Oral Oncology 46 (2010) 423–425

Contents lists available at ScienceDirect

Oral Oncology
journal homepage: www.elsevier.com/locate/oraloncology

Review

Potentially malignant disorders of the oral and oropharyngeal mucosa; present

concepts of management
Isaäc van der Waal *
Department of Oral and Maxillofacial Surgery/Pathology, VU University Medical Center (VUmc)/Academic Centre for Dentistry Amsterdam (ACTA),
P.O. Box 7057, 1007 MB Amsterdam, The Netherlands

a r t i c l e i n f o s u m m a r y

Article history: In spite of tremendous progress in the field of molecular biology there is yet no single marker that reliably
Available online 21 March 2010 predicts malignant transformation of a potentially malignant disorder of the oral mucosa. Therefore, it is
recommended to excise or laser any oral of oropharyngeal leukoplakia/erythroplakia, if feasible, irrespec-
Keywords: tive of the presence or absence of dysplasia. However, it is actually unknown whether such removal truly
Oral leukoplakia prevents the possible development of a squamous cell carcinoma. Therefore, lifelong follow-up is recom-
Oral lichen planus mended at intervals of no more than 6 months.
Potentially malignant oral disorders
At present, oral lichen planus is more or less accepted as being a potentially malignant disorder. There
are no means to prevent such event. The efficacy of follow-up of oral lichen planus is questionable.
Ó 2010 Elsevier Ltd. All rights reserved.

Introduction lesion (‘‘erythroleukoplakia”), that may be either irregularly flat

In this treatise, attention mainly will be paid to leukoplakia,
erythroplakia and lichen planus. Other potentially malignant disor-
ders such as actinic cheilitis, submucous fibrosis, xeroderma pig-
mentosum and Fanconi’s anemia have recently been discussed
elsewhere.1
Leukoplakia
Leukoplakia is defined as ‘‘A white plaque of questionable risk
having excluded (other) known diseases or disorders that carry
no increased risk for cancer”.2 It should be realized that there are
several white lesions, including amalgam associated leukoplakic
or lichenoid lesions, that cannot always be clearly distinguished
from leukoplakia and yet may carry an increased risk of malignant
transformation.3
The estimated prevalence of oral leukoplakia, worldwide, is
approximately two percent.4 There are some geographical differ-
ences with regard to the gender distribution. Leukoplakia is much
more common among smokers than among non-smokers. Alcohol
is thought to be an independent risk factor,5 but definitive data are
still lacking. There are conflicting results of studies related to the
possible role of human papillomavirus infection.6
Clinically, leukoplakia can be subdivided in a homogeneous type
(flat, thin, uniform white in colour) and a non-homogeneous type.
The non-homogeneous type has been defined as a white-and-red
* Tel.: +31 20 444 4039; fax: +31 20 444 4046.
E-mail address: i.vanderwaal@vumc.nl
(speckled) or nodular. Verrucous leukoplakia is yet another type
of non-homogeneous leukoplakia. Although verrucous leukoplakia
usually has a uniform white appearance, its verrucous texture is
the distinguishing feature from homogeneous (flat) leukoplakia.
Proliferative verrucous leukoplakia (PVL) is a subtype of verrucous
leukoplakia, being characterized by multifocal presentation, resis-
tance to treatment and a high rate of malignant transformation.7
Histopathologically, a distinction can be made between dys-
plastic and non-dysplastic leukoplakia. There may be considerable
intra- and interobserver variation among pathologists in the
assessment of the presence and the degree of epithelial dysplasia.
Verrucous leukoplakia may show a spectrum of histopathological
changes, ranging from hyperkeratosis without dysplasia to verru-
cous hyperplasia and verrucous carcinoma.
An annual malignant transformation rate of approximately 1% is
probably a realistic figure for all types of leukoplakia together.
Malignancies may develop within the site of pre-existing leukopla-
kia, but may also occur elsewhere in the oral cavity or the upper
aerodigestive tract. The commonly recognized factors that statisti-
cally carry an increased risk of malignant transformation into a
squamous cell carcinoma are listed in Table 1. Of these risk factors,
the presence of epithelial dysplasia – often correlating with a clin-
ical non-homogeneous, erythroleukoplakic subtype – is in general
regarded the most important indicator of malignant potential.
However, in a few studies large size (>200 mm2) and location on
the tongue were shown to be the most relevant predictors of
malignant transformation.8,9 DNA ploidy analysis of the leukopla-
kic epithelium may have some prognostic value, aneuploidy appar-
ently carrying an increased of malignant progression.10 In spite of

1368-8375/$ - see front matter Ó 2010 Elsevier Ltd. All rights reserved.
doi:10.1016/j.oraloncology.2010.02.016
424 I. van der Waal / Oral Oncology 46 (2010) 423–425

Table 1 The most commonly used treatment modalities consist of surgi-

Reported risk factors of statistical significance for malignant transformation of
leukoplakia, listed in an at random order.
 Female gender
 Long duration of leukoplakia
 Leukoplakia in non-smokers
 Location on the tongue and/or floor of the mouth
 Size > 200 mm2
 Non-homogeneous type
 Presence of epithelial dysplasia
 DNA aneuploidy
tremendous progress in the field of molecular biology, there is as
yet no single marker or set of markers that reliably enables to pre-
dict malignant transformation of leukoplakia in an individual pa-
tient with leukoplakia.11
A flowchart for the management of leukoplakia has been pre-
sented in Table 2. In the presence of possible aetiological factors,
including tobacco habits, an observation period of not more than
a somewhat arbitrarily chosen 2–4 weeks seems acceptable to ob-
serve a possible regression after elimination of such factors.1
Although there is no scientific evidence that treatment, of what-
ever modality, truly prevents the possible future development of
a squamous cell carcinoma,12 it seems safe practice to treat all oral
leukoplakias, irrespective of the presence of epithelial dysplasia.
Cessation of smoking after surgical removal may reduce the risk
of recurrences, development of new lesions or malignancies.13 On
the other hand, the efficacy of continuous follow-up of oral leuko-
plakia patients, even in the presence of dysplasia, is virtually
unknown.
cal excision or CO2 laser therapy. In widespread leukoplakias pho-
todynamic therapy should be considered.14 Recurrence rates after
any type of treatment may vary from almost zero up to 30%, prob-
ably mainly depending on the length of follow-up.
Erythroplakia
Erythroplakia is defined in a similar way as leukoplakia, being a
‘‘A fiery red patch that cannot be characterized clinically or patho-
logically as any other definable disease”.2 Instead of a patch, the
clinical appearance is often a flat or even depressed erythematous
change of the mucosa; for that reason the term ‘‘erythroplasia”
may be more appropriate. In case of a mixture of red and white
changes such lesion is categorized as non-homogeneous leukopla-
kia (‘‘erythroleukoplakia”). Tobacco and alcohol use are considered
important aetiologic factors. Reported prevalence figures vary be-
tween 0.02% and 0.83%.15 Erythroplakia mainly occurs in the mid-
dle aged and the elderly, usually in a solitary fashion. This solitary
presentation is often helpful in clinically distinguishing erythropla-
kia from erosive lichen planus and erythematous candidiasis, since
these lesions occur almost always in a bilateral, more ore less sym-
metrical pattern.
Histopathologically, erythroplakia commonly shows at least
moderate or severe dysplasia. Probably by far the majority of ery-
throplakias will undergo malignant transformation. Erythroplakia
needs to be treated because of its high risk of malignant transfor-
mation. Besides, most erythroplakias are symptomatic. Surgery,
either by cold knife or by laser excision, is the recommended treat-
ment modality. There are no data from the literature about the
recurrence rate after excision of erythroplakias.

Table 2
Management of leukoplakia.

LEUKOPLAKIA
(Provisional clinical diagnosis)

Elimination of possible cause(s), such as mechanical irritation, No possible cause(s)

amalgam restoration in direct contact with the white lesion, (Definitive clinical diagnosis)
including tobacco habits (2-4 weeks to observe the result)

Good response No response Biopsy

(Definitive clinical diagnosis )

Histopathologically proven diagnosis

(By exclusion of "other known lesions")

Known lesion Non-dysplastic leukoplakia Dysplastic leukoplakia Known lesion

• Management accordingly • Management accordingly

Treatment (if feasible, e.g. < 2-3 cm) Treatment

• Follow-up in both treated • Follow-up in treated patients
and untreated patients at intervals of 6 months; lifelong (?)
at intervals of 6 months; lifelong (?)
 I. van der Waal / Oral Oncology 46 (2010) 423–425
Lichen planus
At present, oral lichen planus is generally regarded to represent
a potentially malignant disorder. The reported annual malignant
transformation rate is probably less than 0.5%. Apparently, such
event may occur in all clinical types of OLP.16 Unfortunately, the is-
sue of malignant transformation in OLP is blurred by the lack of
clinicopathologic correlation in the diagnosis.17 There are no possi-
bilities to truly prevent malignant transformation of oral lichen
planus. The efficacy of continuous follow-up of oral lichen planus
patients is questionable,18 although such follow-up has been rec-
ommended by various authors.19
Conflicts of interest statement
None declared.
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