1. By: Dr.Faris Mohsin Al-abeedi

2.  Premalignant or precancerous (also referred to as
“potentially malignant”) oral lesions involve the skin
lining of the mouth (known as the epithelium) and
may be at risk for becoming (transforming into) an
oral cancer, although it is difficult to predict which
lesions will transform and how long it will take (see
below)


3.  As we grow older our risk of developing cancer
increases. The same is true for premalignant lesions.
Most lesions are detected in people over the age of 40
and those with similar risk factors for oral cancer, such
as tobacco and/or heavy alcohol use, although such
lesions can also be found in younger individuals
and/or those without classic risk factors.

4. 1- Patches that are, red, white or mixed red/white in
color, or that may also be ulcerated (ie an area where
the lining epithelium is lost), especially when found
on “high-risk” sites such as the side (lateral surface),
underside of the tongue (ventral surface), floor of
mouth, or at the back of mouth/top of the throat
(oropharynx).

5. 2- A white patch that cannot be wiped off with gauze
and for which an explanation is not obvious to the
dentist may be defined as a leukoplakia. Similarly,
reddish patches with no obvious cause can be defined
as erythroplakia and mixed red and white areas termed
erythroleukoplakia .

6. 3- Lesions with a red component carry the highest
potential for being premalignant or becoming
malignant. Some dentists use additional technologies
to look for or characterize suspicious lesions (known as
diagnostic adjuncts). It is essential to establish an
accurate diagnosis for all such lesions that raise
suspicion.

8. There are three possible outcomes: benign (most
frequently), premalignant, or cancer. The pathology report
will use pathologic diagnoses such as epithelial
hyperplasia/hyperkeratosis or other benign diagnoses,
epithelial dysplasia
 (for premalignant lesions), or squamous cell carcinoma
(the most common type of cancer seen in the oral cavity).
 In epithelial dysplasia, the cells making up the layers of the
epithelium look abnormal (atypia), and depending on the
amount of abnormal cells seen microscopically, dysplasia
may be graded as mild, moderate, severe,
 or carcinoma in situ (where the atypical cells are in all
layers of the epithelium). In squamous cell carcinoma these
abnormal cells are no longer confined just to the
epithelium but have invaded below the epithelium into
deeper tissues

10.  Oral epithelial dysplasia is not associated with any
specific clinical appearance. However, leukoplakia and
erythroplakia are the lesions classically associated with
dysplastic changes. Thus white, red, or mixed white
and red changes are those most frequently revealing
epithelial dysplasia. The frequency of epithelial
dysplasia in leukoplakia varies between < 1 and > 30%

11.  Patients with high-grade dysplasia (severe or carcinoma-in-
situ) generally have a higher chance for malignant
transformation than those with lower-grade dysplasias. It is
extremely important that patients with oral epithelial
dysplasia be followed by a specialist who is trained to
manage these types of lesions. Eliminating high-risk
behaviors and promoting protective behaviors (such as a
healthy diet) are essential. Surgical removal of a
premalignant lesion may or may not be warranted.
Regardless of removal, periodic close follow-up of the
patient for any visual changes to the lesion site is critical
because lesions can recur and transformation into a
malignant lesion is possible at anytime.

12.  Loss of polarity of basal cells
 The presence of more than one layer of cells having a basaloid
appearance
 Increased nuclear-cytoplasmic ratio
 Drop-shaped rete ridges
 Irregular epithelial stratification
 Increased number of mitotic figures
 Mitotic figures that are abnormal in form
 The presence of mitotic figures in the superficial half of the epithelium
 Cellular and nuclear pleomorphism
 Nuclear hyperchromatism
 Enlarged nuclei
 Loss of intercellular adherence
 Keratinization of single cells or cell groups in the prickle cell layer

13.  Leukoplakia
 The term leukoplakia is sometimes used
inappropriately to indicate a premalignant condition.
In fact, the term describes a white plaque that does not
rub off and cannot be clinically identified as another
entity. Most cases of leukoplakia are a hyperkeratotic
response to an irritant and are asymptomatic,
but about 20% of leukoplakic lesions show evidence of
dysplasia or carcinoma at first clinical recognition.

14. However, some anatomic sites (floor of mouth and
ventral tongue) have rates of dysplasia or carcinoma as
high as 45%. There is no reliable correlation between
clinical appearance and the histopathologic presence
of dysplastic changes except that the possibility of
epithelial

16.  dysplasia increases in leukoplakic lesions with
interspersed red areas. In one large study, lesions with
an erythroplakic component had a 23.4% malignant
transformation rate, compared with a 6.5% rate for
lesions that were homogeneous. The term
erythroleukoplakia has been used to describe
leukoplakias with a red component.

18.  Figure 1.
Biopsy of leukoplakia in floor of mouth showing severe
dysplasia/carcinoma in situ. Note normal epithelium in
left side. The dysplastic area is especially characterized by
an increased nuclear-cytoplasmic ratio, an increased
number of mitotic figures including abnormal mitoses and
mitoses occurring in the middle and upper parts of the
epithelium, nuclear hyperchromatism, and enlarged
nuclei. H&E, X90
 Figure 2.
Biopsy of leukoplakia at lateral border of the tongue
showing mild to moderate epithelial dysplasia. Note
normal stratification and cytology in superficial half of the
epithelium. H&E, X190.

19.  Erythroplakia
An erythroplakia is a red lesion that cannot be
classified as another entity. Far less common than
leukoplakia, erythroplakia has a much greater
probability (91%) of showing signs of dysplasia or
malignancy at the time of diagnosis.(3) Such lesions
have a flat, macular, velvety appearance and may be
speckled with white spots representing foci of
keratosis.

21.  The premalignant or malignant potential of lichen
planus is in dispute. Some believe that the occasional
epithelial dysplasia or carcinoma found in patients
with this relatively common lesion may be either
coincidental or evidence that the initial diagnosis of
lichen planus was erroneous.
 It is frequently difficult to differentiate lichen planus
from epithelial dysplasia; one study found that 24% of
oral lichen planus cases had 5 of the 12 World Health
Organization (WHO) diagnostic criteria for epithelial
dysplasia, and only 6% had no histologic features
suggestive of that disorder.

22.  However, Oral Cancer Background Papers as many
reports on lichen planus patients followed over
time indicate a higher than expected rate of
malignant transformation, it is prudent practice to
biopsy the lesion at the initial visit to confirm the
diagnosis and to monitor it thereafter for clinical
changes suggesting a premalignant or malignant
change.

23.  Conventional clinical (subtype of leukoplakia) and
histopathological (presence or absence of epithelial
dysplasia) characteristics are still the most important
parameters for the prediction of malignant
transformation in oral pre-malignant lesions in
routine diagnostic oral pathology. Thus, careful oral
examination and a biopsy are usually required for
optimal management to be determined. In particular,
a non-homogeneous type of leukoplakia and the
presence of distinct epithelial dysplasia are indications
of a lesion at risk for malignant change

24.  The use of molecular biological markers for predicting
malignant transformation of oral pre-malignant
lesions is intriguing and rapidly evolving. So far, these
studies have not demonstrated methods that are
readily applicable for routine diagnostic work. There is
little doubt, however, that future developments will
render these biological markers as valuable diagnostic
tools