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Leukoplakia: Histopathology – Epithelial Dysplasia


Author: Sanketh DS, MDS


Microscopically leukoplakia may reveal hyperplastic epithelium with hyperkeratosis, mild, moderate or severe epithelial dysplasia, carcinoma in situ or at times squamous cell carcinoma. Usually around 4-25% of leukoplakias may reveal dysplasia.

Before going into the details of how dysplasia is graded, let us brush through some basics of different terminologies to get a better perspective of things!

When a cell is insulted due to a carcinogen, the cell undergoes reversible cell damage and is in a phase of adaptation, meaning, the damaged cell could revert to normalcy if the insult is removed. However, the cell could slip into a stage irreversible damage if the insult is persistent and cannot become normal even on withdrawal of the stimulus.

In such a scenario, the apoptotic genes of the cell are activated to eventually cause programmed death of the cell. But carcinogens could cause sufficient mutation of the cell during the phase of insult, helping  it escape homeostatic control (apoptosis) and become a tumor cell.

In the context of leukoplakia, irritants like tobacco or inherent genetic mutations help in the epithelial cells becoming tumor cells. Firstly, there is a phase of adaptation, where there is an accelerated growth of cells presenting as a hyperplastic epithelium. But note that the cells in this phase are normal. If the irritants are persistent, accumulating mutations could help in transition of these normal cells to atypical cells. At this point, in the cellular level, there is epithelial atypia. Now this atypia, as well as the collective disruption of the architectural orientation is called dysplasia.

Criteria used for diagnosing oral epithelial dysplasia were proposed by WHO, lastly modified in 2005. There are numerous sets of other criteria available for grading epithelial dysplasia, but the WHO criteria are widely followed.

So, dysplastic features can be categorised as those affecting/disrupting the architecture of the epithelium and those changes manifesting as cellular atypia.


1. Irregular stratification refers to the haphazard differentiation of cells. The normal epithelium consists of tall basal cells which become larger and flatter squames in the upper most layers. But there is a disorganised differentiation of these cells with many cells in the strata becoming basal cell like (basaloid).

2. Basal cells in the dysplastic epithelium have a chaotic organization and lose their orientation, referred to as loss of polarity.

3. Long tube shaped rete ridges become bulbous and drop shaped in a dysplastic epithelium

4. Mitotic figures increase in number
as compared to normal epithelium. However more important is the presence of mitotic figures in the superficial layers of the epithelium unlike normal epithelium. Another feature is these mitotic figures becoming abnormal or atypical.

5. Atypical epithelial cells may abnormally produce keratin within a single cell which is referred to as dyskeratosis.

6. Numerous abnormal cells may produce abnormal keratin which accumulates in focal areas as pools of keratin. These foci of abnormal keratin are called keratin pearls.


Abnormal nuclear morphology
The nuclei become disproportionately large for the cell and the nuclear : cytoplasmic ratio is increased to 1:1 as compared to 1:4 – 1:6 normally. The shape of the nucleus is irregular and may show coarse clumping of chromatin making the nucleus appear hyperchromatic! Large nucleoli, often many in number, also appear in the nucleus.

Abnormal cellular morphology
The cells may also show abnormal variation in size and shape and do not appear to be uniform throughout the layers of the epithelium. Some may appear large and some very small and primitive!


WHO advocates grading of dysplasia as mild, moderate and severe.

Mild dysplasia is defined when architectural disturbance is limited to the lower third with minimal cytological atypia.

For grading moderate dysplasia, firstly architectural disturbance must extend to the middle third of the epithelium. The atypical cytological features are then verified. If cellular atypia is mild, the lesion is graded as moderate. However if there is severe cellular atypia despite not extending beyond the middle third, it is justified to be graded severe.

A lesion is graded severely dysplastic if the architectural changes extend to the upper 2/3rds of the epithelium together with cytological atypical features. 

Carcinoma in situ refers to a lesion with dysplastic features extending to the full length of the epithelium. It is generally considered to be carcinoma with an absence of invasion/infiltration.


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Warnakulasuriya S, Reibel J, Bouquot J, Dabelsteen E. Oral epithelial dysplasia classification systems: predictive value, utility, weaknesses and scope for improvement. J Oral Pathol Med 2008;37(3):127-133.

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