Cutaneous Angiosarcoma Subtypes: A Quantitative Systematic Review of Demographics, Treatments, and Outcomes Within Published Patient-Level Cases.

BACKGROUND: Cutaneous angiosarcoma (cAS) is a highly aggressive malignancy arising from the vascular endothelium. Given its rarity, there is insufficient data detailing patient demographics, management, and survival outcomes. OBJECTIVE: To systematically compile published patient-level cases of cAS and to quantify and analyze data on demographics, management, and outcomes while determining prognostic indicators. MATERIALS AND METHODS: Searches of EBSCOhost, MEDLINE, EMBASE, and the Cochrane Library generated 1,500 cases of cAS with individual level data available. PRISMA guidelines were followed. RESULTS: Cutaneous angiosarcoma presented most often on the scalp of elderly men. Metastasis occurred in 36.3% of cases. Aggregate 5-year survival was 31.6% with the median survival of 25 months. The best 5-year survival was in the radiation-associated subtype (48.8%), whereas the worst was in the Stewart-Treves subtype (21.6%). Using multivariate analysis, gender, age group, disease subtype, treatment modality, and metastasis at presentation had significant effects on survival outcomes ( p < .05). CONCLUSION: The breadth of information obtained enables this study to serve as a resource that clinicians may reference when they encounter cAS.

Generalized Pustular Psoriasis: A Review of the Pathophysiology, Clinical Manifestations, Diagnosis, and Treatment.

Generalized pustular psoriasis (GPP) is a rare severe variant of psoriasis that is characterized by the abrupt widespread onset of small pustules accompanied by systemic manifestations of inflammation. It can arise in patients with a history of psoriasis as well as in those without, sometimes due to medication initiation or withdrawal, pregnancy, or infection. Generalized pustular psoriasis is thought to be driven primarily by innate immunity and unrestrained IL-36 cytokine activity. Recent genetic analyses have identified 3 genetic mutations that are associated with GPP-IL36RN, CARD14, and AP1S3-though these mutations only account for a minority of cases. There are many cutaneous pustular diseases that must be ruled out in the evaluation of a patient with suspected GPP, especially acute generalized exanthematous pustulosis (AGEP), and histologic analysis is the cornerstone of diagnosis. Although the quality of evidence to generate treatment recommendations for GPP is limited, management often includes utilization of systemic agents and/or biologics, usually with adjunctive topical treatment. Accumulating evidence suggests that biologic agents, especially infliximab, may be considered as first-line treatment of GPP, especially in severe acute cases, due to their abrupt onset of action and favorable side-effect profiles compared with oral systemic agents.

Soft Tissue Dermal Filler-Associated Necrosis and Impending Necrosis: A Systematic Review of the Literature.

BACKGROUND: Cosmetic soft tissue fillers are a popular minimally invasive procedure. Necrosis is a rare yet devastating complication of soft tissue fillers. To date, the relationship between soft tissue fillers and necrosis has not been fully described. OBJECTIVE: To systematically compile published cases of soft tissue fillers resulting in necrosis and collect data regarding the injection, treatment, and outcome. METHODS AND MATERIALS: Using PRISMA protocol, a comprehensive search for soft tissue filler necrosis was performed using no time constraints, resulting in 97 articles encompassing 192 cases of soft tissue filler necrosis containing individual-level data. RESULTS: Of the cases analyzed, 66.1% had progressed to necrosis, whereas 33.9% of patients had impending necrosis. Necrosis most commonly resulted from injection of the nasolabial fold (32.4%, n = 88). The filler material most commonly used was hyaluronic acid (71.9%, n = 138). Hyaluronidase was used most frequently as an initial treatment agent (19.1%, n = 88). Forty-three patients (22.4%) with necrosis had a prior minor procedure or surgery. CONCLUSION: This systematic review is an extensive overview of necrosis as a complication of soft tissue fillers. It serves as a reference tool for any clinician who injects soft tissue fillers and any provider who encounters soft tissue filler necrosis.

Cutaneous Squamous Cell Carcinoma Arising in Immunosuppressed Patients: A Systematic Review of Tumor Profiling Studies.

As solid organ transplantation becomes more prevalent, more individuals are living as members of the immunosuppressed population with an elevated risk for cutaneous squamous cell carcinoma (cSCC). Although great progress has been made in understanding the pathogenesis of cSCC in general, little is known about the drivers of tumorigenesis in immunosuppressed patients and organ-transplant recipients, specifically. This systematic review sought to synthesize information regarding the genetic and epigenetic alterations as well as changes in protein and mRNA expression that place this growing population at risk for cSCC, influence treatment response, and promote tumor aggressiveness. This review will provide investigators with a framework to identify future areas of investigation and clinicians with additional insight into how to best manage these patients.

Sequencing of Cutaneous Squamous Cell Carcinoma Primary Tumors and Patient-Matched Metastases Reveals ALK as a Potential Driver in Metastases and Low Mutational Concordance in Immunocompromised Patients.

Cutaneous squamous cell carcinoma is a common skin cancer that is responsible for 1,000,000 cases and up to 9,000 deaths annually in the United States. Metastases occur in 2-5% of patients and are responsible for significant morbidity and mortality. The objective of this study is to perform targeted next-generation sequencing on a cohort of squamous cell carcinoma primary tumors and patient-matched lymph node metastases. An oncology 76-gene panel was run from formalin-fixed paraffin-embedded samples of patient-matched primary squamous cell carcinomas (10) and resultant metastases (10). ALK was discovered to be a driver mutation in metastases using two different algorithms, oncoCLUSTand dNdScv. Mutational concordance between primary tumors and metastases was notably lower in immunosuppressed patients, especially among pathogenic mutations (41.7% vs. 83.3%, P = 0.01). Sequencing of matched squamous cell carcinoma primary tumors and lymph node metastases identified genes and pathways that may have clinical importance, most notably ALK as a potential driver mutation of metastasis. Sequencing of both primary tumors and metastases may improve the efficacy of targeted therapies.

Patient willingness to receive full-body skin exams based on the sex and/or gender and training level of provider: a survey study.

Full-body skin examinations (FBSEs) involve examination of the patient's skin from head to toe, and may be uncomfortable for some patients. While many patients prefer same-sex providers for pelvic, genital and rectal exams, desire for same-sex providers for FBSEs is not well characterized. This may be further magnified when FBSE is performed by medical trainees. We surveyed 566 subjects using Amazon Mechanical Turk (AMT), an online crowdsourcing platform, to assess the public's willingness to receive FBSEs based on the sex and/or gender and the level of training of the healthcare provider (HCP). The overall willingness by all respondents to undergo FBSE performed by a dermatologist, dermatology resident and medical student was 84.3%, 77.5% and 65.7%, respectively, if the HCP was the same sex/gender, compared with 60.6%, 54.8% and 45.7% if the HCP was a different sex/gender (P < 0.001). In our cohort, unwillingness for FBSEs was greater if the patient was female, if the HCP was a different gender/sex from the patient and if the HCP was a medical student.

Deep Sweet Syndrome Secondary to Pegfilgrastim.

Sweet syndrome, or acute febrile neutrophilic dermatosis, is a skin condition consisting of erythematous papules and plaques in association with fever, neutrophilia, and a neutrophilic infiltrate that typically involves the papillary dermis. Although development is most commonly idiopathic, medications are also frequently associated with the eruption, notably, the granulocyte colony-stimulating factor (G-CSF), filgrastim. Pegylated G-CSF, despite similar activity, is not commonly reported, with only four published cases. We present a case of drug-induced sweet syndrome with unique histologic features (deep inflammatory infiltrate) in association with the usage of pegfilgrastim in the treatment of invasive ductal carcinoma of the breast. J Drugs Dermatol. 2022;21(4):422-424. doi:10.36849/JDD.4794.

Rare Cutaneous Malignancies in Skin of Color.

BACKGROUND: There is a scarcity of information regarding the clinical characteristics of rare cutaneous malignancies in skin of color that has yet to be comprehensively explored. OBJECTIVE: To review and compile the racial differences in epidemiology, clinical presentation, histology, treatments, and outcomes of 3 rare skin cancers: dermatofibrosarcoma protuberans (DFSP), Merkel cell carcinoma (MCC), and sebaceous carcinoma (SC). METHODS: Several searches with keywords denoting specific skin cancer type and race were conducted on PubMed to complete this narrative review. RESULTS: We analyzed 50 sources that were relevant to the initial objective. CONCLUSION: The literature demonstrates that there are nuances in DFSP, MCC, and SC unique to African Americans, Asians/Pacific Islanders, and Hispanics that may differ significantly from Caucasian counterparts. African Americans consistently suffer from the worst clinical outcomes in all 3 rare cutaneous malignancies reviewed. Greater physician awareness and knowledge of the discussed racial differences is the preliminary step to address these disparities.

Moraxella nonliquefaciens-Associated Ecthyma Gangrenosum in a Pediatric Patient With Cancer.

ABSTRACT: In this brief report, we describe a 16-year-old patient with pre-B-cell acute lymphoblastic leukemia on chemotherapy who presented to the emergency department with a fever and "bruise-like" area on his left forearm. Empiric antibiotic therapy was initiated, and initial tissue biopsy demonstrated findings consistent with ecthyma gangrenosum. On day 4 of admission, initial blood cultures grew Moraxella nonliquefaciens, and targeted antibiotic therapy was initiated and continued for a total of 21 days. The patient was discharged after 6 days of in-patient therapy and made a full recovery. M. nonliquefaciens has been reported to be associated with multiple types of infection, but no cases of M. nonliquefaciens-associated ecthyma gangrenosum were identified in the literature review for this report. Given this unique case and the empiric risks and broad differential associated with cutaneous manifestations in immunocompromised patients, obtaining a skin biopsy for histological examination is imperative for diagnostic workup.

Analysis of mutations in cutaneous squamous cell carcinoma reveals novel genes and mutations associated with patient-specific characteristics and metastasis: a systematic review.

Cutaneous squamous cell carcinoma (SCC) causes approximately 1,000,000 cases and 9000 deaths each year in the United States. While individual tumor sequencing studies have discovered driver mutations in SCC, there has yet to be a review and subsequent analysis synthesizing current studies. To conduct a comprehensive synthesis and analysis of SCC sequencing studies with individual patient-level data, a comprehensive literature search was performed. Statistical analyses were performed to identify trends. Studies meeting inclusion criteria included a total of 279 patients (189 localized SCCs, 90 metastatic SCCs). Several mutations were correlated with demographic characteristics (TP53, MLL4, BRCA2, COL4A1). TP53, TERT, SPEN, MLL3, and NOTCH2 mutations were significantly more likely to be found in metastatic versus localized SCCs even after the Bonferroni correction for multiple comparisons. Silent mutations were found more in localized SCCs than metastatic SCCs, and nonsense mutations were found more in metastatic SCCs than localized SCCs (p = 0.0003 and p = 0.04, respectively). Additional mutations were identified that have not yet been explored in SCC including AHNAK2, LRP1B, TRIO, MDN1, COL4A2, SVIL, VPS13C, DST, DMD, and DYSF. Overall, novel mutations were identified and differences between mutation patterns in localized and metastatic SCCs were found. These findings may have clinical applications.

Arsenic Exposure and Melanoma Among US Adults Aged 20 or Older, 2003-2016.

OBJECTIVES: Chronic exposure to arsenic has been reported as a risk factor for nonmelanoma skin cancer, notably squamous cell carcinoma. However, current knowledge is limited about the association between arsenic exposure and melanoma. Our objectives were to (1) measure the association between total urinary arsenic levels and melanoma compared with nonmelanoma skin cancer and no cancer and (2) analyze the association between water source and melanoma and nonmelanoma skin cancer. METHODS: We collected cross-sectional data from the 2003-2016 cycles of the National Health and Nutrition Examination Survey. We conducted univariate and multivariate logistic regressions. To evaluate the possible association of skin cancer with source of tap water, we calculated odds ratios for participants with melanoma and nonmelanoma skin cancer, compared with participants with no cancer. RESULTS: White race, higher education, higher socioeconomic status, and smoking history were associated with melanoma and nonmelanoma skin cancer in the full study population. After adjusting for age and race/ethnicity, the adjusted odds ratio of participants with >50 µg/L of total urinary arsenic for melanoma or nonmelanoma skin cancer was 1.87 (95% CI, 0.58-6.05) and 2.23 (95% CI, 1.12-4.45) times higher compared with no cancer, respectively. Participants with nonmelanoma skin cancer had 2.06 increased odds of reporting a nonmunicipal water source compared with participants without cancer. CONCLUSIONS: We did not find a relationship between the incidence of melanoma and exposure to arsenic among US adults. Nonmunicipal water sources were associated with nonmelanoma skin cancer and should be further investigated.

Evaluation of cerebrospinal fluid white blood cell count criteria for use of the BioFire® FilmArray® Meningitis/Encephalitis Panel in immunocompromised and nonimmunocompromised patients.

We implemented the BioFire® FilmArray® Meningitis/Encephalitis Panel (MEP) with guidance for use based on patient age, cerebrospinal fluid (CSF) white blood cell (WBC) count and immune system status. MEPs results over 2 years (1/1/2017 to 12/31/18) were reviewed and clinical significance of positive MEP results in patients with CSF WBC ≤ 10 evaluated. Overall, 12% (51/453) of MEPs were positive with 4/184 (2%) positive in nonimmunocompromised (non-IC) with ≤ 10 CSF WBCs. Among positive results in non-IC patient with ≤10 CSF WBCs, none were judged clinically significant. Four of 6 results in immunocompromised patients with ≤10 CSF WBCs were clinically significant. Redundant testing was common and guideline adherence could have safely decreased MEPs use 41% saving >$56,000. Guideline adherence was poor and MEP use can be safely avoided in non-IC adults with <10 CSF WBC, but clinically significant results did occur in IC patients with low CSF WBC. Clinical decision support could reduce unneeded testing and result in significant cost savings.

What's Eating You? Culex Mosquitoes and West Nile Virus.

West Nile virus (WNV) commonly presents cutaneously as a maculopapular rash on the trunk and extremities that most often appears around the time of defervescence and may serve as a positive prognostic indicator. Several laboratory tests can aid in diagnosis of WNV, including an IgM enzyme-linked immunosorbent assay (ELISA), but an antibody response may not be detectable for up to 8 days after symptom onset. Taking a comprehensive history in any patient presenting with a generalized maculopapular rash, fever, nonspecific symptoms, or neurologic changes can aid the astute dermatologist in promptly recognizing the possibility of WNV.

Patient Outcomes and Satisfaction After Mohs Micrographic Surgery in Patients With Nonmelanoma Skin Cancer.

BACKGROUND: Quality in medicine is increasingly being measured through patient-reported outcome measures. Given the rising incidence and costs for nonmelanoma skin cancer (NMSC) treatment, it is imperative to define quality measures specific to dermatologic surgery. OBJECTIVE: This study aims to evaluate patient-reported outcomes and satisfaction with Mohs micrographic surgery (MMS) together with patient and tumor factors to better define their use in developing treatment strategies and quality measures. METHODS AND MATERIALS: A prospective study was conducted among 226 patients undergoing MMS for treatment of NMSC. Patient demographics, quality of life, functional status, satisfaction, and prognostic factors were gathered. Postoperative outcomes were measured at 1 month and included patient-reported problems and provider-reported complications. Relationships between patient factors and outcomes were evaluated through statistical analysis. RESULTS: Average patient satisfaction in the domain of general satisfaction of the Patient Satisfaction Questionnaire-18 was 4.34 of 5. General patient satisfaction did not differ across age, final defect size, sex, or prognostic scores. At 1-month postoperatively, 97 percent of patients expressed willingness to undergo future MMS if indicated. CONCLUSION: Patients are generally satisfied with MMS for treatment of NMSC. Specific patient factors that may affect satisfaction include smoking status and anticoagulation use.

Basal Cell Carcinoma Gene Mutations Differ Between Asian, Hispanic, and Caucasian Patients: A Pilot Study.

BACKGROUND: Basal cell carcinoma (BCC) is the most common malignancy worldwide. While most BCCs are treated surgically, advanced BCCs are often treated with gene-targeted therapies. While there has been a lot of research in BCC from Caucasian patients, research is lacking in patients with skin of color. OBJECTIVE: To identify potential variations in BCC gene mutations between Asian, Hispanic, and Caucasian patients. METHODS: A cohort study was performed from 2015 to 2017 with 23 patients treated for BCC at an urban academic hospital. Gene mutations were assessed using a targeted mutation panel for 76 cancer-associated genes from formalin-fixed paraffin-embedded (FFPE) samples. RESULTS: Groups studied comprised Asian (n=5), Hispanic (n=10), and Caucasian (n=8) patients. The Hispanic cohort had the highest number of mutations per patient on average (3.4 versus 2.8 for both Caucasian and Asian cohorts). GATA3 mutations were more prevalent in Hispanic patients (P=0.02, single factor ANOVA). ARID1A and PTEN mutations co-occurred in the Hispanic cohort (P<0.05). The most common mutation in the Asian cohort was TP53 (2/5). The Caucasian cohort had the highest percent of UVB mutations (68.4%). CONCLUSIONS: This study shows potential differences in the prevalence of somatic gene mutations for BCC patients of different races and ethnicities, which could inform the underlying pathogenesis, impact the efficacy of therapies in specific populations, and may also help identify novel therapeutic targets. J Drugs Dermatol. 20(5): doi:10.36849/JDD.5884.