Oral Glycogenic Acanthosis: A Clinicopathological Analysis of 13 Cases and Narrative Literature Review

Glycogenic acanthosis (GA) is a benign epithelial lesion characterized by intracellular glycogen accumulation, most seen in the esophagus. In the oral cavity, it is rarely reported and clinical recognition is low. We retrospectively analyzed 13 cases of oral GA diagnosed between 2017 and 2025, assessing clinical presentation, histopathological characteristics and follow-up data. Thirteen cases were identified, with a median age of 61 years (range: 34–71) and a male predominance (76.9%). Lesions were asymptomatic, thin, homogeneous, often well-demarcated milky white plaques, located on the lateral or ventral surfaces of the tongue (84.6%) or the soft palate (15.4%), all mimicking oral leukoplakia. All patients reported alcohol use; 46.2% were never smokers. Histologically, lesions showed glycogen-rich clear cells in the spinous layer of epithelium, without dysplasia. Follow-up data (available in 9 cases, 3 months to 8 years) showed that most lesions remained stable following initial diagnosis, except for one case that regressed by 80% without treatment after nearly 4 years, and another that focally progressed to mild dysplasia after 7 years in a smoking patient with HIV. This study presents the largest series of oral GA to date and proposes a list of distinguishing clinical and histopathological features to assist in the diagnosis of this condition. Our findings are consistent with the seven previously published reports, further supporting that oral GA is an under-recognized lesion that can clinically mimic homogenous leukoplakia. While current evidence suggests a benign long-term course, additional studies using standardized diagnostic criteria and molecular approaches are needed to better understand its pathogenesis and prognosis. Greater clinician awareness is essential to minimize misdiagnosis and ensure appropriate management.