IJDA, 1(1), 2009 38

Department of Oral pathology

Meenakshi Ammal Dental College, Abstract
Chennai, Tamilnadu, India
Change in the colour of the oral mucosa reflects the underlying
health status either local or systemic. Change in color is brought
about by pigmentation, and these could be physiological or
pathological. Pigmentation in pathological conditions may range
from a localized anomaly of limited significance to a potentially life-
threatening disease. Since the dental professionals encounter a
number of pigmented conditions of the oral cavity in the oral cavity
it is important to have a thorough knowledge about their etiology,
clinical manifestations, and their management. In the following
review various pigmented lesions of the oral cavity are discussed.
Key words: Melanin, Pigmented Oral Lesions
Email for correspondence:
bsabarin@gmail.com
INTRODUCTION
Oral mucosa is deeply colored when compared
to skin. Color reflects the clinical state of the mucosa;
inflamed tissues are red, because of the increase in
number and dilation of blood vessels, whereas
normal healthy tissues are pale pink. This coloration
is the net result of many factors, one of which is
pigmentation. Pigment is any coloring matter in the
living tissues. Pigments are present throughout the
human body including the oral cavity.
Oral pigmentation is a relatively common
condition that may involve any part of the oral cavity.
These pigmentations may arise from intrinsic
and extrinsic factors and can be physiological or
pathological. If pathological, it may represent a
localized anomaly of limited significance or the
presentation of potentially life-threatening disease.
As dental professionals encounter a number of
pigmented conditions in the oral cavity it is
important to differentiate between normal and
pathological pigmentations. Pigmentation is of two
types - exogenous and endogenous.
Endogenous refers to arise from within the
tissues and exogenous, caused by foreign material
introduced into the body.
1
The color of the oral mucosa is due to two main
endogenous pigments namely- Melanin and
hemoglobin.
MELANOCYTES
Melanin is produced by a specialized pigment
producing cell called Melanocyte situated in the
epidermis and basal layer of the epithelium and are
developed from the neural crest cells.
LIGHT MICROSCOPIC APPEARANCE
In hematoxylin-eosin(H&E) stained sections,
melanocytes appear as randomly dispersed cells
Article Info
Received: 10th July, 2009
Review Completed: 18th August, 2009
Accepted: 2nd September, 2009
Available Online: 18th January, 2010
NAD, 2009 - All rights reserved
Sr. Lecturer
1
Professor and Head
2
Post Graduate Student
3
Pigmentation
Sabrinath B
1
, Sivapathasundharam B
2
, Gaurav Ghosh, Dhivya
3
INDIAN JOURNAL OF DENTAL ADVANCEMENTS
Jour nal homepage: www. nacd. i n
REVIEW
IJDA, 1(1), 2009 39
wedged between the basal cells of the epidermis,
having a small, dark staining nucleus and a clear
cytoplasm, largely as a result of shrinkage. It is also
called as low level clear cells.
The average number of melanocytes in H&E
stained sections is 1 of 10 cells in the basal layer.
Because only 10 precent of the cells in the basal layer
is melanocytes, each melanocyte supplies several
keratinocytes with melanin, forming with them an
Epidermal- Melanin unit.
2
SPECIFIC METHODS OF IDENTIFICATION
Silver staining by Masson-Fontana method
Treatment with strong oxidizing agents like
hydrogen peroxide and potassium
permanganate.
DOPA reaction.
Immunohistochemically by antibodies directed
against S-100 and HMB-45.
MELANOGENESIS
Melanin formation begins by tyrosinase
dependant hydroxylation of tyrosine to Dihydroxy-
phenyl alanine (DOPA) and the oxidation of DOPA to
dopa quinone, which is subsequently polymerized
into melanin.
Melanin is synthesized within the rER of
melanocytes from where it is transferred to the Golgi
apparatus where it is modified and packed into as
small membrane bound structures called
melanosomes. These melanosomes gradually move
from the cytoplasm of the melanocyte to the
dendritic processes. As the content of melanin
increases in the melanosomes the concentration of
melanogenic enzyme decreases.
The development of the melanosomes takes
place in four stages.
Stage I melanosomes are round, measure about 0. 3
mm in diameter and possess very intense enzyme
activity concentrated along filaments. They contain
no melanin.
Stage II melanosomes are ellipsoid and measure
approximately 0. 5 mm in length, as do the
melanosomes of stage III and IV. They contain
longitudinal filaments that are cross-linked with one
another. Enzyme activity is present both on the
enveloping membrane and on the filaments. Melanin
deposition on the cross-linked filaments begins at
this stage.
Stage III melanosomes have only little tyrosinase
activity but show continued melanin deposition,
partially through non enzymatic polymerization.
Stage IV melanosomes no longer possess tyrosinase
activity. Melanin, which is formed entirely by
nonenzymatic polymerization, fills the entire
organelle and obscures its internal structure.
2
MELANIN TRANSFER
Formed melanin is transferred to the
keratinocytes takes place by exocytosis,
cytophagocytosis, plasma membrane fusion or
transfer by membrane vesicles.
PIGMENTED ORAL LESIONS
Developmental Disorders
Pigmented cellular nevus
Labial and Oral melanotic macule
Forbes-Albright syndrome
Polyostotic fibrous dysplasia
Neurofibromatosis
Peutz-Jeghers syndrome
Functional/Physiologic Variants
Racial pigmentation
Chloasma
Specific Agents
Dental Amalgam
Chewing/Smoking of Tobacco
Betel nut chewing
Lead
Silver
Drugs
Pigmentation Sabrinath, et, al.
IJDA, 1(1), 2009 40
Busulfan
Chlorpromazine
Minocycline
Quinacrine
Deficiency Disorders
Vitamin B12 deficiency
Endocrine Disorders
Addisons disease
Cushings syndrome
Acromegaly
Hyperthyroidism
Neoplastic Disorders
compound Nevus
Malignant Melanoma
PIGMENTATION DUE TO DEVELOPMENTAL
DISORDERS
Pigmented cellular nevus
Nevus is also called birth mark. Pigmented
cellular nevus is benign proliferation of the nevus
cells either in the epithelium or connective tissue and
is categorized as hamartoma or developmental
malformation. Melanocytic nevi can be congenital
or acquired. Congenital melanocytic nevi are
classified into two types according to their size: Giant
congenital melanocytic nevi (also called as the
Garment nevus, Bathing trunk nevus or Giant hairy
nevus) are greater than 20cm in diameter and Small
congenital nevi, which are usually less than 1. 5 cm
in their greatest dimension.
3
Acquired melanocytic nevus, commonly referred
to as the mole is seen occurring frequently on the
skin. Intra orally, they occur on the hard palate.
Histologically, they are classied as junctional,
intradermal or intramucosal, and compound nevi
based on the location of the nevus cells.
4
Junctional
nevi are at and dark brown in colour because the
nevus cells proliferate at the tips of the rete pegs close
to the surface. Intramucosal and compound nevi are
typically light brown, dome-shaped lesions.
Blue nevi are characterized by proliferation of
dermal melanocytes within the deep connective
tissue at some distance from the surface epithelium,
which accounts for the blue colour. Although
transformation of oral pigmented nevi to melanoma
has not been well documented, it is believed that nevi
represent precursor lesions to oral mucosal
melanoma. It is therefore recommended that these
lesions be excised and submitted for histopathologic
examination.
5
Labial Melanotic Macule (labial lentigo)
The labial melanotic macule occurs in the lips,
more commonly in the lower lip. It shows a
predilection for occurrence in women but can also
occur in males.
6
The lesion appears as a solitary well-
defined, oval, brownish-black, flat patch ranging from
1 to 8mm in diameter. Exposure to UV radiation is
thought to be the most important etiologic factor in
the pathogenesis of the lesion
7
(Fig 1).
Oral Melanotic Macule
Macule is a non elevated discoloration. The oral
melanotic macule is a flat, brown mucosal
discoloration produced by a focal increase in melanin
deposition along with an increase in the number of
melanocytes. They may appear as solitary or multiple
macules and can involve the gingiva, lip, palate,
buccal mucosa, and alveolar ridge. Microscopically,
the melanin deposition is seen mainly in the basal
cell layers.
4
Polyostotic Fibrous Dysplasia
Fibrous dysplasia principally affects the bone
wherein bone is replaced by a dysplastic fibrous
tissue. It is classified according to the number of
bones affected as monostotic (single bone) and
polyostotic (multiple bones). The polyostotic form is
associated sometimes with syndromes like Jaffe-
Lichtenstein and Mc Cune Albright, where Caf au lait
pigmentation is a common clinical presentation.
8
Neurofibromatosis
Neurofibromatosis (NF) is an autosomal
dominant disorder with a high degree of penetrance
and variable expressivity. Two sub types are known
Neurofibromatosis 1 (NF1) and Neurofibromatosis 2
(NF2). NF 1 is commonly associated with Caf au lait
Pigmentation Sabrinath, et, al.
IJDA, 1(1), 2009 41
pigmentation of the skin. They appear as oval-shaped
light brown patches greater than 0. 5cm in diameter.
It is also known as Von Recklinghausens disease of
the skin.
9
Peutz-Jeghers Syndrome
Peutz-Jeghers syndrome is an autosomal
dominant disorder with a high degree of penetrance
and is commonly associated with benign intestinal
polyposis, most commonly in the jejunum and
ileum.
10
The typical presentation is irregular
pigmented patches of dark brown or black up to five
millimeters in diameter on the buccal mucosa and
perioral region. The lesions may also be found on
the gingiva and palate.
11
Physiologic (Racial) Pigmentation:
Physiologic pigmentation occurs due to an
increased melanocytic activity rather than an
increase in the number of melanocytes. The colour
ranges from light to dark brown. The attached
gingiva is the most common intraoral site of such
pigmentation. It appears as a bilateral, well
demarcated, ribbon-like, dark brown band. The
marginal gingiva is usually not affected. The buccal
mucosa, hard palate, lips and tongue may also be
affected. This pigmentation is asymptomatic which
requires no treatment.
5
(Fig 2)
PIGMENTATION DUE TO SPECIFIC AGENTS
Amalgam Tattoo and Other Foreign-Body
Pigmentation
Amalgam tattoo is one of the most common
causes of intraoral pigmentation. Amalgam tattoos
are twice as common as melanotic macules and ten
times as common as oral nevi.
12
The gingiva and
alveolar mucosa are most commonly involved, it may
also occur in the floor of the mouth and buccal
mucosa. It presents clinically as a localized, bluegrey
lesion. In periapical view radiographs the amalgam
particles are usually seen as radiopaque granules. In
case of doubt, a biopsy should be performed to
demonstrate the presence of amalgam particles in
the connective tissue.
Sometimes, graphite may be incorporated into
the oral mucosa through accidental injury with a
graphite pencil. This type of lesion occurs frequently
in children especially in the anterior palate. Clinically,
it appears as an irregular grey to black macule. It is
mandatory to differentiate this lesion from
melanoma since it commonly occurs on the palate.
5
Smokers Melanosis
Smoking may cause oral pigmentation with
increased production of melanin. It may provide a
biologic defence against the noxious agents present
in tobacco smoke. Smokers melanosis occurs in up
to 21. 5 percent of smokers. The intensity of the
pigmentation is related to the duration and amount
of smoking. Women are more commonly affected
than men, which suggest a possible synergistic effect
between the female sex hormones and smoking. The
brownblack lesions most often involve the anterior
labial gingiva followed by the buccal mucosa.
Smokers melanosis usually disappears within three
years of smoking cessation. Biopsy should be
performed if there is surface elevation or increased
pigment intensity or if the pigmentation is in an
unexpected site.
13
(Fig 3)
Heavy Metal Pigmentation
Increased levels of heavy metals (e. g., lead,
bismuth, mercury, silver, arsenic and gold) in the
blood are commonly known to cause oral mucosal
discoloration. In adults, the most common cause is
occupational exposure to heavy metal vapors.
Treatment with drugs containing heavy metals, such
as arsenicals for syphilis, was a common cause in the
past.
In children, exposure to lead-contaminated
water or paint and mercury or silver-containing drugs
represents a common cause. For example,
pigmentation due to lead poisoning appears as a
blueblack line along the marginal gingiva known
as Burtonian line
5
.
Drug-Induced Pigmentation
Oral mucosal pigmentation may occur as a side
effect of drug therapy. Drugs commonly associated
Pigmentation Sabrinath, et, al.
IJDA, 1(1), 2009 42
with oral mucosal pigmentation include Zidovudine,
estrogen, cyclophosphamide, ketaconazole,
chloroquine and minocycline.
14
This pigmentation
occurs due to synthesis of melanin under the
influence of the drug, deposits of the drug or one of
its metabolites. These drugs commonly cause
pigmentation of the hard palate where it commonly
produces a blue-grey or blue-black discoloration.
Laboratory studies have shown that these drugs may
produce a direct stimulatory effect on the
melanocytes.
Minocycline, a synthetic tetracycline causes
pigmentation of the alveolar bone, which can be seen
through the thin overlying oral mucosa as a grey
discolouration.
15
Post inflammatory Pigmentation
Mucosal diseases in particular lichen planus can
cause mucosal pigmentation which is clinically seen
as multiple brownblack-pigmented areas adjacent
to reticular or erosive lesions of lichen planus.
Histologically, there is increased production of
melanin by the melanocytes and accumulation of
melanin- laden macrophages in the superficial
connective tissue.
10
PIGMENTATION DUE TO ENDOCRINE DISORDERS
Addisons Disease
Addisons disease, or primary hypoadrenalism, is
due to progressive bilateral destruction of the
adrenal cortex by autoimmune disease, infection or
malignancy. The increased production of ACTH
induces melanocyte-stimulating hormone, which
results in diffuse pigmentation of the skin and oral
mucosa. Oral involvement presents as diffuse brown
patches which affects the gingiva, buccal mucosa,
palate and tongue.
Cushings syndrome, acromegaly and
hyperthyroidism also show pigmentation similar to
Addisons disease.
10
COLOURED LESIONS OF VASCULAR ORIGIN
Hemangioma and Vascular Malformation
Hemangioma is a benign proliferation of the
endothelial cells, endothelial lined vessels or spaces.
Vascular malformation is a structural anomaly of
blood vessels without endothelial proliferation.
Vascular malformation occurs during birth and
regresses as the patient ages.
8
The lesion may be at
or slightly raised and varies in color from red to bluish
purple depending on the type of vessels involved
(capillaries, veins or arteries) and the depth of the
lesion in the tissues. The most commonly affected
site is the lip, although any region in the oral cavity
may be involved.
4
Varix and Thrombus
Varices are abnormally dilated veins. The most
common intraoral location is the ventral surface of
the tongue, where varices appear as multiple bluish
purple, irregular, soft elevations that blanch on
pressure. If the varix contains a thrombus, it presents
as a bluish purple nodule that does not blanch on
pressure. Thrombi are more common on the lower
lip and buccal mucosa.
Hemorrhagic Lesions
Petechiae, purpurae and ecchymoses are sub
mucosal hemorrhages. They all have the same
mechanism of presentation and differ only in size.
Telangiectasia is a small, red, macular lesion that is
composed of dilated capillaries under the epithelium.
Petechial and ecchymotic patches are usually seen
at the junction of hard and soft palate.
10
(Fig 4)
Kaposis Sarcoma
Kaposis sarcoma (KS) is a multifocal vascular
malignancy seen predominantly in HIV-infected
individuals. The development of this tumor is
considered diagnostic of AIDS progression. A human
herpes virus (HHV-8, also called Kaposis sarcoma-
associated herpes virus) has been implicated as the
cause.
16
KS in the oral mucosa most commonly
affects the hard palate, gingiva and tongue. Early
lesions appear as at or slightly elevated brown to
purple lesions that are often bilateral. Advanced
lesions appear as dark red to purple plaques or
nodules that may exhibit ulceration, bleeding and
necrosis. Definitive diagnosis requires biopsy, which
shows a proliferation of spindle-shaped cells
surrounding poorly formed vascular spaces or slits
with numerous extravasated red blood cells.
5
Pigmentation Sivapathasundharam, et, al.
IJDA, 1(1), 2009 43
PIGMENTATION DUE TO SUN EXPOSURE
Actinic Lentigo (Solar lentigo)
Actinic lentigo is a benign, brown macule that
occurs due to chronic ultra violet damage to the skin.
It commonly occurs on the dorsum of the hands and
face
4
. (Fig 5)
Melasma
It is an acquired, symmetric hyperpigmentation
of the sun exposed skin of face and neck. It is seen
on the upper lip
4
.
PIGMENTATION DUE TO HYPERPLASTIC
PROCESS
Lentigo simplex
It is a benign cutaneous melanocytic hyperplasia
of unknown cause. It usually occurs on skin not
exposed to sunlight. Oral lesions are also seen. The
lesions appear as sharply demarcated macule less
than five millimeters in diameter.
Oral Melanoacanthoma
Oral melanoacanthoma is an uncommon benign
pigmented reactive lesion of the oral mucosa with
no malignant potential. The buccal mucosa is the
most common site of occurrence
17
. Clinically, the
lesion appears at or slightly raised and is
hyperpigmented, the colour ranging from dark
brown to black. It is characterized by proliferation of
dendritic melanocytes scattered throughout the
thickness of an acanthotic and hyperkeratotic surface
epithelium. This lesion, in contrast to most of the
benign pigmented lesions has a tendency to enlarge
rapidly, which raises the possibility of a malignant
process in the clinical differential diagnosis
18
.
PIGMENTED MALIGNANT LESION
Malignant melanoma
Melanoma is a malignant neoplasm of the
epidermal melanocytes. Certain lesions are said to
be precursor lesions of melanoma, including the
common acquired nevus, dysplastic nevus,
congenital nevus and cellular blue nevus
19
.
Criteria for clinical diagnosis of melanoma
(ABCDE-rule)
Asymmetry- in which one half does not match
the other half
Border irregularity- with blurred, notched or
ragged edges
Colour irregularity- pigmentation is not uniform.
Brown, black, tan, red, white and blue can all
appear in a melanoma.
Diameter- greater than 6 mm. Growth in itself is
also a sign.
Elevtaion- a raised surface can also be a sign.
Types of melanoma:
1. Superficial spreading
2. Nodular melanoma
3. Lentigo maligna melanoma
4. Acral lentiginous melanoma
5. Mucosal lentiginous melanoma
20
.
Of these, Acral lentiginous and Mucosal
lentiginous melanoma commonly occur in the oral
cavity. Most frequently seen in the hard palate, where
it appears as a brown to black macule with irregular
borders
21
. (Fig 6)
CONCLUSION
It is clear that oral pigmentation is a relatively
common condition that can occur in any portion of
the oral cavity and arises from intrinsic and extrinsic
factors and can be physiological or pathological. The
dentist may be the first health care professional to
observe the colour changes in the oral cavity which
may be a manifestation of the underlying
pathological process.
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IJDA, 1(1), 2009 45
Fig 1: Labial melanotic macule of the lower lip
Fig 2: Physiologic racial pigmentation of the gingiva.
Fig 3: Smoker's melanosis
Fig 4: Ecchymotic patch of the hard palate
Fig 5: Solar lentigo of the lower lip
Fig 6: Malignant melanoma of the hard palate.
Pigmentation Sabrinath, et, al.