Diagnosis of oral cancerDr.Huda Moutaz Ismail Department of oral & maxillofacial surgery

University of Baghdad /college of dentistry

• 5-year survival for localized disease is 76%

• 5-year survival for metastatic disease is 19%

Early Detection Saves Lives Cancer of the oral cavity is a major public health problem with approximately 300,000 new cases reported annually worldwide.

The majority present with locally advanced disease (stage III and IV) with dismal 5-year survival rates of 20-50%.

Dentists and hygienists are the best overall defense against oral cancer – they are, in fact, a lifesaver.

In all primary oral malignant tumours, 92% are the squamous cell carcinomas.

Approximately 70% of oral SCC develop in the floor of the Mouth , tongue or retromolar region , Squamous cell carcinoma can arise from oral epithelium itself and from the terminal portions of the ducts of the salivary glands.

retromolar region tongue floor of the Mouth

Overview

▬ Typically males, 50–70 years, drinking ,smokers.

▬ Painless mass

▬ Predilection areas:

▬ Lymph node involvement in 30–65% when diagnosed.

• Proper lighting• Dental mouth mirror• Gauze squares• Gloves• 5 minutes

1-Visual examination

Tools and Time

Premalignant lesion is a morphologically altered tissue in which cancer is more likely to occur than its apparently normal counterpart

Types of precancerous lesions :• 1. Leukoplakia * Nicotine stomatitis *Tobacco pouch keratosis• 2. Erythroplakia • 3-Oral epithelial dysplasia

• The precancerous conditions is a generalized state associated with a significantly increased risk of cancer. If left untreated, these conditions may lead to cancer.

include-• 1. Oral submucous fibrosis • 2. Lichen planus• 3. Epidermolysis bullosa • 4. Discoid lupus erythematous. DLE may affect the lips and inside the

mouth, causing ulcers and scaling, and predisposing to squamous cell carcinoma (SCC)

Warning Signs-Leukoplakia* white , Speckled leukoplakia (red & white ) patch in the mouth that is persistent . white and warty (verrucous leukoplakia)

,

-Erythroplakia

Speckled leukoplakia warty leukoplakia)

A poorer prognosis is suggested by:• surface nodularity• erythema• ulceration• increased firmness and induration• unexplained hemorrhage.

• Other Possible Warning Signs-Lump or thickening of oral soft tissue , crust or eroded area in the lips

-Mouth sore that does not heal or bleed spontaneously .

-Soreness or “lump” in throat

-Difficulty in swallowing , speaking , or moving the tongue .

-Hoarseness

-Numbness of tongue or mouth

-Swelling of the jaw , mobility of teeth .

-Erythroplakia Microscopically, the tissue exhibits severe epithelial dysplasia, carcinoma-in-situ, or invasive squamous cell carcinoma in 90% of cases.

Visual examination /Examples of malignant lesion How you can suspect malignancy by visual examination Early signs of melanoma are summarized by the mnemonic "ABCDE":• Asymmetry• Borders (irregular)• Color (variegated)• Diameter (greater than 6 mm)• Evolving over time

Melanoma

Note: Unexplained pigmented oral lesions are of concern if they are new or changed. Biopsy is recommended unless the pigmented area has been present and unchanged for 5 years or longer

Squamous cell carcinoma presenting as an ulcer with rolled indurated margins on the lip and at a variety of intra-oral sites.

2nd example

Adjunctive clinical technique (oral cancer screening tools ) such as :

-Toulidine blue-Exfolitive cytology-Brush biopsy -Chemiluminescence -Tissue autofluorescence-Photodynamic detection

VITAL STAININGTolonium chloride (toluidine blue), a nuclear dye that has been applied to the mouth as an oral rinse. Abnormal areas of mucosa stain blue .

The method used for-Aid in identification of clinically suspicious mucosal abnormalities-As a useful way of demarcating the extent of a potentially malignant lesion prior to excision .

29 Blue-stained mucosa in the palate followingtopical application of tolonium chloride.

Toluidine blue staining test was reliable in precancerous and cancerous lesions, which present as erosive and red-white lesions.

Toluidine blue

.The patient rinses for 20 seconds with 1% acetic acid to clean the area; then 20 seconds with plain water; then 60 seconds with 1% aqueous toluidine blue solution; then again 20 seconds with a 1% acetic acid; and finally with water for 20 seconds.. Lesions that exhibited dark blue (or) stippled staining were considered as a "positive" test >> then immediately biopsy , while those that stained faintly (or) not at all were considered as "negative" test.

• It may give false positive results in inflammatory lesion but never false negative

toluidine blue positive

Toluidine blue staining is a highly sensitive and specific test for carcinoma in situ and invasive oral cancer

A distinctive lesion in an area of atrophic mucosa

Dye taken up by the area, which on biopsy showed epithelial dysplasia

TB is a metachromatic vital dye that may bind preferentially to tissues undergoing rapid celldivision (such as inflammatory, regenerative and neoplastic tissue), to sites of DNA change . The binding results in the staining of abnormal tissue in contrast to adjacent normal mucosa.

EXFOLIATE CYTOLOGYExfoliate cytology is a sampling method that involves the microscopic examination of cells obtained from the surface of mucosal lesions as a mean of detecting malignancy & microbiological changes

Indication of exfolitive cytology

-Diffuse ,large or multiple lesions-Urgent result is required-patient is not indicated for surgery

-Scrap the lesion with stainless steel spatula or moistened tongue depressor -Cells smeared on glass slide -Fixation with solution or fixation spray & allow the slide to dry-Stained for microscopic examination .

Oral exfoliative cytology has diagnostic value in cancer patients than in precancers patients.

Brush biopsy This uses a specially designated circular brush called (Oral CDX brush) as a

sampling device to reach deeper layers of the oral epithelium .Major limitations are cost and high false-negative rates. It employs the application of a brush to the lesion to collect a sample that includes not only superficial cells but also those from the basal layer , the brush is rotated until pinpoint bleeding occur which noted entry to the lamina propria thus obtaining cells through full thickness of epithelium . These techniques have been developed as a method of monitoring epithelial dysplasia and detecting squamous cell carcinoma.

28 Cytobrush.

Steps for oral brush biopsy

Plain swabVariant of exfoliative cytology is swab which look for the presence of microorganism A plain microbiologic swab can be used to detect the presence of bacteria , fungi, herpes

simplex viruses, or varicella zoster virus. Swabs should be sent to the laboratory promptly.

-Viral swabs should be placed in a transport medium-After taking swab deposit the result in petri-dish and recheck the dish in 24hr to look for colonies growth

Swab of an angle of the mouth.

ChemiluminescenceIt is clinical inspection of oral mucosa with the aid of chemiluminescent Blue/white light (vizilite system) was recently suggested to improve the identification of mucosal abnormalities It involve the use of an oral rinse 1% acetic acid for 1 minute followed by examination of the oral mucosa under diffuse chemiluminescent low-energy blue /white light with wave length of (490-510nm)

The theory behind this the acetic acid will remove glycoprotein and slightly desiccate oral mucosa ,the abnormal cells will absorb & reflect the light in different way in respect to normal cells .Hence the normal mucosa will appear blue while the abnormal mucosa will reflect the light due to high nuclear /cytoplasm ratio & appear more aceto white ,brighter ,sharper &more destinct margin .

How ViziLite Works

How ViziLite Plus WorksThe normal epithelium take on blue hue while the abnormal (acetowhite lesion ) appear distinctly white , Now days the vizilite system modified to include the use of toluidine blue stain.

Tissue fluorescent imaging

Fluorescence technology, in particular, is a noninvasive approach for assessing and aiding in the visualization of chemical and morphological patterns of the various tissues and substances within the oral cavity.

Every cell in the body contain molecules which have characteristic feature of become fluorescent when excited by ultraviolet or violet range radiation of suitable wave length ,the molecular changes occured in abnormal cells will alter their interactions with light .

Products such as the VELscope Vx™  and the DentLight Oral Exam Light Kit  enable clinicians to visually scan the entire oral cavity for changes in the fluorescence pattern of tissue, which may indicate an area of concern.

When the tissue illuminated with short wave length light (usually violet or blue ) the cells become excited and emit longer wave length (low energy)

Normal cells >> emit green light Abnormal cells >> emit dark light

Exposure to blue light spectra (400-460 nanometers) may maximizea differential profile in areas undergoing neoplastic change in which a loss of fluorescencevisualization is reported.

VELscope

VELscope

The Identafi oral cancer screening device uses a multispectral fluorescence and reflectance technology to enhance visualization of mucosal abnormalities. The small, cordless handheld device uses a three-wavelength optical illumination and visualization system that allows dental professionals to identify oral mucosal abnormalities. Identafi’s three separate wavelengths of light—white, violet, and green-amber—excite oral tissue, As a result, biochemical changes can be monitored with fluorescence, while morphological changes can be monitored with reflectance

, providing the clinician three different illumination perspectives to visualize the area being examined. A disposable mirror attachment assists in visualizing the area in an indirect manner.

• Wearing reusable Identafi® filtered eyewear to enhance visual effects and allow transmission of reflected light, the health professional then switches to Violet for a second observation.

• The clinician’s photosensitive glasses block the violet excitation light and allow the observance of the tissues natural fluorescence. Violet light enhances normal tissue’s natural fluorescence; however, suspicious tissue appears dark because of its loss of fluorescence.

• When suspect abnormalities are present the selector is switched to Amber light, which enhances normal tissue’s reflectance properties so the clinician may directly observe the difference between normal and abnormal tissue’s vasculature. This independent view of vascular architecture may assist in the assessment of confounders when screening for oral cancer.

Photodynamic detection PDD

It is diagnostic technique involving administration of light activating chemical (photosensitizer) to enhance cell fluorescence to the target cells that is stimulated usually by short wave light then collected (different wavelength with less energy ) & analyzed by spectroscope .

• Immunohistochemical identification of tumour markers

• The identification of tumoral markers, notably cytokeratins in smears from the oral cavity has attracted considerable interest. Cytokeratin expression profile provides useful information on cell differentiation status but its potential for early diagnosis of oral cancer is limited . However, certain cytokeratins, such as K8 and K19 are useful if not definitive indicators of malignancy, particularly if their presence is interpreted in conjunction with other information, such as DNA profile

* Cytokeratins are proteins of keratin-containing intermediate filaments found in the intracytoplasmic cytoskeleton of epithelial tissue.

Surgical biopsy

Biopsy. The gold standard diagnostic test for oral mucosal lesions that are suggestive of premalignancy or malignancy remains tissue biopsy and histopathological examination.

-Incisional biopsy

-Excisional biopsy

Indications for biopsy include lesions that:• have neoplastic or potentially malignant features• are enlarging• persist > 3 weeks• are of uncertain etiology• fail to respond to treatment• cause concern.

Incisional biopsy : is removal of the representive portion of the target lesion & part of normal tissue Key points• Use a scalpel when a bullous disorder is suspected as a punch might tear the fragile tissue .• Hold the tissue with suture or forceps to avoid squeezing and causing crush artifacts.

• Snap-freeze specimen in liquid nitrogen or place in Michel solutionif for immunostaining; if for other staining, place it in 10% neutral buffered formalin.

Figure 3.2 Biopsy kit. Figure 3.3 Scalpel and punch.

• Incisional biopsy • Figure 4. Homogenous leukoplakia affecting the right lateral and ventral areas of the tongue (a). Incisional biopsy is used to

sample a thick, keratotic region at the anterior aspect of the tongue. Infiltration of local anesthetic (b) is followed by tracing of an ellipse (c and d). The anterior edge of the ellipse is gently raised with tissue forceps, which allows detachment of a canoe-shaped sample (e and f). Hemostasis is achieved with single interrupted sutures (g).

• Excisional biopsy : is the removal of whole lesion with 2-3mm of surrounding normal tissue

with the 3:1 rule (ie, the specimen should be 3 times longer that it is wide)Closure is facilitated by developing an ellipse that is 3 times longer than it is wide.

The excision of lip lesions, In general, excision lines should be parallel to the nerves and vessels; however, a substantial excision from the lip parallel to its long axis may result in a decrease of visible vermilion after healing. The white roll of the lip may be pulled in because of the loss of tissue and contracture during healing. Although this excision is unlikely to produce a major deformity, the esthetics may be compromised.Excisions made perpendicular to the long axis of the lip are far less likely to produce this type of distortion

Punch biopsy :The instrument consist of cylindrical cutting blade (2-8mm in diameter ) .It may be difficult on freely movable oral tissues and probably offers no advantage compared with scalpel biopsy .The technique may be appropriate in the hard palate and other sites with better support and tissue that is bound down. The wound heals by secondary intention, and discomfort may persist longer than anticipated by the clinician and the patientMost biopsies can be performed with a 3 or 5 mm punch, without suturing.

Other techniques of biopsy include the use of a needle, biopsy punch, biopsy forceps, laser, or electrocautery device.

Needles may be appropriate in sampling cells from mass lesions, but they are of no benefit in the evaluation of surface lesions.

Electrocautery produces thermal damage and artifact, which make evaluation of the specimen difficult; therefore, electrosurgery should be avoided during oral mucosal biopsy.

• A carbon dioxide or Nd:YAG laser produces a zone of thermal coagulation smaller (approximately 500 µm) than that of electrocautery

If a laser is used for incisional or excisional biopsy, a 0.5-mm margin should be maintained between the cut and the representative area to be sampled. Although this technique may result in good local hemostasis and minimal postoperative discomfort, it is associated with potential shortcomings, including thermal artifact that may have an adverse affect on the histologic interpretation of the specimen.

Biopsy forceps are long-handled instruments with biting ends that are cup-shaped to harvest an adequate amount of mucosa. They are particularly

useful in pharyngeal lesions for which the use of a scalpel is more challenging.

FNAC of major salivary glandsFine-needle aspiration (FNA) biopsy as a diagnostic procedure which use 23- or 25-

gauge needles. It is well established and widely used to evaluate palpable lesions and, with the aid of imaging studies, is equally applicable to deep-seated lesions.

Deep lesions that are less than 1 cm in diameter are best aspirated under ultrasonographic or CT scanning guidance.

FNAB is rarely used in the oral cavity; however, some authors do describe using FNAB in the diagnosis of oral cavity and oropharyngeal lesions.

• Figure 1. FNA biopsy equipment is simple and inexpensive. It includes an alcohol wipe, 4X4-inch gauze pads, 10-mL plastic syringes, 25-gauge 1 1/2-inch stiff, noncutting, bevel-edged needles, glass slides, alcohol bottles, and a pistol-grip mechanical syringe holder.

The skin is cleaned with an alcohol swab. A 25- or 23-gauge needle is used on a plastic disposable 10- or 20-mL syringe attached to a plastic or metal holder. The nodule is immobilized between the fingers, and the needle tip is rapidly directed through the skin into the nodule , and a specimen is obtained by negative pressure. The material within the syringe is spread onto a slide and fixed.

• Advantages of Fine-Needle Aspiration in parotid gland :

• Differentiation of inflammatory from neoplastic disease: This is especially important in patients who are immunosuppressed.

• Culture for suspected infectious masses• Differentiation of benign from malignant disease• Differentiation of the specific tumor cell type• Determination of site of origin, ie, whether the tumor has arisen from the

parotid or if it is metastatic

• Note Disadvantage :  • malignant salivary gland lesions have always been difficult to classify

with fine-needle aspiration (FNA) alone

• A highly cellular mucoepidermoid carcinoma may appear to be squamous cell carcinoma by fine-needle aspiration (FNA) cytology.

• Fine needle aspiration cytology can be used to diagnose metastatic neck nodes to help in treatment planning.

• Open biopsies should never be performed as it violates the field and can cause seeding of cancer.

Radiographical assessment of oral cancer >>> to determine the presence or extent of oral cancer

Ct scan :

Right mandibular body osteosarcoma in an 18-year-old man. Multiplanar reformatted sagittal CT scan, bone algorithm, shows show a periosteal reaction (white arrows)

• MRI is used primarily for evaluating soft tissues because bone always produces a low signal (black) due to a relative paucity of hydrogen protons. While some information about osseous tissue can be obtained (particularly about alterations in the bone marrow),

• detailed study of bone is usually reserved for CT. In dentistry, the primary uses of MRI have been the evaluation of various pathologic lesions (such as tumors) and the assessment of the TMJ.

• Imaging Features (Oral Carcinomas)• ▬ Isodense to muscle, moderate contrast enhancement• ▬ Surrounding structures invaded• ▬ T1-weighted MRI; isointense to muscle signal• ▬ T2-weighted MRI: inhomogeneous increased signal• ▬ T1-weighted post-Gd MRI: moderate enhancement• ▬ Non-contrast T1-weighted MRI reported most• useful sequence to assess tumor extent

Squamous cell carcinoma of tongue invading floor ofmouth; 22-year-old male with history of tongue cancer,now with recurrence.Coronal T1-weighted post-Gd MRIshows moderately contrast-enhanced tumor penetratingmylohyoid muscle and platysma (arrow). Note normalmylohyoid muscle on contralateral side (arrowhead)

B Sagittal T2-weighted MRI shows mass in tongue base (arrow).

Clear-cell carcinoma of tongue base; 47-year-old female with hemoptysis, presents with lump in vallecula, vascular granuloma” clinically.

Squamous cell carcinoma of cheek with and without blowing cheek; 74-year-old male with lump in cheek. A Axial CT image with blowing cheek shows soft-tissue tumor in buccal mucosa (arrow). B Axial CT without blowing cheek cannot reveal origin of tumor

A B

• Nuclear Medicine-Radionuclide imaging is the technique of producing diagnostic

images by analyzing the radiation emitted from a patient who has previously been given radioactive medications

-Nuclear medicine differs from most other imaging modalities in that the tests primarily show the physiological function

• Tumour recurrence & staging — the assessment of the sites and extent of bone metastases & recurrent tumor .

• FIGURE 3. TP PET/CT in 53-y-old man with cancer of left oral tongue. Primary tumor is not well seen on noncontrast CT (A) but is clearly delineated on PET (B) and PET/CT fusion (C) images. (D) CT shows borderline lymph node in right level II neck but no abnormality in left neck. However, PET shows moderate18F-FDG uptake (SUV, 4.4) in left neck (E), which on fusion images clearly localizes to a small left level II node (F).

FIGURE 3.Right gum SCC (arrows) with submandibular gland invasion (arrowheads) is falsely interpreted as level I metastatic nodes on 18F-FDG PET (A) but is well demonstrated on CT (B).

• Imaging FindingsNUCLEAR MEDICINE PET/CT STATED REASON FOR REQUEST: Restaging left oropharyngeal carcinomaRADIOPHARMACEUTICAL ADMINISTERED: 12.04 mCi 18F FDG IV. TECHNIQUE: Emission scanning from the top of the skull through the abdomen was obtained approximately one hour post injection. Images were reconstructed with and without attenuation correction using the CT attenuation coefficients from the corresponding CT portion of the exam. BLOOD GLUCOSE: 99 mg/dL

Bone Scan:Mandibular squamouscell carcinoma.

Three-phase bone scan -flow assessment: image is taken within 60 sec during IV administration of tracer - blood pool image: immediately after the flow study ,it reflect tissue hyperemia

-delayed static views acquisition : Three hours after radiotracer administration, the bony uptake of technetium-99m labeled diphosphonates is maximal, and a significant proportion of the unbound tracer will have been excreted by the kidneys.It is performed to evaluate (trauma, inflammatory,primary bone tumor)

Infection and osteomyelitis after a fracture may be evaluated by means of triple-phase technetium-99m (99m Tc) bone scanning.

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