Leukoplakia: Histopathology – Epithelial Dysplasia

Leukoplakia: Histopathology – Epithelial Dysplasia

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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 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 cell death. But carcinogens could cause sufficient mutation of the cell during the phase of insult, helping it escape homeostatic control and become a tumour 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. Irregular epithelial 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 in a dysplastic epithelium, there is a disorganised differentiation of these cells with many cells in the strata becoming basal cell like (basaloid). Basal cells in the dysplastic epithelium have a chaotic organization and lose their orientation. This is referred to as loss of polarity. Long test tube shaped rete ridges become bulbous and drop shaped in a dysplastic epithelium 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. Atypical epithelial cells may abnormally produce keratin within a single cell which is referred to as dyskeratosis. 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. An atypical epithelial cell may show
abnormal nuclear morphology. The nucleus become disproportionately large for the cell and the nuclear:cytoplasmic ratio is increased to 1:1 as compared to 1:4– 1:6 in the normal cell. 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. 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 dysplasia. However, if there is severe cellular atypia
despite not extending beyond the middle third, it is justified to be graded as severe dysplasia. 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. Carcinoma in situ It is generally considered to be carcinoma with an absence of invasion/infiltration.

18 thoughts on “Leukoplakia: Histopathology – Epithelial Dysplasia”

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