High-frequency ultrasound accuracy in preoperative cutaneous melanoma assessment: A meta-analysis.

BACKGROUND: High-frequency ultrasound (HFUS) can safely and efficiently visualize cutaneous tumour characteristics including depth. OBJECTIVES: We aimed to evaluate its accuracy in measuring melanoma depth against the gold standard, histopathology, for treatment planning. METHODS: A review of publications was conducted in March 2023 through five electronic databases. Thirty-six included articles studied patients who received HFUS (≥10 MHz) measurements, melanoma biopsy or excision, and reported a tumour depth correlation coefficient between HFUS and histopathology. We analysed correlation coefficients between HFUS and histopathology, measured tumour depths and shed light on reasons for mismeasurements. Additionally, we identified the reporting of critical metrics including, lesion characteristics, melanoma subtype, type of correlation coefficient, 95% confidence intervals for Pearson coefficients and sample size. RESULTS: The most common tumour imaged was superficial spreading melanoma on the trunk and extremities, followed by head/face. Maximum ultrasound frequencies ranged from 13 MHz to 100 MHz with participants ranging from 5 to 264. Histopathology and HFUS correlation coefficients ranged from 0.417 to 0.997 (median: 0.94, mean: 0.89 and SD: 0.13). Lower frequency probes (10-20 MHz) were less accurate in assessing melanoma thickness, with a cumulative mean correlation coefficient of 0.87 compared to 0.94 (20-25 MHz) and 0.98 (≥70 MHz). Studies demonstrated higher sonographic accuracy in melanomas >0.75 mm. Additionally, ultrasound may report increased melanoma depth compared to histopathology for reasons including lymphocytic infiltration, presence of a nevus and shrinkage during specimen processing. Furthermore, we found a gap in the reporting of details such as fundamental characteristics of lesion populations. Specifically, 86% (31 out of 36) of the studies failed to report one or more critical metrics, such as mean, median or range of lesion depths. CONCLUSIONS: HFUS may serve as a supplementary tool for preoperative melanoma assessment, with increased accuracy in thicker tumours. Frequencies <20 MHz are less reliable in assessing depth. Frequencies ≥70 MHz demonstrate stronger correlations to histopathology. Higher ultrasound accuracy was seen for melanomas with Breslow depth >0.75 mm.

Targeting the Angiotensin Pathway in the Treatment of Cutaneous Fibrosis: A Systematic Review.

Acting on the renin-angiotensin-aldosterone system, angiotensin-converting enzyme inhibitors (ACE-Is) and angiotensin receptor blockers (ARBs) are mechanisms of some of the most prescribed medications in the world. In addition to their routine use for the treatment of hypertension, such agents have gained attention for their influence on the angiotensin receptor pathway in fibrotic skin disorders, including scars and keloids. To evaluate the current level of evidence supporting the use of these agents, a systematic review related to ACE-Is/ARBs and cutaneous scarring was conducted. We searched MEDLINE, Embase, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and Scopus from database inception through January 26, 2022. Two independent reviewers identified eligible studies for inclusion and extracted data. Data were insufficient for meta-analysis and are presented narratively. Of 461 citations identified, seven studies were included (199 patients). The studies included two randomized clinical trials, one comparative observation study, and four case reports. All the included studies reported statistically significant improvement in cutaneous scarring in patients using ACE-Is/ARBs compared with that in those treated with placebo/control using various outcome measures such as scar size and scar scales. However, much of the literature on this subject to date is limited by study design.

Cutaneous Metastasis of Alveolar Rhabdomyosarcoma in a Child.

ABSTRACT: Rhabdomyosarcoma (RMS) is one of the most common soft tissue sarcomas in children. This lesion is classically included in the generic group of "small round blue cell tumors" along with other entities that share similar microscopic features. Although the head and neck region is a frequent site for primary tumors, cutaneous metastases of RMS involving this anatomical location are rare in the pediatric population. We report a case of a 12-year old girl previously diagnosed with a primary alveolar RMS involving the left maxillary sinus, presenting with a metastatic lesion on the skin of the left temple area. Along with a brief review of the previous case reports on the topic, we highlight the initial immunohistochemistry panel useful for diagnosing this tumor.

Association of Patient Proximity to Dermatologic Care With Melanoma Stage at Diagnosis and Outcome.

This cohort study evaluates the association of proximity to dermatologic clinicians with stage at diagnosis and cancer-specific survival among adults with cutaneous melanoma in Iowa.

Orf Virus in Humans: Case Series and Clinical Review.

Ecthyma contagiosum (orf), a worldwide cause of the hand pustule, is caused by orf virus, a member of the genus Parapoxvirus, which causes an epitheliotropic zoonotic infection that spreads from ruminants (even-toed ungulate mammals such as sheep or goats) to humans. Similar members within the poxvirus family can cause a clinically identical viral pustule, which is spread to humans from the respective animal host reservoirs. These entities are impossible to clinically differentiate in the absence of social history or specific polymerase chain reaction studies, though their frequency does vary based on location across the globe.Although its 1-cm solitary hand pustule often is easily diagnosed by the experienced dermatologist, the goal of this review is to expand the understanding of the presentation, differential diagnosis, and treatment of this condition. We present 5 clinical cases of orf. Special care also has been taken to expand on our report of the unique associated cultural and social elements that the expert diagnostician should obtain to determine etiology.Early and rapid diagnosis of this classic condition are critical to prevent unnecessary biopsies or extensive testing, and determination of etiology can be important to prevent reinfection or spread to other humans by the same infected animal.

The Genetics of Early-Stage Melanoma in a Veteran Population.

To improve understanding of the genetic signature of early-stage melanomas in Veterans, hotspot mutation profiling using next-generation sequencing (NGS) was performed on melanoma tissue samples from patients at the Iowa City Veterans Affairs Medical Center (VAMC). Genetic analysis identified BRAF (36.3%), TP53 (25.9%), NRAS (19.3%), CDKN2A (11.1%), KIT (8.1%), and BAP1 (7.4%) mutations with the highest prevalence. Although common variants in BRAF were detected at lower rates than what is reported for the general population, 55.6% of cases showed activating mutations in the RAS/RAF pathways. Variants in TP53 and KIT were detected at higher rates than in the general population. Veterans with prior history of melanoma were at significantly higher odds of having TP53 mutation (OR = 2.67, p = 0.04). This suggests that TP53 may be a marker for recurrent melanoma and possibly alternative exposures in the military population. This study provides new information regarding the genetics of melanoma in a Veteran population and early-stage melanomas, highlighting risk factors unique to this population and contributing to the conversation about preventing melanoma deaths in US Military personnel.

Skin Injury Activates a Rapid TRPV1-Dependent Antiviral Protein Response.

The skin serves as the interface between the body and the environment and plays a fundamental role in innate antimicrobial host immunity. Antiviral proteins (AVPs) are part of the innate host defense system and provide protection against viral pathogens. How breach of the skin barrier influences innate AVP production remains largely unknown. In this study, we characterized the induction and regulation of AVPs after skin injury and identified a key role of TRPV1 in this process. Transcriptional and phenotypic profiling of cutaneous wounds revealed that skin injury induces high levels of AVPs in both mice and humans. Remarkably, pharmacologic and genetic ablation of TRPV1-mediated nociception abrogated the induction of AVPs, including Oas2, Oasl2, and Isg15 after skin injury in mice. Conversely, stimulation of TRPV1 nociceptors was sufficient to induce AVP production involving the CD301b+ cells‒IL-27‒mediated signaling pathway. Using IL-27 receptor‒knockout mice, we show that IL-27 signaling is required in the induction of AVPs after skin injury. Finally, loss of TRPV1 signaling leads to increased viral infectivity of herpes simplex virus. Together, our data indicate that TRPV1 signaling ensures skin antiviral competence on wounding.

A case of idiopathic acquired leukonychia totalis in a 17-year-old boy.

Whitening of the nail, or leukonychia, can have a wide range of etiologies including genetic disorders, trauma, poisoning, autoimmune disorders, and infections. Here we detail a case of idiopathic acquired leukonychia totalis in a 17-year-old boy. This condition has been reported 13 times in the literature previously, with only young boys being affected. Proper diagnosis may help minimize unnecessary investigations and prevent additional psychological stress over whether an underlying disease is present.

Each patient is a research biorepository: informatics-enabled research on surplus clinical specimens via the living BioBank.

The ability to analyze human specimens is the pillar of modern-day translational research. To enhance the research availability of relevant clinical specimens, we developed the Living BioBank (LBB) solution, which allows for just-in-time capture and delivery of phenotyped surplus laboratory medicine specimens. The LBB is a system-of-systems integrating research feasibility databases in i2b2, a real-time clinical data warehouse, and an informatics system for institutional research services management (SPARC). LBB delivers deidentified clinical data and laboratory specimens. We further present an extension to our solution, the Living µBiome Bank, that allows the user to request and receive phenotyped specimen microbiome data. We discuss the details of the implementation of the LBB system and the necessary regulatory oversight for this solution. The conducted institutional focus group of translational investigators indicates an overall positive sentiment towards potential scientific results generated with the use of LBB. Reference implementation of LBB is available at https://LivingBioBank.musc.edu.

Morphea following treatment with pembrolizumab for melanoma with metastatic lymph nodes: case report and review of literature.

Pembrolizumab is a humanized IgG4 isotype mAb that the targets and blocks the programmed cell death protein 1 receptor on lymphocytes. Its use in treating metastatic melanoma is associated with increased overall survival compared to other older immunotherapies. Several adverse effects have been noted including both systemic and cutaneous manifestations. As a relatively novel treatment option, many new cutaneous manifestations are still being observed, occurring at various times after initiation of therapy. Previously noted cutaneous adverse effects include sarcoid-like reactions, rash, and changes in preexisting lesions or scars. Here we present a case in which biopsy-proven morphea developed after completion of pembrolizumab therapy.

Chemoprevention agents for melanoma: A path forward into phase 3 clinical trials.

Recent progress in the treatment of advanced melanoma has led to unprecedented improvements in overall survival and, as these new melanoma treatments have been developed and deployed in the clinic, much has been learned about the natural history of the disease. Now is the time to apply that knowledge toward the design and clinical evaluation of new chemoprevention agents. Melanoma chemoprevention has the potential to reduce dramatically both the morbidity and the high costs associated with treating patients who have metastatic disease. In this work, scientific and clinical melanoma experts from the national Melanoma Prevention Working Group, composed of National Cancer Trials Network investigators, discuss research aimed at discovering and developing (or repurposing) drugs and natural products for the prevention of melanoma and propose an updated pipeline for translating the most promising agents into the clinic. The mechanism of action, preclinical data, epidemiological evidence, and results from available clinical trials are discussed for each class of compounds. Selected keratinocyte carcinoma chemoprevention studies also are considered, and a rationale for their inclusion is presented. These data are summarized in a table that lists the type and level of evidence available for each class of agents. Also included in the discussion is an assessment of additional research necessary and the likelihood that a given compound may be a suitable candidate for a phase 3 clinical trial within the next 5 years.

Drug-induced linear IgA bullous dermatosis in a patient with a vancomycin-impregnated cement spacer.

Linear IgA bullous dermatosis (LABD) is an autoimmune blistering rash caused by IgA autoantibodies against the epidermal basement membrane zone. It commonly is drug induced, often in association with systemic vancomycin. We report a case of a previously healthy 77-year-old man who developed a diffuse macular rash and hemorrhagic bullae on the left leg 10 days after placement of a vancomycin-impregnated cement spacer (VICS) during a revision knee arthroplasty and initiation of postoperative treatment with intravenous (IV) vancomycin. The lesions initially were limited to the leg in which the hardware was placed, but the patient later developed painful palmoplantar and oropharyngeal blisters as well as edematous, erythematous plaques on the back and buttocks. A punch biopsy from a lesion on the left thigh revealed neutrophil-rich subepidermal bullae, and immunofluorescence revealed linear IgA and C3 deposition along the dermoepidermal junction, confirming a diagnosis of LABD. This report illustrates the importance of considering antibiotic-impregnated cement spacers, which frequently are used to manage prosthetic joint infections, as potential culprits in patients with cutaneous eruptions.

Skin cancer in the military: A systematic review of melanoma and nonmelanoma skin cancer incidence, prevention, and screening among active duty and veteran personnel.

BACKGROUND: Occupational sun exposure is a well-studied risk factor for skin cancer development, but more work is needed to assess melanoma and nonmelanoma skin cancer risk among US military personnel to improve education and screening efforts in this population. OBJECTIVE: To conduct an extensive review of skin cancer risks for US military personnel to inform preventive education, diagnosis, and treatment efforts to better protect these individuals from future skin cancer development. METHODS: A systematic review of published studies on the subject of melanoma and nonmelanoma skin cancer in military personnel was conducted. RESULTS: A total of 9 studies describing skin cancer incidence in the US military were identified, with 4 studies specific to melanoma. The study findings reveal an increased risk for melanoma associated with service in the military or prisoner of war status. Service in tropical environments was associated with an increased incidence of both melanoma and nonmelanoma skin cancer among World War II soldiers. Two studies found that increased melanoma risk was also branch dependent, with the highest rates among the United States Air Force. Several of the reviewed studies implicated increased sun exposure during military service and lack of sufficient sun protection as the causes of higher rates of skin cancer among US military and veteran populations as compared with among the nonmilitary population in the United States. LIMITATIONS: The reviewed articles have variable results; a prospective randomized controlled trial would be helpful to develop interventions that mitigate skin cancer risk in the US military. CONCLUSION: This review identifies an abundance of evidence for an increased risk for skin cancer development among US active duty and veteran populations.