Cutaneous T cell Lymphoma in Skin of Color: A Review.

People of color (POC) affected by skin cancer suffer disproportionately from worse morbidity and mortality. Although skin cancers occur most frequently in White individuals overall, cutaneous T-cell lymphoma (CTCL) is an exception. CTCL is a rare skin cancer comprising several subtypes of non-Hodgkin lymphoma; each contains a unique clinical profile that varies with race. Our aim is to review and compile the differences in epidemiology, clinical presentation, treatments, and outcomes of the CTCL subtypes in Black, Asian or Pacific-Islander (API), and Hispanic patients. The current literature supports that there are nuances in the course of CTCL that differ with race. Across multiple studies, racial differences in incidence patterns have been reported, with the highest rates among Black patients. Cutaneous manifestation of CTCL are highly variable in POC, and the predilection for clinical CTCL variants often differs with race, as well as severity of cutaneous involvement (BSA). Response to and type of treatment also differs among POC, and may be partially attributable to the varying CTCL subtypes experienced by certain races. Prognostic factors tend to vary with race, although Black patients consistently experience poor outcomes, while API patients may have a more favorable prognosis. Currently, there is no definitive conclusion to account for differences observed in CTCL skin of color patients, however biologic and socioeconomic factors have been proposed as potential drivers. As POC comprise an increasing portion of our population, adequate physician awareness and knowledge of racial nuances in CTCL are necessary to begin addressing these disparities.

Misclassification of Aggressive Basal Cell Carcinoma Subtypes and Implications for Management.

BACKGROUND: Management of basal cell carcinoma (BCC) varies by histopathologic subtype; however, biopsies may inadequately characterize them as nonaggressive, risking potential suboptimal treatment. OBJECTIVE: To characterize the rate of undetected aggressive BCC subtypes by size, location, and histopathology type. MATERIALS AND METHODS: Retrospective cohort study of 928 BCCs treated with Mohs Micrographic Surgery (MMS) at a tertiary academic institution from 2015 to 2017, comparing patient and tumor characteristics and histopathologic subtype on biopsy versus Mohs. RESULTS: Among the 825 BCCs with known subtypes on biopsy, 68% (561/825) were classified as nonaggressive, 28% (159/561) of which were subsequently found to have aggressive subtypes on MMS. Aggressive features were more often underrepresented in biopsy samples taken from Area H compared with Area M/L (odd ratio [OR] 2.65, 95% confidence interval [CI] 1.73-4.08, p < .001) or those with nodular subtypes (OR 2.19, CI 1.08-4.45, p = .03). Of concern, these unsuspected aggressive BCCs required more Mohs stages for clearance (mean 2.37, SD 0.72, p < .001) compared with BCCs that remained nonaggressive on both biopsy and Mohs (mean 1.50, SD 0.75). CONCLUSION: Given the high percentage of BCCs with unsuspected aggressive subtypes, higher clinical suspicion for undiagnosed high-risk BCCs should be given to nodular BCCs and to BCCs on Area H.

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.

Next-generation sequencing identifies novel single nucleotide polymorphisms in high-risk cutaneous squamous cell carcinoma: A pilot study.

BACKGROUND: Cutaneous squamous cell carcinoma (SCC) causes 1 million cases in the United States annually. There are germline single nucleotide polymorphisms (SNPs) that result in an increased risk of SCC and altered response to therapy. PREMISE: There may be biologically relevant SNPs not detected using traditional GWAS studies. HYPOTHESIS: There are clinically and biologically relevant SNPs in high-risk SCC that may only be appreciated with next-generation sequencing. HOW TO TEST HYPOTHESIS: We performed next-generation sequencing (NGS) on primary SCCs using a targeted mutation panel with 76 cancer-associated genes. We analysed the presence of SNPs in a cohort of 20 high-risk SCCs compared to the American population (AP) (dbSNP). RELEVANCE AND PERSPECTIVES: Missense rs3822214 was present in significantly more SCC cases versus the AP. While the remainder is synonymous SNPs, there is growing evidence suggesting clinical relevance of these variants. A larger cohort to validate these findings would be useful.

Defining skin cancer local recurrence.

Definitions of skin cancer recurrence are variable and nonstandardized, which can lead to inconsistent and potentially inappropriate management of tumors of uncertain recurrence status. Defining recurrence is important given the potential association with metastasis in both melanoma and nonmelanoma skin cancer. A review of the literature across multiple disciplines involved in the care of skin cancer patients reveals that although criteria for recurrence are provided in the majority of cases, most are vague and inconsistent. Given the presumably increased morbidity and mortality associated with recurrent tumors, accurate identification and appropriate management is paramount. In addition, value-based health care necessitates validated and relevant outcome measures that are standardized and, thus, enable tracking of comparable and corresponding outcomes. A universal definition of localized skin cancer recurrence would ultimately allow for improved surveillance and informed therapeutic strategies to decrease morbidity and mortality of patients afflicted with skin cancer, the most common cancer nationwide.

A Retrospective Cohort Study of Cutaneous Squamous Cell Carcinoma With Lymph Node Metastasis: Risk Factors and Clinical Course.

BACKGROUND: The single most important prognostic indicator for mortality in patients with cutaneous squamous cell carcinoma (SCC) is the development of nodal metastasis (NM). OBJECTIVE: To characterize the risk factors for and clinical course of cutaneous SCC with NM. METHODS: Ten-year retrospective cohort study (2006-2017) at an academic tertiary care center reviewing 53 cutaneous SCC tumors with NM. RESULTS: Most patients were men (84.6%, 44/52), and almost all primary tumors were on the head and neck (96.2%, 51/53). Most primary tumors were characterized by known "high-risk features" including perineural invasion (56.6%, 30/53), diameter ≥2 cm (54.7%, 29/53), invasion beyond subcutaneous fat (43.4%, 23/53), and poor differentiation (32.1%, 17/53). In addition, many tumors were recurrent (52.8%, 28/53), and many patients were immunosuppressed (30.8%, 16/52). Disease-free survival after treatment of nodal disease was 7.5% (4/53) at 5 years. CONCLUSION: To the best of the authors' knowledge, this study is the largest retrospective cohort of cutaneous SCC with NM to date. The results verify the significance of "high-risk features" used by current staging systems while highlighting additional features that may have prognostic value. This study may be used to refine current staging systems, improve early detection, and optimize management for these aggressive tumors.

Virtual Reality to Improve the Experience of the Mohs Patient-A Prospective Interventional Study.

BACKGROUND: Nonmelanoma skin cancer is the most common cancer in the United States with significant quality of life impact. OBJECTIVE: To assess the utility of a highly immersive virtual reality (VR) experience in the context of outpatient skin cancer surgery as a means to minimize patient-reported feelings of anxiety or pain. The authors also sought to assess the effects on patient-reported overall satisfaction. MATERIALS AND METHODS: Patients completed a pre-VR experience survey after completion of their first Mohs surgery layer, followed by a 10-minute VR experience, and a post-VR experience survey. Differences in the pre-VR survey and post-VR survey were compared using the chi-square test. The anxiety scores were compared using a t-test. RESULTS: In all but 2 questions, there was a trend toward improvement of the anxiety-related sensations after completion of the VR experience. There were statistically significant differences for 4 questions: "Are you currently feeling unable to relax" (p = .0013), "are you currently feeling fear of the worst happening" (p < .0001), "are you currently feeling terrified or afraid" (p = .0046), and "are you currently feeling nervous" (p < .0001). CONCLUSION: Virtual reality experiences during the Mohs surgical day significantly improved measures of anxiety and patient satisfaction.

Clinical Presentations of Melanoma in African Americans, Hispanics, and Asians.

BACKGROUND: Skin cancer has traditionally been studied in Caucasian skin. Although it does occur with increased relative frequency in Caucasians, patients with skin of color suffer from elevated morbidity and mortality when diagnosed with skin cancer. OBJECTIVE: To detail the unique demographic, clinical, and genetic features of melanoma in patients with skin of color, including Hispanic, African American, and Asian patients. MATERIALS AND METHODS: A PubMed search was conducted spanning dates 1947 to June 2017. A total of 246 articles were screened, from which 69 were included in this review. RESULTS: Relative to Caucasians, melanoma has unique demographic, clinical, and genetic features in African Americans, Hispanics, and Asians that include gender and subtype predominance. CONCLUSION: Familiarization with these unique presentations of skin cancer in skin of color is imperative to accurate identification and treatment of cutaneous malignancies in these populations and ultimately to improved disease-related outcomes.

Cetuximab as a Component of Multimodality Treatment of High-Risk Cutaneous Squamous Cell Carcinoma: A Retrospective Analysis From a Single Tertiary Academic Medical Center.

BACKGROUND: Cutaneous squamous cell carcinoma (cSCC) is the second most common form of skin cancer and has potential for regional or distant metastasis. Despite the standardization of features associated with high-risk cSCC, an advanced subset of cSCC, there is no established consensus regarding proper management of this tumor. OBJECTIVE: To evaluate the efficacy of cetuximab, add to existing management options, and aid in the development of standardized treatment for this tumor. MATERIALS AND METHODS: Medical records were searched using Current Procedural Terminology codes for cetuximab and cSCC. Demographic data and tumor characteristics, along with treatment regimens and follow-up times, were collected. A total of 20 cases were examined. RESULTS: Of the 20 cases, 3 experienced a complete response and 7 experienced a partial response, yielding an overall response of 50% and a combined median disease-free survival of 6.35 months (range 1-46.8 months). CONCLUSION: As most of the patients who experienced a response received cetuximab as part of a multimodality treatment approach, cetuximab may be most efficacious when administered with concurrent therapies such as surgery or radiation. Further larger prospective studies to determine the optimal dosing and frequency of cetuximab and the utility of concurrent therapies are warranted.

Review of Endovenous Thermal Ablation of the Great Saphenous Vein: Endovenous Laser Therapy Versus Radiofrequency Ablation.

BACKGROUND: Endovenous thermal ablation is a popular treatment for varicose veins of the greater saphenous vein. Two common techniques of thermal ablation are endovenous laser therapy (EVLT) and radiofrequency ablation (RFA). OBJECTIVE: The authors compare EVLT and RFA in vein therapy. METHODS: A review was conducted using PubMed. Studies comparing the treatment modalities were gathered and compared on the basis of 5 main standpoints, including: efficacy, side effects, serious complications, recurrence, and quality of life. RESULTS: It was found that EVLT and RFA are both highly efficacious (>80%). Endovenous laser therapy seems to be slightly more efficacious than RFA in numerous studies but its significance is uncertain. Side effect profiles varied regarding postoperative pain and bruising because both were seen to be significantly less using RFA. Serious complications were found to be rare in both with no significant difference in incidence. Recanalization rate was observed to be higher using RFA with uncertainty in significance among various studies. Quality of life improved after both procedures with no significant difference among the 2. CONCLUSION: Efficacy and recurrence rate seem to favor EVLT, whereas postoperative pain and bruising favor RFA. Further studies are needed to validate the significance of the differences found.

Review of Nonmelanoma Skin Cancer in African Americans, Hispanics, and Asians.

BACKGROUND: Skin cancer has traditionally been studied in Caucasian skin. Although it does occur with increased relative frequency in Caucasians, patients with skin of color suffer from elevated morbidity and mortality when diagnosed with skin cancer. OBJECTIVE: To detail the unique demographic and clinical features of nonmelanoma skin cancer (NMSC) in patients with skin of color, including Hispanic, African American, and Asian patients. MATERIALS AND METHODS: A complete PubMed search was conducted spanning dates from 1947 to June 2017 yielding a total of 185 manuscripts, from which 45 were included in this review. RESULTS: Relative to Caucasians, NMSC, comprised squamous cell carcinoma and basal cell carcinoma, has unique demographic and clinical features in African Americans, Hispanics, and Asians. CONCLUSION: Familiarization with these unique presentations of skin cancer in skin of color is imperative to accurate identification and treatment of cutaneous malignancies in these populations and ultimately to improved disease-related outcomes.

Eccrine Porocarcinoma: New Insights and a Systematic Review of the Literature.

BACKGROUND: Eccrine porocarcinoma (EPC) is a rare cutaneous neoplasm with high potential for morbidity and mortality. Due to its rarity, there is a paucity of data profiling diagnosis, work-up, and management. OBJECTIVE: To consolidate reported information on demographics, diagnostics, clinical behavior, treatment modalities, and patient outcomes in EPC to provide a reference tool to optimize diagnosis and management. METHODS: A comprehensive PubMed search was performed from 1963 to November 2017 using PRISMA guidelines. This yielded 155 articles detailing 206 cases of porocarcinoma. RESULTS: Eccrine porocarcinoma most often presents in elderly patients on the head and neck or lower limbs. Metastatic disease at presentation is not uncommon (22%). Primary tumor location is significantly correlated with presence of metastasis (p = .038). The most common treatment is excision followed by Mohs micrographic surgery (MMS), although the outcomes after MMS were superior to those after surgical excision. CONCLUSION: This systematic review of individual patient data reveals that all patients should have a histological diagnosis with imaging considered for high-risk cases. Primary tumor location should also be considered in diagnostic and therapeutic decision-making. Although wide local excision (WLE) is currently the first-line treatment, MMS is becoming increasingly used, with evidence indicating improved outcomes as compared to those seen with WLE.

Hypothyroidism Potentially Linked to Cutaneous Squamous Cell Carcinoma: Retrospective Study at a Single Tertiary Academic Medical Center.

BACKGROUND: There are multiple known risk factors for the development of cutaneous squamous cell carcinoma (SCC). OBJECTIVE: To determine whether patients with cutaneous SCC have a higher prevalence of hypothyroidism than the general US population. MATERIALS AND METHODS: A retrospective review was performed for patients seen at the University of Southern California with cutaneous SCC. Chart review was performed for the presence of hypothyroidism and thyroid replacement therapy before the diagnosis of SCC for each patient. Multiple prevalence studies were gathered from the literature for comparison, reporting the prevalence of overt and subclinical hypothyroidism in the general US population and/or elderly US population. RESULTS: Of the 265 patients diagnosed with SCC of the skin, 61 (23%) of patients were found to have a preceding diagnosis of hypothyroidism. The prevalence of hypothyroidism among the population of SCC patients was significantly greater than the prevalence of hypothyroidism (overt and subclinical) in any general and/or elderly US population reported. CONCLUSION: Patients with SCC of skin are more likely to have a history of hypothyroidism than the general population. The authors conclude that hypothyroidism may be linked to the development of cutaneous SCC.

SLNB in cutaneous SCC: A review of the current state of literature and the direction for the future.

The concept of the sentinel lymph node biopsy (SLNB) has been universally accepted for melanoma, however, remains controversial for squamous cell carcinoma (SCC). We performed a quantitative review on 260 cases of SCC that had a SLNB. The positivity rate was found to be 14.6%. Literature was qualitatively reviewed to determine whether a positive SLNB has any bearing on prognosis in SCC cases, finding a significant relationship between poor prognosis and a positive SLN (P = 0.0082).

Safety of Cochlear Implants in Electrosurgery: A Systematic Review of the Literature.

BACKGROUND: The implications of electrosurgical instrument use in patients with cochlear implants (CIs) are becoming increasingly relevant for dermatologic surgeons as the number of implanted CI devices continues to grow. The literature, however, fails to provide clear recommendations for appropriate treatment of these patients. OBJECTIVE: To systematically consolidate and critique the current literature regarding electrosurgical instrument use in patients with CI, to determine implications of various electrosurgical devices and settings on CI function and health of cochlear tissues, and to devise recommendations for appropriate use. MATERIALS AND METHODS: The manuscript was created based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) criteria. A broad search of PubMed, Access Medicine, Clinical Key, Ovid, Scopus, the Cochrane Library, and Web of Science was performed using key words such as CI, electrosurgery, and/or electrosurgical device. Criteria for inclusion included being written in English language and institutional access to manuscript. All years were included. Additional references were obtained from personal communication with CI manufacturers. Study biases were assessed through evaluation of funding and/or sponsoring agencies for included studies. RESULTS: The authors' search yielded a total of 8 studies, 5 of which were a level of evidence 5, 2 of which were level of evidence 4, and 1 of which was a level of evidence 3. The remaining study was relegated only to device testing. These studies were complicated by inaccurate terminology and inconsistent recommendations. CONCLUSION: The body of evidence evaluating electrosurgical instrument use in patients with CI is severely limited in number and quality. Thus, vague and inconsistent recommendations have emerged that place patients at risk of serious and costly adverse effects. In light of this, the authors suggest use of the most conservative recommendations available for electrosurgical instrument use in patients with CI.