Premalignant lesions and biopsy.

Premalignant lesions and biopsy.Presented by- dr. sujay patil Part ii mds

neoplasm is fundamentally a disease of regulation of tissue growth.

The first premise of the tissue organization field theory (TOFT) states that carcinogenesis takes place at the tissue level of biological organization, as does normal morphogenesis

The SMT explicitly assumes that molecular changes in the DNA of a founder cell will make this cell unable to control its proliferation and this, in turn, will result in the formation of a tumor 1

What is a premalignant lesion?A premalignant lesion is "a morphologically altered tissue in which oral cancer is more likely to occur than its apparently normal counterpart."

These precancerous lesions mainly include Leukoplakiaerythroplakia

The main purpose of identifying oral premalignant lesions is to prevent malignant transformation

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Premalignant conditionA premalignant condition is "a generalized state associated with significantly increased risk of cancer." The precancerous conditions include Submucous fibrosis, Lichen planus, Epidermolysis bullosa, Discoid lupus erythematous.

What is dysplasia?If cell division becomes poorly regulated, cells may lose some of their morphological characteristics and/or functions. The tissue becomes disordered in appearance, often with an increase in the numbers of immature cells, and greater variability between cells. This appearance is calleddysplasia. It should be emphasized that dysplasia does not necessarily show that the cells have become cancerous; however, it does suggest underlying changes in the cells, which may predispose to cancer.

In this sense dysplasia may be a stage on the way to cancer development.

HISTOLOGICAL VIEW

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Neoplasiais the term used to describe the development of tumours or cancerous tissue. The development of a tumour requires a series of changes in the biology of the cell, with progressive loss of the controls that limit cell division. Even a cell which is undergoing uncontrolled proliferation will not necessarily be malignant. Malignancy typically arises when the dividing cells invade the normal tissue and move away from their site of origin.

A series of several mutations to certain classes of genes is usually required before a normal cell will transform into a cancer cell.The cells in carcinoma have the potential to invade (and definitely will, if left alone and untreated).

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LeukoplakiaThe term leukoplakia was first used by schwimmer in 1877 to describe a white lesion of tongue A whitish patch or plaque that cannot be characterized clinically or pathologically as any other disease. It is most common percancerious lesion ,in which between 5% and 25% of these lesions are premalignantIn Indian studies the rate of malignant transformation ranges from 0.13 to 2.2% per yr.

The definition of leukoplakia has often been confusing and controversial

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Leukoplakia: EtiologyNo etiologic factor can be identified for most persistent oral leukoplakias (idiopathic leukoplakia). Known causes of leukoplakia include the following:Trauma (eg, chronic trauma from a sharp or broken tooth or from mastication may cause keratosis)Tobacco use: Chewing tobacco is probably worse than smoking.AlcoholInfections (eg, candidosis, syphilis, Epstein-Barr virus infection): Epstein-Barr virus infection causes a separate and distinct nonpremalignant lesion termed hairy leukoplakia.Chemicals (eg, sanguinaria)Immune defects: Leukoplakias appear to be more common in transplant patients.

Classification There are 3 clinical forms of oral leukopliakiaHomogenious Speckeled Proliferative verrucous.

Clinical features..HOMOGENOUSWhite asymptomatic homogenous plaque Surface is usually smooth or wrinkled. It has low risk of transformation.It is the most common form.

Homogeneous Leukoplakia

12Caption: Picture 1. Homogeneous leukoplakia.

SPECKLED Red background with multiple small white macules. C. Albicans infection is often present.High risk for malignant transformation (20-30%)Rare form.

PROLIFERATIVE VERRUCOUSWhite exophytic papillary surface. Tendency for prompt extension. High risk of malignancy transformation (30-40%).Very rare form.

Verrucous or Nodular Leukoplakia

Leukoplakia- HistopathologyFeatures highly variableRanging from hyperkaratosis and hyperplasia to atrophy and severe dysplasia.Significant intrapathologist and interpathologist variation in diagnosing dysplasia.Molecular studies indicated.

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Diagnosis Biopsy and histological examination is the key to define the nature and relative risk of leukoplakiaMolecular biological and immunohistochemical techniques(p53 antigen, HPV 16,18,33) are important for detection of leukoplakia with high risk of malignant transformation.

Differential DiagnosisLichen planusDiscoud lupus erythematous CandidiasisHairy leukoplakiaUremic stomatitis

Treatment plan Surgical excision is the mainstay of the treatment of leukoplakiaCo2 laser surgery may be used as an alternative test.In wide spread or multiple leukoplakia oral administration of 13-cis retinoic acid ( 1 mg / kg of body weight daily for 2-3 months) may be used with limited successTopical application of retinoic acid has been used in the treatment of selective cases Homogenous leukoplakia without epithelial dysplasia may disappear or diminish in size with in 2-3 months after cessation of habit.

Erythroplakia (Erythroplasia)Erythroplakia or Erythroplasia of Queyrat is a rare and dangerous precancerous lesion characterized by red non specific plaque on oral mucosa that cannot be attributed to any other known disease. Red oral lesions usually are more dangerous than white oral lesions.Carcinomas are seen 17 times more frequently in erythroplakias than in leukoplakias, but leukoplakias are far more common.

Erythroplakia

Etiology

Etiology of erythroplakia is unknown.Predisposing factors are mainly smoking, alcohol, and HPV

Clinical featuresErythroplakia mainly involves glance penis . Oral involvement is rareFiery red, slightly elevated or flat plaque of varying size Usually asymptomatic More than 90-95% of cases of erythroplakia demonstrate histologically severe epithelial dysplasia, carcinoma in situ or invasive squamous cell carcinoma at the times of diagnosis.

Erythroplakia

25Figure 16-5 Erythroplakia. A, Lesion of the maxillary gingiva. B, Red lesion of the mandibular alveolar ridge. Biopsy of both lesions revealed carcinoma in situ.

Diagnosis

Biopsy and hispathologic examination conforms the diagnosis and determines the risk of carcinoma DIFFRENTIAL DIAGNOSISSpeckeled leukoplakia Erythematous candidiasisEarly sq. cell carcinoma Local irritationDrug reaction

Treatment planSurgical management is the mainstay of treatement of erythroplakia.The extent of excision depends on histopathologic findings.Interventional laser surgery is an alternative treatement for oral erythroplakia.Topical 5% imiquimod cream and 5- aminolevulinic acid has been used with for success of traetement.

Smokeless tobacco keratosisSmokeless tobacco keratosis is white keratotic lesion of mandibular vestibule encountered in user of smokeless tobacco or snuff.ETIOLOGYMucosal contact with smokeless tobacco stored in vesibular area.

Clinical features Thin gray-white translucent plaque that appers fissured or rippledIt usually takes 1-5 yrs for the lesion to developThe white plaque may thicken gradually to the point of appearing nodularThe lesion is usually confined to the area of placement of smokeless tobacco, and does not detachGingival recession and staining of the roots of the teeth in the area may be present as well.

Diagnosis

The diagnosis is based on the history and the clinical features.Biopsy is occasionally necessary to rule out premalignant and malignant changes.DIFFRENTIAL DIAGNOSISLEUKOPLAKIACANDIDIASISLICHEN PLANUS

TREATEMENT

Cessation of habit.Surgical excision of lesion.

WHAT IS A BIOPSY?Biopsy is the removal of tissue for the purpose of diagnostic examination.

Accurate diagnosis of premalignant or malignant oral lesions depends on the quality of the biopsy.

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CLINICAL EVALUATIONThe anatomic location of the lesion/massThe physical character of the lesion/massThe size and shape of the lesion/massSingle vs. multiple lesionsThe surface of the lesionThe color of the lesionThe sharpness of the boundaries of the lesionThe consistency of the lesion to palpationPresence of pulsationLymph node examination

LABORATORY INVESTIGATIONComplete heamogramHIV HbsAgBTCTBSLPTINRDetermination of serum calcium, phosphorus, and alkaline phosphatase and protein can be very useful in excluding certain pathological processes.

INDICATIONS FOR BIOPSYAny lesion that persists for more than 2 weeks with no apparent etiologic basis.Any inflammatory lesion that does not respond to local treatment after 10 to 14 days.Persistent hyperkeratotic changes in surface tissues.Any lesion that has the characteristics of malignancy

TYPES OF BIOPSYOral cytologyAspiration cytologyIncisional biopsy Excisional biopsyPunch biopsy

WHEN TO REFER FOR BIOPSYWhen the health of the patient requires special management that the dentist feel unprepared to handle.The size and surgical difficulty is beyond the level of skill that the dentist feels he/she possesses.If the dentist is concerned about the possibility of malignancy.

ORAL CYTOLOGYDeveloped as a diagnostic screening procedure to monitor large tissue areas for dysplastic changes.Most frequently used to screen for uterine cervix malignancyMay be helpful with monitoring post radiation changes, herpes, pemphigus.

THE DISADVANTAGE OF ORAL CYTOLOGICAL PROCEDURES INCLUDE:Not very reliable with many false positives.Expertise in oral cytology is not widely availableThe lesion is repeatedly scraped with a moistened tongue depressor or spatula type instrument. The cells obtained are smeared on a glass slide and immediately fixed with a fixative spray or solution.

ASPIRATION CYTOLOGYAspiration cytology is the use of a needle and syringe to penetrate a lesion for aspiration if its contents.Indications:To determine the presents of fluid within a lesionTo a certain the type of fluid within a lesionWhen exploration of an intraosseous lesion is indicated

ASPIRATION CYTOLOGYAn 18 gauge needle on a 5 or 10 ml syringe is inserted into the area under investigation after anesthesia is obtained.The syringe is aspirated and the needle redirected if necessary to find the fluid cavity.

INCISIONAL BIOPSYAn incisional biopsy is a biopsy that samples only a particular portion or representative part of a lesion.If a lesion is large or has different characteristics in various locations more than one area may need to be sampled

Indications:Size limitations Hazardous location of the lesionGreat suspicion of malignancyTechnique:Representative areas are biopsied in a wedge fashion.Margins should extend into normal tissue on the deep surface.Necrotic tissue should be avoided.A narrow deep specimen is better than a broad shallow one.

HOW AN INCISONAL BIOPSY IS PERFORMED

EXCISIONAL BIOPSYAn excisional biposy implies the complete removal of the lesion.Indications:Should be employed with small lesions. Less than 1cmThe lesion on clinical exam appears benign.When complete excision with a margin of normal tissue is possible without mutilation.

HOW EXCISIONAL BIOPSYIS PERFORMED

PUNCH BIOPSYA punch biopsy is a type of biopsy where a round area of skin and underlying tissue is removed using a sharp hollow cutting instrument.Punch biopsy is done to diagnose certain types of cancer that appear on or in the skin most common usebasal cell carcinomasquamous cell carcinoma

HOW THE PUNCH BIOPSY IS DONE

PRINCIPLES OFSURGERYTO BE PERFORMED

ANESTHESIABlock anesthesia is preferred to infiltrationWhen blocks are not possible distant infiltration may be usedNever inject directly into the lesion

TISSUE STABILIZATIONDigital stabilizationSpecialized retractors/forcepsRetraction sutures

HEMOSTASISSuction devices should be avoided.Gauze compresses are usually adequate.Gauze wrapped low volume suction may be used if needed.

INCISIONIncisions should be made with a scalpel.They should be convergingShould extend beyond the suspected depth of the lesionThey should parallel important structuresMargins should include 2 to 3mm of normal appearing tissue if the lesion is thought to be benign.5mm or more may be necessary with lesions that appear malignant, vascular, pigmented, or have diffuse borders.

HANDLING OF THE TISSUE SPECIMENDirect handling of the lesion will expose it to crush injury resulting in alteration the cellular architecture.

SPECIMEN CAREThe specimen should be immediately placed in 10% formalin solution, and be completely immersed.

MARGINS OF THE BIOPSYMargins of the tissue should be identified to orient the pathologist. A silk suture is often adequate. Illustrations are also very helpful and should be included.

SURGICAL CLOSUREPrimary closure of the wound is usually possible Mucosal undermining may be necessary Elliptical incision on the hard palate or attached gingiva may be left to heal by secondary intention.

Incisional biopsies only require removal of a section of tissueSoft tissue overlying the lesion should be reapproximated following thorough irrigation of the operative site.The specimen should be handled as previously described

NO ONE IS ALONE AGAINST THE FIGHT OF CANCER

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