Faculty Bibliography

BACKGROUND:While Brigham and Women's Hospital (BWH) T1 cutaneous squamous cell carcinomas (CSCCs) 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 was 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 [PNI]) on poor outcomes. Cumulative incidence function (CIF) plots were created for time to poor outcomes by number of minor risk factors. RESULTS:15,481 BWH 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. CIF 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/CONCLUSIONS:Retrospective design, limited number of major poor outcomes. CONCLUSION/CONCLUSIONS: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.

Primary cutaneous squamous cell carcinoma (cSCC) is responsible for ~10,000 deaths annually in the United States. Stratification of risk of poor outcome at initial biopsy would significantly impact clinical decision-making during the initial post operative period where intervention has been shown to be most effective. Using whole-slide images (WSI) from 163 patients from 3 institutions, we developed a self supervised deep-learning model to predict poor outcomes in cSCC patients from histopathological features at initial diagnosis, and validated it using WSI from 563 patients, collected from two other academic institutions. For disease-free survival prediction, the model attained a concordance index of 0.73 in the development cohort and 0.84 in the Mayo cohort. The model's interpretability revealed that features like poor differentiation and deep invasion were strongly associated with poor prognosis. Furthermore, the model is effective in stratifying risk among BWH T2a and AJCC T2, known for outcome heterogeneity.

BACKGROUND:Impaired immunity may drive the increased incidence and aggression of cutaneous squamous cell carcinoma (cSCC) in patients with hematologic malignancy; however, precise mechanisms and prognostic biomarkers remain undefined. CD73 maintains elevated immunosuppressive adenosine levels and is associated with poor prognosis in several tumor microenvironments. OBJECTIVE:Identify poor outcome biomarkers in patients with cSCC and hematologic malignancy. MATERIALS AND METHODS/METHODS:Differentially expressed genes in tumors from patients with hematologic malignancy experiencing good (n = 8) versus poor (n = 7) outcomes were identified by NanoString analysis. Results were validated at the protein level using CD73 immunohistochemistry in cSCC patients with (n = 38) and without (n = 29) hematologic malignancy. RESULTS:Forty-eight genes were differentially expressed in tumors from patients with hematologic malignancy experiencing good versus poor outcomes. CD73 gene expression was >2-fold higher in patients with poor versus good outcomes or normal skin. Significantly increased CD73 protein levels were observed in cSCC tumors with poor versus good outcomes from patients with hematologic malignancies (p < .01), whereas no differences were noted in tumors with poor versus good outcomes from patients without hematologic malignancies (p = .49). CONCLUSION/CONCLUSIONS:CD73 is highly expressed in poor prognosis cSCC from patients with hematologic malignancy and may represent a useful biomarker and potential therapeutic target.

There is a paucity of information on racial and ethnic disparities relating to barriers to care in healthcare access and utilization in patients with cutaneous malignancies. We conducted a cross-sectional analysis of adults with melanoma, basal cell carcinoma (BCC) and cutaneous squamous cell carcinoma (cSCC) in the National Institutes of Health (NIH) All of Us Research Program collected between May 2018 and July 2022. Participants included adults (aged 18 or older) with cutaneous malignancy who completed the Health Care Access and Utilization survey. We identified 5,817 adults who were diagnosed with BCC (67%), cSCC (28.9%), and melanoma (23.9%). Non-Hispanic Black (NHB) and Hispanic patients were more likely than non-Hispanic White (NHW) patients to delay a primary care visit due to cost (p = 0.005 and p = 0.015, respectively). NHB patients were also more likely to delay care due to lack of transportation (p < 0.001). NHB and Hispanic patients were more likely to place importance on seeing a provider from the same background (NHB p < 0.002; Hispanic p = 0.002) and also were more likely to report never being able to see such a provider (NHB p < 0.001; Hispanic p = 0.002). Medicaid/Medicare patients, non-college graduates, and those with lower incomes also faced increased barriers to care, including delays due to cost and transportation issues. People of color with cutaneous malignancies are more likely to delay care in seeing primary care providers due to cost or transportation issues. This study provides important insights on disproportionate healthcare usage among racial/ethnic groups that may help mitigate healthcare disparities.

BACKGROUND/UNASSIGNED:A deeper understanding of acute rejection in vascularized composite allotransplantation is paramount for expanding its utility and longevity. There remains a need to develop more precise and accurate tools for diagnosis and prognosis of these allografts, as well as alternatives to traditional immunosuppressive regimens. METHODS/UNASSIGNED:Twenty-seven skin biopsies collected from 3 vascularized composite allotransplantation recipients, consisting of face and hand transplants, were evaluated by histology, immunohistochemistry staining, and gene expression profiling. RESULTS/UNASSIGNED:significantly predicted inflammation specific to vascularized composite allografts that required therapeutic intervention. CONCLUSIONS/UNASSIGNED:The mechanism of vascularized composite allograft-specific inflammation and rejection appears to be conserved across different patients and skin on different anatomical sites. A concise gene signature can be utilized to ascertain graft status along with a continuous scale, providing valuable diagnostic and prognostic information to supplement current gold standards of graft evaluation.

IMPORTANCE/UNASSIGNED: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/UNASSIGNED:To define standardized reporting measures for retrospective CSCC studies. FINDINGS/UNASSIGNED: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/UNASSIGNED: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.

BACKGROUND:Limited access to dermatologic care may pose an obstacle to the early detection and intervention of cutaneous malignancies. The role of artificial intelligence (AI) in skin cancer diagnosis may alleviate potential care gaps. OBJECTIVE:The aim of this systematic review was to offer an in-depth exploration of published AI algorithms trained on dermoscopic and macroscopic clinical images for the diagnosis of melanoma, basal cell carcinoma, and cutaneous squamous cell carcinoma (cSCC). METHODS:Adhering to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines, a systematic review was conducted on peer-reviewed articles published between January 1, 2000, and January 26, 2023. RESULTS AND DISCUSSION/CONCLUSIONS:Among the 232 studies in this review, the overall accuracy, sensitivity, and specificity of AI for tumor detection averaged 90%, 87%, and 91%, respectively. Model performance improved with time. Despite seemingly impressive performance, the paucity of external validation and limited representation of cSCC and skin of color in the data sets limits the generalizability of the current models. In addition, dermatologists coauthored only 12.9% of all studies included in the review. Moving forward, it is imperative to prioritize robustness in data reporting, inclusivity in data collection, and interdisciplinary collaboration to ensure the development of equitable and effective AI tools.