Identifying critical quality metrics in Mohs Surgery: A national expert consensus process.

BACKGROUND: Amid a movement toward value-based healthcare, increasing emphasis has been placed on outcomes and cost of medical services. To define and demonstrate the quality of services provided by Mohs surgeons, it is important to identify and understand the key aspects of Mohs micrographic surgery (MMS) that contribute to excellence in patient care. OBJECTIVE: The purpose of this study is to develop and identify a comprehensive list of metrics in an initial effort to define excellence in MMS. METHODS: Mohs surgeons participated in a modified Delphi process to reach a consensus on a list of metrics. Patients were administered surveys to gather patient perspectives. RESULTS: Twenty-four of the original 66 metrics met final inclusion criteria. Broad support for the initiative was obtained through physician feedback. LIMITATIONS: Limitations of this study include attrition bias across survey rounds and participation at the consensus meeting. Furthermore, the list of metrics is based on expert consensus instead of quality evidence-based outcomes. CONCLUSION: With the goal of identifying metrics that demonstrate excellence in performance of MMS, this initial effort has shown that Mohs surgeons and patients have unique perspectives and can be engaged in a data-driven approach to help define excellence in the field of MMS.

Considering Sun Safety Policies in the United States.

As they are collectively the most common malignancies, the personal and systemic burden of skin cancers represent a significant public health concern in the United States. Ultraviolet radiation from the sun as well as from artificial sources such as tanning beds is a carcinogen well-known to increase the risk of developing skin cancer in individuals. Public health policies can help mitigate these risks. In this perspectives article, we review sunscreen and sunglasses standards, tanning bed utilization, and workplace sun protection guidelines in the US and provide focused examples for improvement from Australia and the United Kingdom where skin cancer is a well-documented public health concern. These comparative examples can inform interventions in the US that have the potential to modify exposure to risk factors associated with skin cancer.

Artificial intelligence in the detection of skin cancer.

Recent advances in artificial intelligence (AI) in dermatology have demonstrated the potential to improve the accuracy of skin cancer detection. These capabilities may augment current diagnostic processes and improve the approach to the management of skin cancer. To explain this technology, we discuss fundamental terminology, potential benefits, and limitations of AI, and commercial applications relevant to dermatologists. A clear understanding of the technology may help to reduce physician concerns about AI and promote its use in the clinical setting. Ultimately, the development and validation of AI technologies, their approval by regulatory agencies, and widespread adoption by dermatologists and other clinicians may enhance patient care. Technology-augmented detection of skin cancer has the potential to improve quality of life, reduce health care costs by reducing unnecessary procedures, and promote greater access to high-quality skin assessment. Dermatologists play a critical role in the responsible development and deployment of AI capabilities applied to skin cancer.

Guidelines of care for the management of actinic keratosis.

BACKGROUND: Actinic keratoses (AK) are rough scaly patches that arise on chronically ultraviolet-exposed skin and can progress to keratinocyte carcinoma. OBJECTIVE: This analysis examined the literature related to the management of AK to provide evidence-based recommendations for treatment. Grading, histologic classification, natural history, risk of progression, and dermatologic surveillance of AKs are also discussed. METHODS: A multidisciplinary Work Group conducted a systematic review to address 5 clinical questions on the management of AKs and applied the Grading of Recommendations, Assessment, Development, and Evaluation approach for assessing the certainty of the evidence and formulating and grading clinical recommendations. Graded recommendations were voted on to achieve consensus. RESULTS: Analysis of the evidence resulted in 18 recommendations. LIMITATIONS: This analysis is based on the best available evidence at the time it was conducted. The pragmatic decision to limit the literature review to English language randomized trials may have excluded data published in other languages or limited identification of relevant long-term follow-up data. CONCLUSIONS: Strong recommendations are made for using ultraviolet protection, topical imiquimod, topical 5-fluorouracil, and cryosurgery. Conditional recommendations are made for the use of photodynamic therapy and diclofenac for the treatment of AK, both individually and as part of combination therapy regimens.

Guidelines of care for the management of actinic keratosis: Executive summary.

BACKGROUND: Actinic keratoses (AK) are rough scaly patches that arise on chronically ultraviolet-exposed skin and can progress to keratinocyte carcinoma. Treatment options for AK include topical medications, photodynamic therapy, cryosurgery, and laser ablation. OBJECTIVE: This executive summary provides a synopsis of the 18 evidence-based recommendations for the treatment of AK detailed in the Guidelines of Care for the Management of Actinic Keratosis. METHODS: A multidisciplinary workgroup conducted a systematic review to address 5 clinical questions on the management of AKs and applied the Grading of Recommendations Assessment, Development and Evaluation approach for assessing the certainty of the evidence and formulating and grading clinical recommendations. Graded recommendations were voted on to achieve consensus. RESULTS: Analysis of the evidence resulted in 18 recommendations, suggesting there are several effective treatments available for AK. LIMITATIONS: The analysis informing the recommendations was based on the best available evidence at the time it was conducted. The results of future studies may necessitate a revision of current recommendations. CONCLUSIONS: Strong recommendations are presented for using ultraviolet protection, topical imiquimod, topical 5-fluorouracil, and cryosurgery. Conditional recommendations are presented for the use of photodynamic therapy and diclofenac for the treatment of AK, both individually and as part of combination therapy regimens.

A Histopathologic Scoring System for Perineural Invasion Correlates With Adverse Outcomes in Patients With Cutaneous Squamous Cell Carcinoma.

BACKGROUND: Perineural invasion (PNI) is a known risk factor for recurrence, metastasis, and death in cutaneous squamous cell carcinoma (cSCC). Current staging systems include PNI, but none define its extent or severity. OBJECTIVE: To identify histopathologic features of cSCC with PNI that may be associated with adverse outcomes. MATERIALS AND METHODS: This is a retrospective cohort study that included 45 patients with cSCC and PNI treated with surgical excision. Histopathologic slides were analyzed for 5 features of PNI: largest affected nerve diameter, number of nerves affected, depth of nerve involvement, intra- versus extratumoral PNI, and focal versus circumferential PNI. RESULTS: The median largest affected nerve diameter was 0.13 mm, and the median number of nerve structures involved was 4. After a median follow-up time of 24 months, 6 patients developed adverse outcomes, including 2 local recurrences, 4 metastases, and 2 tumor-related deaths. Univariate logistic regression analysis revealed that nerve diameter and number of affected nerves were significantly associated with adverse outcome. A composite PNI score, calculated from 5 histopathologic features, was the strongest predictor of adverse outcome (p = .020). CONCLUSION: Histopathologic features of PNI can be quantified with a composite PNI score that is significantly associated with adverse outcomes in cSCC.

Photodynamic therapy for cutaneous squamous cell carcinoma in situ: Impact of anatomic location, tumor diameter, and incubation time on effectiveness.

BACKGROUND: Photodynamic therapy (PDT) has been reported as a treatment for cutaneous squamous cell carcinoma in situ (SCCis), but only limited data are available on the effectiveness of PDT with aminolevulinic acid (ALA-PDT). OBJECTIVE: To review the outcomes of SCCis treated with ALA-PDT and examine factors associated with response. METHODS: A retrospective review identified 58 patients with 68 primary SCCis lesions treated with ALA-PDT and blue light illumination. Patient demographics, lesion features, treatment details, clinical response, and subsequent recurrence were extracted from medical record reviews. RESULTS: On completion of PDT the initial complete response rate was 77.9% and was not associated with the number of PDT treatments. On multivariate analysis factors associated with response were location on the face, tumor diameter <2 cm, and longer ALA incubation time. Lesions treated with a maximum incubation time of <3 hours had a 53.3% response compared with 84.9% for longer incubation. Subsequent recurrence of SCCis was noted in 7 of 53 cases (13.2%) at a median time of 11.7 months. LIMITATIONS: This was a retrospective study performed at a single institution without systematic follow-up. CONCLUSIONS: ALA-PDT may be an effective treatment for selected cases of SCCis. Effectiveness is impacted by anatomic location, tumor diameter, and ALA incubation time.

Squamous proliferations on the legs of women: Qualitative examination of histopathology, TP53 sequencing, and implications for diagnosis in a series of 30 cases.

BACKGROUND: Women with multiple squamous cell carcinomas (SCCs) of the legs have a striking clinical phenotype. Numerous tumors can develop in a short period of time. OBJECTIVE: Because histopathologic findings can vary in women with multiple SCC lesions, from keratoacanthoma-like to well-differentiated SCC, we hypothesized that TP53 variants might shed light on the appropriate classification. METHODS: We sequenced TP53 in 30 SCCs from 6 women who had multiple SCCs on their legs during a 21-month time frame. RESULTS: Histopathologic analysis showed 16 of the 30 lesions did not have prominent cytologic atypia and were distinguished by having expanded follicle-like structures composed of large, glassy, eosinophilic keratinocytes; these lesions resembled keratoacanthoma and were categorized as keratoacanthoma-like squamous proliferations (KASPs). The 14 remaining tumors had more prominent cytologic atypia and remained classified as SCC. Twenty of 30 tumors (including the KASPs) from the 6 different patients lacked detectable TP53 mutations. Ten of the 14 tumors that remained classified as SCC had detectable TP53 mutations. LIMITATIONS: This is a small series. CONCLUSION: These findings suggest that some cutaneous squamous proliferations on the legs of women with multiple lesions lack prominent cytologic atypia as well as TP53 mutations and might be more akin to keratoacanthoma than SCC or might represent a reactive phenomenon.

Well-differentiated neuroendocrine tumors in skin: Terminology and diagnostic utility of cytokeratin 5/6 and p63.

BACKGROUND: Well-differentiated neuroendocrine tumors (WDNETs) in skin include metastases from visceral primary sites and very uncommonly, primary cutaneous carcinoid tumors. Cutaneous WDNET may present a diagnostic challenge and in particular can be mistaken for a benign skin adnexal tumor. In contrast to cutaneous adnexal tumors, metastatic adenocarcinomas to the skin are cytokeratin 5/6 (CK5/6) and p63 negative in the majority of cases. It is unclear if failure to stain with CK5/6 and p63 would be helpful in differentiating WDNETs from cutaneous adnexal neoplasms. METHODS: We reviewed 10 cases of cutaneous WDNETs (8 cases of metastatic disease and 2 presumed primary carcinoid tumors of the skin) and performed immunohistochemical stains for CK5/6 and p63 on all cases. RESULTS: All 10 cases were negative with both CK5/6 and p63. CONCLUSION: Negative staining for CK5/6 and p63 can be helpful to distinguish WDNETs from cutaneous adnexal neoplasms. It is important to consider WDNETs in the differential diagnosis of cutaneous adnexal neoplasms as low-grade tumors may be the first sign of aggressive metastatic disease.

Histopathologic assessment of depth of follicular invasion of squamous cell carcinoma (SCC) in situ (SCCis): Implications for treatment approach.

BACKGROUND: Squamous cell carcinoma in situ (SCCis) has been reported to involve the hair follicle epithelium. Deep follicular invasion is often cited as a cause of treatment failure. OBJECTIVE: We sought to define the frequency and the depth of hair follicle invasion by SCCis. METHODS: The study included both a retrospective review of intraoperative pathology specimens from 42 SCCis cases treated with Mohs micrographic surgery and a prospective evaluation of serially sectioned SCCis tissue from 12 additional patients. Pathology specimens were analyzed for follicular invasion of SCCis. RESULTS: SCCis invasion of the superficial hair follicle infundibulum was observed in 61.3% to 87.5% of cases in the 2 cohorts, whereas invasion of the isthmus and lower follicle was observed in only 8.3% to 12.5% of cases. In most tumors the depth of follicular invasion was comparable with the thickness of the surrounding epidermis. The maximum observed depth of follicular invasion was 0.82 mm. LIMITATIONS: The study was performed on a limited number of cases referred for surgery at a single institution. CONCLUSIONS: Although SCCis invasion of the upper hair follicle infundibulum is common, deep invasion below the level of the surrounding epidermis is rare. This may have implications for optimal therapy of this condition.

Histopathologic features of multiple cutaneous squamous cell carcinomas of the lower extremity.

Recent studies suggest cutaneous squamous cell carcinomas (SCCs) of the leg, particularly those occurring multiply in sun exposed skin of nonimmunosuppressed women, are a distinct clinical subtype. There are few reports of the histopathologic features of this subtype. A retrospective chart review of 4 patients with multiple SCCs on the leg was performed and a total of 35 biopsies from the legs examined. Histopathologically, the tumors lacked adjacent actinic keratosis (AK) and often had adjacent basaloid retiform proliferations. Most lesions (all but one) were well differentiated and about 40% could be classified histopathologically as keratoacanthoma. Perineural invasion was absent in all but one case. Using the American Joint Committee on Cancer (AJCC) staging criteria for SCC, 21 tumors were Stage I, and 9 Stage II. During 7-10 years of follow-up, no recurrence or metastasis occurred. Patients with multiple SCCs on the lower extremities can have a range of histopathologic features, from keratoacanthoma-like to well-differentiated SCC.

Indoor tanning and the MC1R genotype: risk prediction for basal cell carcinoma risk in young people.

Basal cell carcinoma (BCC) incidence is increasing, particularly in young people, and can be associated with significant morbidity and treatment costs. To identify young individuals at risk of BCC, we assessed existing melanoma or overall skin cancer risk prediction models and built a novel risk prediction model, with a focus on indoor tanning and the melanocortin 1 receptor gene, MC1R. We evaluated logistic regression models among 759 non-Hispanic whites from a case-control study of patients seen between 2006 and 2010 in New Haven, Connecticut. In our data, the adjusted area under the receiver operating characteristic curve (AUC) for a model by Han et al. (Int J Cancer. 2006;119(8):1976-1984) with 7 MC1R variants was 0.72 (95% confidence interval (CI): 0.66, 0.78), while that by Smith et al. (J Clin Oncol. 2012;30(15 suppl):8574) with MC1R and indoor tanning had an AUC of 0.69 (95% CI: 0.63, 0.75). Our base model had greater predictive ability than existing models and was significantly improved when we added ever-indoor tanning, burns from indoor tanning, and MC1R (AUC = 0.77, 95% CI: 0.74, 0.81). Our early-onset BCC risk prediction model incorporating MC1R and indoor tanning extends the work of other skin cancer risk prediction models, emphasizes the value of both genotype and indoor tanning in skin cancer risk prediction in young people, and should be validated with an independent cohort.

Melanoma in situ: Part I. Epidemiology, screening, and clinical features.

The incidence of melanoma has steadily increased over the past 3 decades, with melanoma in situ comprising a disproportionately high percentage of the rising incidence. Our understanding of melanoma in situ has been shaped by epidemiologic and clinical studies. Central to a review of melanoma in situ is a focus on its epidemiology, pathology, biologic behavior, treatment, and clinical outcome, which may differ significantly from that of malignant melanoma. Part I of this continuing medical education article reviews the epidemiology, risk factors, and clinical features of melanoma in situ; part II covers the histopathology, treatment options, and clinical management.

Melanoma in situ: Part II. Histopathology, treatment, and clinical management.

Melanoma in situ (MIS) poses special challenges with regard to histopathology, treatment, and clinical management. The negligible mortality and normal life expectancy associated with patients with MIS should guide treatment for this tumor. Similarly, the approach to treatment should take into account the potential for MIS to transform into invasive melanoma, which has a significant impact on morbidity and mortality. Part II of this continuing medical education article reviews the histologic features, treatment, and management of MIS.

A strategy for the successful management of dermatofibrosarcoma protuberans.

BACKGROUND: Dermatofibrosarcoma protuberans (DFSP) is a rare, locally invasive soft tissue sarcoma with extensive subclinical involvement. The National Comprehensive Cancer Network guidelines recommend immediate reconstruction in most cases. Our study reviewed the methods of treatment of DFSP at our institution, examined the types of closure used after surgical excision, and analyzed the prevalence of positive margins on permanent pathology after immediate closure after conventional non-Mohs excision of DFSP. METHODS: The charts of 25 patients treated with surgical excision and 16 with Mohs surgery from 1990 to 2009 for lesions consistent with DFSP were reviewed for clinical variables including disease state, tumor site, closure type, permanent pathology margin status, disease recurrence/persistence, and excisional margin size. RESULTS: The trunk, followed by the head and neck, were the most common sites for DFSP. No patients had distant metastasis at diagnosis or experienced recurrence in either the surgical excision or the Mohs surgery group. Twelve (48%) patients were found to have positive margins after initial surgical resection. All lesions treated with Mohs surgery had clear histological margins at completion. Average margin size for surgical excision patients was 2.33 cm (range, 0.75-4.5 cm), and 1.36 cm (range, 0.74-2.55 cm) for Mohs excision. The average duration of follow-up was 107.9 months. CONCLUSIONS: The extent of DFSP is difficult to determine intraoperatively with traditional surgical excision, which leads to a higher rate of positive margins. Considering this difficulty and the complications of reconstruction with positive margins, we believe that reconstruction after tumor resection should be dependent on definitive pathologic clearance of the tumor.

Novel gene identified in an exome-wide association study of tanning dependence.

Growing evidence suggests that some individuals may exhibit symptoms of dependence to ultraviolet light, a known carcinogen, in the context of tanning. Genetic associations with tanning dependence (TD) have not yet been explored. We conducted an exome-wide association study in 79 individuals who exhibited symptoms of TD and 213 individuals with volitional exposure to ultraviolet light, but who were not TD based on three TD scales. A total of 300 000 mostly exomic single nucleotide polymorphisms primarily in coding regions were assessed using an Affymetrix Axiom array. We performed a gene burden test with Bonferroni correction for the number of genes examined (P < 0.05/14 904 = 3.36 × 10(-6) ). One gene, patched domain containing 2 (PTCHD2), yielded a statistically significant P-value of 2.5 × 10(-6) (OR = 0.27) with fewer individuals classified as TD having a minor allele at this locus. These results require replication, but are the first to support a specific genetic association with TD.

Cutaneous squamous cell carcinomas of the lower extremity: a distinct subset of squamous cell carcinomas.

BACKGROUND: Some patients develop a disproportionate number of cutaneous squamous cell carcinomas (SCCs) on their lower extremity (LE). OBJECTIVE: We sought to characterize the clinical features, treatment, and outcome in patients who develop multiple LE SCCs. METHODS: We identified 22 patients with 4 or more biopsy-diagnosed LE SCCs during a 4.5-year study period. The location, size, treatment, and clinical outcome of each LE SCC were recorded. RESULTS: Of the 22 patients studied, 18 were female. Of the 360 SCCs our patients developed, 260 (72.2%) were on the LE. The incidence of SCCs in these patients was nearly 7 times greater than the incidence of basal cell carcinoma in the same patients. LIMITATIONS: The number of patients is small and limits definitive conclusions about prevalence of SCCs on the LE in the general population. CONCLUSIONS: LE SCCs are a distinct subset of cutaneous SCCs and may have distinctive clinical features and biologic behavior requiring additional study.