finding dangerous mucosa...wavelengths of light to excite oral tissue in distinct and unique ways....
TRANSCRIPT
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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
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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
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• 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
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Leukoplakia – A Clinical Diagnosis
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Erythroplakia - Erythroplasia – A Clinical Diagnosis
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Normal
Epithelial Dysplasia – a Histologic Diagnosis
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Severe Epithelial Dysplasia
Normal
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Carcinoma-in-Situ
Normal
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Squamous Cell Carcinoma
Normal
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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
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Diagnostic Biopsy
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Diagnosis of Oral Squamous Cell Carcinoma
• Incisional or excisional biopsy is required for definitive diagnosis
Get a manly biopsy!
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Scalpel Biopsy
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Scalpel Biopsy - Incisional
Fixation in 10% neutral, buffered formalin
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Punch Biopsy
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Punch Biopsy
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Punch Biopsy
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Punch Biopsy - Incisional
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Punch Biopsy
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Punch Biopsy
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Excisional Biopsy
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Biopsy Artifacts
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Local Anesthetic Injection Site with Fibrin Clot
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Minor Salivary Gland Biopsy
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Crush Artifact
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Crush Artifact
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Cautery Artifact
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Cautery Artifact
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Cautery Artifact
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Cautery Artifact
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Forceps Squeeze
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Forceps Squeeze
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Forceps Squeeze
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Saline Artifact
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Pemphigus vs Saline Artifact
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Suction Artifact
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Suction Artifact
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“Air knot”
Suture Artifact
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Freezing Artifact
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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
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Adjunctive Diagnostic Procedures
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• Vital staining – toluidine blue
• Exfoliative cytology
• Reflectance
• Fluorescence
• Transepithelial brush biopsy
Adjunctive procedures
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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
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Toluidine Blue Vital Staining
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• 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
Toluidine Blue Vital Staining
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Toluidine Blue Vital Staining
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Toluidine Blue Vital Staining
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Toluidine Blue Vital Staining
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Toluidine Blue Vital Staining
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Toluidine Blue Vital Staining
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Toluidine Blue Vital Staining
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Oral Exfoliative Cytology
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Exfoliative Cytology of Uterine Cervix
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85
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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Exfoliative Cytology
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88
Exfoliative Cytology
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Exfoliative Cytology
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Exfoliative Cytology
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92
Exfoliative Cytology
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• Contraindications – Keratotic surface
– Suspicious for malignancy
• Indications
– Herpetic lesions
– Candidiasis
Oral Exfoliative Cytology
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94
Oral Exfoliative Cytology for Diagnosis of Viral Infections
Herpes
Viral Cytopathic Effect (CPE)
Normal Squames
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Oral Exfoliative Cytology for Diagnosis of Fungal Infections
Candidal Yeast Forms
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Oral Exfoliative Cytology for Diagnosis of Fungal Infections
96
Candidal
Pseudohyphae
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Evidenced-Based Clinical Recommendations for Screening for Oral Squamous Cell Carcinoma JADA, May 2010
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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)
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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)
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Acetic Acid
• Under blue-white illumination, abnormal squamous epithelium is reported to be distinctly white (acetowhite)
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MicroLux/DL
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MicroLux/DL
• DL = Diagnostic Light
• 1% Acetic acid rinse
• Blue-white (440nm) LED light source
• Tranlumination tip
• Lighted mirror
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Orascoptic DK
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Orascoptic DK
• DK = Diagnostic Kit
• 1% Acetic acid rinse
• Blue-white (440nm) LED light source
• Tranlumination tip
• Lighted mirror
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Orascoptic DK
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Vizilite Plus
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Vizilite Plus
• Plus = Toluidine Blue
• 1% Acetic acid rinse
• Blue-white (440nm) LED light source
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Visilite - Plus
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Visilite - Plus
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Visilite - Plus
http://www.youtube.com/watch?v=gKTBE7v45VQ
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Visilite - Plus
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Velscope
Tissue Fluorescence
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c
VELscope - Tissue Fluorescence
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VELscope - Tissue Fluorescence
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VELscope - Tissue Fluorescence
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VELscope Tissue Fluorescence
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VELscope - Tissue Fluorescence
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VELscope - Tissue Fluorescence
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Transition from Normal Epithelium to Dysplastic Epithelium
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Leukoplakia – Mild Epithelial Dysplasia
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Leukoplakia – Mild Epithelial Dysplasia – January 2007
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Leukoplakia – Recurrence - February 2008
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Leukoplakia – Recurrence - February 2008
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Leukoplakia – Retreatment- 6 Weeks Postop
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Leukoplakia – Retreatment- 6 Weeks Postop
v
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Leukoplakia – Retreatment- 6 Weeks Postop
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Leukoplakia – Retreatment- 6 Weeks Postop
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Identafi 3000
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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
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Fine Needle Aspiration
Biopsy
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Fine Needle Aspiration Biopsy
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Fine Needle Aspiration Biopsy Fine Needle Aspiration Biopsy
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Fine Needle Aspiration Biopsy
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Fine Needle Aspiration Biopsy
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Transepithelial Brush Biopsy
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Transepithelial Brush Biopsy
• Oralscan Laboratories, Suffern, NY
• OralCDx test kit
• Computer assisted oral brush biopsy analysis
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Transepithelial Brush Biopsy
• Complete transepithelial sample
• Adequate sample
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• 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
Transepithelial Brush Biopsy
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Transepithelial Brush Biopsy
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• Negative - no cellular abnormalities
• Positive – epithelial
dysplasia or carcinoma - Scalpel biopsy indicated
• Atypical - abnormal
epithelial changes - Scalpel biopsy indicated
OralCDx Brush Biopsy Report
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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
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• Acute myelogenous leukemia
• Bone marrow transplant
• Graft versus host disease
• Scleroderma
• Leukoplakia
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• 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
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May 2007
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April 2008
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Proliferative Verrucous Leukoplakia
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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
Proliferative Verrucous Leukoplakia
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Proliferative Verrucous Leukoplakia
• 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
Proliferative Verrucous Leukoplakia
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Proliferative Verrucous Leukoplakia
Oct 1988
Proliferative Verrucous Leukoplakiac
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Proliferative Verrucous Leukoplakia
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Proliferative Verrucous Leukoplakia
Oct 1988
Proliferative Verrucous Leukoplakia
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Proliferative Verrucous Leukoplakia
Jan 1989
Proliferative Verrucous Leukoplakia
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Proliferative Verrucous Leukoplakia
Proliferative Verrucous Leukoplakia
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Proliferative Verrucous Leukoplakia
Proliferative Verrucous Leukoplakia
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Proliferative Verrucous Leukoplakia
Proliferative Verrucous Leukoplakia
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Proliferative Verrucous Leukoplakia Proliferative Verrucous Leukoplakia