Clinical Versus Histologic Margins for Cutaneous Squamous Cell Carcinoma: Comparing Outcomes for High-Risk Tumors Treated With Mohs Micrographic Surgery.

BACKGROUND: High-risk cutaneous squamous cell carcinoma (cSCC) is associated with poor clinical outcomes. Traditionally, preoperative clinical tumor size ≥2 cm, based on Brigham and Women's Hospital (BWH) staging criteria, is high risk. OBJECTIVE: To compare outcomes of cSCC treated with Mohs micrographic surgery (MMS) with a preoperative size ≥2 cm (clinically ≥2 cm) versus cSCC with preoperative size <2 cm and postoperative defect size ≥2 cm (histologically ≥2 cm). METHODS: Prospective data were collected from January 1, 2014, to December 31, 2020, on MMS cases for cSCC with a preoperative and/or postoperative size ≥2 cm. Clinical outcomes were followed until March 15, 2023. Data were analyzed using multivariate regression. RESULTS: Three hundred thirty cases of MMS for cSCC were included. Cutaneous squamous cell carcinoma clinically ≥2 cm occurred more frequently in elderly patients; cSCC histologically ≥2 cm were more commonly located in the H region, required wider surgical margins, and more MMS stages to achieve clearance. There were no significant differences in rates of recurrence and metastasis between the groups. CONCLUSION: These data suggest that postoperative (histologic) MMS defect size may allow for better risk stratification of high-risk cSCC and improved staging of cSCC.

Management of androgenic alopecia: a systematic review of the literature.

We aimed to determine the efficacy of the various available oral, topical, and procedural treatment options for hair loss in individuals with androgenic alopecia. Using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, a systematic review of the National Library of Medicine was performed. Overall, 141 unique studies met our inclusion criteria. We demonstrate that many over the counter (e.g. topical minoxidil, supplements, low-level light treatment), prescription (e.g. oral minoxidil, finasteride, dutasteride), and procedural (e.g. platelet-rich plasma, fractionated lasers, hair transplantation) treatments successfully promote hair growth, highlighting the superiority of a multifaceted and individualized approach to management.

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.

Survival outcomes of rare cutaneous malignancies within an insured cohort of patients, 1988-2018.

BACKGROUND: There are limited survival data on cutaneous angiosarcoma (CAS), dermatofibrosarcoma protuberans (DFSP), Merkel cell carcinoma (MCC), and sebaceous carcinoma (SC). OBJECTIVE: To analyze survival trends in CAS, DFSP, MCC, and SC among a racially diverse, insured cohort of patients. METHODS: Using data from the Kaiser Permanente Southern California Cancer Registry, we identified adults diagnosed with CAS, DFSP, MCC, or SC between January 1, 1988 and December 31 2018, followed through December 31, 2021. RESULTS: Our cohort consisted of 83 diagnoses of CAS, 490 diagnoses of DFSP, 411 diagnoses of MCC, and 249 diagnoses of SC. Our analysis revealed no significant differences in overall or disease-specific 1000 person-years mortality rates among our populations of non-Hispanic Whites, Hispanics, African American/Blacks, and Asian American/Pacific Islanders diagnosed with CAS, DFSP, MCC, or SC. On multivariate analysis, controlling for patient and tumor characteristics, there was similarly no increased risk of overall mortality for minorities diagnosed with CAS, DFSP, MCC, or SC. LIMITATIONS: Retrospective nature of the analysis and small sample size. CONCLUSION: Contrary to existing literature, our results show a notable lack of racially driven survival disparities among insured individuals with CAS, DFSP, MCC, and SC, emphasizing the importance of health care coverage.

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.

Review of radiofrequency microneedling: history, devices and uses.

Radiofrequency microneedling (RFM) has recently become a popular choice for the treatment of various dermatologic conditions and rejuvenation. Many studies have sought to evaluate the efficacy of RFM. However, its role in the management of these conditions remains unclear. A comprehensive literature search including randomized controlled trials, cohort studies, and case series evaluating the efficacy of RFM in various skin conditions was performed. In this review, we discuss the history and mechanism of RFM, describe various device features, and discuss the use of RFM in various skin conditions and rejuvenation.

From Centimeters to Millimeters: The Evolution of the Surgical Margins for Melanoma-A Historical Review.

BACKGROUND: With an improved understanding of tumor biology and behavior, the recommended margins for the surgical treatment of melanoma have evolved. OBJECTIVE: We describe the progression of these surgical margins, detailing the historical basis for the 5-cm margin and transitioning to current practice, in which Mohs micrographic surgery (MMS) with immunohistochemistry (IHC) has become increasingly used. METHODS/MATERIALS: We searched PubMed and Google Scholar for articles published between January 2019 and April 2023 describing the use of MMS for melanoma in situ (MIS) and invasive melanomas. RESULTS: We identified 12 articles focusing on the use of MMS for MIS and invasive melanomas: 3 meta-analyses and 9 retrospective studies. Two retrospective analyses documented no differences in overall survival between MMS and wide local excision (WLE) and 2 found improved overall survival for MMS compared with WLE. Three retrospective analyses and 3 meta-analyses demonstrated low recurrence rates after the use of MMS for both MIS and invasive melanomas. Finally, 2 retrospective studies documented the success of MMS with IHC using MART-1. CONCLUSION: Over the past century, the surgical margins for the treatment of melanoma have undergone a marked transformation. MMS with IHC has become increasingly popular given its ability to reliably produce superior clinical outcomes.

Permanent section margin concordance after Mohs micrographic surgery with immunohistochemistry for invasive melanoma and melanoma in situ: A retrospective dual-center analysis.

BACKGROUND: Mohs micrographic surgery (MMS) for melanoma practices vary among dermatologic surgeons. The implementation of immunohistochemical staining in MMS for melanoma mitigates challenges associated with slide interpretation; however, the reliability of melanoma antigen recognized by T cells 1 (MART-1), the preferred immunostain for melanoma, has yet to be compared with permanent section pathology. OBJECTIVE: To assess concordance rates of MART-1 frozen sections and permanent section pathologic interpretation of melanoma treated with MMS. METHODS: A dual-center retrospective analysis was conducted to collect concordance and demographic data. Chi-square tests were performed for group comparisons of categorical variables. RESULTS: Of the 379 permanent sections sent, 367 were concordant with frozen section pathology for an overall concordance rate of 96.8%. Cases were stratified into indeterminately concordant and indisputably concordant. Twenty-two (6%) of cases were indeterminately concordant, whereas 345 (94.0%) of cases were indisputably concordant. LIMITATIONS: The concordance rate is derived from a comparison of adjacent tissue margins, an inevitable consequence of utilizing 2 techniques. CONCLUSION: To the author's knowledge, this study represents the largest investigation examining concordance rates of MART-1 frozen sections in Mohs for melanoma. High concordance disputes the ongoing need for additional permanent margins when using MART-1 in routine cases.

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.

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.

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.

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.