PATHOLOGY OF ORAL CAVITY.

MANIFESTATIONS OF DISEASES OF THE ORAL CAVITY

-pain- the oral cavity- richly supplied with sensory nerve endings- pain is a feature of all diseases, including disorders of the teeth -changes of the oral mucosa - such as ulcerations, vesicular lesions (blisters), changes in colour
-ulcers- occur in many diseases, including infections, allergy, trauma, and neoplasns -blisters- infections, such as herpes virur, and immunologic diseases

-leukoplakia- white plaques on the mucosa- in hyperkeratosis, in dysplasia

-melanin pigmentation- Peutz-Jeghers syndrome-is rare congenital syndrome with autosomal dominance, characterized by melanotic pigmentation of mucosal and skin surfaces, and increased risk of carcinoma of pancreas, breast, lung and ovary, in addition patients have multiple polyps in small intestine and colon Addison disease -uncommon condition characterized by melanin pigmentation of skin and mucosa following destruction of the adrenal cortex, this results in increased stimulation of pituitary gland, high level of ACTH and MSH -mass lesions- solid or cystic

NON-NEOPLASTIC DISORDERS OF THE ORAL MUCOSA 1. Developmental anomalies 2. White lesions and patches 3. Infections 4. Pseudotumors
DEVELOPMENTAL ANOMALIES -oral mucosa is subject to the same range of developmental anomalies such as skin, and may be involved in head and neck syndromes, but also there are anomalies confined to the oral mucosa itself

1. Fordyce spots- heterotopic development of sebaceous glands in oral mucosaproduce yellow spots and nodules 2. Peutz-Jeghers syndrome- (periorifacial lentiginosis)- autosomal dominant condition with nearly complete penetrance, it is composed of melanocytic

macular pigmentation of the lips, oral mucosa, skin together with intestinal polyposis, most numerous hamartomatous polyps in small intestine, the polyps have a low malignant potential, those in colon with higher risk -the patients are in higher risk of malignancies at other sites, including ovary, uterus and breast -the facial pigmentation is around lips, eyes and nose and may disappear in adulthood -mucosal pigmentation tends to persist to adulthood

3. Congenital epulis- present at birth as mass attached to the gingiva, histologically composed of large granular cells with eosinophilic cytoplasm, covered by stratified hyperplastic squamous epithelium- completely benign
WHITE PATCHES. White sponge naevus- is rare autosomal dominant inherited condition, may be congenital or develop later in life - mainly affects buccal mucosa, may involve lips and other oral mucosa -family history can be detected in all cases -histologically: there is acanthosis, parakeratosis, and edema with hydropic degeneration of the cells in the stratum spinosum, epithelium is not dysplastic, there is no inflammation, no relation to tumor Frictional keratosis- is a common cause of intraoral white patches and may be due to sharp edges of teeth or to cheek and lip sucking, it is a response to low grade irritation microscopy may show acanthosis or epithelial atrophy, thick layer of orthokeratosis and prominent granular cell layer, or less commonly hyperparakeratosis with absent granular cell layer -there is no significant dysplasia, but sometimes inflammation of the underlying corium, no relation to tumor development clinically- the lesions tend to form diffuse keratotic plaques smoking related keratosis- smoking can result in intraoral plaque formation -histologically-atrophic or hyperkeratotic epithelium with patchy inflammation and melanin pigment in the underlying corium- pigmentary incontinence-release of melanin from demaged cells -there is no significant dysplasia -may be seen in reverse smokers, who hold the burning end of cigarette inside the mouth, this one may be associated with dysplasia

 acute oral candidosis-oral infections with candida albicans are common, it forms creamy white plaques which can be rubbed off to leave a dry, red mucosa -histologically-loose parakeratotic plaques infiltrated by leukocytes (intraepithelial microabscesses) with hyphae- difficult to be seen in HE stained sections but are readily visualised by staining with PAS or silver impregnation methods, such as Grocott -wide variety of factors predispose to infection, such as depressed cellular immunity, and inhibition of normal oral flora by broad spectrum antibiotics chronic hyperplastic candidosis (candidal leukoplakia) -Candida albicans can be present in persistent, adherent white plaques- solitary or multiple microscopy- shows a parakeratotic plaque infiltrated by leukocytes, acanthosis and inflammatory infiltrate in the corium, epithelium has elongated rete ridges with thinning of the suprapapillary epithelium giving a resemblance to cutaneous psoriasis, candidal hyphae can be visualized within parakeratotic layer hairy leukoplakia- patients infected with HIV frequently develop painless, white plaques on the lateral border of the tongue and occassionally elsewhere in the mouth microscopy-shows irregular parakeratosis with or without candidal hyphae, vacuolated cell with dark pyknotic nuclei ( koilocytes) in the stratum spinosum, no inflammatory infiltrate in the corium, Epstein-Barr capsid antigen can be detected in the epithelial cell nuclei -similar lesions have been reported occasionally in patients receiving immunosupressant drugs following organ transplantations geographic tongue- relatively common idiopathic condition typically characterized by areas with loss of papillae, mild chronic inflammation in corium, leukocytic microabscesses in the epidermis INFECTIONS- VIRAL, BACTERIAL AND FUNGAL infections of the oral mucosa are comparatively infrequent given the number of microorganisms present in the mouth

VIRAL: -1) herpes simplex stomatitis- caused by HSV type 1- common viral infection- usually is subclinical
-in only few per cent of infected indiviuals, there are more severe symptoms presenting as widespread gingivostomatitis, characterized by multiple vesicles and ulcers- in children and young adults- systemic symptoms- like fever are present

-locally severe, painful, but self-limited disease- healing occurs within two weeks, recurrent infections may be associated with abnormalities of cellmediated immunity -HS virus passes up the nerve trunks and infects the ganglia in acute phase, it remains in latent form for long time there

-herpes labialis-in some patients- attacks of reactivation of the infection as painful localized vesicular and ulceral lesion -reactivation is always precipitated by exposure to sunlight, fever, common cold, etc. -2) herpangina -is uncommon infection of the oral mucosa by coxsackie virus A, occurs as vesicular lesion on the palate -3) aphtous stomatitis- common lesion characterized by recurrent attacks of painful shallow ulcers on the oral mucosa- nonspecific acute infiltrate
- cause is unknown- no infectious agent has been identified- self-limited lesion

-4) viral warts- viral warts of the oral mucosa present as a lesion similar to condyloma accuminatum histologically: features suggestive of viral etiology such as koilocytosis, numerous mitoses, viral inclusions can be present- detection of HPV DNA sequences within the tissue using in situ hydridization technique assists in diagnosis- HPV type 6, 11 and 16 will be present (human papilloma virus) Bacterial: 1.) Acute ulcerative gingivitis:
-painful condition with ulceration of the interdental papillae between teeth, the ulcers have irregular margins and are covered with fibrinous exudate -etiology is unclear, and is partly relate to poor oral hygiene -smears from ulcers show mixed population of spirochetes, and fusiform bacteria

2.) Actinomycosis- infection of oral mucosa by actinomyces presents as swelling of the mucosa, the organisms are normally present in the mouth- infection is opportunistic 3.) Tuberculosis- infection of oral mucosa by tbc bacili is now uncommon, presents with tuberculosis ulcers that are secondary to pulmonary tuberculosis 4.) Syphilis- syphilitic infection of the oral mucosa is rare in this country, the chancre of the primary infect may occur on the lips or inside the mouth, mucous patches and ulcers may develop in secondary stage, and tertiary syphilis may present with gumma in the tongue or palate fungal: -1) candidosis -is caused by Candida albicans, which is present as normal commensal of the mouths of about one-half of the population

-clinical infection of the oral mucosa is an example of opportunistic infectionoccurs for example in patients with increased susceptibility (with immunosupression, in AIDS, in newborns, in patients receiving anti-cancer therapy or long-lasting antibiotic therapy, patients with diabetes mellitus) morphology: edema of the epithelium, ulcerations, Candida produces inflammation, white patches- the budding yeasts and pseudohyphae of Candida can be identified in smears and biopsy specimens from the lesions

PSEUDOTUMORS AND HYPERPLASTIC LESIONS OF THE ORAL MUCOSA

epulis -pseudotumors of gingiva -these are reactive lesions of gingiva, grosslypolypoid masses, most common types are

-granulomatous epulis- pyogenic granuloma -reactive inflammatory proliferation of nonspecific granulation tissue
grossly: small, bright red nodule with ulceration of the mucosal surface -it occurs quite commonly in pregnancy-and it resolves spontaneously

-giant cell epulis -distinctive lesion of gingiva composed of multinucleated giant cells and spindle mononuclear cells, giant cell epulides tend to be highly vascularized, there can be considerable amounts of hemosiderin, osseous metaplasia is rather common
-not true neoplasm-most likely a reactive lesion, however, the lesion tends to recur after excision

-fibromatous epulis -composed of fibroblasts and myofibroblasts, the lesions show variable degree of cellularity and collagen, dystrophic calcification may occur, osseous metaplasia is common -osteofibromatous epulis
-congenital epulis- usually seen in newborn as a polypoid lesion in the anterior maxilla, often protrude from the mouth as a reddish swelling, histologically - the lesion is composed of large eosinophilic cells with granular cytoplasm- the lesion is entirely benign -fibrous hyperplasia common tumor-like swelling of oral mucosa, these lesions are considered to be a response to low grade irritation -polypoid swellings may be sessile and pedunculated -microsopically consist of collagen bundles and moderately cellular fibrous tissue

-papillary hyperplasia typically seen in hard palate, belong to spectrum of denture-related , induced stomatitits -generalized gingival fibrous hyperplasia familiar or drug induced

-hereditary gingival fibromatosis- rare condition with AD trait, may be associated with hypertrichosis, neurological problems, such as epilepsy -drug-induced gingival hypertrophy- seen in about half of patients treated with anti-epileptic drug phenytoin for long period, other drug may roduce similar- cyclosporin

-orofacial granulomatosis characterized by chronic granulomatous inflammation of oral mucosa, the cause is unknown, dg after exclusion of Crohns disease, tbc and sarcoidosis
-Melkersson-Rosenthal disease-cheilitis granulomatosa,fissured tongue, facial nerve palsy

PRECANCEROUS CONDITIONS AND TUMORS OF THE ORAL MUCOSA

-the most important neoplasm of the mouth is squamous cell carcinomadespite the accessibility of the mouth to visual inspection, most oral cancers are detected late and their prognosis is comparable to that of squamous cell carcinoma of the esophagus -other malignancies and benign tumor are rare, except of squamous cell papilloma, and salivary gland-derived tumors of the oral mucosa

BENIGN TUMORS OF ORAL MUCOSA

-benign tumors in the oral cavity may arise - from squamous epithelium, from mesenchymal tissue, from the minor salivary glands -squamous papilloma- are usually small, sessile or pedunculated lesions -tehy are composed of fibrovascular core, extensions of which are covered by acanthotic stratified squamous epithelium- no evidence of dysplasia, but koilocytic metaplasia may be present -majority of papillomas are viral in origin- koilocytosis is a feature of viral infections -koilocytes- clear cell with polymorphic hyperchromatic nucleus pushed to one side -there is no tendency for malignant change -fibroma, lipoma, neurofibroma- benign mesenchymal tumors -granular cell tumor- (myoblastoma)- is not uncommon tumor of the skin and mucosal surfaces, they arise particularly in the mouth, where the dorsum of the tongue is a typical site,

histologically-striking pseudoepitheliomatous hyperplasia of the overlying epithelium with usually incospicuous granular cell tumor in the corium (simulates squamous cell carcinoma), the tumor consists of large cells with abundant finely granular cytoplasm- these cells were once thought to originate from muscle cells, however despite the fact that they seem to fuse with muscle, they appear to be of Schwann cell origin

ORAL PRE-MALIGNANCIES
-there is a wide range of mucosal disorders in which squamous cell carcinoma has been shown to develop more easily - pre-malignant lesions- which show histologically detactable mucosal changes - pre-malignant conditions- more widespread or systemic disorders affecting oral mucosa where cancer is statistically more likely to developalthough the site is unpredictable -pre-malignant lesions include: for example leukoplakia, palatal changes associated with smoking, and pre-malignant conditions- sideropenic atrophy and dysphagia caused by iron deficiency

LEUKOPLAKIA- this is a term best defined clinically to denote a white patch or plaque
-according to this definition - heterogenous group of lesions among which epithelial dysplasias- have pre-malignant potential - in most cases leukoplakia represents only simple hyperkeratosis resulting from chronic irritation, in minority of cases- there is dysplasia- persistent leukoplakia should be biopsied Epithelial dysplasia- lesions characterized by disordered cell maturation and proliferation associated with increased risk of progression to maligancy histologically-irregular hyperplasia of cells with basal cell morphology, rete ridges show a drop-shaped configuration, loss of both polarity of cells and normal stratification of the epithelium, nuclear changes, such as increased nuclear-cytoplasmic ratio, hyperchromatism and pleomorpism, mitoses in the upper layers of epithellium, abnormal mitoses, individual cell keratinisation often in deep layers (dyskeratosis or premature keratinisation), and loss of celllular cohesion -three degrees of dysplasia can be distinguished- mild, moderate, and severe

MALIGNANT TUMORS OF ORAL MUCOSA 1) Oral squamous cell carcinoma -accounts for over 90% of all malignant tumors of oral cavity- more common in older men
it is important to consider the site of involvement -most commonly it arises in the lower lip (40%), lateral margin of the tongue (20%), floor of mouth (15%)involvement of the upper lip, palate, gingiva and tonsillar area is less common -etiologic factors include cigarette and pipe smoking, alcohol, the lip is more commonly affected in white-skinned people exposed to prolonged sun lightparticularly high male predominance -grossly- the lesion oral cancer mainly presents as an ulcer, lump, or red or white

-histologically- majority of oral cancers are well or moderatelly differentiated squamous cell carcinomas

well-differentiated carcinoma- is composed of epithelial islands which resemble normal stratified squamous epithelium, except that they are invading the underlying tissues and show aberrant abnormal keratinization, there is often a prominent keratin formation in the infiltrating islands, usually strong host response of lymphocytes in the stroma, the tumor may be frankly deeply invasive poorly differentiated carcinoma- are associated with poorer prognosis, keratin formation is minimal, malignant cells do not exhibit distinction between basal and suprabasal population, mitoses are more frequent, and host response is usually less conspicuous than in better differentiated carcinomas
-poorly differentiated carcinomas are sometimes difficult to be distinguished from other malignancies, such as high grade lymphomas, malignant melanomas and sarcomas- correct diagnosis can be helped by means of immunohistochemistry using antibodies against epithelial markers (cytokeratin), mesenchymal markers (vimentin, desmin, actin), and melanoma markers, etc -patterns of spread- muscle, adipose tissue and other connective tissue tend to be invaded readily by oral cancer, salivary gland tissue and bone provide some resistence to invasion -lymph node spread is a relatively late feature of oral cancer- the pattern follows the main anatomical drainage pathways from the primary site- most commonly involved is submandibular lymph node

prognosis and treatment : depends on the stage of the disease and on the site of primary tumor

- compared with favourable prognosis for lip cancer- treated by surgery alone or combination of surgery and radiotherapy- five-year survival is around 70% -intraoral cancer has poor prognosis- 5-year survival lower than 40% -other significant adverse factor is the size of tumor at presentation -lymph node metastases, old age (more than 70), and poor histological differentiation- adverse prognostic factors

2) verrucous carcinoma- is a variant of oral squamous cell carcinoma with predominantly exophytic growth pattern, with minimal invasion,
microscopy- shows acanthosis with low degree of epithelial atypia, the advancing margin of the tumor forms pushing margin rather than the finger-like invasion of squamous cell carcinoma -it tends to have a rather indolent course with minimal if any capacity for metastases- very good prognosis- treatment - only surgery, radiotherapy should be avoided