James F. Drummond, DDS, MSD, PhD

DIFFERENTIAL DIAGNOSIS OF FLAT PIGMENTED LESIONS

Our approach to flat pigmented lesions of the oral cavity is based on the possibility that

the lesion may represent malignant melanoma--a rare, but extremely deadly disease. The axiom for pigmented lesions is: If you cannot explain the existence of a pigmented lesion that persists for more than two weeks, do an excisional biopsy (when in doubt, get it out). What follows is an organized approach to differential diagnosis of flat pigmented lesions and a short discussion of these lesions.

Most oral pigmented lesions arise either from pigments introduced from the external environment (extrinsic pigments-e.g. metals, graphite, dyes or certain drugs) or from naturally occurring internal pigments (intrinsic pigments--e.g. melanin or blood products). Thus the flat oral pigmented lesions can be simply categorized in tabular form as follows:

I. Extrinsic Pigments

1. Metals - Amalgam and other metals, graphite 2. Dyes -Tattoos 3. Drugs - Antimicrobial and chemotherapeutic drugs

II. Intrinsic Pigments

1. Melanin - drug related melanosis, smokers melanosis, systemic disease,

racial (ethnic) pigmentation, focal melanosis, nevus and malignant melanoma

2. Blood or blood products - Hemangioma and hematoma

The Amalgam tattoo is the most common oral pigmented lesion. It results from accidental implantation of amalgam in the tissue. In some cases, the amalgam particles are large enough to be seen on a radiograph; while in others, they are finely ground and cannot be detected. Amalgam tattoos present as blue-grey to black flat lesions of varying size and shape. They are asymptomatic and may be diffuse, but most are well defined. No treatment is indicated as long as their existence can be explained. Graphite tattoos result from implanting graphite particles in the tissue, usually from a pencil stab.

Decorative tattoos result from deliberate implantation of dyes in the submucosal tissues. Diagnosis is usually not difficult since they are in the form of words or figures. Also the patient is aware of their origin. No treatment is indicated.

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Certain drugs, such as antimalarial drugs and tranquilizers cause deposition of pigmented metabolic by-products resulting in diffuse blue-black pigmentation of the palatal and buccal mucosa. Long-term use of minocycline (a tetracycline derivative) causes dark green discoloration of the alveolar bone. This shows through the mucosa as a diffuse blue-gray pigmentation of the attached facial gingiva and palatal mucosa. Diagnosis is based on the history of using these drugs.

Other drugs, such as estrogens and chemotherapeutic agents can stimulate

melanocytes causing deposition of melanin in the mucosa. This presents clinically as diffuse brownish pigmentation of the oral mucosa.

Smokers melanosis results from exposure of the oral mucosa to nicotine and benzpyrene compounds in cigarette smoke. These compounds stimulate melanin production resulting in diffuse brown pigmentation of the anterior facial gingiva. The degree of pigmentation often correlates with the number of cigarettes smoked per day . Cessation of smoking results in gradual disappearance of the pigmentation over 2-3 years. Diagnosis is based on the history and disappearance with cessation.

Racial (ethnic) pigmentation results from deposition of melanin pigment at the

epithelial-connective tissue interface. It is commonly seen in individuals of African, Middle Eastern and Mediterranean origin. It usually presents as diffuse brown to black pigmentation that commonly involves the gingiva, alveolar mucosa and buccal mucosa; however, any area of the mucosa can be affected. It is considered normal and no treatment is indicated.

Certain systemic diseases cause oral melanin pigmentation. Most appear to result

from either an overproduction of normal ACTH (Adrenocorticotropic hormone) by the pituitary gland, such as seen in Addison's Disease, or ectopic formation of ACTH, as seen with chronic pulmonary disease and bronchiogenic carcinoma. Included among the functions of ACTH is stimulation of melanin synthesis. Lesions associated with Addison's disease present as diffuse grey-black pigmentation of the oral mucosa along with bronzing of the skin. Oral lesions associated with pulmonary disease usually present as well-defined brown-black areas of pigmentation identical to focal melanosis.

Focal melanosis is the oral counterpart of a freckle on the skin. It is a benign lesion

caused by localized accumulation of melanin pigment in the basal cell layer of the epithelium. These lesions are usually flat, well circumscribed areas of brown pigmentation. The most common site is the vermilion border of the lip, but these lesions can occur anywhere on the oral mucosa. Treatment usually consists of surgical excision to rule out the possibility of an early melanoma; however, some long-standing, unchanging lesions on the lip may be followed clinically.

The nevus (commonly called a mole) is a benign proliferation of melanin-forming nevus cells localized near the epithelial-connective tissue interface. It presents as a brown to black lesion and can occur anywhere on the oral mucosa. It usually grows to a certain size and then

Pigmented Lesions James F. Drummond, DDS, MSD, PhD Page 3 stabilizes. However, the intraoral nevus can be confused with an early melanoma and should therefore be excised.

Malignant melanoma is a malignant tumor of melanocytes. It occurs primarily on the skin but can be seen, in rare instances, intraorally. It presents as a dark brown to blue-black lesion that may be flat, nodular or ulcerated. The prognosis for intraoral melanoma is very poor. Treatment includes radical surgical resection of the affected area and cancer chemotherapy.

The hemangioma is a lesion caused by benign proliferation of blood vessels. Most occur in childhood and either continue to enlarge or gradually regress with age. The oral cavity is a common site and it presents as a blue to purple to red lesion that varies in size and shape. Although some are flat, many present as raised submucosal masses. Some hemangiomas are left untreated while others are treated either by surgical removal or with sclerosing agents.

A hematoma (commonly known as a bruise) is a localized collection of extravasated blood and blood pigments within a tissue space. Hematomas can be caused either by trauma or as a result of bleeding diathesis such as hemophilia, thrombocytopenia, or anticoagulant therapy. Most of these lesions resolve in 1-2 weeks without treatment.

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FLAT PIGMENTED LESIONS I. Extrinsic Pigments

I. Metals - Amalgam, gold, graphite and others

2. Dyes - Tattoos

3. Drugs - Antimicrobial and chemotherapeutic drugs II. Intrinsic Pigments

I. Melanin - Focal Melanosis, Nevus, Malignant Melanoma, Systemic Diseases (i.e. Addison's) and Racial (ethnic) pigmentation

2. Blood or Blood Products - Hematoma, Hemangioma (most are submucosal

masses)

APPROACH TO FLAT PIGMENTED LESIONS

I. Our approach is based on the possibility (though remote) that the lesion may be a

malignant melanoma. 2. Take a radiograph to determine if it is an amalgam tattoo (only large amalgam particles

will show up). If positive, no treatment is indicated. 3. If not, obtain a thorough history about the existence of the lesion (i.e. when it was first

noticed and has it changed with time). Also, is it diffuse or localized. 4. If you cannot explain its existence, excisional biopsy is indicated.

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