Search Results (255)

Background/Objectives: Skin adnexal tumors (SATs) are rare neoplasms originating from sebaceous glands, hair follicles, and sweat glands, often presenting diagnostic challenges due to their histopathological diversity and clinical resemblance to other lesions. This epidemiological and clinicopathological study aimed to evaluate SATs diagnosed between January 2018 and October 2024 across two medical centers in Turkey. Methods: A total of 652 cases were analyzed based on demographic features, tumor size, anatomical localization, and histological subtypes per the 2018 WHO classification. The study also explored the predictors of malignancy, including tumor size and multifocality. Results: Among the cases, 98% were benign and 2% malignant. Sebaceous tumors were the most common (34.5%), followed by eccrine/apocrine (34.2%) and follicular tumors (31.3%). Benign tumors showed a slight female predominance (56.6%), while malignant tumors were more frequent in males (61.5%). The majority of tumors were located in the head and neck region (84.6%), and a tumor size >20 mm was significantly associated with malignancy. Conclusions: This study, one of the largest series from Turkey, highlights the importance of clinicopathological correlation in SATs. It contributes to the literature by identifying size-based cut-off values for malignancy prediction and by assessing interobserver agreement, multifocality, and tumor subtype distribution. Full article

Skin cancers are associated with a significant psychological burden across all age groups, particularly as their global incidence continues to rise. Ultraviolet (UV) radiation—primarily UVA and UVB—remains the leading etiological factor, inducing DNA mutations in key genes such as TP53 and BRAF. Among skin cancers, basal cell carcinoma (BCC) is the most prevalent and typically indolent. In contrast, squamous cell carcinoma (SCC) tends to be more invasive, while melanoma is the most aggressive and prone to metastasis. Melanoma is especially concerning due to its rapid dissemination and its occurrence not only on the skin but also in ocular, mucosal, and nail tissues. These challenges, along with rising treatment resistance and mortality, underscore the urgent need for novel anticancer agents. Berberine—a plant-derived isoquinoline alkaloid—has attracted increasing attention for its broad-spectrum anticancer potential, including against skin cancers. In this review, we summarize current evidence regarding berberine’s mechanisms of action in melanoma and SCC, emphasizing both its preventive and therapeutic effects. We further explore its potential as an adjuvant agent in combination with conventional treatments, offering a promising avenue for enhancing the clinical outcomes of skin cancer therapy. Full article

Systemic mastocytosis (SM) is a rare and heterogeneous disorder characterized by clonal proliferation and accumulation of neoplastic mast cells in one or more organs, most commonly the bone marrow, liver, spleen, and skin. Among its clinical variants, aggressive SM (ASM) presents organ damage and debilitating symptoms due to extensive mast cell infiltration. The management of ASM remains challenging, primarily because treatment must address both symptom control and disease progression. Background/Objectives: Recent therapeutic approaches have focused on tyrosine kinase inhibitors (TKIs) that target the oncogenic KIT driver mutation, predominantly the D816V mutation, which is implicated in mast cell proliferation. We report a case series of four patients diagnosed with ASM to highlight the real-world experience in the management of ASM. All patients had confirmed KIT D816V mutations and presented with signs of advanced organ dysfunction, such as marked hepatosplenomegaly, cytopenia, and significant bone marrow infiltration. First-line therapies, including cytoreductive agents or other TKIs were used. Responses varied in these patients, and ultimately, they were initiated on or transitioned to midostaurin, a multikinase TKI. Results: All four patients, after the initiation of midostaurin, presented clinical and biological improvement—at least a clinical improvement response according to the International Working Group-Myeloproliferative Neoplasms Research and Treatment & European Competence Network on Mastocytosis (IWG-MRT-ECNM) criteria. These findings highlight the benefits of KIT inhibition in managing ASM, especially for patients with inadequate responses to traditional therapies. The impact of midostaurin on organ function, mast cell burden, and symptom control emphasizes the importance of the timely integration of TKIs into therapeutic protocols. However, optimal treatment duration, long-term safety, and the development of acquired resistance remain critical questions that warrant further studies. Larger prospective trials are needed to better delineate the prognostic factors associated with sustained response, refine patient selection, and explore combination strategies that may enhance therapeutic efficacy. Conclusions: The patients presented in this case series benefited from midostaurin therapy, showing either a clinical improvement or partial response according to the IWG-MRT-ECNM criteria. Our case series illustrates that KIT inhibitors can offer meaningful clinical benefit in ASM, reinforcing their position as an emerging cornerstone option in ASM management. 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

Cutaneous manifestations can serve as early and sometimes the first clinical indicators in various hereditary cancer predisposition syndromes. This review provides a comprehensive overview of the dermatological signs associated with these syndromes, aiming to facilitate their recognition in clinical practice. Hereditary Breast and Ovarian Cancer syndrome is notably linked to an increased risk of melanoma. BAP1 tumor predisposition syndrome is characterized by BAP1-inactivated melanocytic tumors. Muir–Torre syndrome, a variant of Lynch syndrome, presents with distinctive cutaneous neoplasms such as sebaceous carcinomas, sebaceous adenomas, and keratoacanthomas. PTEN hamartoma tumor syndrome commonly features hamartomatous growths, trichilemmomas, acral keratoses, oral papillomas, and genital lentiginosis. Gorlin syndrome is marked by basal cell carcinomas and palmoplantar pits, while Peutz–Jeghers syndrome is identified by mucocutaneous pigmentation. In familial adenomatous polyposis, the cutaneous findings include epidermoid cysts, fibromas, desmoid tumors, and lipomas. Additionally, we examined monogenic disorders associated with cancer risk and skin involvement, such as xeroderma pigmentosum, neurofibromatosis type 1, familial atypical multiple-mole melanoma syndrome, and Fanconi anemia. The early recognition of these dermatologic features is essential for a timely diagnosis and the implementation of appropriate surveillance strategies in individuals with hereditary cancer syndromes. Full article

Background: The opportunistic pathogen Staphylococcus aureus causes skin and soft tissue infections that are associated with biofilm formation, and in immunocompromised patients can progress to surgical site infections, pneumonia, bacteremia, sepsis, and even death. Most antibiotics actively damage living, dividing cells on the surface of the biofilm, where there is a high concentration of nutrients and oxygen, while in the depths, where these factors are scarce, slowly growing cells remain. Objectives: The aim of our study was to evaluate the antibiofilm potential of ethyl acetate roots (EtOAcR) and aerial parts (EtOAcAP) extracts from the perennial Bulgarian plant Geum urbanum L. against methicillin-resistant S. aureus (MRSA) NBIMCC 8327. Methods: The effects of both extracts on the expression of biofilm-related genes, icaA and icaD, were investigated. The cytotoxicity of EtOAcR and EtOAcAP on A-375 (human melanoma), A-431 (epidermoid skin cancer) and HaCaT (normal keratinocytes) cell lines, and the induction of apoptosis were determined. Finally, the in vivo skin irritation potential of the most active extract was studied. Results: Both tested extracts inhibited biofilm formation at concentrations that did not affect bacterial growth. Interestingly, the expression of icaA and icaD was upregulated, although the biofilm development was inhibited 72.4–90.5% by EtOAcAP and 18.9–20.4% by EtOAcR at sub-MICs. EtOAcAP extract showed a more favorable cytotoxic profile on non-tumorigenic cells and stronger antineoplastic activity (IC₅₀ = 6.7–14.68 µg/mL) as compared to EtOAcR extract (IC₅₀ = 8.73–23.67 µg/mL). Therefore, a skin irritation test was performed with the EtOAcAP extract at ten-times higher concentrations than the minimum inhibitory one, and, resultantly, the primary irritation index was equal to zero (no skin irritation observed). Conclusions: The EtOAcAP extract was proven to be an effective antistaphylococcal agent with favorable skin tolerance. The extract showed strong antineoplastic activity and antibiofilm effect at sub-MICs, which outlines new prospects for its development as a natural product for specific skin applications in medical practice. Full article

Myeloid/lymphoid neoplasms with tyrosine kinase gene fusions (MLN-TK) represent a distinct group of hematologic malignancies recognized in the latest WHO classification due to shared clinical, morphological, and molecular features, and their responsiveness to tyrosine kinase inhibitors (TKIs). Among these, fusions involving the SYK gene, such as ETV6::SYK and ITK::SYK, have emerged as rare but potentially targetable genetic events in both myeloid and lymphoid neoplasms. SYK, a non-receptor tyrosine kinase critical for hematopoietic signalling, can become constitutively activated through gene fusions, driving oncogenesis via the PI3K/AKT, MAPK, and JAK-STAT pathways. ETV6::SYK has been primarily associated with myeloid neoplasms, often presenting with eosinophilia, bone marrow dysplasia, and skin involvement. In vitro and in vivo models confirm its leukemogenic potential and identify SYK as a therapeutic target. Although SYK inhibitors like fostamatinib have shown transient efficacy, resistance mechanisms, possibly involving alternative pathway activation, remain a challenge. The ITK::SYK fusion, on the other hand, has been identified in peripheral T-cell lymphomas, particularly of the follicular helper T-cell subtype, with similar pathway activation and potential for targeted intervention. Additional rare SYK fusions, such as PML::SYK and CTLC::SYK, have been reported in myeloid neoplasms and juvenile xanthogranuloma, respectively, expanding the spectrum of SYK-driven diseases. Accumulating evidence supports the inclusion of SYK fusions in future classification systems and highlights the need for broader molecular screening and clinical evaluation of SYK-targeted therapies. Full article

Background/Objectives: A history of cancer has been linked to stress and concerns about its recurrence. We aimed to test the benefits of an evidence-based self-help stress reduction method, the Clinical Emotional Freedom Technique (EFT), in survivors of cutaneous melanoma, and to contrast its effects on wellbeing and perceptions of cancer recurrence when delivered in a group versus individual instruction setting. Methods: This study was preregistered at clinicaltrials.gov (NCT05421988, 3 April 2022). Fifty-three patients aged 18 and above, diagnosed with melanoma (stage T1a–T2a) at least 6 months prior, and not in active treatment were recruited from a private skin cancer clinic. After consent, all participants were randomized in one step into three condition groups: Group EFT (G-EFT; n = 16), Individual EFT (I-EFT; n = 18), and a waiting-list control condition (CC; n = 19). G-EFT and I-EFT participants attended weekly treatment sessions for four weeks. Perceptions of cancer recurrence and wellbeing measures were obtained pre- and post-intervention and at three-months follow-up using online questionnaires. Subjective units of distress (SUDs) were recorded by the EFT instructor at the beginning and end of each session. Results: Two-way repeated measures ANOVAs revealed significant improvements from pre- to post-intervention in both EFT conditions in terms of participants’ understanding of how to prevent recurrence and in their spiritual wellbeing. No statistically significant effects were found for fear of recurrence, recurrence perceptions, and affect. Significant decreases in SUD scores were observed in both EFT conditions. Over 80% of the experimental conditions’ participants reported positive changes and satisfaction. Conclusions: The findings provide support for offering EFT instruction as a non-pharmacological and noninvasive self-help method to ameliorate the stress of cancer diagnosis and treatment, and for its similar effectiveness in either a group or individual format. Full article

Background/Objectives: Cowden syndrome (or PTEN hamartoma tumor syndrome) (CS/PHTS) belongs to a group of inherited disorders associated with the development of multiple hamartomas. The clinical presentation of patients may include dysmorphic facial features, macrocephaly, developmental delay, and multiple benign and malignant tumors of various localizations. At the same time, only thyroid cancer is thought to have an increased risk in childhood. Skin lesions in CS/PHTS occur in 90–100% of patients and include multiple tricholemmoma, papilloma, acral keratosis, pigmentation changes, as well as rarer forms like vascular malformations, fibromas, neuromas, melanoma, and basal cell carcinoma. Methods: Next-generation sequencing and Sanger sequencing were used to search for PTEN genetic variants. A histological and immunohistochemical examination of tumor biopsies and skin lesions was performed. Results: A total of 13 patients from six families with CS/PHTS, including 10 children, were described. Seven pediatric patients belonged to families with paternal transmission of the PTEN pathogenic variants, while three others were de novo cases. Atypical manifestations in CS/PHTS were diffuse large B-cell lymphoma in one adult, a renal cell carcinoma, three germ cell tumors, and a linear epidermal nevus in pediatric patients. A literature review of the identified pathogenic variants in the PTEN gene was performed, assessing their clinical significance and analyzing the traditional and modified diagnostic criteria as applied to the pediatric population. Conclusions: Taking into account the low incidence of CS/PHTS, the data presented significantly expand our current understanding of this disease and guide physicians to consider a wider range of possible malignant neoplasms in pediatric patients with CS/PHTS. Full article

Despite significant progress in its prevention, diagnosis, and treatment, head and neck cancer (HNC) remains a major global health issue due to its multifactorial pathogenesis. Indeed, HNCs have been found to be associated with different environmental and lifestyle factors, as well as with infection with oncogenic viruses. To date, seven viruses are recognized for their tumorigenic properties and have been proposed as implicated in HNC development, including Merkel Cell Polyomavirus (MCPyV). MCPyV is well recognized as the major etiological agent of Merkel cell carcinoma (MCC), a rare but rapidly metastasizing skin neoplasm. Specifically, in almost 80% of MCC cases, viral genome integration occurs, and a truncated form of Large T Antigen (tLT) is expressed. Although MCC is a rare cancer, MCPyV is a ubiquitous virus, widely distributed among the human population. Therefore, a plausible role of the virus has been proposed, even for other tumors. The current review provides an overview of the available data describing the presence of MCPyV in non-MCC tumors, such as HNCs, with the aim of elucidating the potential contribution of MCPyV to oral cancer. Understanding the role of viral infections in the etiology of cancer opens up the opportunity for developing preventive measures and targeted therapies that effectively address HNC progression while reducing treatment-related side effects. Full article

A causal analysis was conducted in order to examine the relationship between residents’ inhalation exposure to PCDDs/PCBs and the incidence of cancer. A significant association was identified between chronic inhalation exposure to 2,3,7,8-TCDD and the overall incidence of malignant neoplasms in the study area. This association was stronger among men (p = 0.0020) than among women (p = 0.0027). A significantly higher overall incidence of malignant neoplasms was observed among the inhabitants of villages (CY, GN) exposed to higher levels of PCDD/F mixture in comparison with the reference village (p < 0.001). The present study observed the phenomenon in both male (p = 0.008) and female (p = 0.013). Moreover, a considerably elevated incidence of morbidity was observed in the male population of the CY village (p = 0.034) in comparison with the female population, where atmospheric air pollution with PCDD/Fs has been recorded at its most elevated levels. A higher frequency of cancers was also observed among the inhabitants of the villages GN and CY compared to the inhabitants of the reference village. The observed differences were consistent in cancers of the digestive system (p < 0.001), respiratory system and thoracic organs (p < 0.001), skin (p = 0.023), urinary system (p < 0.001), lymphatic and hematopoietic system (p = 0.032), as well as cancers occurring in women (p = 0.041). Full article

Cutaneous metastases from internal organ cancers are diagnosed in approximately 0.2% of skin biopsies. This diagnosis can be the first sign of a previously undiagnosed malignancy with an internal organ origin. We conducted a retrospective study that included all cases of cutaneous metastases diagnosed in our hospital. A total of 25 patients were identified (14 females and 11 males). The average age of the patients included was 62.3. The most common primary cancer site was the lung for male patients, while for female patients it was the breast. In seven of our cases, cutaneous metastases were the first sign of an internal organ cancer. Common sites for cutaneous metastases in our study involved the anterior thoracic wall, the abdomen, and the scalp. Our study aims to highlight the importance of recognizing the histopathology of metastatic tumors and differentiating them from primary skin neoplasms. Immunohistochemistry is a mandatory tool for differential diagnosis in all cases, especially for patients who do not have a history of neoplasia. Full article

Background/Objectives: Immune cells determine the role of the tumor microenvironment during tumor progression, either suppressing tumor formation or promoting tumorigenesis. This study aimed to fully characterize immune cell responses during skin tumor progression. Methods: Using single-cell RNA sequencing, we analyzed the profile of immune cells in the tumor microenvironment of control mouse skins and skin tumors at the single-cell level. Results: We identified 15 CD45⁺ immune cell clusters, which broadly represent the most functionally characterized immune cell types including macrophages, Langerhans cells (LC), conventional type 1 dendritic cells (cDC1), conventional type 2 dendritic cells (cDC2), migratory/mature dendritic cells (mDC), dendritic epidermal T cells (DETC), dermal γδ T cells (γδT), T cells, regulatory T cells (Tregs), natural killer cells (NK), type 2 innate lymphoid cells (ILC2), neutrophils (Neu), mast cells (Mast), and two proliferating populations (Prolif.1 and Prolif.2). Skin tumor progression reprogramed immune cells and led to a marked increase in the relative percentages of macrophages, cDC2, mDC, Tregs, and Neu. Macrophages, the largest cell cluster of immune cells in skin tumors. In addition, macrophages emerged as the predominant communication ‘hub’ in skin tumors, highlighting the importance of macrophages during skin tumor progression. In contrast, other immune cell clusters decreased during skin tumor progression, including DETC, γδT, ILC2, and LC. In addition, skin tumor progression dramatically upregulated Jak2/Stat3 expression and the interferon response across various immune cell clusters. Further, skin tumor progression activated T cells and NK cells indicated by elevated expression of IFN-γ and Granzyme B in skin tumors. Meanwhile, a pronounced infiltration of M2-macrophages and Tregs in skin tumors created an immunosuppressive microenvironment, consistent with the elevated expression of the Stat3 pathway in skin tumors. Conclusions: Our study elucidates the immune cell landscape of epidermal neoplasms, offering a comprehensive understanding of the immune response during skin tumor progression and providing new insights into cancer immune evasion mechanisms. 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

Background: Squamoid eccrine ductal carcinoma (SEDC) is an exceedingly rare and aggressive cutaneous adnexal malignancy, with fewer than 100 reported cases. Its histopathologic overlap with squamous cell carcinoma (SCC) frequently leads to misdiagnosis, delaying appropriate management. Unlike SCC, SEDC exhibits biphasic differentiation, deep infiltration, and a high rate of perineural invasion, contributing to significant morbidity and poor long-term outcomes. Given the absence of standardized treatment protocols, managing SEDC remains a challenge. Case Presentation: We report an unusual case of an 80-year-old female presenting with progressive numbness, nasal deviation, and a subcutaneous indurated lesion in the left nasofacial region. The early neurological symptoms were an atypical feature, suggesting perineural invasion (PNI) before visible tumor progression. Initial histopathologic evaluation was inconclusive, raising suspicion of SCC, necessitating immunohistochemical analysis, which confirmed ductal differentiation, leading to the final diagnosis of SEDC. The patient underwent radical resection with intraoperative margin assessment (Mohs micrographic surgery; MMS) followed by adjuvant radiotherapy (62 Gy/31 fractions) due to high-risk features, including perineural and perivascular invasion. Despite initial disease control, a local recurrence involving the left orbit and nasal bone occurred 20 months postoperatively, demonstrating the aggressive nature of SEDC despite clear surgical margins and adjuvant therapy. Due to disease progression and refusal of further surgery, only palliative care was provided. During follow-up, the patient contracted COVID-19, further complicating her clinical status and contributing to her demise. While COVID-19 was not directly linked to SEDC progression, its impact on patient management was significant. Conclusions: This case underscores the diagnostic and therapeutic challenges of SEDC, emphasizing the need for early suspicion, extensive histopathologic assessment, and aggressive multimodal treatment. The importance of multidisciplinary management—particularly in elderly and immunocompromised patients—and long-term surveillance due to high recurrence risk and PNI is crucial. Full article