When, Why and How to Biopsy Oral Lesions Wednesday

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When, Why and How to Biopsy Oral Lesions
Mark A. Lerman, D.M.D.
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December 4, 2013
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When, Why, and How to
Biopsy Oral Mucosal Lesions
Mark A. Lerman, D.M.D.
Diplomate, American Board of Oral and Maxillofacial Pathology
Contact Information
• Mark A. Lerman, D.M.D.
• marklermandmd@gmail.com
• 617-732-6974 (clinical appointments)
• www.brighamandwomens.org
Leading Causes of Death in USA
•
•
•
•
•
•
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Heart Disease
25%
Cancer
23%
Cerebrovascular Disease 6%
Respiratory Disease
5%
Accidents
5%
Alzheimer Disease
3%
Diabetes Mellitus
3%
US Mortality Data 2007, National Center for Health Statistics, Centers for Disease Control
and Prevention, 2010
Oral/Pharyngeal Cancer
41,380 ESTIMATED NEW CASES in 2013
• 7,890 estimated deaths
• Incidence more than twice as high in men
• 3% of all cancers
• 8th most common type of cancer diagnosed
• Overall 5 year survival rate = 61%
• Mortality rate improved slightly in last 50 years
American Cancer Society, Cancer Facts and Figures 2013
Clinical Staging
Stage
Stage I
Stage II
Stage III
Stage IV
5 year survival
T1N0M0
T2N0M0
T3 or any T w/ N1
T4 or any T w/ N2 or M1
85%
66%
41%
9%
The patient’s best chance
for improved survival is
early detection
Oral Cancer
• Squamous cell carcinoma
• Everything else
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Lymphoma
Salivary gland malignancies
Bone and soft tissue sarcomas
Melanoma
Odontogenic tumors
Metastasis
Clinical Presentation of Oral
Squamous Cell Carcinoma
• Leukoplakia
• Erythroplakia
• Non-healing
ulceration
• Exophytic
mass
White Lesions
May appear white due to:
– Membrane or plaque covering mucosa
– Accumulation of fluid within epithelium
– Thickened epithelium
– Alteration of epithelium
Etiology of White Lesions
• Developmental
• Infectious
• Immunemediated
• Reactive
• Neoplastic/
Dysplastic
Leukoplakia
White patch or plaque that cannot be
characterized clinically or
pathologically as any other disease
Leukoplakia
Localized vs. Multi-focal
Homogenous
Non-homogenous
Speckled
Nodular
Verrucous
Leukoplakia
Waldron & Shafer analyzed 3,256 cases:
Hyperkeratosis or hyperplasia
Mild or moderate dysplasia
Severe dysplasia or ca-in-situ
Squamous cell carcinoma
80%
12%
4%
3%
Verrucous Hyperplasia
Proliferative Leukoplakia
• Proliferative verrucous leukoplakia
• Multifocal leukoplakia that recurs
with a tendency to undergo
malignant transformation
• Female predilection
• Less often associated with a
history of tobacco or alcohol use
Lichen Planus
Oral Lichen Planus
• Clinical Features
– Reticular
– Erosive/erythematous
– Ulcerative
Lichenoid Mucositis
Associated with:
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NSAIDs
anti-hypertensive agents
cholesterol lowering agents
anti-hyperglycemic agents
cinnamon flavoring agents
herbal remedies
amalgam restorations
Lichen Planus
Treatment
• Fluocinonide gel 0.05%
• Warn patient
• Dexamethasone elixir
• Follow-up
Erythroplakia
Erythroplakia
Waldron & Shafer analyzed 58 cases
Mild to moderate dysplasia
Severe dysplasia or ca-in-situ
Squamous cell carcinoma
9%
40%
51%
Leukoplakia and Erythroplakia
• Non-specific benign diagnoses
(esp. in high risk sites) warrant
close follow-up and/or complete
removal when clinically
appropriate
• Biopsy-proven dysplasias require
complete removal and long term
follow-up
Ulcers
Recurrent Aphthous Ulcers
Immune-mediated disorder
characterized by RECURRENT ulcers
Recurrent Aphthous Ulcers
Subtypes
• Minor (canker sores)
• <0.5cm, heal <2 weeks, no scarring
• Major
• >0.5cm, heal >2 weeks, scarring
• Herpetiform
• Multiple crops of pinpoint ulcers, may
involve hard palate
• Complex
• Continuous ulcers
Recurrent Aphthous Ulcers
Diagnosis
• History and clinical presentation
• Cultures/cytology/biopsy may be
necessary in atypical cases or
for variants excluding minor
aphthous ulcers
Recurrent Aphthous Ulcers
Treatment
• Topical steroids are first line of
treatment
• Intra-lesional triamcinolone for
major aphthous ulcers
Recurrent Aphthous Ulcers
Systemic conditions
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Bechet syndrome
Immunocompromise
Nutritional deficiencies
Celiac disease
Inflammatory bowel disease
Cyclic neutropenia
Herpetic Ulcers
Aphthous Ulcers vs. Herpetic Ulcers
• Etiology
– Immune-mediated vs. viral
• Morphology
– Ulcers vs. vesicles
• Location
– Non-keratinized vs. keratinized mucosa
Herpetic Ulcers
• Primary herpetic gingivostomatitis
• Secondary recrudescent herpetic
reactivation
Secondary Herpetic Eruptions
Diagnosis
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History and clinical presentation
Cultures
Cytology
Biopsy
Herpetic Ulcers
Treatment
• Topical acyclovir ointment 5%
• Systemic valacyclovir tablets
• 500mg
• 2g stat, then 500mg BID for 5 days, starting
as soon as prodromal signs appear
Oral Squamous Cell Carcinoma
Risk Factors
Tobacco
Alcohol
Immune suppression
History of cancer
Family history of
cancer
• Human
papillomavirus
infection
• Areca nut
• Actinic damage
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Oral Squamous Cell Carcinoma
• Male:female ratio = 2.5:1
• Average age at diagnosis = 62
• Increasing incidence before age 40
Oral Squamous Cell Carcinoma
Field cancerization
• Patients with one oral carcinoma
have an increased risk for additional
oro-pharyngeal carcinomas
• 35% of patients with oral cancer
develop another primary tumor
within five years of initial diagnosis
Oral Squamous Cell Carcinoma
High-risk locations
– Ventro-lateral tongue
– Floor of mouth
– Soft palate
Clinical Staging
T1S- Ca-in-situ
T1 - Primary <2 cm
T2 - Primary between 2-4cm
T3 - Primary >4cm
T4 - Invasion of contiguous tissue
N0
N1
N2
N3
- No LN mets
- One ipsilateral node <3cm
- One node >3-6cm or multiple nodes
- node >6cm
M0 - no distant metastasis
M1 - evidence of distant metastasis
Clinical Staging
Stage
Stage I
Stage II
Stage III
Stage IV
5 year survival
T1N0M0
T2N0M0
T3 or any T w/ N1
T4 or any T w/ N2 or M1
85%
66%
41%
9%
For the patient with
a mucosal lesion
• Take a good history
• Formulate a differential diagnosis
• Arrive at a definitive diagnosis
Exfoliative Cytology
Indications
• Herpetic lesions
• Candidiasis
• Oral hairy leukoplakia
Where do I biopsy?
Areas to avoid
• Ulcers
• Thickly keratinized sites
Biopsy
• Informed consent; sequelae
• pain, infection, bleeding, swelling, scar
• 2% lidocaine with 1:50,000 epinephrine
• Perform biopsy
• Hemostasis
• Post-operative instructions
• Written and oral
• Send to pathology
Requisition Form
Essential data to include
• Date of procedure
• Clinician name
• Patient information
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Name (ALSO ON SPECIMEN JAR)
Date of birth
MEDICAL insurance
History and clinical information
Biopsy site
Clinical diagnosis
•Duration
•Symptoms
•Description
•Number
•Location
•Color
•Size
•Shape
•Morphology
•Other habits
•Clinical diagnosis
•Biopsy site
Additional Information
• Provide as much information as
possible to the pathologist along with
the specimen to aid in the diagnosis
• History
• Clinical photographs
• Radiographs
Diagnostic Aids
• Cytology
• Light-based detection
• Fluorescence-based detection
Nomenclature
• Predictive values
– Refer to the likelihood that patients with positive
test results (PPV) or negative test results (NPV)
actually have or do not have disease
• Sensitivity
– Associated with a LOW FALSE NEGATIVE rate
– Of the people tested who ACTUALLY HAVE a
disease, a sensitive test will report that most are +
• Specificity
– Associated with a LOW FALSE POSITIVE rate
– Of the people tested who are DISEASE-FREE, a
specific test will report that most are negative
Nomenclature
• Screening
– Technique applied to patients without
signs or symptoms
• Case-Finding
– Technique applied to patients with
abnormal signs or symptoms to
confirm a diagnosis
Cytology
• OralCDx BrushTest
– Introduced in 1999
– Designed for evaluation of
clinically-innocuous lesions
– Does NOT provide a definitive
diagnosis
Tolonium Chloride
• Toluidine Blue
– Dye designed to stain
nucleic acids and
abnormal tissues
– False positives in reactive
lesions
– Sensitivity ranges from
78-100%
– Specificity ranges from
31-100%
Light-Based Detection
• Designed for evaluation of cervical
lesions
• Removes debris and dehydrates
cells to better visualize nuclei
Vizilite+
• Disposable light
packet
• Tolonium
chloride
– Mehrotra et al.
• 102 biopsies
• 24 false positives
• All 4 dysplasias false
negatives
– Awan
• 77% sensitivity
• 28% specificity
Narrow Emission
Tissue Fluorescence
• Velscope
– Normal mucosa emits a
pale green color under
400-460nm
Narrow Emission
Tissue Fluorescence
• Velscope
– Mehrotra et al.
• 156 biopsies
• 50% sensitivity
• 6% PPV
– Awan et al.
• 116 biopsies
• 84% sensitivity; 15% specificity
• 7 false negatives; NPV= 61%
Narrow Emission
Tissue Fluorescence
• Velscope
– November 2012: McNamara et al.
• 130 patients
• 42 DVL
– 41 false positives
• 1 false negative
Oral Cancer
• Oral cancer clinical presentations
– Leukoplakia
– Erythroplakia
– Non-healing ulceration
– Exophytic mass lesions
• High risk locations
– Ventro-lateral tongue
– Floor of mouth
– Soft palate
Thank You