EPITHELIAL TUMORS OF ORAL CAVITY

• Willis defined neoplasia as

‘An abnormal mass of tissue, the growth of which exceeds that of normal tissues and persists in the same excessive manner after the cessation of the stimuli which evoked the change.’

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• A benign, focal malformation that resembles a neoplasm in the tissue of its origin.

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• It develops and grows at the same rate as normal tissue and is not likely to compress or invade adjacent structures (in contrast to a neoplasm).

• A rare benign tumour consisting of microscopically normal tissue derived from germ cell layers foreign to that body site

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• A mass of histologically normal tissue in an abnormal location

Choristoma

• A true neoplasm made up of different types of tissue, which may not belong to the area in which it occurs.

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• It develops from multipotent cells of more than one primitive embryonic layer (ectoderm, endoderm, mesoderm), which differs in prognosis according to the organ involved and degree of maturation of the tissues.

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• Benign or malignant

• Benign
• Papilloma
• Keratoacanthoma

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• Malignant
• Squamous cell carcinoma
• Basal cell carcinoma
• Verrucous carcinoma
• Malignant melanoma

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• Generic disease process representing localized epithelial proliferations that typically have a roughened surface (exophytic growth).

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• Usually associated with HPV

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• Oral papillomas include:
• Squamous Papilloma
• Verruca Vulgaris
• Condyloma Acuminatum

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• Benign proliferation of stratified squamous epithelium.

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• It produces a papillary or verruciform mass.

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• It the fourth most common oral mucosal mass .

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• The growth may be induced by HPV virus; usually Type 6 and 11.

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• Double stranded DNA virus of papovirus family

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• Buccal epithelial cells of 81% normal adults have at least one type of HPV

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• Higher levels are present in disease and lower in normal cells

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• The exact mode of transmission is not known but person to person spread by sexual and non sexual routes transmission has been proposed

• Equally in males and females.

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• Any age but more common in persons between 30 and 50 years

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• May develop at any intraoral site; tongue, lips, buccal musosa, soft palate

• It appears as soft, painless, pedunculated exophytic nodule with numerous finger like projections on its surface

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• This is termed as a verruciform or cauliflower like growth

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• The growth is white, red or of normal colour, depending on the amount of keratin present

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• Papillomas are generally solitary and enlarge to a maximum size of about 0.5 cms

• Proliferation of keratinized stratified squamous epithelium, in the form of rounded finger like projections
• Each epithelial projection has a central core of fibrovascular connective tissue
• The surface keratin layer is thickened in lesions with a whiter clinical appearance
• Features of mild atypia like basilar hyperplasia and few mitotic figures may be seen in the epithelium

• Koilocytes, (virus altered epithelial cells

appear as clear cells with small dark

pyknotic nuclei in the spinous cell layer

• Common wart, associated primarily with HPV types 2, 4,6 & 40
• Very common on the skin, uncommon on oral mucosa
• Usually occurs in the anterior aspect of the oral cavity due to autoinoculation

in colour

• Oral lesions are always white indicating heavy keratinization.
• Very contagious lesion

Differences from squamous papilloma

1. The epithelial projections are pointed and narrow.
2. The elongated reteridges converge towards the centre ‘cupping effect’
3. Keratin layer is very thick
4. Stratum granulosum is prominent with eosinophilic intranuclear inclusions
5. Significant number of koilocytes are seen

• Venereal/genital wart, typically associated with HPV 6,11,16,18,53,54. Oncogenic HPV 16 & 18 are common in anogenital lesions but less common in the oral cavity
• Typically seen in the anterior aspects of the mouth and on the lingual frenulum .
• This is a STD with lesions developing at site of sexual contact or trauma

of child

• When seen in children, indicative abuse.
• Incubation period is 1 -3 months
• The lesion is highly contagious

• Condylomas may be multiple, are typically non-keratinized, and are thus the same colour as surrounding tissue.
• Histologically, shows broader papillomas than the squamous papilloma
• Koilocytes are prominent in cervical lesions.

• Surgical excision , including the base of the lesion
• Recurrence is unlikely
• No reports of malignant transformation
• Non surgical modes of excision like laser ablation, cryotherapy, topical agents like

high risk for

podophyllotoxin are also used

• Anogenital lesions are at malignant transformation

• Also called as self healing cancer.
• Clinically and histopathologically, it resembles a squamous cell carcinoma.
• It originates in the pilosebaceous glands.
• It is relatively common low grade malignancy that originates in pilosebaceous gland.

• Exposure to sunlight.
• Exposure to coal tar.
• Trauma.
• HPV (9,11,13,16,18,24,25,33,37,57)
• Genetic factors.
• Immunocompromised state.

• Solitary firm, round papules, which rapidly progress to dome shaped nodules, with central crateriform ulceration or keratin plug which projects like a horn.

• Clinical course is very typical.
• It starts as a small firm nodule which grows in size over 4-8 weeks.
• It remains static for next 4-8 weeks.
• It then undergoes spontaneous regression over next 4-8 weeks by expulsion of the keratin and resorption of the mass.
• Overall duration of the lesion as long as 2 yrs.
• The rapid growth which is seen leads to suspicion of malignancy.

• Hyperplastic squamous epithelium which grows into the underlying connective tissue.
• The epithelium shows hyper parakeratosis or hyper orthokeratosis.
• Central plugging of keratin is seen.
• At the deep epithelial margin, the islands of epithelium appears to be invading the connective tissue.
• This leads to suspicion of squamous cell carcinoma.

• Clinical features and histologic features suggestive of malignancy.
• However it heals on its own without any treatment.
• Thus termed as ‘Self healing cancer’.

POTENTIALLY MALIGNANT DISORDERS

• A premalignant lesion is “A morphologically altered tissue in which oral cancer is more likely to occur than in its apparently normal counterpart”

-WHO workshop 1978

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• Premalignant condition is ‘a generalized state associated with a significantly increased risk of cancer’.-

-WHO workshop 1978

• It was recommended in WHO workshop of 2005 to abandon the distinctions between precancerous lesions and conditions and to use the term “Potentially Malignant Disorders” instead, incorporating both the terminologies.

Definition

• ‘It is a group of disorders of varying etiologies, usually tobacco; characterized by mutagen-associated, spontaneous or hereditary alterations or mutations in the genetic material of oral epithelial cells with or without clinical and histomorphological alterations that may lead to oral squamous cell carcinoma transformation.

DYSPLASIA:

• Definition: It comprises a loss in the uniformity of individual cells, as well as loss in their

architectural orientation.

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• It is characteristically associated with protracted chronic irritation or inflammation.

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Histomorphological changes of dysplasia

1. Loss of basal cell polarity
2. Parabasilar hyperplasia
3. Increased nuclear:cytoplasmic ratio
4. Drop-shaped rete ridges
5. Irregular epithelial stratification
6. Increased mitotic activity
7. Mitoses in the superficial half of the surface epithelium
8. Cellular pleomorphism
9. Nuclear hyperchromatism
10. Enlarged nucleoli
11. Loss of cellular cohesiveness
12. Individual cell keratinization in the spinous cell layer.

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Loss of basal cell polarity�

Parabasilar hyperplasia�Increased nuclear:cytoplasmic ratio��

Drop-shaped rete ridges�

Irregular epithelial stratification�

Increased mitotic activity�

Individual cell keratinization

1. Leukoplakia
2. Proliferative Verrucous Leukoplakia
3. Intraepithelial carcinoma (Carcinoma in situ)
4. Erythroplakia
5. Smoker’s palate
6. Palatal changes associated with reverse smoking
7. Oral submucous fibrosis

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LEUKOPLAKIA�

• Originates from Greek words – “leucos” - white and “plakia” – patch

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• “ A predominantly white lesion of the oral mucosa that cannot be characterised as any other definable lesion.”

Classification of leukoplakia

• Based on CLINICAL TYPE:
• Homogenous :

Smooth

Furrowed

Ulcerative

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• Non homogenous :

Ulcerative

Verrucous

Speckled

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• Based on ETIOLOGY:
• Tobacco associated
• Idiopathic

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• Based on EXTENT:
• Localized
• Diffuse

Etiology

• Smoking
• Alcohol
• Candida albicans
• Role of viral agents (HPV 16 & 18)

Clinical presentation

• Male predilection
• Mostly occurs in 4^th to 7^th decade of life.
• Solitary or multiple, “White patches”
• Varies from a non-palpable faintly translucent white area to a thick fissured, papillomatous or indurated lesion

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• 70% in buccal mucosa, commissural areas, followed by lower lip, floor of the mouth, palate & gingiva

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Histopathological aspects

• Leukopakia is a clinical term and it is recommended that the histological report should always include a statement on the presence or absence of epithelial dysplasia.

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• Range from mild to severe.

CLINICAL STAGING

• A clinical staging system for oral leukoplakia (OL-system) on the lines of TNM staging was recommended by WHO in 2005 taking the size (L) and the histopathological features (P) of the lesion into consideration.

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• Lx: Size not specified.
• L1: Single or multiple lesions together <2 cm.
• L2: Single or multiple lesions together 2-4 cm.
• L3: Single or multiple lesions together >4 cm.

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• Px: Epithelial dysplasia not specified.
• P0: No epithelial dysplasia.
• P1: Mild to moderate epithelial dysplasia.
• P2: Severe epithelial dysplasia.

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• Stage I: L1 P0.
• Stage II: L2 P0.
• Stage III: L3 P0 or L1/ L2 P1.
• Stage IV: L3 P1 or Lx P2.

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Malignant potential

• 5 – 18 %
• Factors associated with greater risk of malignant change
• Nonhomogenous leukoplakia
• A proliferative verrucous appearance
• Tongue and floor of mouth
• Presence of multiple lesions
• h/o not smoking cigarettes

DIFFERENTIAL DIAGNOSIS

• White sponge nevus
• Acute pseudomembranous candidiasis
• Leukoedema
• Lichen planus (plaque type)

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TREATMENT AND PROGNOSIS

• The first step in treatment is to arrive at a definitive histopathologic diagnosis.
• Therefore, a biopsy is mandatory and will guide the course of treatment. Tissue to be obtained for biopsy, should be taken from the clinically most "severe" areas of involvement .
• Multiple biopsies of large or multiple lesions may be required

I . NON-SURGICAL TREATMENT

Chemoprevention

• L-Ascorbic Acid (Vitamin C)
• α-Tocoferol (Vitamin E)
• Retinoic Acid (Vitamin A)
• Vitamin A derivative, isotretinoin, and 13-cis retinoic acid: 28,500IU per day.
• Beta-carotene 150,000 IU of beta-carotene twice per week for six months.
• Bleomycin-Topical bleomycin in treatment of oral leukoplakia was used in dosages of 0.5%/day for 12 to 15 days or 1%/day for 14 days.

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II. Surgical Management

SURGICAL MANAGEMENT:

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1. Scalpel excision / Stripping
2. Electrocautery
3. Cryotherapy
4. CO2 Laser therapy

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Proliferative Verrucous Leukoplakia �

• Hansen et al , 1985
• Aggressive form of oral idiopathic leukoplakia
• Strong potential for malignant transformation.

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• Histological spectrum :
• Verrucous hyperplasia
• Varying degrees of dysplasia
• Three forms of SCC : Veruccous, conventional and papillary SCC

Intraepithelial carcinoma (Carcinoma in situ) �

• Most severe stage of epithelial dysplasia

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• Striking feature – dysplastic epithelial cells do not invade into connective tissue

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• Common among elderly, with a male prediliction

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• Present as white plaques or ulcerated, & reddened areas

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• Site – floor of the mouth, tongue, lips

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• Has combined features of leuko & erythroplakia

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Treatment

• This occurs frequently on the skin(Bowen’s disease) but also on mucous membrane.

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• No accepted treatment

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• Surgical excision, irradiation & cauterization

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ERYTHROPLAKIA

• Also known as ERYTHROPLASIA OF QUEYART

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• This was first described by Queyart in 1911 as a lesion occurring on glans-penis.

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WHO definition :-

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• A fiery red patch that cannot be characterized clinically or pathologically as any other definable disease.

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Incidence -

• It is more common in males and occurs more frequently in the 6th and 7th decade of life.

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CLINICAL FEATURE

• Red, often velvety, well-defined patches.
• Most commonly present on floor of mouth, retromolar trigone area, lateral tongue.
• Usually asymptomatic.
• May be smooth to nodular.

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• Homogenous form which appears as a bright red, soft velvety lesion with straight or scalloped well demarcated margins, often quite extensive in size, commonly found on the buccal mucosa and sometimes on the soft palate, more rarely on the tongue and floor of the mouth.

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• Speckled leukoplakia / erythroplakia which is soft, red lesions that are slightly elevated with an irregular outline and a granular or fine nodular surface speckled with tiny white plaques.

Differential Diagnosis-

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• Erythematous (atrophic) candidiasis
• Kaposi’s sarcoma
• Ecchymosis
• Contact stomatitis
• Vascular malformation
• Squamous cell carcinoma
• Geographic tongue/ erythema migrans

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Histopathologic features

• Epithelium shows lack of keratin production and is often atrophic.

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• Underlying connective tissue often demonstrates chronic inflammation.

Management

• Biopsy should be performed

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• Treatment guided by histopathologic diagnosis

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• Recurrence , multifocality common

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• Careful long term follow up

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SMOKER’S PALATE �(Nicotinic Stomatitis)

• Seen among conventional smokers.

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• Consists of greyish white palate with small nodular excrescences having small central red spots corresponding to the inflamed orifices of the minor salivary glands.

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• Exhibits neither great variability nor malignant transformation.

Palatal changes associated with reverse smoking��

• Palatal changes associated with reverse smoking are on the other hand multimorphic and precancerous.

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• Palatal changes include keratosis, excrescences, patches, red areas, ulcerated or non-pigmented areas.

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• Histological features include hyperorthokeratosis, epithelial dysplasia and inflammatory cells in the connective tissue.
• Melanin deposits were noted in the lamina propria

Oral submucous fibrosis

DEFINITION: “It is an insidious chronic disease affecting any part of the oral cavity and sometimes the pharynx. Although occasionally preceded by or associated with vesicle formation ,it is always associated with juxta-epithelial inflammatory reaction followed by a fibro-elastic changes of the lamina propria with epithelial atrophy leading to stiffness of the oral mucosa and causing trismus and inability to eat.”

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• (J.J Pindborg and Sirsat 1966)

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• First described by Shwartz by a descriptive term ‘atropia idiopathica mucosae oris’

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• Later Joshi in 1953 redesignated the condition as oral submucous fibrosis.

Etiology of OSMF:

Exact etiology is unknown. The predisposing factors are,

• Chronic Irritation

- Chilies, Lime, Areca nut, Tobacco.

• Defective iron metabolism
• Bacterial Infection
• Collagen disorder
• Immunological disorders
• Genetic disorder

Chronic irritation:-

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🞭 Pathogenesis of OSMF lies in the continuous action of mild irritants.

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Chillies:-

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🞭 "Capsaicin" an active extract from capsicum.

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🞭 The active principle irritants of chillies (Capsicum annum and Capsicum

frutescence) .

Areca nut

It contains,

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🞭 ARECOLINE, ARECAIDINE

-Fibroblast proliferation

-Stimulate collagen synthesis

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🞭 TANNIN, CATHECHIN-

- Makes collagen fibrils resistant to

collagenase.

Initial symptoms

• Burning sensation on eating spicy food

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• Blisters on the palate

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• Ulceration or recurrent stomatitis

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• Excessive salivation

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• Defective gustatory sensation

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• Dryness of mouth.

Later

• Difficulty in opening mouth

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• Inability to whistle, blow
• Difficulty in swallowing
• Referred pain to the ear
• Changes in tone of the voice due to vocal cord involvement
• Sometimes deafness due to occlusion of eustachian tubes

COMMON SITES INVOLVED-

🞭 Buccal mucosa, faucial pillars, soft palate, lips and hard palate.

🞭 The fibrous bands in the buccal mucosa run in a vertical direction, sometimes so marked that the cheeks are almost immovable.

🞭 In the soft palate the fibrous bands radiate from the pterygomandibular raphe or the faucial pillars and have a scar like appearance.

🞭 The uvula is markedly involved, shrinks and appears as a small fibrous bud.

🞭 The faucial pillars become thick, short,

and extremely hard.

🞭 The tonsils may be pressed between the fibrosed pillars.

🞭 The lips are often affected and on palpation, a circular band can be felt around the entire lip mucosa.

🞭 When gingiva is affected, it is fibrotic, blanched and devoid of its normal stippled appearance.

PALE AND BALD TONGUE

TRISMUS

Clinical stages

Three stages based on physical findings:

• Stage 1: Stomatitis includes erythematous mucosa, vesicles, mucosal ulcers, melanotic mucosal pigmentation & mucosal petechiae
• Stage 2: Fibrosis occurs in ruptured vesicles & ulcers when they heal, hallmark of this stage
• Stage 3: Sequelae of OSMF
• Leukoplakia is found in more than 25% of individuals with OSMF
• Speech and hearing deficits may occur because of involvement of the tongue and the eustachian tubes

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(Pindborg,1989)

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Histopathological findings -

🞭 Atrophic Oral epithelium.

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🞭 Loss of rete pegs .

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🞭 Epithelial atypia may be observed.

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🞭 Hyalinization of collagen bundles.

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🞭 Fibroblasts decreased and blood vessels obliterated.

Histological staging of oral submucous fibrosis

Group I ‑ very early

• Fine fibrillar collagen network interspersed with marked edema, blood vessels dilated and congested, large aggregate of plump fibroblasts with abundant cytoplasm, inflammatory cells mainly PMN with few eosinophils. Epithelium normal, with occasional hyperplasia

Group II ‑.early

• Juxta‑epithelial hyalinization with collagen present as thickened but separate bundles, blood vessels dilated and congested, moderate number of young fibroblasts, inflammatory cells mainly PMN, eosinophils, and occasional plasma cells. Epithelium shows flattening/shortening of retepegs with varying degree of keratinization.

Group III ‑ moderately advanced

• Juxta‑epithelial hyalinization is present.
• Faintly discernible collagen bundles separated by very slight, residual edema.
• Muscle fibers interspersed within collagen fibers reveal the beginning of degeneration and irregularity of striae.
• Blood vessels constricted, mature fibrocytes with scanty cytoplasm, and spindle‑shaped nuclei.
• Inflammatory cells, mainly lymphocytes and plasma cells.
• Epithelium markedly atrophic with total loss of rete pegs.

Group IV ‑ advanced

• Collagen hyalinized as a smooth sheet eliminating all evidences of individual bundles.
• Extensive fibrosis obliterating the mucosal blood vessels.
• Fibroblasts markedly absent within hyalinized zones.
• Extensive degeneration of muscle fibers.
• Total loss of rete pegs with mild to moderate atypia

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MANAGEMENT -

Various modalities of treatment have been tried.

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1. Restriction of habits/ Behavioral therapy.
2. Non-surgical therapy.
3. Surgical therapy.
4. Oral Physiotherapy.

NON-SURGICAL THERAPY:-

🞭 Antioxidants

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🞭 Intralesional injections of hyaluronidase. Hydrocortisone

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🞭 Use of Placentrix 2ml solution at interval of 3 days.

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🞭 Topical application -

1.

4% Acetic acid (At PH 6.5) 3 times daily.

2.

5 Fluorouracil

Systemic administration of immunomodulators -

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🞭 Levamisole 150mg for 3 weeks ,orally

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🞭 Dapsone 75 mg O.D for 90 days, orally

MALIGNANT EPITHELIAL NEOPLASMS

• SQUAMOUS CELL CARCINOMA

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• VERRUCOUS CARCINOMA

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• BASAL CELL CARCINOMA

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• MALIGNANT MELANOMA

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• EPIDERMOID CARCINOMA

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• Squamous cell carcinoma is a malignant epithelial neoplasm exhibiting squamous differentiation as characterized by formation of keratin and presence of intercellular bridges

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• Most common malignant neoplasm of oral cavity.

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• Squamous cell carcinoma comprises 90- 95% of all oral malignancies

SQUAMOUS CELL CARCINOMA

• Males----Lungs and stomach.
• Females--------Breast and cervix.
• Head and neck cancers are 3^rd most common group of malignancy.
• Oral cancer most common group in head and neck cancers.

• The cause of oral squamous cell carcinoma is multifactorial.

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• No single agent or factor is identified.

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• But both extrinsic and intrinsic factors may be involved in carcinogenesis.

• Extrinsic factors are external agents like tobacco smoke, alcohol, syphilis and sunlight.

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• Intrinsic factors are systemic or generalized states like malnutrition and iron deficiency anemia, immunocompromised.

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• Heredity is not a factor in oral carcinoma.

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• Many cases are preceded by precancerous lesion like leukoplakia.

• The risk of oral cancer in smokers is dose dependent.
• The risk is also increased, the longer a person smokes.
• The risk of palatal cancer is greatly increased in persons who practice reverse smoking.

• Paan or betel quid is a combination of areca nuts, betel leaf, slaked lime, and sometimes tobacco.

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• The slaked lime (chuna) enhances absorption of the other substances into the mucosa.

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• Risk of oral cancer is increased by 8% in those who chew paan.

2. Alcohol : Synergistic effect with tobacco in causation of oral cancer.

3. Syphilis: This is not relevant in present times because syphilis is treated in early stages with good antibiotics.

• Syphilis used to be treated with arsenic and that may have been cause for high incidence of cancer associated with syphilitic glossitis

4. Sunlight or Actinic radiation

• This was significant only for basal cell carcinoma of the lips
• The incidence is higher in males who are generally more exposed to sunlight
• It is commoner in fair skinned persons

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5. Orodental Factors

• Poor oral hygiene, faulty restorations, sharp teeth, and ill-fitting dentures are co-factors
• These are synergistic factors with tobacco habit

6. Diet and deficiency states

• Dietary deficiencies play a contributory role in development of oral cancer

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• Relationship between Sideropenic Dysphagia and oro pharyngeal cancer is well recognized

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• Certain deficiency states like anemia, Vitamin A deficiency make the epithelium atrophic and thus more vulnerable to action of carcinogen like tobacco.

Sideropenic Dysphagia: Plummer-Vinson syndrome, Patterson - Kelly syndrome

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• A precancerous condition.

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• It is characterized by iron deficiency anemia, generalized fatigue, difficulty in swallowing due to formation of oesophageal webs, angular chelosis, mucosal pallor, smooth glossy tongue etc.

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• It is associated wih an elevated risk of squamous cell carcinoma of the esophagus, oropharynx and posterior mouth.

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• Malignancies develop at an earlier age in persons with iron deficiency anemia.
• These persons have impaired cell mediated immunity.

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7.Viruses:Role of Oncogenic viruses

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• Viruses induce cancers by altering the DNA and chromosomal structure of host cells and then inducing the cells to proliferate in an uncontrolled manner

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• HPV is implicated in etiology of oral cancer

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• HPV 16 and 18 are the high risk strains of HPV

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• Viral proteins E6 and E7 are responsible for carcinogenesis
• HPV related oral cancer has better prognosis

8. Immunosuppression-

• Malignant cells may not be recognized and destroyed at an early stage
• People with AIDS, those on immunosuppressive therapy for organ transplants, auto immune diseases are at risk

9. Genetic abnormalities-

• Normal proto oncogenes may be converted into oncogenes by viruses, chemicals or radiation
• These oncogenes stimulate cell division
• Thus oncogenes are involved in initiation and progression of various neoplasm, including oral squamous cell carcinoma
• Ras, myc, EGFR (c-erb B1) are commonly mutated oncogenes

Genetic abnormalities

• Tumour suppressor genes may be inactivated due to mutation
• Thus they permit genetically abnormal cells to progress in the cell cycle
• Accumulation of these abnormal cells will ultimately result in tumor formation
• P53, Rb, p16 are commonly mutated tumour suppressor genes

A varied clinical presentation

1. Exophytic growth: fungating, papillary or verrucous.
2. Endophytic: invasive, burrowing, ulcerated lesion.
3. Leukoplakic patch.
4. Erythroplakic patch
5. Erythroleukoplakic patch.

• The exophytic lesion shows irregular, fungiform, papillary or verruciform projections above the surface
• It may appear red to white depending on keratin and vascularity
• Surface may be ulcerated
• On palpation, the edges are hard and indurated

• The endophytic lesion shows a depressed area, which may be ulcerated in the centre
• The surrounding border has a rounded or rolled appearance
• This is due to downward and lateral growth of the tumour under the epithelium

• When the tumour spreads into bone, it appears as a “moth eaten” radiolucent lesion with ill defined margins

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• Nerve invasion is characterized by paresthesia and numbness

• OSCC arises from dysplastic surface epithelium
• Characterized by invasive islands and cords of malignant squamous epithelial cells
• Invasion means extension of the dysplastic epithelium through the basement membrane into the connective tissue
• Dysplastic cells extend into adipose tissue, muscle and bone.
• Cells also surround and destroy blood vessels and lymphatics

• The dysplastic epithelium induces a immune response in the connective tissue which is seen as an inflammatory reaction
• Areas of necrosis may be seen
• Dysplastic epithelium induces formation of blood vessels ( neo angiogenesis)
• It can also induce dense fibrosis in the connective tissue ( Desmoplasia)

• Histologically squamous cell carcinomas are graded into well differentiated, moderately differentiated and poorly differentiated tumors. ( Broders grading system)
• Differentiation refers to the extent to which the tumor cell resembles the cell of origin, both structurally and functionally.

• The resemblance of the tumor cell to squamous epithelial cells and the amount of keratin they produce helps to determine the histological grade of the tumour.
• Epithelial atypia

1. Most of the tumour cells are identifiable as squamous epithelial cells
2. Large amounts of keratin is seen in the form of keratin pearls of varying sizes
3. Malignant cells show dysplastic features like cellular pleomorphism, nuclear hyperchromatism, increased nuclear – cytoplasmic ratio, individual cell keratinization, abnormal mitoses

1. The cells still resemble squamous epithelial cells, but the similarity is less pronounced
2. The islands or clusters of cells are smaller in size. Some cells are seen lying free in the connective tissue
3. Amount of keratin formation is reduced

1. Tumor cells show no similarity with squamous epithelial cells. It is difficult to even identify them as epithelial cells
2. Keratin formation is almost absent
3. The tumor cells showing all dysplastic features are scattered throughout the connective tissue.
4. The cells show an even greater lack of cohesiveness

• Refers to clinical evaluation of the extent of disease.
• Helps clinician to plan treatment.
• Helps to evaluate various treatment options.
• Helps in standardizing the disease for communication between doctors.

T: Primary Tumor size

• TX: Primary tumour cannot be assessed
• T0: No evidence of primary tumor
• Tis: Carcinoma in situ

• T1:
• T2:
• T3:

Primary tumor less than 2cms diameter. Primary tumor 2-4 cms in diameter.

Primary tumor more than 4cms diameter.

• T4: Tumour invading adjacent structures eg: cortical bone, tongue, skin of neck.

N: Regional lymph nodes

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• NX: Regional lymph nodes cannot be assesed.
• N0: No palpable lymph nodes.
• N1: Metastasis in a single ipsilateral lymph node, 3 cm or less in greatest dimension
• N2a : Metastasis in a single ipsilateral lymph node, more than 3 cm but not more than 6 cm in greatest dimension
• N2b : Metastasis in a multiple ipsilateral lymph nodes, none more than 6 cm in greatest dimension
• N2c : Metastasis in a bilateral or contralateral lymph nodes, none more than 6 cm in greatest dimension
• N3: Metastasis in a lymph node, more than 6 cm in greatest dimension.

M: Distant metastases

• MX: Presence of distant metastasis can’t be assessed
• M0: No distant metastases.
• M1: Clinical and radiographic evidence of distant metastases.

T4 N0M0

Any patient with M1

• Prognosis of oral squamous cell carcinoma on all locations except on the lower lip is poor
• Poor prognosis due to late diagnosis and late initiation of treatment
• Survival rate depends on clinical stage of the disease and the intraoral site which is involved
• Treatment modalities are surgery, radiotherapy or a combination of both
• Chemotherapy is used as adjunct therapy
• Targeted therapy is the future of management of OSCC

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• Small tumors are treated surgically
• Larger tumors receive combined therapy
• If lymph nodes are palpable, elective neck dissection is done along with neck irradiation
• Sentinel node biopsy is also done if occult metastasis is suspected

• Prognosis is determined by 5 year survival rate
• Varies from 68% for Stage 1 tumors to 27% for Stage 4 disease
• In case of lower lip, survival ranges between 83% and 47%

• This is a low grade variant of oral squamous cell carcinoma ( metastasis is extremely rare)
• First described by Ackerman in 1948
• It is associated with habit of chewing tobacco (Smokeless tobacco or snuff tobacco)

of all oral squamous cell

• Ill filling dentures
• It represents 1-10% carcinomas

• Also reported in nonchewers; maybe associated with HPV 16 and 18

• More common in men of older age group (60- 70years)

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• The site of lesion corresponds to site where the tobacco quid is placed

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• Most common sites are mandibular vestibule, gingiva, buccal mucosa, tongue

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• Other sites are alveolar ridge, palate and floor of mouth.

• Lesion appears as a well demarcated, painless thick plaque with papillary or verruciforn surface projections

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• Lesions are usually white due to heavy keratinization

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• Some lesions appear red to pink if there is less keratin and significant inflammatory response

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• As the lesion grows into the underlying tissue, bone, cartilage, muscle and salivary glands may be destroyed

• Benign appearance microscopically.
• The surface is papillary or verrucous form.

• Typically reteridges

there that

are elongated, ‘push’ into the

wide deeper

connective tissue

• Therefore, verrucous carcinoma is an

exophytic and endophytic growth.

• No significant cellular atypia is seen

• Surface is covered with thick layer of parakeratin.
• Parakeratin also fills the spaces between the surface projections.
• This is called ‘parakeratin plugging’-Hallmark
• Dense infiltration with chronic inflammatory cells is seen in the subepithelial connective tissue

• This is a low grade malignancy
• Treatment of choice is surgical excision with a wide margin but no radical neck dissection
• If SCC is present along with verrucous carcinoma, it must be treated like a SCC
• Radiotherapy is used in inoperable cases
• Chemotherapy may be used as a adjunct.
• The prognosis is much better than SCC.

• Rolled out margins with central ulceration.
• The most common skin cancer.
• 80% of BCC occur on the skin of head and neck region.
• Locally invasive malignancy, which does not metastasize.
• Pathogenesis- BCC is believed to arise from pleuripotent stem cell compartments of basal layer of epidermis as well as follicular structures(hair follicle stem cell just below the sebaceous gland duct)

Etiology

• Chronic exposure to UV radiation

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• Sunburns and freckles in childhood are at an increased risk.

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• Chemicals such as arsenic

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• Genetic skin disorders

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• Immunocompromised

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• It is usually seen in adults with a fair complexion (FOURTH DECADE OF LIFE).

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• Male to female ratio 3:2.

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• Most frequently seen in middle third of face.

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• It is a locally invasive, slow growing epithelial malignancy which does not metastasize.

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• BCC does not occur on oral mucosa except by extension

• Nodular basal cell carcinoma (most common type)

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• Pigmented BCC (contains several normal melanocytes, therefore appears brown, black or blue)

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• Superficial BCC (appears as multiple scaly lesions)

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• Cystic BCC ( translucent blue grey cystic nodules that may mimic benign cystic lesions)

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• Micronodular BCC (aggressive type; yellow to white in color, firm to touch)

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• Morpheaform and infiltrating BCC

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• Most common variety .Begins as a firm painless papule with a central depression(Umblicated appearance).

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• One or more telangiectatic blood vessels are seen coursing over the border around the central depression.

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• Ulceration starts in the centre.

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• Intermittent bleeding and healing is reported.

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• If untreated, it keeps enlarging slowly with destruction of the underlying structures bone and cartilage.

• The different clinical types have variable histopathologic appearances
• In the nodular BCC, the tumour cell is an ovoid, dark staining basaloid cell with moderate sized nuclei and little cytoplasm
• The cells are arranged in well demarcated islands and strands.
• The cells appear to arise from the basal cell layer of overlying epidermis
• Palisading of peripheral cells is evident

• Cleft formation,known as artifactual retraction may be seen between the epithelial islands and the connective tissue
• This is due to shrinkage of mucin during tissue processing

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• In pigmented BCC,benign melanocytes are present around the tumour produces large amount of melanin.

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• In superficial BCC,buds of basaloid cells attached to the undersurface of epidermis. Nests of various sizes are seen in upper dermis.

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• In morpheaform and infilterating type,strands of tumour cells embedded in dense fibrous connective tissue stroma.

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• Depends on the site and size of the lesion
• Small lesions< 1cm are treated by surgical excision and laser ablation(X-ray radiation)
• At least 5 mm margin of normal tissue is excised.
• Recurrence and metastasis are rare
• In patients with large lesions, death may be due to local invasion into vital structures
• Treated patients should be reviewed at regular intervals as there is 30% chance of second tumour developing within 3 years of treatment

• Malignancy of epidermal melanocytes

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• Can develop de novo or from a benign melanocytic lesion

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• This is the third most common skin cancer.

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• Oral mucosal melanoma is rare as compared to skin melanomas.

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• The mucosal melanomas are diagnosed at a later stage and are more aggressive than the skin lesion .

• Sun exposure
• Relative with history of melanomas
• Fair complexion
• Light coloured hair
• Tendency to sunburn easily and history of several episodes of blistering sunburn in childhood
• Personal history of congenital or dysplastic nevus

Two growth phases.

Radial .

• Initial phase.
• Spreads horizontally in

the epidermis.

• This phase may last for several years.
• No metastasis

Vertical.

• Neoplastic cells proliferate into the dermis.
• Reflects increased virulence of cells or decrease in host immunity.
• Metastasis is common.

• Not all melanomas show both phases.
• Some are in vertical growth phase from the beginning

• Superficial spreading melanoma.
• Nodular melanoma.
• Lentigo maligna melanoma(Hutchinson melanoma)
• Acral lentiginous melanoma.
• Mucosal lentiginous melanoma
• Amelanotic melanoma

• Most common type of cutaneous melanoma in caucasians.(65%)
• It does not usually spread into connective tissue. It shows radial growth phase.
• Also called melanoma in situ or premalignant melanosis.
• If it infilterates into the connective tissue, there is increase in size,colour,nodularity and ulceration.
• The lesion presents as tan , brown , black or admixed lesion on sun-exposed skin.

• It accounts for approximately 13% of cutaneous melanomas.
• An aggressive infilterative form of lesion
• Colour may be pink-brown or black
• It shows vertical growth from the start
• Sometimes the cells are so poorly differentiated that lesion becomes depigmented and has same colour as normal mucosa ( amelanotic melanoma)
• Predilection- back,head,neck skin of men

• 10% of cutaneous melanomas
• Lentigo maligna is a precursor lesion for melanoma. (Melanotic freckle of Hutchinson)
• It is melanoma in situ it consists of malignant cells but does not show invasive growth.
• It can remain in this non-invasive form for years.
• The lesion occurs as a macular lesion on the malar skin of middle aged and elderly caucasians.
• It occurs more often in women than men
• It shows radial growth phase

• When lentigo maligna develops into melanoma, the resulting lesion is called lentigo maligna melanoma.
• The transition to melanoma is marked by the appearance of a bumpy surface.

• 50% Commonest form of melanoma in Black races and Asian skin
• The tumour is macular,lentiginous pigmented area around a nodule
• Commonest form of oral melanoma
• It develops on non hair bearing surfaces of the body which may or may not be exposed to sunlight. ( palm, sole, nailbed)
• Aggressive form of disease.
• Initially it is a macular lesion ( radial growth), later it becomes lobulated and exophytic ( vertical growth)

Mucosal lentiginous melanoma

• Atypical melanocytes are seen at epithelium- connective tissue junction
• The cells spread horizontally and vertically
• Single or groups of abnormal cells are seen in the epithelium
• The tumour cells contain melanin granules
• The intraepithelial component(radial growth phase) of superficial spreading melanoma is characterised by presence of large,epithelioid melanocytes distributed in a so called “pagetoid” manner.

• When vertical growth occurs, cords or sheets of atypical melanocytes are seen in the deep connective tissue
• Amelanotic tumour cells can be identified by positive reaction to S-100 ( indicating neural crest origin), HMB -45 ( indicating a melanocytic tumour), Melan A ( Indicating melanocytes)

A----Asymmetrical growth of lesion,one half does not match the other half.

B----Border irregularity with blurred,notched or ragged edges.

C----Colour variation from red to brown to black to blue in the same lesion.

D----Diameter larger than 6 mm.

E----The lesion is raised or elevated above the surface.

• The treatment of cutaneous malignant melanoma is surgical excision
• Elective lymph node dissection is performed if regional lymph nodes are palpable.
• Sentinel node biopsy is done if regional lymph nodes are not palpable
• Chemotherapy,immunotherapy and radiation therapy for cutaneous melanoma

• Oral melanomas have a very poor prognosis than cutaneous melanoma.
• The site does not affect survival.
• Younger patients have better survival than older patients.
• The 5-year survival rate for such tumours is approximately 7%.
• Invasion to depth more than 0.75mm is indicative of very poor prognosis

classification for skin melanomas

Grading based on depth of invasion of the tumour- CLARK SYSTEM

• Level 1: Tumour cells only in epidermis
• Level 2: Tumour cells in papillary dermis
• Level 3: Tumour cells in whole of papillary dermis
• Level 4: Tumour cells in reticular dermis
• Level 5: Tumour cells invading subcutaneous fat-

Frequently asked questions�Long essays

1. Define potentially malignant disorders of oral cavity. Describe in detail etiology, clinical features and histopathology of oral squamous cell carcinoma

2. Define oral potentially malignant disorders. Enumerate the conditions and discuss in detail leukoplakia.

3. Classify red and white lesions. Descriibe clinical features and histopathology of leukoplakia. Add a note on its malignant potential.

Short essays

1. Etiopathogenesis of oral submucous fibrosis.
2. Clinical and histological fatures of leukoplakia.
3. Oral melanotic nevi.
4. Clinical features and histopathology of verrucous carcinoma.
5. Squamous cell carcinoma.

Short notes

1. Histological features of oral submucous fibrosis.
2. Epithelial dysplasia.
3. ABCDE rule.
4. Rodent ulcer.
5. TNM staging.
6. Keratoacanthoma.