Report

Prevalence and clinical features of pigmented oral lesions

Yazan Hassona1, BDS, FFDRCSI, PhD, Faleh Sawair1, PhD, Omar Al-karadsheh1, DClinDent,
and Crispian Scully2, MD, PhD

1
Department of Oral and Maxillofacial
Surgery, Oral Medicine and Periodontology,
Faculty of Dentistry, The University of
Jordan, Amman, Jordan, and 2University
College London, London, UK
Correspondence
Yazan Hassona, BDS, FFDRCSI, PhD
Assistant Professor of Oral Medicine and
Special Needs Dentistry
Faculty of Dentistry
The University of Jordan
Queen Rania Street
PO Box 11942, Amman
Jordan
E-mails: Yazan_hasoneh@yahoo.com or
Yazan@ju.edu.jo
Conflicts of interest: None.
Abstract
Background To examine the relative prevalence, types, and clinical features of pigmented
lesions of the oral mucosa in 1275 patients attending a university hospital for dental care.
Methods Patients attending dental clinics at The University of Jordan Hospital over a
1-year period were examined for the presence of oral pigmentations. Histopathological
examination was performed on focally pigmented lesions with a suspicious or uncertain
clinical diagnosis.
Results A total of 386 (30.2%) patients were found to have oral pigmentations. Of these,
racial pigmentation (39.9%) and smokers’ melanosis (32.9%) were the most common
causes of oral pigmentations. Other causes included amalgam tattoo (18.9%), focal
melanotic macules (5.7%), postinflammatory pigmentation (1.6%), pigmentation due to
medications or systemic disease (0.52%), heavy metal deposits (0.26%), and oral nevus
(0.26%). Gingivae and buccal mucosae were the most common sites for oral
pigmentations.
Conclusion Pigmentations of the oral mucosa are common. Gingivae and buccal mucosae
are the most common sites for oral pigmentations. Proper history and recognition of clinical
features are important for effective management.

metal pigmentation, and melanosis associated with various

Introduction
The color of the oral mucosa varies depending on degree
of keratinization, thickness, vascularization, number and
activity of melanocytes, and type of submucosal tissue.1
The physiologic color of oral mucosa ranges from red–
purple in light-skinned people to dark brown in dark-
skinned people.1,2 Melanin is produced by melanocytes in
the epithelial basal layer and transferred via melanosomes
to adjacent keratinocytes.3 The amount of melanin is
genetically determined; however, various stimuli such as
trauma, inflammation, hormones, medications, and radia-
tion may result in an increased melanin production.3
Pigmented mucosal lesions are common in the mouth.
Accurate diagnosis can be challenging because such lesions
may result from a variety of causes, both exogenous and
endogenous, including physiologic, reactive, neoplastic,
systemic, and idiopathic processes.4 Pigmented lesions of
the oral mucosa can be classified clinically into focal pig-
mentations (e.g., oral melanotic macule, amalgam tattoo,
melanocytic nevus, melanoma, and melanoacanthoma) and
multifocal or diffused macular pigmentations, including
entities such as physiologic (ethnic) pigmentation, drug-in-
duced melanosis, smoking-associated melanosis, heavy
systemic diseases5 (Fig. 1).
The literature is replete with studies about prevalence of
oral mucosal lesions in different populations from both
developed and developing countries.6–9 However, only a
few studies specifically examined the relative frequency of
pigmented oral lesions.10,11 For example, De Giorgi
et al.,10 reported that the prevalence of solitary pigmented
oral lesions in patients attending a dermatology center in
Italy as 5.7%. Buchner et al.,11 reviewed a total of 89,430
oral mucosal biopsies from patients in Israel and reported a
0.83% prevalence of solitary pigmented oral lesions.
The availability of data about types, prevalence, and
clinical features of pigmented oral lesions could help
healthcare professionals in their diagnosis. The purpose
of this study therefore was to examine types, clinical fea-
tures, and relative frequency of pigmented oral lesions in
a group of patients attending a university hospital for
dental care.
Materials and methods
The Faculty of Dentistry Research and Ethics Committee
(FDREC) at the University of Jordan, Amman, reviewed and
1005

ª 2015 The International Society of Dermatology International Journal of Dermatology 2016, 55, 1005–1013
1006 Report Oral pigmentations
Figure 1 Differential diagnoses. and typical clinical features of pigmented oral lesions.
approved the study, which was conducted over a12-month
period (from February 2014 to February 2015). The research
was conducted in full accordance with the World Medical
Association Declaration of Helsinki.
New adult patients attending dental clinics at The University
of Jordan Hospital were examined for the presence of oral
mucosal pigmentation by a single oral medicine specialist (YH)
according to the World Health Organization method.12 All
patients provided formal informed consented. The diagnosis of
pigmented oral lesions considered clinical features such as the
number, distribution, site, size, shape, color of the lesion, and
its relation to metal-filled teeth. The history included inquiries
about the onset and duration of the lesion, presence of
associated skin hyperpigmentation, use of prescription and
over-the-counter medications, family history of pigmentary
disorders, and presence of systemic signs and symptoms (e.g.,
fever, malaise, fatigue, weight loss, abdominal pain,
gastrointestinal upset). Data about social habits such as
smoking, narghile (shisha) use, and alcohol consumption were
obtained from all participants. Patients with pigmented oral
lesions were also asked about any associated symptoms and
whether they were aware of the presence of oral pigmentations.
International Journal of Dermatology 2016, 55, 1005–1013
Hassona et al.
Diagnostic biopsies were obtained under local anesthesia in
patients with focally pigmented lesions with uncertain clinical
diagnosis and in cases demonstrating suspicious clinical
features such as irregular borders, large size (>6 mm),
asymmetry, and color variations. In addition, diagnostic biopsies
were obtained in all cases that presented with solitary raised
lesions, or when patients reported a change in size or color.
Consent was obtained from all patients before biopsy.
Statistical analysis was performed using GraphPad Prism 6.0
(GraphPad Software Inc., La Jolla, CA, USA). Frequency
distributions were obtained, and chi-squared and Student t-tests
were used to compare differences between groups. Statistical
significance was set at P < 0.05.
Results
The study population consisted of 1275 (704 females and
571 males) adult dental patients whose main characteris-
tics are summarized in Table 1. The mean age of patients
was 39.2  12.6 years (range: 18–86 years). Of the total
group investigated, 34.8% were smokers and 7.3%
reported alcohol consumption (Table 1). A total of 386
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Hassona et al. Oral pigmentations Report 1007

Table 1 Demographic characteristics of patients in study

n %

Gender
Male 571 46.1
Female 704 53.9
Age
<35 590 46.3
35–55 415 32.6
>55 269 21.1
Tobacco 443 34.8
Cigarettes 221 17.4
Narghile 142 11.2
Both 79 6.2
Alcohol 93 7.3

(30.3%) patients (246 males and 140 females) were found

to have oral pigmentations. The mean age of patients
with pigmented oral lesions was 41.3  11.1 years. More
than half (53.1%) of these patients smoked tobacco, and
2.3% consumed alcohol. The presence of oral mucosal
pigmentations was significantly associated with male gen-
der and history of smoking (P < 0.05). No significant
association was found between the presence of oral pig-
mentations and age or alcohol consumption (P > 0.05). Figure 2 Relative frequency of oral pigmented lesions in
None of the patients diagnosed with oral mucosal pig- study patients.
mentations reported a family history of melanoma or
other pigmentary disorder.
Diffuse or multifocal pigmentation was identified in the
majority of cases (75.2%), while a focal pattern was identi-
fied in 24.8%. Overall, the gingiva (56.2%) and buccal
mucosa (39%) were the most commonly affected sites, and
other affected sites included labial mucosa (31.5%), tongue
(6.9%), palate (5.9%), lower vermilion (4.7%), floor of the
mouth (1.1%), and upper vermilion (0.9%). Racial pig-
mentation and smoker’s melanosis were the most common
causes of oral pigmentations. Other causes included amal-
gam tattoo, focal melanotic macules, postinflammatory
pigmentation, pigmentation due to medications or systemic
Figure 3 Racial (physiologic) pigmentation presenting as
disease, heavy metal deposits, and oral nevus (Fig. 2). Most
well-defined dark brown band on the attached gingiva.
cases were diagnosed solely based on history and clinical
features; diagnostic biopsies were obtained in 21 lesions
(5.2%) presented with uncertain clinical diagnosis or with exhibited a multifocal pattern of homogeneous bilaterally
suspicious clinical features. Melanoacanthoma and mela- symmetrical brownish pigmentation (Fig. 3). Gingiva was
noma were not encountered in this study. affected in most cases (72%), and other affected sites
None of the patients with pigmentations reported any included buccal mucosa (46%), labial mucosa (26%),
symptoms, and only 92 patients (23.8%) were aware of tongue (13%), and palate (4%).
the existence of oral pigmentation. Female patients were
more likely than males to be aware of oral mucosal pig- Smoker’s melanosis
mentation (P < 0.05). Smoker’s melanosis was encountered in 127 patients (102
males and 25 females; P < 0.05). Labial mucosa was the
Racial (physiologic pigmentation) most commonly affected site (63%) followed by buccal
Racial pigmentation was encountered in 154 patients (97 mucosa (56%), gingiva (31%), palatal mucosa (13.2%),
males and 57 females; P < 0.05). Racial pigmentation and tongue (4%). Smoker’s melanosis appeared as

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1008 Report Oral pigmentations
multifocal gray to brown patches with random distribu-
tion and irregular pattern (Fig. 4).
Amalgam tattoos
Seventy-three patients (36 males and 37 females;
P > 0.05) had amalgam tattoos. Amalgam tattoos
appeared as small (2–8 mm) blue to gray macules, mainly
on the gingivae adjacent to amalgam-filled teeth. Few
cases (9.5%) were encountered at atypical sites such as
palate, buccal mucosa, and floor of the mouth. Excisional
biopsy of such cases confirmed the diagnosis of amalgam
tattoo (Fig. 5).
Melanotic macules
We observed 22 cases (14 females and eight males;
P > 0.05) of melanotic macules. Most cases were labial
Figure 4 Smoker’s melanosis presenting as diffuse brown
patches with irregular distribution on the buccal mucosa.
(a) (b)
International Journal of Dermatology 2016, 55, 1005–1013
Hassona et al.
melanotic macules in the lower vermilion (82%). Other
affected sites included gingivae (10%), upper vermilion
(4%), and buccal mucosae (4%). Melanotic macules
appeared as small (2–6 mm) well-circumscribed brown to
black macules (Fig. 6).
Postinflammatory pigmentation
Postinflammatory pigmentation was encountered in six
cases (four females and two males). Five patients had oral
lichen planus, and one had pemphigus vulgaris. Postin-
flammatory pigmentation appeared as multifocal light
brown patches at sites of mucosal inflammation (Fig. 7).
Pigmentation due to systemic disease or medications
We encountered two cases of oral pigmentations due to
systemic diseases or medications. One patient was a 28-
year-old woman diagnosed with Addison’s disease 1 year
before presentation. The pigmentation appeared as dif-
fused faint brown patches on the lateral borders of the
tongue and both buccal mucosae (Fig. 8); macular pig-
mentations were also seen on dorsal hands and palms.
The other patient was a 33-year-old woman using proges-
terone–estrogen-based oral contraceptive pills. The pig-
mentation appeared as diffuse macular pigmentations
mainly on the upper and lower labial mucosae (Fig. 9).
Pigmentation due to heavy metals
We encountered one case of pigmentation due to heavy
metals. The patient was a 42-year-old non-smoker male
working in a battery factory for 7 years. The pigmenta-
tion appeared as a linear blue–gray patch on the lower
labial gingiva (Fig. 10). No pigmentations were encoun-
tered at other mucosal sites. Although no formal measure-
ment of blood lead level was performed, the patient
demonstrated clinical features suggestive of lead toxicity,
including headache, constipation, and numbness of the
extremities. Blood film showed hypochromic microcytic
anemia with basophilic stippling of red blood cells.
Figure 5 Amalgam tattoo at atypical
site. (a) Blue–gray macule on the floor
of the mouth. (b) Histopathological
examination showed scattered
arrangement of dark solid fragments
along blood vessels and collagen
fibers. No significant chronic
inflammation was noticed
(hematoxylin and eosin stain, 9 20,
9 140).
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Hassona et al. Oral pigmentations Report 1009

Figure 6 Melanotic macule on upper vermilion.

Oral nevus
One patient, a 38-year-old woman, had an oral nevus. It
appeared as an elevated well-circumscribed black nodule
(6 mm in diameter) on the right buccal mucosa. Exci-
sional biopsy showed proliferation of benign hypermelan-
Figure 8 Diffuse brown pigmentation on the tongue of a
otic cells arranged in compact nests in the subjacent
patient with Addison’s disease
connective tissue (intramucosal nevus) (Fig. 11).

Similar to other studies, we identified racial (physio-

Discussion
There is paucity of information in the literature regarding
the relative prevalence of oral mucosal pigmentations,
despite the high frequency. The present study examined
the relative frequency, types, and clinical features of pig-
mented oral lesions in 1275 patients attending dental clin-
ics at the University of Jordan Hospital, which is the
main public hospital in Jordan attended by patients from
various socioeconomic backgrounds. The overall preva-
lence of oral mucosal pigmentation in our study was
30.2%.
logic pigmentation) and smoker’s melanosis as the main
causes of oral mucosal pigmentation.10,11,13–16 The
amount of melanin produced by melanocytes is geneti-
cally determined, and several pathways, including the
adrenalin/b2-adrenoceptor/cAMP/MITF pathway, a-MSH/
MC1R/cAMP/MITF pathway, and b-endorphin/l-opioid
receptor/PKCb isoform signaling pathway, have been
identified as main regulators.17,18 Substantial variations in
the degree of melanin pigmentations exist between per-
sons from different racial backgrounds.3 Oral racial pig-
mentations are more frequently encountered in dark-

(a) (b)

Figure 7 Postinflammatory
pigmentation in a patient with history
of oral lichen planus. (a) Diffuse
brown pigmentation with reticular
pattern on buccal mucosa. (b)
Histopathological examination
showed deposition of melanin in the
lamina propria along with chronic
inflammatory cell infiltrate
(hematoxylin and eosin, 9 20, 9 40).

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1010 Report Oral pigmentations
Figure 9 Diffuse macular brown pigmentation on upper lip
and labial mucosa in a patient receiving oral contraceptives.
Figure 10 Heavy metal pigmentation due to lead toxicity
presenting as diffuse linear blue patches on the attached
gingiva.
skinned populations, and several studies have reported a
correlation between skin color and oral mucosal pigmen-
tation.14,19
(a)
Figure 11 Oral melanocytic nevus (intramucosal type). (a) Brown nodule on the right buccal mucosa. (b) Histopathological
examination showed superficial epithelioid-like oval cells with abundant cytoplasm and large round or oval nuclei containing
melanin pigmentation (type A nevus cells) and lymphoid-like cells (type B nevus cells) in the middle portion of the lesion
containing no melanin (hematoxylin and eosin, 9 20, 9 40).
International Journal of Dermatology 2016, 55, 1005–1013
Hassona et al.
A stimulant effect of tobacco constituents on melano-
cytes has been proposed as a possible mechanism for
tobacco-associated oral pigmentation (smoker’s melano-
sis).3 It has been hypothesized that melanin may play a role
in the detoxification of polycyclic amines and benzopyre-
nes;20,21 smoker’s melanosis might therefore represent a
mucosal protective mechanism from the harmful effects of
smoking. Clinical distinction between smoker’s melanosis
and racial pigmentation might be difficult in some cases
because both conditions present as diffused brown pigmen-
tations involving mainly the gingivae and labial and buccal
mucosa. A history of lesion evolution and smoking habits
might help to distinguish between the two conditions. In
addition, racial pigmentation tends to be homogeneous and
bilaterally symmetrical, while smoker’s melanosis exhibits
an irregular or a random pattern of distribution.
Less commonly, diffuse oral pigmentation might result
from systemic diseases or as an adverse effect of medica-
tions. In the present study, we encountered a patient with
oral pigmentation due to Addison’s disease and one due to
oral contraceptives. Although Addison’s disease is relatively
uncommon, hyperpigmentation of skin and mucosal sur-
faces can occur in up to 92% of affected patients.22 Hyper-
pigmentation associated with Addison’s disease occurs due
to overproduction of lipotropin, a proopi-
omelanocortin by-product, which is secreted in excess
amounts concomitantly with corticotropin from the pitu-
itary gland because of the lack of feedback inhibition.23
The clinical appearance of Addisonian oral mucosal pig-
mentation is not specific and appears similar to other
causes of diffuse oral pigmentation such as smoking and
physiologic pigmentation. The presence of systemic fea-
tures of adrenal insufficiency, such as hypotension, cuta-
neous pigmentation fatigue, orthostasis, weight loss, and
nausea, might help distinguish this type of pigmentation,
(b)
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Hassona et al.
but reduced serum cortisol levels would confirm the
diagnosis. Diffuse oral mucosal pigmentation has also
been reported in association with other systemic diseases,
including Puetz–Jeghers syndrome, Laugier–Hunziker
syndrome, McCune–Albright syndrome, Cowden syn-
drome, Carney complex, AIDS, hemochromatosis, Nel-
son syndrome, and hyperthyroidism.24–32 Many drugs
can induce diffuse pigmentation of oral mucosa, includ-
ing quinine derivatives, antineoplastic drugs, antiretroviral
drugs, oral contraceptives, anticonvulsants, minocycline,
amiodarone, premarin, and clofazamine.33 The pathogene-
sis of drug-induced pigmentation varies according to the
causative drug and includes deposition of drug or its
metabolites, stimulation of melanin-related pathways, or
bacterial metabolism, alone or in combination.4,34 Drug-in-
duced pigmentation can range from brown (e.g., with oral
contraceptives) to blue–black (e.g., hydroxychloroquine).
Heavy metals, such as lead, bismuth, mercury, gold,
arsenic, cooper, cobalt, chromium, and magnesium, can
Figure 12 Evaluation and management of pigmented oral lesions. *Palate and gingivae are considered subsites at risk for
melanoma development.
ª 2015 The International Society of Dermatology
Oral pigmentations Report 1011
be a cause for oral mucosal pigmentation. This typically
presents as a bluish-black line, known as Burton’s line,
along the gingival margin and seems to be proportional
to the amount of gingival inflammation.33 In cases with
little or no gingival inflammation, other oral sites, such as
the attached gingiva and buccal mucosa, might be
affected. The diagnosis of such cases can be challenging;
however, a history of occupational or environmental
exposure to heavy metals, and recognition of clinical
signs and symptoms of heavy metal toxicity can help to
reach the correct diagnosis, and measurement of blood
levels of the suspected heavy metal will confirm the diag-
nosis. Longstanding inflammatory mucosal diseases can
cause mucosal pigmentation, sometimes called pigmentary
incontinence.33 In the present study, we identified six
cases of oral mucosal pigmentation due to chronic oral
mucosal diseases, primarily lichen planus. The pathogene-
sis of this type of pigmentation remains unclear, but there
is increased production of melanin, possibly induced by
International Journal of Dermatology 2016, 55, 1005–1013
1012 Report Oral pigmentations
the chronic inflammatory microenvironment and accumu-
lation of melanin-laden macrophages in the superficial
layer of connective tissue.33
Focal pigmented lesions of oral mucosa are relatively
uncommon, and reported prevalences range from 0.83 to
5.7%.10,11 The prevalence of solitary pigmented oral
lesions in our study was 7.2%. Similar to other studies,
amalgam tattoos and melanotic macules were the main
causes of focal oral pigmentation.13–15 An amalgam tat-
too results from accidental or iatrogenic implantation of
amalgam particles into oral soft tissues during dental pro-
cedures, resulting in bluish-gray macular pigmentation
often near an amalgam-filled tooth. Findings of our study
confirmed that gingivae and alveolar mucosa are the most
common sites for amalgam tattoo.35,36 Occasionally,
amalgam tattoos appear in atypical sites such as palate
and floor of the mouth. In these cases, particularly when
a radiograph fails to show any evidence of the radiopaque
remnants of amalgam, excisional biopsy might be needed
to confirm the diagnosis. Histologically, the amalgam tat-
too appears as discrete dark granules or fragments
arranged mainly around collagen bundles and blood ves-
sels causing little inflammatory reaction.35,36 Inquiry
about previous history of trauma, particularly with pen-
cils, is important because implantation of foreign bodies
(e.g., graphite) into oral mucosa can produce lesions simi-
lar to an amalgam tattoo. Melanotic macules appear as
well-circumscribed brown–black flat lesions, mainly on
the lower vermilion. Similar to other studies, we found a
higher prevalence of melanotic macules among female
patients.10,11 The pathogenesis of melanotic macule is
controversial, but physiologic, reactive, and genetic fac-
tors have been suggested.4
Nevi are uncommon in the oral cavity; a study from
the Netherlands revealed an estimated annual incidence
of 4.35 cases per 10 million population per year.37 In the
present study, we encountered one patient with an oral
nevus (0.07%) on the right buccal mucosa. Oral nevi typ-
ically appear as a solitary brown–black mucosal nodule,
mainly on the palate and buccal mucosa. The pathogene-
sis of oral nevi is not known; however, it is currently
believed that nevi represent benign neoplasms that fre-
quently harbor oncogenic serine/threonine-protein kinase
B-Raf or, less commonly, neuroblastoma ras viral onco-
gene homolog mutations.38 Malignant transformations of
oral nevi are not reported, and there is no evidence to
suggest an increased risk of oral melanoma in patients
with oral melanocytic nevi.37 Clinical appearance of oral
melanoma is variable and ranges from an asymptomatic
brown to black patch with asymmetrical and irregular
borders to a rapidly growing mass associated with sinister
features such as pain, ulceration, bleeding, and bone
destruction, often in the palate.39
International Journal of Dermatology 2016, 55, 1005–1013
Hassona et al.
Conclusions
Oral mucosal pigmentations, particularly physiologic pig-
mentation and smoker’s melanosis, are common. Focal
causes, including amalgam tattoo, melanocytic nevi, and
melanotic macules, are less common. Recognition of clini-
cal features is important for effective management.
Detailed history, including family history, medical his-
tory, social history, environmental and occupational his-
tory, and history of previous trauma and dental
treatment, is essential in all cases. Histopathological
examination is necessary when the clinical diagnosis is
uncertain or when lesions exhibit suspicious features such
as an increase in size, non-homogeneous color, irregular
borders, and change in color, rapid growth, ulceration,
bleeding, or pain (Fig. 12).
Acknowledgments
The authors would like to thank Mrs. Najwa Yaseen for
help in administrative work.
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