Role of Insulin Use and Social Determinants of Health on Non-melanoma Skin Cancer: Results From the Behavioral Risk Factor Surveillance System.

BACKGROUND: Non-melanoma skin cancer (NMSC) is a frequent type of malignancy with a steadily increasing incidence rate worldwide. Although NMSC was shown to be associated with diabetes, no studies have addressed the extent to which insulin use influences the risk of NMSC in light of social determinants of health (SDOH). We conducted a quantitative study that examined the interplay between insulin use, SDOH, additional covariates, and NMSC among individuals with diabetes. METHODS: We based our analysis on the 2020 Behavioral Risk Factor Surveillance System (BRFSS), a national survey conducted yearly in the US. We performed weighted chi-squared test, logistic regression, and survival analyses on 8685 eligible participants with diabetes enrolled in the BRFSS. RESULTS: Kaplan Meier survival curves showed higher probability of NMSC event-free survival for participants with diabetes using insulin compared to participants with diabetes not using insulin (log-rank test P < .001). Significant associations were detected between insulin use and reduced odds of NMSC (OR .56; 95% CI: .38-.82), and decreased hazard (HR .36; 95% CI: .21-.62), along with indices of SDOH. CONCLUSIONS: Our findings suggest that socioeconomic differences related to the healthcare system and behavioral patterns are linked to discrepancies in the use of insulin and the development of NMSC.

Cyclic AMP-regulatory element-binding protein: a novel UV-targeted transcription factor in skin cancer.

Common therapeutics in relation to melanoma and non-melanoma cancers include the use of kinase inhibitors. The long-term benefits of kinases, however, are limited by development of drug resistance. An alternative approach for treatment would be to focus on transcription factors. Cyclic AMP-regulatory element-binding protein (CREB) is a transcription factor that is commonly overactivated or overexpressed in many different cancers including skin cancer. Ultraviolet radiation (UVR), one of the main causes of skin cancer, can activate CREB in both melanocytes and keratinocytes. In addition, CREB has been found to be activated in skin cancers. Considering the prominent role that CREB plays in skin cancers, the studies reviewed herein raise the possibility of CREB as a potential prognostic and diagnostic marker of skin cancer and a novel target for therapeutic intervention.

Previous radiotherapy increases the efficacy of cemiplimab in the treatment of locally advanced and metastatic cutaneous squamous cell carcinoma: A retrospective analysis.

BACKGROUND: Cemiplimab, a programmed cell death-1 inhibitor approved in 2018 for patients with locally advanced or metastatic cutaneous squamous cell carcinoma (cSCC) who are ineligible for curative therapies, lacks clarity regarding the optimal patient selection despite its known efficacy. OBJECTIVE: This retrospective study aims to assess the real-world treatment patterns and outcomes in patients with cSCC at our institution. METHODS: A retrospective analysis of consecutively treated patients with cemiplimab for cSCC was conducted. Progression-free survival (PFS) and overall survival were evaluated alongside clinical-pathologic characteristics. RESULTS: Forty-five patients were included, of which 73.3% were male with a median age of 77 years. After 18 months of median follow-up median PFS and overall survival were not reached with a mean of 21.3 months ± 2.2 months and 25.3 ± 2.1 months, respectively. Univariate and multivariate analyses revealed significant correlations only between PFS and previous radiotherapy (P values: .043 and .046, respectively). LIMITATIONS: Limitations include its retrospective nature, the low number of patients analyzed, and the potential for inherent biases. CONCLUSIONS: The study reveals a significant association between prior radiotherapy and improved PFS in cemiplimab-treated cSCC, suggesting the potential for combining radiotherapy with cemiplimab. Further exploration of this combined approach is warranted.

Cutaneous squamous cell carcinoma tumor accrual rates in immunosuppressed patients with autoimmune and inflammatory conditions: A retrospective cohort study.

BACKGROUND: Immunosuppression is a known risk factor for the development of cutaneous squamous cell carcinoma (CSCC), especially in solid organ transplant recipients and chronic lymphocytic leukemia. However, this risk is less well defined in autoimmune and inflammatory conditions. OBJECTIVE: Assess the impact that disease-type, duration of immunosuppression, and systemic medications have on CSCC accrual rates, defined as the number of CSCCs a patient develops per year, in autoimmune and inflammatory conditions. METHODS: Retrospective review of 94 immunosuppressed (rheumatoid arthritis: 31[33.0%], inflammatory bowel disease: 17[18.1%], psoriasis: 11[11.7%], autoimmune other (AO): 24[25.5%], inflammatory other: 21[22.3%]) and 188 immunocompetent controls to identify all primary, invasive CSCCs diagnosed from 2010 to 2020. RESULTS: Immunosuppressed patients had higher CSCC accrual rates than immunocompetent controls (0.44 ± 0.36): total cohort (0.82 ± 0.95, P < .01), rheumatoid arthritis (0.88 ± 1.10, P < .01), inflammatory bowel disease (0.94 ± 0.88, P < .01), psoriasis (1.06 ± 1.58, P < .01), AO (0.72 ± 0.56, P < .01), and inflammatory other (0.72 ± 0.61, P < .01). There was an association between increased tumor accrual rates and exposure to systemic medications including, immunomodulators, tumor necrosis factor-alpha inhibitors, non-tumor necrosis factor inhibitor biologics, and corticosteroids, but not with number of systemic medication class exposures or duration of immunosuppression. LIMITATIONS: Retrospective, singlecenter study. CONCLUSION: Patients with autoimmune and inflammatory conditions accrue CSCCs at higher rates than immunocompetent patients.

Keratinocyte carcinomas in survivors of childhood cancer: A report from the childhood cancer survivor study.

BACKGROUND: Childhood cancer survivors (CCS) are at increased risk for keratinocyte carcinomas (KC) however, the long-term incidence of single and multiple KC is not well established. OBJECTIVE: Identify risk factors and quantify KC cumulative incidence and multiple-incidence burden in CCS. METHODS: KC were identified among Childhood Cancer Survivor Study participants, a cohort of 5-year cancer survivors diagnosed <21 years of age between 1970 and 1999 in North America. Cumulative incidence was estimated and multivariable models assessed relative rates of KC associated with survivor and treatment characteristics. RESULTS: Among 25,658 participants, 1446 developed 5363 KC (93.5% basal cell carcinoma, 6.7% squamous cell carcinoma; mean age 37.0 years (range 7.3-67.4), mean latency 25.7 years; 95.3% White and 88.4% with radiotherapy). Mean lesion count was 3.7 with 26.1% experiencing ≥4. Radiotherapy imparted a 4.5-fold increase in the rate of any KC and 9.4-fold increase in the rate of ≥4 KC. Allogeneic and autologous hematopoietic cell transplant were associated with a 3.4- and 2.3-fold increased rate of KC, respectively. LIMITATIONS: Participant self-reporting of some data including race without skin phototype and past medical history may have impacted analysis. CONCLUSIONS: The burden of KC in CCS remains high, but predictable risk factors should guide screening.

Factors associated with residual tumor at time of Mohs micrographic surgery for basal cell and squamous cell carcinomas.

BACKGROUND: Residual tumor is not always clinically apparent following biopsy of cutaneous carcinomas, which may prompt patients to question the need for definitive treatment. OBJECTIVE: We investigated the percentage of cases in which residual tumor was histologically present at the time of Mohs micrographic surgery (MMS) for basal cell carcinomas (BCCs) and squamous cell carcinomas (SCCs) and investigated factors associated with residual tumor. METHODS: We examined 483 MMS cases performed for biopsy-proven BCC (n = 287) and SCC (n = 196) between October 2022 and April 2023. Single-stage MMS specimens were step-sectioned en face to exhaust the block. Univariate and multivariable logistic regression models were created. RESULTS: Residual tumor was identified in 83.3% of BCC and 66.8% of SCC at the time of MMS (P = .01). In patients clinically appearing tumor-free following biopsy, residual histologic tumor was identified in 68.2% of BCC and 41.5% of SCC. Residual tumor was significantly more likely in men (P = .04), high-risk sites (P = .002), smaller biopsy sizes (P = .0003), and larger preoperative sizes (P < .0001). LIMITATIONS: Single center, retrospective cohort. CONCLUSION: The majority of patients with BCC and SCC have residual histologic tumor at the time of MMS, oftentimes even when tumor is not clinically apparent. Multiple factors impact the presence/absence of residual tumor.

Neoadjuvant Immunotherapy in Non-melanoma Skin Cancers of the Head and Neck.

OPINION STATEMENT: Neoadjuvant immunotherapy will change the standard of care for advanced resectable cutaneous squamous cell carcinoma (cSCC) and possibly other non-melanoma skin cancers. With pathological complete response rates around 50% for cSCC in early studies, neoadjuvant therapy allows patients the possibility of significant reduction in tumor size, de-escalation of adjuvant therapy, and improved long-term outcomes. Patients must be carefully selected to ensure that there is a margin of safety with respect to resectability, such that if a tumor progresses on neoadjuvant therapy, there remains a curative surgical option that is acceptable to the patient. The optimal treatment paradigm is an area of active research, with many researchers questioning whether adjuvant therapy, or even local therapy, is necessary in patients who seem to have a complete response. The ability to predict who will respond will become even more critical to answer, as a significant number of patients do not want to risk their disease progressing, especially in cosmetically sensitive areas of the head and neck. Recent studies in melanoma show promise for improved response rates using combination therapies, and these strategies may apply to cSCC as well. The use of LAG-3 inhibitors or mRNA vaccine technology may further improve the utility of neoadjuvant strategies.

Neoadjuvant Photodynamic Therapy: An Updated Therapeutic Approach for Non-Melanoma Skin Cancers.

OPINION STATEMENT: Non-melanoma skin cancers (NMSCs) are the most common malignancy and surgical excision is considered treatment of choice for the majority of cases. However, surgery can be very extensive in cases of large, multiple, or cosmetic-sensitive tumors located on areas such as scalp and face or genital region, leading to significant functional and cosmetic deficit. Aminolaevulinic acid photodynamic therapy (ALA-PDT) has emerged as a widely used approach in a variety of skin diseases, demonstrating remarkable efficacy in treatment of actinic keratosis, Bowen disease and basal cell carcinoma. Besides, when employed as a preoperative intervention, ALA-PDT effectively reduces tumor size and minimizes subsequent local surgical morbidity. With its minimally invasive nature and proven effectiveness, ALA-PDT holds significant promise as a neoadjuvant treatment option for NMSCs. In cases where the tumor is large, invasive, multiple, or located in cosmetically and functionally sensitive areas, or when considering patient factors such as age, comorbidity, willingness to undergo surgery, and post-operative quality-of-life, surgical intervention or radiotherapy alone may be impracticable or unacceptable. In such scenarios, neoadjuvant ALA-PDT can offer remarkable outcomes. In order to further ensure the maximum benefit of patients from neoadjuvant PDT, collaboration with multidisciplinary teams and whole-process management may be in need.

Invasive squamous cell carcinoma within a plaque of circumscribed palmar hypokeratosis.

Circumscribed palmar hypokeratosis (CPH) is a localized disorder of epidermal keratinization that is presented as a well-delimited, depressed, erythematous plaque on the palms or on the soles. It is histopathologically characterized by an abrupt thinning of the corneal epidermal layer. CPH is considered a benign condition, but a few cases with dysplastic changes/carcinoma in situ in the hypokeratotic epidermis have been described. We report hereby a case of invasive squamous cell carcinoma developed within a plaque of CPH. The pathogenesis of the malignant changes in this disorder remains to be clarified. Clinicians should be aware of the potential for developing malignancy in CPH and carry out a closer follow-up of this disorder.

Changes in the Use of Hydrochlorothiazide and Other Antihypertensive Drugs in Switzerland in Association With the Swissmedic Safety Alert Regarding Non-melanoma Skin Cancer: An Interrupted Time-Series Analysis Using Swiss Claims Data.

PURPOSE: Long-term use of hydrochlorothiazide increases the risk of non-melanoma skin cancer. We aimed to evaluate potential changes in the use of hydrochlorothiazide in Switzerland after a direct healthcare professional communication (DHPC) in November 2018 by Swissmedic. METHODS: We performed interrupted time-series analyses using a large Swiss healthcare claims database (2015-2021). Within monthly intervals, we quantified the total number of claims and the total dispensed 'defined daily doses' (DDD) for preparations containing (1) hydrochlorothiazide, (2) angiotensin-converting enzyme (ACE) inhibitors and angiotensin-II-receptor blockers (ARB), (3) calcium-channel blockers (CCB) and (4) thiazide-like diuretics per 10 000 persons. Using segmented linear regression, we quantified the pre-DHPC trend, the immediate change and the post-DHPC change in trend for total claims and DDD for the four drug classes weighted for the demographic distribution of the Swiss population. RESULTS: ACE inhibitors and ARB were the most frequently claimed antihypertensive drugs with 300-400 claims per 10 000 persons, which increased by 5.4% during the study period. The average number of hydrochlorothiazide claims (157/10 000 persons in 2015) declined by 35% between 2015 and 2021. The decrease started prior to the DHPC, but the DHPC was associated with an immediate 6.1% decline and an accelerated decline in claims over time after the DHPC (similar results for DDD). This coincided with a 23% increase in claims of CCB (dihydropyridine type) over 7 years, whereas use of other antihypertensives increased less. CONCLUSION: Our results suggest that the DHPC by Swissmedic in 2018 accelerated a pre-existing decline in the use of hydrochlorothiazide in Switzerland.

Epidemiological and clinical analysis of exposure-related factors in non-melanoma skin cancer: A retrospective cohort study.

BACKGROUND: The incidence of non-melanoma skin cancers (NMSCs) increased over last decades, probably due to environmental concerns or to the increase of frail patients with age related comorbidities. Currently, the relationship of increasing global skin cancer rates with increased ultraviolet radiations (UVRs) resulting from stratospheric ozone depletion, global warming, and air pollution from fossil-fuel combustion. AIMS: We conducted a retrospective epidemiological study including 546 NMSC patients managed at the Dermatology Unit of the Tor Vergata Hospital to highlight different trends of sun exposure or different comorbidities. METHODS: Descriptive and inferential statistical analyses were performed to evidence differences between continous variable and Spearman rank test for dicotomical variables. Charlson Comorbidity Index was calculated to obtain the 10-years survival rate in order to identify the mean comorbidity burden of our patients. RESULTS: Considering patients with comorbidities (73.81%), actinic keratoses (AKs) was the most frequent lesion. In patients with a history of previous melanoma, basal cell carcinoma (BCC) was predominant (ANOVA test, p < 0.05) with a statistically significant correlation (rho = 0.453; p < 0.01). Squamous cell carcinoma (SCC) showed a higher rate in arterial hypertension patients, followed by the chronic heart failure and hematologic neoplasms (60%, 29.7% and 32.1%, respectively) groups. Men were more affected than women, representing 61.54% of patients. Chronic sun exposure is directly correlated with SCC rho = 0.561; p < 0.01), whereas BCC correlated with a history of sunburns (rho = 0.312; p < 0.05). CONCLUSIONS: History of photo-exposition had an important role on NMSC development especially for work or recreational reasons. Sex, age, and presence of comorbidities influenced different NMSC types. BCC was more frequent in younger patients, associated with melanoma and sunburns. The presence of SCC is associated with older patients and the hypertension group. AKs were diagnosed predominantly in oldest men, with a chronic sun-exposure history, and hematologic neoplasms group.

Clinician's Ability to Identify Non-Melanoma Skin Cancer on 3D-Total Body Photography Sectors that Were Initially Identified during In-Person Skin Examination with Dermoscopy.

INTRODUCTION: Non-melanoma skin cancer (NMSC) is a cause of significant morbidity and mortality in high-risk individuals. Total body photography (TBP) is currently used to monitor melanocytic lesions in patients with high risk for melanoma. The authors examined if three-dimensional (3D)-TBP could be useful for diagnosis of NMSC. METHODS: Patients (n = 129; 52 female, 77 male) with lesions suspicious for NMSC who had not yet had a biopsy underwent clinical examination followed by examination of each lesion with 3D-TBP Vectra®WB360 (Canfield Scientific, Parsippany, NJ, USA) and dermoscopy. RESULTS: The 129 patients had a total of 182 lesions. Histological examination was performed for 158 lesions; the diagnoses included basal cell carcinoma (BCC; n = 107), squamous cell carcinoma (SCC; n = 27), in-situ SCC (n = 15). Lesions were located in the head/neck region (n = 138), trunk (n = 21), and limbs (n = 23). Of the 182 lesions examined, 12 were not visible on 3D-TBP; reasons for not being visible included location under hair and on septal of nose. Two lesions appeared only as erythema in 3D-TBP but were clearly identifiable on conventional photographs. Sensitivity of 3D-TBP was lower than that of dermoscopy for BCC (73% vs. 79%, p = 0.327), higher for SCC (81% vs. 74%, p = 0.727), and lower for in-situ SCC (0% vs. 33%, p = 125). Specificity of 3D-TBP was lower than that of dermoscopy for BCC (77% vs. 82%, 0.581), lower for SCC (75% vs. 84%, p = 0.063), and higher for in-situ SCC (97% vs. 94%, p = 0.344). Diagnostic accuracy of 3D-TBP was lower than that of dermoscopy for BCC (75% vs. 80%), lower for SCC (76% vs. 82%), and lower for in-situ SCC (88% vs. 89%). Lesion location was not associated with diagnostic confidence in dermoscopy (p = 0.152) or 3D-TBP (p = 0.353). If only lesions with high confidence were included in the calculation, diagnostic accuracy increased for BCC (n = 27; sensitivity 85%, specificity 85%, diagnostic accuracy 85%), SCC (n = 10; sensitivity 90%, specificity 80%, diagnostic accuracy 83%), and for in-situ SCC (n = 2; sensitivity 0%, specificity 100%, diagnostic accuracy 95%). CONCLUSION: Diagnostic accuracy appears to be slightly lower for 3D-TBP in comparison to dermoscopy. However, there is no statistically significant difference in the sensitivity and specificity of 3D-TBP and dermoscopy for NMSC. Diagnostic accuracy increases, if only lesions with high confidence are included in the calculation. Further studies are necessary to determine if 3D-TBP can improve management of NMSC.

High Risk of Non-Melanoma Skin Cancer in Actinic Keratosis Patients with Skin of Color: A Nationwide Register-Based Cohort Study.

INTRODUCTION: Actinic keratoses (AKs) are rough, scaly patches from UV exposure, increasing the risk of non-melanoma skin cancer (NMSC). This study examines AK incidence in Korea and its role as a risk factor for NMSC. METHODS: A retrospective nationwide register-based cohort study analyzed 2,917 AK patients and 14,585 controls from 2002 to 2019. Patients diagnosed with AK were followed until NMSC occurrence, death, emigration, or December 2019. RESULTS: AK incidence reached 44.8 per 100,000 person-years in 2019. The adjusted hazard ratio for NMSC in AK patients was 8.91 (95% confidence interval, 5.72-13.90). Higher NMSC risk was observed in female AK patients, those under 60 years, and those with lower income levels. The 16-year cumulative incidence of NMSC was 4.19% in AK patients versus 0.44% in controls. CONCLUSION: AK significantly increases the risk of NMSC in Koreans, highlighting the need for tailored surveillance and treatment strategies.

Transmission of Genetic Material and Malignant Cells of Cutaneous Origin via Surgical Sutures.

BACKGROUND: Seeding of skin cancer cells following diagnostic or therapeutic surgical procedures can occur and might cause local recurrences. As current preferred therapy for skin malignancy is surgical excision, seeding of tumour cells by manipulating malignant tissue or suturing can be another factor leading to recurrences. OBJECTIVE: To evaluate whether genetic material and malignant cells adhere to standard suture materials. METHODS: This prospective study included patients who underwent excision of skin lesions. Monofilament and braided sutures were examined. Sutures were passed through the observed tumour or healthy skin margins and were examined for DNA material and cells by cytological analysis, cell culture and characterization, and DNA analysis. RESULTS: Twenty-two patients and 148 sutures were included. DNA quantification showed DNA material on all sutures, with no significant difference between braided and monofilament sutures. Cytological analysis showed that all slides prepared from cell blocks contained normal squamous and atypical cells. Cell culture and characterization showed viable cells adhering to the sutures under direct light microscopy. Cell cultures showed rapid proliferation of epithelial cells from squamous cell carcinoma specimens. CONCLUSION: Suture materials carry DNA material and cells, including malignant cells of cutaneous origin and may seed them at distant sites.

Incidence of Nonmelanoma Skin Cancers in Alberta, Canada, From 2007 to 2018.

BACKGROUND: Nonmelanoma skin cancer (NMSC) is the most common malignancy affecting Caucasian populations and has been seeing steady increases in incidence globally for decades. Our previous study (from Alberta, Canada) had shown a plateau in the incidence rates for NMSC. This contrasts with data from other regions within Canada and throughout the world that indicated a continued increase in incidence rates of NMSCs. OBJECTIVES: The objective of this study was to provide an update on the trends in incidence of NMSC in Alberta, Canada, from 2007 to 2018. METHODS: A retrospective analysis of patients from Alberta diagnosed with NMSC from 2007 to 2018 inclusive was conducted with data retrieved from Alberta Cancer Registry. Sex-, age-, anatomical location-, NMSC subtype-, stage-specific incidence rates and trends were examined. RESULTS: From 2007 to 2018, overall incidence rates of NMSC increased by 36%. Invasive squamous cell carcinoma (SCC) and in situ SCC demonstrated the most significant increase, invasive SCC [annual percentage change (APC) 3.48, P = .014] and in situ SCC (APC 5.61, P = .0001). In addition, we were able to determine that females had the most significant increases in NMSC incidence rates from 2007 to 2018 particularly invasive SCC (APC 3.03, P = <.0001) and in situ SCC (APC 5.08, P = <.0001). CONCLUSIONS: After initial levelling of NMSC incidence in Alberta in the early part of 21st century, the incidence of NMSC continues to increase over the past decade. The reasons for this change are not clear and likely multifactorial.

Fragile hands: targeting nonmelanoma skin cancer on older hands using 595 nm pulsed dye laser.

PURPOSE: The mainstay of treatment for nonmelanoma skin cancer (NMSC) on thin skin remains surgical, but procedures on older hands may be complicated by skin fragility and dermal atrophy. Used without cooling, 595 nm (nm) pulsed dye laser (PDL) has the capability of destroying NMSC through nonspecific thermal necrosis. The purpose of this study was to understand recurrence of NMSC on dorsal hands of older patients after one or two treatments using 595 nm PDL. METHODS: A retrospective chart review identified 147 cases of NMSC located on the dorsal hands treated with 595 nm PDL. Cases of basal cell carcinomas (BCCs) and squamous cell carcinomas (SCCs) were included. All patients received one to two treatments with PDL. The primary outcome was the recurrence of carcinoma. RESULTS: Among NMSC cases treated with PDL, recurrence occurred in 12 patients (8.2%). No cases of BCC recurred during the study period. Recurrence of SCC was 4.7% for SCC in situ and 10.4% recurrence for invasive SCC (p = 0.34). Among 71 patients treated once, recurrence occurred in 10 patients (14.1%), and among 76 cases treated twice, recurrence occurred in 2 patients (2.6%, p = 0.01). CONCLUSION: Two treatments of PDL for NMSC on the dorsal hands of older patients was well tolerated, had low recurrence, and seemed more effective than one treatment.

Mohs micrographic technique in high-risk basal cell carcinoma: a 3D prediction of safety margins.

OBJECTIVE: Compared with standard excision with a two-dimensional histological examination, Mohs micrographic surgery offers a lower recurrence rate and a greater extent of healthy tissue sparing for the treatment of high-risk basal cell carcinoma (BCC). The aims of this study were to first quantify the healthy tissue spared through the micrographic technique compared to traditional surgery for high-risk tumours. Then, to speculate, through the analysis of the distal micrographic resection margin, the adequate width of safety margins for standard excision. METHOD: A cohort of patients with high-risk BCC was treated with Mohs surgery. Safety margins, tumours residual final breach and hypothetical standard excision safety margins areas were recorded. RESULTS: A total of 96 patients were included. A reduction of 27.96% (95% Confidence Interval (CI): 17.90-38.02) of healthy skin removed was observed using a micrographic method compared to the standard approach. Standard excision with a 6mm safety margin was associated with 86.46% (95% CI: 79.62-93.30) of complete excision. Greater margins were not associated with a statistically significant improvement of complete excision. CONCLUSION: Mohs surgery should be considered the gold standard operative treatment for high-risk BCC. However, if micrographic techniques are not feasible, the standard excision with a predetermined margin of 6 mm, should be considered as the best option.

The Anticancer Activities of Natural Terpenoids That Inhibit Both Melanoma and Non-Melanoma Skin Cancers.

The prevalence of two major types of skin cancer, melanoma and non-melanoma skin cancer, has been increasing worldwide. Skin cancer incidence is estimated to rise continuously over the next 20 years due to ozone depletion and an increased life expectancy. Chemotherapeutic agents could affect healthy cells, and thus may be toxic to them and cause numerous side effects or drug resistance. Phytochemicals that are naturally occurring in fruits, plants, and herbs are known to possess various bioactive properties, including anticancer properties. Although the effects of phytochemicals are relatively milder than chemotherapeutic agents, the long-term intake of phytochemicals may be effective and safe in preventing tumor development in humans. Diverse phytochemicals have shown anti-tumorigenic activities for either melanoma or non-melanoma skin cancer. In this review, we focused on summarizing recent research findings of the natural and dietary terpenoids (eucalyptol, eugenol, geraniol, linalool, and ursolic acid) that have anticancer activities for both melanoma and non-melanoma skin cancers. These terpenoids may be helpful to protect skin collectively to prevent tumorigenesis of both melanoma and nonmelanoma skin cancers.

Micro RNA Dysregulation in Keratinocyte Carcinomas: Clinical Evidence, Functional Impact, and Future Directions.

The keratinocyte carcinomas, basal cell carcinoma (BCC), and cutaneous squamous cell carcinoma (cSCC), are the most common cancers in humans. Recently, an increasing body of literature has investigated the role of miRNAs in keratinocyte carcinoma pathogenesis, progression and their use as therapeutic agents and targets, or biomarkers. However, there is very little consistency in the literature regarding the identity of and/or role of individual miRNAs in cSCC (and to a lesser extent BCC) biology. miRNA analyses that combine clinical evidence with experimental elucidation of targets and functional impact provide far more compelling evidence than studies purely based on clinical findings or bioinformatic analyses. In this study, we review the clinical evidence associated with miRNA dysregulation in KCs, assessing the quality of validation evidence provided, identify gaps, and provide recommendations for future studies based on relevant studies that investigated miRNA levels in human cSCC and BCC. Furthermore, we demonstrate how miRNAs contribute to the regulation of a diverse network of cellular functions, and that large-scale changes in tumor cell biology can be attributed to miRNA dysregulation. We highlight the need for further studies investigating the role of miRNAs as communicators between different cell types in the tumor microenvironment. Finally, we explore the clinical benefits of miRNAs as biomarkers of keratinocyte carcinoma prognosis and treatment.

Grover's Disease Association with Cutaneous Keratinocyte Cancers: More than a Coincidence?

Better mechanistic understanding of desmosome disruption and acantholysis in Grover's disease (GD) may improve management of this disease. Recent molecular studies highlighted promising pathways to be explored by directly comparing GD and selected features of associated skin diseases. The association between GD and cutaneous keratinocyte carcinomas, the most prevalent non-melanoma skin cancers (NMSC), is not completely characterized. To review the medical literature regarding GD-associated cutaneous keratinocyte cancers, focusing on molecular features, pathophysiological mechanisms, and disease associations, to help guide future research and patient management. GD has been associated with a variety of skin conditions, but its association with skin cancers has been rarely reported. Between 1983 and 2024, only nine scientific papers presented data supporting this association. Interestingly, we found that GD may mimic multiple NMSCs, as few authors reported GD cases misdiagnosed as multiple cutaneous squamous cell carcinomas for more than 4 years or the presence of superficial basal cell carcinoma-like areas associated with focal acantholysis. In conclusion: (a) GD may be an imitator of multiple NMSCs, and (b) the relationship between GD and NMSCs may reveal promising pathways for the mechanistic understanding of desmosome disruption and acantholysis in GD and may even lead to its reclassification as a distinctive syndrome.