Search Results (186)

Cutaneous hematologic neoplasms in children are relatively rare and encompass a wide range of lymphoproliferative and myeloproliferative disorders. This review explores and updates the classification, clinical presentation, diagnostic challenges, histopathology, and management of pediatric lymphomas, lymphoproliferations, and leukemias that may be seen in the skin. The most frequent of them are lymphomatoid papulosis (LyP) and mycosis fungoides (MF), and are discussed first, with a particular focus on differential diagnosis and overlaps with benign lesions—mainly pityriasis lichenoides—which raises questions regarding the delineation of these entities and their potential interconnection. It is important to underline that most cutaneous lymphoproliferations are indolent in children: primary cutaneous CD4+ small/medium T-cell lymphoproliferative disorder, subcutaneous panniculitis-like T-cell lymphoproliferation (non-associated with HAVCR2 mutations), primary cutaneous marginal zone lymphoproliferative disorder, and EBV-related lymphoproliferative disorders. However, aggressive hematologic malignancies, although rarer, must not be missed; these are mostly leukemias (but not all forms) and blastic plasmacytoid dendritic cell neoplasm. We emphasize the importance of clinical–pathological correlation, with clonality studies playing a crucial role in some cases. Management strategies are briefly reviewed, ranging from skin-directed therapies like phototherapy and corticosteroids to systemic treatments for more aggressive forms of leukemia cutis and lymphomas. Full article

Cutaneous pseudolymphomas are benign reactive lymphoid proliferations that often mimic cutaneous lymphomas both clinically and histologically. A diverse array of inflammatory, infectious, and drug-induced dermatoses can closely resemble cutaneous T-cell lymphomas (CTCLs), particularly mycosis fungoides (MFs), posing significant diagnostic challenges. These mimickers may show histopathological features such as epidermotropism, dense lymphocytic infiltrates, or even clonality, making accurate differentiation crucial to avoid overtreatment. This review endeavors to comprehensively discuss the clinicopathologic features of the various inflammatory and infectious dermatoses that may simulate CTCL, drawing on illustrative examples across disease categories. By highlighting important comparative features and emphasizing the importance of clinicopathologic correlation, this review outlines practical strategies for distinguishing true lymphoma from its inflammatory mimics. Full article

Hydrogen is widely considered a promising clean energy carrier because of its high energy density and environmental benignity, yet the development of safe and reversible hydrogen storage materials remains a major challenge. Two-dimensional materials are particularly attractive for this purpose owing to their large specific surface area, fully exposed active sites, and highly tunable electronic structures. Here, using crystal structure prediction combined with first-principles calculations, we predict a stable metallic Li₃B₂N₂ monolayer as a potential hydrogen storage material. This monolayer can adsorb up to six H₂ molecules per unit cell with an average adsorption energy of ∼0.23 eV/H₂, yielding a high hydrogen storage capacity of ∼7.8 wt.%. Further analysis reveals that hydrogen adsorption is governed by the synergistic effects of electrostatic polarization and orbital hybridization. Moreover, calculations on the temperature- and pressure-dependent hydrogen storage behavior show that all hydrogen-adsorbed structures remain stable at room temperature under a pressure of 3.7 MPa. The van’t Hoff analysis indicates that the maximum desorption temperature at atmospheric pressure is 316 K, suggesting favorable reversibility under near-ambient conditions. These results establish Li₃B₂N₂ as a promising intrinsic two-dimensional material for high-density and reversible hydrogen storage. Full article

Oral cancer is a significant public health concern and is among the most common malignant tumors of the head and neck. Its incidence and mortality rates remain persistently high, especially in regions where smoking and betel nut chewing are prevalent. Due to its high mortality rate, early detection is crucial for improving patient outcomes. However, early symptoms of oral cancer often resemble benign oral lesions, leading to delayed diagnosis. In this study, a vision transformer (ViT) model with Optuna (ViTOPT) is employed to perform classification tasks of identifying oral cancer images. The Optuna is used to determine hyperparameters in ViT. Histological images are obtained from a publicly available dataset. Three classification tasks with histological images namely classifying oral squamous cell carcinoma (OSCC) and leukoplakia (LEUK), classifying the presence of dysplasia, and classifying OSCC and leukoplakia with or without dysplasia are performed in this study. Numerical results reveal that the proposed ViTOPT framework is able to provide satisfactory performance in oral cancer recognition. Thus, the proposed ViTOPT model is a feasible and effective alternative in identifying oral cancer. Full article

Pulmonary nodules detected in patients with a history of malignancy are often clinically presumed to represent metastatic disease until proven otherwise. Granular cell tumor (GCT) is an uncommon, usually benign neoplasm of presumed Schwannian origin, which rarely occurs in the lung. Our aim is to emphasize the diagnostic challenges and the crucial role of histopathology in preventing overtreatment in oncology patients. Herein, we report the case of a 56-year-old woman with a previous history of papillary renal cell carcinoma diagnosed one year earlier, staged as pT1, WHO/ISUP grade 2, and treated with partial nephrectomy, with no evidence of residual disease or distant metastases at follow-up. During routine surveillance, she developed a solitary pulmonary nodule. Chest computed tomography (CT) showed a 12 mm solid nodule in the left upper lobe which was then further investigated with a positron emission tomography with 2-[¹⁸F] fluoro-2-deoxy-D-glucose [(¹⁸F)-FDG PET/CT, revealing a low glucidic uptake (SUVmax 4 and SUV mean 1.4). Endobronchial ultrasound-guided biopsy was non-diagnostic. Given the patient’s oncological history, the solid appearance on CT, and the mild FDG uptake, metastatic disease could not be excluded, and a parenchyma-sparing diagnostic wedge resection was performed. Histology showed a well-circumscribed proliferation of epithelioid cells with abundant granular eosinophilic cytoplasm and bland nuclei. Immunohistochemistry demonstrated diffuse S100 and CD68 positivity, supporting the diagnosis of primary pulmonary granular cell tumor. This case underscores the critical role of histopathological evaluation in the assessment of solitary pulmonary nodules, emphasizing that lesions identified during oncologic surveillance are not invariably indicative of malignancy. Full article

Background: The early detection of prostate and testicular tumors remains challenging as standard diagnostic tools often lack sensitivity and produce ambiguous results. Seminal fluid is a biologically rich medium that closely reflects the state of male reproductive tissues and has therefore emerged as a promising source of non-invasive molecular biomarkers. Objective: This study aimed to critically evaluate the evidence regarding cell-free DNA, RNA, proteins and metabolites in seminal fluid, and to assess their potential for improving the early detection of male reproductive cancers. Methods: A systematic review was performed according to PRISMA guidelines. Comprehensive searches of the PubMed and Scopus databases were conducted to identify original clinical studies analyzing molecular biomarkers in seminal fluid from patients with prostate or testicular tumors. For each study, data were extracted on biomarker types, cohort characteristics, analytical methods and diagnostic performance. Results: Forty-two eligible studies were included, covering multiple biomarker classes. Most were observational, single-center investigations classified as level 3b evidence. Across the different types of biomarkers, seminal fluid was associated with tumor-associated molecular changes. Alterations in the concentration, fragmentation and methylation patterns of cell-free DNA (e.g., GSTP1, RARβ2, LGALS3 and OCT3/4) distinguished malignant from benign conditions with sensitivities of up to 80–100%. RNA-based markers, including microRNAs, small non-coding RNAs, and tRNA fragments, showed improved performance in several studies, with multimarker models achieving areas under the curve (AUCs) of 0.85–0.93. Proteomic analyses identified high-specificity candidates such as TGM4, AMACR, PROS1 and DKK3. Metabolomic profiling further strengthened the diagnostic potential; reduced seminal citrate outperformed prostate-specific antigen (AUC 0.748 vs. 0.548), and reproducible shifts in amino acid and lipid profiles were observed in testicular tumors. However, substantial heterogeneity in study design, patient selection, and analytical platforms was observed. Risk of bias varied, and large prospective validation cohorts were lacking. Conclusions: Current evidence suggests that seminal fluid contains molecular signals associated with tumors that could be used for diagnosis. However, the available data are predominantly exploratory and methodologically heterogeneous. Before seminal fluid-based biomarkers can be considered for routine clinical implementation, robust prospective studies with standardized protocols are required. Full article

With increasing environmental pollution and a high incidence of respiratory infections, pulmonary nodules (PN) are being detected more frequently. Although most are benign, they are often accompanied by chronic inflammation and localized fibrosis, which may predispose patients to progression toward idiopathic pulmonary fibrosis (IPF). However, the biological relationship between benign pulmonary nodules (BPNs) and IPF remains poorly understood. Therefore, this study aims to investigate the shared molecular mechanisms and identify potential biomarkers linking BPN and IPF, with the goal of elucidating the pathogenic transition from BPN to IPF. In this study, microarray data from GEO datasets were systematically analyzed to explore shared molecular mechanisms, immune infiltration characteristics, and potential early intervention strategies linking BPN and IPF. Differential expression analysis, protein–protein interaction (PPI) networks, weighted gene co-expression network analysis (WGCNA), and integrative machine learning approaches identified MME and ANKRD23 as key hub genes associated with the transition from BPN to IPF. Both genes demonstrated strong diagnostic performance, with Area Under the Curve (AUC) values exceeding 0.7, and were significantly correlated with immune cell infiltration, particularly effector memory CD8⁺ T cells. Functional enrichment and gene set enrichment analyses indicated that these genes were mainly involved in immune-related processes in BPN, while in IPF, ANKRD23 was linked to cytoskeletal organization and genomic stability, and MME was enriched in profibrotic pathways such as TGF-β signaling. The diagnostic value of these biomarkers was further validated in a bleomycin-induced IPF mouse model using quantitative polymerase chain reaction (qPCR). In addition, drug–gene interaction prediction and molecular docking analyses highlighted several naturally derived compounds with favorable binding affinity and anti-inflammatory properties, among which folic acid, curcumin, and arbutin emerged as promising candidates for safe early intervention. Collectively, these findings identify MME and ANKRD23 as potential biomarkers for early identification of BPN patients at risk of developing IPF and provide a theoretical basis for early diagnosis and targeted preventive strategies. Full article

Background: Merkel cell carcinoma (MCC) is a rare, aggressive primary cutaneous neuroendocrine carcinoma with a marked propensity for early regional lymph node metastasis. Although MCC most often arises on sun-exposed head and neck skin in older adults, tumors of the lower extremity are uncommon and may be mistaken for benign hemorrhagic lesions. Case presentation: A 54-year-old woman developed a rapidly enlarging, hemorrhagic mass in the left suprapatellar thigh. Magnetic resonance imaging demonstrated an extracompartmental subcutaneous soft-tissue mass without quadriceps muscle invasion. Wide local excision including the quadriceps fascia was performed. Histopathologic examination showed a dermal/subcutaneous small blue round cell neoplasm with brisk mitotic activity. Immunohistochemistry demonstrated diffuse cytoplasmic synaptophysin positivity, paranuclear dot-like CK20 reactivity, chromogranin A positivity, and negative MCPyV staining; TTF-1, S100, melan-A, HMB-45, and hematolymphoid markers were negative. Staging positron emission tomography/computed tomography identified ipsilateral inguinal nodal involvement. Therapeutic inguinal lymph node dissection revealed metastatic MCC in one of four lymph nodes without extranodal extension. The final stage was pT3 pN1b cM0 (AJCC 8th edition), corresponding to stage IIIB disease. Adjuvant radiotherapy (57 Gy in 20 fractions) was delivered to the primary bed and ipsilateral inguinal basin. The patient remains disease-free at 5-year follow-up. Conclusions: Lower-extremity MCC can mimic hemorrhagic or post-traumatic lesions, contributing to diagnostic delay. Persistent or rapidly enlarging “hematoma-like” lesions warrant early biopsy, and timely pathologic nodal staging is essential. Multimodal management can achieve durable control even in node-positive disease Full article

T-cell non-Hodgkin lymphomas, which arise from post-thymic mature T cells, constitute approximately 10–15% of all non-Hodgkin lymphomas. Their leukemic presentations, referred to here as mature T-cell leukemias, are relatively uncommon and present significant diagnostic and therapeutic challenges requiring an informed approach to diagnosis and management. The initial presentation is often persistent T-cell lymphocytosis that must be distinguished from reactive (non-malignant) causes. Unlike B-cell lymphocytosis, where clonality usually indicates malignancy, T-cell clonality can be detected in benign conditions such as autoimmune disorders and viral infections. Thus, establishing clonality is helpful but not sufficient, and a systematic diagnostic approach integrating clinical features, morphology, immunophenotype, and molecular findings is critical. This review outlines our approach to the diagnosis and treatment of four major subtypes of mature T-cell leukemias: T-cell prolymphocytic leukemia (T-PLL), adult T-cell leukemia/lymphoma (ATLL), T-large granular lymphocytic leukemia (T-LGL), and Sézary syndrome (SS). Each section includes a discussion of clinical features, workup, and treatment options. Full article

Pituitary neuroendocrine tumors (PitNETs) are usually benign intracranial neoplasms that may exhibit invasion of the cavernous sinus, complicating surgery and increasing the risk of recurrence. This study aimed to investigate membranous E-cadherin (mE-cad) expression across PitNET subtypes and transcription factor (TF) lineages, including Pit-1 (pituitary-specific positive transcription factor 1), SF-1 (Steroidogenic Factor 1), and TPIT (T-box pituitary transcription factor), and its association with tumor invasiveness in sixty-nine patients. mE-cad expression was evaluated as the percentage of positive cells (0%, 1–10%, >10%) and by immunoreactive score (IRS). Staining intensity was scored as: 0, no staining; 1, weak; 2, moderate; 3, strong. The proportion of positive cells was scored as: 0, none; 1, <10%; 2, 10–50%; 3, 51–80%; 4, >80%. Mean mE-cad expression was 5.2% in gonadotroph, 3.2% in corticotroph, 0.5% in lactotroph, and 17.5% in plurihormonal PitNETs. By TF lineage, the mean expression was 5.3% for Pit-1, 3.2% for TPIT, and 5.1% for SF-1. Low mE-cad expression (IRS 1–2) was associated with higher odds of cavernous sinus invasion compared with IRS 3–6 (adjusted OR = 6.0, 95% CI 1.08–33.4, p = 0.04), independent of tumor volume (adjusted OR = 4.0, 95% CI 1.50–10.7, p = 0.01). After restricting the analysis to the gonadotroph PitNET group, tumors with an IRS of 1–2 showed significantly higher invasiveness compared with those with an IRS of 3–6 (p = 0.012). These findings suggest that mE-cad may serve as a biomarker of PitNET invasiveness, with expression varying according to TF lineage and tumor subtype. Full article

This study presents an efficient, environmentally benign approach for synthesizing chitosan-entrapped titanium dioxide (TiO₂) nanocomposites utilizing aqueous orange peel extract playing its role in reduction and stabilization of the nanoparticles and exploring its anticancer activity in vitro. TiO₂ nanoparticles were initially synthesized via a modified sol-gel method incorporating the orange peel extract. Subsequently, these nanoparticles were entrapped within a chitosan matrix. The orange peel extract was thoroughly characterized using analysis of phytochemicals present, and Gas Chromatography–Mass Spectrometry (GC–MS) analysis of a reconstructed methanolic extract to identify potential biomolecules responsible for the reduction and capping processes. The synthesized chitosan-entrapped TiO₂ nanoparticles were subjected to comprehensive characterization using various analytical techniques, like UV–visible spectroscopy, Dynamic Light Scattering (DLS) and Zeta Potential analysis, X-ray Diffraction (XRD), FTIR, High-Resolution Scanning Electron Microscopy (HR-SEM) and Energy-Dispersive X-ray Spectroscopy (EDAX). An absorption peak was observed at 296 nm, a hydrodynamic diameter of 400 nm, a+ 35.88 mV zeta potential, and an SEM image showing a diameter in the range of 300–645 nm, indicating polymer entrapment with enhanced size. Brine shrimp assay, MTT assay using normal fibroblasts, 3T3-L1, and zebrafish embryo assay were done to observe the biocompatibility of the synthesized nanostructure. The concentration of 50 μg/mL was found to be inert in both in vitro and in vivo. Furthermore, cervical cancer cells, SiHa, were treated with the nanoparticles to exhibit their cancer-killing capability with an IC₅₀ value of 30.74 μg/mL. The results demonstrate the effectiveness of orange peel extract as a sustainable agent for TiO₂ nanoparticle synthesis and the successful formation of a stable chitosan-entrapped nanocomposite. This approach offers a promising pathway for producing functional metal oxide nanomaterials with reduced environmental impact and enhanced properties for diverse biomedical applications. Future studies using other types of cancer cells and animal models for cancerous tumors need to be explored. Full article

Background/Objectives: Extranodal NK/T-cell lymphoma, nasal type (ENKTCL-NT), is a rare and extremely aggressive subtype of non-Hodgkin lymphoma that most frequently involves the nasal cavity and upper aerodigestive tract. Primary isolated oral manifestation is exceptionally uncommon and may mimic odontogenic or infectious diseases, delaying diagnosis. We report a case of ENKTCL-NT presenting initially as a destructive oral lesion without sinonasal involvement at diagnosis. Methods: A 32-year-old man with progressive palatal ulceration underwent clinical and imaging assessment (panoramic radiography and staging ^18F-FDG PET–CT) and repeated biopsies. Diagnosis was established using histopathology (H&E), immunohistochemistry (T-cell markers and cytotoxic profile), EBV detection by EBER in situ hybridization, and T-cell receptor gamma (TCRG) gene rearrangement analysis. Results: The lesion presented as a hemorrhagic, ulcerative palatal destruction covered by pseudomembranous exudate and was complicated by fungal infection, periostitis, and severe dental inflammatory foci, contributing to diagnostic delay. Histopathological examination revealed extensive necrosis with a dense atypical lymphoid infiltrate; angiocentric and angiodestructive growth was identified in one biopsy specimen. Tumor cells expressed T-cell markers (CD2, CD3, CD5, CD7; heterogeneous) and cytotoxic markers (TIA-1) and showed CD30 and CD56 positivity, with EBV positivity confirmed by EBER in situ hybridization. Molecular analysis demonstrated monoclonal TCRG rearrangement, and Ki-67 indicated high proliferative activity. Initial PET–CT demonstrated an intensely FDG-avid, locally invasive lesion without distant organ involvement. The patient was treated with L-asparaginase-based SMILE chemotherapy followed by radiotherapy (50 Gy), achieving marked initial clinical improvement and partial metabolic response; however, systemic relapse subsequently occurred with refractory disease despite salvage therapy and immunotherapy. Conclusions: This case highlights the substantial diagnostic challenge posed by isolated oral extranodal NK/T-cell lymphoma, nasal type, which may closely mimic benign inflammatory or infectious conditions and lead to significant diagnostic delay. Persistent, progressive, or therapy-resistant oral ulcerations should prompt early consideration of hematologic malignancy. Timely biopsy with comprehensive immunophenotyping, EBV testing, and close multidisciplinary collaboration are essential for accurate diagnosis and may contribute to earlier diagnosis and improved patient outcomes in these rare and atypical presentations. Full article

Introduction: Chronic lymphocytic leukemia (CLL) is a common adult leukemia often treated with fludarabine, cyclophosphamide, and rituximab (FCR). While effective, FCR can lead to therapy-related myeloid neoplasms (t-MN), including aggressive therapy-related acute myeloid leukemia (t-AML). Stem cell transplantation offers the best chance for long-term remission in these cases. Here, we report a rare case of t-AML with plasmacytoid dendritic cells (pDC-AML) developing after FCR treatment for CLL that was successfully treated with haplotransplantation. Case Presentation: A 57-year-old woman with CLL-B was treated with six cycles of FCR, achieving a complete response. Six years later, at age 63, she developed t-AML with a rare morphophenotypic subtype: acute myelomonocytic leukemia with plasmacytoid dendritic cells (pDC-AML) and monosomy 8. Diagnostic challenges included distinguishing this subtype from blastic plasmacytoid dendritic cell neoplasm (BPDCN). She was treated with high-dose cytarabine followed by haploidentical stem cell transplantation from her son. Haploidentical transplantation was prioritized due to the urgent clinical need in a patient with high-risk acute leukemia (therapy-related leukemia secondary to prior chemoimmunotherapy and failure to achieve complete remission following the standard 3 + 7 induction protocol). In this critical setting, the patient’s son was immediately available as an HLA-haploidentical donor. Prior to the performance of the haploidentical stem cell transplant from her son, no HLA-matched unrelated donor (MUD) could be identified. Another viable alternative would have been the utilization of umbilical cord blood-derived stem cells harvested from the patient’s twin granddaughters. She was closely monitored post-transplant for potential complications, including graft-versus-host disease (GVHD), post-transplant lymphoproliferative disorder, and thyroid dysfunction, all of which were ruled out during follow-up. The patient remains in complete remission 15 years after her initial CLL diagnosis and 8 years after the t-AML diagnosis and haplotransplantation. Notably, no residual CLL clone was detected at the time of t-AML development, and a benign polyclonal lymphocytosis observed between 2018 and 2020 spontaneously resolved without intervention. Conclusions: This case illustrates the potential for long-term survival in high-risk patients with therapy-related AML developed after cytotoxic treatment for lymphoid malignancies. Haplotransplantation from a semi-identical Human Leukocyte Antigen (HLA) donor proved to be a viable and effective treatment option despite the patient’s age and dual hematologic malignancies. Full article

Background and Clinical Significance: CEUS enhances the visualization of vascular patterns within liver lesions, enabling differentiation between benign and malignant lesions, including hemangiomas, focal nodular hyperplasia, and hepatocellular carcinoma, with high accuracy. Lymphangiomas are rare benign lymphatic-system tumors, with intra-abdominal lymphangiomas accounting for approximately 5% of cases, most of which occur in the pediatric population. Intra-abdominal lymphangiomas commonly occur in multiple localizations due to lymphangiomatosis, but solitary lymphangiomas in adults are rare and easy to be misdiagnosed due to asymptomatic cases or non-specific symptoms. Case Presentation: A 65-year-old male with a history of left nephroadrenalectomy due to clear renal-cell carcinoma and paraaortic lymphadenectomy (staging pT3bN0M0V1R0) presented for a routine contrast-enhanced abdominal computer tomography examination. The scan showed several hypervascular structures that accumulate contrast in the arterial phase in the right liver lobe. Three years later, the patient developed complaints of abdominal pain and night sweats. Multiple MRI and CT examinations were performed, followed by a CEUS and a liver-core biopsy, which supported the diagnosis of hepatic lymphangioma. Conclusions: CEUS may be a more valuable evaluation method for follow-up examination than repeating CT and MRI scans. The real-time diagnostic possibility and tissue-perfusion data provide more profound information about the lesion of interest. Thus, it can be used as a primary diagnostic tool when a biopsy is performed. Although this method is relatively new, it can be applied in clinical settings with great value, and it saves time and resources. Full article

In the male body, zinc accumulates most abundantly in prostatic cells, where it plays a key role in producing high amounts of citrate in seminal fluid. Intraprostatic accumulation of Zn increases during the development of benign prostatic hyperplasia (BPH), one of the most common diseases in men over 50 years of age. Continuing our investigations on intraprostatic androgens, in this study, we analyzed the mineral content (Zn, Ca, Cu, K, Mg, Mn, and Na) in the transitional zone (TZ) of the prostate using inductively coupled plasma optical emission spectrometry (ICP-OES). The concentrations of testosterone (T) and dihydrotestosterone (DHT) were determined by liquid chromatography–mass spectrometry (LC-MS). Group-wise and correlation analyses demonstrated a descriptive trend toward a volume-dependent increase in Zn concentrations within TZ tissue, whereas other elements exhibited heterogeneous covariance patterns; intraprostatic hormone levels, although elevated in larger prostates, showed no consistent linear correlations with elemental concentrations. Given the observational design of the present study, the reported tissue Zn profiles cannot be interpreted as evidence supporting supplementation in BPH, and any potential clinical implications warrant evaluation in rigorously designed interventional studies. Full article