Clinical versus Histological Assessment of Basal Cell Carcinoma Subtype and Thickness of Tumours Selected for Photodynamic Therapy.

Photodynamic therapy is an approved treatment for primary, superficial, and small nodular basal cell carcinomas with a thickness of < 2 mm located on low-risk sites. Histologically verified basal cell carcinomas clinically assessed as suited for photodynamic therapy were included. The study aimed to investigate the agreement between clinical and histological assessments of basal cell carcinoma subtypes and thickness of tumours selected for photodynamic therapy with histopathological evaluation as a reference. A total of 343 tumours were included. The agreement between clinical and histological diagnosis of basal cell carcinoma subtype was 72% (p < 0.001). Clinical assessment of subtype had a sensitivity of 93% and specificity of 55% for superficial tumours and a sensitivity of 55% and specificity of 85% for nodular tumours. The mean ± SD thickness values by clinical and histological assessments were 0.95 ± 0.53 and 0.86 ± 0.75. The difference of 0.09 mm was statistically significant (p = 0.017), but not considered to be clinically relevant, although the differences between specific subgroups could be relevant. Among basal cell carcinomas clinically diagnosed as superficial, 91% were histologically consistent with the current photodynamic therapy criteria. The main results suggest that histopathological evaluation should precede photodynamic therapy to ensure selection of suitable basal cell carcinomas. In selected cases, the clinical diagnosis alone may be adequate before proceeding with photodynamic therapy.

Autofluorescence Excitation Imaging of Nonmelanoma Skin Cancer for Margin Assessment Before Mohs Micrographic Surgery: A Pilot Study.

BACKGROUND: Autofluorescence photography can detect specific light-tissue interactions and record important pathophysiological changes associated with nonmelanoma skin cancer (NMSC), which has been ascribed to the fluorescence of an aromatic amino acid, tryptophan. OBJECTIVE: To assess the impact of a novel, autofluorescence imaging (AFI) device on margin control for NMSCs before Mohs micrographic surgery (MMS) in an effort to decrease overall operating time. METHODS: Before the initial stage of MMS, NMSCs were measured with a 2-mm margin as standard of care (normal margin). The tumor was then imaged with the AFI device. A 2-mm margin was drawn around the fluorescent area captured by the AFI device and was referred to as the camera margin. The tumor was excised based on the normal margin and evaluated on frozen histological section. RESULTS: Imaging based on the AFI device resulted in appropriate recommendations for margin control in 8 of 11 tumors. Four of these tumors did not fluoresce and demonstrated a lack of tumor residuum on stage I specimen, as anticipated. There were no side effects from the AFI device. CONCLUSION: This is an initial pilot study that supports the use of a novel, noninvasive imaging device to help with margin assessment before MMS. On optimization, this device has potential to extend applicability to surgical excisions for tumors that do not fulfill criteria for MMS.

A deep learning algorithm to detect cutaneous squamous cell carcinoma on frozen sections in Mohs micrographic surgery: A retrospective assessment.

Intraoperative margin analysis is crucial for the successful removal of cutaneous squamous cell carcinomas (cSCC). Artificial intelligence technologies (AI) have previously demonstrated potential for facilitating rapid and complete tumour removal using intraoperative margin assessment for basal cell carcinoma. However, the varied morphologies of cSCC present challenges for AI margin assessment. The aim of this study was to develop and evaluate the accuracy of an AI algorithm for real-time histologic margin analysis of cSCC. To do this, a retrospective cohort study was conducted using frozen cSCC section slides. These slides were scanned and annotated, delineating benign tissue structures, inflammation and tumour to develop an AI algorithm for real-time margin analysis. A convolutional neural network workflow was used to extract histomorphological features predictive of cSCC. This algorithm demonstrated proof of concept for identifying cSCC with high accuracy, highlighting the potential for integration of AI into the surgical workflow. Incorporation of AI algorithms may improve efficiency and completeness of real-time margin assessment for cSCC removal, particularly in cases of moderately and poorly differentiated tumours/neoplasms. Further algorithmic improvement incorporating surrounding tissue context is necessary to remain sensitive to the unique epidermal landscape of well-differentiated tumours, and to map tumours to their original anatomical position/orientation.

Cost-effective device for locating and circumscribing superficial tumors with contrast enhancement and fluorescence quantification.

BACKGROUND: Two Bispectral contrast enhancement approaches for the fluorescence diagnosis with chlorine-e6 and a wide field-of-view imaging system with fluorescence excitation at 405 nm and time-resolved background suppression were analyzed and compared. METHODS: Two techniques for the contrast enhancement of a fluorescent video system (Red/Green (R/G) ratio and Red-Green (R-G)) with time-resolved background suppression for fluorescent diagnosis (FD) were tested in four patients with basal cell carcinoma (BCC). RESULTS: The results of both contrast enhancement methods were compared for the diagnostic efficiency for FD of BCC. Both techniques successfully determined the boundaries of the lesions and the fluorescence intensity. CONCLUSIONS: Both contrast enhancement modes have proven effective in identifying tumor borders in cases of low contrast in BCC FD with Ce6. While the Red/Green (R/G) mode provides sharper lesion borders, the Red minus Green (R-G) mode visualizes more fluorescent features and makes it easier to assess the lesion margins.

Assessment of therapeutic efficacy in seven cases of basal cell carcinoma in the ear and nose region treated with new surgical excision and immediate photodynamic therapy.

BACKGROUND: Basal cell carcinoma (BCC) is the most prevalent non-melanoma skin tumor. It commonly affects exposed areas. Currently, surgical resection is considered the primary approach for BCC treatment. However, BCC frequently affects exposed facial areas, leading to visible scars after surgery. PDT has garnered increasing recent attention, demonstrating superior efficacy and favorable cosmetic outcomes for superficial BCCs. However, it shows limited treatment effectiveness for deep-seated tumors. Most of the current literature focuses on the combination of surgery and postoperative PDT, while no studies have reported on the use of standard surgical excision with intraoperative margin pathological monitoring and immediate PDT. Therefore, we implemented a treatment protocol combining surgery and immediate PDT. Accordingly, this paper aimed to explore the effectiveness, cosmetic outcomes, and other relevant advantages of this therapeutic approach. METHODS: We aimed to evaluate this approach in seven patients with BCC on the nose and ears. Standard surgical excision of skin lesions was performed, with intraoperative frozen section examination of the margins, followed by immediate postoperative PDT for the wounds, and continued periodic PDT during the second phase of wound healing. RESULTS: All seven cases demonstrated significant improvement. The cosmetic rating was 100 % and no cases of recurrence existed among the seven patients. CONCLUSIONS: This approach effectively minimized the surgical wound, improved tumor clearance, achieved precise therapeutic effects, and reduced the recurrence rate. Moreover, it produced favorable cosmetic outcomes.

Immunotherapy for keratinocyte cancers. Part I: Immune-related epidemiology, risk factors, pathogenesis, and immunotherapy management of keratinocyte cancers.

The important role of the immune system in the surveillance and control of keratinocyte cancers (KCs), namely squamous and basal cell carcinomas, is increasingly appreciated, as new immunotherapies have recently become available. As the field of immunotherapy is rapidly evolving, this review synthesizes key concepts and highlights important cellular components within the immune system responsible for attacking KCs. We review the most current data on the epidemiology, risk factors, and immunotherapy management for KCs. Patients will seek advice from dermatologists to help explain why immunotherapies work for KCs and whether they might be appropriate for different clinical scenarios. Collaboration with medical colleagues across different disciplines to evaluate KCs for response to immunotherapy and early recognition of immune-related adverse events will help to optimize patient outcomes.

Exploring knowledge gaps in the understanding of peripheral and deep en face margin assessment.

In 2022, National Comprehensive Cancer Network updated the phrase of "complete circumferential peripheral and deep margin assessment (CCPDMA)" to "peripheral and deep en face margin assessment (PDEMA)," which was meant to create more consistency across all treatment modalities and provide clarity to the meaning of total margin evaluation. The aim of this project was to investigate the interpretation of PDEMA across pertinent specialties and to identify any existing knowledge gaps in hopes of improving clinical performance of institutional practice. An electronic survey was administered to medical professionals within the divisions of dermatology and otolaryngology retrieving demographic data and assessing respondents' knowledge on tissue processing techniques and PDEMA. Of the four knowledge-based assessment questions administered, dermatology respondents answered three questions with > 80% accuracy and one question with < 65% accuracy. Otolaryngology respondents answered one question with > 80% accuracy and three with < 65% accuracy. Both groups answered the knowledge-based question evaluating the concept of "what must be true for Mohs or PDEMA to have value" with under 65% accuracy. When comparing dermatology and otolaryngology respondents, only one question which evaluated the proper methods to "achieve processing of the epidermal edge and the base of the tumor along a single plane in the lab" significantly differed between groups, with a percentage correct of 96% for dermatologists compared to 54% for otolaryngologists (p < 0.001). Results were found to be similar when resident physicians were removed from analysis. The overall percent correct for knowledge-based questions was shifted higher for dermatologists compared to otolaryngologists (p = 0.014). This trend was also redemonstrated when analyzing the data excluding residents (p = 0.053).

Anatomic Locations of Procedurally Treated Keratinocyte Carcinomas in the US Medicare Population.

Importance: Keratinocyte carcinomas are the most common cancers in the US. However, keratinocyte carcinomas are not included in US national cancer registries, and information on the anatomic locations of keratinocyte carcinomas is lacking. Objective: To investigate the anatomic location of keratinocyte carcinomas in the US using a large claims data set. Design, Setting, and Participants: We performed a cohort study using a deidentified, random sample of 4 999 999 fee-for-service Medicare beneficiaries aged 65 years or older (2009-2018). Main Outcomes and Measures: Proportion of procedurally treated keratinocyte carcinomas at each anatomic location, identified by linking diagnosis and treatment codes. Results: A total of 2 415 514 keratinocyte carcinomas were identified in 792 393 beneficiaries. The mean (SD) age was 76.6 (8.1) years, 410 364 (51.8%) were women, and 96.7% were White. Of the 2 415 514 keratinocyte carcinomas, 796 542 could be subtyped into basal cell carcinoma (33.0%), 927 984 into squamous cell carcinoma (38.4%), and 690 988 (28.6%) could not be subtyped. The most common location of squamous cell carcinomas was the head and/or neck (44.3%) followed by upper limbs (26.7%). The most common location of basal cell carcinomas was head and/or neck (63.8%), followed by trunk (14.9%). In women, keratinocyte carcinomas were most common on the head and/or neck (47.3%) followed by upper and lower limb (18.5% and 16.6%, respectively). In men, keratinocyte carcinomas were most common on the head and/or neck (58.7%) followed by upper limb and trunk (17.3% and 11.4%, respectively). Conclusions and Relevance: The results of this large Medicare cohort study highlight the anatomic locations of keratinocyte carcinomas over recent years and show the predominance of lesions occurring at head and/or neck anatomic location. This foundational information on keratinocyte carcinoma anatomic locations in the US is valuable for improved keratinocyte risk factor differentiation and skin cancer surveillance.

Years of dermatology experience and geographic region are associated with outlier performance of excision or destruction for nonmelanoma skin cancer.

INTRODUCTION: Treatments for nonmelanoma skin cancer (NMSC) include excision (surgical removal) and destruction (cryotherapy or curettage with or without electrodesiccation) in addition to other methods. Although cure rates are similar between excision and destruction for low-risk NMSCs, excision is substantially more expensive. Performing destruction when appropriate can reduce costs while providing comparable cure rate and cosmesis. OBJECTIVE: To identify characteristics associated with exclusive (outlier) performance of excision or destruction for NMSC. METHODS: The study consisted of malignant excision and destruction procedures submitted by dermatologists to Medicare in 2019. Proportions of services for each method were analyzed with respect to geographic region, years of dermatology experience, median income of the practice zip code, and rural-urban commuting area (RUCA) code. RESULTS: Fewer years of experience predicted a higher proportion of excisions (R2 = 0.7, p < .001) and higher odds of outlier excision performance. Outlier performance of excision was associated with practicing in the South, Midwest, and West, whereas outlier performance of destruction was associated with practicing in the Northeast and Midwest. CONCLUSIONS: Dermatologists with less experience or in certain geographic regions performed more malignant excision relative to destruction. As the older population of dermatologists retires, the cost of care for NMSC may increase.

Non-invasive imaging techniques in presurgical margin assessment of basal cell carcinoma: Current evidence.

BACKGROUND: The diagnosis of basal cell carcinoma (BCC) is based on clinical and dermoscopical features. In uncertain cases, innovative imaging techniques, such as reflectance confocal microscopy (RCM) and optical coherence tomography (OCT), have been used. The main limitation of these techniques is the inability to study deep margins. HFUS (high-frequency ultrasound) and the most recent UHFUS (ultra-high-frequency ultrasound) have been used in various applications in dermatology, but they are not yet routinely used in the diagnosis of BCC. A key point in clinical practice is to find an imaging technique that can help to reduce post-surgical recurrences with a careful presurgical assessment of the lesional margins. This technique should show high sensitivity, specificity, reproducibility and simplicity of execution. This concept is very important for the optimal management of patients who are often elderly and have many comorbidities. The aim of the paper is to analyse the characteristics of current imaging techniques and the studies in the literature on this topic. MATERIALS AND METHODS: The authors independently searched the MEDLINE, PubMed, Embase, Scopus, ScienceDirect and Cochrane Library databases for studies looking for non-invasive imaging techniques for the presurgical margin assessment of BCC. RESULTS: Preoperative study of the BCC subtype can help to obtain a complete excision with free margins. Different non-invasive imaging techniques have been studied for in vivo evaluation of tumour margins, comparing the histologic evaluation with a radical surgery. The possibility to study the lateral and deep margins would allow a reduction of recurrences and sparing of healthy tissue. CONCLUSION: HFUS and UHFUS represent the most promising, non-invasive techniques for the pre-operative study of BCC facilitating the characterization of vascularization, deep lateral margins and high-risk subtypes, although they are limited by insufficient literature unlike RCM and OCT.

Determining the clinical applicability of machine learning models through assessment of reporting across skin phototypes and rarer skin cancer types: A systematic review.

Machine learning (ML) models for skin cancer recognition may have variable performance across different skin phototypes and skin cancer types. Overall performance metrics alone are insufficient to detect poor subgroup performance. We aimed (1) to assess whether studies of ML models reported results separately for different skin phototypes and rarer skin cancers, and (2) to graphically represent the skin cancer training datasets used by current ML models. In this systematic review, we searched PubMed, Embase and CENTRAL. We included all studies in medical journals assessing an ML technique for skin cancer diagnosis that used clinical or dermoscopic images from 1 January 2012 to 22 September 2021. No language restrictions were applied. We considered rarer skin cancers to be skin cancers other than pigmented melanoma, basal cell carcinoma and squamous cell carcinoma. We identified 114 studies for inclusion. Rarer skin cancers were included by 8/114 studies (7.0%), and results for a rarer skin cancer were reported separately in 1/114 studies (0.9%). Performance was reported across all skin phototypes in 1/114 studies (0.9%), but performance was uncertain in skin phototypes I and VI from minimal representation of the skin phototypes in the test dataset (9/3756 and 1/3756, respectively). For training datasets, although public datasets were most frequently used, with the most widely used being the International Skin Imaging Collaboration (ISIC) archive (65/114 studies, 57.0%), the largest datasets were private. Our review identified that most ML models did not report performance separately for rarer skin cancers and different skin phototypes. A degree of variability in ML model performance across subgroups is expected, but the current lack of transparency is not justifiable and risks models being used inappropriately in populations in whom accuracy is low.

Complete Margin Assessment Versus Sectional Assessment in Surgically Excised High-Risk Keratinocyte Carcinomas: A Systematic Review and Meta-Analysis.

BACKGROUND: Keratinocyte carcinomas (KCs) are the most diagnosed cancers worldwide and are commonly excised via complete margin assessment (CMA) or excision with sectional assessment (SA). National Comprehensive Cancer Network guidelines encourage CMA for KC with high-risk features. OBJECTIVE: To systematically compare recurrence outcomes for CMA vs SA in high-risk KC based on National Comprehensive Cancer Network guidelines criteria. MATERIALS AND METHODS: EMBASE and MEDLINE were searched for articles reporting recurrences of high-risk KC undergoing excision using CMA or SA. High-risk KCs were defined as recurrent, having perineural invasion (PNI), or basal cell carcinomas (BCC) with aggressive histology. Chi-squared tests and risk ratios evaluated differences between CMA and SA groups, and a random-effects meta-analysis was performed. RESULTS: Twenty-eight studies met inclusion criteria. Pooled percentages of locoregional recurrences were significantly lower with CMA vs SA for all KCs (3.9% [95% CI: 2.9-4.9] vs 13.5% [7.7, 19.2, p = .001]), cutaneous squamous cell carcinoma with PNI (9.8% [5.4-14.1] vs 32.0% [25.0-39.0], p < .001), and recurrent BCC (4.4% [2.9-5.9] vs 11.9% [8.0-15.8], p < .001). CONCLUSION: For high-risk KCs, recurrence risk was over 3-times greater with SA compared with CMA. Expanded access to CMA for high-risk KC is likely to reduce recurrence risk and improve clinical outcomes.

Association of Tumor Characteristics With Insurance Type Among Patients Undergoing Mohs Micrographic Surgery for Nonmelanoma Skin Cancer.

Importance: Little is known about the association between insurance type and tumor or treatment characteristics among patients undergoing Mohs micrographic surgery (MMS) for nonmelanoma skin cancer (NMSC). Objective: To investigate whether there are differences in tumor and treatment characteristics among patients undergoing MMS for NMSC by insurance type. Design, Setting, and Participants: This retrospective cohort study included patients with NMSC who presented for surgery at an academic MMS practice between May 2017 and May 2019. Main Outcomes and Measures: Preoperative and postoperative tumor diameters, number of MMS stages, type of closure, and number of high-risk tumors were compared based on insurance type among uninsured and underinsured patients and those with private insurance, Medicare, and Veterans Affairs (VA) insurance. Results: A total of 1397 patients with NMSC (978 [70%] male; mean [SD] age, 68.5 [12.4] years) underwent 1916 MMS procedures. Of these patients, 868 (45%) had Medicare, 570 (30%) had private insurance, 299 (16%) had VA insurance, and 179 (9%) were treated at a safety net clinic or were uninsured. Compared with patients with private insurance, uninsured and underinsured patients had significantly larger preoperative tumor bed diameters (difference, 28%; 95% CI, 14%-43%; P < .001) and postoperative defect sizes (difference, 28%, 95% CI, 16%-41%; P < .001). Patients with Medicare and VA insurance did not have significantly different preoperative tumor bed diameters compared with patients with private insurance. Patients with VA insurance had larger postoperative defect sizes than patients with private insurance (difference, 12%; 95% CI, 2%-23%; P = .02). The number of MMS stages and type of closure did not significantly differ based on insurance type. Conclusions and Relevance: In this cohort study of patients undergoing MMS for NMSC, larger preoperative tumor and postoperative defect sizes were associated with being uninsured or underinsured compared with privately insured. Future studies are required to determine why these differences exist to deliver optimal care to all patients.

Real-world assessment and treatment of locally advanced basal cell carcinoma: Findings from the RegiSONIC disease registry.

BACKGROUND: Limited information is available regarding real-world treatment patterns and their effectiveness and safety in patients with locally advanced basal cell carcinoma, including patients not typically represented in clinical trials. The purpose of the current study was to describe how clinicians diagnose and treat locally advanced basal cell carcinoma in the United States. METHODS: This prospective, multicenter, observational registry study included patients with newly diagnosed, Hedgehog pathway inhibitor-naive locally advanced basal cell carcinoma without basal cell carcinoma nevus syndrome (n = 433) treated at 75 US academic and community practices, including dermatology, Mohs surgery, and medical oncology sites. The main outcomes of this study were treatment patterns and associated effectiveness and safety for patients with locally advanced basal cell carcinoma in real-world settings. RESULTS: Determination of locally advanced basal cell carcinoma was mainly based on lesion size (79.6% of patients), histopathology (54.3%), extent of involvement (49.0%), and location (46.2%). Within 90 days of determination of locally advanced disease, 115 patients (26.6%) received vismodegib, 251 (58.0%) received surgery/other (non-vismodegib) treatment, and 67 (15.5%) had not yet received treatment (observation). Vismodegib-treated patients had a higher prevalence of high-risk clinical features predictive for locoregional recurrence than those with non-vismodegib treatment or observation. Clinical response rate was 85.1% with vismodegib and 94.9% with non-vismodegib treatment (primarily surgery). The most common adverse events with vismodegib were ageusia/dysgeusia, muscle spasms, alopecia, and weight loss. Rates of cutaneous squamous cell cancers were comparable between vismodegib and non-vismodegib treatment. CONCLUSIONS: This prospective observational study offers insight on real-world practice, treatment selection, and outcomes for a nationally representative sample of US patients with locally advanced basal cell carcinoma. For patients with lesions that were not amenable to surgery, vismodegib treatment was associated with effectiveness and safety that was consistent with that observed in clinical trials.

Disparities in nonmelanoma skin cancer in Hispanic/Latino patients based on Mohs micrographic surgery defect size: A multicenter retrospective study.

BACKGROUND: There is limited literature regarding potential disparities in nonmelanoma skin cancer for patients with skin of color. OBJECTIVE: Use the sizes of Mohs micrographic surgery defects to examine disparities in nonmelanoma skin cancer among Hispanic/Latino patients with a secondary aim to examine the effect of insurance type. METHODS: We conducted a multicenter retrospective study using data from 3 major institutions in Los Angeles County. A total of 3486 Mohs micrographic surgeries of basal cell, squamous cell, and basosquamous cell carcinomas were analyzed. RESULTS: Mohs micrographic surgery defect sizes were 17% larger among Hispanic/Latino patients compared with non-Hispanic White patients. More notably, when comparing defect sizes of squamous cell carcinomas to those of basal cell carcinomas, defects were 80% larger among Hispanic/Latino patients compared to non-Hispanic White patients who had 25% larger defect sizes. Compared to patients with Medicare, patients with health maintenance organization and Medicaid/health maintenance organization had 22% and 52% larger defect sizes, respectively, whereas patients with preferred provider organization, had 10% smaller defect sizes. LIMITATIONS: The data included were from a single county population. CONCLUSION: Disparities regarding nonmelanoma skin cancer exist between patients with skin of color and White patients. Patients and the medical community need to be cognizant that skin cancer can develop in patients regardless of their race and ethnicity.