Pigmented Lesions of the Oral Mucosa: Clinical Presentation, Histology, and Recommendations for Management

Pigmented lesions of the oral cavity can present significant diagnostic challenges because of their diverse etiologies and similar clinical presentations. Understanding these lesions is crucial for correct diagnosis and management because the biologic behavior ranges from benign physiologic variations to aggressive malignancies. The spectrum of oral lesions can include melanin-associated and exogenous pigmented lesions such as physiologic pigmentation and an amalgam tattoo, reactive processes such as smoker's melanosis and post-inflammatory pigmentation, benign neoplasms such as melanocytic nevi, and malignant conditions such as oral mucosal melanoma. Unlike cutaneous malignant melanomas, mucosal melanomas show distinct molecular profiles, with a lower prevalence of BRAF^V600E mutations and a higher prevalence of c-KIT (CD117) mutations, which impacts therapeutic approaches. While most oral pigmented lesions are benign, they require a careful clinical evaluation, and when indicated, a biopsy for definitive diagnosis. This comprehensive review enables clinicians to navigate the complicated spectrum of oral pigmented lesions for optimal patient care.