Leukoplakia and Look-alikes: How to Diff ern ate and Manage

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Leukoplakia and Look-alikes:
How to Differn ate and Manage
Sook-Bin Woo, D.M.D.
Wednesday
December 4, 2013
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Information
Title: Leukoplakia and Look-alikes: how to
differentiate and manage.
By Dr. Sook-Bin Woo
(1) Half Day Seminar (3 hrs); Wednesday,
December 4, 2013; 9:00 – 12:00PM
Leukoplakia and Look-alikes: How to
Differentiate and Manage
By
Sook-Bin Woo DMD FDSRCS (Edin)
Associate Professor, Harvard School of
Dental Medicine, Boston
BWH website
www.partners.org>Brigham and Women’s
Hospital>Depts and
Services>Surgery>Oral Medicine>For
Professionals>For Staff Professionals
Provides patient information
For oral pathology/radiology/oral medicine
symposium in September, email me at
[email protected] – 6 CE credits
What makes a lesion white?
• Thick keratin
• Thick epithelium
• Altered epithelium - benign
• Benign (swelling and edema of cells)
• Degeneration of cells (using caustic dentifrices)
• Altered epithelium – premalignant and
malignant
• Pre-cancerous or dysplastic
• Cancerous
What makes a lesion white?
• Are all white lesions leukoplakia (leuko: white;
plak: plaque)?
• No! Name is misleading
History of leukoplakia definition
• 1978 (WHO): white patch or plaque that
cannot be characterized clinically or
pathologically as any other disease
• 1984: white patch or plaque that cannot be
characterized clinically or pathologically as any
other disease and is not associated with any
physical or chemical causative agent except
use of tobacco
History of leukoplakia definition
• 1996 (WHO): predominantly white lesion of
the oral mucosa that cannot be characterized
as any other definable lesion: some
leukoplakias will transform into cancer ……
frictional lesions are excluded…..biopsy is
mandatory…..
Current definition of leukoplakia
• 2007 (WHO): White plaque of questionable
risk having excluded (other) known diseases or
disorders that carry no increased risk for
cancer.
• It is a clinical term only; modified after
histopathologic evaluation.
Classification of white lesions
By etiology and frequency – questions you ask as clinician
– Is this lesion…….
• Developmental/congenital/genetic
• Reactive
• Physical/mechanical trauma
• Chemical trauma
• Others
•
•
•
•
Infectious
Immune-mediated/autoimmune
Pre-neoplastic and Neoplastic
Metabolic
Defined white lesions that are not
leukoplakias
• Developmental
•
•
•
•
•
Cannon white sponge nevus
Hereditary benign intraepithelial dyskeratosis
Oral Darier disease/warty dyskeratoma
Dyskeratosis congenita
Pachyonychia congenita
• Extremely rare
Reactive
• Reaction to mild local injury – most common
•
•
•
•
•
Leukoedema (eg. smoking)
Contact desquamation (eg. Listerine)
Smokeless tobacco lesion
Nicotinic stomatitis - salivary duct injury
Frictional keratoses
• Morsicatio mucosae oris
• Benign alveolar ridge keratosis
• Other frictional keratosis
• Hairy tongue
• Infectious
• Candidiasis
• Hairy leukoplakia (EBV-associated)
• Immune-mediated
• Migratory glossitis
• Lichen planus/lichenoid lesions
• Autoimmune
• Lupus erythematosus
• Chronic graft-vs.-host disease
• Dysplastic, neoplastic
• Leukoplakia (without obvious dysplasia) –
keratosis of unknown significance
• Dysplastic leukoplakia
• Including verrucous leukoplakia
• Invasive squamous cell carcinoma
Clinical help hint for diagnosis of
leukoplakia
• Sharply demarcated at least around part of
the lesion – suggesting that a CLONE of
genetically altered cells have proliferated
• Fissuring
• Noted in > 90% of cases
Leukoedema
• Clinical
• Variation of normal ?
• Associated with very mild topical injury (eg
smoking, mouth wash use)
• Stretching eliminates appearance
• POORLY DEMARCATED
• Is this a leukoplakia?
Management
• Discontinue offending agent (eg. smoking)
• Change to milder toothpaste or mouthwash
Contact desquamation
• Clinical presentation
• Delicate, white wisps of tissue with underlying
normal mucosa
• Culprits – Tartar-control toothpaste, Pro-Health
toothpaste, Listerine (21.6-26.9% alcohol)
• POORLY DEMARCATED
• Is this a leukoplakia?
Management
• Change to a milder tooth paste or mouthwash
Smokeless Tobacco Lesion
• Clinical
• Grey-white opalescent area with parallel ridges
where tobacco is placed
• Painless
• Cells are edematous like leukoedema
• Is this a leukoplakia?
Management
• Early lesions: Lesions will resolve if remove the
irritant – smokeless tobacco – is removed
• Late lesions: Once leukoplakia develops,
lesions unlikely to resolve and should be
removed.
• Smokeless tobacco has very low association
with cancer unless leukoplakia has developed.
• Used for “risk reduction” in some patients
Nicotinic stomatitis
• Caused by heat especially of pipe smoking,
and not by nicotine
• See in patients who drink very hot liquids
regularly
• Appearance caused by inflammation of
excretory salivary ducts that open onto the
surface
• Is this a leukoplakia?
Management
• Discontinue habit
• However, once it is established, difficult to
return tissues to normal
Morsicatio mucosae oris/Chronic factitial/bite
injury
• Clinical
• Occurs in 1% to 2% of the population
• White papules and plaques, shaggy surface, focal
erosions, erythema, sometimes ulcerations
• POORLY DEMARCATED
• Is this a leukoplakia?
Management
• Reassure patient
• No treatment
• Bite guards not been shown to be helpful
Benign alveolar ridge keratosis (BARK)
• Clinical
• White plaque on the alveolar ridge, painless, may
be rough; poorly demarcated
• Often in the area of previously extracted
mandibular third molar (wisdom tooth)
• POORLY DEMARCATED
• Is this a leukoplakia?
Management
• Reassure patient
• No treatment required if retromolar pad
• Reline and/or remake denture as necessary.
Hairy/coated tongue
• Painless, but patient may report stale or foul
taste in mouth; gagging
• White thick mat on dorsum, may be
pigmented
• Often a history of antibiotic use and
misdiagnosed as candidiasis
• No other plaques or papules elsewhere
• Is this a leukoplakia?
Hairy Tongue
• Etiology:
• Elongated of filiform papillae because of retention
of keratin from
• Dehydration, increased mucous and decreased serous
(watery saliva)
• Smoking
• Reduced keratin loss because not eating coarse foods
• Idiopathic
• Increased chromogenic bacterial growth – green,
brown, yellow
Management
• Get a good history
• No treatment is necessary
• Hydrate well
• Return to eating a healthy diet with fresh fruits
and vegetables
Candidiasis
• Often burning sensation or sensitivity
• Pseudomembranous candidiasis (thrush) curdy white papules and plaques on
erythematous base
• May or may not wipe off
• Is this a leukoplakia?
Other forms of candidiasis
•
•
•
•
Erythematous or atrophic candidiasis
Angular cheilitis
Median rhomboid glossitis
Hyperplastic candidiasis
Treatment
All for 7-10 days
• Nystatin 100,000 iu/ml; dispense 300 ml, swish x 3-5 min,
and spit out 5 ml (1 teaspoon) QID
• Clotrimazole 10 mg troches; suck on one troche QID
• Mycolog (mycostatin and triamcinolone) under denture
TID, treat denture
• Vytone (iodoquinol and hydrocortisone) under denture
Compliance is a big issue because of need for multiple
doses.
• Fluconazole 100 mg QD x 5-7 days for generally healthy
patients
Hairy leukoplakia
• Painless, unless super-imposed candidiasis
• Bilateral, symmetric, usually on lateral tongue
• Immunocompromised – AIDS, organ
transplantation
• This is not a TRUE leukoplakia; name is
confusing. It is an Epstein Barr virus infection
without any malignant potential.
Management
•
•
•
•
Reduce immunosuppression
Treat candidiasis if present
No specific therapy
If HIV/AIDS related, HAART will usually resolve
lesions
Migratory Glossitis/Stomatitis
Geographic tongue
• Clinical
• 1% to 2% of the population
• Tongue dorsum and ventrum has red, bald areas
delineated by curving ring-like white lines
• May affect other mucosal sites
• Is this a leukoplakia?
Benign Migratory Glossitis
• What to do?
• Up to 1/3 of patients are atopic so get a good
history
• How do you elicit a history of atopy?
• Asthma
• Eczema
• Hayfever
• Food Intolerance
Does immediate family member have them?
Did/do you have these conditions?
• Associated with some forms of psoriasis
Benign Migratory Glossitis
• Treatment and follow-up
• No treatment necessary unless severe in which
case topical steroids may be used
• Topical anesthetics such as 2% viscous lidocaine or
diphenhydramine (Benadryl)
• Patient education and information
Lichen planus
• Clinical
•
•
•
•
•
White: keratotic, reticulated, papular
Red: erosive, erythematous
Yellow: ulcerative
If on gingiva, may have gingival-genital syndrome
This is not a leukoplakia
Etio-pathogenesis
• Local causes
• Amalgam (used to be called galvanism)
• Cinnamic aldehyde (in Tartar control and other
toothpastes, chewing gum)
• Systemic causes
• Medications (esp. anti-hypertensives such as
hydrochlorthiazide, allopurinol, sulfasalazine,
carbamazepine, statins, TNF alpha inhibitors etc)
• Hepatitis C esp. in patients living around Mediterranean
• Lupus erythematosus, chronic graft-vs-host disease
Autoimmune diseases that are
“lichenoid”
• Red and white areas of the mucosa, bilaterally
symmetric
• Hepatitis C
• Lupus erythematosus
• Chronic graft-vs.-host disease after
hematopoietic cell (bone marrow)
transplantation
Management of lichen planus
• If due to hypertensive agents, changing
medication not usually helpful – all classes can
cause lichenoid reactions
Topical steroids
• Class I
• Clobetasol 0.05% gel
• Betamethasone 0.05%
• Class II
• fluocinonide gel 0.05%
Place in stent for 30 min BID if only gingiva involved.
• Important to avoid vermilion – cause atrophy with chronic use
• Class IV steroid
• Kenalog (triamcinolone 0.1%) in Orabase
• Dexamethasone (0.1 mg/ml) swish with 5 ml, hold for 3-5 min and
spit out
• Steroid inhalers eg. fluticasone (Flonase), budesonide (Rhinocort)
Treatment of lichen planus
• Other topical immunosuppresive agents
• Calcineurin-inhibitors
• Tacrolimus (0.1% ointment or rinse, swish and spit out)
• Intralesional steroid injections
• Kenalog-40 (40 mg triamcinolone/ml)
• Systemic therapy
• Prednisone (1 mg/kg)
• Hydroxychloroquin (Plaquenil)
Plaque-type lichen planus
• Current thinking
• If striations are not present, not a sub-type of
lichen planus - leukoplakia
• If striations are present, may be development of
leukoplakia within lichen planus
• Must be biopsied and completely
removed/ablated
• May be associated with malignant transformation
in lichen planus
Plaque-type lichen planus
• Current thinking
• If striations are not present, not a sub-type of
lichen planus - this is a leukoplakia
• If striations are present, may be development of
leukoplakia within lichen planus
• Must be biopsied and completely
removed/ablated
• May be associated with malignant transformation
in lichen planus
Current definition of leukoplakia
• 2007 (WHO): White plaque of questionable
risk having excluded (other) known diseases or
disorders that carry no increased risk for
cancer.
• It is a clinical term only; modified after
histopathologic evaluation.
• 1-3% of general population
• 50-70% of patients with leukoplakia smoke
Occurrence of dysplasia/SCCa
• Prior to 2005
• 10-20% of all leukoplakias are dysplasia or
carcinoma at the time of biopsy
• New data
• 40-45% of all leukoplakias are dysplasia or
carcinoma at the time of biopsy
Occurrence of dysplasia/SCCa
• Prior to 2005
• 10-20% of all leukoplakias are dysplasia or
carcinoma at the time of biopsy
• New data
• 40-45% of all leukoplakias are dysplasia or
carcinoma at the time of biopsy
Leukoplakia
• Localized leukoplakia
• Homogenous - well-demarcated, fissured
• Non-homogenous – not as well-demarcated
• speckled (erythroleukoplakia)*
• Verrucous*
• Nodular*
• Proliferative leukoplakia (PL)
• Non-homogenous
• Verrucous (most common – proliferative verrucous leukoplakia)
• Erythroleukoplakia
*Non-homogenous forms and PL have a higher association with
dysplasia and carcinoma
Prognosis
• 3-15% transform to invasive squamous cell
carcinoma
• Non-homogenous leukoplakias more likely to
do this
• Proliferative leukoplakia show 70-100%
transformation to squamous cell carcinoma
over time
Leukoplakia
• Clinical
• common sites are tongue, floor of mouth and
gingiva
• lesions on the floor of mouth, ventral tongue and
soft palate have a higher association with
dysplasia or carcinoma than other sites (>50%)
• Helpful sign – sharp demarcation at least in parts
of the lesion
Risk factors
• Same as with SCCa
•
•
•
•
•
•
•
•
•
Cigarette smoking
Alcohol use
Areca nut use
Sunlight (mostly lip)
Age
Immunosuppression
History of previous cancer
Family history of cancer
HPV (mostly oropharyngeal and tonsillar)
Helpful clinical features
• Applies mainly to homogenous lesions that
can resemble other conditions
• Sharp demarcation at least along part of the
lesion
• Fissuring
Be careful!
• If you get a diagnosis on a pathology report
“Hyperkeratosis, no dysplasia”
BE CAREFUL!
Verrucous white lesions
• Verrucous leukoplakia
• White plaque (leukoplakia) that has a rough, warty surface
configuration but is not a mass lesion
• Proliferative (verrucous) leukoplakia
• Verrucous leukoplakia but extensive at one site, or
multifocal
• Progressive, persistent
• Usually female, often gingival
• Biopsies show “hyperkeratosis, no dysplasia”
• 70-100% develop verrucous or SCCA
Pathology report
• Hyperkeratosis and epithelial hyperplasia
with chronic inflammation, no dysplasia
present
Check clinical lesion again
• Is this “hyperkeratosis” frictional/reactive or
not?
• If not frictional/reactive, it is a TRUE
leukoplakia
What does it mean for you?
• All true leukoplakias are potentially cancerous
lesions.
• If just “hyperkeratosis”, re-evaluate the clinical
lesion.
Re-evaluate the lesion
•
•
•
•
•
•
•
•
Is it at least partially welldemarcated?
Has it ever resolved completely?
Could it be frictional?
If unlikely to be frictional, what can
be causing the hyperkeratosis? Early
dysplasia?
Are there risk factors in patient?
Is this a “high risk” site?
Is it verrucous?
What would you do if this was in your
mouth
Weigh carefully no treatment vs.
treatment
•
•
•
•
•
•
Do we know if this will become invasive?
Do we know when it will become invasive?
How morbid, difficult, expensive is removal?
Is the patient healthy and what age?
Can we safely watch and see what happens?
If we watch with the option to remove it later,
have we lost valuable time?
Diagnosis: Hyperkeratosis, no dysplasia
• Watch
•
•
•
•
•
Get smaller
Stay the same
Get bigger
Change in appearance
Change in symptoms
• Remove
• Is this too morbid?
• Easier to follow
Management of localized leukoplakia
• All dysplastic lesions must be excised,
preferably with clear margins.
• Even if not dysplastic, conservative or narrow
excision should be considered, if no clear
etiology is identified.
• Wide excision of recurrent lesions
It got smaller – NO
It stayed the same –
NO
It got bigger – YES
It became nodular –
YES
It became stiff - YES
Some important concepts
• Silverman et al. 1985: 16% of “benign
hyperkeratosis” became SCCa over time.
• Many “benign hyperkeratosis” are already
dysplastic genetically.
• Why should “benign” hyperkeratosis become
invasive carcinoma?
Normal-appearing cells
on microscopy but
hyperkeratotic
Normal
Normal
cell
cell
Genotypic
dysplasia
Critical accumulation
of genetic mutations
Phenotypic
Dysplasia:
Cytologic
Architectural
Abnormal-appearing
on microscopy
Invasive
cancer
Acceptable risk
• What level of risk of cancer development is acceptable
to watch a leukoplakia without dysplasia in your
mouth?
• 1 in 10,000 – acceptable to watch?
• 1 in 1000 – acceptable to watch?
• 1 in 100 – acceptable to watch?
• If we use very conservative numbers, it is 2-3% - 1 in
30.
• If we use the high frequency, 16% of benign
hyperkeratosis become dysplasia or cancer – 1 in 5
Diagnosis: Hyperkeratosis,
acanthosis, non-specific, no
dysplasia
Re-evaluate for causative
factors esp. friction
Localized leukoplakia
Poorly demarcated
Proliferative leukoplakia
Well-demarcated
Likely frictional
Large > 3 cm
Small < 3 cm
Morsicatio
mucosae oris
Watch x q 3
mo, rebx q 12 mo.
Excise/ablate
narrowly;
follow q 3 mo
No
recurrence;
follow q 3-6
mo
Recurred;
excise with 23 mm. margin
Benign alveolar
ridge keratosis
Non-specific
reactive
No treatment
No
recurrence;
follow q 3-6
mo.
Watch,
rebiopsy, excise
nodular or
verrucous area;
follow q 3 mo
Photodynamic
therapy
Management of proliferative
leukoplakia
• Multiple biopsies with close follow-up (every
3-6 months); use of adjunctive tests may or
may not be useful
• Laser ablation
• Chemo-prevention
• Photodynamic therapy
HPV and oral cancer
• Strongly associated with the number of sex
partners; 26 vaginal-sex; 6 oral sex (D’Souza
2007)
• Mostly male in early 7th decade
• Weak to no association with smoking
• Mostly oropharyngeal and tonsillar; usually with
cervical node metastasis when first diagnosed
• Better prognosis even when metastasis has
occurred to cervical lymph node (82% vs 57% 3year survival, Ang et al. 2010)
HPV-associated dysplastic leukoplakia
20 cases in our laboratory
•
•
•
•
Mostly males
Median age 60 years
Most lesions ventral tongue
2/20 became squamous cell carcinoma and 1
recurred
HPV leukoplakia
• Clinically just a leukoplakia
• Histologically specific: HPV apoptotic epithelial
dysplasia; high risk HPV positive and always
p16 positive
• Not sure of prevalence because newly
identified.
A Case
• This 56 year old woman presented with this
asymptomatic lesion of the left lateral tongue
of unknown duration.
• 2 ppd smoker X 40 years
• She returns 18 months later after nursing her
sister who subsequently died of breast cancer.
Take home message
• Not all white lesions are leukoplakias
• Most white lesions are frictional keratoses on
the buccal mucosa, tongue and ridge
• ~ 40% of true leukoplakias are dysplastic or
cancer at the time of diagnosis
• Be careful of the sharply demarcated plaque
that has no obvious dysplasia – consider
removing it.