Definition
A melanocytic nevus (“mole”) is a benign neoplasm formed by collections of nevus (melanocytic) cells located within the epithelium, the underlying connective tissue, or both. It is classified by the location of these cells into junctional, compound, intramucosal, and blue nevus subtypes. Oral melanocytic nevi are rare and have a very low risk of malignant transformation.
Etiology and Pathophysiology
Contributory factors :
- Benign neoplasm consisting of collections of nevus (melanocytic) cells in the epithelium, the supporting connective tissue, or both.
- Melanocytic nevi derive from melanocytes that originate from the neural crest.
- Acquired lesions in which both environmental and genetic factors are thought to play a role (for cutaneous lesions); sun exposure is a recognised environmental factor for cutaneous nevi.
- Cutaneous nevi show somatic activating mutations in the BRAF, HRAS, and NRAS proto-oncogenes; it remains unclear whether similar mutations cause oral melanocytic nevi.
- Pathogenesis of oral nevi is poorly understood. Melanocytic proliferation proceeds through phases corresponding to the subtypes: proliferation at the epithelial–connective tissue junction (junctional) → migration into the connective tissue (compound) → loss of the junctional component so all cells lie subepithelially (intramucosal).
- May present at any age, including at birth (congenital).
Prevalence
- Considered rare intraorally.
- Cutaneous nevi are common, usually developing in childhood (most present before age 35) and more frequently in Caucasians than in black or Asian individuals.
- Oral melanocytic nevi are most frequently observed in the third to fourth decades of life; more common in females (although total nevus counts are higher in males).
- Relative frequency of oral subtypes (Contemporary OM / Cawson): intramucosal nevus most common (~64–80%), followed by blue nevus (~8–17%), compound nevus (~6–17%); junctional and combined nevi are uncommon. (Blue nevi reported to account for up to ~35% of oral nevi in one source.)
Histological Features
- Characterised by nests of pigmented nevus cells; subtypes are categorised by the location of the nevus cells:
- Junctional nevus — nevus cells confined to the basal layer at the epithelium–connective tissue interface, especially at the tips of the rete ridges.
- Compound nevus — combination of junctional and intramucosal patterns; nests of benign melanocytes within the lower epithelium and connective tissue, often forming bulbous rete ridges.
- Intramucosal nevus — nevus cells located only in the connective tissue, separated from the epithelium (in late lesions by a band of fibrous tissue); melanocytes are heavily pigmented near the surface. Nevus cells are pale-staining with occasional nuclear vacuoles.
- Blue nevus — intramucosal/submucosal proliferation of pigment-laden, spindle-shaped melanocytes within densely collagenous (fibrotic) lamina propria, without melanocytic hyperplasia in the epithelium; melanin lies deep so reflected light appears blue. (Cellular type also shows larger round/ovoid melanocytes.)
Clinical Features
Location
- The hard palate is the most common intraoral site.
- Other affected sites: buccal and labial mucosae, gingiva, mucobuccal fold, and lip vermilion.
Appearance
- Small, elevated papules or nodules; may also be macular.
- Usually asymptomatic, solitary, well-circumscribed, and <1 cm.
- Colour: brown, blue-grey, or black.
- May be non-pigmented in approximately 10–15% of cases.
- Oral melanocytic nevi have no distinguishing clinical characteristics and can clinically mimic other focally pigmented lesions, including melanoma.
Differential Diagnoses
- Oral/labial melanotic macule
- Amalgam tattoo
- Malignant melanoma
- (Clinically, melanotic lesions should first be distinguished from vascular lesions — a vascular lesion blanches/disappears on pressure with a glass slide.)
Relevant Clinical Investigations
- Biopsy is required to establish an accurate diagnosis, as the clinical presentation resembles other focally pigmented lesions including malignant melanoma.
- Clinically, nevi look similar to melanotic macules but differ histologically.
Patient Management
- Conservative surgical excision is the indicated treatment; recurrence is rarely reported.
- Excision is generally recommended to ensure an accurate diagnosis and to rule out melanoma.
- Malignant transformation of oral melanocytic nevi is highly unlikely, and current evidence does not suggest oral nevi are markers for development of oral malignant melanoma. (Note: a high number of cutaneous nevi, e.g. >50, is an independent risk factor for cutaneous melanoma.)
- These are benign lesions; patients should not be referred as urgent cases.