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.
2.
3.
II.

Metals - Amalgam and other metals, graphite

Dyes -Tattoos
Drugs - Antimicrobial and chemotherapeutic drugs

Intrinsic Pigments
1.

2.

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

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

Pigmented Lesions
Page 2

James F. Drummond, DDS, MSD, PhD

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
Page 3

James F. Drummond, DDS, MSD, PhD

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.

Pigmented Lesions
Page 4

James F. Drummond, DDS, MSD, PhD

FLAT PIGMENTED LESIONS

I.

II.

Extrinsic Pigments
I.

Metals - Amalgam, gold, graphite and others

2.

Dyes - Tattoos

3.

Drugs - Antimicrobial and chemotherapeutic drugs

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.

Jhd13