Racial and ethnic disparities in melanoma awareness: A cross-sectional survey.

BACKGROUND: Hispanics are among the fastest growing population in the United States and are predicted to account for one third of the nation by 2060. Although melanoma is more common among white patients, Hispanic individuals are at greater risk of late-stage diagnosis, increased tumor thickness, and poorer survival. OBJECTIVE: To better understand public awareness of melanoma and evaluate change over the last 21 years, particularly among high-risk minority populations. METHODS: A cross-sectional survey collecting information on knowledge and awareness of melanoma was conducted on 285 participants from May through November 2017. RESULTS: Approximately 39% of participants were unaware of melanoma. Sixty-five percent successfully identified early signs of disease. Approximately 86% of Fitzpatrick skin types (FST) I and II identified melanoma as a cancer, compared to 46.3% of FST III and IV and 57.6% of FST V and VI. Hispanic particiapnts were less likely to know what melanoma was compared to white participants (odds ratio [OR], 0.27; 95% confidence interval [CI], 0.65-0.11; P = .0037). US natives (OR, 2.38; 95% CI, 5.56-1.04; P = .0403) and patients with any college education (OR, 2.86; 95% CI, 5.26-1.54; P = .0007) were more likely to know the meaning of melanoma. CONCLUSION: White participants and those with any college education were more likely to know the meaning of melanoma. Individuals of racial and ethnic minorities would benefit from educational programs geared toward early detection.

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.

Survival outcomes of mucosal melanoma in the USA.

Background: Mucosal melanomas (MM) arise within the lining of the gastrointestinal (GI), genitourinary (GU) and head and neck (HN) systems. Method: A retrospective analysis of the National Comprehensive Database identified 4,961 MM patients. Primary objective was to compare survival outcomes across the different locations. Results: Overall survival for GI melanomas was significantly shorter than HN and GU melanomas. Median survival (95% confidence interval) was 19.5 (18.0-21.5), 26.4 (24.9-28.3), and 43.9 (38.8-47.8), months for GI, HN and GU cases, respectively (p<0.0001). Conclusion: This is the largest study of MM in a US based population, demonstrating worse overall survival for GI MM in comparison to HN and GU melanomas.

Extensive CD34-to-CD90 Fibroblast Transition Defines Regions of Cutaneous Reparative, Hypertrophic, and Keloidal Scarring.

BACKGROUND: CD90 fibroblasts have been described arising from and replacing the homeostatic CD34 network in scleroderma, but have not been specifically examined in other forms of cutaneous fibrosis. OBJECTIVES: To address expression, timelines, and spatial relationships of CD90, CD34, and smooth muscle actin (SMA) expressing fibroblasts in scars and to examine for the presence of a CD34-to-CD90 transition. METHODS: One hundred and seventeen scars (reparative/hypertrophic/keloidal) were evaluated for CD90, CD34, and SMA expression. Double-staining immunohistochemistry for CD90/CD34 was performed to identify CD90/CD34 transitioning cells, confirmed by double-color immunofluorescence. In addition, some scars were double-stained with CD90/SMA, CD90/procollagen-1, or SMA/procollagen-1 to evaluate spatial relationships and active collagen synthesis. Expression was graded as diffuse, minority, and negative. RESULTS: Most scars demonstrate a CD90/CD34 pattern, and dual CD90/CD34 fibroblasts were observed in 91% of scars. In reparative scars, CD90 expression reverses to a CD34/CD90 state with maturation. Pathologic scars exhibit prolonged CD90 expression. Both CD90 and SMA fibroblasts collagenize scars, although CD90 fibroblasts are more prevalent. CONCLUSIONS: CD90 fibroblasts likely arise from the resting CD34 fibroblastic network. Actively collagenizing scar fibroblasts exhibit a CD90/CD34 phenotype, which is prolonged in pathologic scars. CD90 fibroblasts are likely important players in cutaneous scarring.

Demographics and outcomes of stage I and II Merkel cell carcinoma treated with Mohs micrographic surgery compared with wide local excision in the National Cancer Database.

BACKGROUND: The optimal surgical approach (wide local excision [WLE] vs Mohs micrographic surgery [MMS]) for treating Merkel cell carcinoma (MCC) is yet to be determined. OBJECTIVE: To compare survival outcomes in patients with early-stage MCC treated with MMS versus with WLE. METHODS: A retrospective review of all cases in the National Cancer Database (NCDB) of MCC of clinical stage I or II MCC treated with WLE or MMS was performed. RESULTS: A total of 1795 cases of stage I or II MCC who underwent WLE (n = 1685) or MMS (n = 110) were identified. There was no difference in residual tumor on surgical margins between the 2 treatment groups (P = .588). On multivariate analysis, there was no difference in overall survival between the treatment modalities (adjusted hazard ratio, 1.02; 95% confidence interval, 0.72-1.45; P = .897). There was no difference in overall survival between the 2 groups on propensity score-matched analysis. LIMITATIONS: Disease-specific survival was not reported, as these data are not available in the National Cancer Database. CONCLUSIONS: MMS appears to be as effective as WLE in treating early-stage MCC.

Amelanotic melanoma arising within a lesion of disseminated superficial actinic porokeratosis: An unusual presentation leading to a novel therapeutic approach.

Disseminated superficial actinic porokeratosis (DSAP) is the most common variant of porokeratosis with a potential for malignant transformation. Its association with malignant melanoma, however, is exceedingly rare. Treatment of DSAP is often ineffective. We report a unique case of amelanotic melanoma arising within a lesion of DSAP. The melanoma was managed surgically, and her DSAP were treated successfully with a novel approach utilizing 5-fluorouracil chemowraps.

Anaplastic large cell lymphoma localized to the left breast years after radiotherapy for breast cancer.

Anaplastic large cell lymphoma (ALCL) is a rare type of non-Hodgkin lymphoma that can involve the skin primarily or secondarily. Our case describes an unusual presentation of eruptive tumors localized to the leftbreast region several years following breast cancer surgery and radiation for carcinoma of the breast. This report highlights the challenges in reachingthe diagnosis of an aggressive systemic lymphoma presenting on the skin.

Benign and malignant hybrid adnexal tumors in a patient with epidermodysplasia verruciformis.

Epidermodysplasia verruciformis (EV) is a genodermatosis characterized by overgrowth of flat warts, pityriasis versicolor-like lesions and an increased propensity for developing cutaneous squamous cell carcinomas due to abnormal susceptibility to infection with beta-human papilloma viruses. Adnexal tumors are not typically associated with EV. Here we report a spectrum of hybrid adnexal tumors with divergent eccrine and folliculosebaceous differentiation, and cytologic features ranging from benign to frankly atypical, in a patient with inherited EV.

Immunocytochemical p63 expression discriminates between primary cutaneous follicle centre cell and diffuse large B cell lymphoma-leg type, and is of the TAp63 isoform.

AIMS: The p63 gene shares structural and functional homologies with the p53 family of transcriptional activators, but differs in exhibiting a consistent expression pattern in normal tissues. Although p63 is rarely mutated in malignancy studies of primary human tumours and cell lines suggest that p63 may promote tumour development. In non-Hodgkin's nodal lymphoma, TAp63 expression in follicular lymphoma (54%) and diffuse large B cell lymphoma (34%) has been described and correlated with the proliferative index. In this study, we analysed a series of primary cutaneous B cell lymphomas for immunohistochemical expression of p63. METHODS AND RESULTS: Thirty cases of diffuse large B cell lymphoma leg type (pcDLBCLL) and 34 cases of follicle centre cell lymphoma (pcFCCL) were stained using a generic antibody to p63, and a subset of these with an antibody specific for delta-Np63 isoform. The results indicate a significant difference between pcDLBCLL (21 of 30) and pcFCCL (four of 34) in p63 expression (P = 0.000); expression correlated strongly with the proliferation rate as assessed by Ki-67 (P = 0.015). None of the p63((+)) cases tested expressed the delta-Np63 isoform, suggesting that expression is of the TAp63 isoform. CONCLUSIONS: Functional studies are required to clarify the significance of p63 overexpression in primary cutaneous B cell lymphoma.

Epidermolytic hyperkeratosis of the vulva: Case report and review of the literature.

Epidermolytic hyperkeratosis is a rare histopathological phenomenon which has been reported in a number of dermatological conditions. It is rare but can cause chronic and intractable symptoms which can impede the quality of life of those affected. Treatment options are variable and not enough data exists to provide a definitive protocol for management. We present this case to highlight a simple, efficacious way for dermatologists to treat the condition and provide a literature review.

Skin cancer in renal transplant recipients: outcomes from a safety net hospital in Boston.

BACKGROUND: Renal transplant recipients (RTRs) are prone to skin cancer due to the immunosuppression required to maintain graft function. Existing studies of skin cancer in RTRs focus on patients with Fitzpatrick skin types I-II, with limited documentation of incidence in skin types III-VI. This study seeks to better characterize skin cancers in RTRs with skin types III-VI. PRIMARY AIMS: Compare the incidence of skin cancer in RTRs of skin types I-II with skin types III-VI. SECONDARY AIMS: Explore the association between the development of skin cancer and other contributing factors in RTRs of skin types I-VI. METHODS: Retrospective chart review of RTRs at a single institution between January 1, 2000 and December 31, 2022. Patients were followed from the date of transplant to the last clinical follow-up or death. 777 RTRs were included in the study, including 245 patients with Fitzpatrick skin types I-II and 532 with skin types III-VI. A total of 48 patients developed NMSCs, 2 patients developed melanoma, and 3 patients developed Kaposi sarcoma. RESULTS AND CONCLUSIONS: There is a higher incidence of skin cancer in RTRs with Fitzpatrick skin types III-VI compared to the reported incidence among non-transplant recipients of the same skin types, but the incidence remains considerably lower compared to RTR of skin types I-II.

Early Detection and Prognostic Assessment of Cutaneous Melanoma: Consensus on Optimal Practice and the Role of Gene Expression Profile Testing.

Importance: Therapy for advanced melanoma has transformed during the past decade, but early detection and prognostic assessment of cutaneous melanoma (CM) remain paramount goals. Best practices for screening and use of pigmented lesion evaluation tools and gene expression profile (GEP) testing in CM remain to be defined. Objective: To provide consensus recommendations on optimal screening practices and prebiopsy diagnostic, postbiopsy diagnostic, and prognostic assessment of CM. Evidence Review: Case scenarios were interrogated using a modified Delphi consensus method. Melanoma panelists (n = 60) were invited to vote on hypothetical scenarios via an emailed survey (n = 42), which was followed by a consensus conference (n = 51) that reviewed the literature and the rationale for survey answers. Panelists participated in a follow-up survey for final recommendations on the scenarios (n = 45). Findings: The panelists reached consensus (≥70% agreement) in supporting a risk-stratified approach to melanoma screening in clinical settings and public screening events, screening personnel recommendations (self/partner, primary care provider, general dermatologist, and pigmented lesion expert), screening intervals, and acceptable appointment wait times. Participants also reached consensus that visual and dermoscopic examination are sufficient for evaluation and follow-up of melanocytic skin lesions deemed innocuous. The panelists reached consensus on interpreting reflectance confocal microscopy and some but not all results from epidermal tape stripping, but they did not reach consensus on use of certain pigmented lesion evaluation tools, such as electrical impedance spectroscopy. Regarding GEP scores, the panelists reached consensus that a low-risk prognostic GEP score should not outweigh concerning histologic features when selecting patients to undergo sentinel lymph node biopsy but did not reach consensus on imaging recommendations in the setting of a high-risk prognostic GEP score and low-risk histology and/or negative nodal status. Conclusions and Relevance: For this consensus statement, panelists reached consensus on aspects of a risk-stratified approach to melanoma screening and follow-up as well as use of visual examination and dermoscopy. These findings support a practical approach to diagnosing and evaluating CM. Panelists did not reach consensus on a clearly defined role for GEP testing in clinical decision-making, citing the need for additional studies to establish the clinical use of existing GEP assays.

Poikilodermatous mycosis fungoides: a study of its clinicopathological, immunophenotypic, and prognostic features.

BACKGROUND: Poikilodermatous mycosis fungoides (MF) is a variant of MF, and its clinicopathological, immunophenotypic, molecular, and prognostic features have not previously been defined in the literature. OBJECTIVE: The purpose of this study was to improve the data available for this variant of MF thus enabling clinicians to apply the appropriate treatment and follow-up. METHODS: In a retrospective single center study we evaluated the clinical, histopathological, immunohistochemical, and molecular characteristics of patients with predominant (>50%) poikilodermatous lesions of MF. RESULTS: In all, 49 patients were identified. The median age at diagnosis was 44 years (15-81 years). Of 49 patients, 43 (88%) had early stage disease (≤IIA) at diagnosis. No patients had stage IV disease at presentation. A frequent association was coexistence of lymphomatoid papulosis (9/49; 18%). Histopathology review showed a high number of cases with CD8(+) CD4(-) atypical lymphocytes (38%). After diagnosis most patients were treated with expectant or skin-directed therapy. Psoralen plus ultraviolet A therapy was most frequently used and had high response rates (83%). Five (10%) of 49 received systemic therapy. The mean follow-up was 11 years, 10 months (1->40 years). In all, 47 (96%) of 49 patients had stable disease and two (4%) of 49 had progressive disease. No patients died during follow-up. LIMITATIONS: As a tertiary center our patient cohort may be expected to have more advanced and aggressive disease. CONCLUSION: Poikilodermatous MF represents a distinct clinicopathological entity from classic patch/plaque MF. It presents at a younger age and is more frequently associated with lymphomatoid papulosis. There is an increased number of cases with predominantly CD8(+) CD4(-) atypical lymphocytes. Overall there is a good response to phototherapy and the overall prognosis appears favorable.

Treatment of unresectable cutaneous squamous cell carcinoma with pembrolizumab.

Currently, there are few effective therapies for locally advanced and metastatic cutaneous squamous cell carcinoma (cSCC); however, there is recent evidence supporting the use of immunological therapies in cSCC given the typically high mutation burden and association with immunosuppressed states. This report describes a 56-year-old man presenting with synchronous, invasive cSCC on the right temple and right dorsum of the hand deemed unfavourable for surgical resection. The patient was treated with nine infusions of programmed cell death protein 1 (PD-1) inhibitor therapy, pembrolizumab, with clinical and radiographical resolution of his lesions. This case illustrates the potential use of anti-PD-1 antibody as a first-line treatment in the setting of advanced, unresectable cSCC.

Comparing survival outcomes in early stage desmoplastic melanoma with or without adjuvant radiation.

Desmoplastic melanoma (DM) due to its rare and locally aggressive nature, can be difficult to study and to treat effectively. Whether the optimal treatment approach for these tumors should include adjuvant radiation has been unclear in the literature. In this retrospective study of the National Cancer Database, 2390 patients with localized DM were included for analysis. 2082 were treated with wide local excision (WLE) and 308 were treated with wide local excision and adjuvant radiation therapy (WLE + RT). Overall survival (OS) in these groups was compared on crude and adjusted analyses utilizing Cox proportional hazards regression modeling. There was no difference in OS at 1, 3, and 5 years on initial analysis. Subsequent multivariate analysis and propensity score analysis showed a survival benefit in those treated with WLE + RT. Multivariate analysis demonstrated significantly decreased OS in cases of residual tumor following surgical excision. Adjuvant radiation was more likely to be performed for tumors on the head and neck, tumors with higher pathologic American Joint Committee on Cancer stage and T classifications, and tumors with positive surgical margins. This is the first study to demonstrate significantly improved OS in early-stage DM patients treated with WLE + RT compared to WLE alone.

Identifying an Optimal Adjuvant Radiotherapy Dose for Extremity and Trunk Merkel Cell Carcinoma Following Resection: An Analysis of the National Cancer Database.

Importance: Merkel cell carcinoma (MCC) is a rare and aggressive cutaneous neuroendocrine neoplasm with a high risk of recurrence following resection. Despite a rising incidence over the past 3 decades, there is a paucity of prospective data owing to the rarity of this disease. Objective: To determine the optimal adjuvant radiation therapy (RT) dose following resection of localized MCC of the extremities or trunk. Design, Setting, and Participants: Using the National Cancer Database, a large national database consisting of a heterogeneous population and treatment settings, we retrospectively analyzed a cohort of 2093 patients 18 years or older with stage I to III MCC of the extremities and/or trunk treated with definitive surgery and adjuvant RT between 1998 and 2011. Exclusion criteria included receiving treatment with palliative intent, preoperative RT, non-external-beam RT, and radiation dose of 30 Gy or lower or 70 Gy or higher. Cox proportional hazards regression model was used to compare overall survival (OS) between RT dose groups, accounting for age, sex, race, stage, surgery type, margin status, comorbidities, and use of chemotherapy. Exposures: Radiation therapy dose was categorized into 4 groups: group 1 received the lowest dose (>30 to <40 Gy); group 2, the next lowest (40 to <50 Gy); group 3, the second highest dose (50 to 55 Gy); and group 4, the highest dose (>55 to 70 Gy). Main Outcome and Measure: Overall survival. Results: Data from 2093 patients were analyzed; there were 1293 men (61.8%) and 800 women (38.2%) (median age, 73 years). After a median follow-up of 37 months for the entire cohort, 904 deaths were reported. The 3-year OS rates for groups 1, 2, 3, and 4 were 41.8%, 69%, 69.2%, and 66%, respectively (omnibus P < .001). Compared with group 3 (50 to 55 Gy), equivalent OS was seen in group 2 (40 to <50 Gy; adjusted hazard ratio [AHR], 0.89; 95% CI, 0.63-1.27; P = .52) and group 4 (>55 to 70 Gy; AHR, 1.18; 95% CI, 0.93-1.48; P = .17), but worse OS was found in group 1 (>30 to <40 Gy; AHR, 2.63; 95% CI, 1.44-4.80; P < .001). Conclusions and Relevance: Adjuvant RT dose from 40 to lower than 50 Gy appears adequate for extremities and/or trunk stage I to III MCC, with OS equivalent to that found at higher-dose regimens (>50 to 70 Gy).