Pigmented oral lesions

Shilpashree.S
Contents
Introduction
Classification
Blue lesions
Brown melanotic lesions
Brown heme associated lesions
Gray / black lesions
Conclusion


Introduction :
Human oral mucosa is not uniformly colored
Chromatic variation may be observed in physiologic and
pathologic conditions
Oral tissues are characterized by different structural
colours
depending on
degree of keratinization
numbers and melanogenic activity of melanocytes
vascularization, and
type of submucosal tissue (muscle, bone, cartilage).

The physiologic colour of the oral mucosa thus ranges
from white to red-purple in light-skinned people,
whereas an evenly black to brown color of gingiva and
buccal mucosa and the lips are characteristic of dark-
skinned people.
Pigments:
Endogenous pigments
1. Melanin
2. Bilirubin
3. Iron
Exogenous pigments
1. Heavy metals
2. Medicine
The term pigmentation of the oral mucosa is
applied to a wide range of lesions or conditions
featuring a change of color of oral tissues

Melanin-associated lesions (Marco Meletti 2008)

Nonmelanin-associated lesions

Melanin-associated lesions
racial pigmentations
smoking associated melanosis
melanocytic macules
lentigines and ephelides
nevomelanocytic nevus
melanoacanthoma
oral malignant melanoma

pigmented neuroectodermal
tumor of infancy
Peutz-Jeghers syndrome
Addison disease and other
endocrine disorders

Nonmelanin-associated lesions
endogenous pigments
Hematomas
petechiae
Purpurae
ecchymoses
hemochromatosis
beta-thalassemia

exogenous pigments
Amalgam pigmentation
Heavy metals
drugs associated
pigmentation
Pigmentation of oral tissues can also be
classified as
1. Blue/ purple vascular lesions
a. Hemangioma
b. Varices
c. Angiosarcoma
d. Kaposi sarcoma
e. H hemorrhagic telengiectasia
2.Brown melanotic lesions
a. Oral melanotic macule
b. Nevocellular and blue nevi
c. Malignant melanoma
d. Drug induced melanosis
e. Physiologic pigmentation



( Burkitt)

f. Cafe au lait pigmentation
g. Smokers melanosis
h. Endocrinopathic pigmentation
i. HIV oral melanosis
j. Peutz-jeghers syndrome

3. Brown heme associated lesions
a. Echymosis
b. Petechiae
c. Hemochromatosis

4. Gray/black pigmentation
a. Amalgam tattoo
b. Graphite tattoo
c. Hairy tongue
d. Heavy metal ingestion
Blue/ purple vascular lesions - HEMANGIOMA
Currently, hemangiomas are considered to be benign tumors of
infancy characterized by a rapid growth phase with endothelial cell
proliferation, followed by gradual involution.
Clinical features
Hemangiomas are present at birth or arise at an early age.
They can be seen on both skin and soft tissues of the head and neck
including the oral cavity.
Intraoral hemangiomas occur most frequently on the tongue, lip or
buccal mucosa but can be seen at other sites too.
Oral hemangiomas appear as deep red or blue, flat or nodular
lesions, reflecting both the venous character of blood in them and
their usual deep mucosal position.
They are painless and blanch on pressure.
Trauma may lead to surface ulceration and secondary infection.
The intramuscular hemangioma is a special from of hemangioma
arising within normal skeletal muscles. Within the oral cavity, it
may occur, though rarely, within the tongue musculature.

Histology
Either capillary or cavernous type.
Capillary hemangioms is composed of many small capillaries lined by a single layer of
endothelial cells supported by a connective tissue stroma of varying density.
In instances of secondary infection, inflammatory infiltrate of varying intensity can be
seen.
The cavernous type of hemangioma consists of large dilated blood sinuses with a thin
endothelial lining. The sinusoidal spaces usually are filled with RBCs.
Treatment modalities
Surgery
Laser Ablation
Cryotherapy
Sclerosing agents

HEREDITARY HEMORRHAGIC TELENGIECTASIA (RENDU
OSLER-WEBER SYNDROME)

Characterized by numerous telangiectatic or angiomatous areas widely
distributed on the skin and mucosa, lips, gingival, B.M and palate.
Congenital, hereditary disease transmitted as a Mendelian dominant trait,
Spider-like telangiectases are present, they become conspicuous only after
puberty.
Earliest signs of the disease, is epistaxis and bleeding from the oral cavity.
The disease is primarily due to defects in the small B.V of skin and mucosa.
A primary intrinsic defect of the endothelial cells or a defect in the
perivascular tissue bed which weakens the blood vessels is thought to be the
cause.


KAPOSIS SARCOMA
Kaposis sarcoma is an unusual vascular neoplasm that was first described in 1872.
Current evidence suggests that Ks is caused by HHV -8.
The lesion most commonly arises from endothelial cells, with some evidence of lymphatic
origin.
5
th
6
th
decades of life, except in Africa where childhood involvement is common, a male
predominance in most studies.
The simple skin lesions usually originate on the extremities, but subsequently involve the
face and oral cavity.
They appear as reddish or brownish red nodules, varying in size and are usually tender
or painful.
The oral lesions are identical in appearance except that the surface may show ulceration.

Oral lesions predominantly involve the palate but other sites may also be
involved.
Lymph node and salivary gland involvement is also fairly common,
particularly in the African form.
Histologically, consist of numerous small capillary type blood vessels, in
which case it may be confused with the capillary hemangioma.
Elsewhere, the lesions may be extremely cellular, consisting of proliferating
masses of embryonic appearing spindle cells of varying morphology and
showing occasional mitoses, with hyperemic vascular slits.
Inflammatory cell infiltration is common.



ANGIOSARCOMA
Rare malignancy of vascular endothelium, which may arise from
either blood or lymphatic vessels.
Early lesions often resemble a simple bruise. The lesion continues
to enlarge, which results in an elevated, nodular or ulcerated
surface.
Oral angiosarcomas - in the mandible producing destructive
expansile lesions in the bone.
Angiosarcomas are characterized by an infiltrative proliferation of
endothelium lined blood vessels that form an anastomosing
network.

The cells appear hyperchromatic and atypical, they often
tend to pile up within the vascular lumina. Increased
mitotic activity may be seen.
Treatment usually consists of surgical excision and
radiotherapy. Head and neck angiosarcomas usually
have a poor prognosis.

Brown melanocytic nevus


Melanocytes

Melanocytes were first identified in the oral
epithelium by Becker in 1927
Isolation from samples of gingival tissue by Laidlaw
and Cahn.
neural crest cells melanoblast dendritic cells
H&N - first part of the body where melanocytes
appear - 10 weeks of gestation
Located in the basal epithelial layer
Do not contact each other
Regularly interspersed between the basal keratinocytes.
Melanocytic dendrites reach a number of keratinocytes
An age-related increase of oral melanocytes has been
observed

Histology
small round nucleus and a small amount of a clear
cytoplasm
slender dendrites extending between adjacent
keratinocytes.
devoid of desmosomes or attachment plates.
Melanosomes - formed within the cytoplasm and
transported along the dendrites.

Demonstration:
argentaffinic melanin-labeling techniques such as the
Masson-Fontana staining
S100 antigen stronger in melanin lacking
melanocytes
HMB-45 monoclonal antibody against
melanosomal glycoprotein

Various stimuli - trauma, hormonal changes,
medication, and radiation - increased production of
melanin.
Melanin functions include absorption of ultraviolet
light and scavenging of some cytotoxic compounds.

Brown melanotic lesions

Racial pigmentation (physiologic pigmentation)

symmetric and persistent and does not alter normal
architecture, such as gingival stippling
seen in persons of any age and no gender predilection
Does not correspond to the degree of cutaneous coloration
gingiva with exclusion of marginal border and buccal mucosa
is the most commonly affected intraoral tissue.
Histopathology:
increased melanin production
melanin is found in surrounding basal keratinocytes and
subjacent connective tissue macrophages.

clinical differential diagnosis
smoking-associated melanosis, Peutz- Jeghers syndrome,
Addison's disease, and melanoma
biopsy is justified only if clinical features are atypical
Racial pigmentation is treated only for aesthetic
reason.
SMOKING ASSOCIATED MELANOSIS:
Abnormal melanin pigmentation of oral mucosa has
been linked to cigarette smoking
designated as smoking-associated melanosis or smoker's
melanosis
a component in tobacco smoke that stimulates
melanocytes
Female sex hormones - modifiers in this type of
pigmentation
Clinical Features :
anterior labial gingiva is the region most typically
affected
Palate and buccal mucosa - pipe smoking
Smokers melanosis is usually black-brown.
No pigmentation with smokeless tobacco
Intensity of pigmentation is time and dose related


Histology-
Melanocytes show increased melanin production, as
evidenced by pigmentation of adjacent basal
keratinocytes.
The microscopic appearance is similar to that seen in
physiologic pigmentation and melanotic macules.



Smokers melanosis does not require treatment
disappearance has been reported after cessation of the
smoking habit
It may, however, potentially mask other lesions or may
be cosmetically objectionable.
MELANOTIC MACULES:
relatively common lesions caused by an increased production and
deposition of melanin within the basal cell layer, the lamina
propria, or both (Eisen D, Lenane P)
Oral melanotic macule (or focal melanosis) are focal pigmented
lesions that may represent
1) an intraoral freckle
2) postinflammatory pigmentation
3) the macules associated with Peutz- Jeghers syndrome or
Addison's disease.

Clinical features:
Pathogenesis is not clear physiologic or reactive
Seen predominantly on the vermilion of the lips (lower lip) and
gingival (ant. Maxilla)
appear on any mucosal surface
Male to female ratio is 2:1
higher incidence in 5
th
decade
They are asymptomatic
have no malignant potential

usually single well circumscribed blue or brown-to-black lesions
homogeneously colored and less than 1 cm in diameter
Intraoral lesions tend to be larger than those located on the lips
Unlike ephelides, melanotic macules do not darken after
exposure to sun radiation
The diagnosis is usually made on clinical grounds alone.



Histopathology


absence of rete ridge elongation and lack of prominent
melanocytic activity
Pigmentation is usually most marked at the tips of the rete
ridges
melanophages in the upper part of lamina propria
lack of atypia of melanocytes
HMB-45 immunoreactyivity is typically lacking.
must be differentiated from early superficial melanomas
confused with blue nevi (palate) or amalgam tattoos
If they are numerous, Peutz-Jeghers syndrome, Addison's
disease, and Laugier-Hunziker syndrome may be possible
clinical considerations
A biopsy may be required to establish a definitive diagnosis of
this lesion
Otherwise, no treatment is indicated.
LENTIGINES AND EPHELIDES:

well defined hyperpigmented lesion of the skin with an increased
number of melanocytes arranged as solitary units along the
epithelial-mesenchymal junction without formation of nests
Lentigines are subdivided into
-simple lentigines and
-solar lentigines

Lentigo simplex
developmental or intrinsic defects in melanocytes homeostasis
melanocytic hyperplasia together with increased melanin
formation
sharply circumscribed light to dark brown pigmentation
single or multiple
In the latter situation being associated with a number of rare
syndromes.
Solar lentigines
sun-induced freckles, lentigo senilis
ultraviolet lightinduced pigmented lesions
increased incidence among the general population over 60 years
of age
associated with epithelial hyperplasia
Melanocytic hyperplasia is minimal in solar lentigines

Ephelides (freckles)
typically affect light-skinned individuals
localized on sun-exposed areas of the body
small (less than 1 cm) red or light to dark brown macules
multiple and uniform in color and regular in outline
confluence leads to irregularly shaped larger patches
most frequently occur in childhood
wax and wane with the degree of solar exposure, being most
conspicuous in the summer months
affect the vermilion border of the lips or the perioral tissues
NEVOMELANOCYTIC NEVUS

Nevus is a general term that may refer to any congenital lesion
of various cell types or tissue type.
However, the term nevus (or mole) is used to refer a
pigmented lesion composed of nevus or melanocytic cells
nevomelanocytic nevus, nevocellular nevus, melanocylic nevus,
or pigmented nevus.

Nevomelanocytic nevi are collections of nevus cells that are
round or polygonal and are typically seen in a nested pattern
They may be found in epithelium or supporting connective
tissue, or both.
The origin of nevus cells
-from cells that migrate from the neural crest to the epithelium
and dermis (submucosa), or
-from altered resident melanocytes.

Clinical Features
Nevomelanocytic nevi of the skin are common acquired papular
lesions that usually appear shortly after birth and throughout
childhood
Intraoral nevomelanocytic nevi are relatively rare lesions that may
occur at any age
Most oral lesions present as small (<0.5 cm) elevated papules or
nodules that are often nonpigmented (20%).
The palate is the most commonly affected site.
buccal mucosa, labial mucosa, gingiva, alveolar ridge, and
vermilion.

Histopathology
subtypes are depending up on the location of nevus cells.
1. junctional nevus
2. intradermal nevus or intramucosal nevus
3. compound nevus
4. blue nevus - cells are spindle shaped and found deep in the
connective tissue.
intramucosal nevi are the most common variety
blue nevi are the second most common
Compound and junctional nevi relatively rare
dysplastic nevus that is commonly seen in skin has not been
observed in oral mucous membranes.
Malignant transformation of an oral benign nevomelanocytic nevus
is highly improbable
As oral nevomelanocytic nevi can mimic melanoma clinically, all
undiagnosed pigmented lesions should undergo a biopsy.

the additional use of immunohistochemical stains may be
required, such as the melanocytic markers.
Melan A, HMB45, and microphthalmia transcription factor
In melanin pigmentladen cells, additional markers, e.g. CD68
marker for macrophages - helpful in identifying the nature of
such cells
helpful in arriving a correct diagnosis of a blue nevus.
Differential Diagnosis
melanotic macule
amalgam tattoo
melanoma
Lesions of vascular origin including hematoma, Kaposi's sarcoma,
varix, and hemangioma
Treatment
Because of the infrequency with which oral nevi occur and their
ability to clinically mimic melanoma, all suspected oral nevi should
be excised.
Since their size is generally less than 1cm, excisional biopsy is
usually indicated.

Melanoacanthoma
a rare benign mixed lesion of keratinocytes and pigment laden
dendritic melanocytes
have reactive nature and usually regresses spontaneously or after
incomplete removal, such as incisional biopsy
Most often noted among Blacks and other non-Caucasians
Occurs more often in women than men by a ratio of 3:1
History of trauma and local irritation
most often on buccal/labial mucosa
develop rapidly and asymptomatic
Unilateral dark plaque; rarely multiple, bilateral
g
Diagnosis
Clinical history of rapid onset
Histologic evaluation
Scattered dendritic melanocytes within spongiotic and
acanthotic epithelium
Increased number of melanocytes along basal layer as single
units
Differential Diagnosis
Melanoma
Drug-induced pigmentation
Smokers melanosis
Mucosal melanotic macule
Mucosal nevus
Amalgam tattoo
Treatment and Prognosis
None after establishing the diagnosis
Often resolves spontaneously
Excellent prognosis
MALIGNANT MELANOMA
Cutaneous Melanoma
2% of all neoplasms
UV exposure
more common in whites than in blacks and Asians.
Predisposing factors
1. extensive sun exposure, particularly
2. fair natural pigmentation, and
3. precursor lesions, such as congenital nevomelanocytic
nevi and dysplastic nevi.
Subtypes:
1. superficial spreading melanoma
2. nodular melanoma
3. Lentigo maligna melanoma, and
4. acral-lentiginous melanoma
all melanomas have two distinct phases of variable duration:
1. radial or horizontal growth phase
2. vertical growth phase
Oral Malignant Melanoma:
aggressive tumor of melanocyte
fortunately rare, 0.5% of all oral malignancies
no racial predilection
blacks and Asians > whites
Most OMMs arise de novo from apparently normal mucosa
30% are preceded by oral pigmentations for several months or
even years
Pigmentary defect - very likely represents an early growth phase
of these lesions and not benign melanosis.

emergence of a mass lesion which is usually pigmented
uniformly brown or black or may show variation of color,
with black, brown, gray, purple, and red shades, or
depigmentations
Satellite foci occasionally surround the primary tumor
In amelanotic melanomas, pigmentation is absent
palate and the maxillary gingiva.
Two biologic subtypes of oral melanoma: (1995 WESTOP Banff workshop)
1. in situ melanoma
2. invasive melanoma
atypical melanocytic proliferation
microscopically difficult oral pigmentations
indicates the presence of unusual numbers of melanocytes with abnormal
morphology at the epithelium-connective tissue interface
The changes are not severe enough to justify the diagnosis of melanoma
regarded as high-risk lesions, rebiopsied or followed indefinitely.

Microscopy:
Early stage: atypical melanocytes at epithelialconnective tissue
interface, occasionally with intraepithelial spread
Later infiltration into lamina propria and muscle
Atypical melanocytes larger, varying degree of pleomorphism
and nuclear hyperchromatism
Amelanotic forms may require use of immunohistochemical
identification: S-100 protein, HMB-45, Melan-A expression
In situ melanoma
Invasive melanoma
Amelanotic Melanoma
Positive HMB-45 stain
Differential Diagnosis
Mucosal nevus
Extrinsic pigmentation
Melanoacanthoma
Kaposis sarcoma
Vascular malformation
Amalgam tattoo
Mucosal melanotic macule
ABCD system of evaluation
- Asymmetry - Border irregularity
- Color variegation - Dia. > 6mm

Treatment:
Surgical excision
Marginal parameters related to depth of invasion and presence of
lateral growth
Wide surgical margins; resection (including maxillectomy) for large,
deeper lesions
Neck dissection in cases of deep invasion (< 1.25 mm)
PIGMENTED NEUROECTODERMAL TUMOR
OF INFANCY
Etiology:
a rare, benign neoplasm that is composed of relatively primitive
pigment-producing cells
Like melanocytes and nevus cells, these cells have their origin in
the neural crest.

Clinical Features:
found in infants usually younger than 6 months of age
occurs typically in the maxilla, also in mandible and skull
presents as a nonulcerated and occasionally darkly pigmented
mass due to melanin production by tumor cells
Radiographs show an illdefined lucency that may contain
developing teeth.

Histopathology.
This neoplasm exhibits an alveolar pattern (i.e., nests of tumor
cells with small amounts of intervening connective tissue)
The variably sized nests of round to oval cells are found within a
well-defined connective tissue margin
Cells located centrally within the neoplastic nests are dense and
compact, resembling neuroendocrine
Differential Diagnosis:
Early childhood malignancies
neuroblastoma, rhabdomyosarcoma or histiocytic tumor

Treated with surgical excision.
CAFE-AU-LAIT MACULE:
Cafe-au-lait macules are discrete melanin-pigmented
patches of skin that have irregular margins and a brown
coloration.
They are noted at birth or soon thereafter and may also
be seen in normal children.
Individuals with six or more large (>1.5 cm in diameter)
cafe-au-lait macules should be suspected of possibly
having neurofibromatosis (NF).

There are two forms of this autosomal-dominant disorder. NF1-
previously called Von Reck-Unghausen's disease and
neurofibromatosis 2 (NF2) formerly known as acoustic
neurofibromatosis.
Although there are some overlapping features, the two conditions
are distinct clinically and genetically.
The condition is characterized by numerous neurofibromas of the
skin, oral mucosa, nerves, central nervous system, and occasionally
the jaw.
Axillary freckling (Crowe's sign) accompanied by the presence of six
or more of these inacules is regarded as pathognomonic for NF1.
The genetic abnormality is in the neurofibromin gene located on
chromosome 17q 11.2 This tumor suppressor gene encodes for
neurofibromin protein, which down-regulates the function of the
p21ras protein.

NF2 is characterized by bilateral acoustic neuromas, one or more
plexiform neurofibromas, and Lisch nodules. The condition is
caused by a mutation in the NF2 tumor suppressor gene located on
chromosome 22ql2, which encodes for the merlin protein, which
shows structural similarities to a series of cytoskeletal proteins.


Cafe-au-lait macules may also be associated with Albright's syndrome
(polyostotic fibrous dysplasia, endocrine dysfunction, precocious puberty,
cafe au- lait macules).
This sporadic disorder is considered to be strongly associated with
mutation of the Gs, alpha gene.
The cafe-au-lait macules of Albright's syndrome tend to be large and
unilateral and have irregular borders.
Microscopically, cafe-au-lait macules are not particularly remarkable.
They generally show excess amounts of melanin in basal keratinocytes and
subjacent macrophages. Melanocytes are normal in appearance and may be
slightly increased in number.
SYSTEMIC DISORDERS ASSOCIATED WITH THE
PRESENCE OF ORAL PIGMENTED
MELANOCYTIC LESIONS
Peutz-Jeghers and other familial hamartoma
syndromes
consists of:
mucocutaneous macules
intestinal hamartomatous polyposis
increased risk of carcinomas of the gastrointestinaltract,
pancreas, breast, and thyroid
disease is associated with germline mutations in the
LKB1/STK11 gene located on the short arm of chromosome 19.
Black-to-brown spots of less than 1 mm in size are typically
localized on the lower lip and in the perioral area
Intraoral, intranasal, conjunctival, and rectal pigmented lesions as
well as spots localized on the acral surfaces may also be present.
The oral lesions are benign and histologically characterized by an
increase in melanin in the basal layer, without an obviously
increased number of melanocytes.
Fading or a disappearance of the spots is usually observed in older
age. Interestingly, oral lesions tend to persist.


Addison disease and other endocrine disorders
Primary hypoadrenalism caused by autoimmune disease, infection, or
malignancy (Addison disease)
deficient production of hormones of the adrenal cortex, leading to
increased production of adrenocorticotropic hormone (ACTH).
may result in a diffuse dark pigmentation of the skin and the oral
mucosa, lips, gingival, buccal mucosa, hard palate, and tongue are
usually involved
Pigmented lesions may be diffuse or localized and usually precede skin
manifestations
anorexia, nausea, and postural hypotension


Diffuse or discrete pigmentations of the lips and oral mucosa
are sometimes observed in monostotic and polyostotic fibrous
dysplasia (McCune-Albright syndrome), hyperthyroidism and
Nelson syndrome.
Treatment usually not required unless discomfort is present.
The disappearance of oral lesions may follow the treatment of
the underlying condition.

DRUGS ASSOCIATED WITH PIGMENTED LESIONS
Many non heavy metal containing drugs can induce discoloration
of oral tissues.
1. Direct deposition on oral surfaces
2. local accumulation after systemic absorption
3. stimulation of melanin-related pathways and
4. bacterial metabolism (alone or in combination)
Nicotine, Phenothiazine, Heroin, oral contraceptives, Busulfan
Zidovudine (AZT), Doxorubicin
Cyclophosphomide pigmentation
Minocycline pigmentation
Other conditions:
Laugier-Hunziker syndrome (idiopathic lenticular
mucocutaneous pigmentations)
Carney complex (spotty skin pigmentations, myxomas and
endocrine overactivity).
HIV - multiple usually well circumscribed melanotic macules
localized on the buccal and palatal mucosa, gingiva, and lips
The histolopathologic appearance is similar to classical
melanotic macules


Chronic inflammatory conditions, such as oral lichen planus,
pemphigus, pemphigoid, and chronic periodontal periodontal
disease, are sometimes associated with deposition of melanin
within the connective tissue, resulting in a darkening of the
mucosal area
Fixed drug reaction after administration with cotrymazole,
tetracycline, colchicine, and ketoconazole also has been
associated with postinflammatory hyperpigmentation.
lesions resembling melanotic macules of the palate in patients
with lung diseases, including cancer
Brown heme associated lesions
Lesions caused by endogenous pigments
(blood related Pigmentations)
Extravasations of blood in hematomas, petechiae, purpurae, and
ecchymoses may cause pigmentation as a result of accumulation and
degradation of haemoglobin to bilirubin and biliverdin
Color of the lesions depend on length of time from trauma and may
range from red to black
Typical traumatic events include biting, traumas with eating, and
iatrogenic procedures

Patients with hemochromatosis (bronze disease)
frequently display bluish-gray pigmentation of the hard palate,
gingiva, and buccal mucosa
The pigmentation is caused by deposition of iron-containing
pigments (ferritin and hemosiderin) within the skin and mucous
membranes
Similarly, a diffuse black-brown pigmentation, most commonly
in the junction between the hard and soft palate, may be
observed in patients with beta-thalassemia.
Gray/black pigmentation

Lesions caused by exogenous pigments
(metallic pigmentations)
Amalgam pigmentation (amalgam tattoo)
Accidental displacement of metal particles in oral soft tissues
Cause can be iatrogenic or traumatic
0.1- 2 cm in size, solitary or multiple
Colors - blue, gray, or black
Gingiva and alveolar mucosa most common sites
In alveolar edentulous ridge- restored antagonistic teeth
diagnosis is based on clinical findings and the relationship with present or
removed amalgam restorations

Buchner and Hansen and Owens et al
condensation of the material in abraded mucosa during routine
amalgam restorative work
introduction of the material within the lacerated mucosa during
removal of amalgam fillings or crowns and bridges
introduction of broken pieces into a socket or the periosteoum
during extraction of teeth
introduction of metal particles in a surgical wound during root
canal treatment with a retrograde amalgam filling.

Radiographic features may show localized radiopacities. Biopsy
is indicated only when suspicion of OMM cannot be ruled out
on clinical grounds alone
Histopathologic investigation reveals amalgam particles
dispersed in the connective tissue and sometimes in the walls of
vessels
particles may also line the basement membrane of the surface
epithelium
Brownish granules within phagocytic cells and fibroblasts
cytoplasm can also be observed


Histopathologic examination of an amalgam tattoo is usually
diagnostic because of the size and shape of the metal particles and
the way they are spread in the tissue.
immunohistochemical markers such as HMB-45 and Melan A
electron-probe microanalysis
Accidental or voluntary introduction of other foreign particles
include graphite from pencil tips, tattoo inks, and chronic contact
with charcoal toothpaste
Heavy metals -
Systemically absorbed metals may induce discoloration of the
oral mucosa, caused by peripheral metal accumulation
These conditions were frequent in the past as result of
occupational exposures to certain drugs
Arsenic, lead, bismuth, mercury, silver, and gold are the metals
most frequently involved
Bismuth - diffuse oral pigmentation and formation of a blue-
black line at the marginal gingiva.
A characteristic feature of plumbism (lead poisoning) is the so-
called burtonian line, a gray linear area of discoloration below the
gingival margin.
Silver (argyria) and gold (chrysiasis) may produce slate-gray oral
pigmentation and purple gingival discoloration, respectively.
Heavy metal intoxication can be associated with a wide range of
systemic signs and symptoms.

Lead poisoning
Conclusion:
Diagnosis of pigmented lesions of the oral cavity and perioral tissues
is challenging.
Diagnosis made on clinical grounds alone, remains provisional.
Definitive diagnosis usually requires histopathologic evaluation.
Occasionally, immunohistochemical stains such as melanocyte
marker HMB-45 and macrophage marker CD68 may be required to
arrive at a correct diagnosis.
Meleti et al
References:
1. Oral Pathology Clinical Pathologic Correlations REGEZI, 4
th

edition
2. Oral & Maxillofacial Pathology NEVILLE, 2
nd
edition
3. Textbook of Oral Pathology SHAFER, 5
th
edition
4. Pigmented lesions of the oral mucosa and perioral tissues -
OOO2008;105:606-16

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