Search Results (87)

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

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: 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

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

Atypical polypoid adenomyoma (APA) is a benign uterine lesion with a premalignant potential and occurs in women of reproductive age. The histological pattern is characterized by irregular epithelial proliferation and muscular stroma. Based on a case report, we performed a systematic review of the literature to assess the main immunohistochemical and molecular markers that contribute to its differential diagnosis against endometrial adenocarcinoma (EC). The distinction is essential for offering to patients a conservative treatment compared to the radical management required for endometrial cancer, a critical issue for the significant physical and psychological consequences that one procedure or another can have on women’s health. We performed a meta-analysis of the immunohistochemical markers used for the histological diagnosis of APA, comparing it with our case study. The evaluated markers were beta-catenin, h-caldesmon, desmin, vimentin, smooth muscle alpha-actin, CD10, Ki67, estrogen receptor (ER), progesterone receptor (PR), pan-cytokeratin, PTEN, PMS2, MSH2, MSH6, p53, MLH1, and p16. Discrepancies were observed in the expression of CD10, h- caldesmon, and p16 when comparing APA with EC. The results of the case evaluated by our team showed beta-catenin nuclear expression and positive immunostaining for pan-cytokeratin, ER, and PR in the glands; smooth muscle actin and desmin positive expression in stromal muscle; and p16 positive immunostaining in squamous morules. Moreover, the c.94G>T p. (Asp132Tyr) mutation in the CTNNB1 gene was detected. This study supports the combination of appropriate immunohistochemical and molecular markers, along with the presumptive histological diagnosis, and determines the correct classification of the lesion as APA and not as other malignant pathologies, allowing for the establishment of a treatment protocol adjusted to the biological reality of this pathology. Full article

Multiple myeloma (MM) is the second most prevalent hematologic malignancy, particularly affecting the elderly. The disease often begins with a premalignant phase known as monoclonal gammopathy of undetermined significance (MGUS), solitary plasmacytoma (SP) and smoldering multiple myeloma (SMM). Multiple imaging modalities are employed throughout the disease continuum to assess bone lesions, prevent complications, detect intra- and extramedullary disease, and evaluate the risk of neurological complications. The implementation of advanced imaging analysis techniques, including artificial intelligence (AI) and radiomics, holds great promise for enhancing our understanding of MM. The integration of advanced image analysis techniques which extract features from magnetic resonance imaging (MRI), computed tomography (CT), or positron emission tomography (PET) images has the potential to enhance the diagnostic accuracy for MM. This innovative approach may lead to the identification of imaging biomarkers that can predict disease prognosis and treatment outcomes. Further research and standardized evaluations are needed to define the role of radiomics in everyday clinical practice for patients with MM. Full article

Oncogene-induced senescence (OIS) is a form of cellular senescence triggered by oncogenic signaling and, potentially, by infection with oncogenic viruses. The role of senescence, along with its associated secretory phenotype, in the development of cervical cancer remains unclear. Additionally, the expression of the senescence-associated secretory phenotype (SASP) has not yet been explored in cervical premalignant lesions infected by the Human Papilloma Virus (HPV). This study aimed to investigate the expression of OIS and SASP markers in HPV-infected cervical precancerous lesions. We used a set of patient-derived precancerous (n = 32) and noncancerous (chronic cervicitis; n = 10) tissue samples to investigate the gene expression of several OIS (LMNB1, CDKN2A, CDKN2B, and CDKN1A), and SASP (IL1A, CCL2, TGFB1, CXCL8, and MMP9) biomarkers using qRT-PCR. OIS status was confirmed in precancerous lesions based on Lamin B1 downregulation by immunohistochemical staining. HPV status for all precancerous lesions was tested. Most of the noncancerous samples showed high Lamin B1 expression, however, precancerous lesions exhibited significant Lamin B1 downregulation (p < 0.001). Fifty-five percent of the precancerous samples were positive for HPV infection, with HPV-16 as the dominant genotype. Lamin B1 downregulation coincided with HPV E6 positive expression. CDKN2A and CDKN2B expression was higher in precancerous lesions compared to noncancerous tissue, while LMNB1 was downregulated. The SASP profile of premalignant lesions included elevated CXCL8 and TGFB1 and reduced IL1A, CCL2, and MMP9. this work shall provide an opportunity to further examine the role of OIS and the SASP in the process of malignant cervical transformation. Full article

Cervical cancer remains a significant global health concern, particularly in low- and middle-income countries. While persistent infection with high-risk human papillomavirus (HR-HPV) is essential for cervical cancer development, it is not sufficient on its own, suggesting the involvement of additional cofactors. The human cytomegalovirus (HCMV) is a widespread β-herpesvirus known for its ability to establish lifelong latency and reactivate under certain conditions, often contributing to chronic inflammation and immune modulation. Emerging evidence suggests that HCMV may play a role in various cancers, including cervical cancer, through its potential to influence oncogenic pathways and disrupt host immune responses. This review explores clinical evidence regarding the co-presence of HR-HPV and HCMV in premalignant lesions and cervical cancer. The literature reviewed indicates that HCMV is frequently detected in cervical lesions, particularly in those co-infected with HPV, suggesting a potential synergistic interaction that could enhance HPV’s oncogenic effects, thereby facilitating the progression from low-grade squamous intraepithelial lesions (LSIL) to high-grade squamous intraepithelial lesions (HSIL) and invasive cancer. Although the precise molecular mechanisms were not thoroughly investigated in this review, the clinical evidence suggests the importance of considering HCMV alongside HPV in the management of cervical lesions. A better understanding of the interaction between HR-HPV and HCMV may lead to improved diagnostic, therapeutic, and preventive strategies for cervical cancer. Full article

Endoscopic ultrasound-guided radiofrequency ablation (EUS-RFA) has emerged as an effective and minimally invasive treatment for pancreatic lesions, particularly in patients at high surgical risk. Utilizing thermal energy, RFA induces the coagulative necrosis of the tissue and potentially triggers immunomodulation by releasing intracellular antigens. Numerous studies have confirmed the technical feasibility, safety, and efficacy of EUS-RFA in pancreatic neuroendocrine tumors and premalignant cystic lesions, with an acceptable profile of adverse events. The technique’s potential immunomodulatory effects offer intriguing implications for the treatment of advanced pancreatic malignancies, encouraging further evaluation. This review paper aims to highlight the EUS-RFA principles, technology, and clinical applications in various pancreatic lesions and safety, and the future research directions. Full article

Objectives: Autoimmune pancreatitis (AIP) type 1, paraduodenal (groove) pancreatitis, and follicular pancreatitis are rare clinical entities whose diagnosis may be challenging, given the potential imaging overlap with pancreatic cancer. Methods: We performed a retrospective analysis of the medical chart of a patient with multiple pancreas pathologies. Results: We present a case with multiple pancreas pathologies, including a poorly differentiated ductal adenocarcinoma of pancreatobiliary type, an intraductal papillary mucinous lesion (pre-existing lesion of IPMN type), and an inflammatory process with complex features, in which paraduodenal (groove) pancreatitis, follicular pancreatitis, and IgG4-related pancreatitis (AIP type 1) were also present. Conclusions: The diagnosis of AIP and paraduodenal pancreatitis is not always straightforward, and in some cases, it is not easy to differentiate them from pancreatic cancer. Surgery should be considered in patients when a suspicion of malignant/premalignant lesions cannot be excluded after a complete diagnostic work-up. Full article

Premalignant lesions within the bronchial epithelium signify the initial phases of squamous cell lung carcinoma, posing challenges for detection via conventional methods. Instead of focusing solely on gene expression, in this study, we explore transcriptomic alterations linked to lesion progression, with an emphasis on protein-coding transcripts. We reanalyzed a publicly available RNA-Seq dataset on airway epithelial cells from 82 smokers with and without premalignant lesions. Transcript and gene abundance were quantified using kallisto, while differential expression and transcript usage analysis was performed utilizing sleuth and RATs packages. Functional characterization involved overrepresentation analysis via clusterProfiler, weighted coexpression network analysis (WGCNA), and network analysis via Enrichr-KG. We detected 5906 differentially expressed transcripts and 4626 genes, exhibiting significant enrichment within pathways associated with oxidative phosphorylation and mitochondrial function. Remarkably, transcript-level WGCNA revealed a single module correlated with dysplasia status, notably enriched in cilium-related biological processes. Notable hub transcripts included RABL2B (ENST00000395590), DNAH1 (ENST00000420323), EFHC1 (ENST00000635996), and VWA3A (ENST00000563389) along with transcription factors such as FOXJ1 and ZNF474 as potential regulators. Our findings underscore the value of transcript-level analysis in uncovering novel insights into premalignant bronchial lesion biology, including identification of potential biomarkers associated with early lung carcinogenesis. Full article

HPV 16 integration is crucial for the onset and progression of premalignant lesions to invasive squamous cell carcinoma (ISCC) because it promotes the amplification of proto-oncogenes and the silencing of tumor suppressor genes; some of these are proteins with PDZ domains involved in homeostasis and cell polarity. Through a bioinformatics approach based on interaction networks, a group of proteins associated with HPV 16 infection, PDZ domains, and direct physical interaction with E6 and related to different hallmarks of cancer were identified. MAGI-1 was selected to evaluate the expression profile and subcellular localization changes in premalignant lesions and ISCC with HPV 16 in an integrated state in cervical cytology; the profile expression of MAGI-1 diminished according to lesion grade. Surprisingly, in cell lines CaSki and SiHa, the protein localization was cytoplasmic and nuclear. In contrast, in histological samples, a change in subcellular localization from the cytoplasm in low-grade squamous intraepithelial lesions (LSIL) to the nucleus in the high-grade squamous intraepithelial lesion (HSIL) was observed; in in situ carcinomas and ISCC, MAGI-1 expression was absent. In conclusion, MAGI-1 expression could be a potential biomarker for distinguishing those cells with normal morphology but with HPV 16 integrated from those showing morphology-related uterine cervical lesions associated with tumor progression. Full article

Colorectal cancer (CRC) screening relies primarily on stool analysis to identify occult blood. However, its sensitivity for detecting precancerous lesions is limited, requiring the development of new tools to improve CRC screening. Carcinogenesis involves significant alterations in mucosal epithelium glycocalyx that decisively contribute to disease progression. Building on this knowledge, we examined patient series comprehending premalignant lesions, colorectal tumors, and healthy controls for the T-antigen—a short-chain O-glycosylation of proteins considered a surrogate marker of malignancy in multiple solid cancers. We found the T-antigen in the secretions of dysplastic lesions as well as in cancer. In CRC, T-antigen expression was associated with the presence of distant metastases. In parallel, we analyzed a broad number of stools from individuals who underwent colonoscopy, which showed high T expressions in high-grade dysplasia and carcinomas. Employing mass spectrometry-based lectin-affinity enrichment, we identified a total of 262 proteins, 67% of which potentially exhibited altered glycosylation patterns associated with cancer and advanced pre-cancerous lesions. Also, we found that the stool (glyco)proteome of pre-cancerous lesions is enriched for protein species involved in key biological processes linked to humoral and innate immune responses. This study offers a thorough analysis of the stool glycoproteome, laying the groundwork for harnessing glycosylation alterations to improve non-invasive cancer detection. Full article