Lasers for the Treatment of Nonmelanoma Skin Cancer: A Systematic Review of the Literature.

BACKGROUND: Lasers may present an alternative treatment modality for the management of nonmelanoma skin cancer (NMSC). OBJECTIVE: To investigate lasers as a definitive treatment of NMSC. METHODS: A comprehensive search was performed on MEDLINE, the Cochrane Library, and the National Institutes of Health (www.clinicaltrials.gov). The Preferred Reporting Items for Systematic Reviews and Meta-Analysis was used to finalize a list of relevant literature studies evaluating the role of laser therapy for NMSC. Articles published through May 1, 2023, were included. RESULTS: The authors identified 37 studies investigating nonablative and ablative lasers alone and in combination with other lasers, noninvasive imaging, and additional modalities for the treatment of basal cell carcinomas, 10 focusing on squamous cell carcinoma in situ and 3 focusing on the treatment of both basal and squamous cell carcinomas. CONCLUSION: Although surgical management continues to be superior to laser therapy for the management of high-risk and cosmetically sensitive tumors, laser therapy may be an acceptable alternative for low-risk lesions on the trunk and extremities. However, further studies are needed to optimize parameters, determine maximal efficacy, and provide long-term follow-up before the adoption of laser therapy for NMSC into daily clinical practice.

Pathologic Upstaging of Cutaneous Melanoma After Mohs Micrographic Surgery.

BACKGROUND: Mohs micrographic surgery (MMS) is used for melanoma in situ (MIS) and thin invasive melanomas, particularly on the head and neck, during which a debulk section is typically prepared. Tumor upstaging occurs if the debulking specimen meets criteria for an increased tumor (T) stage per the American Joint Committee on Cancer 8th edition compared with the initial biopsy. Upstaging can alter survival and recurrence outcomes, resulting in increased patient morbidity and mortality. OBJECTIVE: To determine the rate of cutaneous melanoma upstaging during MMS. MATERIALS AND METHODS: A multicenter study was performed. Information from electronic medical records from 3 dermatologic surgeons performing MMS for cutaneous melanoma were logged from January 1, 2017 to December 31, 2021. Deidentified information regarding patient demographics and tumor characteristics was recorded. RESULTS: Three-hundred and ten cases of cutaneous melanoma treated with MMS were identified. 2.3% of cases were upstaged, ranging from T1a to T3a. No significant risk factors for upstaging were identified. CONCLUSION: Our data demonstrate a lower rate of cutaneous melanoma upstaging during MMS than the current literature. Differences may be accounted for because of differing patient populations, cutaneous melanoma detection at an earlier clinical stage, and evolving melanoma histologic criteria.

Antibiotic Use and Surgical Site Infections in Immunocompromised Patients After Mohs Micrographic Surgery: A Single-Center Retrospective Study.

BACKGROUND: As Mohs micrographic surgery becomes more widely used in immunosuppressed patients, it is important to understand the risks in this unique population. OBJECTIVE: To determine whether immunosuppressed patients are at an increased risk for surgical site infection and evaluate the utility of postoperative antibiotics for the prevention of surgical site infection. MATERIALS AND METHODS: A single-center retrospective review of patients who underwent Mohs micrographic surgery between October 9, 2014, and August 20, 2021, was performed. RESULTS: Five thousand eight hundred eighty-six independent cases were identified. Factors associated with an increased incidence of antibiotic use included preoperative lesion size >40 mm (86.7%, n = 13; p < .01) and high-risk lesion location (46.4%, n = 1,268; p < .01). Patients were not more likely to be prescribed antibiotics if immunosuppressed (37.0%, n = 269 vs 34.2%, n = 1765; p = .14), and immunosuppression was not independently associated with antibiotic use on multivariate analysis (odds ratio 1.2, 95% confidence interval 1.0-1.5). Infection rates were similar between immunocompromised patients and immunocompetent patients (2.1%, n = 15 vs 1.6%, n = 80, respectively; p = .30). In immunosuppressed patients, antibiotic use did not decrease the likelihood of infection (3.0%, n = 8 vs 1.5%, n = 7; p = .19). CONCLUSION: There was no association between immunosuppression and surgical infection rate. Furthermore, postoperative antibiotics should not be indicated in these patients unless other high-risk criteria exist.

Immunohistochemistry for Preferentially Expressed Antigen in Melanoma in the Differential Diagnosis of Melanocytic Lesions of the Nail Apparatus.

ABSTRACT: Nail unit melanocytic lesions present a unique set of diagnostic challenges because of the unfamiliarity with clinical assessment and the lack of experience with histologic examination. Because the first surgical specimen received in the pathology laboratory is typically small, sometimes suboptimal biopsy, the distinction between melanoma and its histologic mimics can be difficult. For this reason, there has been a continued interest in the development of ancillary markers that may assist in the differential diagnosis of nail unit melanocytic lesions. Upregulation of preferentially expressed antigen in melanoma (PRAME) has been reported to be a common event in melanomas, and PRAME immunohistochemistry has been shown to be helpful in evaluating various melanocytic neoplasms. In this study, we evaluated PRAME protein expression in a series of nail unit melanocytic lesions. Twenty-five nail unit melanomas (including small biopsy and amputation specimens) and 32 control benign melanocytic lesions were retrospectively retrieved. Nuclear PRAME staining was scored as percentage and intensity labeling. All melanoma cases showed the nuclear expression of PRAME, which was usually diffuse and strong. In specimens where the neoplastic cells are limited in number, the staining was restricted to the tumor cells, corresponding to the initial H&E impression. All control cases were negative for PRAME expression. PRAME expression is helpful in distinguishing between melanomas and other nail unit melanocytic lesions. This antibody also proved to be diagnostically valuable in detecting melanoma cells in small specimens with minimal disease.

Development and Validation of a Modified Pathologic Nodal Classification System for Cutaneous Melanoma.

Importance: Given the evolving patterns of lymph node evaluation for cutaneous melanoma, it is unclear whether the current nodal classification system will continue to accurately reflect prognosis in the modern era. Existing nodal staging for cutaneous melanoma was developed primarily for patients undergoing completion lymph node dissection (CLND) for node-positive disease and does not produce groups with continuously increasing mortality. Objective: To develop and validate a modified nodal classification system for cutaneous melanoma. Design, Setting, and Participants: This retrospective cohort analysis included 105 785 patients with cutaneous melanoma undergoing surgery and nodal evaluation from January 1, 2004, to December 31, 2015, in the National Cancer Database. Extent of lymph node dissection was available for patients diagnosed in 2012 and onward. Multivariable models were generated with number of positive lymph nodes modeled using restricted cubic splines. A modified nodal classification system was derived using recursive partitioning analysis (RPA). The proposed lymph node classification system was validated in 85 499 patients from the Surveillance, Epidemiology, and End Results (SEER-18) database. Data were analyzed from April 9, 2020, to May 28, 2021. Main Outcomes and Measures: Overall survival. Results: Among the 105 785 patients included in the analysis (62 496 men [59.1%]; mean [SD] age, 59.9 [15.5] years), number of positive lymph nodes (hazard ratio [HR] per lymph node for 0 to 2 positive lymph nodes, 2.48 [95% CI, 2.37-2-61; P < .001]; HR per lymph node for ≥3 positive lymph nodes, 1.10 [95% CI 1.07-1.13; P < .001]), clinically detected metastases (HR, 1.35; 95% CI, 1.27-1.42; P < .001), and in-transit metastases (HR, 1.48; 95% CI, 1.34-1.65; P < .001) were independently associated with mortality. An RPA-derived system using these variables demonstrated continuously increasing mortality for each proposed lymph node classification group, with HRs of 1.83 (95% CI, 1.76-1.91) for N1a, 2.72 (95% CI, 2.58-2.86) for N1b, 3.79 (95% CI, 3.51-4.08) for N2a, 4.56 (95% CI, 4.22-4.92) for N2b, 6.15 (95% CI, 5.59-6.76) for N3a, and 8.25 (95% CI, 7.64-8.91) for N3b in the proposed system (P < .001). By contrast, the current American Joint Committee on Cancer (AJCC) nodal classification system produced a more haphazard mortality profile, with HRs of 1.83 (95% CI, 1.76-1.91) for N1a, 3.81 (95% CI, 3.53-4.12) for N1b, 2.59 (95% CI, 2.30-2.93) for N1c, 2.71 (95% CI, 2.56-2.87) for N2a, 4.51 (95% CI, 4.17-4.87) for N2b, 3.44 (95% CI, 2.60-4.55) for N2c, 6.06 (95% CI, 5.51-6.67) for N3a, 8.15 (95% CI, 7.54-8.81) for N3b, and 6.90 (95% CI, 5.60-8.49) for N3c. As a sensitivity analysis, the proposed system continued to accurately stratify patients when excluding those undergoing CLND for microscopic lymph node metastases. This system was validated for overall survival and cause-specific mortality in SEER-18. Last, a new overall staging system for node-positive patients was developed by RPA and demonstrated improved concordance vs the AJCC, 8th edition system (C statistic, 0.690 [95% CI, 0.689-0.691] vs 0.666 [95% CI, 0.666-0.668]). Conclusions and Relevance: The findings of this cohort study suggest that a modified nodal classification system can accurately stratify mortality risk in cutaneous melanoma in an era of increasing use of sentinel lymph node biopsy without CLND and should be considered for future staging systems.

Detection of viral gene expression in risk-stratified biopsies reveals no active HPV in cutaneous squamous cell carcinoma.

BACKGROUND: Human papillomavirus (HPV) infection is known to promote the development of mucosal squamous cell carcinoma (mSCC), including pathologically high-grade lesions, but its role in cutaneous squamous cell carcinoma (cuSCC) remains unclear, particularly in lesions that are considered high risk. OBJECTIVE: We aimed to determine whether enhanced HPV transcriptional activity can be detected in high-risk cuSCC samples compared with low-grade SCC samples or normal skin. METHODS: We performed RNA sequencing of cuSCC across 23 risk-stratified skin lesions. A subset of samples was tested for the presence of HPV DNA. High-quality, non-human reads from each sample group were used for viral analysis using Microbiome Coverage Profiler. RESULTS: None of the samples analysed had detectable expression of HPV RNA, while 64% of samples tested positive for HPV DNA. All samples were found to have expression of human endogenous retrovirus, and multiple samples showed expression of other viruses. CONCLUSIONS: Viral and prophage gene expression can be monitored in cuSCC or normal skin biopsies, yet no sample in our study showed evidence of active HPV gene expression despite evidence of HPV genome presence. This suggests HPV transcription does not play a role in differentiating high-risk cuSCCs from low-risk cuSCCs or normal skin.

Quantitative metastatic lymph node burden and survival in Merkel cell carcinoma.

BACKGROUND: Current lymph node (LN) staging for Merkel cell carcinoma (MCC) does not account for the number of metastatic LNs, which is a primary driver of survival in multiple cancers. OBJECTIVE: To determine the impact of the number of metastatic LNs on survival in MCC. METHODS: Patients with MCC undergoing surgery were identified from the National Cancer Database (NCDB). The association between metastatic LN number and survival was modeled with restricted cubic splines. A novel nodal classification system was derived by using recursive partitioning analysis. MCC patients undergoing surgery in the Surveillance, Epidemiology, and End Results (SEER) Program were used as validation cohort. RESULTS: Among 3670 patients in the NCDB, increasing metastatic LN number was associated with decreased survival (P < .001). Mortality risk increased continuously with each additional positive LN when using multivariable, nonlinear modeling. According to a novel staging system derived via recursive partitioning analysis, the hazard ratio for death in multivariable regression compared with patients without LN involvement was 1.24 (P = .049), 2.08 (P < .001), 3.24 (P < .001), and 6.13 (P < .001) for the proposed N1a (1-3 metastatic LNs with microscopic detection), N1b (1-3 metastatic LNs with macroscopic detection), N2 (4-8 metastatic LNs), and N3 (≥9 metastatic LNs), respectively. This system was validated in the SEER cohort and showed improved concordance compared with the American Joint Committee on Cancer, Eighth Edition. LIMITATIONS: Retrospective design. CONCLUSIONS: Number of metastatic LNs is the dominant nodal factor driving survival in patients with MCC.

Improved survival in women versus men with merkel cell carcinoma.

BACKGROUND: Studies have observed that women have better outcomes than men in melanoma, but less is known about the influence of sex differences on outcomes for other aggressive cutaneous malignancies. OBJECTIVE: To investigate whether women and men have disparate outcomes in Merkel cell carcinoma (MCC). METHODS: Patients with nonmetastatic MCC undergoing surgery and lymph node evaluation were identified from the National Cancer Database (NCDB) and the Surveillance, Epidemiology, and End Results (SEER) database. Kaplan-Meier analysis and Cox proportional hazards regression models were used for overall survival, and competing-risks analysis and Fine-Gray models were used for cause-specific and other-cause mortality. RESULTS: The NCDB cohort (n = 4178) included 1516 (36%) women. Women had a consistent survival advantage compared with men in propensity score-matched analysis (66.0% vs 56.8% at 5 years, P < .001) and multivariable Cox regression (hazard ratio, 0.68; 95% confidence interval, 0.61-0.75; P < .001). Similarly, women had a survival advantage in the SEER validation cohort (n = 1202) with 457 (38.0%) women, which was entirely due to differences in MCC-specific mortality (5-year cumulative incidence: 16.4% vs 26.7%, P = .002), with no difference in other-cause mortality (16.8% vs 17.8%, P = .43) observed in propensity score-matched patients. LIMITATIONS: Potential selection bias from a retrospective data set. CONCLUSION: In MCC, women have improved survival compared with men, driven by MCC-related mortality.

The association between facility volume and overall survival in patients with Merkel cell carcinoma.

BACKGROUND: Merkel cell carcinoma is an uncommon malignancy often requiring multidisciplinary management. The purpose of this study was to determine whether high-volume facilities have improved outcomes in patients with Merkel cell carcinoma relative to lower-volume facilities. METHODS: A total of 5304 patients from the National Cancer Database with stage I-III Merkel cell carcinoma undergoing surgery were analyzed. High-volume facilities were the top 1% by case volume. Multivariable Cox regression and propensity score-matching were performed to account for imbalances between groups. RESULTS: Treatment at high-volume facilities (hazard ratio: 0.74; 95% confidence interval: 0.65-0.84, P < .001) was independently associated with improved overall survival (OS) in multivariable analyses. In propensity score-matched cohorts, 5-year OS was 62.3% at high-volume facilities vs 56.8% at lower-volume facilities (P < .001). Median OS was 111 months at high-volume facilities vs 79 months at lower-volume facilities. CONCLUSION: Treatment at high-volume facilities is associated with improved OS in Merkel cell carcinoma. Given the impracticality of referring all elderly patients with Merkel cell carcinoma to a small number of facilities, methods to mitigate this disparity should be explored.

Overview of Deep Dermal Fillers.

Dermal fillers have become an integral part of both medical and cosmetic dermatology. Our expanding knowledge of the aging face has allowed us to shift the focus from skin-reduction lifting procedures to soft tissue augmentation. Within the past 5 years alone, nine new dermal fillers have been approved by the U.S. Food and Drug Administration for soft tissue augmentation. The rise in both the use and number of dermal fillers in recent years is a testament to their safety and efficacy. Dermal fillers can be broken down to three major types: temporary, semipermanent, and permanent. The former, which include hyaluronic acid based fillers, provide safe and effective correction but only for a limited time, typically approximately 1 to 2 years at best. This review will cover the semipermanent (poly-L-lactic acid and calcium hydroxylapatite) and permanent (polymethylmethacrylate and liquid silicone) injectable fillers. These so-called deep dermal fillers are valuable, durable tools in correcting the aging face. Given their extended duration of effect, these fillers inherently carry their own risk for potential adverse events. Thus, it is essential that clinicians have a thorough understanding of these products to best counsel, recommend, and perform soft tissue augmentation using these fillers.

Examining the Relevance to Patients of Complications in the American College of Mohs Surgery Registry: Results of a Delphi Consensus Process.

BACKGROUND: Surgical registries are valuable tools for tracking outcomes. Incorporating patient input allows registries to address the interests of this important stakeholder group. OBJECTIVE: The aim of this study was to identify a list of "patient-selected complications" and to explore the relevance to patients of previously published physician-identified complications. METHODS: Delphi process with 2 rounds using patients to identify complications that are highly relevant for tracking by the proposed American College of Mohs Surgery (ACMS) National Registry. RESULTS: Complications that physicians identified as highly relevant (death from any cause, hospitalization related to the procedure, functional loss attributable to surgery, bleeding requiring a second procedure, and surgical site infection) were each rated as highly relevant by patients. Patients also identified scarring, recurrence, and wound dehiscence as highly relevant outcomes for registry tracking. CONCLUSION: Incorporating patient input into the ACMS registry design process identified 2 additional complication outcomes to be considered for inclusion within the registry-wound dehiscence and scarring. Patient input also corroborated the relevance of complications previously identified by ACMS physicians for inclusion in the registry. Furthermore, the importance of tracking local recurrence was confirmed from a patient-centered perspective.

A clinical and biological evaluation of a novel, noninvasive radiofrequency device for the long-term reduction of adipose tissue.

BACKGROUND AND OBJECTIVE: A novel, noninvasive technology, utilizing suction-coupled radiofrequency (RF) heating and ultra-short pulse duration, high-voltage electrical pulses was studied for its efficacy and safety on adipose tissue reduction. METHODS: Twenty-one subjects underwent treatment of their abdominal fat once weekly for 6 weeks. Clinical outcomes including abdominal circumference, adipose tissue thickness (measured by ultrasound), adipose tissue weight, body weight, and clinical photographs were obtained at visits 1 and 3 months after last treatment. Adverse events were recorded. Three subjects, who were undergoing a future elective abdominoplasty, were treated with the same protocol, but on only one side of the abdomen before abdominoplasty. Biopsies from the RF-treated and untreated sides were harvested during abdominoplasty and cultured; measurements of adipocyte size and shape, rate of apoptosis, collagen production, and dermal thickness were determined. RESULTS: Significant clinical improvements (P < 0.05) were observed for the following clinical outcomes: reduction of abdominal circumference (113.4-110.7 cm), reduction of subcutaneous adipose tissue thickness (40.5-38.5 mm), and reduction in adipose tissue weight (32.2-30.7 kg) at 3-month follow-up visits. Overall patient weight also decreased, which was statistically significant at 1-month follow-up, but was not statistically significant at 3-month follow-up (73.9-73.3 kg, P = 0.609). Histologically, adipocytes were observed to have decreased size and withered shape, with increased levels of apoptosis; increased collagen synthesis, with compaction and reorganization of the dermis was also observed. Only minor, transient side effects were reported. CONCLUSIONS: This novel, noninvasive RF device was effective for improving subcutaneous fat, reducing abdominal circumference and reducing subcutaneous fat layer thickness. Histologically, these improvements appear to be partly related to increased adipocyte apoptosis.

An unusual presentation and distribution of generalized eruptive syringomas.

A 19-year-old Caucasian man presented with numerous erythematous to flesh-colored papules that appeared in crops on his neck, axillae, buttocks, and lower back. The lesions started on his anterior neck at age 12. At 18 years, new crops of papules appeared on his axillae, back, and buttocks over several months. He reported pruritus in the lesions following exercise and perspiration. He denied any family history of similar lesions. His primary care physician treated him with topical triamcinolone 0.1% cream, which made the lesions smaller, less erythematous, and less pruritic; however, the papules never fully resolved. After discontinuation of the steroids, these erythematous pruritic papules gradually recurred in the same areas of his body. The patient denied any other medical complaints.

Acquired perforating dermatosis associated with metastatic colon cancer.

Acquired perforating dermatosis (APD) is a type of perforating disorder that is traditionally thought to be associated with diabetes, chronic renal failure, or occasionally liver disease. We report a case of APD in a patient with stage IV colon cancer with hepatic metastases. Although rare, APD associated with colon cancer is an important entity to consider; APD may be associated with a broader range of systemic diseases than previously recognized.

Role of endothelial nitric oxide synthase in the regulation of SREBP activation by oxidized phospholipids.

Oxidized-1-palmitoyl-2-arachidonyl-sn-glycero-3-phosphorylcholine (Ox-PAPC), found in atherosclerotic lesions and other sites of chronic inflammation, activates endothelial cells (EC) to synthesize chemotactic factors, such as interleukin (IL)-8. Previously, we demonstrated that the sustained induction of IL-8 transcription by Ox-PAPC was mediated through the activation of sterol regulatory element-binding protein (SREBP). We now present evidence for the role of endothelial nitric oxide synthase (eNOS) in the activation of SREBP by Ox-PAPC. Ox-PAPC treatment of EC induced a dose- and time-dependent activation of eNOS, as measured by phosphorylation of serine 1177, dephosphorylation of threonine 495, and the conversion of L-arginine to L-citrulline. Activation of eNOS by Ox-PAPC was regulated through a phosphatidylinositol-3-kinase/Akt-mediated mechanism. These studies also demonstrated that pretreatment of EC with NOS inhibitor, Nomega-nitro-L-arginine-methyl ester (L-NAME), significantly inhibited Ox-PAPC-induced IL-8 synthesis. Because SREBP activation had been previously shown to regulate IL-8 transcription by Ox-PAPC, we examined the effects of L-NAME on Ox-PAPC-induced SREBP activation. Our data demonstrated that Ox-PAPC-induced SREBP activation and expression of SREBP target genes were significantly reduced by pretreatment with L-NAME. Interestingly, treatment of EC with NO donor, S-nitroso-N-acetylpenicillamine, did not activate SREBP, suggesting that NO alone was not sufficient for SREBP activation. Rather, our findings indicated that superoxide (O2*-), in combination with NO, regulated SREBP activation by Ox-PAPC. We found that Ox-PAPC treatment generated O2*- through an eNOS-mediated mechanism and that mercaptoethylguanidine, a peroxynitrite scavenger, reduced SREBP activation by Ox-PAPC. Taken together, these findings propose a novel role for eNOS in the activation of SREBP and SREBP-mediated inflammatory processes.