Potentially malignant diseases of the oral mucosa

Introduction

Potentially malignant lesions (PML) are conditions that are a priori benign, however the risk of malignant transformation is possible.
Early detection by systematic examination of the entire oral cavity is the rule.
Regular monitoring of these lesions allows for early treatment and therefore a better prognosis.
The latest work of the WHO expert group on precancerous lesions dates back to 2007. They analyzed all existing systems, taking into account the latest knowledge of the biology of oral mucosal cancer. They focused on clarifying nomenclature, definitions, and classifications for easy diagnosis in clinical practice; they recommended abandoning the distinction between lesions and precancerous conditions. The term to be used is “potentially malignant conditions.”

Interest in the study of potentially malignant diseases
- Recognize these potentially malignant conditions and treat them to prevent cancerization,
- Monitor them
- Evaluate the evolution to better understand the genesis of CB cancers
Etiology

Tobacco and chewing tobacco
Alcohol
The alcohol-smoking association
Human papillomavirus (HPV)
Hygiene, sun, diet, age

Definition

According to the WHO , a precancerous lesion corresponds to a morphologically altered tissue where the risk of cancer appearing is higher than in healthy homologous tissue.

Classification

WHO Classification 2007

Leukoplakia
Erythroplakia
Reverse smoker’s palatal lesions
Submucosal fibrosis
Actinic cheilitis
Oral lichen planus
discoid lupus erythematosus
Hereditary conditions: dyskeratosis congenita and epidermolysis bullosa

Pathological changes
Keratinization anomaly: Keratosis
- Either superficial:
  - Orthokeratosis

Disappearance of cell nuclei of the stratum corneum and the stratum granulosum

Parakeratosis

Disappearance of the granular layer and preservation of pyknotic nuclei in the horny layer

Either interstitial and more or less deep:
- Dyskeratosis: abnormalities in the constitution of keratin

Hyperacanthosis

Significant thickening of the epithelium due to an increase in the number of cell layers of the Malpighian mucous body, with the appearance of epithelial expansions penetrating into the underlying chorion.

Atrophy

It is a reduction in the thickness of the epithelium by reducing the number of cell layers.

Epithelial dysplasia

It is a disorder of the multiplication, growth, differentiation and maturation of keratinocytes.

Screening

It consists of the detection of a lesion during a systematic examination carried out on any newly seen or previously known patient, during a consultation.

This examination must be even more rigorous and attentive in a patient at obvious risk.

“alcoholic-smoker” or patient over 50 years old.

Diagnosis of potentially malignant lesions

a. Clinical examination

Age, lifestyle and risk factors
Functional signs
Circumstances and conditions of appearance of lesions
Medical history
Intraoral examination
Examination of the lesion: color, shape, consistency and its relationship with neighboring organs
Additional examinations
- Biopsy

This is the removal of part of the lesion, with a view to confirming or invalidating the clinical diagnosis, or to providing additional details.

choose an area representative of the entire lesion, preferably straddling the lesion and peripheral mucosa
avoid inflammatory ulcerations and areas of necrosis
for diffuse and multiple lesions, taking several samples is preferred to a more extensive sample
the piece taken must be of sufficient volume, in length, in width, in thickness: 2 to 3 mm in diameter and 4 to 5 mm in thickness.
General shape will be either elliptical called “orange quarter”, triangular
Cut deep enough to have as much damaged tissue as possible
Fixing:
The sampled fragment is immersed in a bottle containing the fixing liquid bearing a label or the information sheet.
Bouin’s fluid is usually used for oral biopsies.
10% formalin is mainly used for large excisions.
- Immunohistochemistry

IHC is a method of localizing proteins in cells in a tissue section, by detecting antigens using antibodies.

It is used for the diagnosis and/or monitoring of cancers by detecting abnormal cancerous cells.

Vital colorants:

The solutions are applied locally. They interact with tissue damage in various ways.

A more intense or particular coloration of the lesion is observed

The toluidine blue test:

A basic vital dye that binds to nucleic acids, which explains its affinity for neoplastic lesions, but also for inflammatory and traumatic lesions.
A simple mouthwash, the pathological areas will retain the dye, it allows to specify the dimensions and the limits of the suspect area.
It is only the first ^localizing phase of a biopsy or cytological sample.
- Exfoliative cytology:

This involves removing epithelial cells from a lesion by scraping them firmly using a foam spatula, a wooden or metal spatula, a cotton roll or a curette.

The use of fairly rigid brushes allows deeper epithelial cell layers to be sampled.

The sample is then gently spread on a slide, then dried and protected before being sent to the laboratory

This examination is indicated in certain dermatoses such as candidiasis, and does not find any indication in precancerous lesions; the sample will only reveal normal-looking cells, or the cancer may remain silent on the smear.

Brush sampling:

The cytobrush explores the entire height of the epithelium up to the lamina propria. It requires no local anesthesia and causes little or no pain or bleeding.

It responds to the same criticisms: too many false negatives and no architectural analysis of the tissues.

Tumor biomarkers P53 phosphoprotein:

P53 overexpression has been reported in 11–80% of cases of head and neck cancer.

According to some, detection of P53 is possible in dysplastic mucosa and even in histologically normal mucosa in the vicinity of cancer.

Immunofluorescence : looking for specific antibodies.
Photographic assessment : allows you to assess progress.

Clinical forms:
Leukoplakia:

Currently, leukoplakia is defined as a white patch of questionable risk excluding other known pathologies that do not carry an increased risk of cancer (according to Warnakulasuriya et al, 2007).

Leukoplakia is a purely clinical term and has no histological specificity.

Histologically, it may correspond to atrophy, hyperplasia and possibly dysplasia.

It is currently agreed to distinguish between two forms of leukoplakia:

-The homogeneous shape: no variation in its color and/or thickness

-The non-homogeneous form: presence of areas of different thicknesses, associated with erythema, erosion or ulceration.

It has a poorer prognosis than the homogeneous form.

– Histology:

Histologically, leukoplakia is not specified.

Histologically, leukoplakia involves epithelial hyperplasia (acanthosis and/or papillomatosis) of varying intensity with hyperkeratosis explaining the white color of the lesion, and which has led some authors to use the term “keratosis”

🙐 Hyperkeratosis,

🙐 A +/- pronounced epithelial dysplasia,

🙐 Hyperacanthosis and lymphoplasmacytic infiltrate in the chorion;

🙐 The basement membrane is still intact and respected.

Differential diagnosis:
Traumatic keratosis
Oral lichen planus
Dysplasia or transformation on lichen planus
Intraepithelial carcinoma
Discoid lupus erythematosus
Candidal keratosis

Treatment :
Elimination of risk factors
Surveillance
Surgical excision
Other therapies: CO2 laser
Therapeutics to avoid: Oral vitamin A, cryotherapy, retinoids

Erythroplakia:

Definition :
It is a precancerous lesion, which manifests as a plaque or a red, non-specific area that cannot be clinically and anatomopathologically classified in any disease.
Its definition by the WHO has not been changed since 1978.
It is a velvety, bright red area, most often uniform without any trace of keratinization, often very extensive but with a clear limit, which distinguishes it from erythema
inflammatory.

Histopathology:
Maximum epithelial atrophy at the level of the roof of the papillae of the chorion and devoid of surface keratinization,
Abnormalities of the chorion,
Epithelial dysplasia lesions characterized by the presence of large cells with vesicular and nucleolated nuclei, clear cytoplasm and sometimes dyskeratotic.

Differential diagnosis:
dermatoses, such as lichen planus erythematosus, lupus or cicatricial pemphigoid.
chronic bacterial or mycotic infections (candidiasis, histoplasmosis).
reactions to physical or chemical attacks,
hypersensitivity immune reactions
erythematous areas symptomatic of anemia, hemangiomas or early lesions of Kaposi’s sarcoma.
Treatment :
Treatment and prognosis depend on histological characteristics.
Surgical excision is recommended for erythroplasias with severe epithelial dysplasia or at the carcinoma in situ stage and regular follow-up for stages below moderate dysplasia

Reverse smoker’s palatal lesion:

This condition is specific to populations who smoke with the glowing end of the cigarette in their mouth.

The lesions are palatal, red, white or mixed.

Chronic actinic cheilitis:

Actinic cheilitis is mainly observed in men over 45 years of age whose profession exposes them for several years to the sun and bad weather (farmers, mountaineers, sailors), especially if their phototype is lighter (blond or redheaded).
Actinic cheilitis more frequently affects the lower lip, which is more exposed to UV rays. These cause alterations in the DNA of basal keratocytes and a reduction in their mitotic activity.

Treatment :
It must be above all prophylactic.
Avoid prolonged and repeated exposure. Sun protection clothing
Initially, local applications of 5-fluorouracil (Efudix®) and superficial destruction with CO2 laser can be proposed.
The treatment of pre-carcinomatous cheilitis is surgical (vermillectomy).

Lichen planus:

Lichen planus is a benign, chronic inflammatory skin and mucosal disease.
The initial clinical description was made by Wilson in 1869 and the histological description by Dubreuil in 1906. It is characterized by a keratinization disorder whose clinical aspects are polymorphic.
Chronic liver disease, cirrhosis, viral hepatitis
Graft versus host disease
Certain medications: NSAIDs, antihypertensives, diuretics, etc.
Dental products: amalgam, nickel, cobalt, etc.
Neurological and psychosomatic factors
Tobacco, alcohol.

Clinical forms:
Clinical forms showing marked activity observed mainly during a more or less recent LP, or in a flare-up.
-Clinical forms indicating often reduced activity observed mainly during a more or less old LP, or the post-lichen state.
-Post-lichenian state.
Lichen planus in a network:
White, streak-like lesions, symmetrical, bilateral and asymptomatic.
The cheek+++
- Lichen planus erythematosus
The erythematous aspect is predominant, the white streaks of the
LP less obvious, sometimes reduced to vague marbling
Erosive lichen planus:

The white streaks of the LP are predominant. The more erosions
or less painful
often limited by
a very fine furrow, their contours are
angular, their base is yellowish fibrinous, their edge erythematous
Bullous lichen planus:

It precedes the erosive form, the roof of the bubble is then
sometimes found on the outskirts
Atrophic lichen planus:

The atrophic form concerns
old LPOs, evolving since
at least 5 to 10 years, sometimes several decades, but
still active, with more or less
less erythema.
Epithelial atrophy occurs
translated by a depapillation of the tongue, often of seat
marginal and symmetrical, and/or by the loss of papillary relief
“orange peel” with smooth appearance of the gum.
Hyperkeratotic and/or verrucous lichen planus:
Hyperkeratosis predominates, sometimes fine, sometimes thick and white, and is located in the areas of predilection of the
LPO.

Pigmented lichen planus (or nigricans):
The blackish-grey pigmentation of the pigmented LP is the consequence of the attack by lymphocytes on the basal layer of the epithelium, which leads to a migration of the melanin pigment into the chorion
Differential diagnosis:

White lesions:

Leukoplakia
White lines in network
Chronic discoid lupus erythematosus

Erythematous and erosive lesions:

oral pemphigus vulgaris
Oral manifestations of erythema multiforme

Treatment :
Quitting alcohol and tobacco
Oral cavity restoration
Erosive lichen planus:
Local corticosteroid therapy
In the absence of results: retinoid which is a derivative of vitamin A
Severe erosive forms or those not responding to local therapies 🡪 General corticosteroid therapy, cyclosporine A, thalidomide
The occurrence of mild to moderate dysplasia requires localized surgical excision.
When lichen becomes complicated by cancer, treatment is surgical combined with chemotherapy. Radiotherapy is not recommended .

Discoid lupus erythematosus

Definition :
Discoid lupus erythematosus is a chronic autoimmune condition of unknown etiology in which the skin’s immune system is abnormally targeted, resulting in inflammation and rash .
Treatment :
Corticosteroids are prescribed to reduce the immune system’s response.
Topical creams that are effective in reducing spread and severity.
Another alternative is a cortisone injection directly into the lesions.
Antimalarial drugs are also effective treatments for discoid lupus.
At the level of the oral cavity:
Often the lesions are asymptomatic
Therapeutic abstention
In the case of troublesome oral lesions (erosions), local corticosteroid therapy may be prescribed.

Dyskeratosis congenita :

Dyskeratosis congenita, or Zinsser-Engman-Cole syndrome, is a very rare autosomal recessive disease, the classic form of which affects boys at the latest around the age of 10.
It was initially defined as constitutional bone marrow aplasia with abnormalities of the skin and mucous membranes.
Indeed, the classic diagnostic triad combines reticulated pigmentation of the skin, mucosal leukoplakia and nail dystrophy.
Malignant degeneration of these oral lesions is to be feared after 10 to 15 years of evolution, hence the need for periodic examinations to detect signs of transformation.
No effective treatment has been reported, apart from long-term retinoids, which are very poorly tolerated at effective doses.

Epidermolysis bullosa:

It is a rare genetic disease that is extremely painful and disabling, transforming the skin, and sometimes the mucous membranes, into a giant wound.
This disease is due to an anomaly in one of the genes involved in the production of proteins that allow cohesion between the different layers of our skin.
These chronic wounds can lead to bacterial superinfections and also skin cancers. They are the leading cause of death in adults.
But these children also often suffer from malnutrition and growth retardation: firstly because they have difficulty feeding due to damage to the mucous membranes.
The only real treatment for this disease is dressings to disinfect the wounds and help them heal. These sessions are long and sometimes so painful that some children are given morphine.
The only hope for these children remains gene therapy, which would involve repairing the defective gene.
The idea is then to be able to graft cells from the genetically corrected epidermis or dermis. Several European teams are working on this, but unfortunately, we are still far from a concrete application.

Conclusion :

Despite the progress made in oral dermatology in recent years, the diagnosis of precancerous lesions and oral cancers remains late, often leading to a poor prognosis .

Bibliography

Bahbah. S et al. Potentially malignant lesions of the oral mucosa. Web J du Dentiste; 2015
Benslama. L. Potentially malignant disorders of the mucosa: nomenclature and classification. RevStomatol Chir Maxillofac 2010; 111:208-212.
Reychler, H et al. Screening and diagnosis of precancerous lesions of the oral mucosa. RevStomatol Chir Maxillofac.2010;111:203-207.

Potentially malignant diseases of the oral mucosa

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Potentially malignant diseases of the oral mucosa