Search Results (241)

Gastric cancer traditionally affects older adults, and its precursor lesions and risk factors are well-documented in this population. Helicobacter pylori (H. pylori) infection remains highly prevalent in Saudi Arabia and contributes to gastric pathology. However, early-onset gastric cancer (EOGC), diagnosed in individuals aged ≤ 45 years, presents unique challenges and remains poorly understood in young populations. Therefore, we conducted an observational cohort study using a prospective longitudinal design (2021–2024) involving 1823 Saudi nationals aged 18–45 years who underwent zoom high-definition chromoendoscopy to evaluate the prevalence of premalignant gastric lesions (PGLs) and EOGC. We found a high H. pylori prevalence (78.0%) with PGLs in 1.9% of participants and EOGC-adenocarcinoma in 0.7% of patients. All EOGC cases arose from dysplasia, with most PGLs being classified as OLGA/OLGIM stage II/III. Multiple risk factorswere significantly associated with PGLs and EOGC, including H. pylori infection (p = 0.022), increasing age (p < 0.001), a family history of gastric cancer (p < 0.001), poor dietary habits (p < 0.001), obesity (p < 0.001), and smoking (p < 0.001). Additional EOGC risk factors include dage of 36–45 years (p = 0.018), EBV infection (p = 0.016), and diabetes mellitus (p = 0.001). These findings demonstrate the notable presence of PGLs and EOGC in young Saudi adults and emphasize the importance of early detection and risk factor management in this vulnerable population. Full article

Background and Clinical Significance: Neurofibromatosis type 1 (NF1) predisposes individuals to various peripheral nerve sheath tumors (PNSTs), including benign neurofibromas, malignant peripheral nerve sheath tumors (MPNSTs), and intermediate lesions known as atypical neurofibromatous neoplasms of uncertain biologic potential (ANNUBP), previously often termed atypical neurofibroma. These atypical lesions are considered premalignant precursors to MPNST. Case Presentation: We present the case of a 33-year-old male with NF1 who developed a rapidly growing, painful mass in his right calf. Clinical examination revealed signs consistent with NF1. Magnetic resonance imaging showed a large, heterogeneous mass in the lateral compartment. Biopsy revealed a neurofibroma with hypercellularity, moderate atypia, scarce S100 positivity, focal CD34 positivity, and an elevated Ki-67 proliferation index of 10–12%, consistent with ANNUBP. The patient underwent wide surgical resection, including the fibula and peroneal muscles. At the 30-month follow-up, there was no local recurrence, though the patient had a mild residual limp. Discussion: This case highlights the clinical presentation, diagnostic features, and management considerations for ANNUBP in NF1, emphasizing the importance of recognizing warning signs and the role of pathology in guiding treatment for these high-risk precursor lesions. Full article

Epithelial–mesenchymal transition (EMT) is one of the key steps in cutaneous carcinogenesis. At the molecular level, this cellular dedifferentiation is modulated by the interaction of signalling pathways that favour basement membrane degradation under the influence of proinflammatory cytokines and matrix metalloproteinases (MMPs). Given the intricate role of these endopeptidases in modulating extracellular matrix turnover, the present study aimed primarily to identify the MMP-2 expression profile during the early stages of cutaneous malignant transformation. Forty-eight lesions with malignant transformation potential were excised in healthy tissue. Following the histopathological diagnosis of keratoacanthoma, Bowen’s disease and actinic keratosis, the biological preparations were deparaffinised and homogenised in order to perform the FRET technique using the “MMP-2 Assay Kit Fluorometric”. The results of the previous part of this research indicate that MMP-2 expression is more intense in lesions of actinic keratosis compared to normal tissues and to keratoacanthoma or Bowen’s disease lesions, inversely proportional to the histopathological degree of dysplasia. Monitoring metalloproteinase activity in dysplastic epithelium may improve the detection of malignant transformation and guide treatment decisions. Full article

Background: Cervical dysplasia is a pre-malignant condition of the uterine cervix and is highly prevalent in Sub-Saharan Africa; especially affecting HIV-infected Black women. The anti-dysplastic effect of vitamin D hormones in cervical dysplasia is poorly understood. Therefore, we conducted a cross-sectional case–control observational study to assess the relationship between serum 25-hydroxycholecalciferol (25(OH)D) and cervical dysplasia, amongst Black women with and without HIV infection. Methods: The study participants attended a gynaecologic oncology clinic at an academic hospital in Pretoria, South Africa (n = 109). Patient clinical data were obtained during consultation. Cervical dysplasia was identified by cytology (PAP smear) which classified the case group as high-grade squamous epithelial lesions (HSILs), and the control group as <HSIL. Serum biochemistry measured 25(OH)D and its covariate biochemical variables. The data were statistically modelled to adjust for clinical and biochemical covariates, identify a significant relationship (p ≤ 0.05) between 25(OH)D and cervical dysplasia, and analyse subgroup interaction between HIV status and cervical dysplasia. Results: The data showed high levels of vitamin D insufficiency and deficiency in Black women with and without HIV infection. After covariate adjustment, 25(OH)D demonstrated an inverse relationship with HSIL in HIV-uninfected Black women. Furthermore, an interaction effect between women with and without HIV infection was observed. Conclusions: The role of 25(OH)D in the primary prevention of cervical dysplasia in Black women without HIV infection is promising, and dosing strategies require investigation. Also, future studies exploring the immunomodulatory role of 25(OH)D in cervical dysplasia in HIV-infected women is warranted. Full article

The histological changes in the gastric epithelium are crucial in the progression from premalignant to neoplastic lesions. TLR4, TLR5 and TLR9 have been localized in the gastric epithelium and studied separately using conventional histological techniques without a focus on the protein or cell interactions within the microenvironment. Therefore, we developed a multiplex immunohistochemistry/immunofluorescence (mIHC/IF) technology for the simultaneous detection of TLR4, TLR5 and TLR9 on a single tissue section of human gastric biopsies from 10 paired cases collected in two independent visits, and its correlation with the OLGA/OLGIM scoring and H. pylori status after eradication. The results confirmed that mIHC/IF is useful for simultaneously interrogating six biomarkers and demonstrated that TLR4 and TLR9 are significantly associated with H. pylori infection. However, only TLR9 is positively related to the presence of intestinal metaplasia. TLR5 was mainly present in goblet cells (TFF3+) but did not show any significant association with H. pylori or the presence of intestinal metaplasia. Our results suggest that a more comprehensive strategy to interrogate the tissue microenvironment in premalignant lesions may improve the interpretation of the earned risk of gastric cancer in patients with chronic gastritis and evidence of failure in H. pylori eradication. Full article

Anal cancer is a rare diagnosis, but incidence has been increasing over the past decade. Anal cancer is associated with the human papilloma virus (HPV), specifically the high-risk subtypes of 16 and 18. In addition, the precursor lesion for anal cancer is high-grade squamous intraepithelial lesions (HSILs) and its treatment and surveillance has been emphasized over the last 5 years. The current standard of care for anal cancer includes the Nigro protocol, concurrent chemoradiation, typically radiation with systemic mitomycin and 5-fluorouracil (5-FU). The protocol’s efficacy laid the foundation for sphincter preservation and non-operative management. This review will detail the essential clinical trials in the treatment and surveillance of premalignant lesions and anal squamous cell cancer, including alterations in radiation dosing, systemic chemotherapy, and immunotherapy over the last several decades. Full article

Early detection of colorectal cancer (CRC) significantly improves overall prognosis and increases 5-year survival rates up to 90%. Current non-invasive screening methods for CRC, such as the Faecal Immunohistochemical Test (FIT), have some drawbacks, namely, low sensitivity and a high false-positive rate. The Sialyl-Tn (STn) antigen, frequently expressed in pre-malignant lesions and adenocarcinomas, has been shown to be detected by the novel monoclonal antibody L2A5. In this study, we explored the potential of L2A5 as a non-invasive CRC screening method in an attempt to overcome current limitations. The subjects were categorised into four groups based on colonoscopy findings: no lesion (NL), low-grade dysplasia (LGD), high-grade dysplasia (HGD), and colorectal cancer (CRC). Slot blot analysis using the L2A5 antibody was performed on stool samples from 95 colonoscopy patients. Our findings showed a differential STn expression between the different clinical groups, evidencing excellent discrimination between NL and CRC (AUC, 0.8252; 95% CI: 0.6983–0.9521; sensitivity, 70%). Moreover, moderate discrimination between the NL+LGD and HGD+CRC groups was discerned (AUC, 0.7766; 95% CI: 0.6792–0.8740; sensitivity, 58%). These findings support the application of L2A5 as a tool for detecting STn, allowing for the identification of advanced lesions in non-invasive CRC screening. Full article

Background: Oncogene-induced senescence (OIS) is a tumor-suppressive mechanism that halts uncontrolled cell proliferation in premalignant lesions. Further investigation into its role in colorectal tumorigenesis is essential. We investigated the expression of OIS transcriptomic landscapes in premalignant colorectal adenomas and whether their resolution is part to adenoma-to-carcinoma progression. Methods: Using a publicly available gene expression dataset (GSE117606), we analyzed 66 paired (matched) adenoma–adenocarcinoma samples. Single-sample gene set enrichment analysis (ssGSEA) was performed to assess OIS and senescence-associated secretory phenotype (SASP) signatures, and differential gene expression analysis was conducted to examine key senescence-related genes. Results: OIS and SASP signatures were significantly enriched in adenomas compared to adenocarcinomas (p < 0.05). Pairwise comparisons confirmed that 65% of patients exhibited higher OIS scores in adenomas, while SASP enrichment declined in 59–61% of cases. Several senescence regulators (CDKN1A, CDKN2B, and E2F3), ECM remodeling genes (MMP10 and TIMP2), and NF-κB-driven SASP factors (CCL2, CXCL2, NFKB1, and NFKB2) were significantly downregulated in adenocarcinomas, indicating the resolution of senescence-associated inflammatory signaling during tumor progression. Conclusions: These findings support the predominance of OIS phenotypes in colorectal adenomas, suggesting their potential role as a temporary barrier to tumorigenesis in colorectal cancer. Full article

Background: Hydroxyurea (HU) is a widely used chemotherapeutic agent for myeloproliferative disorders, yet its long-term use can rarely trigger a dermatomyositis-like (DM-like) eruption characterized solely by cutaneous manifestations without muscle involvement or serologic markers. This study presents a case of HU-induced DM-like eruption and reviews the literature regarding this rare occurrence. Methods: A 77-year-old woman with polycythemia vera on long-term HU therapy developed a progressively worsening, erythematous, scaly, and crusted eruption on the face, neck, and anterior thorax. Comprehensive clinical evaluations, laboratory tests (including normal muscle enzymes and negative autoimmune panels), and skin biopsies were performed. In parallel, a systematic literature review was conducted using databases such as PubMed, Scopus, and Google Scholar, incorporating case reports and series published prior to January 2025 that provided detailed individual clinical data. Results: The patient exhibited hallmark DM-like cutaneous features—interface dermatitis with basal vacuolar degeneration and prominent dermal mucin deposition—without evidence of muscle weakness or positive myositis-specific antibodies. The literature review of 23 cases revealed a median latency of 5 years from HU initiation to skin eruption, with the dorsal hands most frequently affected. HU discontinuation, often combined with systemic and topical corticosteroids (and, in some cases, steroid-sparing agents), resulted in lesion resolution in over 90% of cases, with a median healing time of approximately 3 months. Conclusions: HU-induced DM-like eruption, though infrequent, is a distinct clinical entity requiring prompt recognition and management. The main treatment is the discontinuation of HU, which, when supplemented by appropriate corticosteroid therapy, leads to significant clinical improvement. Ongoing dermatologic surveillance is recommended for patients on long-term HU therapy due to the potential risk of premalignant skin changes. Full article

Background/Objectives: Endometrial cancer (EC) is a common malignancy in developed countries, with incidence closely linked to lifestyle factors and genetic predispositions, notably Lynch syndrome. Traditional biopsy methods for diagnosis and monitoring are invasive. This study aims to develop and validate a non-invasive diagnostic method for EC using liquid biopsy, specifically examining circulating tumor DNA (ctDNA) for its potential in early detection and disease monitoring. Methods: A cohort of 63 patients with EC or atypical endometrial hyperplasia (AEH) was recruited from the Gynecological Unit of the Azienda Ospedaliera Universitaria Federico II. Plasma samples were processed to extract ctDNA, which was sequenced and analyzed for mutations. Matched tumor tissue and germline DNA were also examined to confirm mutation concordance and assess potential genetic predispositions. Results: Pathogenic mutations were identified in plasma ctDNA in 59 out of 63 cases (93%), with a 65% concordance between plasma ctDNA mutations and those found in solid tumor samples. Key mutations in genes such as PTEN, PIK3R1, and KMT2C were significantly associated with a higher tumor grade and advanced stage disease, such as myometrial infiltration. Conclusions: Liquid biopsy shows promise as a minimally invasive diagnostic and monitoring tool for EC, offering real-time insights into tumor biology. The high mutation concordance between the plasma ctDNA and tumor tissue underscores the potential of a liquid biopsy in managing EC, particularly for patients at risk of recurrence. Further longitudinal studies are needed to establish ctDNA as a standard tool in EC diagnosis and monitoring. Full article

Background/Objectives: Research on colorectal adenoma is significantly less comprehensive compared to studies on colorectal carcinoma. Although colorectal adenoma is a precursor of the majority of sporadic colorectal cancers, not all adenomas develop into carcinomas. The complex interaction of immune responses in the premalignant tumor microenvironment might be a factor for that. Methods: In this systematic review, we aim to provide a thorough analysis of the current research examining the immune infiltration patterns in sporadic colorectal adenoma tissues in the context of immune cell-based, cytokine-based, and other immunological factor-related changes along the conventional adenoma–carcinoma sequence. The articles included in the review extend up to December 2024 in PubMed and Web of Science databases. Results: Most included studies have shown significant differences in immune cell counts, densities, and cytokine expression levels associated with premalignant colorectal lesions (and/or colorectal cancer). No consensus on the immune-related tendencies concerning CD4+T cells and CD8+T cells was reached. Decreasing expression of mDCs and plasma and naïve B cells were detected along the ACS. The increased density of tissue eosinophils in the adenoma tissue dramatically diminishes after the transition to carcinoma. As the adenoma progresses, the increasing expression of IL-1α, IL-4, IL-6, IL-8, IL-10, IL-17A, IL-21, IL-23, IL-33, and TGF-β and decreasing levels of IL-12A, IL-18, IFN—γ, and TNFα cytokines in the invasive carcinoma stage is being detected. The over-expression of COX-2, PD-1/PD-L1, CTLA-4, and ICOS/ICOSLG in the colorectal adenomatous and cancerous tissues was also observed. Conclusions: Further studies are needed for a better understanding of the whole picture of colorectal adenoma-associated immunity and its impact on precancerous lesion’s potential to progress. Full article

Background: Intraductal papillary mucinous neoplasms (IPMNs) are pre-malignant pancreatic lesions that may progress to invasive pancreatic ductal adenocarcinoma (PDAC). IPMN-associated invasive carcinoma (iIPMN) has been associated with more favorable survival outcomes compared to non-iIPMN-derived PDAC. Here, we aim to investigate the genetic landscape of IPMNs to assess their relevance to oncologic outcomes. Methods: This retrospective study used a large single-institution prospectively maintained database. Patients who underwent curative-intent pancreatic resection between 2016 and 2022 with histologically confirmed diagnosis of IPMN were included. Demographic, pathologic, molecular, and oncologic outcome data were recorded. Kaplan–Meier survival analyses were performed. PDAC data from public genetic databases were used for mutational correlation analysis. p-value ≤ 0.05 was considered as significant. Results: A total of thirty-nine patients with resected IPMN with complete clinical and sequencing data were identified and included in the final cohort. The male-to-female distribution was 21:18, and the mean age was 70.1 ± 9.1 years. GNAS mutations occurred in 23.1% of patients, and 89.7% of patients had iIPMN. In iIPMN patients, GNAS mutation was strongly associated with improved disease-free survival: all GNAS-mutant patients survived to follow-up with significantly fewer recurrences than in GNAS wild-type (WT) patients (p = 0.013). Mutated GNAS closely co-occurred with wild-type KRAS (p < 0.001), and further analysis of large genomic PDAC datasets validated this finding (OR 3.47, p < 0.0001). Conclusions: Our study suggests prognostic value of mutational status in malignant resected IPMNs. WT GNAS, mutant P53, and mutant KRAS each correlate with recurrence and decreased survival. Further studies are required to validate these preliminary observations. Full article

Background: This study aimed to investigate the relationships between kymographic parameters derived from high-speed videoendoscopy (HSV) and simultaneously recorded acoustic signals. The research provides insights into the vibratory dynamics of various glottal pathologies, assessed across different glottal widths, and their mutual relations with audio data. Methods: The study included 192 participants categorized as normophonic or having functional or organic lesions (benign, premalignant, and malignant). Parameters describing vocal fold oscillations were calculated using HSV kymography for three glottal widths, along with corresponding acoustic data. Initially, linear correlations between these parameters were assessed. Next, the consistency in cycle detection and its influence on the correlation levels were evaluated. Results: The fundamental frequency (F0) and mean Jitter (Jita) showed the highest correlations between the HSV- and audio-determined parameters (F0: 0.97, Jita: 0.40–0.70), with even stronger correlations when the number of detected cycles was consistent (F0: 0.99, Jita: 0.68–0.98). The correlations for other parameters ranged from low to moderate, with no significant differences observed between the diagnostic subgroups (functional changes and benign and malignant glottal lesions). However, in the premalignant lesions group, high correlations (0.77–0.9) were observed between the HSV and audio parameters, but only for measures describing period perturbations. Beyond F0 and mean Jitter, consistency in cycle detection did not significantly affect correlation levels. Conclusions: The simultaneous audio signal proved useful in verifying the accuracy of HSV quantification measures, particularly for F0, which showed strong agreement between the methods. Discrepancies in other parameters and low correlations between HSV-derived kymography and audio data may suggest the influence of the throat, mouth, and nose resonators, which are added to the glottal signal. While the kymographic analysis based on HSV provides detailed descriptions of vocal fold oscillations, it does not fully capture the three-dimensional structure and complex functionality of the vocal folds. Full article

Background: Oral epithelial dysplasia (OED) is considered one of the premalignant lesions for oral squamous cell carcinoma (OSCC), for which the five-year disease-free survival rate may vary widely. There has emerged in recent years, therefore, a significant niche for optical coherence tomography (OCT) to non-invasively examine tissue morphology. The present study was conducted to evaluate the diagnostic performance of OCT in distinguishing between mild, moderate, and severe dysplasias and carcinoma in situ (CIS) with histopathological correlations. Methods: This prospective, single-centre study included 120 patients with clinically suspicious oral lesions. All lesions underwent in vivo OCT imaging followed by surgical excision and a histopathological examination. The sensitivity, specificity, and AUC (area under the curve) were calculated as measures of diagnostic accuracy. Results: OCT demonstrated high diagnostic performance with sensitivity and specificity above 80% for all grades of dysplasia. The AUC values were highest for moderate dysplasia at 0.91 and mild dysplasia at 0.89. The Bland–Altman analysis revealed a high degree of agreement between OCT and histopathology regarding the tumour depth measurements. Interobserver agreement was substantial to almost perfect, with kappa values ranging from 0.74 to 0.85. OCT provided the key imaging features of epithelial thickening, basement membrane disruption, and architectural disorganization. These had good correlations with the grade of dysplasia: r = 0.75–0.82, p < 0.001. Conclusions: OCT is an established diagnostic technique that is non-invasive in nature for the diagnosis of OED; it can provide fine differentiation among grades of dysplasia and define the margins of a lesion. Full article

Objectives: Vulvar squamous cell carcinoma (VSCC) is a rare gynecologic malignancy, with most cases arising from differentiated vulvar intraepithelial neoplasia (dVIN). Approximately one-third of VSCC cases originate from high-grade squamous intraepithelial lesions (HSILs), which are associated with persistent infection by varieties of high-risk human papillomavirus (hrHPV). This study aimed to quantify the circulating microRNAs (miRNAs) in the plasma of patients with premalignant conditions (dVIN and HSILs) and VSCC using TaqMan Low-Density Arrays. Methods: Plasma samples were collected from 40 patients, including those treated for HSILs, dVIN, and VSCC. Quantitative real-time PCR (qRT-PCR) identified the circulating miRNAs differentially expressed in the plasma of VSCC patients compared to patients with precancerous lesions. Results: A total of 31 differentially expressed miRNAs (DEMs) were found to be significantly upregulated in plasma from VSCC patients compared to precancerous cases. None of the analyzed miRNAs were able to distinguish VSCC cases based on hrHPV tumor status. Conclusions: This study provides strong evidence that a distinct set of miRNAs can differentiate between plasma samples from VSCC patients and those with precancerous lesions. Thus, these DEMs have potential diagnostic and prognostic value. “Predisposing” DEMs could be developed as biomarkers to aid in the assessment of vulvar lesions, helping to exclude or confirm progression toward cancer. Full article