Potentially Malignant Oral Disorders

*Márcio Campos Oliveira, Igor Ferreira Borba de Almeida, Almira Oliveira Pereira and Maria da Conceição Andrade*

#### **Abstract**

Most cancerous lesions are derived from potentially malignant oral disorders (PMOD). The World Health Organization (WHO) points out the following lesions as the main PMOD: leukoplakia, erythroplakia, actinic cheilitis, submucous fibrosis, and lichen planus. Leukoplakias are white plaques or spots that cannot be removed by scraping, and these lesions aren't characterized clinically or pathologically like any other diseases. Erythroplakias are red lesions of the oral mucosa that also cannot be characterized clinically or pathologically as another definable disease. Actinic cheilitis is an injury that affects the vermilion of the lower lip and has this anatomical location due to its etiological factor, which is the progressive and excessive exposure to ultraviolet rays of sunlight. Submucous fibrosis is a chronic disease of the mouth that presents as an inflammatory subepithelial reaction, followed by an alteration in the submucous fibroelastic tissue. Lichen planus is a dermatological disease characterized by white patches or striations, symmetrical and bilateral, and its treatment is basically done with topical corticosteroids.

**Keywords:** potentially malignant oral disorders, leukoplakia, erythroplasia, actinic cheilitis, lichen planus

#### **1. Introduction**

Head and neck cancer is a worldwide public health problem, and according to the International Agency for Research on Cancer (IARC) in 2018, 1,454,892 new cases of head and neck cancer worldwide have been estimated. When all the sites involving the head and neck region added, these tumors occupy the third place, behind only the lung tumors (2,093,876) and the breast (2,088,849) [1]. By analyzing the sexes separately, head and neck tumors are the fourth most common cause of cancer in men (796,946 cases), behind lung, prostate, and colorectal cancer. In women, they are also the fourth most common cause (657,966 cases), behind breast, colorectal, and lung cancer, and thyroid tumors are the most frequent in this population (436,344 cases). In Brazil, according to the National Cancer Institute (INCA), there is an estimated 11,200 new cases of cancer of the oral cavity in men and 3,500 in women for each year of the 2018–2019 biennium, placing this neoplasm in fifth place in the prevalence [2].

The incidence can change by region of the world. In developing countries, in men, lip and oral cavity cancer alone is the third in incidence, partly because of the high disease rate in India, which accounts for 36% of the population of countries with low human development index (IDH) [2].

Understanding the world statistics on cancer, more specifically on head and neck cancer, is essential in order to propose measures of prevention and early diagnosis, such as anti-smoking policies, HPV vaccination, and improvement of the oral health and diet of the population. Such measures would have a significant impact on the incidence and mortality of this disease [2].

Among the risk factors, potentially malignant oral disorders have a prominence, since they are generally the first indication of the disease [3]. The World Health Organization (WHO), in its latest publication, has defined PMSD as clinical presentations that carry a risk of developing oral cavity cancer, a clinically defined precursor lesion or clinically normal oral mucosa [4]. The WHO identifies as PMOD the following disorders: erythroplakia, erythroleukoplakia, leukoplakia, oral submucous fibrosis (OSF), congenital dyskeratosis, smokeless tobacco keratosis, palatine lesions associated with reverse smoking, chronic candidiasis, lichen planus, discoid lupus erythematosus, glossitis syphilitic, and actinic cheilitis. In this chapter, we will discuss the most common PMODs with the highest potential for malignant transformation, which are leukoplakias, erythroplasias, oral lichen planus, actinic cheilitis and oral submucous fibrosis [1, 4].

## **2. Leukoplakia**

According to the WHO, leukoplakia is defined as a white, variable-risk plaque, excluding (other) known diseases or disorders that do not carry an increased risk of cancer; therefore, the nomenclature is restricted only to the clinical aspect and histological changes. Due to the fact that its clinical diagnosis is basically made by exclusion, this disorder makes a differential diagnosis with other well-known lesions and with very similar clinical characteristics such as pseudomembranous candidiasis, Lichen planus, leukoedema, and lupus erythematosus [5]. The specific causative factors of leukoplakia are still unknown; however, it is known that the smoking habit is closely linked to the progression of leukoplakia. In addition, other risk factors have been associated with the development of this disorder, the consumption of alcohol that would act synergistically with tobacco, trauma, as well as infestations of microorganisms such as human papillomavirus (HPV) [6].

Oral leukoplakia is the most common PMOD, presenting a prevalence of 1% and an annual malignant transformation risk of 2%. It is found in equal proportion between men and women, rarely occurs in the first two decades of life, and is more prevalent among individuals, and this is their main etiological factor. The anatomical sites in which about 70% of the leukoplakia are found are jugal mucosa, gingiva, and vermillion of the lip; however, lesions located on the tongue and floor of the mouth contribute to over 90% of the cases that present some level of dysplasia or even a carcinoma [6–8].

Clinically the leukoplakias are subdivided into homogeneous and nonhomogeneous. Homogeneous leukoplakias are characterized as uniformly flat and thin lesions that have a low percentage of malignant transformation, as well as spontaneous regression after elimination of risk factors, especially smoking habit (**Figure 1**) [3, 9]. Nonhomogeneous leukoplakias are described as white and red lesions (erythroleukoplakias), which may appear irregularly flat or nodular, and are subdivided into a variety of subtypes, such as erythematous or speckled, nodular and verrucous (**Figure 2**). Verrucous leukoplakia, one of the most misdiagnosed subtypes of nonhomogeneous leukoplakia because of its challenging clinical appearance, although presenting as a uniform white lesion, its verrucous texture is the characteristic that differentiates it from homogeneous leukoplakia (**Figure 3**) [10]. Proliferative

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**Figure 3.**

verrucous leukoplakia (PVL) is a very rare form and falls between nonhomogeneous leukoplakias and is a subtype of verrucous leukoplakia. It's a distinct, multifocal, progressive course associated with high rates of recurrence and malignant transformation [4]. PVL mainly affects middle-aged women with no harmful habits such as smoking and presents clinically as a diffuse and homogeneous white

*Exuberant verrucous leukoplakia in the alveolar ridge. Source: author's file.*

*Nonhomogeneous leucoplakia on the back and lateral edge of the tongue. Source: author's file.*

*Potentially Malignant Oral Disorders*

**Figure 1.**

**Figure 2.**

*DOI: http://dx.doi.org/10.5772/intechopen.88580*

*Homogeneous leucoplakia on the floor of the mouth. Source: author's file.*

*Potentially Malignant Oral Disorders DOI: http://dx.doi.org/10.5772/intechopen.88580*

#### **Figure 1.**

*Oral Diseases*

Understanding the world statistics on cancer, more specifically on head and neck cancer, is essential in order to propose measures of prevention and early diagnosis, such as anti-smoking policies, HPV vaccination, and improvement of the oral health and diet of the population. Such measures would have a significant impact

Among the risk factors, potentially malignant oral disorders have a prominence,

According to the WHO, leukoplakia is defined as a white, variable-risk plaque, excluding (other) known diseases or disorders that do not carry an increased risk of cancer; therefore, the nomenclature is restricted only to the clinical aspect and histological changes. Due to the fact that its clinical diagnosis is basically made by exclusion, this disorder makes a differential diagnosis with other well-known lesions and with very similar clinical characteristics such as pseudomembranous candidiasis, Lichen planus, leukoedema, and lupus erythematosus [5]. The specific causative factors of leukoplakia are still unknown; however, it is known that the smoking habit is closely linked to the progression of leukoplakia. In addition, other risk factors have been associated with the development of this disorder, the consumption of alcohol that would act synergistically with tobacco, trauma, as well as

infestations of microorganisms such as human papillomavirus (HPV) [6].

Oral leukoplakia is the most common PMOD, presenting a prevalence of 1% and an annual malignant transformation risk of 2%. It is found in equal proportion between men and women, rarely occurs in the first two decades of life, and is more prevalent among individuals, and this is their main etiological factor. The anatomical sites in which about 70% of the leukoplakia are found are jugal mucosa, gingiva, and vermillion of the lip; however, lesions located on the tongue and floor of the mouth contribute to over 90% of the cases that present some level of dysplasia or

Clinically the leukoplakias are subdivided into homogeneous and nonhomogeneous. Homogeneous leukoplakias are characterized as uniformly flat and thin lesions that have a low percentage of malignant transformation, as well as spontaneous regression after elimination of risk factors, especially smoking habit (**Figure 1**) [3, 9]. Nonhomogeneous leukoplakias are described as white and red lesions (erythroleukoplakias), which may appear irregularly flat or nodular, and are subdivided into a variety of subtypes, such as erythematous or speckled, nodular and verrucous (**Figure 2**). Verrucous leukoplakia, one of the most misdiagnosed subtypes of nonhomogeneous leukoplakia because of its challenging clinical appearance, although presenting as a uniform white lesion, its verrucous texture is the characteristic that differentiates it from homogeneous leukoplakia (**Figure 3**) [10]. Proliferative

since they are generally the first indication of the disease [3]. The World Health Organization (WHO), in its latest publication, has defined PMSD as clinical presentations that carry a risk of developing oral cavity cancer, a clinically defined precursor lesion or clinically normal oral mucosa [4]. The WHO identifies as PMOD the following disorders: erythroplakia, erythroleukoplakia, leukoplakia, oral submucous fibrosis (OSF), congenital dyskeratosis, smokeless tobacco keratosis, palatine lesions associated with reverse smoking, chronic candidiasis, lichen planus, discoid lupus erythematosus, glossitis syphilitic, and actinic cheilitis. In this chapter, we will discuss the most common PMODs with the highest potential for malignant transformation, which are leukoplakias, erythroplasias, oral lichen planus, actinic

on the incidence and mortality of this disease [2].

cheilitis and oral submucous fibrosis [1, 4].

**2. Leukoplakia**

even a carcinoma [6–8].

**76**

*Homogeneous leucoplakia on the floor of the mouth. Source: author's file.*

#### **Figure 2.**

*Nonhomogeneous leucoplakia on the back and lateral edge of the tongue. Source: author's file.*

**Figure 3.** *Exuberant verrucous leukoplakia in the alveolar ridge. Source: author's file.*

verrucous leukoplakia (PVL) is a very rare form and falls between nonhomogeneous leukoplakias and is a subtype of verrucous leukoplakia. It's a distinct, multifocal, progressive course associated with high rates of recurrence and malignant transformation [4]. PVL mainly affects middle-aged women with no harmful habits such as smoking and presents clinically as a diffuse and homogeneous white

**Figure 4.** *Proliferative verrucous leukoplakia affecting the hard palate and alveolar ridge. Source: author's file.*

plaque at the onset, which gradually becomes erythematous and exophytic with the progression of the disorder, affecting mainly the gingiva, alveolar mucosa, and palate (**Figure 4**) [4, 6, 11].

Regarding the histopathological characteristics of leukoplakia, a thick layer of keratin in the epithelium (hyperkeratosis) is present, with or without thickening of the thorny layer (acanthosis). It is still possible to observe in some leukoplakia the presence of hyperkeratosis with epithelial atrophy. Generally, leukoplastic lesions do not exhibit epithelial dysplasias, but the presence of them would be a worrying sign for a possible malignant transformation, a fact that is most observed among nonhomogeneous leukoplakias [4, 6].

The diagnosis of leukoplakia is basically by excluding other diseases or disorders that do not carry increased risk of malignant transformation. In order to perform an accurate diagnosis of leukoplakia, different levels of leukoplakia must be followed by certainties (factor C) that lead us from a primary clinical diagnosis to the definitive diagnosis based on the histopathological examination of the lesion [4, 6].

Thus, in the van der Waal factor, C1 evidence is obtained in a single visit, in the first contact between the dental surgeon and patient, applying only palpation and inspection as the primary means for diagnosis, in addition to anamnesis to collect data that may make up this provisional clinical diagnosis. In the certainty factor C2, evidence is obtained from negative results of elimination of etiological factors such as mechanical irritation, during a period of follow-up of 2–4 weeks or in the absence of any suspicious etiological factors (definitive clinical diagnosis). Factor C3 is similar to C2 but complemented by incisional biopsy (provisional histopathological diagnosis), and C4 is the evidence obtained from surgical excision of the lesion followed by histopathological examination of the resected specimen (definitive histopathological diagnosis) [11, 12]. Performing biopsy in the diagnosis of leukoplakia is important because only through this examination it is possible to determine whether to perform the histopathological diagnosis or not of epithelial dysplasias, thus guiding the treatment [12].

The treatment of leukoplastic lesions is dependent on the result found in the histopathological examination; in this way, the treatment plan is often individualized according to the histological findings, such as the degree of dysplasia found in the epithelium. The WHO in its latest manual for the classification of head and neck tumors (2017) defines dysplasias as architectural and cytological epithelial changes caused by an accumulation of genetic alterations associated with an increased risk of progression to squamous cell carcinoma. Therefore, in lesions that present mild dysplasia or do not present dysplasia, more conservative measures should be taken,

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**Figure 5.**

*Potentially Malignant Oral Disorders*

patients every 6 months [10].

**3. Erythroplakia**

*DOI: http://dx.doi.org/10.5772/intechopen.88580*

carcinoma or even relapse of the leukoplakial lesion [6, 7, 10].

such as clinical follow-up of the lesion every 6 months throughout life, evaluation of the need for new biopsies, and end of smoking [3, 10]. In leukoplakias that present moderate or severe dysplasia/carcinoma in situ, it is recommended that the lesion be removed completely, if possible, or by CO2 laser therapy. However, even with the surgical treatment, there appears to be no reduction in the risk of developing a

Regarding the prognosis of leukoplastic lesions, recurrence rates after any type of treatment can range from almost 0 to 30%, which means regular follow-up of

Erythroplakia is defined as "a red spot that can't be characterized clinically or pathologically like any other definable disease" [4]. When a mixture of red and white changes occurs, this lesion would be classified as a nonhomogeneous leukoplakia called erythroleukoplakia [10]. Erythroplakia is multifactorial, since no isolated etiological factor has been evident, but several intrinsic and extrinsic etiological factors have contributed to the origin of this disorder, such as smoking, alcohol consumption, candida infection, and even nutritional deficiencies such as iron and vitamin A deficiency [6]. Erythroplakia in comparison to leukoplastic lesions is rare and has a prevalence rate in South and Southeast Asia ranging from 0.02 to 0.83% but presents a high percentage of malignant transformation ranging from 14 to 50%, and about 90% of cases already present moderate or severe dysplasia/carcinoma in situ. Because of the high rates of malignant transformation and the presence of high-grade dysplasias, many specialists have already considered it a primordial clinical sign of squamous cell carcinoma. It is a prevalent disorder in middle-aged adults in the elderly, aged between 45 and 74 years, with no prevalence among the genders [6, 10, 13].

Clinically, erythroplakia presents as a well delimited, asymptomatic, reddish, smooth and shiny stain or plaque with a soft and velvety texture [3, 6]. If hardened areas are observed in the lesion, it is already indicative of the presence of a possible invasive carcinoma at the site. The preferred anatomical location is the floor of the mouth, but it can be observed anywhere in the oral cavity, such as the lip, hard palate, or oral mucosa [3]. The clinical presentation of a solitary lesion is consistently useful to clinically differentiate erythroplakia from erosive lichen planus, lupus erythematosus, and erythematous candidiasis, as these lesions always appear

bilaterally and are more or less symmetrical (**Figure 5**) [10].

*Erythroplakia affecting palate and superior alveolar ridge. Source: author's file.*

#### *Potentially Malignant Oral Disorders DOI: http://dx.doi.org/10.5772/intechopen.88580*

such as clinical follow-up of the lesion every 6 months throughout life, evaluation of the need for new biopsies, and end of smoking [3, 10]. In leukoplakias that present moderate or severe dysplasia/carcinoma in situ, it is recommended that the lesion be removed completely, if possible, or by CO2 laser therapy. However, even with the surgical treatment, there appears to be no reduction in the risk of developing a carcinoma or even relapse of the leukoplakial lesion [6, 7, 10].

Regarding the prognosis of leukoplastic lesions, recurrence rates after any type of treatment can range from almost 0 to 30%, which means regular follow-up of patients every 6 months [10].
