Risk factors associated with clinical-histopathologic discordance in keratoacanthoma diagnosis

Summary: Keratoacanthomas (KA) are rapidly growing cutaneous tumors that closely resemble squamous cell carcinoma (SCC), leading to frequent diagnostic uncertainty. Same-day treatments such as ED&C are often performed on clinical suspicion alone. However, misclassification of SCC as KA can result in undertreatment of aggressive disease, while unnecessary excision of KA may lead to overtreatment. This study examines risk factors for clinical-histopathologic discordance in KA diagnosis to better guide treatment decision-making. We conducted a retrospective cohort study analyzing 477 consecutive tumors from a single academic medical center from 2010-2014 with KA listed in the clinical differential. Clinical and histopathologic diagnoses were compared, and univariate logistic regression identified risk factors for diagnostic discordance. Of the suspected KA cases, 122 (25.6%) were confirmed as KA, 223 (46.8%) were well-differentiated SCC, and 132 (27.7%) were non-well differentiated SCC. The non-well differentiated group included 66 well-moderate, 56 moderate, 8 moderate-poor, and 2 poorly differentiated SCC. KA and well-differentiated SCC were combined into a single reference group due to similar treatment guidelines and prognoses. Significant predictors of discordance included male sex (OR: 2.07, 95% CI: 1.38–3.15, p < 0.001), history of SCC (OR: 1.87, 95% CI: 1.24-2.83, p = 0.003), history of BCC (OR: 1.57, 95% CI: 1.05–2.36, p = 0.027), history of ≥2 SCC (OR: 1.76, 95% CI: 1.17–2.66, p = 0.007), and head/neck tumor locations (OR: 4.53, 95% CI: 2.90–7.11, p < 0.001). Given the risks of clinical-histopathologic discordance, clinicians should take a personalized approach to management and decision-making. For patients at high-risk for discordance, deferring same-day treatment until histopathologic confirmation may improve diagnostic accuracy and treatment outcomes. James Feng¹, Payal C. Shah², Hayden Doughty², Arthur Marka³, Joshua Levy⁴, Robert LeBlanc⁵, Joi Carter² 1. Dartmouth College Geisel School of Medicine, Hanover, NH, United States. 2. Dermatology, Dartmouth Health, Lebanon, NH, United States. 3. Seacoast Dermatology, Portsmouth, NH, United States. 4. Pathology, Cedars-Sinai Medical Center, Los Angeles, CA, United States. 5. Pathology, Dartmouth Health, Lebanon, NH, United States. Clinical Research: Interventional Research