Background While Brigham and Women's Hospital T1 cutaneous squamous cell carcinomas are overall low risk, a small subset develop poor outcomes. Objective To evaluate the impact of minor risk factors on poor outcomes in T1 tumors. Methods Data were collected retrospectively from 11 centers. Univariable and multivariable regression analyses were performed evaluating the impact of minor risk factors (moderate differentiation, diameter 1-2 centimeters, fat invasion, and small-caliber perineural invasion) on poor outcomes. Cumulative incidence function plots were created for time to poor outcomes by number of minor risk factors. Results A total of 15,481 Brigham and Women'’s Hospital T1 tumors were included, of which 90 (0.58%) developed major poor outcomes and 332 (2.1%) developed any poor outcome. Minor risk factors that were significant on multivariable analysis included moderate differentiation, diameter, and subcutaneous fat invasion. Cumulative incidence function plots demonstrated an increased risk of poor outcomes with presence of multiple minor risk factors; the risk of metastasis and major poor outcomes exceeded 5% in tumors with 3 minor risk factors. Limitations Retrospective design, limited number of major poor outcomes. Conclusion T1 tumors with multiple minor risk factors may be eligible for closer surveillance. Future staging systems should consider incorporating both major and minor risk factors.

Kimball, Kelly M. MD; Chirumamilla, Varshita BS; Carr, David R. MD, MPH; Shahwan, Kathryn T. MD Author Information

Basal cell carcinoma (BCC) is the most frequently diagnosed form of skin cancer, and its incidence continues to rise, particularly among older individuals. This trend puts a significant strain on health care systems, especially in terms of histopathologic diagnostics required for Mohs micrographic surgery (MMS), which is used to treat BCC in sensitive locations to minimize tissue loss. This study aims to address the challenges in BCC detection within MMS whole-slide images by developing and evaluating a deep learning model that bridges weakly supervised learning with interpretable segmentation-based methods through attention maps. Utilizing data sets from 2 medical centers, the model demonstrated an average area under the receiver operating characteristic curve (AUC) of 0.958 on internal testing and an AUC of 0.934 on an independent third external data set despite no fine-tuning or preprocessing for the latter. Attention maps provided insights into the model's decision making, highlighting critical regions for slide-level classification. The sensitivity of the attention maps in localizing tumor regions was 0.853 when no filtering was applied and gave 8 revision false positives per slide on average and was reduced to an average of 2 false positives per slide with a sensitivity of 0.873 when detections smaller than 200 mm were removed from the attention maps. These findings indicate that the deep learning model is highly effective in detecting BCC in MMS whole-slide images, with robust performance across different data sets and conditions. The use of attention maps enhances the model's interpretability, making it a promising tool for aiding dermatopathologists and MMS surgeons. (c) 2024 THE AUTHORS. Published by Elsevier Inc. on behalf of the United States & Canadian Academy of Pathology. This is an open access article under the CC BY license (http://creativecommons.org/ licenses/by/4.0/).

Background Cutaneous squamous cell carcinoma (CSCC) is a prevalent disease for which improved risk stratification strategies are needed. Objective To develop a novel prognostic model (herein “riSCC”) for CSCC and compare riSCC performance to Brigham and Women's Hospital and American Joint Committee on Cancer Staging eighth edition T staging systems. Methods Retrospective 12-center, multinational cohort study of CSCCs from 1991 to 2023. Clinical and pathologic risk factors, treatments, and outcomes were collected. Fine-Gray model was employed for each outcome with inverse probability of treatment weighting. A final model was trained for prospective use and estimation of hazard ratios. Results Twenty-three thousand one hundred sixty-six localized CSCC tumors were included. riSCC prognostic model performed superiorly to American Joint Committee on Cancer eighth edition and Brigham and Women's Hospital T staging for all outcomes. At 5 years, the C-index for riSCC ranged from 0.74 for local recurrence to 0.87 for disease specific death. Limitations Retrospective study design. Conclusion riSCC prognostic model offers fine-grained risk estimates and improved stratification for important CSCC outcomes compared to T staging systems.

BACKGROUND Deep learning has been used to classify basal cell carcinoma (BCC) on histopathologic images. Segmentation models, required for localization of tumor on Mohs surgery (MMS) frozen section slides, have yet to reach clinical utility. OBJECTIVE To train a segmentation model to localize BCC on MMS frozen section slides and to evaluate performance by BCC subtype. MATERIALS AND METHODS The study included 348 fresh frozen tissue slides, scanned as whole slide images, from patients treated with MMS for BCC. BCC foci were manually outlined using the Grand Challenge annotation platform. The data set was divided into 80% for training, 10% for validation, and 10% for the test data set. Segmentation was performed using the Ultralytics YOLOv8 model. RESULTS Sensitivity was .71 for all tumors, .87 for nodular BCC, .79 for superficial BCC, .74 for micronodular BCC, and .51 for morpheaform and infiltrative BCC. Specificity was .75 for all tumors, .59 for nodular BCC, .58 for superficial BCC, .83 for micronodular BCC, and .74 for morpheaform and infiltrative BCC. CONCLUSION This study trained a segmentation model to localize BCC on MMS frozen section slides with reasonably high sensitivity and specificity, and this varied by BCC subtype. More accurate and clinically relevant performance metrics for segmentation studies are needed.

Poor differentiation is strongly associated with poor outcomes in cutaneous squamous cell carcinoma (CSCC). In addition, the National Comprehensive Cancer Network (NCCN) guidelines designate poorly differentiated tumors as “very high risk”. Despite its clear prognostic implications, there is no standardized grading system for CSCC differentiation in common use today. CSCC differentiation is graded inconsistently by both dermatopathologists and Mohs surgeons, and reliability studies have demonstrated suboptimal inter- and intra-rater reliability in both of these groups. The absence of a standardized and reliable grading system has impeded the use of differentiation in CSCC staging, despite its apparent correlation with disease outcomes. We performed a comprehensive review of the literature summarizing historical CSCC differentiation grading systems, as well as grading systems in non-cutaneous head and neck SCC as a point of reference. Relevant articles were identified by searching Embase and PubMed, as well as by reviewing reference lists for additional articles and histology textbook excerpts. CSCC grading systems that were identified and summarized include the historical Broders system, the World Health Organization system, the College of American Pathologists’ system, and a system described by a 2023 Delphi consensus panel of dermatopathologists.

BACKGROUND:Solid organ transplant recipients with cutaneous squamous cell carcinoma (CSCC) have an increased risk of poor outcomes. However, a recent study demonstrated that immunosuppression is not an independent risk factor for these poor outcomes after controlling for primary tumor stage. OBJECTIVE:To evaluate whether transplant status is an independent risk factor for poor outcomes in CSCC. MATERIALS AND METHODS:A database of CSCCs treated at an academic center over 10 years was used to perform a retrospective cohort study comparing the risk of poor outcomes (local recurrence, regional and distant metastases, and disease-specific death) in solid organ transplant recipients and controls. Subjects were matched on age, tumor stage, sex, tumor site, and time to poor outcome. RESULTS:There were 316 tumors from 78 transplant patients and 316 tumors from 262 controls. On multivariate analysis, tumor stage and location on the head and neck were predictive of poor outcomes. There was no significant difference in the risk of poor outcomes in the transplant group versus the control group. CONCLUSION:Transplant status was not an independent risk factor for poor squamous cell carcinoma outcomes after controlling for stage, age, sex, site, and time to poor outcome.

To the Editor: Large language models (LLMs) are programs that are trained on datasets with supervised or unsupervised learning to create artificial neural networks that process data inputs. ChatGPT is an example of an LLM that utilizes natural language processing and provides human-like responses to text-based prompts. With increased accessibility of medical records, patients have sought to better understand their conditions using online resources, including ChatGPT.1 Furthermore, providers without formal dermatologic training could use ChatGPT in clinical decision making.

BACKGROUND:Poor differentiation predicts adverse outcomes in cutaneous squamous cell carcinoma (CSCC), but there is no standardized, reliable grading system. OBJECTIVE:To explore which histologic features have the greatest impact on CSCC differentiation interrater agreement. MATERIALS AND METHODS:In a prior study, 40 raters graded differentiation for 45 squamous cell carcinomas, and percent interrater agreements were calculated. Cases graded as well/moderately differentiated with 100% agreement (10), those graded as poorly differentiated with ≥80% agreement (5), and those that received a variety of grades with ≤60% agreement (7) were pulled for the current study. Three raters graded individual histologic features for each case, and percent interrater agreements were calculated using both the well/moderately/poorly differentiated grading system and a dichotomized system. RESULTS:The percent interrater agreements were 34.8% for mitoses, 53% for pleomorphism, 59.1% for keratinization, 66.7% for cellular cohesion/intercellular bridges, and 78.8% for tumor edges. Percent agreements improved with dichotomous grading; the largest improvement was seen within the group of cases that had been graded as well/moderately differentiated with 100% agreement in the prior study. CONCLUSION:Future squamous cell carcinoma differentiation grading systems would benefit from eliminating mitotic rate, clearly defining how to grade other features, and dichotomous grading.

BACKGROUND:The performance of staging systems in non-head and neck cutaneous squamous cell carcinomas has not been well established. OBJECTIVE:To evaluate the performance of the American Joint Committee on Cancer 8th Edition and Brigham and Women's Hospital staging systems in non-head and neck squamous cell carcinomas. MATERIALS AND METHODS:Eligible tumors were identified and staged from an existing retrospective database. Cumulative incidence function curves of any poor outcome were generated. Distinctiveness, sensitivity, specificity, positive and negative predictive value, and concordance index were calculated. RESULTS:1,042 primary tumors were included, with 38 resulting in any poor outcome and 16 in any major poor outcome. High-stage tumors represented 2.2% and 3.5% of tumors; these accounted for 10/38 of the poor outcomes (26.3%) and 8/16 of the major poor outcomes (50%). High-stage tumors predicted major poor outcomes with a sensitivity of 0.5 and specificity of 0.99 for the Brigham and Women's Hospital system, and a sensitivity of 0.5 and specificity of 0.97 for the American Joint Committee on Cancer 8th edition system. The concordance index for both was 0.74. CONCLUSION:Current staging systems can be used to predict poor outcomes in cutaneous squamous cell carcinomas off the head and neck.

Importance:Cutaneous squamous cell carcinoma (CSCC) is the second most common malignant disease in the US. Although it typically carries a good prognosis, a subset of CSCCs are highly aggressive, carrying regional and distant metastatic potential. Due to its high incidence, this aggressive subset is responsible for considerable mortality, with an overall annual mortality estimated to equal or even surpass melanoma. Despite this morbidity, CSCC is excluded from national cancer registries, making it difficult to study its epidemiology and outcomes. Therefore, the bulk of the CSCC literature is composed of single-center and multi-institutional retrospective cohort analyses. Given variations in reporting measures and analyses in these studies, interpretability between studies and the ability to pool results are limited. Objective:To define standardized reporting measures for retrospective CSCC studies. Findings:An expert panel was convened to determine standardized guidelines for recording and analyzing retrospective CSCC data. A total of 13 dermatologists and dermatologic surgeons with more than 5 years of posttraining experience and considerable experience with performing CSCC outcomes research were recruited to the panel. Consensus recommendations were achieved for CSCC retrospective study reporting measures, definitions, and analyses. Conclusions and Relevance:The recommendations in this report present the potential to standardize future CSCC retrospective studies. With such standardization, future work may have greater interstudy interpretability and allow for pooled analyses.

Mafee, Mariam MD; Yi, Michael D. BS; Carr, David R. MD, MPH; Alam, Murad MD, MSCI, MBA Author Information

Background: Mohs micrographic surgery (MMS) is a promising treatment modality for melanoma in situ (MIS). However, variations in surgical technique limit the generalizability of existing data and may impede future study of MMS in clinical trials. Methods: A modified Delphi method was selected to establish consensus on optimal MMS techniques for treating MIS in future clinical trials. The Delphi method was selected due to the limited current data, the wide range of techniques used in the field, and the intention to establish a standardized technique for future clinical trials. A literature review and interviews with experienced MMS surgeons were performed to identify dimensions of the MMS technique for MIS that (1) likely impacted costs or outcomes of the procedure, and (2) showed significant variability between surgeons. A total of 8 dimensions of technical variation were selected. The Delphi process consisted of 2 rounds of voting and commentary, during which 44 expert Mohs surgeons across the United States rated their agreement with specific recommendations using a Likert scale. Results: Five of eight recommendations achieved consensus in Round 1. All 3 of the remaining recommendations achieved consensus in Round 2. Techniques achieving consensus in Round 1 included the use of a starting peripheral margin of ≤5 mm, application of immunohistochemistry, frozen tissue processing, and resecting to the depth of subcutaneous fat. Consensus on the use of Wood’s lamp, dermatoscope, and negative tissue controls was established in Round 2. Conclusions: This study generated 8 consensus recommendations intended to offer guidance for Mohs surgeons treating MIS. The adoption of these recommendations will promote standardization to facilitate comparisons of aggregate data in multicenter clinical trials.

Understanding patient non-adherence to prescribed antibiotics can inform clinical practices, patient counseling, and antibiotic efficacy study design in dermatology. The primary objective was to determine the rate of and reasons for antibiotic non-adherence in the dermatologic surgery setting. The secondary objective was to test the applicability of previously studied survey questions for antibiotic non-adherence screening in the dermatologic surgery setting. Five academic outpatient dermatologic surgery centers across the United States conducted one multicenter prospective cohort study. Dermatologic surgery patients ≥ 18 years of age who were prescribed an antibiotic were included as part of this study. 15.2

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. ( J Am Acad Dermatol 2024;90:798805.)

Reconstruction of an extensive conchal bowl defect with notable cartilage loss is challenging due to the unique shape of the concha, the need for adequate structural support, and the lack of adjacent tissue reservoirs. Repair of a full-thickness conchal bowl defect has included 3-stage approaches, such as the anterior pedicled retroauricular flap. For an extensive conchal defect with substantial cartilage loss but intact posterior auricular skin, we recommend consideration of the retroauricular pull-through sandwich flap, which combines a cartilage graft and retroauricular interpolation flap pulled through a posterior auricular incision to resurface the anterior ear.

ABSTRACT:Nevus spilus, or speckled lentiginous nevus, is a relatively common lesion that presents at birth or in early childhood. It consists of a background tan patch, which appears similar to a café au lait macule or lentigo simplex on histology, studded with various types of nevi. Rarely, these nevi can undergo malignant transformation to melanoma. When melanoma develops within a heavily photodamaged nevus spilus, evaluating excision margins may be challenging because the combined histologic features of nevus spilus and severe dermatoheliosis can mimic melanoma in situ. We report a case of an elderly man with extensive sun damage who developed malignant melanoma within an occult nevus spilus, resulting in multiple excisions with false-positive margins.