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Simple Summary: Actinic keratoses are lesions with a variable potential for malignant transformation, but with a difficult predictability of evolution towards this type of lesions. Non-invasive skin imaging methods represent diagnostic tools that allow a better evaluation of actinic keratoses lesions, as well as the establishment of a diagnosis with greater specificity and sensitivity. This review aims to identify all skin imaging methods that are useful in the diagnosis and monitoring of the treatment of actinic keratoses, as well as to identify those lesions at risk of transforming into squamous cell carcinoma. Non-melanocytic skin cancers represent an important public health problem due to the increasing incidence and the important local destructive potential. Thus, the early diagnosis and treatment of precancerous lesions (actinic keratoses) is a priority for the dermatologist. In recent years, non-invasive skin imaging methods have seen an important development, moving from simple observational methods used in clinical research, to true diagnostic and treatment methods that make the dermatologist's life easier. Given the frequency of these precancerous lesions, their location on photo-exposed areas, as well as the long treatment periods, with variable, imprecise end-points, the need to use non-invasive imaging devices is increasingly evident to complete the clinical observations in the diagnosis and treatment of these lesions, with the aim of increasing accuracy and decreasing the adverse effects due to long treatment duration. This is the first review that brings together all skin imaging methods (dermoscopy, reflectance confocal microscopy, ultrasonography, dermoscopy-guided high frequency ultrasonography, and optical coherence tomography) used in the evaluation of actinic keratoses and their response to different treatment regimens. [ABSTRACT FROM AUTHOR]

Bowenoid papulosis is a cutaneous disease that is part of the spectrum of genital in situ carcinomas, caused primarily by infection with oncogenic strains of the HPV virus. The potential to transform into squamous cell carcinoma requires the diagnosis and treatment of the lesions. We present the case of a 34-year-old non-smoker without medical history who presented to our clinic for the appearance of multiple, asymptomatic, well-defined, flat, pigmented violaceous papules at the root of the penis in evolution for a year. Reflectance confocal microscopy (RCM) suggested the diagnosis of bowenoid papulosis, which was confirmed by histopathological examination. The treatment with Imiquimod 5% (3 times/week) and Isoprinosine (4 g/day) was initiated, followed by monitoring of the lesions by repeated RCM examination. The evolution of the patient at 6 weeks of therapy was favourable, with clinical remission of lesions and improvement in RCM aspects of the evaluated skin. In conclusion, RCM represents a useful noninvasive examination method that allows not only the diagnosis but also the follow-up of the treatment response in order to decide the appropriate length of therapy. [ABSTRACT FROM AUTHOR]

An early diagnosis is of overwhelming importance for the management and prognosis of mucocutaneous cancer. Actinic cheilitis (AC), defined by the clonal expansion of genomically unstable keratinocytes, is the most common potentially malignant lesion affecting the lips. Squamous cell carcinoma (SCC) is the most frequent oral malignancy, and there is strong evidence that the majority of the SCCs of the lip originate from AC. There is considerable difficulty in discerning between dysplasia and invasive carcinomas solely on a clinical basis. Although dermoscopy has become an essential tool for skin tumor evaluation, reflectance confocal microscopy (RCM) is a non-invasive imaging technology that has proved itself extremely useful in the diagnosis and monitoring of several skin diseases, including AC and SCC. The present study aimed to re-emphasize the usefulness of RCM in the early detection of malignant transformation, using AC and SCC of the lips as working examples. Due to the apparent innocuousness of AC for numerous patients, it is not possible to overstress the importance of a correct and early diagnosis, proper treatment and long-term patient follow-up as being essential for preventing the progression to lip SCC, or for its timely diagnosis. [ABSTRACT FROM AUTHOR]

Non-melanoma skin cancers represent the most common cancer in white-skinned individuals, with a continuous increasing global incidence. The main risk factor for their development is chronic exposure to sunlight. Unlike basal cell carcinoma, squamous cell carcinoma arises from precancerous lesions such as actinic keratoses. The diagnosis of non-melanoma skin cancer is based on clinical examination and dermoscopy, while histopathology certifies the diagnosis. The following article will present the main types of non-melanoma cancers with their respective clinical features, along with diagnostic methods and available therapeutic options. [ABSTRACT FROM AUTHOR]

Squamous cells carcinoma (SCC) is the second most frequent of the keratinocyte-derived malignancies after basal cell carcinoma and is associated with a significant psychosocial and economic burden for both the patient himself and society. Reported risk factors for the malignant transformation of keratinocytes and development of SCC include ultraviolet light exposure, followed by chronic scarring and inflammation, exposure to chemical compounds (arsenic, insecticides, and pesticides), and immune-suppression. Despite various available treatment methods and recent advances in noninvasive or minimal invasive diagnostic techniques, the risk recurrence and metastasis are far from being negligible, even in patients with negative histological margins and lymph nodes. Analyzing normal, dysplastic, and malignant keratinocyte proteome holds special promise for novel biomarker discovery in SCC that could be used in the future for early detection, risk assessment, tumor monitoring, and development of targeted therapeutic strategies. [ABSTRACT FROM AUTHOR]

Simple Summary: In this study, we assess the prognostic potential of immune and inflammatory elements determined preoperatively in the peripheral blood of patients with oral squamous cell carcinoma (OSCC). Preoperative plasma fibrinogen (Fib) and platelet-to-lymphocyte ratio (PLR) show strong correlations with patients' outcomes. Analyzed together, in a new parameter named Fibrinogen-PLR Algorithm (FiPLA), predictive power increases significantly. Clinicians can use this new, easy, cost-effective, and globally available tool for risk stratification of patients with OSCC, as early as from the moment of diagnosis. (1) Background: Oral squamous cell carcinoma (OSCC) is a common malignancy, and the impact of immune and inflammatory mechanisms in its development and progression are of major interest. The aim of our study is to assess the prognostic potential of circulating immune and inflammatory elements determined preoperatively in patients with OSCC, as well as the development of a new compound parameter with predictive value. (2) Methods: We assessed preoperative fibrinogen (Fib) and the platelet-to-lymphocyte ratio (PLR) in 111 OSCC patients. Using a mathematic algorithm, we determined a composite parameter with cumulative information from Fib and PLR, named Fibrinogen-PLR Algorithm (FiPLA). Survival analysis, followed by bivariate and multivariate analyses, was subsequently conducted. (3) Results: Increased preoperative Fib and PLR levels were associated with poor outcome in OSCC (p = 0.0001 and p = 0.0015, respectively). Preoperative FiPLA values were also associated with poor patient survival (p < 0.0001). Multivariate analysis confirmed the independent prognostic role for FiPLA only (CI95% 1.232–67.770, p = 0.03), showing the superior predictive value of FiPLA compared to its individual components. (4) Conclusions: Preoperative assessments of circulating immune and inflammatory elements can provide high-quality prognostic information, and they represent valuable tools in clinical practice, facilitating the early risk stratification of patients with OSCC. [ABSTRACT FROM AUTHOR]

Background: squamous cell carcinoma (SCC) is the second most common type of malignancy worldwide. Skin and mucosa of the head and neck areas are the most frequently affected. An aggressive behavior in SCC is not easily detected, and despite all efforts, mortality in these types of cancer did not show major improvements during recent decades. In this study, we aim to determine the role of histological features available through standard pathology assessment in SCC and their relation with tumor behavior and patients' survival. Method: in a group of one hundred patients diagnosed with SCC involving the head and neck areas, we assessed the presence of four histological features (tumor/stroma ratio, immune infiltration at the front of invasion, tumor-budding activity, and tumor necrosis), their correlations with tumor type (mucosal or cutaneous), tumor clinicopathological characteristics, and their prognostic potential. Results: the comparison between histological features in cutaneous versus mucosal SCC reveals no significant differences for any of the four parameters assessed. We found significant correlations between tumor/stroma ratio and lymphatic metastasis (p = 0.0275), perineural invasion (p = 0.0006), and clinical staging (p = 0.0116). Immune infiltration at the front of invasion revealed similar correlations with lymph node involvement (p = 0.002), perineural invasion (p = 0.0138), and clinical staging (p = 0.0043). Tumor budding and tumor necrosis correlated with the size of the tumor (p = 0.0077 and p = 0.0004) and the clinical staging (p = 0.0039 and p = 0.0143). In addition, tumor budding was significantly correlated with perineural invasion (p = 0.0454). In mucosal SCC, patients with improved outcome revealed high values for the tumor/stroma ratio (p = 0.0159) and immune infiltration at the front of invasion (p = 0.0274). However, the multivariate analysis did not confirm their independent prognostic roles. Conclusions: extended histological assessments that include features such as tumor/stroma ratio, immune infiltration at the front of invasion, tumor budding, and tumor necrosis can be an easy, accessible method to collect additional information on tumor aggressiveness in skin and mucosa SCC affecting the head and neck areas. [ABSTRACT FROM AUTHOR]

Simple Summary: Oral cancer is a common malignancy with high morbidity and mortality. Tumor-infiltrating immune cells play key roles in its pathogenesis, influencing tumor behavior and evolution. The aim of our study was to assess the prognostic character of tumor-infiltrating CD4+, CD8+ and CD56+ cells in oral squamous cell carcinoma. We found major differences in CD4+ and CD8+ lymphocyte density at the front of invasion compared to the intratumor compartment. In addition, intense infiltration with CD8+ lymphocytes in both compartments carried a positive prognostic character. Moreover, we found that a higher intratumor infiltration with CD56+ cells significantly correlated with locoregional disease control and improved survival. Our study confirms the key role of innate and adaptive immune systems in oral squamous cell carcinoma. The predictive characteristics of CD8+ and CD56+ cells can be implemented as independent prognostic tools and can provide important elements in developing individualized therapy in the fight against oral cancer. (1) Background: The immune microenvironment plays an important role in carcinogenesis and has prognostic potential in many types of cancer. In this study we assess the prognostic character of tumor-infiltrating immune cells CD4+, CD8+ and CD56+ in resectable oral squamous cell carcinoma (OSCC); (2) Methods: We have evaluated the densities of CD4+, CD8+ and CD56+ in two distinct compartments, intratumor and invasion front, in 90 patients with OSCC; (3) Results: Significant differences were found between the tumor compartments for the CD4+ and CD8+ lymphocytes. An improved outcome (OS) was seen in patients with high densities of intratumor CD8+ lymphocytes (p = 0.0086), CD8+ lymphocytes at the front of invasion (p = 0.0011) and for intratumor CD56+ cells (p = 0.0016). Multivariate analysis confirmed the independent prognostic role of CD8+ at the front of invasion (OR = 3.75, CI95% 1.17–12.35, p = 0.026) and for intratumor CD56+ cells (OR = 3.669, CI95% 1.09–15.37, p = 0.035); (4) Conclusions: Tumor-infiltrating CD8+ lymphocytes at the front of invasion and CD56+ in the intratumor compartment display predictive traits in OSCC. A reach immune infiltration with these types of cells is associated with an improved patient outcome. [ABSTRACT FROM AUTHOR]

Actinic cheilitis (AC) is one of the most frequent pathologies to affect the lips. Studies show that the most commonplace oral malignancy, squamous cell carcinoma (SCC), often emerges from AC lesions. Invasive diagnostic techniques performed on the lips carry a high risk of complications, but reflectance confocal microscopy (RCM), a non-invasive skin imaging technique, may change the current diagnostic pathway. This retrospective study was aimed at consolidating the RCM diagnostic criteria for AC and lip SCC. The study was conducted in two tertiary care centers in Bucharest, Romania. We included adults with histopathologically confirmed AC and SCC who also underwent RCM examination. Of the twelve lesions included in the study, four were AC and eight were SCC. An atypical honeycomb pattern and the presence of target cells in the epidermis were RCM features associated with AC. SCC was typified by the presence of complete disruption of the epidermal architecture and dermal inflammatory infiltrates. The mean blood vessel diameter in SCC was 18.55 µm larger than that in AC (p = 0.006) and there was no significant difference (p = 0.64) in blood vessel density, as measured by RCM, between SCC and AC. These data confirm that RCM can be useful for the in vivo distinction between AC and lip SCC. [ABSTRACT FROM AUTHOR]