The Expression of Forkhead Box P3 T Regulatory Lymphocytes as a Prognostic Factor in Malignant Melanomas.

Since transcription factor Forkhead Box P3 (FoxP3) was identified as a specific regulatory T cell (Treg) marker, researchers have scrutinized its value as a potential novel therapeutic target or a prognostic factor in various types of cancer with inconsistent results. The present analysis was performed to assess the influence of Treg FoxP3 expression on the prognosis of primary melanoma and to evaluate the correlations with various clinicopathological prognostic factors. We analyzed all eligible patients with stage pT3 primary malignant melanomas treated in a tertiary cancer center. Immunohistochemical staining for Treg FoxP3 expression was performed on retrospectively identified paraffin blocks and subsequently correlated with the outcomes of the patients. A total of 81% of the patients presented a positive Treg FoxP3 expression, being correlated with a higher risk of lymph node metastasis, tumor relapse, and death. Moreover, positive expression was statistically associated with a shorter OS. The tumor relapse rate was estimated at 36.7%. A positive expression of Treg FoxP3 and lymph node metastasis were associated with a higher risk of death based on multivariate analysis. Treg FoxP3 expression may be used as an independent prognostic factor in patients with malignant melanoma to evaluate tumor progression and survival.

Atrophy and Inflammatory Changes in Salivary Glands Induced by Oxidative Stress after Exposure to Drugs and Other Chemical Substances: A Systematic Review.

Background and Objectives: Oxidative stress is involved in the alterations at the level of salivary glands, being the cause of oral pathologies like xerostomia, periodontitis, gingivitis, leucoplakia, and cancer. It is known that antioxidants can reverse changes induced by drugs or other chemicals in some organs, but the question is whether these substances can reduce or revert the effects of oxidative stress at the salivary gland level. Our aim was to find histopathological data at the level of salivary glands supporting the hypothesis of the reversal of oxidative stress-induced changes after the treatment with substances with antioxidant effect. Materials and Methods: A systematic search was conducted in PubMed, Science Direct, and Springer databases, including research articles on oxidative stress histological aspects and oxidative stress biomarkers induced by drugs or other chemicals on salivary glands. Results: Out of 1756 articles, 25 articles were selected with data on tissue homogenate used for biochemical analysis of oxidative and antioxidative markers, along with routine hematoxylin eosin (HE) and immunohistochemical analysis used for histopathological and immunohistochemical diagnosis. Drugs (antineoplastic drugs, antibiotics, and analgesics), alcohol, heavy metals, and fluoride can cause oxidative stress, resulting in morphological changes in different tissues, including in salivary glands. There are many antioxidants but only a few were evaluated regarding the effects on salivary glands in animal studies, such as hesperidin and selenium, which can reverse the damage induced by cyclophosphamide; 10-dehydrogingerdione (10-DHGD), a compound extracted from ginger, which has a protective effect against the oxidative stress and apoptosis induced by tramadol; and glycyrrhizic acid, which may repair the injuries incurred after the administration of sodium nitrite. Conclusions: Substances such as hesperidin, selenium, 10-dehydrogingerdione, and glycyrrhizic acid are antioxidants with proven restorative effects on salivary glands for the damage induced by oxidative stress after exposure to drugs and other chemical substances; however, demonstrating their similar effects in human salivary glands is challenging.

[Syndroms associated with benign skin tumors]. / Gutartige nichtmelanozytäre Hauttumoren bei Syndromen.

Benign skin tumors represent a wide category of diseases. The diagnosis is usually provided by the clinical aspect and the patient history. The pathological examination is not always considered necessary and in most cases the treatment is removal of the lesion by cryotherapy, electrosurgery or laser ablation. Deep phenotyping, including genetic and epigenetic findings, provided the basis of a new understanding of the pathogenetic mechanisms. Some benign skin tumors can be part of syndromes and the dermatologist should be aware of the extracutaneous associations defining these rare disorders: epidermal nevus can be associated with vascular malformations; nevus sebaceous can be associated with cerebral, ocular, and skeletal defects; nevus Becker is associated with cerebral, ocular, and skeletal defects; pilomatricomas appear earlier than colorectal cancer in Gardner's syndrome; tuberous sclerosis complex can associate not only central nervous system lesions but also pulmonary, cardiac or renal manifestations.

Predictive Value of HPV, p53, and p16 in the Post-Treatment Evolution of Malignant Tumors of the Oropharynx and Retromolar Trigone-Oropharynx Junction.

Background and objectives: Knowledge of the interactions and influences of infectious, genetic, and environmental factors on the evolution and treatment response of malignant tumors is essential for improving the management of the disease and increasing patient survival. The objective of this study was to establish the contribution of human papillomavirus (HPV), as well as p53 and p16 tumor markers, alongside associated factors (smoking and alcohol consumption), in the progression of malignancies located in the oropharynx and at the retromolar trigone-oropharyngeal junction. Materials and Methods: We performed a prospective study including 50 patients with malignant tumors of the oropharynx and retromolar trigone-oropharyngeal junction. In all patients, the presence and type of HPV were determined, as well as the status of the tumor markers p53 and p16. The associated risk factors, biopsy results, treatment method, and post-treatment evolution were all documented. Statistical analyses were performed to evaluate the correlations between the determining factors and their influence on the post-treatment evolution. An overall increased survival rate was found in HPV(+) patients. Results: Our study outlined the prevalence of different high-risk subtypes of HPV from the ones presented by other studies, suggesting a possible geographic variation. Correlations between the p53 and p16 statuses and patient survival could be established. The association of smoking and alcohol consumption strongly correlated with an unfavorable evolution. Conclusions: Awareness of the differences in the post-treatment evolution of the patients in relation to the presence of the factors determined in our study could change the future management of such cases for ensuring improved treatment outcomes.

Regression and Sentinel Lymph Node Status in Melanoma Progression.

BACKGROUND The purpose of this study was to assess the role of regression and other clinical and histological features for the prognosis and the progression of cutaneous melanoma. MATERIAL AND METHODS Between 2005 and 2016, 403 patients with melanoma were treated and followed at our Department of Dermatology. Of the 403 patients, 173 patients had cutaneous melanoma and underwent sentinel lymph node (SLN) biopsy and thus were included in this study. RESULTS Histological regression was found in 37 cases of melanoma (21.3%). It was significantly associated with marked and moderate tumor-infiltrating lymphocyte (TIL) and with negative SLN. Progression of the disease occurred in 42 patients (24.2%). On multivariate analysis, we found that a positive lymph node and a Breslow index higher than 2 mm were independent variables associated with disease free survival (DFS). These variables together with a mild TIL were significantly correlated with overall survival (OS). The presence of regression was not associated with DFS or OS. CONCLUSIONS We could not demonstrate an association between regression and the outcome of patients with cutaneous melanoma. Tumor thickness greater than 2 mm and a positive SLN were associated with recurrence. Survival was influenced by a Breslow thickness >2 mm, the presence of a mild TIL and a positive SLN status.

Melanoma as Subsequent Primary Malignancy in Hematologic Cancer Survivors-A Literature Review.

The occurrence of second primary malignancies is becoming increasingly important among cancer survivors. Melanoma, an aggressive neoplasm originating from the melanocytes, is responsible for most skin cancer-related deaths. This review aims to explore the risk of melanoma occurrence as a second primary cancer after the most common subtypes of hematologic neoplasia, a malignant disease originating from myeloid or lymphocytic cell lineages. Chronic lymphocytic leukemia (CLL) and non-Hodgkin lymphoma (NHL) are among the most associated subtypes with melanoma development. We also discuss the underlying hypotheses that may explain the associations between these malignancies and the impact of melanoma on survival. The review emphasizes the importance of increasing awareness of melanoma risk in hematologic cancer survivors, as it can lead to prompt recognition, improved skin surveillance, and better survival outcomes.

Nodular/Keloidal Scleroderma with No Systemic Involvement-A Case Report and a Review of the Literature.

Nodular or keloidal scleroderma is a rare condition with unclear cause and sporadic mentions in the medical literature. It was first recognized in the 19th century, yet its classification is still debated due to the limited number of reported cases. This rare variant of scleroderma is associated with either progressive systemic sclerosis or localized morphea. Clinically, it presents with asymptomatic nodules or plaques, resembling spontaneous keloid formation, often found on the trunk and proximal extremities. Recent literature reviews show a predominance of women with a mean age of 44 years. Diagnosis relies on clinical and histopathological findings, which usually show overlapping features of both scleroderma and true keloids, secondarily to an excessive fibrosing reaction attributed to collagen formation. We present an unusual case of a 70-year-old female patient who displayed the coexistence of two distinct subtypes of morphea (nodular/keloidal and linear), and exclusive skin involvement, which contrasts with the typical presentation of nodular/keloidal scleroderma, often associated with organ-specific disease. However, recent publications have diverged from previous ones regarding systemic sclerosis, with no systemic involvement reported between 2018 and 2024, which we evaluated in our descriptive literature review. With less than 50 cases reported in total, our case underlines the importance of recognizing this rare disease, ensuring appropriate evaluation, treatment, and follow-up.

Antioxidants as Protection against Reactive Oxygen Stress Induced by Formaldehyde (FA) Exposure: A Systematic Review.

BACKGROUND AND OBJECTIVES: Formaldehyde induces oxidative stress and is carcinogenic, particularly squamous cell carcinoma of the nasopharyngeal area. Around us, in exhaust gases, cigarette smoke, and various industrial products, FA primarily affects the respiratory tract and other organs like the cornea, liver, kidneys, brain, and cardiovascular system. This study aims to determine if antioxidants can mitigate FA's harmful effects. MATERIALS AND METHODS: Several databases, including PubMed, Science Direct, Springer, and Wiley, were systematically searched. Research publications on antioxidants mitigating FA-induced oxidative damage were included, but reviews and articles lacking complete texts were excluded. SYRCLE's risk of bias tool for animal studies has been used. Tables were used for data synthesis. Out of 8790 articles, 35 publications detailing tissue homogenate for biochemical analysis, standard hematoxylin-eosin staining, and immunohistochemistry markers for histopathological and immunohistochemical diagnosis were selected. Most studies were case-control studies, utilizing rat or mouse models. Additionally, one cohort study on industrial workers was analyzed. CONCLUSIONS: Antioxidants, including plant extracts, vitamins, and pigments, can prevent or heal FA-induced lesions. However, human studies, particularly biopsies, remain challenging, and animal trials are limited. Further research is needed to confirm FA's long-term effects and optimize antioxidant dosages.

Lentigo Maligna Treatment-An Update.

Lentigo maligna (LM) is a melanoma in situ that is prevalent in chronically sun-damaged skin. Characterized by a slow growth pattern and high mutation rates due to chronic UV exposure, LM poses diagnostic and therapeutic challenges, particularly given its tendency to mimic other skin lesions and its occurrence in cosmetically sensitive areas. Its diagnosis is based on an integrated approach using dermoscopy and reflectance confocal microscopy (RCM). Despite its slow progression, LM can evolve into lentigo maligna melanoma (LMM), making its treatment necessary. Treatment modalities encompass both surgical and non-surgical methods. Surgical treatments like Wide Local Excision (WLE) and Mohs Micrographic Surgery (MMS) aim for clear histological margins. WLE, a standard melanoma surgery, faces challenges from LM's subclinical extensions, which increase the recurrence risk. MMS, effective for large or poorly defined lesions, is defined by precise margin control while considering cosmetic outcomes. Non-surgical options, including radiotherapy and imiquimod, are alternatives for non-surgical candidates. Radiotherapy has been effective since the 1950s, offering good control and cosmetic results, especially for older patients. Imiquimod, an immunomodulator, shows promise in treating LM, though its application remains off-label. The increasing incidence of LM/LMM necessitates a balance in treatment choices to minimize recurrence and maintain cosmetic integrity. A multidisciplinary approach, integrating clinical examination with dermoscopy and RCM and histological assessment, is essential for accurate diagnosis and effective LM management.

The effects of the COVID-19 pandemic on the diagnosis and prognosis of melanoma 2 years after the pandemic in two Romanian counties.

Background: The COVID-19 pandemic disrupted the healthcare system and negatively affected the diagnosis and management of melanoma worldwide. The purpose of this study is to investigate the long-term effects of the COVID-19 pandemic on the diagnosis and prognosis of melanoma. Materials and methods: This retrospective cohort study included histopathologically confirmed melanoma cases from March 2019 to February 2023 in Cluj and Bihor counties. Data from the post-COVID-19 period (March 2021 to February 2023) were compared to the pre-COVID-19 period (March 2019 to February 2020) and the COVID-19 period (March 2020 to February 2021). Patient characteristics, monthly diagnostics, histological subtypes, and key histological features were analyzed using statistical tests. Results: The number of melanoma cases diagnosed annually decreased by 31.37 and 23.75% in the first and second post-pandemic years, respectively, compared to pre-pandemic numbers. Diagnostic rates also decreased by 14.9 and 5.4% in the first and second post-pandemic years, respectively, compared to the pandemic period. Prognostic factors worsened in the post-pandemic period, with higher Breslow index and mitotic rate, and increased ulceration and thick melanomas compared to the pre-pandemic period. Conclusion: The COVID-19 pandemic had a long-lasting impact on the diagnosis of melanoma in Romania, resulting in advanced stages and unfavorable prognostic factors. Larger global studies are needed to comprehensively understand the pandemic's long-term effects on the diagnosis of melanoma.

SARS-CoV-2 Infection-A Trigger Factor for Telogen Effluvium: Review of the Literature with a Case-Based Guidance for Clinical Evaluation.

Telogen effluvium post-COVID-19 is a condition characterized by the diffuse and reversible loss of scalp hair in the period following infection with SARS-CoV-2, and it is currently the second cause of alopecia in women. In the context of the COVID-19 infection, intense psychological stress contributes to alopecia appearance, along with systemic inflammation, autoimmune reactions, oxidative stress, and virally induced hypoxia. Cytokines with proinflammatory action and vasoactive substances negatively modulate the metabolism of some molecules, such as proteoglycans, involved in the hair follicle's growth cycle. Studies show that a large percentage of hairs will suddenly enter the catagen phase during a moderate to severe COVID-19 infection. In the present paper, we update the data from the literature with a clinical example. Our case highlighted that the telogen effluvium after infections with SARS-CoV-2 is reversible with appropriate dermatological treatment. For therapeutic success, informing the patient about this pathology's self-limited and reversible character is essential to reduce the emotional stress that may aggravate the disease.

Multiple primary melanomas: A literature review.

Survival rates for melanoma have increased in recent years, a higher number of patients survive after diagnosis, and, therefore, are at an increased risk of developing second primary melanoma. The aim of this literature review is to identify and integrate the incidence rates and other characteristics of multiple primary melanomas. A total of 36 independent studies were included in this review. The incidence of multiple primary melanomas reported ranged from 1.1% to 20.4%. Synchronous melanomas account for 5% to 66% of the reported lesions. The most common site for both first and subsequent melanomas is the trunk. Superficial spreading melanoma is the most common histological type in both first and subsequent primary melanoma. Regarding the mean Breslow index, subsequent melanomas appeared to be thinner than first melanomas. Our review suggests that melanoma patients are at a higher risk of developing a second primary melanoma and long-term surveillance is needed.

Various Surgical Interventions in Treating Odontogenic Keratocyst: A Radiological Case Report.

The odontogenic keratocyst (OKC) is among the most aggressive odontogenic cysts because of its high recurrent rate. This study's objective was to describe a 7-year radiological and clinical follow-up of an OKC with two recurrences and a combination of surgical treatments. The cyst contents were drained at the biopsy to allow decompression, and then marsupialization (Partsch I) was carried out with good results. In the following two years, the endodontic and radiological evaluation of the neighboring teeth indicated endodontic avoidance. The remaining OKC enucleation (Partsch II) with chemical curettage and suture was performed two years after the first presentation, and the multifocal recurrences developed were also treated by enucleation and chemical curettage. At the last radiological follow-up, no recurrence was evident. Based on our experience, we concluded that patients diagnosed with a OKC should be radiologically evaluated at least once a year for at least 7 years, the endodontic diagnosis and treatment of neighboring teeth should be performed as early as possible, and the combination of surgical treatment and the long follow-up period is challenging.

Actinic Cheilitis - From Risk Factors to Therapy.

Actinic cheilitis or solar cheilosis is considered a precursor of malignancy or even an in situ squamous cell carcinoma (SCC) of the lip, located most frequently on the lower lip. Actinic cheilitis (AC) has a higher likelihood of developing into invasive SCC of the lip, which is one of the deadliest non-melanoma skin cancers. Risk factors include chronic UV exposure, increasing age, male gender, fair phototypes, chronic scarring, immunosuppressive therapy, and tobacco use. From a clinical point of view, AC is characterized by dryness, scaling, atrophy, indistinct borders, and erosions. Ulceration and the appearance of a nodule often suggest the progression to invasive SCC. Dermoscopic examination reveals white structureless areas, scales, erosions, and white halos of the vermilion. Reflectance confocal microscopy shows disruption of the stratum corneum, parakeratosis, an atypical honeycomb pattern, solar elastosis, and dilated and tortuous blood vessels with increased blood flow. The rate of malignant transformation ranges from 10 to 30% and early diagnoses and treatment are essential in preventing the development of invasive SCC. Optimal treatment has not been established yet, but invasive and topical treatments can be tried. The present paper aims to review the existing data regarding epidemiology, risk factors, clinical picture, non-invasive imaging, diagnosis, and therapy in AC.

Dermoscopy in the diagnosis of cutaneous lymphoma (Review).

Cutaneous lymphomas are a group of rare and distinct diseases that present varying clinical manifestations, histopathology and prognosis. Optimal and early management relies on accurate diagnosis. Unfortunately, clinical diagnosis in early stages is difficult due to the clinical overlap with other dermatologic conditions. In numerous cases, several consultations and multiple biopsies are required. Dermoscopy is frequently used for the evaluation of melanocytic skin tumors, but its value has been recognized for non-melanocytic neoplasms and inflammatory skin diseases, and in the last few years it has assisted with the diagnosis of cutaneous lymphoproliferative disorders (LPD). Studies have shown that dermoscopy may be useful in the evaluation of cutaneous lymphomas, offering a link between clinical and histopathological examination, but the features are not diagnostic and histopathological confirmation is mandatory. However, dermoscopy can raise suspicion of cancer, leading to a skin biopsy. Furthermore, larger and prospective studies are required to define the exact dermoscopic features of every subtype of cutaneous lymphoma.

Impact of the COVID-19 Pandemic on Melanoma Diagnosis in Romania-Data from Two University Centers.

The COVID-19 pandemic affected the healthcare system in our country and led non-COVID patients to postpone medical visits that were not urgent. The purpose of this study was to investigate the impact of the first year of the COVID-19 pandemic on the trends in melanoma diagnosis and to compare the pathological characteristics of melanoma patients before and during the pandemic. The number of primary cutaneous melanomas diagnosed each month between 1 March 2019 and 29 February 2020 (pre-COVID-19) and between 1 March 2020 and 28 February 2021 (COVID-19) in the North-Western Region of Romania (Cluj and Bihor counties) was determined. The pathological characteristics of melanomas diagnosed in the two intervals were compared. The number of melanoma diagnoses substantially decreased during the pandemic, with 66 (-19.3%) fewer cutaneous melanomas being diagnosed in the first year of the pandemic when compared with the previous year. The tumor thickness and mitotic rate were significantly higher in cases found during the COVID-19 pandemic. Our study suggests that COVID-19 has delayed diagnosis in patients with melanoma, leading to the detection of thicker melanomas that may increase morbidity and mortality. Further studies are needed to determine the consequences of this delay on outcomes.

Role of Dermoscopy in the Assessment of Basal Cell Carcinoma.

Basal cell carcinoma is one of the most common cancers in white people, with a continuous increase worldwide. Dermoscopy, a non-invasive technique, allows early diagnosis based on the presence of typical vascular structures, pigmented structures, and ulceration and the absence of specific melanocytic structures. Moreover, dermoscopy is useful in basal cell carcinoma management, enabling the differentiation between multiple histological subtypes, between pigmented and non-pigmented variants and allowing a more accurate assessment of surgical margins. After non-ablative therapies, dermoscopy allows the accurate detection of residual disease. The purpose of this review is to highlight the dermoscopic features encountered in basal cell carcinoma and to outline the role of dermoscopy for diagnosis and therapeutic response in this cancer.

Dermatoscopic Features of Naevi During Pregnancy-A Mini Review.

Changes in melanocytic naevi and development of new naevi have been reported in pregnant women. The association between pregnancy and melanoma is a controversial topic. We conducted this review to identify the dermatoscopic changes that occur in naevi during pregnancy that could facilitate in distinguishing benign from suspicious lesions. Medline, Scopus, and Embase datasets were reviewed for clinical studies on dermatoscopic characteristics of melanoma and naevus in pregnancy. Six cohort studies with a total of 258 patients with 1,167 skin lesions that were examined fulfilled the conditions to be included in the review. None of the patients developed melanoma. Development of new naevi, when reported, was observed in less than half of the participants. The most frequent observed dermatoscopic change among the studies was the increase in the number of dots. Development of new vessels, hypo- and hyperpigmentations and changes in the pigment network were common described changes. The included studies were heterogeneous not allowing head-to-head comparisons between them. Robust and larger studies of dermatoscopic evaluation of naevi in pregnant women are needed to determine high-risk dermatoscopic characteristics.

Multiple primary melanomas: Our experience.

Patients with melanoma have an increased risk of having other neoplasms, and particularly other melanomas and non-melanoma skin cancers. The study aimed to describe multiple primary melanomas in a large medical university centre from Romania (Cluj-Napoca) from 2004 to 2020. Out of 699 patients with melanoma included in the study, 26 (3.71%) developed multiple tumours. The 26 patients developed a total of 59 melanomas, corresponding to a mean of 2.3 melanomas per patient. The site and histological subtype of the first and second melanomas were not consistent. The proportion of subsequent melanomas that were in situ (51.5%) or thin melanomas (<1 mm, 24.2%) was higher compared with first melanomas (7.7%, respectively 11.5%). The median and mean time to diagnosis was 2.75 months, respectively, 28.09 months. In total, 76.92% of second melanomas were detected within three years, but we were able to document a subsequent melanoma more than ten years after the first diagnosis. The study highlights the importance of follow-up in patients diagnosed with melanoma, not only in the first years after the primary diagnoses but for the entire life.