Search Results (29)

Background and Objectives: Urothelial carcinoma of the urinary bladder is a heterogeneous disease with diverse morphological and molecular characteristics. This study aims to analyze the expression of HER2 in 100 consecutive cases of muscle-invasive bladder carcinoma (MIBC), with a special attention to the different histological subtypes and consensus molecular variants determined by IHC methods. Materials and Methods: A retrospective single-center study was conducted on 100 consecutive cases of MIBC (2021–2024). HER2 status is assessed by immunohistochemistry (IHC) (scores 0, 0+, 1+, 2+, 3+), and the results are compared with the published data. Results: We have established that over half of the tumors (~60%) show some level of HER2 expression, with strong expression (3+) present in 25%. There are significant differences among the IHC-based molecular variants: luminal tumors, including papillary tumors, exhibit a frequent HER2 overexpression, whereas those with a basal immunophenotype (e.g., squamous, sarcomatoid variants) are almost entirely HER2-negative. The micropapillary subtype and some other rare subtypes can also express HER2. Conclusions: HER2 is an important biomarker with heterogeneous expression in urothelial carcinoma of the bladder. The present study showed that the frequency and level of HER2 expression vary substantially among different histopathological subtypes and molecular variants. In therapeutic terms, interest in HER2 as a target is growing—new antibody–drug conjugates show a promising activity even in cases with low HER2 expression, which will likely lead to the integration of HER2-directed therapies and routine testing in the future. Full article

Background/Objectives: This study aimed to profile the molecular variants of muscle-invasive bladder cancer (MIBC) based on immunohistochemical analysis and to make a correlation with morphological characteristics in a series of 100 consecutive patients. Methods: A retrospective single-center study was conducted on 100 consecutive cases of MIBC (2021–2024). A selected immunohistochemical (IHC) panel (including CK5/6, CK20, and p16) was applied in all cases to classify the tumors into known molecular variants (luminal papillary, luminal non-specified, luminal unstable, stroma-rich, basal/squamous, neuroendocrine-like). Results: Seven molecular subtypes are identified: basal (33%), luminal papillary (24%), luminal unstable (16%), luminal non-specified (10%), basoluminal (double-positive) (9%), neuroendocrine-like (double-negative with neuroendocrine morphology) (6%), and stroma-rich (2%). This distribution largely matches published data (Consensus Classification and The Cancer Genome Atlas (TCGA)), with minor differences (e.g., a lower share of the stroma-rich variant). A strong correlation is found between the histological subtypes of some tumors and their molecular variant (χ², p < 0.001): for example, all cases of urothelial carcinoma with squamous differentiation are basal, micropapillary tumors are entirely luminal, and small-cell carcinomas are neuroendocrine-like. Conclusions: The results demonstrate that the morphological subtype of urothelial carcinoma largely predetermines the molecular profile. Combining classic histopathology with IHC-based profiling allows for a more complete characterization of the tumor and aids prognosis and personalized treatment in MIBC. Full article

Background: Hand tumors encompass a heterogeneous spectrum of benign, malignant, and tumor-like lesions with diverse clinical behavior. While international studies have reported epidemiological and clinicopathological features, large-scale data in Italian populations are scarce. This retrospective analysis represents one of the largest Italian surgical series of histologically confirmed hand tumors. The objective was to evaluate clinicopathological characteristics, anatomical distribution, and surgical outcomes of these lesions over a 5-year period. Methods: A total of 250 patients who underwent surgery for hand tumors at the Department of Plastic and Reconstructive Surgery, University Hospital “G. Martino,” Messina, Italy, from January 2020 to December 2024, were retrospectively reviewed. Data from clinical records, imaging, and histopathology were categorized as tumor-like lesions, benign neoplasms, or malignant tumors. Demographic and clinical variables were compared across diagnostic groups. Results: The cohort included 127 males and 123 females (mean age 49.3 ± 18.6 years). Lesions were most frequently located in the digits (62%), followed by palm (21%), dorsum (11%), and wrist (6%). Tumor-like lesions represented 37.6% of cases, predominantly mucous cysts and foreign body granulomas. Benign tumors accounted for 49.2%, with giant cell tumors of the tendon sheath as the most common (31.7%). Malignant tumors were rare (10.4%), mainly squamous cell carcinoma, basal cell carcinoma, and melanoma. Patients with malignant lesions were significantly older (67.4 years) compared with those with benign or tumor-like lesions (p < 0.01). Conclusions: Benign and tumor-like lesions predominate among hand tumors, whereas malignancies are infrequent but clinically important. Surgical excision remains the treatment of choice, guided by preoperative imaging and confirmed histopathologically. Expanding this cohort and integrating molecular diagnostics with patient-reported outcomes may enhance future management strategies. Full article

Background/Objectives: Skin cancer is the most common cancer worldwide, creating a significant burden on healthcare systems. According to the World Health Organization, 1.5 million new cases are reported annually, though the actual number is likely higher due to underreporting. The main risk factor is UV radiation, with additional contributors such as smoking, older age, and outdoor work. Basal cell carcinoma (70–80%) and squamous cell carcinoma are the most prevalent non-pigmented skin cancers. This study assessed the knowledge of patients undergoing surgical treatment for facial skin cancer regarding risk factors, prevention, treatment, and health-related behaviors. The goal was to guide educational strategies aimed at reducing disease incidence and improving outcomes. Methods: A cross-sectional study of 220 patients treated at the UCK Department of Plastic Surgery (April–August 2024) was conducted. Participants completed anonymous questionnaires on demographics, medical history, beliefs about lesions, and sun-protective behaviors. Clinical data included tumor location, size, histopathology, and excision completeness. Statistical significance was set at p < 0.05. Results: Patients were on average 71 years old; 61% had a secondary education. Sun protection habits varied by education and gender. SPF use was higher among those with higher education (79.55%) and among women (55.83%). SPF users had smaller lesion diameters (p < 0.001). However, 71% delayed seeking care for over a year, often due to misperceptions. Conclusions: There is a notable lack of awareness about skin cancer, especially prevention and early detection. Education and gender influence protective behaviors. Tailored educational initiatives may help reduce incidence and promote earlier diagnosis. Full article

Skin cancer is the most common cancer worldwide. The incidence of skin cancer has been increasing worldwide. Nearly 75% of all skin cancers are basal cell carcinomas (BCC), cutaneous squamous cell carcinoma (cSCC) represents approximately 20%, and those remaining are melanomas (4%) or other rare tumors (1%). Given the high cure rates and the ability to histologically confirm tumor clearance, surgical therapy is the gold standard for the treatment of skin cancer. Conventional surgery is the most employed technique for the removal of non-melanoma skin cancer (NMSCs). Mohs Micrographic Surgery (MMS) is the most precise surgical method for the treatment of non-melanoma skin cancer, allowing for 100% margin evaluation, being the gold-standard method for surgical treatment of non-melanoma skin cancer. Whenever it is possible to obtain wide margins (4 to 6 mm), cure rates vary from 70% to 99%. Imiquimod, a synthetic imidazoquinolinone amine, is a topical immune response modifier approved by the U.S. Food and Drug Administration (FDA) for the treatment of external anogenital warts, actinic keratosis (AK), and superficial basal cell carcinoma (sBCC). The efficacy of imiquimod is primarily attributed to its ability to modulate both innate and adaptive immune responses, as well as its direct effects on cancer cells. Imiquimod exerts its immunomodulatory effects by activating Toll-like receptors 7 and 8 (TLR7/8) on various immune cells, including dendritic cells, macrophages, and natural killer (NK) cells. Upon binding to these receptors, imiquimod triggers the MyD88-dependent signaling pathway, leading to the activation of nuclear factor kappa B (NF-κB) and interferon regulatory factors (IRFs). This cascade leads to the production of pro-inflammatory cytokines, including interferon-alpha (IFN-α), tumor necrosis factor-alpha (TNF-α), interleukin-12 (IL-12), and interleukin-6 (IL-6). These cytokines enhance local inflammation, recruit additional immune cells to the tumor site, and stimulate antigen presentation, thereby promoting an anti-tumor immune response. Radiation therapy (RTh) may be employed as a primary treatment to BCC. It may also be employed as an adjuvant treatment to surgery for SCC and aggressive subtypes of BCC. RTh triggers both direct and indirect DNA damage on cancer cells and generates reactive oxygen species (ROS) within cells. ROS trigger oxidative damage to DNA, proteins, and lipids, exacerbating the cellular stress and contributing to tumor cell death. Recently, immunotherapy emerged as a revolutionary treatment for all stages of SCC. Cemiplimab is a human programmed cell death 1 (PD-1)-blocking antibody that triggers a response to over 50% of patients with locally advanced and metastatic SCC. A randomized clinical trial (RCT) published in 2022 revealed that cemiplimab was highly effective in the neoadjuvant treatment of large SCCs. The drug promoted a significant tumor size decrease, enabling organ-sparing operations and a much better cosmetic effect. A few months ago, a RCT of cemiplimab on adjuvant therapy for locally aggressive SCC was published. Interestingly, cemiplimab was administered to patients with local or regional cutaneous squamous cell carcinoma after surgical resection and postoperative radiotherapy, at high risk for recurrence owing to nodal features, revealed that cemiplimab led to much lower risks both of locoregional recurrence and distant recurrence. Full article

Background: Squamous cell carcinoma (SCC) is a heterogeneous group of epithelial malignancies with varied morphologies and clinical behaviors. While histopathology is the diagnostic gold standard, it can be limited in distinguishing SCC from morphologic mimics. Immunohistochemistry (IHC) has therefore become a critical adjunct, enhancing diagnostic accuracy and providing prognostic insights. Objective: This narrative review aims to evaluate the diagnostic, differential, and prognostic roles of commonly used IHC markers in SCC, with particular emphasis on their utility in distinguishing SCC from histologic mimickers across different anatomical sites. Methods: One hundred and five peer-reviewed articles were analyzed for their relevance to the immunohistochemical characterization of SCC. Markers were categorized based on their diagnostic function, role in differential diagnosis, and prognostic value. Results: Key markers such as p40, p63, CK5/6, and DSG3 consistently demonstrated high sensitivity and specificity for SCC, reinforcing their value in confirming squamous differentiation. Conversely, exclusion markers like Ber-EP4, CK7, TTF-1, S100, and SOX10 were essential in ruling out basal cell carcinoma, adenocarcinoma, and melanoma. Additionally, markers such as Ki-67, p16, and CD44 offered prognostic information regarding tumor aggressiveness, HPV status, and therapy response. These findings confirm the critical role of IHC not only in diagnosing SCC but also in resolving complex differential diagnoses. Conclusions: IHC markers serve as indispensable tools in the diagnostic workup of SCC, particularly in distinguishing it from other neoplasms with overlapping histologic features. The clear correlation between marker expression and diagnostic categories supports the systematic use of IHC to improve diagnostic precision and inform prognosis. Future integration with molecular diagnostics may further refine personalized treatment approaches in SCC. Full article

This study explores the advanced imaging of skin vasculature using Line-Field Confocal Optical Coherence Tomography (LC-OCT), which offers high-resolution, three-dimensional (3D) visualization of vascular structures, especially within skin tumors. The research aims to improve the understanding of tumor angiogenesis and the complex vascular morphology associated with malignancies. The methodology involves converting original image stacks into negative images, manually tracing vessels using the Simple Neurite Tracer (SNT) plugin, and creating smoothed binary masks to reconstruct 3D models. The study’s results highlight the ability to visualize serpiginous, corkscrew-like, and irregular vessels across various skin cancers, including melanoma, squamous cell carcinoma, and basal cell carcinoma. These visualizations provide insights into vessel morphology, spatial arrangements, and blood flow patterns, which are crucial for assessing tumor growth and potential therapeutic responses. The findings indicate that 3D reconstructions from LC-OCT can uncover vascular details previously undetectable by two-dimensional imaging techniques, making it a valuable tool in dermatology for both clinical diagnostics and research. This method allows for better monitoring of skin cancer treatment and understanding of the role of vascular polymorphism in tumor development. Full article

Non-melanoma skin cancers (NMSC), including basal cell carcinoma (BCC), cutaneous squamous cell carcinoma (cSCC), and Merkel cell carcinoma (MCC), are increasingly common and present significant healthcare challenges. Neutrophil extracellular traps (NETs), chromatin fibers expulsed by neutrophil granulocytes, can promote immunotherapy resistance via an impairment of CD8⁺ T cell-mediated cytotoxicity. Here, to identify a potential therapeutic target, we investigate the expulsion of NETs and their relation to CD8⁺ T cell infiltration in NMSC. Immunofluorescence staining for neutrophils (CD15) and NETs (H3cit), as well as immunohistochemistry for cytotoxic T cells (CD8⁺) on human cSCCs (n = 24), BCCs (n = 17) and MCCs (n = 12), revealed a correlation between neutrophil infiltration and ulceration diameter in BCC and MCC, but not in cSCC. In BCC and cSCC, neutrophil infiltration also correlated with the cross-sectional area (CSA). NETs were not associated with established risk factors but with the presence of an ulceration, and, in cSCC, with abscess-like structures. CD8⁺ T cell infiltration was not reduced in tumors that were NET-positive nor in those with a denser neutrophil infiltration. This study is the first to report and characterize NETs in NMSC. Thus, it gives an incentive for further research in this relevant yet understudied topic. Full article

Cancer stem cells (CSCs) represent a subpopulation of cancer cells that are believed to initiate and drive cancer progression. In animal models, xenotransplanted CSCs have demonstrated the ability to produce tumors. Since their initial isolation in blood cancers, CSCs have been identified in various solid human cancers, including oral squamous cell carcinoma (OSCC). In addition to their tumorigenic properties, dysregulated stem-cell-related signaling pathways—Wnt family member (Wnt), neurogenic locus notch homolog protein (Notch), and hedgehog—have been shown to endow CSCs with characteristics like self-renewal, phenotypic plasticity, and chemoresistance, contributing to recurrence and treatment failure. Consequently, CSCs have become targets for new therapeutic agents, with some currently in different phases of clinical trials. Notably, small molecule inhibitors of the hedgehog signaling pathway, such as vismodegib and glasdegib, have been approved for the treatment of basal cell carcinoma and acute myeloid leukemia, respectively. Other strategies for eradicating CSCs include natural compounds, nano-drug delivery systems, targeting mitochondria and the CSC microenvironment, autophagy, hyperthermia, and immunotherapy. Despite the extensive documentation of CSCs in OSCC since its first demonstration in head and neck (HN) SCC in 2007, none of these novel pharmacological approaches have yet entered clinical trials for OSCC patients. This narrative review summarizes the in vivo and in vitro evidence of CSCs and CSC-related signaling pathways in OSCC, highlighting their role in promoting chemoresistance and immunotherapy resistance. Additionally, it addresses methodological challenges and discusses future research directions to improve experimental systems and advance CSC studies. Full article

The diagnosis of basal cell carcinoma (BCC) in dark phototypes can be a challenging task due to the lack of relevant clues and its variable presentation. In this regard, there is growing evidence that dermoscopy may benefit the recognition of BCC even for skin of color (SoC). The objective of this review is to provide an up-to-date overview on clinical and dermoscopic patterns of BCC in SoC, also comparing such findings with those of the main clinical mimickers reported in the literature. A comprehensive search of the literature through the PubMed electronic database was carried out in order to identify papers describing the clinical and dermoscopic features of BCC in dark phototypes (IV–VI). By finding macroscopic clinical presentations of BCCs in SoC patients and any possible clinical mimickers considered in the retrieved papers, we built a differential diagnosis list and analyzed the dermoscopic findings of such conditions to facilitate the diagnosis of BCC. BCC in darker skin may present as pigmented nodular lesions, pigmented patches or plaques, ulcers, erythematous nodular lesions, erythematous plaques or patches, or scar-like lesions, depending on its subtype and body site. The differential diagnosis for BCC in patients with SoC includes squamous cell carcinoma, melanoma, nevi, adnexal tumors and sebaceous keratosis. Additionally, it differs from that of Caucasians, as it also includes lesions less common in fair skin, such as dermatosis papulosa nigra, melanotrichoblastoma, and pigmented dermatofibrosarcoma protuberans, and excludes conditions like actinic keratosis and keratoacanthoma, which rarely appear in darker skin. The resulting differences also include infectious diseases such as deep cutaneous mycosis and inflammatory dermatoses. The most prevalent differentiating dermoscopic feature for BCC includes blue, black and gray dots, though arborizing vessels still remain the predominant BCC feature, even in dark phototypes. Diagnostic approach to BCC in dark-skinned patients varies due to the prevalence of dermoscopy findings associated with hyperpigmented structures. Clinicians should be aware of such points of differentiation for a proper management of this tumor in SoC. Full article

A cutaneous carcinosarcoma (cCS) is a rare and aggressive skin cancer characterized by both carcinomatous (epithelial) and sarcomatous (mesenchymal) components, making it a biphasic tumor. Despite its occurrence in various organs, a cCS is exceptionally rare in the skin, predominantly affecting older males. The etiology of a cCS is unclear, but it may originate from a single progenitor cell capable of dual differentiation or from a collision of carcinoma and sarcoma cells. Clinically, a cCS presents as a rapidly growing, painful, ulcerated nodule or plaque on sun-exposed skin, with a high risk of local invasion and metastasis. Histopathologically, a cCS includes various epithelial components, such as squamous cell carcinoma and basal cell carcinoma, along with undifferentiated sarcomatous components resembling atypical fibroxanthoma. The tumor may also exhibit heterologous differentiation like angiosarcomatous or rhabdomyosarcomatous features. We present three cases of a cCS, highlighting their clinical and histological characteristics and comparing them with previously reported cases. Understanding a cCS is complicated by its rarity and diverse presentation, emphasizing the need for further research to elucidate its pathogenesis and optimal management. Full article

Bladder cancer is a heterogenous disease, and molecular subtyping is a promising method to capture this variability. Currently, the immune compartment in relation to subtypes is poorly characterized. Here, we analyzed the immune compartment in bladder tumors and normal bladder urothelium with a focus on T cell subpopulations using flow cytometry and RNA sequencing. The results were investigated in relation to tumor invasiveness (NMIBC/MIBC) and molecular subtypes according to the Lund Taxonomy system. Whereas the NMIBC/MIBC differed in the overall immune infiltration only, the molecular subtypes differed both in terms of immune infiltration and immune compartment compositions. The Basal/Squamous (Ba/Sq) and genomically unstable (GU) tumors displayed increased immune infiltration compared to urothelial-like (Uro) tumors. Additionally, the GU tumors had a higher proportion of regulatory T cells within the immune compartment compared to Uro tumors. Furthermore, sequencing showed higher levels of exhaustion in CD8⁺ T cells from GU tumors compared to both Uro tumors and the control. Although no such difference was detected at the transcriptomic level in Uro tumors compared to the controls, CD8⁺ T cells in Uro tumors showed higher expression of several exhaustion markers at the protein level. Taken together, our findings indicate that depending on the molecular subtype, different immunotherapeutic interventions might be warranted. Full article

Chemokines play a key role in cancer processes, with CXCL1 being a well-studied example. Due to the lack of a complete summary of CXCL1’s role in cancer in the literature, in this study, we examine the significance of CXCL1 in various cancers such as bladder, glioblastoma, hemangioendothelioma, leukemias, Kaposi’s sarcoma, lung, osteosarcoma, renal, and skin cancers (malignant melanoma, basal cell carcinoma, and squamous cell carcinoma), along with thyroid cancer. We focus on understanding how CXCL1 is involved in the cancer processes of these specific types of tumors. We look at how CXCL1 affects cancer cells, including their proliferation, migration, EMT, and metastasis. We also explore how CXCL1 influences other cells connected to tumors, like promoting angiogenesis, recruiting neutrophils, and affecting immune cell functions. Additionally, we discuss the clinical aspects by exploring how CXCL1 levels relate to cancer staging, lymph node metastasis, patient outcomes, chemoresistance, and radioresistance. Full article

Basal cell carcinoma is the most common malignant skin tumor of the eyelids in Caucasians, followed by squamous cell carcinoma and sebaceous gland carcinoma. The primary treatment for these tumors is radical excision. In cases where malignant eyelid tumors are advanced and have invaded the orbit, orbital exenteration is necessary. In this retrospective study, we aimed to determine the correlation between the risk of orbital infiltration and various factors like tumor location, size, histological type, and patient age. This study revealed that tumors in multiple regions increased the risk of orbital infiltration by 3.75 times. Tumors with a diameter of 21–30 mm raised the likelihood of requiring exenteration by 15.5 times compared to smaller tumors (up to 10 mm). Age was also associated with the likelihood of orbital invasion in periocular tumors. Interestingly, no correlation was found between the histological type of the tumor and the risk of orbital infiltration. Notably, the conjunctiva of the eyeball was the most commonly infiltrated orbital structure, followed by the orbital fat. Timely treatment and well-planned procedures are crucial for patients with malignant periocular skin tumors to avoid multiple reoperations and the potential need for orbital exenteration. Full article

Merkel cell carcinoma (MCC) is recognized as one of the most malignant skin tumors. Its rarity might explain the limited exploration of digital color studies in this area. The objective of this study was to delineate color alterations in MCCs compared to benign lesions resembling MCC, such as cherry angiomas and hemangiomas, along with other non-melanoma skin cancer lesions like basal cell carcinoma (BCC) and squamous cell carcinoma (SCC), utilizing computer-aided digital color analysis. This was a retrospective study where clinical images of the color of the lesion and adjacent normal skin from 11 patients with primary MCC, 11 patients with cherry angiomas, 12 patients with hemangiomas, and 12 patients with BCC/SCC (totaling 46 patients) were analyzed using the RGB (red, green, and blue) and the CIE Lab color system. The Lab color system aided in estimating the Individual Typology Angle (ITA) change in the skin, and these results are documented in this study. It was demonstrated that the estimation of color components can assist in the differential diagnosis of these types of lesions because there were significant differences in color parameters between MCC and other categories of skin lesions such as hemangiomas, common skin carcinomas, and cherry hemangiomas. Significant differences in values were observed in the blue color of RGB (p = 0.003) and the b* parameter of Lab color (p < 0.0001) of MCC versus cherry angiomas. Similarly, the mean a* value of Merkel cell carcinoma (MCC) compared to basal cell carcinoma and squamous cell carcinoma showed a statistically significant difference (p < 0.0001). Larger prospective studies are warranted to further validate the clinical application of these findings. Full article