Original StudyA Single-Institution Cohort Study With Nevi of Special Site: Recurrence, Progression to Melanoma, and Patterns of ManagementElkeeb, Dena M. MD, MS*,†; Hopkins, Zachary H. MD‡; Bolender, Caitlin M. MD†; Moreno, Christopher MD§; Florell, Scott R. MD†; Bowen, Anneli R. MD†; Vitale, Patricia MD†; Zussman, Jamie MD†; Duffy, Keith MD†; Grossman, Douglas MD, PhD†,¶; Secrest, Aaron M. MD, PhD†,‖; Wada, David A. MD†,¶ Author Information *Department of Dermatopathology, Mercy Health, Cincinnati, OH; †Department of Dermatology, University of Utah Health, Salt Lake City, UT; ‡Broward Health Medical Center, Fort Lauderdale, FL; §Department of Dermatology, University of Arizona, Tucson, AZ; ¶Huntsman Cancer Institute, Salt Lake City, UT; and ‖Department of Population Health Sciences, University of Utah Health, Salt Lake City, UT. Correspondence: Dena M. Elkeeb, MD, MS, Department of Dermatology, University of Utah and Mercy Health Rookwood Dermatology, Dermatopathology, Mercy Health 4101 Edwards Road, Second Floor, Cincinnati, OH 45209 (e-mail: [email protected]). D. M. Elkeeb and Z. H. Hopkins have contributed equally. D. M. Elkeeb had full access all data in this study and takes full responsibility for data integrity and the accuracy of the analyses. Conceptualization: D. M. Elkeeb, Z. H. Hopkins, D. Grossman, D. A. Wada. Data Curation: Z. H. Hopkins, C. M. Bolender, C. Moreno. Formal Analysis: Z. H. Hopkins. Funding Acquisition: D. M. Elkeeb, D. A. Wada. Investigation: D. M. Elkeeb, Z. H. Hopkins, A. M. Secrest, D. A. Wada. Methodology: Z. H. Hopkins, A. M. Secrest. Project Administration: D. M. Elkeeb. Resources: D. M. Elkeeb, D. A. Wada. Supervision: D. A. Wada. Visualization: Z. H. Hopkins. Writing– Original Draft Preparation: Z. H. Hopkins. Writing–Review and Editing: D. M. Elkeeb, Z. H. Hopkins, A. M. Secrest, C. M. Bolender, C. Moreno, D. Grossman, D. A. Wada. This study was deemed exempt by the Institutional Review Board. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's Web site (www.amjdermatopathology.com). The American Journal of Dermatopathology 45(1):p 28-39, January 2023. | DOI: 10.1097/DAD.0000000000002134 Buy SDC Metrics Abstract Nevi of specialized sites (NOSS) occur on the scalp, ears, flexural, acral, and genital areas and display atypical clinical and histologic features. We assessed NOSS recurrence and progression to melanoma, management patterns, and associations between histologic features and treatment recommendations. We queried all histologic diagnoses of NOSS (n = 275) from 2012 to 2017 from a large U.S. academic medical center with reference dermatopathology laboratory and matched these to clinical records. A blinded panel of dermatopathologists re-evaluated lesions, catalogued histologic findings, and gave management recommendation. Associations with dermatopathologist decision and concordance between new and original recommendations were assessed. Of 117 cases with follow-up, 2 locally recurred (1.46%) and none eventuated in melanoma. Clinical features were not associated with original treatment recommendations. After histopathologic review, large melanocytes [odds ratio ratio (ORR) = 8.00, 95% CI, 1.35–47.4] and junctional mitotic figures (ORR = 65.0, 6.5–650) predicted excision recommendation. Likewise, accumulation of many (>9) high-risk features was associated with excision recommendation. Panel review changed treatment recommendation in 27% of cases. Fair concordance existed between original and panel recommendations (κ = 0.29, 0.15–0.44). The low rate of recurrence and lack of melanoma occurrence suggest that despite an atypical clinical and histopathologic appearance, these nevi have limited potential for malignant transformation. Histopathologic findings seem to be principal drivers behind the recommendation for excision in this analysis. Variability existed in treatment recommendations; the panel's consensus recommendation tended to downgrade treatment. This highlights the importance of further outcomes-based studies to identify true high-risk features and refine management guidelines. Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.