Influence of Anatomic Locations of T1b Melanomas and Patient Age on Outcomes.

BACKGROUND: There are no guidelines on when to more strongly recommend sentinel lymph node biopsy (SLNB) for T1b melanomas. OBJECTIVE: To examine whether anatomic locations of T1b melanomas and patient age influence metastases. METHODS: We conducted a retrospective study using data from two hospitals in Los Angeles County from January 2010 through January 2020. RESULTS: Out of 620 patients with primary melanomas, 566 melanomas were staged based on the American Joint Committee on Cancer 8th edition melanoma staging. Forty-one were T1b, of which 13 were located on the face/ear/scalp and 28 were located elsewhere. T1b melanomas located on the face/ear/scalp had an increased risk of lymph node or distant metastasis compared with other anatomic sites (31% vs 3.6%, P=0.028). For all melanomas, the risk of lymph node or distant metastasis decreased with age of 64 years or greater (P<0.001 and P=0.034). For T1b melanomas, the risk of distant metastasis increased with increasing age (P=0.047). LIMITATIONS: Data were from a single county.  Conclusion: T1b melanomas of the face/ear/scalp demonstrated a higher risk of lymph node or distant metastasis and may help guide the recommendation of SLNB, imaging, and surveillance. Younger patients may be more strongly considered for SLNB and older patients with T1b melanomas may warrant imaging.  J Drugs Dermatol. 2024;23(5):306-310. doi:10.36849/JDD.7667.

The Use of Natural Therapies in Patients With Skin Cancer: A Scoping Review.

Complementary and alternative medicine (CAM) use has become a field of growing interest in dermatology. However, the prevalence of CAM use is difficult to quantify as it varies based on many factors. Given the exploratory nature of the topic, a scoping review was conducted to identify studies that quantify biologically based CAM use in skin cancer patients. A comprehensive search of Embase, PubMed, and Web of Science databases from inception to August 28th, 2023, was performed. A total of 3,150 articles were identified through the database search. After article screening, 6 studies were suitable for inclusion in this review. Articles included were all questionnaire, survey, or interview style. Biologically based CAM use is prevalent in skin cancer patients. It can be associated with many factors such as location, stage of cancer, and age. CAM use can interact with conventional therapy; therefore, physicians should employ a culturally competent approach to inquiring about CAM use in order to improve patient outcomes and identify patterns and predictors of use.J Drugs Dermatol. 2024;23(5):322-326. doi:10.36849/JDD.8077.

Metastatic Merkel Cell Carcinoma After Simultaneous Pancreas-Kidney Transplantation: Fatal Outcomes.

Merkel cell carcinoma (MCC) is a rare, highly aggressive cutaneous malignancy. Immunosuppression increases the risk of MCC and is associated with poor prognosis. Organ transplant recipients (OTR) have worse overall survival (OS) than patients with immunosuppression due to other causes. Treating MCC after organ transplantation is challenging, as checkpoint inhibitor immunotherapy, the standard of care for treating MCC, increases the risk of transplant rejection. This paper reviews the cases of two simultaneous pancreas-kidney transplant (SPKT) recipients with MCC and explores the role of immunosuppression in the development of MCC. Immunosuppression was discontinued and checkpoint inhibitor therapy was initiated in the first patient and considered by the second patient. In both cases, treatment failed, and the patients died shortly after developing metastatic MCC. These cases illustrate the need for improved multidisciplinary treatment regimens for MCC in OTRs. J Drugs Dermatol. 2024;23(5):376-377.     doi:10.36849/JDD.8234  .

The Representation of Skin Tones in Google Images of Skin Cancers.

Skin self-examinations play a vital role in skin cancer detection and are often aided by online resources. Available reference photos must display the full spectrum of skin tones so patients may visualize how skin lesions can appear. This study investigated the portrayal of skin tones in skin cancer-related Google Images, discovering a significant underrepresentation of darker skin tones. J Drugs Dermatol. 2024;23(5):e132-e133.     doi:10.36849/JDD.7886e.

High-throughput lipidomic profiles sampled with electroporation-based biopsy differentiate healthy skin, cutaneous squamous cell carcinoma, and basal cell carcinoma.

BACKGROUND: The incidence rates of cutaneous squamous cell carcinoma (cSCC) and basal cell carcinoma (BCC) skin cancers are rising, while the current diagnostic process is time-consuming. We describe the development of a novel approach to high-throughput sampling of tissue lipids using electroporation-based biopsy, termed e-biopsy. We report on the ability of the e-biopsy technique to harvest large amounts of lipids from human skin samples. MATERIALS AND METHODS: Here, 168 lipids were reliably identified from 12 patients providing a total of 13 samples. The extracted lipids were profiled with ultra-performance liquid chromatography and tandem mass spectrometry (UPLC-MS-MS) providing cSCC, BCC, and healthy skin lipidomic profiles. RESULTS: Comparative analysis identified 27 differentially expressed lipids (p < 0.05). The general profile trend is low diglycerides in both cSCC and BCC, high phospholipids in BCC, and high lyso-phospholipids in cSCC compared to healthy skin tissue samples. CONCLUSION: The results contribute to the growing body of knowledge that can potentially lead to novel insights into these skin cancers and demonstrate the potential of the e-biopsy technique for the analysis of lipidomic profiles of human skin tissues.

Long-term survival after anti-PD-1 discontinuation in advanced cutaneous squamous cell carcinoma (cSCC): a proof of concept of benefit of concomitant cemiplimab and radiotherapy.

BACKGROUND: In a princeps study we conducted in patients with advanced cutaneous squamous cell carcinoma treated with concomitant anti-Programmed cell death protein 1 (PD-1) and radiotherapy, we demonstrated a clinico radiological response to cemiplimab that appeared to persist over time, 1 year after treatment discontinuation. METHOD: We conducted a single-center descriptive study at Caen Hospital from September 1, 2021 to September 2023, in 14 patients with advanced carcinoma treated with cemiplimab until September 1, 2021. The aim of this update is to examine clinical and radiological follow-up 2 years after discontinuation of cemiplimab. RESULTS: Of the 12 patients with a partial or complete response, we report 8 (66.7%) persistent responses 2 years after stopping cemiplimab, with only 2 patients progressing to distant disease, one lost to follow-up, and one death a priori unrelated to the disease. CONCLUSION: Our study confirms a long-term and persistent effect despite discontinuation of cemiplimab at least up to 2 years later.

Clinical outcomes of adjuvant nivolumab in resected stage III melanoma: comparison of CheckMate 238 trial and real-world data.

OBJECTIVES: Nivolumab is approved as adjuvant therapy for resected stage III/IV melanoma based on the phase 3 CheckMate 238 trial. This analysis compared outcomes from CheckMate 238 with those from the real-world Flatiron Health electronic health record-derived de-identified database in patients with resected stage III melanoma (per AJCC-8) treated with adjuvant nivolumab. MATERIALS: Outcomes included baseline characteristics, overall survival (OS) in the CheckMate 238 cohort (randomization until death or last known alive), and real-world overall survival (rwOS) in the Flatiron Health cohort (nivolumab initiation until death or data cutoff). rwOS was compared with OS using unadjusted and adjusted Cox proportional hazards models. Inverse probability of treatment weighting (IPTW) was combined with the adjusted model to reduce baseline discrepancies. RESULTS: The CheckMate 238 and real-world cohorts included 369 and 452 patients, respectively (median age, 56.0 and 63.0 years; median follow-up, 61.4 vs. 25.5 months). rwOS was not different from OS in the unadjusted (hazard ratio [HR] 1.27; 95% CI 0.92-1.74), adjusted (HR 1.01; 95% CI 0.67-1.54), and adjusted IPTW (HR 1.07; 95% CI 0.70-1.63) analyses. In the adjusted analysis, 2-year OS and rwOS rates were 84%. Median OS and rwOS were not reached. After IPTW, OS and rwOS were not different (HR 1.07; 95% CI 0.70-1.64). CONCLUSIONS: In this comparative analysis, OS in the CheckMate 238 trial was similar to rwOS in the Flatiron Health database after adjustments in patients with resected stage III melanoma (per AJCC-8) treated with adjuvant nivolumab, validating the trial results.

[Clinical characteristics and research progress of ocular Merkel cell carcinoma].

Merkel cell carcinoma (MCC) is a rare, aggressive epithelial and neuroendocrine tumor. MCC typically presents as painless nodules or patches rapidly growing in sun-exposed skin areas. Ocular MCC accounts for approximately 2.5% of all cases and may be misdiagnosed as granuloma or basal cell carcinoma. Risk factors for development include advanced age, ultraviolet exposure, male gender, immunosuppression, and Merkel cell polyomavirus infection. Treatment involves wide local excision with adjuvant radiotherapy, chemotherapy is typically reserved for metastatic disease, and immunotherapy and targeted therapy are currently under investigation showing promising early outcomes. This article summarizes the clinical characteristics and research progress of ocular MCC.

Automated Prediction of Malignant Melanoma using Two-Stage Convolutional Neural Network.

PURPOSE: A skin lesion refers to an area of the skin that exhibits anomalous growth or distinctive visual characteristics compared to the surrounding skin. Benign skin lesions are noncancerous and generally pose no threat. These irregular skin growths can vary in appearance. On the other hand, malignant skin lesions correspond to skin cancer, which happens to be the most prevalent form of cancer in the United States. Skin cancer involves the unusual proliferation of skin cells anywhere on the body. The conventional method for detecting skin cancer is relatively more painful. METHODS: This work involves the automated prediction of skin cancer and its types using two stage Convolutional Neural Network (CNN). The first stage of CNN extracts low level features and second stage extracts high level features. Feature selection is done using these two CNN and ABCD (Asymmetry, Border irregularity, Colour variation, and Diameter) technique. The features extracted from the two CNNs are fused with ABCD features and fed into classifiers for the final prediction. The classifiers employed in this work include ensemble learning methods such as gradient boosting and XG boost, as well as machine learning classifiers like decision trees and logistic regression. This methodology is evaluated using the International Skin Imaging Collaboration (ISIC) 2018 and 2019 dataset. RESULTS: As a result, the first stage CNN which is used for creation of new dataset achieved an accuracy of 97.92%. Second stage CNN which is used for feature selection achieved an accuracy of 98.86%. Classification results are obtained for both with and without fusion of features. CONCLUSION: Therefore, two stage prediction model achieved better results with feature fusion.

Skin cancer-associated genodermatoses in skin of color patients: a review.

Skin cancers are associated with a large number of genodermatoses. Existing knowledge and guidelines on the presentations of these genodermatoses focus disproportionately on White patients. Our goal is to identify notable characteristics in location, frequency, and severity of cutaneous findings along with the median age of skin cancers in skin-of-color (SOC) patients with skin-cancer-associated genodermatoses to improve diagnosis rates. We searched for genodermatoses on six databases. Each case report or case series was reviewed, including reports, published in English, containing adult patient descriptions. Duplicate manuscripts were removed using EndNote. The following case-level data were collected from the manuscripts: age, gender, patient country or region of origin, author country/continent of residence, skin cancer-related, and other key dermatologic features. 381 published articles, with a total of 578 SOC patients, met criteria for inclusion. SOC patients can present with fewer classic findings, such as a lower incidence of basal cell carcinomas (44%) in SOC Gorlin syndrome patients than palmar pits (66%) and mandibular cysts (66%). Differences between SOC populations were also noted, such as leukoplakia being more common in Asian dyskeratosis congenita patients (80%) in comparison to African dyskeratosis congenita patients (44%). SOC patients also have varying onset of skin cancer depending on the genodermatosis, from a median of 25 years of age in Rothmund-Thomson syndrome to 53 in Muir-Torre syndrome. In this review, SOC patients with genodermatoses can have varying presentations. Being cognizant of these characteristics may lead to earlier diagnosis and interventions to mitigate skin-cancer-related morbidity in SOC patients.

Joinpoint regression analysis of recent trends in desmoplastic malignant melanoma incidence and mortality: 15-year multicentre retrospective study.

BACKGROUND: Recent data reveal a marked rise in the detection and mortality rates of Desmoplastic Malignant Melanoma (DMM). This trend underscores the imperative for an in-depth analysis of DMM's epidemiology, which is crucial for the formulation of precise medical and public health strategies. This investigation seeks to elucidate the variations in the incidence and mortality of DMM over a 15-year period (2005-2019). METHODS: Data on DMM patients was sourced from the Surveillance, Epidemiology, and End Results (SEER) database. Both incidence and incidence-based mortality rates (IBM) were directly extracted from the SEER database. Joinpoint regression was used to analyze and calculate the average annual percent change (AAPC) and its 95% confidence interval (CI). RESULTS: Between 2005 and 2019, 3,384 DMM cases were identified, boasting an age-adjusted incidence rate of 36.3 cases per 1000,000 person-years (95% CI 3.51-3.76) and an IBM of 1.65cases per 1000,000 person-years (95% CI 1.57-1.74). Of these, 2,353 were males (69.53%) and 1,031 were females (30.47%). There were 1894 patients (55.97%) who were over 70 years old. Predominantly, DMM lesions manifested in exposed areas: Limbs (955, 28.22%), Face (906, 26.77%), and Scalp and Neck (865, 25.56%). The incidence of DMM increased significantly at a rate of APC = 0.9% during 2005-2019, while the incidence-based mortality showed a significant upward trend (APC = 7%) during 2005-2012, and slowly increasing trend (APC = 0.6%) during 2012-2019. In contrast to the modest upward trajectory in female incidence and mortality, male incidence initially surged, later declining, while male mortality peaked and stabilized post-2012. The primary sites for incidence and mortality were chronically sun-exposed areas: Face, Scalp and Neck, and Limbs. CONCLUSIONS: In recent years, the incidence and incidence-based mortality of DMM have significantly increased. Each subgroup analysis has different trends, and these trends can provide better support for our exploration of DMM.

(NDMA) METFORMIN AND (NTTP) SITAGLIPTIN INDUCED CUTANEOUS MELANOMAS: LINKS TO NITROSOGENESIS, NITROSO-PHOTOCARCINOGENESIS, ONCOPHARMACOGENESIS AND THE METABOLIC REPROGRAMMING.

Changing the vision, understanding, interpretation and analysis of certain data or scientific dilemmas is what is able to change the status quo and revitalize a mission, an impulse or important thoughts, thus creating the conditions for it to increase immensely the chances of bringing it to success. Or, following Albert Einstein's postulate: ˝We cannot solve our problems with the same thinking we used when we created them˝, we should think: ˝Where does the road to success start? How do we solve or neutralize a problem? ˝ And the answer is: ˝ By taking a consistent and systematic approach, analyzing each component! And we eliminate every possibility of negative influence.˝ These thoughts apply with full force to cancer rates in general, but also to melanoma rates in particular: the murderous tempo of globalization and modernization in medicine has not yet led to the desired decrease in these rates; on the contrary, they are rising headlong and remain largely unpredictable and difficult to regulate. The conclusion is that a solution should be sought by refracting light through another prism: that of Nitrosogenesis and Pharmaco-Oncogenesis. A step-by-step and systematic approach to solving a problem requires patience, determination, and perseverance. As this perseverance is needed mainly to overcome the general ignorance, neglect, disinterest, uneducation and uncertainty of others, rather than doubt in one's own thesis, analysis, and the need for an active approach. Careful analysis of concepts such as ˝Drug Mediated Nitrosogenesis˝ and ˝Onco-pharmacogenesis/Pharmaco-oncogenesis˝ of skin cancer would certainly contribute to the elucidation of skin carcinogenesis in the context of polymedication of the contamination and polymorbidity worldwide. The FDA has already in 2019 taken this much needed first step of universal awareness and its ˝arm˝ has been taken seriously and responsibly solely by dermatologists and dermatosurgeons. It was this guild and only this guild that launched its independent, never-ending observations, logically grounded (hypo)theses, remaining to date confirmatory, unshakable, and enigmatic regarding the unit: intake of potentially contaminated medication and subsequent development of melanomas. It is this and only this branch of the medical guild that has also become the guarantor of safety and objectivity in science, and thus of safety in the fight for survival of a huge number of skin cancer patients. Contaminated oral antidiabetic drugs in the face of Metformin and Sitagliptin do not make an exception in this respect. Similarly to cutaneous melanomas occurring (and published in the scientific literature) after combined intake (or monomedication) of/ between ranitidine, valsartan, olmesartan, candesartan, telmisartan, irbesartan, losartan, enalapril, lisinopril, perindopril, hydrochlorothiazide, nifedipine, amlodipine, propafenone, bisoprolol, nebivolol, melitracen and a number of others, we inform about another rare but not unexpected clinical observation: occurrence of cutaneous melanomas after taking another class of drugs- oral antidiabetic ones. Or after the intake of nitrosamine-contaminated antidiabetic drugs. And whether this contamination is "real or potential" is left to regulators and manufacturers to decide. We accept it as `real-potential' or `potentially-real' because of the fact that neither the regulators nor the manufacturers know what it is or whether it is there or how it arose. The data shared in patients one and two in the presented scientific work are confirmatory in relation to the potential pathogenetic action of nitrosamine contaminated drugs such as 1) bisoprolol/ nebivolol/ candesartan/ hydrochlorothiazide and amlodipine, as well as 2) furosemide in the direction of cutaneous melanoma. Patient 3 in fact also represents the first formally described patient with subsequent melanoma development worldwide, having developed it following intake of potentially/actually nitrosamine-contaminated metformin and metformin/sitagliptin (both drugs are themed in the FDA's Potentially Contaminated Drug Bulletin: 1) metformin, multiple times between 2020-21, due to its contamination with NDMA and 2) sitagliptin, as of September 2022, due to its contamination with NTTP). It should not be seen as surprising to anyone that the intake of relatively similar carcinogens/nitrosamines or NDSRIs, but as an unofficial component of heterogeneous drugs, produces a relatively monomorphic clinical picture- that of cutaneous melanoma. Or to put it metaphorically: ˝The wolf changes its hair, but not its mood˝. A carcinogen remains a carcinogen, regardless of whether it is ingested in a lemonade, a tablet, a sandwich, or a bonbon. Similarly to the intake of nitrosamines in food. Future studies should address the important tasks/dilemmas to elucidate 1) the phototoxic/photocarcinogenic effect of unmetabolized nitrosamines identified in drug formulations; 2) the phototoxic/photocarcinogenic effect of DNA adducts generated after their metabolization, and 3) the availability of specific DNA adducts in lesional/tumor tissue and blood of patients after ingestion of nitroso-containing drug formulations. This level of evidence is likely to lead to a reconsideration of the arguments for the introduction of permanent elimination regimes for nitrosamines in medicines. Metabolic reprogramming (and its relationship to UVB radiation) due to the availability of nitrosamines in cigarette smoke is also currently a proven reality. Based on the available clinicopathological correlations, we believe that nitrosamines in drugs have a similar effect and are part of the key pathway activating skin carcinogenesis under the influence of solar radiation. Intake of contaminated medication is associated with skin cancer generation and progression. It is up to regulators and manufacturers to justify the merits and benefits of the self-imposed presence of carcinogens in drugs or the benefits of such drugs. Apart from the "cancer-generating benefit", of course, which is already widely known. And let us not forget that: "A lie stops being a lie and becomes a truth the moment it is officially refuted".

Good clinical response to cemiplimab in a young patient with locally advanced cutaneous squamous cell carcinoma on preexisting recessive dystrophic epidermolysis bullosa.

Recessive dystrophic epidermolysis bullosa (RDEB) is a rare genetic skin disease caused by mutations in the type VII collagen gene (COL7A1; 3p21.31). Mutations in this gene lead to an alteration in function or reduced amounts of collagen VII. This alteration of collagen VII leads to skin fragility and lesions at minor injuries with difficult healing. Cutaneous squamous cell carcinoma (cSCC) is more frequent in patients with RDEB than in the general population because of chronic wound formation; it constitutes a major cause of morbidity and is often cited as a cause of death for these patients. There is little experience with the treatment of cSCC in patients with RDEB. We report the case of a 19-year-old female patient with RDBE and inoperable locally advanced cSCC of the left arm. Because of the lack of therapy options, therapy with cemiplimab was started at a dose of 350 mg administered intravenously every 3 weeks. A confirmed clinical response was observed after the second cycle of treatment with no toxicity. During follow-up, the patient had a notable clinical response with no auto-immune adverse reactions. This shows that cemiplimab has a good safety profile for cSCC in patients with RDEB and is a valuable therapy option.

Observation of lymphadenopathy, systemic symptoms, and treatment in suspected indolent cutaneous B-cell lymphomas.

BACKGROUND: Following the initial diagnosis of a marginal zone or follicle center lymphoma on skin biopsy, patients undergo staging to determine the extent of disease. OBJECTIVE: We sought to characterize the frequency that these patients were found to have a systemic nodal disease upon work-up as well as the impact of imaging on disease management. METHODS: We conducted a retrospective chart review of patients presenting with a working diagnosis of PCMZL or PCFCL treated at The Ohio State University from 1990 to 2022. Data collected included: patient history, progress notes, virtual encounters, laboratory results, presentation features, imaging, and pathology. Biomarkers included ANA, SSA/SSB, BCL6 and H. Pylori labs, bone marrow biopsies, positive imaging, and need of systemic medication and mortality. RESULTS: 71 patients with suspected PCMZL and PCFCL were identified. 66 of 71 patients underwent imaging. Of this group, 12 patients (9 with suspected PCFCL and 3 with suspected PCMZL) demonstrated lymphadenopathy on imaging. Of these 12 patients, 5 underwent biopsy of suspected lymph nodes, and 3 had biopsy-proven nodal involvement and received systemic therapy. Of the remaining 7 patients with evidence of lymphadenopathy on imaging, 4 were thought to have reactive lymph nodes, and 3 were treated empirically with systemic chemotherapy due to the extent or progression of their disease. Of patients with imaging negative for lymphadenopathy, 3 of 52 (5.8%) patients with received systemic treatment, while 49 of 52 patients (94.2%) received localized treatment. LIMITATIONS: Most of the relationships between this data were correlational and patients selected for this study were limited to a single institution. CONCLUSION: Prospective study of the role of imaging without subsequent lymph biopsy to direct treatment decisions is warranted.

Signatures of epigenetic, biological and mitotic age acceleration and telomere shortening are associated with arsenic-induced skin lesions.

Chronic arsenic exposure is a global health hazard significantly associated with the development of deleterious cutaneous changes and increased keratinocyte cancer risk. Although arsenic exposure is associated with broad-scale cellular and molecular changes, gaps exist in understanding how these changes impact the skin and facilitate malignant transformation. Recently developed epigenetic "clocks" can accurately predict chronological, biological and mitotic age, as well as telomere length, on the basis of tissue DNA methylation state. Deviations of predicted from expected age (epigenetic age dysregulation) have been associated with numerous complex diseases, increased all-cause mortality and higher cancer risk. We investigated the ability of these algorithms to detect molecular changes associated with chronic arsenic exposure in the context of associated skin lesions. To accomplish this, we utilized a multi-algorithmic approach incorporating seven "clocks" (Horvath, Skin&Blood, PhenoAge, PCPhenoAge, GrimAge, DNAmTL and epiTOC2) to analyze peripheral blood of pediatric and adult cohorts of arsenic-exposed (n = 84) and arsenic-naïve (n = 33) individuals, among whom n = 18 were affected by skin lesions. Arsenic-exposed adults with skin lesions exhibited accelerated epigenetic (Skin&Blood: + 7.0 years [95% CI 3.7; 10.2], q = 6.8 × 10-4), biological (PhenoAge: + 5.8 years [95% CI 0.7; 11.0], q = 7.4 × 10-2, p = 2.8 × 10-2) and mitotic age (epiTOC2: + 19.7 annual cell divisions [95% CI 1.8; 37.7], q = 7.4 × 10-2, p = 3.2 × 10-2) compared to healthy arsenic-naïve individuals; and accelerated epigenetic age (Skin&Blood: + 2.8 years [95% CI 0.2; 5.3], q = 2.4 × 10-1, p = 3.4 × 10-2) compared to lesion-free arsenic-exposed individuals. Moreover, lesion-free exposed adults exhibited accelerated Skin&Blood age (+ 4.2 [95% CI 1.3; 7.1], q = 3.8 × 10-2) compared to their arsenic-naïve counterparts. Compared to the pediatric group, arsenic-exposed adults exhibited accelerated epigenetic (+ 3.1 to 4.4 years (95% CI 1.2; 6.4], q = 2.4 × 10-4-3.1 × 10-3), biological (+ 7.4 to 7.8 years [95% CI 3.0; 12.1] q = 1.6 × 10-3-2.8 × 10-3) and mitotic age (+ 50.0 annual cell divisions [95% CI 15.6; 84.5], q = 7.8 × 10-3), as well as shortened telomere length (- 0.23 kilobases [95% CI - 0.13; - 0.33], q = 2.4 × 10-4), across all seven algorithms. We demonstrate that lifetime arsenic exposure and presence of arsenic-associated skin lesions are associated with accelerated epigenetic, biological and mitotic age, and shortened telomere length, reflecting altered immune signaling and genomic regulation. Our findings highlight the usefulness of DNA methylation-based algorithms in identifying deleterious molecular changes associated with chronic exposure to the heavy metal, serving as potential prognosticators of arsenic-induced cutaneous malignancy.

Spindle cell lipoma: a rare case report on the hallux.

Spindle cell lipomas are a rare type of lipoma usually presenting in middle-aged to older men, often located on the posterior neck or shoulder; presentation on the foot is exceptionally uncommon. We report a 24-year-old man with spindle cell lipomas on the hallux of his left foot. He experienced an uneventful recovery after excision of the mass. We discuss clinical, radiologic, and histopathologic features of spindle cell lipomas and we review the differential diagnosis at this anatomic site.

Verrucous carcinoma presenting as recalcitrant verruca plantaris.

Verrucous carcinoma (VC) is a rare, low-grade variant of well-differentiated squamous cell carcinoma. Plantar verrucous carcinoma presents as a slow-growing, exophytic, verrucous plaque on weight bearing areas of the foot. Verrucous carcinomas have low metastatic potential, but are high risk for local invasion. We describe a patient with a 20-year history of a slowly growing, ulcerated, verrucous plaque on the sole of the left foot that was erroneously treated for years as verruca plantaris and was eventually diagnosed as invasive verrucous carcinoma. Verrucous carcinomas are a diagnostic challenge due to clinical and histopathologic mimicry of benign lesions. Mohs micrographic surgery should be employed to allow the ability to intraoperatively assess tumor margins while excising the minimal amount of necessary tissue. It is important for clinicians to recognize the characteristics and accurately diagnose verrucous carcinomas. Delays in treatment may require more extensive dissection or amputation.

Basal cell carcinoma in situ of the skin revisited: case reports of the superficial type and fibroepithelioma type of this in situ cutaneous neoplasm.

Cutaneous basal cell carcinoma in situ is a recently proposed subtype of this skin cancer. It is characterized by either restriction of the tumor cells within the epidermis or the presence of tumor cells contiguous with the overlying epidermis that extend into the underlying dermis, or both. Importantly, cancer invasion-demonstrated by non-contiguous aggregates of basaloid tumor cells in the dermis-is not a feature of in situ basal cell carcinoma of the skin. A 63-year-old woman with cutaneous basal cell carcinoma in situ-superficial type that presented as an erythematous scaly plaque on her abdomen and a 61-year-old man with a cutaneous basal cell carcinoma in situ-fibroepithelioma type that presented as a flesh-colored smooth exophytic nodule on his back are reported. The characteristics of in situ basal cell carcinoma of the skin in these individuals are summarized. In conclusion, similar to other cutaneous malignant neoplasms-such as squamous cell carcinoma, malignant melanoma, and Merkel cell carcinoma-basal cell carcinoma of the skin can also present as an in situ cancer.