POTENTIALLY MALIGNANT LESIONS OF THE ORAL MUCOSA

POTENTIALLY MALIGNANT LESIONS OF THE ORAL MUCOSA

Plan : 

    Introduction

1. Definition 

Precancerous lesions 

Precancerous conditions 

2.  Anatomical and histological reminders  

2.1 The epithelium 

2.2 The basement membrane  

2.3 The Chorion

3. Etiological factors 
4. Clinical study

4.1 Leukoplakia 

4.2 lichen plan 

4.3 Submucosal fibrosis

4.5 Erythroplakia

4.6 Chronic actinic cheilitis

5. Precancerous conditions 
6. Therapeutic support

     Conclusion 

POTENTIALLY MALIGNANT LESIONS OF THE ORAL MUCOSA

Introduction :

Oral cavity cancers have common features, including: 

•  Histology: frequency of squamous cell carcinomas 
•  Their etiologies: alcohol and tobacco poisoning

One of the factors that explains this poor prognosis is the delay in diagnosis. 

“This delay is not acceptable because it significantly changes the prognosis, while requiring more aggressive and more mutilating treatment.” 

Also, better results will only be obtained in the fight against these cancers through screening , diagnosis and early treatment of at-risk lesions , precancerous lesions and early cancers. 

 Similarly, monitoring of these lesions should allow early treatment of cancers. 

It is true that in almost 17% of cases, squamous cell carcinoma is preceded by chronic lesions, but most often it occurs on an apparently healthy mucosa.

1. Definition:

 Precancerous lesions:

or potentially malignant lesion according to the WHO, “is a morphologically altered tissue in which cancer will develop more readily than in healthy tissue”. These lesions meet three criteria: it must precede the onset of cancer, be related to cancer, but be different from cancer.

  Precancerous conditions:

  A precancerous condition is defined by the WHO as a “generalized condition associated with a significantly increased risk of cancer.”

             Keratosis:

This term refers to any white lesion of the oral mucosa secondary to an abnormality of keratinization of the epithelium.

The term keratosis must be supplemented by a qualifier specifying its etiology; we therefore speak of:

Galvanic keratosis

Infectious keratosis 

Thermal keratosis

Drug-induced keratosis

Traumatic keratosis

2. Anatomical and histological reminders: 

            It is the mucous membrane that covers the inner wall of the lips and the oral cavity; it is continuous with the skin at the vermilion junction, the outer side of the lips.

It continues behind with the digestive (pharynx) and respiratory (larynx) mucosa.

The oral cavity is entirely lined by a mucosa resting on the connective, muscular and bony planes. The mucosa consists of a lining epithelium resting on the lamina propria through a basement membrane. 

2.1. The epithelium:

It is paved, multi-stratified, keratinized or not depending on the location. It includes:

• A germinative cell layer (stratum germinatum), backed by the basement membrane. Consisting of cubic cells on one or two layers; these cells are the least differentiated of the epithelium. This layer also contains melanocytes and Langerhans dendritic cells.
• A Malpighian mucous body (stratum spinosum). The cells are larger and begin to flatten (this phenomenon becomes more pronounced as the cells migrate towards the surface.
• A granular layer (stratum granulosum) which is only present in areas of keratinized mucosa; is made up of large, flattened cells containing grains of keratohyalin (sulfur protein which will give keratin). 
• A superficial layer whose cells desquamate (stratum corneum). In this layer, the elongated, disunited cells contain organelles, their nucleus more or less degenerated. 

POTENTIALLY MALIGNANT LESIONS OF THE ORAL MUCOSA

2.2 Basement membrane:

It constitutes the interface between the epithelium and the chorion. It is a thin strip which follows the undulations of the epithelial ridges.

The basement membrane plays an important role, filtering exchanges, allowing the attachment of keratinocytes, influencing their differentiation and renewal and its rupture is decisive in the invasion of cancers.

2.3.  The Chorion

It is made up of fibroblastic connective tissue with varied aspects depending on the territory. It is loose, richly vascularized in its superficial or papillary part. It contains mixed accessory salivary glands (sero-mucous) or mucous and nerve endings.

3. Etiological factors: 

 The main causes are:

• Tobacco and alcohol: Tobacco and excessive alcohol consumption increase the risk of oral cancer. The combination of the two poses a greater risk than the consumption of either alone.
• Sun: Prolonged and unprotected exposure to the sun’s rays poses a risk of lip cancer.
• Age: Precancerous lesions are more common in older people because of their longer exposure to risk factors.
• Hygiene: Poor oral hygiene contributes to the development of precancerous lesions. 
• Diet: While a healthy diet reduces the risk of cancer, a poor diet, on the other hand, promotes its appearance in one form or another.
• Chronic trauma (prosthesis).

4. Clinical study

4.1. LEUKOPLASIA:

Definition : 

“A predominantly white lesion of the oral mucosa and does not correspond to any other known nosological entity; it is a real precancerous lesion”

    It is a white lesion of the oral mucosa, which cannot be detached by scraping. The diagnosis of leukoplakia can be attributed to any white lesion, provisionally.

   Tobacco is the only etiopathogenic factor currently retained, by definition. 

The different definitions of leukoplakias attributed over the past decades (Warnakulasuriya et al, 2007). (6)

WHO (1978)	A white spot or plaque that cannot be clinically or histologically assimilated to any other pathology.
First International Conference on Oral Leukoplakia. Malmo, Sweden.	A white spot or plaque that cannot be clinically or histologically assimilated to any other disease and that is not associated with any physical or chemical causative agent except tobacco.
InternationalSymposiumUppsala, Sweden	A predominantly white lesion of the oral mucosa that cannot be assimilated to any other definable pathology.
WHO (1997)	A predominantly white lesion of the oral mucosa that cannot be assimilated to any other definable lesion.
Warnakulasuriya et al (2007)	The term leukoplakia should be used to recognize white spots of questionable risk excluding other known pathologies that do not carry an increased risk of cancer.

Clinical aspects:

  – The clinical aspect of homogeneous leukoplakia: 

• Spot with a predominantly uniform white appearance, slightly or not at all raised, 
• Hyperkeratotic surface often in mosaic form, 
• Does not come off by scratching,
• Without or with discreet erythema and uniform shape without erosion.

POTENTIALLY MALIGNANT LESIONS OF THE ORAL MUCOSA

  – Inhomogeneous leukoplakia: manifests itself either in the form of:

• Whitish, raised, rounded nodule with reddish or whitish growths, 
• Either in the form of a warty beach that is always white, pearly, sometimes with cracks, 
• Or even in the form of a lesion combining an erythematous appearance with a whitish appearance, with very irregular relief and edges.

POTENTIALLY MALIGNANT LESIONS OF THE ORAL MUCOSA

Histology: The definitive diagnosis is confirmed histologically. Leukoplakia is characterized by hyperkeratosis, more or less pronounced epithelial dysplasia, hyperacanthosis and a lymphoplasmacytic infiltrate in the chorion; the basement membrane is always intact and respected.

Proliferative verrucous leukoplakia: 

• Very degenerative, 
• It is multifocal, more or less homogeneous, exophytic. 
• It occurs mainly in older women and has no etiology. 
• It almost always turns into carcinoma.

Evolution of leukoplakia: 

• These lesions can either regress, which is often the case after stopping smoking, or persist. 
• They become malignant in 5 to 20% of cases (Paré and Joly 2017). 
• Whatever the type of injury, the doctor must guide his patient to reduce the risk factors. 
• Treatment of single, small homogeneous lesions involves excision, lesion analysis, and regular monitoring. 
• When the lesion is extensive, biopsies are performed regularly although they cannot allow the entire tissue to be analyzed systematically. 
• When the lesion is inhomogeneous, excision is often preferred (Piette and Reychler 2016). 

4. 2. BUCCAL LICHEN PLATO:

  – Lichen planus is a chronic inflammatory skin and mucosal condition that can affect the skin and appendages (hair, nails), and the malpighian mucosa (especially the oral mucosa, but also the genital and anal mucosa).

Clinical studies:

• Oral lichen planus is present in about 40% of patients with cutaneous lichen planus; oral lichen planus without cutaneous lichen planus is rarer. It predominates between the ages of 30 and 70 years.

Clinical forms:

• According to the World Health Organization classification in 1997, LPB includes the following clinical forms: reticulate, erosive, and atrophic.
• The posterior-inferior jugal region represents the selective site, often with bilateral and grossly symmetrical involvement. 

Reticulated lichen planus

• Discovered during hypersensitivity or tingling when in contact with food.
• The basic lesion is a papule.
• Recent reticular lesions consist of dots confluent in sheets or plaques.
• The appearance varies depending on the seat 

POTENTIALLY MALIGNANT LESIONS OF THE ORAL MUCOSA

Erosive lichen planus:

• It appears as painful, bright red, varnished erosions with an edematous base, of variable size, sometimes rounded or oval or irregular in shape, slightly protruding.
• They are most often located on the inner side of the cheek, in the posterior half, and in the pelvic-lingual grooves, on the dorsal side of the tongue, the lateral edges of the tongue and on the attached gingiva.
• These erosive forms are rarely isolated and one should always look for keratotic plaques resembling lichen on the cheek or on the back of the tongue.

Histology:

Histopathologically, lichen planus presents a pathognomonic physiognomy:

• Parakeratotic hyperkeratosis with islands of orthokeratosis.
• irregular hypergranulosis.
• hyperacanthosis with interpapillary extensions tapered in a “sawtooth” shape.
• arcuate cut of the basal, lymphocytic infiltrate of the upper part of the chorion nibbling away at the basal; arrangement called “lichenoid”.

Evolution:

Slow, extending over years, sometimes even decades, with periods of quiescence and growth.

In the vast majority of cases, lichen planus has a benign course, but malignant transformation can occur in a small proportion, usually estimated at 1%. These transformations occur mainly in chronic, atrophic or erosive forms, justifying monitoring and treatment.

4. 3. Submucosal fibrosis

 Submucosal fibrosis is a chronic condition of the oral cavity, most commonly seen in India but also in other parts of Asia. 

It is believed to be linked to dietary habits of spicy food intake, vitamin B deficiencies, betel nut chewing and smoking.

 The disease is most common between the ages of 20 and 40. 

Clinically, submucosal fibrosis presents with intense burning sensation and vesicle formation (especially on the palate and tongue) followed by superficial ulcerations.

 The fibrous stage results in a whitening of the mucosa which appears smooth, atrophic and gradually loses its elasticity. Tongue mobility is limited and areas of papillary atrophy are observed. Mouth opening, chewing and swallowing become difficult. Submucosal fibrosis is well recognized as a potentially malignant condition. There is no specific treatment.

4.4 . Erythroplasia

 Erythroplakia of the oral mucosa is still considered the lesion with the highest potential for malignant transformation. 

The definition used by the WHO is: “a chronic, red mucous macule that cannot be linked to another diagnosis and cannot be attributed to a traumatic, vascular or inflammatory cause”. This is a diagnosis of exclusion. Erythroplakia defines a purely clinical lesion. 

The most common site is the floor of the mouth in men, the alveolar gingival mucosa and the mandibular sulci in women. The soft palate is also often reported. The typical appearance is a velvety, bright red area, most often uniform without trace of keratinization, often very extensive but with a clear limit.

4.5 Chronic actinic cheilitis:

• Mostly seen in men over 45 years old, and due to exposure to the sun 
• Predominance in the lower lip, more exposed to ultraviolet rays.
• Erythematous macule 🡺 desquamative and fissural hyperkeratotic cheilitis, punctiform hemorrhages.
• Poor hygiene + smoking accentuate the lesions.

POTENTIALLY MALIGNANT LESIONS OF THE ORAL MUCOSA

5. Precancerous conditions:

• Xeroderma pigmentosum (XP) 
•    HIV infection:
• Chemotherapy 
•  Radiotherapy 
•  Dyskeratosis congenita (Zinsser-Engman-Cole syndrome) 
•  Plummer-Vinson syndrome (or Kelly-Patterson)
•  Gougerot-Sjögren syndrome (dry syndrome) 
•  Fanconi anemia 

6. Therapeutic support 

Management begins with screening for these lesions during each routine examination of the oral cavity, the ease of access of which allows for early diagnosis and close monitoring.

 The role of the dentist is to

• Detect the lesion and specify its nature even roughly in order to classify it
• Alert the patient to the danger of such injury. 
• Draw the patient’s attention to the need to eliminate carcinogenic factors (tobacco, alcohol) and warn him of the role of these in maintaining and possibly worsening the intraoral pathological manifestation. 

Therapeutic indication:  

Leukoplakia:

• Good oral hygiene should be recommended, 
• A restoration of the oral cavity, 
• The elimination of any physical, chemical or mechanical source of irritation, 
• Stopping smoking intoxication.

 Lichen planus: 

Treatment of oral lichen planus is much more difficult than that of cutaneous lichen planus because of the extremely chronic and recurrent nature of the lesions. 

Asymptomatic forms: 

• Good oral hygiene should be recommended, 
• A restoration of the oral cavity, 
• The elimination of any physical, chemical or mechanical source of irritation, 
• Stopping smoking (rarely associated).
• Treatment of general diseases that may be related to the occurrence of LPB is necessary. These may include diabetes, high blood pressure, neoplasia, liver disease
• Regular monitoring should be maintained.
• Symptomatic forms: the previous measures are of course necessary, but must be associated with drug, physical or surgical treatment.
• The combination of local and general corticosteroids appears to be more effective.

• Local corticosteroid therapy will be preferred from the outset to general corticosteroid therapy in erythematous and erosive forms. 
• General corticosteroid therapy (prednisone 1 mg/kg/day) is reserved for severe recurring forms and in cases of resistance to local treatments. The dosage is only gradually reduced when the lesions have disappeared.
• Cyclosporine in BB or ointment form
• immunomodulators (Tacrolimus, Pimecrolimus)
• The occurrence of mild to moderate dysplasia on lichen lesions requires localized surgical excision.

 Erythroplakia:   

Most often, surgical excision of the lesion is indicated, ensuring careful monitoring after treatment.

Submucosal fibrosis:

There is no specific treatment, and general or local corticosteroids only have a temporary effect.

POTENTIALLY MALIGNANT LESIONS OF THE ORAL MUCOSA

CONCLUSION:  

Precancerous lesions are a priori benign lesions, however the risk of malignant transformation is possible.

Early detection by a meticulous and systematic examination of the entire oral cavity allows them to be revealed even before there are any symptoms, and this has been reinforced by the advent of new examination techniques.

Regular monitoring of these lesions allows early treatment and therefore a better prognosis.

Bibliographic references: 

1. Ben Slama L. Potentially malignant disorders of the oral mucosa: nomenclature and classification. RevStomatolChirMaxillofac 2010;111:208-212.
2. Bombeccari GP et al. Oral lichen planus and malignant transformation: a longitudinal cohort study. Oral Surg Oral Med Oral Pathol Oral RadiolEndod. 2011;112(3):328-334.
3. Gupta PC, Mehta FS, Daftary DK, et al. Incidence rates of oral cancer and natural history of oral precancerous lesions in a 10-year follow-up study of Indian villagers. Community Dent Oral Epidemiol 1980;8:287-333.
4. Hardy H, Persac S, Péron J.-M. Erythroplasia of the upper aerodigestive tract. RevStomatolChirMaxillofac 2010;111:213-215.
5. Lombardi T, Samson J. Malignant transformation in actinic cheilitis 
6. chronic in a redheaded subject. Med Buccale Chir Buccale 2013;19(4):273-274.
7. Warnakulasuriya S, ReibelJ, BouquotJ, DabelsteenE. Oral epithelial dysplasia: classification systems: predictive value, utility, weaknesses and scope for improvement. J Oral Pathol Med 2008;37:127-133.

Dental crowns are used to restore the shape and function of a damaged tooth.
Bruxism, or teeth grinding, can cause premature wear and often requires wearing a retainer at night.
Dental abscesses are painful infections that require prompt treatment to avoid complications. Gum grafting is a surgical procedure that can treat gum recession. Dentists use composite materials for fillings because they match the natural color of the teeth.
A diet high in sugar increases the risk of developing tooth decay.
Pediatric dental care is essential to establish good hygiene habits from an early age.
 

POTENTIALLY MALIGNANT LESIONS OF THE ORAL MUCOSA