Development Of Cutaneous Malignancies Research Articles

Psoriasis as a Risk Factor for Skin Cancer: An International, Propensity-Matched Retrospective Cohort Study

Psoriasis, a chronic immune-mediated skin disorder impacting millions globally, is increasingly recognized for its links to various disease processes. As our understanding of immune dysregulation in psoriasis progresses, acknowledging the pivotal role of dysregulated T-cells in the pathogenic development of the persistent inflammatory state becomes crucial. This immune dysregulation and the resulting prevalent inflammatory state have raised concerns about psoriasis potentially serving as a significant comorbidity in cancer development among patients. To contribute to this discussion, we conducted a global retrospective cohort study with propensity score matching (PSM) using the TriNetX Analytics platform. The study aimed to investigate whether patients diagnosed with psoriasis face an elevated risk in the development of cutaneous malignancies, encompassing both melanoma and non-melanoma skin cancers. Our findings confirmed a noteworthy concern, revealing a significantly increased risk of developing cutaneous neoplasms in individuals with psoriasis. In conclusion, our study underscores the importance of heightened awareness and the necessity for routine skin cancer screenings in this unique patient population. The observed association between psoriasis and an increased risk of cutaneous neoplasms highlights the need for proactive medical interventions and emphasizes the potential impact of psoriasis as a comorbidity in the context of cancer development.

Mast Cell: A Mysterious Character in Skin Cancer.

Cutaneous malignancies represent a real concern and burden for the healthcare system, not only due to their increased frequency, but also due to the significant number of deaths attributed to these types of cancer. The genesis of tumors, their progression and metastasis are highly complex and researched subjects; apparently, mast cells (MCs) constitute an important piece in the complicated jigsaw puzzle of cancer. This article reviews the current knowledge of the roles MCs might play in the development of cutaneous malignancies. Besides their well-known and studied role in allergic reactions, MCs are linked to multiple and various disorders, including cancer. MCs exhibit incredible heterogeneity, being able to secrete numerous mediators that influence the tumor microenvironment and tumor cells. They are involved in many physiological and pathological processes, such as inflammation and angiogenesis. In this context, it is paramount to explore the advancements made so far in elucidating the roles that MCs have in skin cancer because they might provide valuable therapeutic targets in the future. Controversial and conflicting results were obtained across the studies examined.

Squamous Cell Carcinoma Arising in Lesions of Discoid Lupus Erythematosus in a Patient with Overlap Syndrome: A Chronic Rare Complication.

Squamous Cell Carcinoma Arising in Lesions of Discoid Lupus Erythematosus in a Patient with Overlap Syndrome: A Chronic Rare Complication.

Risk of cutaneous carcinogenesis with phototherapy in Indian subpopulation: A 10‐year analysis and a review of literature

Phototherapy is an extremely effective and established therapeutic modality in a variety of dermatological disorders. However, there has been a constant concern with respect to its long-term usage as some of the studies have identified the risk of cutaneous malignancy associated with phototherapy. The carcinogenic potential of PUVA has been demonstrated in most US studies; however, the studies done on Asian and Arabian-African population have not corroborated similar findings, thus suggesting that the darker skin may confer protection against the development of cutaneous malignancy following phototherapy. The main aim of the present study was to assess the safety of phototherapy (bath PUVA and NBUVB) in Indian population (Fitzpatrick skin types IV and V) with respect to its carcinogenic potential and to determine the maximum cumulative dose that our patients could tolerate without developing any untoward complications such as cutaneous malignancy. All patients who received phototherapy between January 2006 and October 2016 were enrolled in the study. Details such as cumulative dose, number of phototherapy sessions received, indication for phototherapy, adverse effects such as pigmentary changes, new growths on the skin surface following the therapeutic sessions were entered in a predesigned proforma. This ambispective study had 1300 patients who had received phototherapy over a period of 10 years. A total of 929 patients had received PUVA, and the remaining 371 patients had received NBUVB for various dermatological indications. The average follow-up period for PUVA was 3 years and 6.5 years for NBUVB. The maximum cumulative dose of UVA and UVB that could be safely administered in our patients was 2085 J/cm2 and 1985 mJ/cm2, respectively. None of our patients developed any features of cutaneous malignancy during their follow-up. Both bath-PUVA and NBUVB are safe and efficacious in treating patients of darker skin types (IV and V). The risk of developing cutaneous malignancy is negligible in this subset of patients. However, more studies need to be done on the Asian population to substantiate the same.

Sunlight

Objective: We assessed the relationship between serum 25 hydroxyvitamin D (OH) D levels and the presence of malignancy in patients who underwent surgery for cutaneous skin lesions. Materials and Methods: Three-hundred and ninety-eight patients operated on for cutaneous lesions, had serum 25 (OH) D levels on file, had no known parathyroid pathology, did not concomitantly take bisphosphonate or Vitamin D supplement, and had accessible pathology results were reviewed upon their consent for the retrospective analysis of their data. Demographic characteristics, diagnosis dates, lesion localizations, pathology results, and serum 25 (OH) D levels were noted. Optimal cutoff value for Vitamin D levels was calculated with receiver operating characteristic (ROC) curve analysis and pathology results of the excised lesions and patient characteristics were analyzed according to this value. Results: ROC analysis showed 90% sensitivity and 64% specificity for vitamin D levels of 18.64 ng/ml (area under the curve [AUC] = 0.905; 95% confidence interval 0.87–0.93, P < 0.001). Review of lesions for pathological characteristics showed 207 (52%) benign and 191 (48%) malignant. While no significant relationship was observed between gender and vitamin D levels, a significant difference was identified between advanced age and low Vitamin D levels and the presence of malignancy (P < 0.001). The one-way analysis of variance and Bonferroni's post hoc analysis revealed higher incidences of malignant lesions in the group with low serum 25 (OH) D levels (P < 0.001), in patients aged 65+ years (P < 0.001), in cases localized to the head and neck (P = 0.026), and in males (P = 0.047). Conclusion: We identified a statistically significant relationship between low serum 25 (OH) D levels and the development of cutaneous malignancy.

Consistency in Distribution of Facial Skin Cancers Treated With Mohs Micrographic Surgery.

Mohs micrographic surgery (MMS) has become the standard of treatment for skin malignancies of the head and neck. However, there is a paucity of literature describing facial distributions of MMS. Anatomical location of skin cancer is an important feature to study as it can affect prognosis as well as pathogenesis of skin cancers. This study aims to analyze consistency in head and neck MMS anatomical distributions and compare differences between multiple centers. The study retrospectively reviews 5871 MMS cases performed at a single center in Chevy Chase, Maryland from January 2014 through December 2019. Results show distributions of skin cancers on the face treated with MMS consistently occur at the same anatomical sites year after year with minimal variance. This knowledge of consistency provides a foundation for future studies because it allows for comparison. Comparing and contrasting data across multiple centers can elucidate regional characteristics that may impact the pathogenesis and distribution of facial skin tumors. Many regional or demographical factors may be important in the development of cutaneous malignancies. This information should be considered when assessing risk factors for cancerous skin lesions.J Drugs Dermatol. 2022;21(5):506-509. doi:10.36849/JDD.6143.

Plant Secondary Metabolites against Skin Photodamage: Mexican Plants, a Potential Source of UV-Radiation Protectant Molecules.

Human skin works as a barrier against the adverse effects of environmental agents, including ultraviolet radiation (UVR). Exposure to UVR is associated with a variety of harmful effects on the skin, and it is one of the most common health concerns. Solar UVR constitutes the major etiological factor in the development of cutaneous malignancy. However, more than 90% of skin cancer cases could be avoided with appropriate preventive measures such as regular sunscreen use. Plants, constantly irradiated by sunlight, are able to synthesize specialized molecules to fight against UVR damage. Phenolic compounds, alkaloids and carotenoids constitute the major plant secondary metabolism compounds with relevant UVR protection activities. Hence, plants are an important source of molecules used to avoid UVR damage, reduce photoaging and prevent skin cancers and related illnesses. Due to its significance, we reviewed the main plant secondary metabolites related to UVR protection and its reported mechanisms. In addition, we summarized the research in Mexican plants related to UV protection. We presented the most studied Mexican plants and the photoprotective molecules found in them. Additionally, we analyzed the studies conducted to elucidate the mechanism of photoprotection of those molecules and their potential use as ingredients in sunscreen formulas.

Skin Cancers and Lung Transplant.

It is well known that solid-organ transplant recipients (SOTRs) have a 65- to 100-fold increase in the risk of developing skin cancer, namely, nonmelanoma skin cancers (NMSCs) such as cutaneous squamous cell carcinoma (cSCC) and basal cell carcinoma (BCC). In addition, these patients are also at increased risk for development of melanoma as well as other less common cutaneous malignancies (Merkel's cell carcinoma, Kaposi's sarcoma). SOTRs with NMSC (namely cSCC) are also at significantly increased risk of poor clinical outcomes including local recurrence, nodal and distant metastasis, and disease-specific death relative to patients who are not immunosuppressed. Increased surveillance and monitoring in patients at risk of aggressive disease and poor outcomes who are on immunosuppression is essential in patients with lung transplants given the high degree of immunosuppression. Increased awareness of risks, treatments, and management allows for improved outcomes in these patients. This article will provide an overview of the risk factors for the development of cutaneous malignancies in organ transplant recipients as well as a detailed discussion of various immunosuppressant and prophylactic medications used in this patient population that contribute to the risk of developing cutaneous malignancies, with an emphasis on NMSC (cSCC and BCC) in lung transplant recipients. Finally, this article includes a discussion on the clinical and dermatologic management of this high-risk immunosuppressed population including a review of topical and systemic agents for field therapy of actinic damage and chemoprevention of keratinocyte carcinomas. In addition, indications for additional treatment and preventive measures such as adjuvant radiation treatment after surgical management of cutaneous malignancies and potential modification of immunosuppressive medication regimens are discussed.

The combination of encorafenib and binimetinib for the treatment of patients with BRAF-mutated advanced, unresectable, or metastatic melanoma: an update

ABSTRACT Introduction: In the treatment of advanced BRAF-mutated melanoma, selective regulation of the MAPK pathway with BRAF and MEK inhibition has emerged as one of the mainstays of therapy. Areas covered: Introduction of MAPK pathway. Current data on BRAF inhibition from phase I, II, and III trials in the setting of unresectable disease. Current data on encorafenib and binietinib, their chemistry, pharmacokinetic, and pharmacodynamic properties. Discussion on use of encorafenib therapy as a single agent as well as in combination with binimetinib and other systemic therapies. Expert opinion: BRAF inhibition with encorafenib exhibits substantial antitumor activity with less paradoxical MAPK pathway activation leading to treatment resistance. Combination therapy with binimetinib improves response rate, progression-free survival, and overall survival in patients with BRAF-mutated unresectable, metastatic melanoma. Serious adverse events, including development of cutaneous malignancies, are reported at lower rates with combination therapy, while less severe events such as pyrexia can be more common.

The Role of Cell Adhesion Molecule 1 (CADM1) in Cutaneous Malignancies.

Cell adhesion ability is one of the components to establish cell organization and shows a great contribution to human body construction consisting of various types of cells mixture to orchestrate tissue specific function. The cell adhesion molecule 1 (CADM1) is a molecule of cell adhesion with multiple functions and has been identified as a tumor suppressor gene. CADM1 has multifunctions on the pathogenesis of malignancies, and other normal cells such as immune cells. However, little is known about the function of CADM1 on cutaneous cells and cutaneous malignancies. CADM1 plays an important role in connecting cells with each other, contacting cells to deliver their signal, and acting as a scaffolding molecule for other immune cells to develop their immune responses. A limited number of studies reveal the contribution of CADM1 on the development of cutaneous malignancies. Solid cutaneous malignancies, such as cutaneous squamous cell carcinoma and malignant melanoma, reduce their CADM1 expression to promote the invasion and metastasis of the tumor. On the contrary to these cutaneous solid tumors except for Merkel cell carcinoma, cutaneous lymphomas, such as adult-T cell leukemia/lymphoma, mycosis fungoides, and Sézary syndrome, increase their CADM1 expression for the development of tumor environment. Based on the role of CADM1 in the etiology of tumor development, the theory of CADM1 contribution will desirably be applied to skin tumors according to other organ malignancies, however, the characteristics of skin as a multicomponent peripheral organ should be kept in mind to conclude their prognoses.

Risk of Cutaneous Malignancy in Mycosis Fungoides Patients Treated with PUVA: A Retrospective Study

Istanbul Universitesi Istanbul Tip Fakultesi, Dermatoloji Anabilim Dali, Istanbul, Turkiye @Telif Hakki 2015 Turk Dermatoloji Dernegi Makale metnine www. turkdermatolojidergisi.com web sayfasindan ulasilabilir. @Copyright 2015 by Turkish Society of Dermatology Available on-line at www.turkdermatolojidergisi.com Melike Umarova Aslan, Istanbul Universitesi Istanbul Tip Fakultesi, Dermatoloji Anabilim Dali, Istanbul, Turkiye E-posta: melikeumarova@hotmail.com Gelis Tarihi/Submitted: 27.08.2014 Kabul Tarihi/Accepted: 02.12.2014 Yazisma Adresi/ Correspondence: Objective: PUVA therapy is mostly used longer than other diseases in mycosis fungoides (MF) patients. We aimed to investigate the chronic side effects of PUVA therapy, including skin cancer to disclose the actual risk in Turkish population. Methods: We screened all MF patients treated with PUVA at the Department of Dermatology and Venereology of Istanbul Medical Faculty and included patients in whom PUVA has first initiated between 1994 and 2006 and administered in one or several courses and who were followed up more than five years with last visit in 2012. Results: Fifty patients with MF had a mean follow-up duration of 10.2±2.8 years. Six patients (12%) had PUVA lentigines. Two of them (4%) developed skin cancer (basal cell carcinoma, Bowen’s disease) during their follow-up. The mean sessions (295.5±7.8 sessions) and total UVA doses (1452 J/cm2) in these patients with skin cancer were higher than those who did not develop skin cancer (128.7±73 sessions and 515±31 J/ cm2, respectively). There was a significant relationship between the PUVA lentigines and development of cutaneous malignancy (p=0.01). Ozgun Arastirma / Original Investigation 12 Turk J Dermatol 2015; 1: 12-7 • DOI: 10.4274/tdd.2413 13 Umarova Aslan ve ark. PUVA Tedavisinde Deri Kanseri Riski. Turk J Dermatol 2015; 1: 12-7 Conclusion: Cutaneous malignancies were detected in 4% of MF patients followed up approximately 10 years. Due to this low risk, we conclude that PUVA therapy is relatively safe in patients with MF in our country. However, UVA should not be applied in high total doses and patients should be followed-up lifelong.

The immune system and skin cancer.

Carcinogenesis involves multiple mechanisms that disturb genomic integrity and encourage abnormal proliferation. The immune system plays an integral role in maintaining homeostasis and these mechanisms may arrest or enhance dysplasia. There exists a large body of evidence from organ transplantation literature supporting the significance of the immune suppression in the development of skin cancer. Nonmelanoma skin cancers are the most frequent neoplasms after organ transplantation, with organ transplant recipients having a 65-fold increase in squamous cell carcinoma incidence and 10-fold increase in basal cell carcinoma incidence. Similarly, UV-radiation (UVR) induced immunosuppression is correlated with the development of cutaneous malignancies in a dose-dependent manner. This was first shown several decades ago by Margaret Kripke, when transplanted tumors were rejected in mice with competent immune systems, but grew unchecked in immunosuppressed specimens. After UV exposure, chromophores initiate a cascade that leads to immunosuppression via derangement of Langerhans cells' antigen-presenting capacity. UV-irradiated Langerhans cells present antigens to Th2 cells, but fail to stimulate Th1 cells. A subset of T regulatory cells, specific for the antigen encountered after UVR, is also stimulated to proliferate. In general UV irradiation leads to a greater number of T regulatory cells and fewer effector T cells in the skin, shiftingthe balance from T-cell-mediated immunity to immunosuppression. These regulatory cells have the phenotype CD4+, CD25+, Foxp3+, CTLA-4+. These and many other changes in local immunity lead to a suppressed immune state, which allow for skin cancer development.

Netherton syndrome - Why ENT surgeons should be aware of this rare disease - report of a case

BackgroundComèl-Netherton syndrome is an inherited ichthyosis that is associated with highly impaired epidermal cornification and barrier function. Literature sparsely reports of the occurrence of early onset skin cancer in people with Netherton syndrome. To the best of our knowledge the suitability of the severely altered skin in patients with Netherton syndrome for techniques of facial plastic reconstructive surgery has not been discussed in literature yet.Case presentationWe present a 31-year-old caucasian female patient with Netherton syndrome who developed a defect of the right nasal ala. Biopsy revealed a well differentiated squamous cell carcinoma.We describe the reconstruction of a full thickness nasal defect with a paramedian forehead flap and an epidermal turn-in flap in Netherton syndrome. Despite the altered skin texture, reconstruction and healing were uneventful and the surgical result was favourable.ConclusionTherefore the authors state that the development of cutaneous malignancies should be included as a possible complication in patients with Netherton syndrome. Standard techniques of surgical facial reconstruction can be applied in these patients; healing and outcome do not appear to be negatively affected by the underlying disease.

Angiosarcoma Arising from the Tongue of an 11-Year-Old Girl with Xeroderma Pigmentosum

Xeroderma pigmentosum (XP) is a rare autosomal recessive defect in DNA endonuclease activity that is associated with the development of cutaneous malignancies, at sun exposed sites, including basal cell carcinoma, squamous cell carcinoma, and melanoma. Squamous cell carcinomas are also known to target the anterior tongue. Patients sometimes develop angiosarcomas, and these invariably arise from sun-exposed skin. A biopsy was taken from a large mass arising in the anterior tongue of an 11-year-old girl with XP and a history of cutaneous basal cell carcinomas. The histopathologic findings demonstrated a high grade epithelioid neoplasm resembling a poorly differentiated squamous cell carcinoma, but the immunohistochemical profile (AE1/AE3 negative, p63 negative, CD31 positive, CD34 positive) established the diagnosis of angiosarcoma. Angiosarcoma is an XP-related tumor that usually arises in sun-exposed skin but can also arise in the oral cavity. For patients with XP who develop epithelioid neoplasms of the oral cavity, epithelioid angiosarcoma should be considered in the differential diagnosis.

Solar radiation induced skin damage: Review of protective and preventive options

Purpose: Solar energy has a number of short- and long-term detrimental effects on skin that can result in several skin disorders. The aim of this review is to summarise current knowledge on endogenous systems within the skin for protection from solar radiation and present research findings to date, on the exogenous options for such skin photoprotection.Results: Endogenous systems for protection from solar radiation include melanin synthesis, epidermal thickening and an antioxidant network. Existing lesions are eliminated via repair mechanisms. Cells with irreparable damage undergo apoptosis. Excessive and chronic sun exposure however can overwhelm these mechanisms leading to photoaging and the development of cutaneous malignancies. Therefore exogenous means are a necessity. Exogenous protection includes sun avoidance, use of photoprotective clothing and sufficient application of broad-spectrum sunscreens as presently the best way to protect the skin. However other strategies that may enhance currently used means of protection are being investigated. These are often based on the endogenous protective response to solar light such as compounds that stimulate pigmentation, antioxidant enzymes, DNA repair enzymes, non-enzymatic antioxidants.Conclusion: More research is needed to confirm the effectiveness of new alternatives to photoprotection such as use of DNA repair and antioxidant enzymes and plant polyphenols and to find an efficient way for their delivery to the skin. New approaches to the prevention of skin damage are important especially for specific groups of people such as (young) children, photosensitive people and patients on immunosuppressive therapy. Changes in public awareness on the subject too must be made.

Epidermodysplasia Verruciformis and Susceptibility to HPV

Purpose of review: Epidermodysplasia verruciformis has been addressed in depth in the recent literature despite its rarity. The disease is characterized by a persistence in human papillomavirus infections and development of cutaneous malignancies, usually happening more frequently and at a younger age than in the general population. Because of the role of immunodeficiency to viral antigens eventually leading to cancer, EV has become a model for understanding a viral role in cutaneous oncogenesis. Susceptibility loci for EV have been mapped and encoded protein functions are becoming better understood. Discoveries of novel mutations and further study of EV-associated HPV serotypes in lesional and nonlesional skin of affected patients and the general population may help generate a cohesive theory regarding the true role of a defective immune barrier in oncogenesis.

Epidermodysplasia verruciformis and susceptibility to HPV.

Purpose of review: Epidermodysplasia verruciformis has been addressed in depth in the recent literature despite its rarity. The disease is characterized by a persistence in human papillomavirus infections and development of cutaneous malignancies, usually happening more frequently and at a younger age than in the general population. Because of the role of immunodeficiency to viral antigens eventually leading to cancer, EV has become a model for understanding a viral role in cutaneous oncogenesis. Susceptibility loci for EV have been mapped and encoded protein functions are becoming better understood. Discoveries of novel mutations and further study of EV-associated HPV serotypes in lesional and nonlesional skin of affected patients and the general population may help generate a cohesive theory regarding the true role of a defective immune barrier in oncogenesis.

Lichen planus

Lichen planus

ULTRAVIOLET LIGHT INDUCED ALTERATION TO THE SKIN

Solar light is the primary source of UV radiation for all living systems. UV photons can mediate damage through two different mechanisms, either by direct absorption of UV via cellular chromophores, resulting in excited states formation and subsequent chemical reaction, or by phosensitization mechanisms, where the UV light is absorbed by endogenous (or exogenous) sensitizers that are excited and their further reactions lead to formation of reactive oxygen species (ROS). These highly reactive species can interact with cellular macromolecules such as DNA, proteins, fatty acids and saccharides causing oxidative damage. Direct and indirect injuries result in a number of harmful effects such as disrupted cell metabolism, morphological and ultrastructural changes, attack on the regulation pathways and, alterations in the differentiation, proliferation and apoptosis of skin cells. Processes like these can lead to erythema, sunburn, inflammation, immunosuppression, photoaging, gene mutation, and development of cutaneous malignancies. The endogenous and exogenous mechanisms of skin photoprotection are discussed.

Squamous cell carcinoma in situ (Bowen's disease) in renal transplant patients treated with 5% imiquimod and 5% 5-fluorouracil therapy.

Depending upon the patient's age at transplant, skin type, sun exposure, and the need for immunosuppressive therapy to prevent rejection, there is escalation in the development of cutaneous malignancies in organ transplant patients a number of years after transplantation. Thus, with the expansion in these procedures over the past decades, and the ever-lengthening survival of these patients, we are seeing an increase in cutaneous malignancies in this patient population. To determine if combined therapy with 5% 5-fluorouracil and 5% imiquimod may be useful in the treatment of squamous cell carcinoma in situ. We present five renal transplant patients, all more than 10 years posttransplantation, three with insulin-dependent diabetes, who developed multiple areas of squamous cell carcinoma (SCC) in situ. All these patients were on chronic immunosuppressive chemotherapy to prevent rejection, but were otherwise doing well. All the patients had biopsy-proven SCC in situ on their lower extremities that even in normal patients may be a challenge to treat. We treated these five patients with a combination of a local immune therapy, imiquimod cream, and a topical chemotherapeutic agent, 5% 5-fluorouracil (5-FU), with clearing of the areas of SCC in situ. Although immunotherapy must be used with caution in organ transplant patients to avoid graft rejection, topical imiquimod is a local immune modulator that potentiates local innate and possible adaptive immunity without measurable effects on systemic immunity. In addition, there is evidence that cytokines induced by imiquimod may improve the therapeutic efficacy of topical 5% 5-FU in the treatment of SCC in situ.