pigmented oral lesion

8/12/2019 Pigmented Oral Lesion

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Pigmented oral lesions

Shilpashree.S


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Contents

Introduction

Classification

Blue lesions

Brown melanotic lesions

Brown heme associated lesions

Gray / black lesions Conclusion


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Introduction :

Human oral mucosa is not uniformly colored

Chromatic variation may be observed in physiologic andpathologic conditions

Oral tissues are characterized by different structuralcolours

depending on

degree of keratinization

numbers and melanogenic activity of melanocytesvascularization, and

type of submucosal tissue (muscle, bone, cartilage).


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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.


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Pigments:

Endogenous pigments

1. Melanin

2. Bilirubin3. Iron

Exogenous pigments

1. Heavy metals

2. Medicine


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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


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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


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Nonmelanin-associated lesions

endogenous pigments

Hematomas

petechiae

Purpurae

ecchymoses

hemochromatosis

beta-thalassemia

exogenous pigments

Amalgam pigmentation

Heavy metals

drugs associated

pigmentation


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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 neckincluding the oral cavity.

Intraoral hemangiomas occur most frequently on the tongue, lip or

buccal mucosa but can be seen at other sites too.


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Oral hemangiomas appear as deep red or blue, flat or nodularlesions, 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.


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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.

5th6thdecades 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.


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Oral lesions predominantly involve the palate but other sites may also beinvolved.

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.


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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.


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Brown melanocytic nevus


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Melanocytes Melanocytes were first identified in the oralepithelium by Becker in 1927

Isolation from samples of gingival tissue by Laidlawand Cahn.

neural crest cells melanoblast dendritic cells

H&N - first part of the body where melanocytes

appear - 10 weeks of gestation


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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


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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.


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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


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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.


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Brown melanotic lesions


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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.


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Histopathology:

increased melanin production

melanin is found in surrounding basal keratinocytes andsubjacent connective tissue macrophages.


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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.


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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


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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


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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.


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Smokers melanosis does not require treatment

disappearance has been reported after cessation of thesmoking habit

It may, however, potentially mask other lesions or may

be cosmetically objectionable.


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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.


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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.


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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.


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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.


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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


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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.


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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


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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


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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.


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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.


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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 (


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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.


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intramucosal nevi are the most commonvariety blue nevi are the secondmost 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.


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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.


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Differential Diagnosis

melanotic macule

amalgam tattoo

melanoma

Lesions of vascular origin including hematoma, Kaposi's sarcoma,

varix, and hemangioma


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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.


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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


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most often on buccal/labial mucosa

develop rapidly and asymptomatic

Unilateral dark plaque; rarely multiple, bilateral


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g


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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


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Differential Diagnosis

Melanoma

Drug-induced pigmentation

Smokers melanosis

Mucosal melanotic macule

Mucosal nevus

Amalgam tattoo


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Treatment and Prognosis

None after establishing the diagnosis

Often resolves spontaneously

Excellent prognosis


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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, and3. precursor lesions, such as congenital nevomelanocytic

nevi and dysplastic nevi.


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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


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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.


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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.


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In situ melanoma


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Invasive melanoma


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Amelanotic Melanoma

Positive HMB-45 stain


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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


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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)


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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.


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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.


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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


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Differential Diagnosis:

Early childhood malignancies

neuroblastoma, rhabdomyosarcoma or histiocytic tumor

Treated with surgical excision.


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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).


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There are two forms of this autosomal-dominant disorder. NF1-previously called Von Reck-Unghausen's diseaseand

neurofibromatosis 2(NF2) formerly known as acoustic

neurofibromatosis.

Although there are some overlapping features, the two conditions

are distinct clinically and genetically.


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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 onchromosome 17q 11.2 This tumor suppressor gene encodes for

neurofibromin protein, which down-regulates the function of the

p21ras protein.


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NF2 is characterized by bilateral acoustic neuromas, one or more

plexiform neurofibromas, and Lisch nodules. The condition is

caused by a mutation in theNF2 tumor suppressor gene located on

chromosome 22ql2,which encodes for the merlin protein,which

shows structural similarities to a series of cytoskeletal proteins.


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SYSTEMIC DISORDERS ASSOCIATED WITH THE

PRESENCE OF ORAL PIGMENTED

MELANOCYTIC LESIONS


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Peutz-Jeghers and other familial hamartoma

syndromesconsists 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


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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 olderage. Interestingly, oral lesions tend to persist.


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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


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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.


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Cyclophosphomide pigmentation


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Minocycline pigmentation


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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 classicalmelanotic macules


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Chronic inflammatory conditions, such as oral lichen planus,

pemphigus, pemphigoid, and chronic periodontal periodontaldisease, 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


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Brown heme associated lesions


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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, andiatrogenic procedures


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Patients withhemochromatosis (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 commonlyin the junction between the hard and soft palate, may be

observed in patients withbeta-thalassemia.


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Gray/black pigmentation


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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


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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.


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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


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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 particlesinclude graphite from pencil tips, tattoo inks, and chronic contact

with charcoal toothpaste


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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.


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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.


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Lead poisoning


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p g


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Meleti et al


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References:1. Oral Pathology Clinical Pathologic Correlations REGEZI, 4th

edition

2. Oral & Maxillofacial Pathology NEVILLE, 2ndedition

3. Textbook of Oral Pathology SHAFER, 5thedition

4. Pigmented lesions of the oral mucosa and perioral tissues -

OOO2008;105:606-16


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Thank you

pigmented oral lesion

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