Oral Cancer

     Click here to download

For Ppt:  http://www.mediafire.com/download/38acan3lrsj634h/Growth&development_clinical_application_(2).pptx

For word file :  http://www.mediafire.com/download/2ttbi2l098slnot/Oral_Cancer.docx


CONTENTS

INTRODUCTION TO ORAL CANCER

TUMOR

—   By definition is an abnormal mass of tissue, growth  of which exceeds and is uncoordinated  with that of normal tissues and persists in the same excessive manner, after  the cessation of the stimuli that evokes the changes.

—  Tumor can either be benign & malignant.

—  Benign tumors are NOT CANCER……..

—  Benign tumors are rarely life-threatening.

—  Generally, benign tumors can be removed, and they usually do not grow back.

— do not invade the tissues around them. and do not spread to other parts of the body. Malignant  tumors  may be life-threatening

—  MALIGNANT TUMORS.

—  Malignant tumors often recur.

• —Cells from malignant tumors can spread to other parts of the body.The cells spread by breaking away from the original cancer (primary tumor) and entering the bloodstream or lymphatic system.
• They invade other organs, forming new tumors and damaging these organs. The spread of cancer is called metastasis.

—   ORAL CANCER

• —  Oral cancer is part of a group of cancers called head and neck cancers.
• —   Oral cancer can develop in any part of the oral cavity or oropharynx.
• —   Most oral cancers begin in the tongue and in the floor of the mouth.
• —   Almost all oral cancers begin in the flat cells (squamous cells) that cover the surfaces of the mouth, tongue, and lips. These cancers are called squamous cell carcinoma

CLASSIFICATION

HISTOLOGICAL CLASSIFICATION OF  CANCER OF ORALMUCOSA

—  CARCINOMA

◦      Squamous cell carcinoma

◦      Verrucous carcinoma

◦      Basaloid squamous cell carcinoma

◦      Adenoid squamous cell carcinoma

◦      Spindle cell carcinoma

◦      Adenosquamous carcinoma

◦      Undifferrentiated carcinoma

◦      ETIOLOGY & PATHOGENESIS

1. Progression of cancer .
2. Carcinogenesis is a  genetic process that lead to change in morphology & in cellular behavior.
3. Major genes involved in OSCC:
4. Proto- oncogenes & tumor suppressor gene.

Four groups of genes involved       

• —  Growth promoting oncogenes
• —  Growth inhibiting proto oncogenes
• —  Genes regulating apoptosis
• —  Genes involved in DNA repair

—  Proto – oncogenes increases cell growth and differentiation and are involved in carcinogenesis.

• —  Proto oncogenes associated with HNSCC include rat sarcoma(ras),bcl-1,bcl-2 ( B- cell lymphoma),int-2,
• —  CK-8 & CK -19
• —  TSG regulate cellgrowth & differentiation.
• —  Functional loss of TSG is common in carcinogenesis.
• —  for this to happen, both copies of a TSG must be lost(LOH) or inactivated. ‘2 hit hypothesis’
• —   TSG involved in HNSCC are P53,Rb(retinoblastoma)  ,P16INK4A.
• —  The current model of carcinogenesis is a multistage process.

• —  Loss of chromosome arm 3p & 9p – early lesion progress from benign to dysplastic.

SQUAMOUS CELL CARCINOMA

• —Also known as epidermoid carcinoma
• Most common malignant neoplasm of the oralcavity.
• 1 of the 10 most common causes of death.
• The majority of oral cancers are squamous cell cancers.
• Approximately 95% of OSCC occurs in people older than 40 yrs. High incidence of oral cancer is found in south asian countries like India,Pakistan,srilanka & Bangladesh
• In most part of the world male: female ratio is approximately 2:1 for oral carcinoma.
• In south east asia oral cancer is the most common cancer in males & 3rd most common cancer in females.

 Major etiological factors:

1. —VIRUS
2. ALCOHOL
3. — SYPHILIS
4. — SUNRAYS
5. — TOBACCO
6. — NUTRITIONAL FACTORS
7. — TRAUMA
8. — IMMUNTY
9. — GENETIC FACTORS

TOBACCO  

• It is the major etiological factor
• Smokeless tobacco : Smokeless "Spit" tobacco contains over 2,000 chemicals, many of which have been directly related to causing cancer.

Tobacco contain potent carcinogen

1.  nitrosamines,
2.  polycyclic aromatic hydrocarbon
3. — nitrosodichthanolamine
4. nitrosoproline
5. polonium.

TOBACCO SMOKING

·     Tobacco smoke contain:

·      CO

·     thiocyanate,

·     hydrogen cyanide,

·     nicotine &

·      Metabolites of these constituents.

o   Pooling of carcinogens in saliva gives rise to cancer in floor of the mouth & ventral & lateral tongue.

o    of TP53gene

o   Smoking is strongly associated with soft palate cancer.

·     ALCOHOL

·     All forms of alcohol including “ hard “ liquor,wine & beer have implicated in the etiology of oral cancer.

·     Synergestic action of alcohol & tobacco  is that alcohol causing dehydration of mucosa & thus increasing mucosal permmeability for potential carcinogens in alcohol or tobacco.

 ACTINIC RADIATIONS

o    Lip cancer

o   Fair skinned people engaged in outdoor  occupation such as farming & fishing.

                  ATMOSPHERIC POLLUTION:

o   Sulphur dioxide & smoke concentration in the atmosphere causes squamous carcinoma of larynx & pharynx.

                 SYPHILIS:

o    Oral malignancy is associated with teritiary stage of syphilis.

o   Previously for the management of syphilis we used potential carcinogens like arsenic & heavy metal

—  NUTRITIONAL FACTORS

Vitamin A deficiency causes excessive keratinisation of skin & mucous membrane.Deficiency can predispose to formation of carcinom Poor nutritional status has been linked to an increased rise of oral cancer, the only convincing nutritional factor that has been associated with oral cancer is iron deficiency of Plummer-Vinson syndrome (Patterson-Kelly syndrome, sideropenic dysphagia)

 IMMUNITY

There is decreased immuno surveillance with :

1. Age
2. It is common in immunosuppressed patients following organ & bonemarrow transplantation.
3. HIV/AIDS patient
4.  Virus

• HPV & HIV virus can lead to oral cancer.
• HPVsubtypes 16. 18. 31 . and 33 are the strains most closely associated with dysplasia and squamous cell carcinoma.

CHRONIC TRAUMA

1. Faulty restoration
2. Sharp teeth
3. Ill fitting dentures
4. Chronic cheek biting habit.
5.  Chronic irritation along with other carcinogens promote transformation of epithelial cells.
6.  High alcohol content in mouth washes have been implicated in oral cancer. 

CLINICAL FEATURES—  

• AGE & SEX: predominantly occurs in males in the ratio 2:1 older than 50 yrs average of 60 yrs.
• Site : most commonly involved are lateral borders of the tongue therefore common site of bony invasion is ,the posterior lingual aspect of the mandible.
• — Lesions of lower lip & anterior floor of the mouth may invade anterior mandible.
• — Also seen on tonsil, softpalate and buccal vestibule.
• — Uncommon on hard palate

—  SIGNS & SYMPTOMS

• Discomfort is the most common symptom that leads a patient to seek care.
• Patient may present with awareness of mass in the mouth & neck. 
• Small lesion is asymptomatic— 
• Large lesion may cause pain or paresthesia & swelling
• Patients complain of persistent ulcer in the oral cavity.
• In advanced diseases,dysphagia ,odynophagia,otalgia ,limited movement,oral bleeding may occur.
• Patient report significant weight loss & feel unwell

— Oral squamous cell carcinoma has a varied clinical presentation including:

1. • Exophytic (mass-forming;  fungating, papillary, verruciform)
2. • Endophytic (Invasive. burrowing. ulcerated)
3. • Leukoplakic (white patch)
4. • Erythroplakic (red patch)
5. • Erythroleukoplakic (Combined red-and white patch)

— 

• Appear initially as white or red ( mixed) irregular patchy lesion of the affected epithelium.
• — With time lesion exhibit central ulceration.
• — Carcinomatous ulcer is irregular in shape,with indurated and raised everted edges.
• — Base is often broad and are dome like and nodular
• — Firm on palpation
• — Exophytic lesion with irregular ,fungating ,papillary and verruciform surface.
• — Surface is ulcerated and base is firm on palpation.

 Endophytic  lesion – depressed irregularly shaped ulcerated central area  with surrounding rolled border Rolled border represents invasion of malignant cells into the adjacent  tissue .

Lymph nodes

• —  Lymph node :superficial  & deep cervical lymph nodes are commonly affected
• —  Lymph nodes become enlarged and firm
• —   Lymph nodes are nontender unless associated with  secondary infection or an inflammatory response.
• —  Fixation of lymph nodes to adjacent structures occur later.
• Effect on adjacent structures

Fixation of primary tumor to adjacent tissues   ie overlying bone suggests involvement of periosteum  and possible spread to bone. 

RADIOGRAPHIC FEATURES

• —  Appearance : semicircular or saucer shaped erosion into the bone.
• —  Margins: there are ragged ill- defined  non corticated borders  that  illustrate varying uneven osteolytic  invasion .
• —  Border may rarely appear smooth without a cortex in the case of underlying bony  erosion.
• —  Finger – like extension: in the case of extensive bone involvement  the periphery appears to have  finger –like extension  preceding a zone of impressive osseous destruction.

INFILTRATION OF BONE

—  Little bays of bone destruction extending into the bone .

—  Margins of the bay appear irregular & jagged.

—  Thus providing a finger like projection  and the appearance is  described as infiltration of bone.

PATHOLOGIC FRACTURE

— The borders show sharpened thinned bone ends with displacement of segments and an adjacent soft 

tissue mass.

— Inferior borer of mandible may be thinned or destroyed. in case of extensive tumor pathologic 

fracture occurs.

— INTERNAL STRUCTURE

— Internal structure of scc in jaw lesion appears totally radiolucent.

— Occasionally small islands of residual normal trabecular bone are seen within radiolucency.




Effect on surrounding tissue

• — Evidence of invasion of bone around tooth may appear as widening of periodontal ligament space with loss of lamina dura. 

• — Teeth appear to float in a mass of radiolucent soft tissue deprived of any bony support. 

• — In extensive tumor , soft tissue mass may grow into the teeth and teeth appears to be grossly displaced from its normal position.

• — Tumors grow along the inferior neurovascular canal and through the mental foramen resulting in loss of cortical boundaries . 
• — Destruction of floor of nose, maxillary sinus & buccal and lingual mandibular plate may occur. 

SITE OF ORAL CANCER

CARCINOMA OF FLOOR OF MOUTH

• — Site: most frequently in anterior portion of floor of the mouth than in the posterior area 

• — Extends fequently into lingual mucosa of the mandible & then into the mandibular proper as well as into the tongue 

• — May invade deeper tissues and extend into the submaxillary & subligual gland. 

• — Metastases commonly into submaxillary group of lymph node ,here lymphatic cross drainage exist contralateral metastases are often present. 

• — It represents almost 15% of all cases of intra oral cancers. 
• — Etiology: Smoking pipe or cigar is the major etiological factor. 

• — Leukoplakia does occur in this region. 

• — Epithelial dysplasia & malignant transformation in the leukoplakia occur with great frequency here . 
• — Appearance: typical carcinoma in the floor of the mouth is an indurated ulcer of varying size situated on one side of midline. 

• — May/maynot be painful. 

• — Treatment & prognosis 

• — Treatment is unsuccessful and more frequently difficult. 
• — X ray radiation & use of radium often give better result. 

CARCINOMA OF LIP
— The disease chiefly occur in elderly men. Lower lip more commonly involved.  Great incidence 

occur in age group between 55 & 75 years.

— Etiology: 

• Use of tobacco through pipe smoking. 
• — The heat, trauma of the pipe stem and the combustion end –products of tobacco may be of significance in the etiology. 

• — Sunlight ,prolonged exposure to sun causes preneoplastic changes. 
• — Poor oral hygiene 
• — Traumatic experience such as cigarette burn, chronic trauma from jagged teeth. 
• — Leukoplakia have been associated. 

CARCINOMA OF TONGUE

• — Most common oral carcinoma 

• — 60% cases arising from anterior 2/3rd of tongue & undersurface of tongue. 

— Etology:

• — physical trauma 
• Syphilis- found to be an active cause 
• – Chronic glossitis & arsenic therapy . 

— The lesions on posterior border of tongue are of high grade malignancy, metastasises early & have poor prognosis.

— Symptoms:

• — Painless mass or ulcer – the most common presenting sign, becomes painful after secondary infection. 
•  Immobility of the tongue: due to extensive carcinomatous infiltration of the lingual musculature. worse when floor of the mouth is involved, it causes difficulty in speech. 
• — Hoarseness of voice & dysphagia: 
• — Carcinoma involve posterior 3rd with involvement of pharynx & larynx. 
• — Salivation : extensive salivation followed by blood stained saliva. 
• — Foetor oris : as the patient is unable to swallow saliva, offensive smell in the mouth occurs due to bacterial stomatitis. 
• — Sore throat: pain & soreness in the throat in case of lesion on the posterior border of the tongue. 

— Signs:4 varieties

—1.   Ulcerative variety:

• — seen near the edge of tongue 
• — ulcer looks irregular and the edges are raised & everted. 
• — Floor is covered by yellowish gray slough. 
• — Base is indurated. 

2. Warty growth

• — It usually possesses a broad and indurated base. 
• — It is developed on excess proliferating growth of filiform papillae. 
• — Rarely it takes cauliflower type of look. 
• An indurated submucous plaque can be felt. 
• A chronic fissure which donot heal is usually presented. 

An indurated submucous plaque can be felt.

A chronic fissure which donot heal is usually presented.

— Local spread : it spreads by infiltration and invasion .

— carcinoma of anterior 2/3rd of the tongue :starts on the lateral margin of the tongue and invades the floor of the mouth early. It — doesnot extend to otherside across the midline.

— Carcinoma of posterior 1/3rd of the tongue :Tends to spread to the tonsil, epiglottis & soft palte.

— Lymphatic spread  Tip of the tongue: drain into submental lymph nodes & jugulo omohyoid nodes.

• — Ant 2/3rd drain into submandibular LN.

• — Posterior 1/3rd –it drains into jugulodigastric group of the upper deep cervical nodes on both sides of the neck.

 CARCINOMA OF BUCCAL MUCOSA

—  Site: lesions develop most frequently along or inferior to a line opposite the plane of occlusion.

—  It usually occurs opposite to the 3^rd molar.

—  Symptoms:  the lesion is often painful.

—  Appearance: tumor begins as small nodules and enlarge to form a wart- like growth which ultimately ulcerates.   

—  Extent :induration and infiltration of deeper tissues .extension into the muscle of neck, alveolar mucosa and ultimately into bone may occur.

—  Exophytic  growth / verrucous growth

—  Metastasis:  submaxillary lymph nodes. 

—

CARCINOMA OF LABIAL MUCOSA

—  Cause : it is frequently encountered in person who habitually keeps a mixture of tobacco lime in the labial vestibule.

—  Common signs & symptoms

◦       growth or swelling ,soreness and ulceration.

—  Extent:

—  advanced lesion  may be ulcerative – infiltrative type  ,showing   exophytic growth.

—  Lymphnode  involvement may be unilateral /bilateral

CARCINOMA OF PALATE

—  Cause : reverse smoking.

—  Sex:   in  females

—  Appearance:

—  palatal cancer usually manifests as poorly defined ulcerated painful lesion on one side of midline.

—  Base & surface:

—  lesions are exophytic ,broad base & nodular surface.

—  Extent:   laterally into tonsillar pillars/uvula.

—  Tumor to hard palate my invade nasal cavity.

—  While infiltrating ,lesion of soft palate extend into nasopharynx.  

CARCINOMA OF MAXILLARY SINUS

—  The tumor arises from metaplastic epithelium of the sinus mucous membrane lining .

—  Typically carcinoma of the maxillary sinus is a disease of elderly persons.

There Is a slight predilection for males.

—  Affected patients generally complain of a chronic unilateral nasal stuffiness or notice an ulceration or  mass of the hard palate or alveolar bone

—  When the second division of the trigeminal nerve is involved, intense pain or paresthesia of the midface or maxilla may occur, perhaps simulating a toothache. .

CARCINOMA OF GINGIVA & ALVEOLAR MUCOSA

—  

Gingivai and alveolar carcinomas are usually pain less

— Site: most frequently arise from a keratinized mucosa in a posterior mandibular site.

— Tumors of the maxillary alveolar ridge may extend onto the hard palate.

— if the tumor is adjacent to a tooth it may mimic periodontal disease or a pyogenic granuloma

— Of all the intra oral carcinomas this one is least associated with tobacco smoking and has the greatest predilection for females.

— when the cancer develops in an edentulous area it may give rise to a mass that "wraps around" a denture flange and superficially resembles inflammatory fibrous hyperplasia

(epulis fissuratum)

— Gingival carcinoma often destroys the underlying bone structure causing tooth mobility.

— This lesion may not become clinically evident until after tooth extraction when it proliferates out of the socket to mimic the hyperplastic granulation tissue of epulis granulomatosis.

                                

                                                  STAGING OF CANCER

TNM STAGING FOR ORAL CANCER

—  T- Primary tumor

—  Tx-primary tumor cannot be assessed.

—  To-no evidence of primary tumor.

—  Tis- carcinoma insitu.

—  T1-Tumor 2cm or less in greatest dimension.

—  T2 – Tumor is larger than 2cm but less than 4cm.

—  T3 – Primary tumor is greater than 4cm.

—  T4- Tumor invading adjacent structures.

—  T4a- locally advanced but resectable tissue.

—  T4b- tumor that is not technically resectable but available for non surgical option such as chemotherapy.

—  REGIONAL LYMPHNODES:

—  Nx : lymph nodes cannot be assessed.

—  No :  No regional lymph nodes

—  N1: metastasis in single ipsilateral lymph nodes less than 3cm in diameter.

—  N1a : lymphnode considered do not contain tumor growth.

—  N1b : lymph node considered do contain tumor growth.

—  N2:metastasis in a single ipsilateral lymph node, more than 3cm but not more than 6 cm in greatest dimension,or in multiple ipsilateral lymph nodes, none more than 6cm in greatest dimension; or in bilateral / contralateral lymphnodes, none more than 6cm in greatest dimension.

—  N2a:metastasis in single ipsilateral lymph node ,more than 3cm but not more than 6cm in greatest dimension.

—  N2b: metastasis in multiple ipsilateral lymph nodes,none more than 6cm in greatest dimension. 
  N2c: metastasis in bilateral or contralateral lymphnodes, none more than 6cm in greatest dimension.
  N3:metastasis in a lymph node more than 6cm in greatest dimension. 

METASTASIS

  M – distant metastasis

—  Mo – no distant metastasis

—  M1- distant metastasis

 

STAGE GROUPING

—  Stage 0           Tis             No                 Mo

—  Stage I            T1              No                Mo

—  Stage II           T2              No                Mo

—  Stage III          T1,T2,         N1                Mo

—                        T3             No,N1           Mo

—  Stage IV A       T1,T2,T3    N2                Mo

                      T4a            No,N1,N2     Mo 

—  Stage 1V B       Any T        N3                Mo

                       T4b           Any N           Mo

—  Stage IV C       Any T         Any N            M1

VARIANTS OF SCC

—  Verrucous carcinoma

—  Basaloid squamous carcinoma

—  Spindle cell carcinoma/ sarcomatoid SCC

—  Adenoid SCC

   VERRUCOUS CARCINOMA

—  Is a slow growing low grade carcinoma.

—  Also known as “snuff dippers cancer” or ackerman’s tumor.

—  Spit tobacco associated malignancy.

—  Tobacco chewers have high percentage of these cases.

—  It occurs in a patient habitual to hold quid in the buccal sulcus. 

CLINICAL FEATURES

—  Age & sex:

—  Generally seen in elder population with mean age of occurences of 60-70 yrs.

—  Men are affected more as compared to women.

—  Common sites: buccal mucosa  and gingiva or alveolar ridge.

—  Symptoms: pain & difficulty in mastication

—  Appearance : can be described clinically as papillary, verrucoid, fungating or cauliflower like.

—  Base: large broad lesion with minimum to extensive elevation above the surface of mucosa.

—  Margins :  well defined,show rim of slightly elevated normal mucosa.

—  Lymphnodes: regional lymph nodes are tender, and enlarged simulating metastatic tumor

—  Rarely spreads to lymph nodes,but the node involvement is usually inflammatory.

—   progress:slow growing,chiefly exophytic,and only superficial invasive.

—  Least metastatic potential.

—  Prognosis: very good.

DIAGNOSIS

—  CLINICAL DIAGNOSIS:

—  Verrucous palillary surface with cleft in between with the history of keeping tobacco at the location where lesion is found.

—  LABORATORY DIAGNOSIS:

—  In biopsy, there is marked epithelial proliferation ,parakeratin plugging and pushing margin. 

DIFFERENTIAL DIAGNOSIS

—  Verrucous hyperplasia : proliferative epithelial lesion with epthelial hyperplastic fold extending above the margin of surrounding mucosa.

—  In verrucous carcinoma fold invade down into connective tissue and hence are below the surrounding normal mucosal region.

—  Chronic hyperplastic candidiasis:

—  Epithelial hyperplasia not so extensive & in verrucous carcinoma cleft – like spaces are often between the heaped up masses of carinomatous epitheli

—  Well- differentiated squamous cell carcinoma- lymph node matastasis  is extensive .

—  Hystopathology should be carried out to confirm diagnosis.

ADENOID SQUAMOUS CELL CARCINOMA

—  Also called as adenoacanthoma.

—  The adenoid structure result from loss of cohesion of the epidermoid tumor cells, without sialomucin production.

—  Clinical features

—  Age & sex: females are affected more with age range from 20 -50 yrs and older.

—  Common site – lip & head & neck region.

—  Lower lip is affected more common than upper lip and also the vermillion  border of the lip.

—  Clinical Diagnosis:

—  lesion on lower lip with nodular surface and scaling will yield in diagnosis.

—  Laboratory diagnosis:

—  In biopsy, epithelium show the characteristic solid & tubular ductal structures which are lined by a layer of cuboidal cells and often contain or enclose acantholysis or dyskeratotic cells.

—  Appearance: it appears as simply elevated nodules, that may be slow crusting, scaling.

—  Usually without surface ulceration.

—  Margins- sometimes elevated or rolled borders of the lesion.

—  Good prognosis with rare metastasis.

SPINDLE CELL CARCINOMA

—  Also called as ‘lane tumor’, ‘poypoid squamous cell carcinoma’or ‘carcinosarcoma’.

—  It is a variant of squamous cell carcinoma.

—  There is a proliferation of spindle cells believed to be arising from the surface epithelium.

—  Many case of spindle cell carcinoma develop as a recurrence after radiotherapy to the squamous cell carcinoma.

—         This phenomenon is “dedifferentiation”.

—  Clinical features:

—  Sex & age distribution- it is more common in male with mean age of occurrence of 57 years.

—  Common site : lower lip ,tongue and alveolar ridge, or gingiva with remainder scattered at other site.

—  Symptoms: there is swelling,pain and prescence of non healing ulcer.

—  Appearance: the initial lesion appear either with a poypoid, exophytic or endophytic configuration.

—  The lesion is fleshy.

—  Progress: it grows rapidly and diagnose at a later stage.

—  Diagnosis

—  Clinical diagnosis:-rapidly growing polypoid exophytic mass can yield in the clinical diagnosis of the lesion.

—  Laboratory diagnosis:biopsy will show proliferation and “dropping off” of basal cell to spindle cell. 

BASALOID SQUAMOUS CELL CARCINOMA

—  Is a form of carcinoma with a mixed composition of basaloid & squamous cells.

—  This is a form of oral carcinoma in which the basaloid component comprises small cells with hyperchromatic nuclei and scant cytoplasm that are crowded together into lobulated sheets or strands focally connected to the surface epithelium.

—  Cells at the periphery of the lobules are often palisaded.`` 

BIBLIOGRAPHY

1. BURKET’S ORAL MEDICINE
2. SHAFER’S TEXT BOOK OF ORAL PATHOLOGY
3. TEXTBOOK OF ORAL MEDICINE –ANIL GOVINDRAO GHOM
4. ORAL & MAXILLOFACIAL PATHOLOGY -NEVILLE