Lohman, Mary E.

Abstract Background Extramammary Paget disease (EMPD) is a rare cutaneous adenocarcinoma. While localized disease has an excellent prognosis, metastatic EMPD is aggressive with no standardized systemic therapy. This study characterizes the clinicopathologic and molecular landscape of metastatic/recurrent EMPD to identify therapeutic vulnerabilities. Patients and methods We conducted a retrospective cohort study of 26 patients with metastatic or distantly recurrent EMPD treated at Mayo Clinic (2000-2025). Descriptive statistics were used to summarize baseline characteristics. Survival outcomes were estimated using Kaplan–Meier methods, with group comparisons performed using log-rank testing. Continuous variables were compared using nonparametric tests, and categorical variables were analyzed using appropriate comparative tests. Pathway-level genomic correlations with TCGA reference cohorts were assessed using Spearman rank correlation. Treatment responses were retrospectively evaluated from radiologic reports. Results The cohort was predominantly male (73.1%) and White (92.3%), with a median age of 68 (IQR, 53-79). Lymph nodes were the most common metastatic site (61.5%). The median overall survival (OS) was 20.0 months (95% CI, 0-40.4). IHC showed universal CK7 and GATA3 positivity, with 80% androgen receptor (AR) expression. HER2 was positive (3+) or amplified in approximately one-third of cases. NGS revealed frequent mutations in TP53 (68.8%), ERBB2 (50%), and CDKN2A/B (50%). A “triple-hit” deletion at the 9p21 locus (CDKN2A/B/MTAP) was identified in 25% of cases. Genomic profiling showed strong similarity to HER2+ breast and urothelial carcinomas. HER2-directed therapy was associated with longer overall survival (median OS 73.0 months [95% CI, 0-177.9] vs 19.0 months [95% CI, 0-41.4]; HR 0.50 [95% CI, 0.0-177.9], P = .3), although this difference did not reach statistical significance. Conclusion Metastatic EMPD exhibits distinct clinicopathologic and molecular features, including high AR and HER2 expression, TP53 and CDKN2A/B alterations, and similarity to systemic HER2+ malignancies. The observed activity of HER2-directed therapies in this cohort suggests the potential value of further investigating biomarker-guided treatment strategies in metastatic EMPD. NGS-guided profiling may inform precision treatment strategies, including AR-targeted therapy and emerging MTAP-directed approaches.

BACKGROUND Guidelines and evidence related to antibiotic prophylaxis in dermatologic surgery have evolved since the authors' previously published advisory statement. OBJECTIVE To provide an updated advisory statement on antibiotic prophylaxis in dermatologic surgery as guided by updated recommendations from the American Heart Association and the American Dental Association with the American Academy of Orthopaedic Surgeons guidelines. METHODS A structured literature review was performed. A multidisciplinary team of specialists from dermatologic surgery, infectious diseases, and pharmacy were convened to review up-to-date data and develop updated comprehensive evidence-based recommendations. RESULTS Consistent with the previous advisory statement, prophylactic antibiotics are recommended for patients with high-risk cardiac or prosthetic joint conditions, when the dermatologic surgical site is infected or if the procedure breaches the mucosa. Significant changes were made for prophylaxis of surgical site infection. Updated recommendations were made regarding antibiotic selection in penicillin-allergic patients and intraoperative use of intraincisional clindamycin in the local anesthetic. LIMITATIONS Reviewed data are predominantly limited to retrospective data. CONCLUSION Recommendations regarding antibiotic prophylaxis around dermatologic surgery are evolving as new data and practices are introduced. The 2025 advisory statement provides the latest recommendations for appropriate use of antibiotic prophylaxis in dermatologic surgery.

A healthy 19-year-old man with Fitzpatrick skin type V presented with a 2-year history of smooth, firm, skin-colored papules on the nasal dorsum and bilateral alae. What is your diagnosis?

AbstractBackgroundPReferentially expressed Antigen in MElanoma (PRAME) immunohistochemical (IHC) staining is used to aid melanoma diagnosis. PRAME expression in nevus‐associated melanoma (NAM) has not been evaluated.MethodsPRAME IHC was applied to cases of NAM; staining for each population of melanocytes (benign and malignant) was graded based on the percentage of labeled cells. No labeling was graded 0, 1% to 25% labeling was 1+, 26% to 50% was 2+, 51% to 75% was 3+, and >76% was 4+.ResultsThirty‐six cases were reviewed. Sixty‐seven percent (24/36) of melanomas were PRAME positive (4+) while no (0/36) nevi showed 4+ positivity. Eighty‐one percent (29/36) of nevi were completely PRAME negative compared to 17% (6/36) of melanomas. In 67% of cases (24/36) PRAME differentiated between benign and malignant melanocyte populations.ConclusionsWe identified a high rate (67%) of differential PRAME staining in adjacent benign and malignant melanocyte populations in NAM. In PRAME positive (4+) melanomas, PRAME differentiates 100% (24/24) of benign and malignant melanocyte populations. When 4+ staining is used as the threshold for positivity, PRAME staining has a sensitivity of 67% (24/36) and a specificity of 100% (36/36). These results support PRAME IHC can assist in distinguishing melanocyte populations in melanoma arising within nevi.