By: Dr.Faris Mohsin Al-abeedi
 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)

 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.
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).
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 .
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.
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
 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%
 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.
 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
 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.
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
 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.
 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.
 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.
 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.
 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.
 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
 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

Premalignant lesion (Doctor Faris Alabeedi MSc, MMedSc, PgDip, BDS.)

  • 1.
  • 2.
     Premalignant orprecancerous (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 wegrow 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 thatare, 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 whitepatch 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 witha 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 threepossible 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 epithelialdysplasia 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 withhigh-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 ofpolarity 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  Theterm 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 anatomicsites (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 increasesin 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 premalignantor 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, OralCancer 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 useof 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