Finding Dangerous Mucosa...wavelengths of light to excite oral tissue in distinct and unique ways. • Biochemical changes can be monitored with fluorescence, while morphological changes

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Finding Dangerous Mucosa

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• Squamous Cell Carcinoma

• Salivary Gland Adenocarcinoma

• Malignant Lymphoma

• Metastatic Carcinoma

• Sarcoma

Oral Cancer

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• For Oral and Oropharyngeal Cancer:

– USA: 35,000 cases per year

– 50% 5-year survival rate

– 93 people develop oral cancer every day

– 1 person dies from oral cancer every hour

Incidence of Cancer in the United States

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Etiologic Agents of Head and Neck Squamous Cell Carcinoma

2003 American Society of Clinical Oncology

Actinic Radiation

Alcohol Tobacco

HPV

EBV

Alcohol Tobacco

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What Does Oral Squamous Cell Carcinoma Look Like Clinically?

• Exophytic – Mass-forming

– Fungating

– Papillary

– Verruciform

• Endophytic – Invasive

– Burrowing

– Ulcerated

• Leukoplakic – a white patch

• Erythroplakic – a red patch

• Erythroleukoplakic – a red-and-white patch

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• Identify precursor lesions – Leukoplakia

– Erythroplakia

• Be suspicious - biopsy clinically

suspicious lesions

Early Diagnosis of Oral Cancer

Hidden Pathology

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Soft Palate

Dorsal Tongue

Uvula

Hidden Pathology

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• Extraoral examination – Inspect head and neck. – Bimanually palpate lymph nodes and salivary glands.

• Lips – Inspect and palpate outer surfaces of lip and vermilion border. – Inspect and palpate inner labial mucosa.

• Buccal mucosa – Inspect and palpate inner cheek lining.

• Gingiva/alveolar ridge – Inspect maxillary/mandibular gingiva and alveolar ridges on both the

buccal and lingual aspects. • Tongue

– Have patient protrude tongue and inspect the dorsal surface. – Have patient lift tongue and inspect the ventral surface. – Grasping tongue with a piece of gauze and pulling it out to each side,

inspect the lateral borders of the tongue from its tip back to the lingual tonsil region.

– Palpate tongue. • Floor of mouth

– Inspect and palpate floor of mouth. • Hard palate

– Inspect hard palate. • Soft palate and oropharynx

– Gently depressing the patient’s tongue with a mouth mirror or tongue blade, inspect the soft palate and oropharynx.

Components of an Oral Cancer Examination

Neville and Day, CA Cancer J Clin 2002;52: 195-215

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Leukoplakia

• A white patch or plaque that can’t be characterized clinically or pathologically as any other disease.

Rule of thumb: 20% of Leukoplakia will be dysplastic

• A red patch that can’t be characterized clinically or pathologically as any other disease.

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Rule of thumb: 90% of Erythroplakia will be dysplastic

Erythroplakia

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Classic Articles on Leukoplakia and Erythroplakia

Leukoplakia – A Clinical Diagnosis

Erythroplakia - Erythroplasia – A Clinical Diagnosis

Normal

Epithelial Dysplasia – a Histologic Diagnosis

Severe Epithelial Dysplasia

Normal

Carcinoma-in-Situ

Normal

Squamous Cell Carcinoma

Normal

Skeletal muscle

Nests of tumor cells

Infiltrating Squamous Cell Carcinoma

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Grading Epithelial Dysplasia

Mild - Lower 1/3

Moderate - Middle 1/3

Severe - Upper 1/3

• Carcinoma in situ – Full thickness change

Diagnostic Biopsy

Diagnosis of Oral Squamous Cell Carcinoma

• Incisional or excisional biopsy is required for definitive diagnosis

Get a manly biopsy!

Scalpel Biopsy

Scalpel Biopsy - Incisional

Fixation in 10% neutral, buffered formalin

Punch Biopsy

Punch Biopsy

Punch Biopsy

Punch Biopsy - Incisional

Punch Biopsy

Punch Biopsy

Excisional Biopsy

Biopsy Artifacts

Local Anesthetic Injection Site with Fibrin Clot

Minor Salivary Gland Biopsy

Crush Artifact

Crush Artifact

Cautery Artifact

Cautery Artifact

Cautery Artifact

Cautery Artifact

Forceps Squeeze

Forceps Squeeze

Forceps Squeeze

Saline Artifact

Pemphigus vs Saline Artifact

Suction Artifact

Suction Artifact

“Air knot”

Suture Artifact

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Freezing Artifact

Requirements for a Good Biopsy

• Representative

• Manly

• Orientable

• Undistorted

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Staging of Oral Cancer

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Tumor size

Metastasis

• Regional lymph nodes

• Distant sites

Stage determines:

• Treatment

• Prognosis

Oral Squamous Cell Carcinoma Staging: TNM Classification

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• Tis CIS

• T1 <2 cm

• T2 2 to 4 cm

• T3 > 4 cm

• T4 Invades adjacent structures

Primary Tumor (T) Size

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• N0 No regional node metastasis

• N1 Metastasis - single ipsilateral node, < 3 cm

• N2 Metastasis - 3 to 6 cm

• N3 Metastasis > 6 cm

Nodal Involvement (N)

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• M0 No distant metastasis

• M1 Distant metastasis

Distant Metastasis (M)

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• T2N1M0

• T3N3M1

• T4N0M0

TNM Staging

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• Stage 0 – Tis N0 M0

• Stage I – T1 N0 M0

• Stage II – T2 N0 M0

• Stage III – T3 N0 M0 – T1 or T2 or T3 N1 M0

• Stage IV – Any T4 lesion – Any N2 or N3 lesion – Any M1 lesion

Stage Grouping

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Clinical Stage and Survival Rates for Oral Cancer

T1

T2

T3

T4

I

II

IV

III

N0 N1 N2-N3, M+

80%

60- 80%

40-60%

20-40%

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Tumor Stage Determines Prognosis Treatment

• Higher stage -> worse prognosis

• Higher stage -> more aggressive treatment

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Five Year Survival by Stage

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• Well differentiated

• Moderately differentiated

• Poorly differentiated

Histologic Grading of Squamous Cell Carcinoma

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• Surgery

• Radiation

• Combined surgery and radiation

Treatment of Head and Neck Squamous Cell Carcinoma

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Multidisciplinary Head and Neck Tumor Board for Treatment Planning

• Surgical oncology

• Medical oncology

• Radiation oncology

• Radiology

• Pathology

• Dentistry – oral surgery, maxillofacial prosthodontics

• Speech pathology

• Social work

• Physical therapy

• Occupational therapy

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• All stages combined 59%

– Local disease 81%

– Regional metastasis 51%

– Distant metastasis 30%

Oral Cavity Cancer Five Year Survival by Stage - ACS

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31F Cigarette Smoker with Painful Red and White Lesion of Ventral Tongue

Adjunctive Diagnostic Procedures

• Vital staining – toluidine blue

• Exfoliative cytology

• Reflectance

• Fluorescence

• Transepithelial brush biopsy

Adjunctive procedures

Adjunctive Diagnostic Techniques

• Elective aids to incisional biopsy

• Not substitutes for biopsy

• Delays in obtaining biopsy

– Delays in referral

– Patient resistance

– Medical reasons

– Low index of suspicion

Toluidine Blue Vital Staining

• Tolonium Chloride binds to DNA

• A positive result means that there may be dysplastic cells present

• A negative result does not

exclude dysplasia

• May be useful to accelerate biopsy or to identify an area to biopsy








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Oral Exfoliative Cytology

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Exfoliative Cytology of Uterine Cervix

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0

20

40

60

80

100

Perc

ent

Gingiva Lip Buccal Mucosa Ventral

Tongue

Soft Palate Floor of

Mouth

Reliability of Oral Exfoliative Cytology Folsom, Journal of Oral Surgery; 33: 61, 1972

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Exfoliative Cytology

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• Contraindications – Keratotic surface

– Suspicious for malignancy

• Indications

– Herpetic lesions

– Candidiasis

Oral Exfoliative Cytology

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Oral Exfoliative Cytology for Diagnosis of Viral Infections

Herpes

Viral Cytopathic Effect (CPE)

Normal Squames

Oral Exfoliative Cytology for Diagnosis of Fungal Infections

Candidal Yeast Forms

Oral Exfoliative Cytology for Diagnosis of Fungal Infections

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Candidal

Pseudohyphae

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Evidenced-Based Clinical Recommendations for Screening for Oral Squamous Cell Carcinoma JADA, May 2010

Adjunctive Screening Aids

• Devices intended to assist in lesion detection

– Devices based on tissue reflectance

• MicroLux/DL (AdDent, Danbury, CT)

• Orascoptic DK (Orascoptic, Kerr, Middleton, WI)

• ViziLite Plus (Zila, Phoenix, AZ)

– Device based on autofluorescence • VELscope (LED Dental, Burnaby, BC, CA)

– Device based on autofluorescence and tissue reflectance • Identifi 3000 (Trimira, Houston, TX)

• Device intended to assist in lesion assessment – Device based on transepithelial cytology

• OralCDx BrushTest (OralCDx Laboratories, Suffern, NY)

Adjunctive Screening Aids

• There is insufficient evidence that commercial devices based on autofluorescence enhance visual detection of potentially malignant lesions beyond that achieved through a conventional visual and tactile examination (III)

• There is insufficient evidence that commercial devices based on tissue reflectance enhance visual detection of potentially malignant lesions beyond that achieved through a conventional visual and tactile examination (III)

• There is insufficient evidence to assess the validity of transepithelial cytology of seemingly innocuous mucosal lesions (III)

• In suspicious mucosal lesions with high potential for malignancy, transepithelial cytology has validity in identifying disaggregated dysplastic cells (III)

(A conclusion of “insufficient evidence” does not necessarily mean that the intervention is or is not effective, but instead means that the panel did not find sufficient evidence to support a recommendation)

Acetic Acid

• Under blue-white illumination, abnormal squamous epithelium is reported to be distinctly white (acetowhite)

MicroLux/DL

MicroLux/DL

• DL = Diagnostic Light

• 1% Acetic acid rinse

• Blue-white (440nm) LED light source

• Tranlumination tip

• Lighted mirror

Orascoptic DK

Orascoptic DK

• DK = Diagnostic Kit



• Tranlumination tip

• Lighted mirror

Orascoptic DK

Vizilite Plus

Vizilite Plus

• Plus = Toluidine Blue



Visilite - Plus

Visilite - Plus

Visilite - Plus

http://www.youtube.com/watch?v=gKTBE7v45VQ

http://www.youtube.com/watch?v=gKTBE7v45VQ

Visilite - Plus

Velscope

Tissue Fluorescence

c

VELscope - Tissue Fluorescence



VELscope Tissue Fluorescence



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Transition from Normal Epithelium to Dysplastic Epithelium

Leukoplakia – Mild Epithelial Dysplasia

Leukoplakia – Mild Epithelial Dysplasia – January 2007

Leukoplakia – Recurrence - February 2008

Leukoplakia – Recurrence - February 2008

Leukoplakia – Retreatment- 6 Weeks Postop


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Identafi 3000

Press Release -Trimira™ LLC :

• Identafi 3000 uses white, violet, and amber wavelengths of light to excite oral tissue in distinct and unique ways.

• Biochemical changes can be monitored with fluorescence, while morphological changes can be monitored with reflectance.

• This multiple wavelength technology identifies abnormal tissue with more accuracy than the single color approaches currently on the market.

• The ability to read metabolic and physiologic differences makes it easier to distinguish between normal and abnormal tissue.

• The combined system of fluorescence and reflectance uses the body's natural tissue properties as an adjunctive tool for oral mucosal examination.

http://www.youtube.com/watch?v=eopbcvYEjlw

http://www.youtube.com/watch?v=CE1IBE0d2dw

Identafi 3000

http://www.youtube.com/watch?v=eopbcvYEjlw

http://www.youtube.com/watch?v=CE1IBE0d2dw

Fine Needle Aspiration

Biopsy

Fine Needle Aspiration Biopsy

Fine Needle Aspiration Biopsy Fine Needle Aspiration Biopsy



Transepithelial Brush Biopsy


• Oralscan Laboratories, Suffern, NY

• OralCDx test kit

• Computer assisted oral brush biopsy analysis


• Complete transepithelial sample

• Adequate sample

• No anesthesia required

• Moisten brush and place either the side or the tip of brush on lesion

• Apply firm pressure and rotate 5 to 10 times

• Assess full thickness harvest by observing micro-bleeding



• Negative - no cellular abnormalities

• Positive – epithelial

dysplasia or carcinoma - Scalpel biopsy indicated

• Atypical - abnormal

epithelial changes - Scalpel biopsy indicated

OralCDx Brush Biopsy Report

OralCDx Transepithelial Brush Biopsy

• Drore Eisen, DDS, MD, Medical Director Oralscan Laboratories

• “The brush biopsy is used to test benign-appearing lesions that have been either watched or ignored in the past.”

• “These are lesions that dentists do not find sufficiently suspicious to warrant referral for scalpel biopsy, not those distinguished by signs and symptoms of malignancy, clear indications for scalpel biopsy.”

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• 1999 - Squamous cell carcinoma of left soft palate - radiation therapy

• 2006 – Carcinoma-in-situ right soft palate - excised

• 2009 – Bit right tongue in January, seen in March

• Acute myelogenous leukemia

• Bone marrow transplant

• Graft versus host disease

• Scleroderma

• Leukoplakia

• Bone marrow transplant

• Graft vs Host disease

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Verrucous Carcinoma

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Verrucous Carcinoma

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Verrucous Carcinoma

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Proliferative Verrucous Leukoplakia

May 2007

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April 2008

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Proliferative Verrucous Leukoplakia Proliferative Verrucous Leukoplakia

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• High-risk, aggressive type of oral leukoplakia

• High potential for malignant transformation

• Not associated with tobacco use

• Women outnumber men


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• Slow-growing

• Begins as hyperkeratosis

• Spreads to become multifocal and verruciform

• Resistant to therapy - recurs

• Malignant transformation

• Diagnosis often retrospective

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Oct 1988


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Oct 1988

Proliferative Verrucous Leukoplakiac

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Oct 1988


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Jan 1989


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Proliferative Verrucous Leukoplakia Proliferative Verrucous Leukoplakia

Documents

Finding Dangerous Mucosa...wavelengths of light to excite oral tissue in distinct and unique ways. • Biochemical changes can be monitored with fluorescence, while morphological changes