**5. Queilite actinic**

Actinic cheilitis is a PMOD that frequently presents in vermilion of the lower lip, attributed to modifications in the keratinocytes of the labial mucosa. The expression cheilitis was first used in 1923, meaning inflammation on the lips, being multicausal, which include prolonged exposure to solar UV rays, allergic reactions, and systemic diseases. The term actinic refers to changes generated by radiant energy [6, 17, 18]. The etiopathogenesis of this disorder is multifactorial, but it is undeniable that the main etiological factor associated with actinic cheilitis lesions is prolonged exposure to the sun's rays, with UV radiation and with its wavelength of 200–400 nm acting as a carcinogenic factor, as it can cause cell damage, thereby generating mutations in the DNA and tumor suppressor genes, especially in the p53 gene. Lately, other risk factors have been associated with actinic cheilitis, such as smoking, immunosuppression, chronic lupus, and lichen planus [17, 18].

This disorder occurs in light-skinned individuals exposed for long periods to solar UV rays, which is more common in men and those performing outdoor work, such as rural and construction workers, or have a history of progressive exposure in the sun. The lesions mainly affect individuals in the age range

**83**

**Figure 8.**

*Potentially Malignant Oral Disorders*

[3, 6, 16, 19].

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

rent ulcers which do not heal (**Figure 8**) [3, 6, 17].

between 50 and 70 years. As previously mentioned, the primary anatomical site is the lower lip, and this is due to the fact that its epithelium is thinner, has a discrete layer of keratin, has fewer melanocytes, and receives direct radiation. Actinic cheilitis has a malignant transformation rate of 17%, with squamous cell carcinoma growing gradually, and metastasis occurs only in the late stages of the lesion

This disorder develops slowly, and the first noticeable clinical changes are atrophy of the border of vermilion of the lower lip, exhibiting a smooth surface with spots of whitish staining. As the lesion progresses, the margin between the vermilion area and the cutaneous portion of the lip is erased. In more advanced states, rough areas with the presence of ulceration can be observed, in addition to the association with leukoplastic lesions. In these late states, in many cases, clinical signs may already be found that indicate malignant transformation, such as recur-

Actinic cheilitis can histologically be characterized by the presence of an atrophic stratified epithelium, hyperkeratinization, atrophy, or thickening of the thorny layer and varying degrees of epithelial dysplasia. In the underlying connective tissue, it is possible to observe an infiltration of chronic inflammatory cells and also collagenous bundles exhibiting basophilic changes resulting from the change from an eosinophilic collagen to a basophilic granular material, called solar elastosis [3, 6, 17]. The diagnosis of actinic cheilitis is basically clinical; because it is a very characteristic lesion, patients usually report a nonelastic sensation of the lips, followed by dryness and increase of volume; besides, the accomplishment of the incisional biopsy is mandatory mainly for its high rate of malignant transformation and also to propose a suitable treatment plan for the lesion. In the absence of dysplasias or presence of mild dysplasia, the use of 5-fluorouracil (Efudix®), which can be applied twice a day for 2–4 weeks, is recommended. Cryotherapy, which consists in freezing a tissue area to potentiate cell destruction without damaging the healthy tissues around the lesion, and the use of laser therapy are possible therapeutic alternatives. In the occurrence of moderate or severe dysplasia/carcinomas in situ, a vermilionectomy is indicated, the affected vermilion mucosa is removed, and the vermilion reconstruction of the lip occurs from the internal labial mucosa [3, 6, 17, 19]. In addition, all patients with actinic cheilitis should be directed to use sunscreens and other forms of protection against UV rays; thus, in the same way as with other PMODs, individuals who have actinic cheilitis should be monitored routinely throughout life.

*Actinic cheilitis in the lower lip exhibiting epithelial atrophy and loss of sharpness of the demarcation line* 

*between the labial mucosa and the epidermis. Source: author's file.*

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

*Oral Diseases*

dysplastic alterations [6, 16].

the same [6, 15].

of dysplasia [6].

planus [17, 18].

**5. Queilite actinic**

Lichen planus has typical histopathological characteristics, but they are not specific for the lesion. Its epithelium has varying degrees of orthokeratosis and parakeratosis, and depending on whether the lesion is reticular or erosive, the thickness of the thorny layer may vary. Epithelial ridges may be absent, atrophic, or hyperplastic but usually exhibit sharp, serrate-like progressions. Another striking feature is the presence of hydropic degeneration, that is, the destruction of the basal cell layer of the epithelium and an intense infiltration of banded inflammatory cells predominantly composed of T lymphocytes. Some lesions of lichen planus may show some degree of dysplasia, being able to present aberrant mitoses and nuclear and cellular pleomorphisms, among other

The diagnosis of OLP is basically made by clinical findings, mainly in the reticular type, by the presence of the pathognomonic signal (Wickham striae). In addition to the clinical diagnosis, the histopathological examination may be requested for a definitive diagnosis. One thing that can make it difficult to diagnose OLP is the existence of candidiasis overlapping with lichen lesion, and for this, it is recommended that the treatment for candidiasis be carried out first and only subsequently the definitive diagnosis of OLP and the respective treatment plan of

As the reticular type does not present symptoms, there is no need for specific treatment, but as already mentioned, candidiasis can occur overlapping with lesions of lichen planus; in this way it is proposed that the antifungal treatment be performed based on topical nystatin, and mouthwash with nystatin or application of Miconazole gel is recommended. In erosive lichen planus, because it has painful symptomatology, treatment with topical corticosteroids initially, such as triamcinolone acetonide and beclomethasone, is suggested. The second line of treatment would be the use of retinoids, cyclosporine, and calcineurin inhibitors prescribed for about 2 weeks. In addition to drug treatment, photodynamic therapy is usually used to relieve symptoms [6, 13]. Lastly, patients with this disorder should be evaluated periodically for 3–6 months, especially in atypical cases with some degree

Actinic cheilitis is a PMOD that frequently presents in vermilion of the lower lip, attributed to modifications in the keratinocytes of the labial mucosa. The expression cheilitis was first used in 1923, meaning inflammation on the lips, being multicausal, which include prolonged exposure to solar UV rays, allergic reactions, and systemic diseases. The term actinic refers to changes generated by radiant energy [6, 17, 18]. The etiopathogenesis of this disorder is multifactorial, but it is undeniable that the main etiological factor associated with actinic cheilitis lesions is prolonged exposure to the sun's rays, with UV radiation and with its wavelength of 200–400 nm acting as a carcinogenic factor, as it can cause cell damage, thereby generating mutations in the DNA and tumor suppressor genes, especially in the p53 gene. Lately, other risk factors have been associated with actinic cheilitis, such as smoking, immunosuppression, chronic lupus, and lichen

This disorder occurs in light-skinned individuals exposed for long periods to solar UV rays, which is more common in men and those performing outdoor work, such as rural and construction workers, or have a history of progressive exposure in the sun. The lesions mainly affect individuals in the age range

**82**

between 50 and 70 years. As previously mentioned, the primary anatomical site is the lower lip, and this is due to the fact that its epithelium is thinner, has a discrete layer of keratin, has fewer melanocytes, and receives direct radiation. Actinic cheilitis has a malignant transformation rate of 17%, with squamous cell carcinoma growing gradually, and metastasis occurs only in the late stages of the lesion [3, 6, 16, 19].

This disorder develops slowly, and the first noticeable clinical changes are atrophy of the border of vermilion of the lower lip, exhibiting a smooth surface with spots of whitish staining. As the lesion progresses, the margin between the vermilion area and the cutaneous portion of the lip is erased. In more advanced states, rough areas with the presence of ulceration can be observed, in addition to the association with leukoplastic lesions. In these late states, in many cases, clinical signs may already be found that indicate malignant transformation, such as recurrent ulcers which do not heal (**Figure 8**) [3, 6, 17].

Actinic cheilitis can histologically be characterized by the presence of an atrophic stratified epithelium, hyperkeratinization, atrophy, or thickening of the thorny layer and varying degrees of epithelial dysplasia. In the underlying connective tissue, it is possible to observe an infiltration of chronic inflammatory cells and also collagenous bundles exhibiting basophilic changes resulting from the change from an eosinophilic collagen to a basophilic granular material, called solar elastosis [3, 6, 17].

The diagnosis of actinic cheilitis is basically clinical; because it is a very characteristic lesion, patients usually report a nonelastic sensation of the lips, followed by dryness and increase of volume; besides, the accomplishment of the incisional biopsy is mandatory mainly for its high rate of malignant transformation and also to propose a suitable treatment plan for the lesion. In the absence of dysplasias or presence of mild dysplasia, the use of 5-fluorouracil (Efudix®), which can be applied twice a day for 2–4 weeks, is recommended. Cryotherapy, which consists in freezing a tissue area to potentiate cell destruction without damaging the healthy tissues around the lesion, and the use of laser therapy are possible therapeutic alternatives. In the occurrence of moderate or severe dysplasia/carcinomas in situ, a vermilionectomy is indicated, the affected vermilion mucosa is removed, and the vermilion reconstruction of the lip occurs from the internal labial mucosa [3, 6, 17, 19]. In addition, all patients with actinic cheilitis should be directed to use sunscreens and other forms of protection against UV rays; thus, in the same way as with other PMODs, individuals who have actinic cheilitis should be monitored routinely throughout life.

#### **Figure 8.**

*Actinic cheilitis in the lower lip exhibiting epithelial atrophy and loss of sharpness of the demarcation line between the labial mucosa and the epidermis. Source: author's file.*

### **6. Oral submucous fibrosis**

Oral submucous fibrosis is a chronic disorder of the mucosa that lines the upper digestive tract that surrounds the oral cavity, oropharynx, and routinely the upper third of the esophagus, and is often found in individuals living in Southwest Asian countries [6, 13]. Before the etiology of this disorder was considered multifactorial and complex, it is now recognized that its appearance is due to the chewing of areca nut; this sachet is composed of areca palm nut and hydrated lime, sometimes with sweeteners and condiments, wrapped in a betel leaf [6, 20]. Because this custom is common in Southwest Asia, the highest frequency of this disorder is in the population of this region, mainly in India. Its frequency is about 0.5% in the population, and estimates suggest that about 2.5 million people are affected. The predominant age group is between 20 and 40 years, since the rural villagers begin the habit of chewing areca nuts very early and for long periods of time, around 16 hours. Oral submucous fibrosis has a malignant transformation rate between 2.3 and 7.6% [3, 11, 19].

Initially oral submucous fibrosis presents as vesicles and ulcers, often on the hard palate and buccal mucosa. With the progression of the disorder, the patient may present with xerostomia, difficulty in moving the tongue, and decreased elasticity of the oral mucosa, lips, and floor of the mouth, and some patients may report oral burning sensation. On palpation examination, dense fibrous bands may be felt, and a change in the color of the buccal mucosa with whitish and opaque tones. In the final stage, generalized fibrosis of the oral cavity and progressing trismus are observed [14].

Histologically, oral submucous fibrosis is described as a submucous deposition of dense collagenous connective tissue that shows little presence of blood vessels but with large numbers of chronic inflammatory cells. In lesions in soft states, the present epithelial alterations are subepithelial vesicles, whereas in lesions in more advanced states, it is possible to observe epithelial atrophy and hyperkeratosis. In addition, about 10–15% of FSO lesions present some level of dysplasia and even present carcinoma in situ [6].

The diagnosis is based on clinical findings and confirmed by biopsy and subsequent histopathological examination. There is no specific treatment for oral submucous fibrosis, but it is imperative that the diagnosed individual ceases the harmful habits. However, it is important to note that the lesion will not regress only with the removal of the habit, but it will prevent a possible malignant transformation. In patients who have mild or moderate cases of the disorder, treatment with corticosteroids applied to the lesion is recommended in order to reduce the symptoms. For later stages, surgical therapy is the most recommended, aiming to relieve trismus by releasing fibrous tissue through conventional techniques of tissue reconstruction, covering local/regional advancement flaps and microvascular flaps. Other treatment options include iron and multivitamin supplements and intralesional injections of lycopene alone or in combination with steroids, and some studies have shown the efficacy of interferon use for improved mouth opening [6, 11, 14, 19, 20]. Patients with oral submucous fibrosis are at least 19 times more likely to develop squamous cell carcinoma than individuals who do not have squamous cell carcinoma that even after the treatment for the symptomatology of the disease, the patients should be monitored routinely [6].

#### **7. Conclusion**

Potentially malignant oral disorders are the first indications of micro- and macroscopic alterations of possible malignant transformations, so knowledge about

**85**

*Potentially Malignant Oral Disorders*

**Acknowledgments**

**Conflict of interests**

**Author details**

and Maria da Conceição Andrade

provided the original work is properly cited.

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

these lesions is of great importance for specific care and prevention against any type of carcinoma. The transformation of normal mucosa to dysplastic mucosa occurs through a complex set of interactions between the individual's organism and environmental factors. Risk factors involving PMOD such as sun exposure, smoking habits, alcohol ingestion, and infection by microorganisms are issues that need to be addressed in order to better treat, prevent, and reduce malignant transformation rates. Thus, it is suggested that clinicians design educational plans aimed at the prevention of PMOD, as well as possible malignant transformations, in this way, enabling their patients against exposure to the causal factors of the disorders. In summary, the diagnosis and treatment plan for potentially malignant oral disorders are fundamental, since lesions that have high degrees of dysplasia should be treated with surgical procedures and those with no or slight degrees of dysplasia should

undergo conservative treatments, such as drug therapy or phototherapy.

Group on Head and Neck Cancer of Feira de Santana, Bahia, Brazil.

The authors declare that there is no conflict of interest.

Oral Cancer Nucleus of the State University of Feira de Santana, and Research

Márcio Campos Oliveira\*, Igor Ferreira Borba de Almeida, Almira Oliveira Pereira

© 2019 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/ by/3.0), which permits unrestricted use, distribution, and reproduction in any medium,

Universidade Estadual de Feira de Santana, Feira de Santana, Brazil

\*Address all correspondence to: marciopatologiaoral@gmail.com

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

*Oral Diseases*

observed [14].

present carcinoma in situ [6].

patients should be monitored routinely [6].

**6. Oral submucous fibrosis**

Oral submucous fibrosis is a chronic disorder of the mucosa that lines the upper digestive tract that surrounds the oral cavity, oropharynx, and routinely the upper third of the esophagus, and is often found in individuals living in Southwest Asian countries [6, 13]. Before the etiology of this disorder was considered multifactorial and complex, it is now recognized that its appearance is due to the chewing of areca nut; this sachet is composed of areca palm nut and hydrated lime, sometimes with sweeteners and condiments, wrapped in a betel leaf [6, 20]. Because this custom is common in Southwest Asia, the highest frequency of this disorder is in the population of this region, mainly in India. Its frequency is about 0.5% in the population, and estimates suggest that about 2.5 million people are affected. The predominant age group is between 20 and 40 years, since the rural villagers begin the habit of chewing areca nuts very early and for long periods of time, around 16 hours. Oral submucous

fibrosis has a malignant transformation rate between 2.3 and 7.6% [3, 11, 19].

Initially oral submucous fibrosis presents as vesicles and ulcers, often on the hard palate and buccal mucosa. With the progression of the disorder, the patient may present with xerostomia, difficulty in moving the tongue, and decreased elasticity of the oral mucosa, lips, and floor of the mouth, and some patients may report oral burning sensation. On palpation examination, dense fibrous bands may be felt, and a change in the color of the buccal mucosa with whitish and opaque tones. In the final stage, generalized fibrosis of the oral cavity and progressing trismus are

Histologically, oral submucous fibrosis is described as a submucous deposition of dense collagenous connective tissue that shows little presence of blood vessels but with large numbers of chronic inflammatory cells. In lesions in soft states, the present epithelial alterations are subepithelial vesicles, whereas in lesions in more advanced states, it is possible to observe epithelial atrophy and hyperkeratosis. In addition, about 10–15% of FSO lesions present some level of dysplasia and even

The diagnosis is based on clinical findings and confirmed by biopsy and subsequent histopathological examination. There is no specific treatment for oral submucous fibrosis, but it is imperative that the diagnosed individual ceases the harmful habits. However, it is important to note that the lesion will not regress only with the removal of the habit, but it will prevent a possible malignant transformation. In patients who have mild or moderate cases of the disorder, treatment with corticosteroids applied to the lesion is recommended in order to reduce the symptoms. For later stages, surgical therapy is the most recommended, aiming to relieve trismus by releasing fibrous tissue through conventional techniques of tissue reconstruction, covering local/regional advancement flaps and microvascular flaps. Other treatment options include iron and multivitamin supplements and intralesional injections of lycopene alone or in combination with steroids, and some studies have shown the efficacy of interferon use for improved mouth opening [6, 11, 14, 19, 20]. Patients with oral submucous fibrosis are at least 19 times more likely to develop squamous cell carcinoma than individuals who do not have squamous cell carcinoma that even after the treatment for the symptomatology of the disease, the

Potentially malignant oral disorders are the first indications of micro- and macroscopic alterations of possible malignant transformations, so knowledge about

**84**

**7. Conclusion**

these lesions is of great importance for specific care and prevention against any type of carcinoma. The transformation of normal mucosa to dysplastic mucosa occurs through a complex set of interactions between the individual's organism and environmental factors. Risk factors involving PMOD such as sun exposure, smoking habits, alcohol ingestion, and infection by microorganisms are issues that need to be addressed in order to better treat, prevent, and reduce malignant transformation rates. Thus, it is suggested that clinicians design educational plans aimed at the prevention of PMOD, as well as possible malignant transformations, in this way, enabling their patients against exposure to the causal factors of the disorders. In summary, the diagnosis and treatment plan for potentially malignant oral disorders are fundamental, since lesions that have high degrees of dysplasia should be treated with surgical procedures and those with no or slight degrees of dysplasia should undergo conservative treatments, such as drug therapy or phototherapy.
