Syphilitic Leukoplakia with Epithelial Dysplasia: A Diagnostic Challenge Highlighted by a Case Report and PRISMA-Compliant Systematic Review

Oral syphilis may present as a non-scrapable white lesion that clinically mimics oral leukoplakia. This combined case report and systematic review aimed to characterize syphilis-associated oral lesions with a white component and to evaluate separately cases classified as syphilitic leukoplakia. PubMed, Scopus, Web of Science, and Embase were searched through December 2025. Eligible English-language reports described a confirmed diagnosis of syphilis and an oral lesion with a white component. Two reviewers independently screened records, data were synthesized descriptively, and the included publications were appraised using the corresponding JBI tools. Sixteen publications met the inclusion criteria; together with the present case, they yielded 28 patients. Most patients were male (85.7%), and the tongue was the most frequently involved site (57.1%). Extraoral or systemic findings were documented in 39.3%, explicitly absent in 25.0%, and unreported in 35.7%. Five cases, including the present case, were classified as syphilitic leukoplakia. All five underwent biopsy, and epithelial dysplasia was identified in three. Among the 18 patients with reported outcomes, complete or near-complete resolution occurred in 17 and partial remission in one after antimicrobial therapy. Syphilis should be considered in the differential diagnosis of unexplained oral white lesions, particularly those resembling leukoplakia, to ensure appropriate serologic testing, histopathological assessment, and treatment.