Pigmented lesions are a common finding in the oral cavity. Oral pigmented lesions may range from solitary to multiple, pinpoint to diffuse, and have a variety of clinical implications. Nearly all solitary pigmented lesions require a biopsy to rule out mucosal melanoma. Oral mucosal melanoma has a grim prognosis and early discovery is of utmost importance. Multiple pigmented lesions in the oral cavity may indicate a systemic condition about which the patient may not be aware. The presentation and management of these various lesions is the focus of this article.
Key points
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Pigmented lesions of the oral cavity are commonly encountered.
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Diffuse pigmented lesions of the oral cavity may be reactive or syndromic in nature.
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Isolated pigmented lesions of the oral cavity often require a biopsy to rule out melanoma.
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Rapidly expanding or changing characteristics of pigmented lesions necessitates a biopsy.
Pigmented lesions have various presentations in the oral cavity. Lesions may range from solitary to multiple, pinpoint to diffuse, and may have numerous different clinical implications. Nearly all solitary pigmented lesions require a biopsy to rule out oral mucosal melanoma; multiple lesions typically indicate a systemic condition. In this article, we will discuss the various common presentations of pigmented lesions of the oral cavity and their management.
Oral melanotic macule
The most common pigmented lesion of the oral cavity is the melanotic macule. Although any mucosal surface may be affected, the lower lip is the most common site. The buccal mucosa, palate, and gingivae are also frequently affected. Although the cause is not known, it may represent a reactive process.
Most lesions are solitary, small, sharply demarcated, and uniform in color. Although they may range in size, it is rare for an oral melanotic macule to present as a larger than 1 cm lesion ( Fig. 1 ). The average age of affected patients is around 43 years with women more likely to present with these lesions when compared with men.
To rule out malignant melanoma, a biopsy is required. Histopathologically, these lesions will show an increase in melanin in the parabasilar layers of the epithelium without a concomitant increase in the number of melanocytes. On confirmation of diagnosis, no further treatment is necessary. Macules do not exhibit any malignant potential and the prognosis is excellent.
Melanocytic nevus
A nevus is a developmental or congenital condition originating on the skin or mucosa. The acquired melanocytic nevus (mole) is the most common of these neoplasms when found on the skin; however, they are uncommon in the oral cavity. Melanocytic nevi are benign tumors derived from the neural crest. Although mutations in the BRAF or NRAS oncogenes are frequent in cutaneous nevi, these mutations may not be associated with nevi of the oral cavity. ,
Clinically, oral melanocytic nevi most commonly are found on the hard palate, followed by the buccal mucosa and vermilion border. These lesions typically are around 0.5 cm in greatest diameter, with approximately 9% presenting as a lesion larger than 1.0 cm. The nevi may present with brown, blue, or black pigmentation, although approximately 15% to 22% are amelanotic , ( Figs. 2 and 3 ). Patients are usually aged older than 30 years at first diagnosis, and women are more commonly affected than men. Caucasians are the most commonly affected group. In the oral cavity, the intramucosal nevus is the most commonly encountered melanocytic nevi, followed by the blue nevus. , A biopsy is required to rule out mucosal melanoma.
Histopathologically, the nevus cells may be confined to the epithelium (junctional nevus), found in both the epithelium and superficial lamina propria (compound nevus), or noted entirely in the mucosa (intramucosal nevus). In the blue nevus, melanin-rich melanocytes are noted deep within the mucosa.
The prognosis for oral melanocytic nevi is excellent; malignant transformation into mucosal melanoma has not been well documented.
Melanoacanthosis
Melanoacanthosis, first described as oral melanoacanthoma in 1978 by Tomich, is an uncommon, reactive process, characterized by the distribution of dendritic melanocytes throughout the entire thickness of the epithelium. , Use of the term melanoacanthosis is currently preferred in order to avoid confusion with the cutaneous lesion, melanoacanthoma of skin. A melanoacanthoma of the skin is considered to be a subtype of seborrheic keratosis and therefore unrelated to the lesion discussed herein.
Melanoacanthosis is found most often in the Black female patient. Clinically, the lesion presents as a solitary, flat or slightly raised, brown macule. The lesion typically exhibits a rapid increase in size before reaching a maximum dimension or approximately 1 to 2 cm within a few weeks. The buccal mucosa is the most frequently involved location, although any oral mucosal surface may be affected. Although typically asymptomatic, pruritus, pain, and a burning sensation have been reported in some cases. Occasionally, patients will report a history of acute or chronic trauma in the area before the lesion appears ( Fig. 4 A, B ).
Incisional biopsy is indicated to rule out oral mucosal melanoma especially in cases where rapid increase in size is reported. Histopathologic evaluation will reveal dendritic melanocytes throughout the epithelium in conjunction with spongiosis ( Fig. 4 C). Often the biopsy procedure serves as an impetus for rapid resolution of the pigmentation. Following histopathologic diagnosis, no further intervention is required; the prognosis is excellent. ,
Smoker’s melanosis
Smoker’s melanosis is a nonneoplastic, reactive increase in oral pigmentation in response to irritants in tobacco smoke. It has been hypothesized that the increase in melanin may serve as a protective function. , This flat, diffuse, brown/black pigmentation typically is noted on the anterior attached gingiva of both arches. Pigmentation tends to appear darker in heavy smokers and has a propensity to occur most often in women, potentially due to a synergistic effect of female sex hormones combined with the effects of smoking. The clinician may make the diagnosis with correlation of smoking history and clinical presentation; staining of the dentition may also serve as a helpful clue to the diagnosis. , No treatment is necessary, although it is prudent to counsel the patient on smoking cessation, if amenable. It has been reported that the pigmentation dissipates 6 to 36 months after cessation. ,
Drug-related discolorations of the oral mucosa
There are numerous medications that may be responsible for discoloration of the oral mucosa via multiple pathways including direct incorporation into the tissue or by inducing melanin production. , Drugs including minocycline, antimalarials, oral contraceptives, chemotherapeutics, zidovudine , ketoconazole, and clofazimine have all been implicated. , , ,
Clinically, these pigmented lesions may vary based on the drug causing the reaction. For example, antimalarial drugs tend to affect only the hard palate, while minocycline can lead to a bluish-black discoloration of the maxilla and mandible leading to dark-appearing gingivae. , Minocycline may also lead to hyperpigmentation of the oral mucosa due to increase in melanin production. Other drugs may cause diffuse, brown pigmentation of any mucosal surface. The gingivae and buccal mucosa are the most frequently affected sites and it may mimic physiologic pigmentation. ,
A biopsy is only considered for drug-related discolorations of the oral mucosa if a definitive clinical correlation with medication use cannot be established. Microscopically, an increase in melanin may be noted in the parabasilar layers or granules of melanin may be seen in the superficial lamina propria. , If the medication is discontinued, the discoloration may fade. However, no further action is warranted after appropriate diagnosis.
Addison disease
Hypoadrenocorticism, or Addison disease, may lead to diffuse pigmentation of the oral cavity. It has been reported this discoloration affects approximately 92% of patients affected by Addison disease. , In fact, hyperpigmentation of mucous membrane and cutaneous surfaces is one of the first signs of Addison disease.
Addison disease is a result of an adrenal cortex disorder that results in insufficient levels of glucocorticoid and mineralocorticoid. Increased adrenocorticotropic hormone is secreted in response to low corticosteroid levels. When this occurs, an increase in α-melanocyte-stimulating hormone occurs, leading to melanogenesis and hyperpigmentation. , , Autoimmune adrenalitis is the most common cause of Addison disease, although other syndromes, autoimmune conditions, and infections may also lead to disease development.
In addition to the hyperpigmentation, Addison disease is characterized by a slow progression of nonspecific symptoms, including fatigue, weight loss, nausea, and vomiting. Patients may also experience hyponatremia and hyperkalemia. In around 50% of patients, the disease presents with an adrenal crisis, which is a life-threating condition delineated by shock and severe dehydration.
In the oral cavity, patients with Addison disease may present with generalized macules of hyperpigmentation. The mucous membranes of the oral cavity often are affected before cutaneous involvement occurs. The differential diagnosis includes physiologic pigmentation, although the onset will be acute in a patient with Addison disease. ,
When a health-care provider suspects Addison disease, referral to the patient’s primary care physician is warranted; the patient may then be referred to an endocrinologist for diagnosis. Addison disease typically is managed by replacing the glucocorticoid and mineralocorticoid hormones with hydrocortisone and fludrocortisone, respectively. Those with primary adrenal insufficiency also may be prescribed for daily dose of dehydroepiandrosterone. If there is a specific cause, such as infection, the underlying etiology also must be addressed.
Although patients should double their daily dose of glucocorticoid when under increased stress, it is not necessary to increase glucocorticoids for simple dental procedures.
Peutz-Jeghers syndrome
Peutz-Jeghers syndrome is an autosomal dominant disease caused by a mutation of the STK11/LKB1 tumor suppressor gene. , The syndrome is characterized by hamartomas of the intestine and an increased risk for malignancies. Intussusception of the bowel and/or obstruction may occur in some patients.
Patients with this condition may present with numerous macules of hyperpigmentation on and around the lips during childhood ( Fig. 5 ). These areas of hyperpigmentation resemble freckles but do not darken with sun exposure. Pigmentation may also occur intraorally; if so, it is most commonly noted on the buccal mucosa. ,
