Oral Melanoacanthoma

Etiology

The etiology of oral melanoacanthoma is yet to be determined, but it is mostly associated with a traumatic process that stimulates melanocyte activity.[3] This is supported by the reactive infiltrate of eosinophils found on histopathology, which corroborates the reactive nature. A review of 56 articles of 115 cases concluded that 77% of authors found an association with a reactive etiology.[1] Chronic trauma, or chemical irritants, stimulates melanocytes, which result in either oral pigmentation or a melanoacanthoma. Regular contact with petroleum derivatives found in toothpaste and mouthwashes may act as an irritant agent. These derivatives include sodium lauryl sulfate, phenolphthalein, nitrophenol, chlorophenol, phenylenediamine sulfate, amine fluoride, and cocamidopropyl betaine. Hydrogen peroxide mouthwashes can also irritate the oral mucosa and cause melanoacanthoma. Silver amalgam has also been described as an etiologic factor that may cause morphologic changes and pigmentation, and dental restoration with other materials.[1] Bruxism, biting of the cheeks, poorly fitted removable prosthesis, implant surgery, and non-specific chronic trauma have been reported features preceding the presentation of an oral melanoacanthoma. Other etiologic factors include patients treated for chronic asthma and ferrous lactate for chronic treatment of iron-deficiency anemia.

Epidemiology

Oral Melanoacanthoma may occur at any stage in adult life, but it is predominantly encountered in the younger age group with a median age of diagnosis of 35 years old. It has a female predilection with a ratio of 3 to 2. It is mostly seen in dark-skinned patients, followed by non-Hispanic Whites and Hispanics.[1][2] Solitary lesions are more frequently observed in the buccal mucosa, unlike multifocal ones that tend to occur mostly on the palate.[4]

Pathophysiology

Oral melanoacanthomas usually grow rapidly, and therefore, they often mimic the radial growth phase of an intraoral melanoma. It has been suggested that chronic mechanical trauma, or chemical irritants, may stimulate melanocytic activity.[1][5]

Histopathology

A biopsy is mandatory for diagnosing oral melanoacanthoma and demonstrating dendritic melanocytes and spinous keratinocytes.[6] The dendritic melanocytes are clearly defined and contained in an acanthotic epithelium.[7][8] This is in contrast to oral melanoma, in which the melanocytes cross the lamina propria. The Masson-Fontana silver impregnation stain usually demonstrates the dendritic melanocytes. The adjacent connective tissue exhibits an inflammatory infiltrate in the great majority of cases.[2]

History and Physical

The presentation typically involves a history of new darkening or dark spots in the mouth, generally brown or black, well-circumscribed, flat, or raised. Almost half of the lesions are located on the buccal mucosa, followed by the palate and lips, and, less commonly, the gums.[1][4][9][4] They are usually asymptomatic, but they may be painful or itchy. History of new mouthwash or toothpaste, teeth whitening agents, recent dental procedures, bruxism, aggressive brushing, or trauma is usually found on inquiry. Because they exhibit radial growth, which can be rapid, they can often be mistaken for melanoma. Melanomas most commonly affect the hard palate. A thorough oral exam to assess for the presence of multiple spots should be performed, as well as a full skin exam to assess for concomitant nevi or suspicious melanocytic lesions. These lesions tend to regress spontaneously and may be characterized by rapid growth before stabilization and regression. In rare instances, patients may present with diffuse oral pigmentation.[10] A family history of pigmented oral lesions or polyposis may suggest Peutz-Jegher syndrome. The palate is more commonly affected by multifocal than by solitary lesions. Multifocal lesions are usually more black with a mean diameter of each lesion smaller than that of the solitary ones. The number of these lesions typically ranges between 2 and 5.[4]

Evaluation

Since oral melanoacanthomas do not exhibit any distinctive clinical features, the diagnosis is made by histopathological findings. Immunohistochemical staining with monoclonal antibodies for S-100 and HMB-45 is a useful tool to confirm the presence of melanocyte dendritic cells.[11]

Treatment / Management

Oral melanoacanthoma is a benign entity without any known risk of malignant transformation, so once diagnosed, further treatment is not necessary.[12] Clinical regression of the lesion is even seen after incisional biopsy with a high frequency. If treatment is desired, the lesion may be excised surgically with a negative margin. Argon plasma coagulation has also been utilized with promising results.[13] Cryotherapy, curettage, and the topical application of fluorouracil 5% are other treatment options described in the literature.(B3)

Differential Diagnosis

The differential diagnosis of pigmented oral lesions spans from benign entities to rare but aggressive conditions such as oral melanoma. Oral melanoacanthoma typically appears as a solitary lesion, though in rare cases it may present in a multifocal or diffuse pattern. Benign melanocytic lesions can be classified as either multifocal or solitary.

• Multifocal melanocytic lesions may include smoker’s melanosis, which occurs in individuals who smoke or chew tobacco. Other causes of multifocal hyperpigmentation include systemic conditions such as HIV infection, Peutz-Jeghers syndrome, neurofibromatosis, McCune-Albright syndrome, Addison disease, and Laugier-Hunziker syndrome, as well as drug-induced pigmentation from agents such as azathioprine, antimalarials, cytotoxic drugs (eg, bleomycin), and oral contraceptives.
• Non-melanocytic diffuse pigmentation may result from heavy metal exposure, trauma, or systemic iron overload (hemochromatosis).
• Focal melanocytic lesions most often represent a melanocytic macule, followed by melanocytic nevi, with oral melanoma being rare but clinically significant. Addison disease causes oral mucosal hyperpigmentation through increased melanocyte-stimulating hormone secondary to elevated ACTH levels in adrenal insufficiency. Laugier-Hunziker syndrome is a rare, benign cause of oral and cutaneous hyperpigmentation, typically affecting older Caucasian males, without associated hamartomas or malignancy, and is diagnosed by exclusion.[14][15] 
• Up to 18% of patients with HIV may develop oral hyperpigmentation, most frequently on the gingival mucosa, independent of antiretroviral therapy, CD4 count, or disease duration.[16]
• Peutz-Jeghers syndrome is an autosomal dominant disorder characterized by benign hyperpigmented buccal macules and gastrointestinal hamartomas or polyposis. It is linked to increased risk of cancers, including those of the stomach, colon, and pancreas. Peutz-Jeghers syndrome often presents in childhood with oral and cutaneous macules affecting the lips, oral mucosa, and perioral skin. Patients with oral/perioral pigmentation and gastrointestinal polyps, or with a family history suggestive of Peutz-Jeghers syndrome, should undergo genetic testing.[17][18] 
• Amalgam tattoos (focal argyria) appear as blue or gray discolorations of the mucosa adjacent to prior dental work such as fillings, implants, or prostheses. These may be radiographically visible, and histology reveals fine black deposits along collagen fibers and blood vessels. If the history does not support a benign, non-melanocytic cause, a biopsy is warranted.[19]
• Oral melanoma should be suspected when lesions exhibit ABCDE warning signs: asymmetry, border irregularity, variation in color, diameter >6 mm, and elevation, or when the lesion is raised. Oral melanoma accounts for nearly 25% of head and neck melanomas and carries a poor prognosis, with an approximate 30% 5-year survival rate due to its aggressive metastatic potential and high recurrence risk. Although rare, its severity warrants a prompt biopsy to exclude the diagnosis.[20][21] 

Prognosis

Oral melanoacanthoma has been reported to spontaneously regress or resolve after the biopsy procedure or cessation of offending agents.[3] Oral melanoacanthoma lesions can be present for periods of weeks up to a year and may exhibit growth or progression before patients seek medical treatment.[4] In some cases, a solitary lesion may progress to multiple lesions or diffuse pigmentation.[12] There are no reported cases of malignancy with features of atypia or dysplasia.[22]

Complications

There are no reported oral melanoacanthoma complications. However, difficulties are mostly secondary to surgical excisions, such as scarring and post-operative pain. Not biopsying an oral pigmented lesion may cause a missed diagnosis of a malignancy, so it behooves the oral surgeon to biopsy all pigmented lesions unless there is a clear component of the patient's history to ascertain the etiology.