Premalignant Lesions Lecture PDF

Made with Xodo PDF Reader and Editor Al-Salam Uni Oral pathology II PREMALIGNANT LESIONS PREMALIGNANT LESIONS o Definitions: Cancer a malignant tumor Carcinoma a malignant epithelial tumor Sarcoma a malignant connect...

Made with Xodo PDF Reader and Editor Al-Salam Uni Oral pathology II PREMALIGNANT LESIONS PREMALIGNANT LESIONS o Definitions: Cancer a malignant tumor Carcinoma a malignant epithelial tumor Sarcoma a malignant connective tissue (mesenchymal) tumor an abnormal mass of tissue, it is independent uncoordinated new growth of tissue which is potentially capable of unlimited Neoplasm proliferation, and which does not regress after removal of the stimulus that produced the lesion Premalignant lesion a morphologically altered tissue that has a greater than normal risk of malignant transformation (precancerous) a state or disease that doesn’t necessarily alter the clinical Premalignant appearance of local tissue but is associated with a greater than condition normal risk of precancerous lesion or cancer development in that tissue (it is not necessarily marked by a pre-existing lesion) Malignant the risk of cancer being present in a precancerous lesion or condition either at initial diagnosis or in the future, usually transformation expressed in percentages potential a term used to sum up various cytological abnormalities of epithelial proliferation and differentiation as seen by light Epithelial dysplasia microscopy in both malignant and premalignant cells. i.e it refers to disordered growth a term indicates an individual feature of epithelial dysplasia. i.e Epithelial atypia it refers to abnormal cellular features the extent to which the dysplastic or neoplastic cells resemble Differentiation comparable normal cells both morphologically and functionally. Dr. Abdelrahman Elhoseny Page |1  Made with Xodo PDF Reader and Editor Al-Salam Uni Oral pathology II PREMALIGNANT LESIONS o Development of cancer  Many cancers related to environmental factors have a very long latent period between exposure to the irritant and development of the tumor. This has led to the concept of a three - stages process of carcinogenesis: 1. cells are initially changed from normal to neoplastic cells by some carcinogenic influence, with no clinical or histologic evidence of neoplasia. 2. Later exposure to some other agents, known as promotors will result in proliferation of these altered cells so that a clinically visible tumor will be produced.  Premalignant lesions may thus be described as oral lesions that may have undergone initiation and may, on being exposed to a promoting factor, be induced to undergo malignant transformation. o Classification Of Oral Premalignant Lesions and Conditions: Premalignant Lesions: Premalignant conditions 1. Idiopathic leukoplakia. 1. Oral submucous fibrosis. 2. Candidal leukoplakia. 2. Kelly - Paterson syndrome 3. Erythroplakia (Plummer — Vinson Syndrome) 4. Syphilitic leukoplakia (3ry stage) 3. Lichen planus. 5. White lesions associated with smokeless tobacco. 4. Discoïde lupus erythematosus. 6. Solar (actinic) Cheilitis 5. Xeroderma pigmentosa 6. Dyskeratosis congenita. Dr. Abdelrahman Elhoseny Page |2  Made with Xodo PDF Reader and Editor Al-Salam Uni Oral pathology II PREMALIGNANT LESIONS PREMALIGNANT LESIONS 1. IDIOPATHIC LEUKOPLAKIA o Definition  Leukoplakia is a clinical term indicating a white patch or plaque of the oral mucosa that cannot be rubbed off and cannot be characterized clinically as any other disease. o Criteria:  The most common premalignant lesion  Studies indicate that the malignant transformation of leukoplakia occur over a range from about 1% to as high as 47%. o Pathogenesis:  The cause of leukoplakia exactly remains unknown although much recent research believe that the initiation of this lesion, like oral cancer, may depend not only upon extrinsic local factors but also upon intrinsic predisposing factors. The most frequent factors are tobacco, alcohol, ultraviolet radiation, infection with several microorganisms such as Candida albicans and Treponema pallidum, oral sepsis, chronic local irritation, vitamin deficiency and industrial hazards. o Clinical Features: Age It is associated with a middle-aged & older population (mainly after 40 years). Trends in the use of smokeless tobacco by high — school students may Cause ultimately result in a shift of this age toward a younger population. Over time there has also been a shift in gender predilection in incidence of Sex leukoplakia due apparently to the change in smoking habits of women. (3:1) o Tongue, mandibular mucosa and buccal mucosa are the predominant sites Site o The palate, maxillary ridge and lower lip are less frequently involved o The floor of the mouth and retromolar areas are involved infrequently. 1) Homogeneous leukoplakia: Leukoplakia may vary from a vague whiteness on a base of uninflamed, normal appearing tissue to a definitive white smooth thin or thickened 2) Speckled Leukoplakia: Red zones may also be seen (47% malignant transformation). Types 3) Granular Leukoplakia may be soft, smooth or finely granular in texture 4) nodular leukoplakia: roughened, nodular indurated 5) verrucous leukoplakia: exophytic, demonstrate sharp or blunt projections  Proliferative verrucous leukoplakia: extend in the mucobuccal fold. Dorsal, ventral and lateral surface of tongue, and buccal mucosa (more dangerous) Dr. Abdelrahman Elhoseny Page |3  Made with Xodo PDF Reader and Editor Al-Salam Uni Oral pathology II PREMALIGNANT LESIONS The term sublingual keratosis is applied to white lesions on the floor of the mouth and ventral surface of the tongue. (premalignant) o Histopathologic features:  Histologic changes for idiopathic leukoplakia range from hyperkeratosis, acanthosis, epithelial dysplasia and carcinoma in situ to invasive squamous cell carcinoma. The dysplastic changes, when present, typically begin in the basal and parabasal portions of the epithelium. These cellular changes are similar to those of squamous cell carcinoma and include the following: 1- Drop - shaped epithelial rete processes. 2- Irregular epithelial stratification. 3- Basilar hyperplasia. 4- Loss of basal cell polarity. 5- Cellular pleomorphism. 6- Nuclear hyperchromatism. 7- Enlarged nucleoli. 8- Increased nuclear - cytoplasmic ratio. 9- Individual cell keratinization within the spinous layer. 10- Increased normal and abnormal mitoses. 11- Reduction or loss of cellular adhesion & “streaming” of the spinous cells. 12- The underlying connective tissue exhibits varying degrees of chronic inflammatory cell infiltration. Dr. Abdelrahman Elhoseny Page |4 Made with Xodo PDF Reader and Editor  Made with Xodo PDF Reader and Editor Al-Salam Uni Oral pathology II PREMALIGNANT LESIONS To assess the intensity or severity of epithelial dysplasia that reflects increased risk of malignant transformation , the following expressions have been suggested: refers to alterations limited principally to the basal and Mild epithelial dysplasia parabasal layers. refers to the involvement from the basal layer to the Moderate epithelial dysplasia midportion of the spinous layer. demonstrates alterations from the basal layer to a level Sever epithelial dysplasia above the midpoint of the epithelium. When the entire thickness of the epithelium is involved with these dysplastic changes. Carcinoma in situ is defined as sever dysplastic epithelial changes that extend from the basal layer to the surface of the mucosa “top- to-bottom change”. The epithelium may be hyperplastic Carcinoma in situ or atrophic. This entity is a precancerous lesion. The important feature of carcinoma in situ is that no invasion has occurred. Additionally, it is not regarded as a reversible lesion although it may take many years for invasion to occur. N.B The presence of epithelial dysplasia does not mean that the particular lesion will become malignant but indicates an increased risk. These changes may persist, regress or progress undergoing malignant transformation o Treatment and prognosis:  The first step in treatment is to arrive at a definitive diagnosis therefore, Complete removal can be accomplished by surgical excision, electrocautary, cryosurgery or laser ablation. Long — term follow up, every 6 months, after removal is extremely important because recurrences are frequent and additional leukoplakias may develop.  The habit, as smoking, cessation is recommended. Dr. Abdelrahman Elhoseny Page |5  Made with Xodo PDF Reader and Editor Al-Salam Uni Oral pathology II PREMALIGNANT LESIONS o Malignant potential  Each clinical appearance or phase of leukoplakia has a different malignant transformation potential. Thin leukoplakia seldom becomes malignant homogeneous thick leukoplakia 1-7% granular, nodular or verruciform leukoplakia 4-15% erythroleukoplakic 18-47%  Malignant transformation is also related closely to the degree of dysplasia present as shown in the this figure. 2. CANDIDAL LEUKOPLAKIA o Definition: The terms candidal leukoplakia and chronic hyperplastic candidiasis have been used to describe such lesions and biopsy may show hyperplastic or dysplastic histopathologic changes. o cause: It is not known whether candida albicans produces dysplasia or secondarily infects previously altered epithelium. But some of these lesions disappear or become less extensive after antifungal therapy. o Microscopically: a heavy infiltration of the superficial layers of epithelium with hyphae of candida (by PAS stain). o In this lesion is more dangerous then idiopathic leukoplakia, as the mitotic activity is four times higher than that found in idiopathic leukoplakias. It has a higher malignant transformation potential than that of ordinary idiopathic leukoplakia, due to increase stimulation and acceleration of cellular division by hyphae of candida Dr. Abdelrahman Elhoseny Page |6  Made with Xodo PDF Reader and Editor Al-Salam Uni Oral pathology II PREMALIGNANT LESIONS 3. ERYTHROPLAKIA o Definition: Erythroplakia is a clinical term denotes “a persistent, predominantly red mucosal patch which cannot be clinically or pathologically diagnosed as any other condition. o Incidence:  Erythroplakia is much less common than leukoplakia that was observed 77 times more often than erythroplakia in a large population study. However, erythroplakia is more potentially dangerous than leukoplakia. Almost all true erythroplakias demonstrate significant dysplasia, carcinoma in situ or invasive carcinoma whereas about 20% of leukoplakias demonstrate these changes.  The rate of malignant transformation in erythroplakia was found to be 80% o The cause of erythroplakia is unknown, may be due to: 1) Use of smokeless tobacco 2) Exposure of UV rays o Clinical features:  It is predominantly between 50 and 70 years of age.  There is no gender predilection. The floor of the mouth, the tongue and the soft palate are the most common sites of involvement. The lesion appears as a red patch with fairly well defined margins. o D. D: 1) Non specific mucositis. 2) Candidiasis. 3) Vascular lesions. o Histopathologic features: 1) It commonly exhibits sever epithelial dysplasia, carcinoma in situ or invasive carcinoma. 2) The epithelium shows a lack of keratin production and often is atrophic. → This allows the underlying microvasculature to show through thereby explaining the red color. (GR) 3) The underlying connective tissue often demonstrates chronic inflammation. o Treatment and prognosis:  Any source of irritation can be identified and removed, a biopsy of such a lesion may be delayed for 2 weeks to allow a clinically similar inflammatory lesion time to regress.  As with leukoplakia, the treatment of erythroplakia is guided by the definitive diagnosis obtained by biopsy. Recurrence and multifocal oral mucosal involvement are common. Hence, long - term follow up is suggested for treated patients. Dr. Abdelrahman Elhoseny Page |7  Made with Xodo PDF Reader and Editor Al-Salam Uni Oral pathology II PREMALIGNANT LESIONS Smokeless Tobacco – Related Keratoses (White lesions associated with smokeless tobacco) o Definition: Tobacco chewing and snuff dipping (holding flavored tobacco powder in the mandibular vestibule) are popular habits in the USA, India, and Southeast Asia. o Clinical features:  It is usually noted in young adult men and in men older than 65 years of age. The tobacco preparations are generally of higher PH (alkaline). The clinical results of long term exposure to smokeless tobacco include: 1. the development of oral mucosal white patches (granular to wrinkled appearance) affecting the non keratinized mucosa, 2. alterations of taste and smell 3. increased periodontal diseases 4. increased incidence of dental caries o Site: Mucobuccal fold of the mandible is the most common affected site. o Histopathologic features: 1. The oral epithelium is hyperkeratinized and acanthotic with or without intracellular vacuolization or edema of superficial cells. 2. Epithelial dysplasia may occasionally develop, especially in long - time users. 3. Salivary gland alterations such as acinar atrophy, interstitial fibrosis and dilated excretory ducts are seen. o Treatment and prognosis: Chronic use of smokeless tobacco is carcinogenic. With discontinuation of tobacco use, some lesions may disappear after several weeks. Persistent lesions should be removed and examined microscopically. ACTINIC KERATOSIS (SOLAR KERATOSIS) o It is a common cutaneous premalignant lesion that is caused by cumulative ultraviolet radiation to sun exposed skin especially in fair-skinned people. 13 - 25% of affected patients will develop squamous cell carcinoma. o N.B: A similar phenomenon, actinic cheilosis, is associated with sun damage to the lower lip vermilion. Dr. Abdelrahman Elhoseny Page |8  Made with Xodo PDF Reader and Editor Al-Salam Uni Oral pathology II PREMALIGNANT LESIONS SYPHILITIC LEUKOPLAKIA o Leukoplakia of the dorsum of the tongue is a characteristic complication of tertiary syphilis. o Site: It typically affects the dorsum of the tongue and spares the margins. It has an irregular outline and surface. Cracks, small erosions or nodules may exhibit histologically foci of invasive carcinoma that is typically a sequel to syphilitic leukoplakia. PREMALIGNANT CONDITIONS 1. ORAL SUBMUCOUS FIBROSIS o Definition: It is a chronic, progressive, scaring, high risk precancerous condition of the oral mucosa seen primarily on the Indian subcontinent and in southeast Asia. o primary importance of submucous fibrosis relates to its premalignant nature. About 30% of cases develop into squamous cell carcinoma o Etiology: several contributing factors such as general nutritional or vitamin deficiencies and hypersensitivity to various dietary constituents as spices. The primary factor appears to be chronic and frequent chewing of the areca (betel nut). o Clinical features  Age: Mostly between the age of 20 and 40.  Site: The buccal mucosa, retromolar area and soft palate are the most commonly affected sites. It may extend to the pharynx and esophagus.  If presents as a whitish yellow lesion that has a chronic insidious biologic course. It may be preceded by or be associated with vesicle formation. In time, the affected mucosa loses its resilience and elasticity, with resultant trismus and considerable difficulty in eating. The process progresses from the lamina propria initially to the underlying musculature. o Histopathologic features:  The principal feature is atrophy of epithelium with variable degrees of dysplastic changes. The superficial portion of the lamina propria is poorly vascularized and hyalinized. The submucosal deposition of extremely dense and avascular collagenous connective tissue. All forms of collagen, although excessive, are morphologically normal. Fibroblasts are few and there is a chronic inflammatory cell infiltrate ranging from minimal to moderate. Dr. Abdelrahman Elhoseny Page |9 Made with Xodo PDF Reader and Editor  Made with Xodo PDF Reader and Editor Al-Salam Uni Oral pathology II PREMALIGNANT LESIONS o Treatment and prognosis: a) Treatment includes stretching exercises and intralesional injections of corticosteroids with surgical excision of fibrous bands & submucosal replacement of placental grafts. b) Restriction or elimination of tobacco use should be attempted, and etiologic dietary agents should be withdrawn. 2. “PLUMMER - VINSON SYNDROM” “Paterson - kelly syndrome” o Definition: It is a rare condition characterized by iron deficiency anemia, glossitis, and dysphagia. It has been associated with a high frequency of both oral and esophageal squamous cell carcinoma as is therefore considered a premalignant condition. o Clinically:  it typically affects middle aged women (30 -50 y).  It is found to be highest in Scandinavian (Sweden) women.  Patients typically complain of burning sensation associated with the tongue and oral mucosa. Marked atrophy of the lingual papillae, which produces a smooth red appearance of the dorsal tongue is seen.  Angular cheilitis is often present and may be sever. Patients also complain of difficulty in swallowing (dysphagia). With endoscopy or esophageal barium contrast, the presence of abnormal bands of tissue in the esophagus called esophageal webs is observed. The nails may be also brittle and show a spoon - shaped configuration.  Fatigue, weakness, and shortness of breath that are characteristic symptoms of anemia are present. o Laboratory findings:  Hematologic studies reveal a hypochromic microcytic anemia that is consistent with an iron - deficiency anemia. o Histopathologic features:  The involved mucosa shows epithelial atrophy with varying degrees of  submucosal chronic inflammation. In advanced cases, criteria of epithelial atypia or dysplasia are observed. Dr. Abdelrahman Elhoseny P a g e | 10