy due to a uterine mass causing persistent abdominal pain. The characteristic triphasic morphology (composed of epithelial, stromal, and blastemal elements) supported by a broad immunohistochemical panel, along with the imaging exclusion of a renal neoplasm, was diagnostic of WT of the uterus. For the first time, a comprehensive genomic profiling of a uterine primary WT was also performed by next-generation sequencing, disclosing alterations at the level of copy number variations in the genes ERBB2, FGFR23, FGF6, FGFR2, and RPS6KB1. All previously reported uterine cases were reviewed, with a summary of their main clinicopathologic characteristics, and the main differential diagnoses are presented. Further reports are needed to improve our knowledge about prognostic factors, clinical behavior and molecular alterations that could guide appropriate therapeutic decision making.

Infectious diseases present a global challenge, requiring accurate diagnosis, effective treatments, and preventive measures. Artificial intelligence (AI) has emerged as a promising tool for analysing complex molecular data and improving the diagnosis, treatment, and prevention of infectious diseases. Computer-aided detection (CAD) using convolutional neural networks (CNN) has gained prominence for diagnosing tuberculosis (TB) and other infectious diseases such as COVID-19, HIV, and viral pneumonia. The review discusses the challenges and limitations associated with AI in this field and explores various machine-learning models and AI-based approaches. Artificial neural networks (ANN), recurrent neural networks (RNN), support vector machines (SVM), multilayer neural networks (MLNN), CNN, long short-term memory (LSTM), and random forests (RF) are among the models discussed. The review emphasizes the potential of AI to enhance the accuracy and efficiency of diagnosis, treatment, and prevention of infectious diseases, highlighting the need for further research and development in this area.

BACKGROUND: Struma ovarii refers to rare mature cystic teratomas containing at least 50% of thyroid tissue, and malignant transformation is known to be even rarer. The synchronous development of malignant struma ovarii and cervical thyroid carcinoma are also scarce and poorly understood due to limited data about molecular features. Here, we present the first report of RET/PTC 1 rearrangement in synchronous metastatic malignant struma ovarii to the abdominal wall and cervical thyroid cancer.
METHODS: We described a 47-year-old multigravida woman with bilateral adnexal and lower abdominal wall masses detected during the evaluation of abnormal uterine bleeding. The patient underwent a hysterectomy, bilateral salpingo-oophorectomy, and surgical removal of abdominal wall mass. Then, the pathological evaluation revealed papillary thyroid carcinoma (PTC) within struma ovarii and metastatic PTC in the abdominal wall fibro adipose tissue. Further, cervical thyroid gland physical examination and ultrasound illustrated a nodule within the left lobe. Subsequently, a total thyroidectomy was performed, and a histological examination revealed PTC. Furthermore, all affected tissue, i.e., struma ovarii, abdominal wall metastasis, and cervical thyroid gland tested for BRAF and RAS mutations and RET/PTC 1 rearrangement. RET/PTC 1 rearrangement was identified among all three different sites. Finally, after six years of follow-up, the patient had no evidence of recurrence or distant metastasis.
CONCLUSIONS: In light of these findings, malignant struma ovarii might yield a clue to cervical thyroid carcinoma, and the molecular analysis could provide valuable information for understanding the underlying mechanism, tumor clinicopathological behaviors, and prognosis.

The classification of many soft tissue tumors remains subjective due their rarity, significant overlap in microscopic features and often a non-specific immunohistochemical (IHC) profile. The application of molecular genetic tools, which leverage the underlying molecular pathogenesis of these neoplasms, have considerably improved the diagnostic abilities of pathologists and refined classification based on objective molecular markers. In this study, we describe the results of an international collaboration conducted over a 3-year period, assessing the added diagnostic value of applying molecular genetics to sarcoma expert pathologic review in a selected series of 84 uncommon, mostly unclassifiable mesenchymal tumors, 74 of which originated in soft tissues and 10 in bone. The case mix (71% historical, 29% contemporary) included mostly unusual and challenging soft tissue tumors, which remained unclassified even with the benefit of expert review and routine ancillary methods, including broad IHC panels and a limited number of commercially available fluorescence in situ hybridization (FISH) probes. All cases were further tested by FISH using a wide range of custom bacterial artificial chromosome probes covering most of known fusions in sarcomas, whereas targeted RNA sequencing was performed in 13 cases negative by FISH, for potential discovery of novel fusion genes. Tumor-defining molecular alterations were found in 48/84 tumors (57%). In 27 (32%) cases the tumor diagnosis was refined or revised by the additional molecular work-up, including five cases (6%), in which the updated diagnosis had clinical implications. Sarcoma classification is rapidly evolving due to an increased molecular characterization of these neoplasms, so unsurprisingly 17% of the tumors in this series harbored abnormalities only very recently described as defining novel molecularly defined soft tissue tumor subsets.

Prostate cancer is one of the most common malignant diseases in men, and it contributes significantly to the increased mortality rate in men worldwide. This study aimed to review the roles of p300 and TMPRSS2 (transmembrane protease, serine 2) in the AR (androgen receptor) pathway as they are closely related to the development and progression of prostate cancer. This paper represents a library-based study conducted by selecting the most suitable, up-to-date scientific published articles from online journals. We focused on articles that use similar techniques, particularly those that use prostate cancer cell lines and immunohistochemical staining to study the molecular impact of p300 and TMPRSS2 in prostate cancer specimens. The TMPRSS2:ERG fusion is considered relevant to prostate cancer, but its association with the development and progression as well as its clinical significance have not been fully elucidated. On the other hand, high p300 levels in prostate cancer biopsies predict larger tumor volumes, extraprostatic extension of disease, and seminal vesicle involvement at prostatectomy, and may be associated with prostate cancer progression after surgery. The inhibition of p300 has been shown to reduce the proliferation of prostate cancer cells with TMPRSS2:ETS (E26 transformation-specific) fusions, and combining p300 inhibitors with other targeted therapies may increase their efficacy. Overall, the interplay between the p300 and TMPRSS2 pathways is an active area of research.

Giant cell-rich lesions of bone represent a heterogeneous group of entities which classically include giant cell tumor of bone, aneurysmal bone cyst, nonossifying fibroma, and Brown tumor of hyperparathyroidism. A recently described subset of giant cell-rich tumors involving bone and soft tissue has been characterized by recurrent HMGA2::NCOR2 fusions and keratin expression. The overlapping clinical, radiographic, and morphological features of these giant cell-rich lesions provide a unique diagnostic challenge, particularly on biopsy. We present 2 additional cases of keratin-positive giant cell-rich tumor of bone with HMGA2::NCOR2 fusions, including 1 patient who developed metastatic disease.

This paper aims to present a detailed overview of fibrolamellar carcinoma (FLC), a variant of hepatocellular carcinoma (HCC) that accounts for approximately 1-9% of all cases a. according to the SEER database. Despite ongoing research, the aetiology of FLC tumours remains unclear. Nevertheless, FLC is believed to have a better overall prognosis than other primary liver tumours, such as hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma. This study aims to present a comprehensive overview of fibrolamellar carcinoma (FLC), with a focus on its epidemiology, pathogenesis, diagnosis, treatment, and prognosis. FLC frequently incorporate features of stomach pain, weight loss, and malaise in their clinical signs and symptoms, which are generally nonspecific Ultimately, the most common physical finding is an abdominal mass or hepatomegaly. With this said, several unusual presentations have been documented such as Budd Chiari syndrome, severe anaemia, non-bacterial thrombotic endocarditis and many more. In regards to this tumour\'s genetic analysis, it is characterised by a 400 kb deletion on chromosome 19 leading to a functional DNAJB1-PRKACA chimeric transcript in addition to tetraploidy in 50% of cases. FLC is chromosomally stable as compared to typical HCC. mTOR pathway activation has also been found to play a critical role in 47% of these tumours and EFGR over-expression is also evident. Fibrolamellar carcinomas (FLCs) exhibit a distinctive gross appearance, characterized by a yellow to pale tan colour, with a consistency that can vary from soft to firm and hard. In addition, a central scar is observed in 60-70% of FLC cases. The central scar is typically white or grey in colour and has a fibrous appearance, which is often surrounded by nodular, tumour-like tissue. Its histologic appearance is characterized by large polygonal cells with abundant eosinophilic cytoplasm, large vesiculated nuclei, large nucleoli, and arranged in lamellar bands of collagen fibres. Lamellar bands of fibrosis, consisting of collagen type I, III and IV, have also been identified as a distinctive histologic feature that is observed under low power magnification. Ultrasound, CT and MRI along with image guided biopsy are the primary modalities in diagnosis. Current management options include systemic therapy which has thus far been unremarkable with platinum-based therapies as well combination therapy with interferon alpha-2b being the most successful options. Surgical resection remains the primary treatment modality and there have been no advances in targeted therapies. Although the prognosis for FLC is favourable as compared to other hepatic cancer subtypes such as intrahepatic cholangiocarcinoma, there is a high rate of recurrence ranging from 33% to 100% with a median recurrence-free survival of 20-48 months. As a result of this there is a low overall cure rate associated with this tumour type and much more research is required to gain an in-depth understanding of the molecular mechanisms occurring in order to provide more adequate treatment to patients who suffer from this condition.