Cytophagic histiocytic panniculitis leading to a diagnosis of acute myeloid leukemia with monocytic differentiation: A case report and literature review.

Cytophagic histiocytic panniculitis (CHP) is associated with a number of systemic conditions and is characterized by the presence of benign phagocytic histiocytes ("bean bag cells"), including phagocytosed erythrocytes, leukocytes, and platelets. We describe a case of a 72-year-old female who presented with a papular eruption that clinically mimicked pityriasis lichenoides et varioliformis acuta (PLEVA). Given that her skin biopsy had multiple features concerning PLEVA, this diagnosis was classified as a superficial pityriasis lichenoides-like variant of CHP. The histopathologic presence of cytophagic histiocytosis prompted workup for a systemic malignancy, leading to a diagnosis of underlying acute monocytic leukemia of myeloid lineage.

Artificial Intelligence for Mohs and Dermatologic Surgery: A Systematic Review and Meta-Analysis.

BACKGROUND: Over the past decade, several studies have shown that potential of artificial intelligence (AI) in dermatology. However, there has yet to be a systematic review evaluating the usage of AI specifically within the field of Mohs micrographic surgery (MMS). OBJECTIVE: In this review, we aimed to comprehensively evaluate the current state, efficacy, and future implications of AI when applied to MMS for the treatment of nonmelanoma skin cancers (NMSC). MATERIALS AND METHODS: A systematic review and meta-analysis was conducted following PRISMA guidelines across several databases, including PubMed/MEDLINE, Embase, and Cochrane libraries. A predefined protocol was registered in PROSPERO, with literature search involving specific keywords related to AI and Mohs surgery for NMSC. RESULTS: From 23 studies evaluated, our results find that AI shows promise as a prediction tool for precisely identifying NMSC in tissue sections during MMS. Furthermore, high AUC and concordance values were also found across the various usages of AI in MMS, including margin control, surgical recommendations, similarity metrics, and in the prediction of stage and construction complexity. CONCLUSION: The findings of this review suggest promising potential for AI to enhance the accuracy and efficiency of Mohs surgery, particularly for NMSC.

Chronic UV radiation-induced RORγt+ IL-22-producing lymphoid cells are associated with mutant KC clonal expansion.

Chronic ultraviolet (UV) radiation exposure is the greatest risk factor for cutaneous squamous cell carcinoma (cSCC) development, and compromised immunity accelerates this risk. Having previously identified that epidermal Langerhans cells (LC) facilitate the expansion of UV-induced mutant keratinocytes (KC), we sought to more fully elucidate the immune pathways critical to cutaneous carcinogenesis and to identify potential targets of intervention. Herein, we reveal that chronic UV induces and LC enhance a local immune shift toward RORγt+ interleukin (IL)-22/IL-17A-producing cells that occurs in the presence or absence of T cells while identifying a distinct RORγt+ Sca-1+ CD103+ ICOS+ CD2+/- CCR6+ intracellular CD3+ cutaneous innate lymphoid cell type-3 (ILC3) population (uvILC3) that is associated with UV-induced mutant KC growth. We further show that mutant KC clone size is markedly reduced in the absence of RORγt+ lymphocytes or IL-22, both observed in association with expanding KC clones, and find that topical application of a RORγ/γt inhibitor during chronic UV exposure reduces local expression of IL-22 and IL-17A while markedly limiting mutant p53 KC clonal expansion. We implicate upstream Toll-like receptor signaling in driving this immune response to chronic UV exposure, as MyD88/Trif double-deficient mice also show substantially reduced p53 island number and size. These data elucidate key immune components of chronic UV-induced cutaneous carcinogenesis that might represent targets for skin cancer prevention.

Considering Sun Safety Policies in the United States.

As they are collectively the most common malignancies, the personal and systemic burden of skin cancers represent a significant public health concern in the United States. Ultraviolet radiation from the sun as well as from artificial sources such as tanning beds is a carcinogen well-known to increase the risk of developing skin cancer in individuals. Public health policies can help mitigate these risks. In this perspectives article, we review sunscreen and sunglasses standards, tanning bed utilization, and workplace sun protection guidelines in the US and provide focused examples for improvement from Australia and the United Kingdom where skin cancer is a well-documented public health concern. These comparative examples can inform interventions in the US that have the potential to modify exposure to risk factors associated with skin cancer.

Outcomes and adverse effects of ablative vs nonablative lasers for skin resurfacing: A systematic review of 1093 patients.

It is generally believed that ablative laser therapies result in prolonged healing and greater adverse events when compared with nonablative lasers for skin resurfacing. To evaluate the efficacy of ablative laser use for skin resurfacing and adverse events as a consequence of treatment in comparison to other modalities, a PRISMA-compliant systematic review (Systematic Review Registration Number: 204016) of twelve electronic databases was conducted for the terms "ablative laser" and "skin resurfacing" from March 2002 until July 2020. Studies included meta-analyses, randomized control trials, cohort studies, and case reports to facilitate evaluation of the data. All articles were evaluated for bias. The search strategy produced 34 studies. Of 1093 patients included in the studies of interest, adverse events were reported in a total of 106 patients (9.7%). Higher rates of adverse events were described in nonablative therapies (12.2% ± 2.19%, 31 events) when compared with ablative therapy (8.28% ± 2.46%, 81 events). 147 patients (13.4%) reported no side effects, 68 (6.22%) reported expected, transient self-resolving events, and five (0.046%) presented with hypertrophic scarring. Excluding transient events, ablative lasers had fewer complications overall when compared with nonablative lasers (2.56% ± 2.19% vs 7.48% ± 3.29%). This systematic review suggests ablative laser use for skin resurfacing is a safe and effective modality to treat a range of pathologies from photodamage and acne scars to hidradenitis suppurativa and posttraumatic scarring from basal cell carcinoma excision. Further studies are needed, but these results suggest that ablative lasers are a superior, safe, and effective modality to treat damaged skin.

Meeting Dermatologic Needs in an Uninsured Population: Lessons Learned from a Referrals Cohort at a Student-Run Free Clinic.

Unmet dermatologic needs of the uninsured patient population are important to identify and address, especially as the COVID-19 pandemic has introduced additional barriers of access to care. We describe the successful collaboration between a student-run free clinic and dermatology practice since 2012, highlighting excellent time to appointment intervals and resolution rates as well as the associated modest financial cost. We believe that the information provided in our report may serve as a proof of concept and facilitate the implementation of such collaborations throughout the United States.

Concomitant use of isotretinoin and lasers with implications for future guidelines: An updated systematic review.

It is generally believed that intervention on skin while on isotretinoin or within 6 to 12 months after treatment can lead to prolonged healing and abnormal scarring. The objective of this systematic review is to evaluate the body of evidence on concomitant use of isotretinoin and lasers for adverse events as a consequence of treatment. A PRISMA-compliant systematic review (Systematic Review Registration Number: CRD42017056492) of 12 electronic databases was conducted for the terms "laser" and "isotretinoin" or associated brand names from inception until June 2020. Subsequent reference search of studies meeting predefined inclusion criteria were conducted, and all articles were evaluated for bias and assigned levels of evidence to facilitate data synthesis. The search strategy produced 29 studies. Of 871 patients included in the studies of interest, 12 experienced transient adverse effects that resolved spontaneously, and only two presented with keloid formation, both from case reports. This systematic review suggests the risk associated with concomitant isotretinoin and laser use is small to absent. Further studies are needed, but these results suggest that current contraindications may be overly cautious.

Synergy of BCL2 and histone deacetylase inhibition against leukemic cells from cutaneous T-cell lymphoma patients.

The presence and degree of peripheral blood involvement in patients with cutaneous T-cell lymphoma (CTCL) portend a worse clinical outcome. Available systemic therapies for CTCL may variably decrease tumor burden and improve quality of life, but offer limited effects on survival; thus, novel approaches to the treatment of advanced stages of this non-Hodgkin lymphoma are clearly warranted. Mutational analyses of CTCL patient peripheral blood malignant cell samples suggested the antiapoptotic mediator B-cell lymphoma 2 (BCL2) as a potential therapeutic target. To test this, we developed a screening assay for evaluating the sensitivity of CTCL cells to targeted molecular agents, and compared a novel BCL2 inhibitor, venetoclax, alone and in combination with a histone deacetylase (HDAC) inhibitor, vorinostat or romidepsin. Peripheral blood CTCL malignant cells were isolated from 25 patients and exposed ex vivo to the 3 drugs alone and in combination, and comparisons were made to 4 CTCL cell lines (Hut78, Sez4, HH, MyLa). The majority of CTCL patient samples were sensitive to venetoclax, and BCL2 expression levels were negatively correlated (r = -0.52; P =018) to 50% inhibitory concentration values. Furthermore, this anti-BCL2 effect was markedly potentiated by concurrent HDAC inhibition with 93% of samples treated with venetoclax and vorinostat and 73% of samples treated with venetoclax and romidepsin showing synergistic effects. These data strongly suggest that concurrent BCL2 and HDAC inhibition may offer synergy in the treatment of patients with advanced CTCL. By using combination therapies and correlating response to gene expression in this way, we hope to achieve more effective and personalized treatments for CTCL.

Copying of Mixed-Sequence RNA Templates inside Model Protocells.

The chemical replication of RNA inside fatty acid vesicles is a plausible step in the emergence of cellular life. On the primitive Earth, simple protocells with the ability to import nucleotides and short oligomers from their environment could potentially have replicated and retained larger genomic RNA oligonucleotides within a spatially defined compartment. We have previously shown that short 5'-phosphoroimidazolide-activated "helper" RNA oligomers enable the nonenzymatic copying of mixed-sequence templates in solution, using 5'-phosphoroimidazolide-activated mononucleotides. Here, we report that citrate-chelated Mg2+, a catalyst of nonenzymatic primer extension, enhances fatty acid membrane permeability to such short RNA oligomers up to the size of tetramers, without disrupting vesicle membranes. In addition, selective permeability of short, but not long, oligomers can be further enhanced by elevating the temperature. The ability to increase the permeability of fatty acid membranes to short oligonucleotides allows for the nonenzymatic copying of RNA templates containing all four nucleotides inside vesicles, bringing us one step closer to the goal of building a protocell capable of Darwinian evolution.

Epidemiology of malignant cutaneous granular cell tumors: A US population-based cohort analysis using the Surveillance, Epidemiology, and End Results (SEER) database.

BACKGROUND: Malignant cutaneous granular cell tumors (mcGCTs) are rare and associated with substantial morbidity and mortality. The literature includes single-institution studies. OBJECTIVE: To examine the incidence, secondary malignancies, treatment, overall survival, and disease-specific survival (DSS) of patients with mcGCT. METHODS: A population-based cohort analysis was conducted in the Surveillance, Epidemiology, and End Results database from 1973 to 2013 for patients with a diagnosis of mcGCT. Risk-adjusted associations between overall survival/DSS and patient characteristics and treatment modalities were assessed by Cox proportional hazard regression. Quantile regression was used to determine median survival times. RESULTS: The 5-year DSS rate was 62.8%. Patients demonstrated an increased risk for renal and pancreatic cancers. In risk-adjusted models, male sex (hazard ratio [HR], 0.21; 95% confidence interval [CI], 0.06-0.82; P = .02), advanced cancer stage (HR, 2.29; 95% CI, 1.40-3.72; P < .01), and surgical resection (HR, 0.06; 95% CI, 0.01-0.59; P = .02) predicted DSS. Median survival time in years increased for males (1.39), earlier stage (0.60), and surgical intervention (5.34). LIMITATIONS: Absent or incorrect reporting in retrospective Surveillance, Epidemiology, and End Results data is possible. The database is more likely to include academic centers. Some subanalyses may be underpowered because of the limited sample size for a rare cancer. CONCLUSIONS: Our study presents an in-depth assessment of factors that identify high-risk patients. Residency in a nonmetro area, black race, female sex, and no surgical resection were each associated with poorer DSS.

The use of lasers in the treatment of skin cancer: A review.

BACKGROUND: In considering skin cancer, a number of factors-including effectiveness, simplicity of treatment, cost, and esthetic outcomes-are important to ensure patient's satisfaction. There are several existing interventions, such as electrodessication and curettage, excision, Mohs surgery, radiation therapy, cryotherapy, and topical/oral treatments. Laser therapy has emerged as a new promising alternative that should be explored. OBJECTIVE: To review the literature on the dermatological use of laser therapy in the treatment of skin cancer. RESULTS: A review of articles available on the MEDLINE and Web of Science databases until May 2017 yielded 24 and 6 studies, respectively, on laser therapy in the treatment of skin cancers, particularly melanoma, basal cell carcinoma, and squamous cell carcinoma. The four laser subtypes included solid-state, diode, dye, and gas lasers. CONCLUSION: Review of the literature demonstrates the progress of dermatological understanding of the clinical implications of laser therapy in the treatment of premalignant and malignant neoplasms of the skin, and suggests that this treatment modality might be a viable option for some patients.

Applications and Best Practices for Geospatial Analysis Research in Dermatology.

Dermatologic diseases often exhibit distinct geographic patterns, underscoring the significant role of regional environmental, genetic, and sociocultural factors in driving their prevalence and manifestations. Geographic information and geospatial analysis enable researchers to investigate the spatial distribution of adverse health outcomes and their relationship with socioeconomic and environmental risk factors that are inherently geographic. Health geographers and spatial epidemiologists have developed numerous geospatial analytical tools to collect, process, visualize, and analyze geographic data. These tools help provide vital spatial context to the comprehension of the underlying dynamics behind health outcomes. By identifying areas with high rates of dermatologic disease and areas with barriers to access to quality dermatologic care, findings from studies utilizing geospatial analysis can inform the design and targeting of policy and intervention to help improve dermatologic healthcare outcomes and promote health equity. This article emphasizes the significance of geospatial data and analysis in dermatology research. We explore the common processes in data acquisition, harmonization, and geospatial analytics while conducting spatially and dermatologically relevant research. The article also highlights the practical application of geospatial analysis through instances drawn from the dermatology literature.