Search Results (220)

Background and Clinical Significance: Angioleiomyoma (ALM) is a benign tumor that generally presents as a single lesion and, according to the updated WHO classification, includes the following three histological subtypes: solid (or capillary), cavernous, and venous. Typically, ALMs are described as well-defined nodules in the lower extremities but are unusually located in the acral locations and toes. We summarize two cases of ALM and perform a systematic review to provide foot surgeons with the most up-to-date and useful information on the epidemiological aspects, anatomical distribution, and specific histological subtypes of ALM in the foot. Materials and Methods: A systematic review was carried out according to the criteria of a PICO framework, and a systematic search and data processing were carried out according to the PRISMA guidelines. We analyzed patient demographics, clinical characteristics, diagnostic workup, treatment, and clinical outcomes. Each one of the included articles was independently assessed for methodological quality and risk of bias by an independent evaluator. The risk of bias of the included studies was assessed based on their characteristics. Results: This systematic review included 14 case series with 172 reported cases of ALM. One hundred and seventy-two (18.57%) were cases of ALM located on foot, excluding the ankle region. The female-to-male ratio was 1.48. The most common location was the hindfoot (41.5%), followed by the forefoot (20.2%) and the midfoot (8.9%). In 29.4% of cases, the location of the lesions could not be determined. The most frequent location of the lesions was subcutaneous (69%), followed by subaponeurotic (16.5%) and skin (14.5%) locations. The most frequent histological presentation was the solid histologic subtype (65%), followed by the venous subtype (21%) and the cavernous subtype (14%), respectively. Of the total reported cases of ALM located in foot, 63.1% presented as solid painful lesions. Calcified presentations occurred in 7% of cases, with more than half of the cases located in the hindfoot. Surgical excision was the treatment of choice in the two herein reported cases of solid ALM located in the hindfoot, one of them with a calcified presentation. No recurrence was observed in either case after two and five years of follow-up, respectively. All cases reviewed after surgical excision showed a low recurrence rate with a favorable prognosis regardless of the histological subtype and a very rare tendency toward malignancy. Conclusions: ALMs of the foot present as well-defined, painful nodules in the subcutaneous tissue of middle-aged women. Solid histological subtypes are the most prevalent. Histopathological analysis is usually essential for confirmation. Treatment consists primarily of direct excision, with remarkably low recurrence rates. Full article

Recent preclinical and clinical studies have confirmed the essential role of interferons in the host’s immune response against malignant cells. Merkel cell carcinoma (MCC) is a rare, aggressive skin cancer strongly associated with Merkel cell polyomavirus (MCPyV). Despite progress in understanding MCC pathogenesis, the role of innate immune signaling, particularly interferon-γ (IFN γ) and its downstream pathways, remains underexplored. This review summarizes recent findings on IFN-γ in MCC, highlighting its dual role in promoting both antitumor immunity and immune evasion. IFN-γ enhances cytotoxic T cell responses, upregulates MHC class I/II expression, and induces tumor cell apoptosis. Transcriptomic studies have shown that IFN-γ treatment upregulates immune-regulatory genes including PD-L1, HLA-A/B/C, and IDO1 by over threefold; it also activates APOBEC3B and 3G, contributing to antiviral defense and tumor editing. Clinically, immune checkpoint inhibitors (ICIs) such as pembrolizumab and avelumab yield objective response rates of 30–56% and two-year overall survival rates exceeding 60% in advanced MCC. However, approximately 50% of patients do not respond, in part due to IFN-γ signaling deficiencies. This review further discusses IFN-γ’s crosstalk with the STAT1/3/5 pathways and emerging combination strategies aimed at restoring immune sensitivity. Understanding these mechanisms may inform personalized immunotherapeutic approaches and guide the development of IFN-γ–based interventions in MCC. Full article

In this review, we explore the complexities of objectively assessing the response to immunotherapy in mycosis fungoides (MF), a prevalent form of cutaneous T-cell lymphoma. The core challenge lies in distinguishing between reactive and malignant lymphocytes amidst treatment, particularly given the absence of uniform pathological biomarkers for MF. We highlight the vital role of emerging histological technologies, such as multispectral imaging and spatial transcriptomics, in offering a more profound insight into the tumor microenvironment (TME) and its dynamic response to immunomodulatory therapies. Drawing on parallels with melanoma—another immunogenic skin cancer—our review suggests that methodologies and insights from melanoma could be instrumental in refining the approach to MF. We specifically focus on the prognostic implications of various TME cell types, including CD8+ tumor-infiltrating lymphocytes, natural killer (NK) cells, and histiocytes, in predicting therapy responses. The review culminates in a discussion about adapting and evolving treatment response quantification strategies from melanoma research to the distinct context of MF, advocating for the implementation of novel techniques like high-throughput T-cell receptor gene rearrangement analysis. This exploration underscores the urgent need for continued innovation and standardization in evaluating responses to immunotherapies in MF, a field rapidly evolving with new therapeutic strategies. Full article

Malignant cutaneous melanoma is among the most aggressive forms of skin cancer, characterized by high metastatic potential and frequent resistance to standard therapies. Hydroxytyrosol, a phenolic compound derived from extra virgin olive oil, has shown promising anticancer properties in various models, yet its effects in 3D melanoma systems remain poorly understood. In this study, we used paired 3D spheroid models of non-tumorigenic (HEMa) and melanoma (C32) to assess the therapeutic potential of hydroxytyrosol. To evaluate the anti-tumoral effect of hydroxytyrosol, we performed cytotoxicity, metastasis, invasiveness, cell cycle arrest, apoptotic, and proteomic assays. Hydroxytyrosol treatment significantly impaired spheroid growth, reduced cell viability, and induced cell cycle arrest and apoptosis in C32 spheroids, with minimal cytotoxicity observed in HEMa models. Proteomic profiling further demonstrated that hydroxytyrosol selectively downregulated a network of oncogenic proteins, including ERBB2, ERBB3, ERBB4, VEGFR-2, and WIF-1, along with suppression of downstream PI3K-Akt and MAPK/ERK signaling pathways. In conclusion, compared to dabrafenib, hydroxytyrosol exerted a broader range of molecular effects and was more selective toward tumor cells. These findings support the use of hydroxytyrosol as a multi-targeted agent capable of attenuating melanoma progression through suppression of kinase signaling and tumor-stromal interactions. Full article

Intravascular lymphoma (IVL) is a rare, aggressive subtype of non-Hodgkin lymphoma (NHL) characterized by the selective proliferation of neoplastic lymphoid cells within small and medium-sized blood vessels, most frequently of B-cell origin (IVLBCL). Its protean clinical presentation, lack of pathognomonic findings, and absence of tumor masses or lymphadenopathies often lead to diagnostic delays and poor outcomes. IVLBCL can manifest in classic, hemophagocytic syndrome-associated (HPS), or cutaneous variants, with extremely variable organ involvement including the central nervous system (CNS), skin, lungs, and endocrine system. Diagnosis requires histopathologic identification of neoplastic intravascular lymphoid cells via targeted or random tissue biopsies. Tumor cells are highly atypical and display a non-GCB B-cell phenotype, often expressing CD20, MUM1, BCL2, and MYC; molecularly, they frequently harbor mutations in MYD88 and CD79B, defining a molecular profile shared with ABC-type DLBCL of immune-privileged sites. Therapeutic approaches are based on rituximab-containing chemotherapy regimens (R-CHOP), often supplemented with CNS-directed therapy due to the disease’s marked neurotropism. Emerging strategies include autologous stem cell transplantation (ASCT) and novel immunotherapeutic approaches, potentially exploiting the frequent expression of PD-L1 by tumor cells. A distinct but related entity, intravascular NK/T-cell lymphoma (IVNKTCL), is an exceedingly rare EBV-associated lymphoma, showing unique own histologic, immunophenotypic, and molecular features and an even poorer outcome. This review provides a comprehensive overview of the current understandings about clinicopathological, molecular, and therapeutic landscape of IVL, emphasizing the need for increased clinical awareness, standardized diagnostic protocols, and individualized treatment strategies for this aggressive yet intriguing malignancy. Full article

Brain metastases (BM), which most commonly originate from lung, breast, or skin cancers, remain a major clinical challenge, with standard treatments such as stereotactic radiosurgery (SRS), surgical resection, and whole-brain radiation therapy (WBRT). The prognosis for patients with BM remains poor, with a median overall survival (OS) of just 10–16 months. Although recent advances in systemic therapies, including small molecule inhibitors, monoclonal antibodies, chemotherapeutics, and gene therapies, have demonstrated success in other malignancies, their effectiveness in central nervous system (CNS) cancers is significantly limited by poor blood–brain barrier (BBB) permeability and subtherapeutic drug concentrations in the brain. Nanoparticle-based drug delivery systems have emerged as a promising strategy to overcome these limitations by enhancing CNS drug penetration and selectively targeting metastatic brain tumor cells while minimizing off-target effects. This review summarizes recent preclinical and clinical developments in nanoparticle-based therapies for BM. It is evident from these studies that NPs can carry with them a range of therapeutics, including chemotherapy, immunotherapy, small molecule inhibitors, gene therapies, radiosensitizers, and modulators of tumor microenvironment to the BM. Moreover, preclinical studies have shown encouraging efficacy in murine models, highlighting the potential of these platforms to improve therapeutic outcomes. However, clinical translation remains limited, with few ongoing trials. To close this translational gap, future work must address clinical challenges such as trial design, regulatory hurdles, and variability in BBB permeability while developing personalized nanoparticle-based therapies tailored to individual tumor characteristics. Full article

Rafoxanide, originally developed as a veterinary anthelmintic for the treatment of parasitic infections in livestock, has recently emerged as a promising therapeutic prospect in oncology. This compound has demonstrated notable antineoplastic effects against a variety of cancers, including skin, gastric, colorectal, and lung cancers, as well as hematological malignancies such as multiple myeloma. Rafoxanide exerts its anticancer activity through multiple complementary mechanisms, including the induction of endoplasmic reticulum stress, cell cycle arrest, apoptosis, and immunogenic cell death. Furthermore, the drug has been reported to inhibit key oncogenic signaling pathways (e.g., STAT3, NF-κB, c-FLIP, survivin) that contribute to tumor growth and metastasis. Preclinical studies in murine models have demonstrated significant reductions in tumor volume of up to 50% and a tumor-free rate exceeding 80%, with effective doses ranging from 7.5 to 40 mg/kg. This multitargeted mode of action distinguishes rafoxanide from conventional therapies and may help overcome resistance mechanisms that often limit the efficacy of cancer treatments. In this review, we summarize and discuss the growing body of evidence supporting rafoxanide’s therapeutic potential in oncology, as well as its possible applications in cancer treatment. Full article

Cutaneous neoplasia is among the most common illnesses in dogs and can pose significant risks. Accurate morphological diagnosis of these conditions is vital for effective treatment and management. In this retrospective study, a total of 3746 canine skin biopsies were submitted to a veterinary reference diagnostic laboratory and evaluated using histopathology. The variables assessed included age, sex, breed, lesion, location, and histopathological diagnosis. Non-neoplastic lesions accounted for 61% of all analyzed samples, while neoplastic tumors accounted for 39%. When looking at age, dogs ranging 3–6 years and 7–9 years had at least six times higher risk of developing malignant neoplasia compared to those aged 0–2 years. Among the malignant neoplasms, mast cell tumors, hemangiosarcoma, and squamous cell carcinoma were the most observed, representing 30%, 18%, and 12% of cases, respectively. The breeds most frequently affected by malignant neoplasms included Pit Bull Terriers, Boxers, and mixed breeds, all of which comprised the majority of mast cell tumor cases at 50.54%. These findings are novel in this field and may assist small animal veterinarians in making preliminary diagnoses, while also helping pet owners understand the importance of skin cancer and its early detection. Full article

Background: Uveal melanoma (UM) is a relatively rare malignancy, yet it remains the most common primary intraocular cancer in adults. Several risk factors have been identified, including light iris color, fair skin tone, and cutaneous freckles. Methods: The aim of this article was an overview of the treatment methods for uveal melanoma, with a particular focus on emerging therapies such as tebentafusp and da-rovasertib. The research method was a review of the latest literature. Results: Genetic studies have uncovered key mutations in GNAQ and GNA11, which significantly contribute to UM pathogenesis. Treatment selection depends on tumor location and disease stage. In localized disease, radiotherapy—especially brachytherapy—is commonly used and generally effective. However, the prognosis worsens significantly once distant metastases, most often to the liver, develop, as no standard systemic therapy has demonstrated high efficacy in this setting. Recent years have seen the emergence of promising therapies, including tebentafusp, which stimulates immune responses against gp100-expressing melanoma cells, and darovasertib, a potent PKC inhibitor that targets MAPK pathway activation driven by GNAQ/GNA11 mutations. Both agents have shown encouraging tolerability; tebentafusp has demonstrated clinical benefit in Phase II and III trials, while darovasertib is still under investigation. Additionally, melphalan-based liver-directed therapy, particularly via hepatic arterial infusion (approved by the FDA), has shown potential in controlling liver-dominant disease in metastatic UM. This localized approach may provide significant benefit for patients with limited extrahepatic spread. Conclusions: Future research should focus on optimizing these novel strategies—tebentafusp, darovasertib, melphalan, and combination therapies—and on expanding our understanding of UM’s molecular drivers to enable the development of more effective, personalized treatments. Full article

Background: Clinical data indicate that at least half of patients with malignancies receive radiotherapy. While radiotherapy effectively kills tumor cells, it is also associated with significant ionizing radiation (IR) damage. Moreover, the increasing emissions of nuclear pollutants raise concerns about the potential exposure of more individuals to the risks associated with IR. The Chinese term for amniotic fluid (AF) is rooted in the Yin–Yang theory of traditional Chinese medicine, where it symbolizes the inception of human life. Chick early AF (ceAF), a natural product, has shown promise in the field of regenerative medicine. There have been no studies investigating the potential efficacy of ceAF in the treatment of IR-induced damage. This study aims to assess the therapeutic potential of ceAF in alleviating IR-induced damage and elucidate its potential molecular mechanism. Methods: In vivo experiments were conducted on 8-week-old male C57BL/6J mice to investigate the effects of ceAF in a radiation injury model induced by whole-body irradiation with X-rays (6 Gy) for 5 min. The ceAF was extracted from chicken embryos aged 7–9 days. Results: We found that the supplementation of ceAF reduces mortality induced by IR, improves exercise capacity in IR mice, and reverses IR-induced skin damage. IR leads to varying degrees of volume atrophy and weight loss in the major internal organs of mice. However, ceAF intervention effectively mitigates IR-induced organ damage, with a notable impact on the spleen. The supplementation of ceAF enhances spleen hematopoietic and immune functions by reducing oxidative stress, alleviating inflammatory responses, and preventing splenic DNA damage from IR exposure, ultimately leading to an overall improvement in health. Conclusions: ceAF effectively alleviates body damage induced by IR, and our findings provide new perspectives and therapeutic strategies for mitigating IR-induced damage. Full article

Skin cancer prevalence has increased during the last decades, with the last years serving as a pivotal moment for comprehending its epidemiological patterns and its impact on public health. Melanoma is one of the most frequently occurring malignancies, arising from a complex interplay of genetic factors, environmental factors, lifestyle and socio-economic conditions. Epigenetic changes play a critical role in tumor development, influencing progression and aggressiveness. Epigenetic therapies could represent novel therapeutic options, while drug repositioning may serve as a viable strategy for cancer treatment. Demethylating agents, commonly used in hematological malignancies, show promising results on solid tumors, including melanoma. Methylation patterns are responsible for tumor development by modulating gene expression, while histone acetylation influences DNA processes such as transcription, replication, repair, and recombination. This review aims to identify existing potential therapeutical approaches using therapeutic agents that can modulate DNA methylation and histone modification, which can lead to tumor inhibition, cell death initiation and reactivation of tumor suppressor genes. Full article

Background/Objectives: Systemic sclerosis (SSc) is associated with high malignancy risk. With improving SSc management, tumor risk could change, therefore re-evaluating the possibility of neoplasms is necessary. Our aim was to observe malignancy prevalence and its risk factors in the Hungarian SSc population, comparing them to our previous and international results. Methods: We retrospectively collected the data of SSc patients followed by and admitted to three Hungarian clinical centers between 2018 and 2024. The collected data included the characteristics of SSc and neoplasms, autoantibody positivities, immunosuppressive treatments, pregnancy and environmental factors. Results: Out of 541 patients, 85 had malignancy and, in total, 96 tumors were registered. Skin cancer was the most common (n = 24), followed by breast (n = 14) and lung cancer (n = 14). Among skin cancers, almost one-third was melanoma. Tumors mostly appeared in two peaks: around the time of SSc diagnosis and 10 years later. The occurrence of anti-RNA Polymerase III (anti-RNAPIII) was significantly higher in cancerous patients. Tumor risk was higher with anti-RNAPIII (Odds Ratio (OR) 4.33, 95% Confidence Interval (95% CI) 1.08, 15.1) and anti-topoisomerase I (ATA) (OR 2.34, 95% CI 0.94, 5.84) positivity. Women and patients with diffuse cutaneous SSc (dcSSc) were more likely to have malignancy. Smoking (OR 1.27, 95% CI 0.53, 3.00) also raised the possibility of carcinogenesis. Cancerous patients were older (p-value = 0.003), and their mortality was worse compared to non-cancerous patients (Hazard Ratio (HR) 4.75, 95% CI 2.12, 10.62). Pregnancy did not provide a protective effect against breast cancer. Conclusions: Malignancy significantly contributes to the increased mortality in SSc. Female gender, dcSSc, anti-RNAPIII positivity, smoking and older age represent a higher risk of tumors. Dermatological cancer screening is necessary for all patients with SSc. Full article

Neoplastic disorders, particularly malignant carcinomas, are complex systemic diseases characterized by unregulated cellular proliferation, the invasion of adjacent tissues, and potential metastasis to distant bodily sites. Among the diverse spectrum of cancer subtypes, malignant melanoma is a highly aggressive form of cutaneous cancer originating in melanocytes, the pigment-producing cells resident in the skin. This malignancy is distinguished by its rapid and uncontrolled growth, as well as its propensity for metastasis to vital organs, thereby posing significant challenges to therapeutic intervention and prognostication. Early detection of melanoma is crucial for optimizing patient outcomes, as diagnosis at an advanced stage often yields a poor prognosis and limited treatment options. Diagnostic modalities for melanoma encompass comprehensive clinical evaluations by dermatologists; radiological imaging techniques such as ultrasonography, magnetic resonance imaging (MRI), computed tomography (CT) scans; and excisional biopsies for accurate histopathological assessment. Malignant melanoma is typically treated with surgery to remove the tumor, followed by immunotherapy to enhance the immune response, targeted therapy for tumors with specific genetic mutations, chemotherapy for advanced stages, radiation therapy to manage metastasis, and other adjunct therapies. This review presents the properties and possible adjunct therapeutic effects against malignant melanoma of quercetin found in the literature and explores, based on the observed physicochemical properties and biological activity, its potential development as a topical formulation for cutaneous application. Quercetin is a naturally occurring flavonoid compound abundant in various plant-based food sources, including apples, onions, berries, and citrus fruits, and has exhibited promising antiproliferative, antioxidant, and anticancer properties. Its distinctive biochemical structure enables quercetin to effectively neutralize reactive oxygen species and modulate key carcinogenic pathways, thereby rendering it a potential candidate for therapeutic intervention in managing malignant tumors, including melanoma. Full article

Basal cell carcinoma (BCC) is the most prevalent form of skin cancer, with infiltrative subtypes presenting significant clinical challenges due to their aggressive behavior and potential for deep tissue and bone invasion. This study aimed to evaluate factors associated with bone infiltration and surgical bone removal in patients with infiltrative BCC. A prospective cohort of 100 patients with histologically confirmed infiltrative BCC was analyzed retrospectively. Clinical, histopathological, and imaging data were assessed to identify predictors of tumor behavior. Tumor size, histological subtype, and disease duration emerged as significant factors associated with bone invasion and resection. Logistic regression analysis identified tumor length as the most significant predictor of both bone infiltration (OR = 1.102, p < 0.001) and surgical bone removal (OR = 1.105, p < 0.001). Aggressive subtypes, such as infiltrative and morpheaform BCC, were more likely to invade bone and exhibited higher recurrence rates. While these findings highlight the importance of early detection and individualized treatment strategies, the absence of data on sun exposure and urban-rural residency limits the broader applicability of the results. Future research addressing these variables will provide a more comprehensive understanding of BCC aggressiveness and improve clinical management of this malignancy. Full article

Ultrasound imaging has become an indispensable diagnostic tool across various medical fields. In recent years, there has been growing interest in the use of ultrasonography for the evaluation of skin lesions. However, scientific reports detailing the precise role of ultrasound in determining the morphology of malignant skin tumors still remain limited. Malignant skin lesions, particularly in the head and neck region—their most common location—pose significant challenges due to the complex anatomy of these areas. The primary treatment for non-melanoma skin cancers, including basal cell carcinoma (BCC) and squamous cell carcinoma (SCC), is surgical excision. Mohs micrographic surgery is considered the gold standard due to its tissue-sparing approach and high cure rates. However, it is a time-consuming and resource-intensive procedure that is not always widely accessible. In contrast, standard surgical excision, while more widely available, often results in incomplete tumor removal, necessitating subsequent surgical radicalization or the use of adjuvant therapies. Routine ultrasound evaluation of both benign and malignant skin lesions could enhance early detection and facilitate timely treatment. However, the current body of evidence for the usage of skin ultrasound in presurgical evaluation is poor and lacks standardization. Given these challenges, in this review, we aim to highlight the potential value of preoperative skin ultrasonography in accurately assessing benign and malignant skin lesion dimensions and morphology. Full article