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Oral Medicine 24 September 2013
Pigmentations of oral and
perioral tissues
Our topic for today is pigmentations; pigmentations mean stains, dyes,
colours so we will talk about the coloured lesion in the oral mucosa.
Sometimes the oral mucosa may be stained with extrinsic dyes, the sources are
from different kinds of food; ice cream, gum, or from the nicotine of the
cigarettes and the tobacco.
We are not concerned much about the extrinsic dyes, we will talk primarily about
the intrinsic dyes that stain the tissues from inside, which could be:
1) Pigments like:
The melanin pigments
Ingestion of heavy metals or heavy metal intoxication
Drugs and chemicals that are neutralized in the body, then
become secreted and deposited beneath the mucosa
The bile is well known for us in the jaundice, that is when the skin,
mucosa and sclera become yellowish in colour because of the bile
Haemosiderin is part of the haemoglobin, and it is deposited
underneath the mucosa as a brown pigmentation.
2) Blood:

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Haemangioma: it is a dilated blood vessel or very high number in
blood vessels, they will show through the skin or the oral mucosa as
red colour, this is the colour of the blood.
In other instances, the blood is not confined inside the blood vessel
like the haematoma, it happens with a big trauma that causes cut to
the blood vessels, but the blood will not come out and it will stay
underneath the mucosa or the skin, therefore, the skin will become
red in colour, then brown, green, yellow
3) Foreign bodies:
Foreign bodies that are introduced underneath the skin like the tattoo
(injecting material with different colours).

Melanocytes:
In all of us, what mainly stains our skin is melanin. The melanin is produced
by the melanocytes; it is believed that the number of the melanocytes on the
proportion of the melanocytes per square area is almost similar between
different individuals. However, their activity in producing melanin is different;
therefore, we have people who are white, fair, black
Melanocytes are generally residing in the epithelium, as you see the
dendritic cell in slide #4. Although they are residing in the epithelium, but they are
not of epithelial origin, they are from the neural crest cells (the doctor did not
mention the neural crest cells but he asked us to search it and so I did). Therefore,
when we classify the tumours according to their origin, melanoma, which is
tumour of the melanocytes, is not tumour of epithelial cells.

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Nevus:
Previously, it was believed that the nevus is a collection of melanocytes and
they produce melanin that is why the colour is collected in a specific area.
Now, they discovered that the nevus has different kind of cells that are called
nevus cells. Nevus cells are producing melanin but they are specialized in
producing nevi, while melanocytes are also producing melanin but they are
responsible of the general staining of the tissue.
The melanocyte has dendritic cell appearance ( ), while the nevus cell is
almost similar to the fibroblast cell.

How is melanin produced?
Inside the melanocyte or the nevus cell, the tyrosine is mixed with the
tyrisonase and converted into melanin, which is the black colour of the oral
mucosa. The colour changes from black to brown to blue, it is depending on:
The number of the melanocytes
The amount of the melanin
The higher the number of the melanocytes, the higher the amount of
melanin, and the darker the colour is.
The proximity of the melanocytes to the surface
The nearer the melanocytes to the surface, the darker the colour is.
Therefore, we have nevi that are coloured with black or brown, and
sometimes those that are deep in the tissue they are coloured with grey.



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Classification:
This is a matter of classification and we will not talk too much about it, but
generally, we have:
Benign lesions of melanocytic origin:
Physiologic pigmentations
Smoking associated melanosis
Ephilis
Lentigo
Oral melanotic macule
Conginetal:
Nevi
Neoplasms:
Melanoma
Neuroectodermal tumour of infancy
Pigmentations caused by deposits
Amalgam tattoo
Heavy metal pigmentations
Drug-induced pigmentations
Physiologic (racial) pigmentation:
Starting with the most common of all pigmented lesions in the oral cavity,
which is racial/physiologic pigmentation.

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It is not a disease. Is it a disease if your skin colour is dark? NO, that is something
congenital/physiologic because you have so active melanocytes. These
melanocytes are active in the skin as well as in the mucosa so they can stain our
mucosa with dark colour ranging from brown to black; this is what we call it racial
pigmentation.
There are characteristic features for it:
It is distributed symmetrically in the oral cavity (on both sides) as you see
the picture in slide #10.
It does not change the tissue architecture; the stippling of the gingiva for
instance is still there.
Mostly it is found on the gingiva
The cause for this pigmentation is the increase in the melanin production; usually
it is seen more clearly in people of dark skin. (You will find a lot of them in the
clinic). It does NOT have any clinical significance.
Histopathology:
Here we are talking about medicine not pathology, however, mainly, the
melanocytes are present typically at the basal cell layer region and loaded with
melanin.
Treatment for racial pigmentation:
Many attempts have been made to treat this stained mucosa for aesthetic
concerns (with gummy smile for instance), they tried to do shaping for the
mucosa, but because it is racial, recurrence is highly possible.


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Post-inflammatory pigmentation:
It is said that many of the chronic inflammatory reactions would stimulate
the melanocytes to produce more melanin. Many of you may have been exposed
to heavy sunray and then they got their skin inflamed and at the end, they are left
with some pigmentation on their skin, which is chronic inflammatory reaction.
People who have some kind of chronic infection on their skin, they might
develop colouration on their skin (brown for example); this is due to chronic
irritation of the skin. This may happen in the oral cavity in TWO scenarios:
1) Extensive herpes simplex infection (see the right picture slide #12),
you can trace where the lesion was, and after the disappearance of
the infective lesion, it will leave a pigmentation/stain on the skin
around the oral cavity.
2) Chronic lesion of lichen planus (see the left picture slide #12), and
all of us know the histopathologic feature of the lichen planus;
intense lymphocytic infiltration, therefore, it is classified among the
chronic inflammatory reaction. In some patients, the lichen planus
lesion will be on a background black colour, which we call it post-
inflammatory pigmentations.
Smoking associated melanosis/smoker melanosis:
It is believed that the tobacco smoke activates/stimulates the melanocytes
presence in the oral mucosa, exactly as when you are get exposed to sunshine,
the melanocytes will be activated and your skin will become tanned.

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This stimulated area will be concentrated where smokes are hitting more inside
the mouth, which is the lower/upper labial gingiva.
This will become more accentuated if a female practices it, because that will
exaggerate the level of the female sex hormone on the melanocytes.
Clinical features:
Mostly on the anterior labial gingiva
Dose and duration dependant; the more and the longer duration you
smoke, the more colour you get.
The treatment is smoking cessation, but it will not disappear next week, it
will need a long time to disappear.
Note: we cannot differentiate between smoking associated melanosis and racial
pigmentation because both of them have the same architecture on the gingiva,
distributed evenly on both sides of the jaw. However, it does not matter to
differentiate between them because both of them are having very little
prognostic importance, they will not transformed into malignant or anything else.

Freckles/Ephilis: (

)
Freckles are different from nevi. They are common on the skin and they
come in fair skin people not dark, unlike the racial pigmentation.
Freckles are more accentuated/provoked with exposure to sunshine. Sometimes,
we can get these freckles on the vermilion border (see slide #16), but usually,
those who are having them on the vermilion border are having them on the skin

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as well, therefore, this is not very significant but we need to recognize these
freckles.
Clinical features:
Common
Less than 5 mm in diameter, they are pinpoint
They become more frequent under the effect of the ultraviolet light

When we do differential diagnosis for pigmented lesion, two syndromes have
been mentioned in the book:

Myxoma syndrome (carneys syndrome):
In myxoma syndrome, we have:
Multiple myxomas, on the heart and the skin
Hyperpigmentation of the skin, and sometimes, inside the oral cavity
It is associated with endocrine hyperactivity (i.e. thyroid)
Therefore, these pigmented lesions on the skin are part of more serious systemic
disease; it is just a manifestation of a systemic disease.
Laugier-hunziker syndrome:
In this syndrome, we have:
Longitudinal pigmentation/melanonychia (pigmentation of the normal nail
plate)
Oral pigmentations

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General pigmentation
(As you see in the pictures in slide #18)

We have already covered other systemic diseases that have oral and skin
pigmentation in oral pathology course:
Multiple neurofibromatosis (NF1 -> common, NF2 -> rare)
(The doctor added another piece of information that I really could not
hear!)
McCune Albright syndrome, which has multiple fibrous dysplasia and caf-
au-lait spots
Addisons disease

Lentigo:
Lentigo is common on the skin of the elderly people who are exposed to
the ultraviolet light, specifically, the hands and feet.
It is yellow/brown stain on the skin; this is due to chronic longstanding exposure
to sunrays, and it must be in those who are working in the field (exposed to the
sun), when they grow up, they will have these stains.
Lentigo has no clinical significance; however, we have to identify it.
(From the slide: it is common on the skin but not intraorally).





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Oral melonetic macule (focal melanosis):
(The doctor emphasized that we must go back to our book to learn the exact
definitions of these clinical terms; macule, papule, etc).
Oral melonetic macule is like the nevus but it is bigger (see the picture on
the top of slide #21), the differential diagnosis is:
Intraoral freckle
Post inflammatory pigmentation
Peutz-jegher syndrome
Addisons disease
Nevi:
We have on the skin what we call it nevus, collection of nevus cells, it is
common on the skin but it is rare in the oral cavity, it is small; less than 0.5 mm,
sometimes it is a little bit elevated. 20% of them are not pigmented; it is the same
colour as the mucosa.
Histopathological classification:
We classify the nevi based on the depth of the nevus cells:
If the nevus cells are inside the epithelium, we call intramucosal nevus
If the nevus cells are on the junction between the epithelium and the
connective tissue, we call it junctional nevus
If it was mixed, some the nevus cells are on the junctional and others are
deep in the connective tissue, we call it compound nevus

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If the nevus cells are very deep with nothing on the junction, we call blue
nevus (clinically it is blue/gray)
Important note: We should know that localized and pigmented lesion in the oral
cavity should be biopsied and all suspected intraoral nevi should be excised
(excisional biopsy).

Melanoma:
Melanoma is a malignant neoplasm of the melanocytes. In the books, it is
named as malignant melanoma even though we do not have a benign form of it,
but they still write it as malignant melanoma in order to describe HOW MUCH
IT IS MALIGNANT! It has very poor prognosis.
Oral melanoma:
The early lesion of the malignant melanoma inside the oral cavity looks
EXACTLY like the melanotic macule or the nevus. We cannot differentiate
between early melanoma, nevus, or melanotic macule. Therefore, whenever we
have a localized pigmented lesion in the oral cavity it is safer to excise it and send
it to histopathology. If the suspected lesion turns out to be nevus or oral
melanotic macule then nothing has to be done, as it has no chance of malignancy
and if it is diagnosed as melanoma, then early diagnosis is the most important
diagnostic factor. We cannot just leave the lesion with regular follow up and
when it gets odd features in the future then we excise it, it would be too late.
Features:
Rare

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No geographic or racial differences
We do not have etiological factors, all the etiological factors for cancers
that we know them, do not apply for melanoma
At the beginning, the lesion starts to spread horizontally, which we call it
radial growth phase, after attaining certain size, it will start to invade down
in the tissue and that we call it vertical growth phase. Therefore, because
the vertical growth is a late feature/phase, if we have two melanomas, one
with 1 mm in depth, and the other one is with 2 mm in depth, sensibly, the
second one is longer standing lesion. In conclusion, the most important
prognostic factor we can find it in the histopathology.
Clinical pathological features:
It is the disease of elderly, more than 50 years
The most common size for melanoma is on gingiva or palate (see the
picture on slide #39). This lesion started as small lesion (nevus) -> radial
growth -> vertical growth)
Asymmetrical colour
Treatment:
There is a variety of treatment options:
Surgery
Chemotherapy
Immunotherapy
Radiotherapy as an adjunct


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Prognosis:
Prognosis depends on:
Histologic subtype
Depth of invasion
Oral lesions generally have poorer prognosis compared with skin
Early detection is the most important prognostic factor
Complete excision is better than partial excision

Skin melanoma:
Melanoma may be found on the skin (it is more common in the skin than
the oral cavity; it is very rare in the oral cavity). It represents 2% of all cancers.
More common in white people who are exposed to sunshine, therefore, those
white people who work under the exposure of the sun should always protect
themselves. By nature, the native people who live in areas with high sunshine
have dark skin, which is too much melanin that will protect them. So those who
are with white skin have less melanin and more liable for skin cancer. (Under the
sun, our body produces melanin to protect itself).
Risk factors include:
Extensive sun exposure
Skin colour
Presence of precancerous lesion or nevus. People who have nevus that is
highly exposed to the sunrays or irritation, they have to remove this nevus
because there is a chance for mutation and malignant transformation. (In

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the slide it written precursor lesion, however, the doctor said
precancerous)
We are not concerned about the types of melanoma, but you should recognize it
on the skin. We said that the nevus is well-localized, almost homogenous area
and very small. While the melanoma (see the pictures on the slide #32) is bigger
than the nevus, lacks its homogeneity with black or brown colour and in some
patients it may be surrounded by erythema, having etching, ulcers, or cracks.
Note: anyone with nevus that started to get features like the melanoma
(erythema, etching, etc), this is should be immediately excised because it may
be nevus that transformed to melanoma.
Features of malignant melanoma (oral cavity or skin):
Asymmetry; it is not round in shape, it is odd shape
The borders are irregular or elevated and sometimes, loss of skin marking
Lack of homogeneity of the colour
Diameter is more than 0.5 mm

Neuroectodermal tumour of infancy:
Unlike other tumours, this tumour happens in infants. Neuroectodermal
tumor of infancy is rare benign neoplasm of primitive pigmented-producing cells
(melanocytes). In this tumour, we have neoplastic changes in the premature
melanocytes (not well-developed melanocytes).


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Clinical features:
Usually occur in infants less than 6 months
Typically in maxilla (see the picture in slide #41)
Non-ulcerated dark pigmented mass (as you see in the picture, the
enlargement on the left side of the maxilla, this is what we call it
neuroectodermal tumour of infancy)
Treatment:
The treatment is surgery and the prognosis is excellent.
Note: I think that the doctor said that the histopathology of that disease is not
required yet I am not 100% sure.

End of the lecture
Done by: Amanda B. Saffoury