Practice Essentials
In 1943, Field and Ackermann described the features characteristic of intraoral nevi. [1] Oral melanocytic nevi are benign proliferations of nevus cells in the epithelial layer, the submucosal layer, or both. As such, they are classified as junctional, intramucosal, and compound nevi. Nevi may also be classified as congenital or acquired. Unlike their cutaneous counterparts, oral melanocytic nevi are rare.
Intramucosal nevi are typically light brown and dome-shaped. These are the most common type, accounting for 64% of all reported oral nevi. [2] Note the image below.
Intramucosal nevus on the lower lip. This brown papule measured 0.6 cm in diameter and was only slightly raised. Melanotic macules are invariably flat.
The common blue nevus is the second most common type found in the oral cavity, accounting for 16.5-36% of all oral nevi. [3] Note the image below.
Blue nevus on the gingiva. This 1-cm saucer-shaped tan macule on the gingiva has histologic features consistent with those of a blue nevus, which is the second most common type of oral nevus. This location is atypical because most blue nevi occur on the palate.
Junctional and compound nevi are uncommon, accounting for only 3-6% and 5.9-16.5%, respectively. [2, 4, 5]
Rarer types include Spitz nevi, cellular blue nevi, congenital nevi, combined nevi, balloon cell nevi, epithelioid blue nevi, plaque-type blue nevi, halo nevi, and neurotized nevi. [6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28] Dysplastic nevi have not been reported in the oral mucosa.
An analysis of 761 oral pigmented lesions in Brazil from 1974-2019 found that the majority (53.6%) were amalgam tattoos. Melanotic macule (18.3%) was the next most common type. [29]
Prognosis
Reports mainly based on case reports and case series have shown that the prognosis for oral melanocytic nevi is excellent. [30] Only 1 case of recurrence, in a compound nevus, has been reported. [31] No documented cases of malignant transformation were reported in a cohort of intraoral nevi with up to 2-8 years of follow-up; however similar clinical presentations with its malignant counterparts put patients at risk, hence histologic sampling is essential in all oral melanocytic nevi, especially when located in the palate, the most common site of oral melanoma, to exclude and presumably prevent such transformation. [21, 30, 32, 28]
Although overall considered "benign", among all the types of oral nevi, one must carefully follow up cases of mucosal cellular blue nevi as these have been reported to have a 5.2-6.3% chance of malignant transformation. [28]
Patient education
Patients should be instructed to observe and report any lesion in the oral cavity, especially those that change in size, that change in color, have nodularity, bleed, and/or ulcerate.
Signs and symptoms
Most oral nevi are solitary and asymptomatic. Congenital melanocytic nevi are present at birth or appear shortly after. Acquired melanocytic nevi begin to appear in early childhood. The lesions are usually detected as an incidental finding on routine dental examination.
Of patients with recorded complaints, 22% described a mass, growth, or pigmented spot. [33] A minority of patients complained of soreness or pain related to another cause, such as an ill-fitting denture. Less than 1 in 10 patients were aware of evolving lesions. Most patients could only speculate about the duration of their condition.
Also see Physical Examination.
Diagnostics
Histology shows nests of nevus cells that would positively express the following immunohistochemical markers: S100, Melan A (MART-1), SOX10, and HMB45. [28] See Histologic Findings. The same tests for cutaneous nevi are available for the assessment of mucosal lesions if concern exists after histologic analysis. Aspiration may be performed to differentiate vascular lesions from melanocytic lesions.
Imaging studies typically are not indicated. Periapical radiography may be helpful in differentiating an amalgam tattoo from a nevus by demonstrating minute opaque particles. Angiography may be performed to exclude vascular anomalies.
Procedures
Biopsy and histologic examination of all pigmented and nonpigmented oral lesions are indicated to confirm the nature of the lesion. The primary diagnostic procedure is excisional biopsy. [34] Incisional biopsy may be performed in lesions larger than 1-2 cm. The incision should be made in the nodular areas, if they exist, and the incisions should start from the center, not from the periphery of the lesion. See the image below.
This biopsy-proven intramucosal nevus on the gingiva is unusual because it is not raised and has an irregular outline.
Treatment
Because oral nevi are not related to sun exposure, they are impossible to prevent.
Regular and thorough oral examinations should be performed; the goal is to exclude malignant lesions.
All melanocytic and amelanocytic lesions in the oral cavity should be viewed with suspicion. Complete excision is suggested to be the most reliable approach to oral melanocytic lesions. [35] Evolving and/or recurrent lesions also necessitate excision and microscopic evaluation.
Patients may be referred to an oral medicine and/or oral pathology specialist for questionable clinical/histologic diagnosis.
Pathophysiology
Nevus cells are derived from the neural crest. These cells migrate to the skin and oral mucous membranes during embryogenesis. Nevus cell formation probably begins with the proliferation of melanocytes along the basal cell layer and is possibly associated with elongation of the rete ridges. Nevus cells either lack contact inhibition or lose it shortly after the proliferation process begins. They retain melanin pigment and form nests or thèques.
Nevus cells have the ability to migrate from the basal cell layer into the underlying submucosa. Eventually, they may separate from the epidermis. Junctional nests may be lost later, and nevus cells may be confined to the submucosa. As the nevus cells penetrate into the submucosa, their pigmentation diminishes.
Genetic analysis has revealed V600E point BRAF mutation in both oral benign and malignant melanocytic lesions. [36]
Dika et al point out that pigmented lesions of the oral cavity and the nails sometimes occur simultaneously and may be indicative of underlying syndromes or systemic conditions. [37]
Epidemiology
Frequency
The incidence is 0.1-1.15% in the United States. [38, 39] Lesions may be underreported because they often go undetected. Oral blue nevi are rare but have been reported. [40]
Race
Oral nevi may occur in persons of all races. They are reported more frequently in white patients (55%) than in black patients (23%). [38] The apparent predominance of oral nevi in whites over Asians (14%) and Hispanics (7%) may be due to the over-representation of this group among patients who underwent biopsies. [41]
Sex
Oral mucosal nevi have a slight female predominance (1.5:1 female-to-male ratio), except for the blue nevi type, which occurs equally in both sexes.4 In a multicenter study of 241 oral pigmented lesions in Thailand by Dhanuthai et al, a 2.49:1 female-to-male ratio was observed. [42]
Age
The average age at diagnosis is 35 years (range, 3-85 y). [4] Male patients tend to be a few years older than female patients. Patients with junctional and compound nevi are relatively younger, with an average age at diagnosis of 22 and 24 years, respectively. A compound melanocytic nevus on the hard palate of a 5-year-old girl was reported in 2022. [43]
In the Thai study mentioned above, patient age ranged from 1 month to 88 years, with a mean ± standard deviation of 38.74 ± 20.96 years. [42]
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This biopsy-proven intramucosal nevus on the gingiva is unusual because it is not raised and has an irregular outline.
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Intramucosal nevus on the lower lip. This brown papule measured 0.6 cm in diameter and was only slightly raised. Melanotic macules are invariably flat.
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Blue nevus on the gingiva. This 1-cm saucer-shaped tan macule on the gingiva has histologic features consistent with those of a blue nevus, which is the second most common type of oral nevus. This location is atypical because most blue nevi occur on the palate.
