key points OPMDs Flashcards
OPMD definition
morphological alterations with an increased potential for malignant transformation
indicate a risk of likely future malignancies elsewhere in (clinically normal appearing) mucosa
what are OPMDs generally higher in?
Asians and males
major risk factors
tobacco (smoked and smokeless)
excessive alcohol consumption
chewing betel quid containing areca nut
HPV role still unclear
clinical features associated with an increased risk of malignant progression
size >200mm2 texture non-homogeneous red/speckled tongue and FOM F >50yrs non-smoker
histologic features associated with an increased risk of malignant progression
severe dysplasia
HPV16+
DNA aneuploidy
many genes involved
progression from dysplasia to cancer over what time frame
usually 2.5 - 8yrs (av 5yrs)
primary prevention
eliminate modifiable risk factors
secondary prevention
oral screening and periodic follow up
diagnostic tools
COE histopathology adjunctive diagnostic tools - vital staining - light-based detection systems - optical diagnostic technologies - salivary biomarkers
describe LP
chronic, inflammatory, mucocutaneous immuno-mediated disorder of unknown aetiology
LP etiopathogenesis
unidentified trigger initiates cell/tissue damage and immune response
immune reaction to an unknown antigenic stimulus in the epithelium
T4 hypersensitivity (delayed type) = T cell mediated immune reaction
- early T4 helper, late T8 cytotoxic cells
LP potential triggers
viral infections bacterial products food allergens mechanical trauma systemic drugs locally delivered drugs contact sensitivity dysplasia
LP epidemiology
1-2% pop
mostly middle-aged adults
- slight F predominance
- no apparent racial predilection
LP oral sites involved
any
common - buccal mucosa bilaterally, borders and dorsum of tongue, gingiva
rarer - palate (hard/soft), lips, FOM
LP EO manifestations
genital lesions - 20% of those with oral
cutaneous lesions - rosy, papular, scaly, itchy, regress and recur, flexor surfaces - 15% of those with oral
which LP lesions tend to be most persistent and difficult to tx?
oral
clinical types of LP
reticular papular plaque atrophic erosive (ulcerative) bullous desquamative gingivitis
3 conditions desquamative gingivitis is seen in
LP
pemphigus
pemphigoid
symptoms of LP
tends to be persistent
reticular/papular lesions rarely symptomatic
- only need tx if symptomatic
erythematous and erosive/ulcerative lesions usually result in varying discomfort/pain
T lymphocytes in LP
accumulate beneath epithelium of oral mucosa and increase rate of differentiation of SSE, resulting in hyperkeratosis and erythema +/- ulceration
LP - which clinical types have the highest malignant potential?
atrophic and ulcerative
LP histopathology
keratinised SSE (ortho/para)
atrophy or hyperplasia
“hugging band” of lymphocytes below epithelium
= epitheliotropism
apoptosis of basal cell layer
“liquefaction degeneration” in basal cell layer
saw tooth rete peg appearance
acantholysis
colloid bodies
well-defined zone of cellular infiltration confined to LP
LP clinical appearance
usually multiple and symmetrical
often white papules which gradually enlarge and coalesce to form reticular, annular or plaque pattern
Wickham’s striae: white lines radiating from the papules
reticular form - lacelike network of slightly raised grey white lines, often interspersed with papules or rings
sometimes erythema, atrophy, ulceration +/- erosions
- bullae rare
desquamative gingivitis
clinical - descriptive term
whole thickness of gingiva can be affected
most often LP - can be pemphigus or pemphigoid
SLS, flavour or preservatives
when should you biopsy LP?
smoker
symptomatic
erosive type
LP tx
CS - topical/systemic retinoids - topical/systemic vit A homeopathic/herbal immunosuppressive agents - azathioprine - methotrexate calcineurin inhibitors - cyclosporin - tacrolimus biological agents
tx for desquamative gingivitis
change toothpaste (SLS free)
improve OH (plaque aggravates lesions)
topical steroids - MDI inhaler or gum shield filled with steroid
topical tacrolimus (immune modulation) rinse or cream
systemic immunosuppression rarely
erythroplakia definition
clinically descriptive term
a fiery red patch that cannot be characterised clinically or pathologically as any other definable disease
risk factors for erythroplakia
tobacco chewing
tobacco smoking
betel quid chewing
+/- tobacco and alcohol usage
erythroplakia epidemiology
much rarer than leukoplakia
varies 0.2-0.7%?
erythroplakia pathogenesis
unknown
indications that it may be related to lichenoid lesions, which would constitute precursors of erythroplakia
erythroplakia clinical features
usually asymptomatic
fiery red macule
sharply demarcated lesion situated at a slightly lower level than surrounding mucosa
smooth, uniform, homogenous colour
may have a velvety feel because of its soft consistency on palpation
rarely multiple/extensive
carries a v high risk of malignancy
histopathological predictors of malignancy
architectural changes - abnormal maturation and stratification
cytological abnormalities - cellular atypia
11 histological features of epithelial dysplasia
increased and abnormal mitoses basal cell hyperplasia drop shaped rete pegs altered basal cell polarity increased area or vol nuclear:cytoplasmic ratio nuclear hyperchromatism enlarged nuclei irregular epithelial stratification pleomorphism abnormal keratinisation loss/reduction of intracellular adhesion
6 hallmarks of cancer
evading apoptosis self-sufficiency in growth signals insensitivity to anti-growth signals tissue invasion and metastasis limitless replicative potential (immortality) sustained angiogenesis
CHC clinical features
often buccal commissures/retrocommissural region
white rough patch, can’t be rubbed off, may be bits of red
stings on eating spicy food
well-demarcated, smooth, homogeneous, raised white plaque
can appear non-homogenous with a nodular or speckled aspect
rarely other oral sites - mainly tongue
chronic multifocal candidiasis
tetrad CHC denture stomatitis angular cheilitis MRG and oval/circular erythematous lesion on palate corresponding (kissing lesion)
CHC risk/predisposing factors
tobacco smoking and chewing alcohol consumption betel quid chewing Fe deficiency diabetes immunocompromised
CHC management
biopsy
smoking cessation
fluconazole and follow up
surgical excision if persistent and dysplasia
tx of concomitant staph infection - topical mupirocin 2% cream
CHC clinical diagnosis
homogeneous/non-homogeneous leukokeratotic plaque-type lesions localised in the retrocommissural area, +/- involvement of the commissure (fissure) and pericommissural area
CHC histopathological diagnosis
hyperortho or hyperparakeratosis (usually without dysplasia in the homogeneous forms)
candidal hyphae invading epithelium
chronic inflammation in LP, polymorphonuclear leukocytes can form “microabscesses” associated with candidal hyphae
CHC malignant transformation
colonisation of the epithelium
ability to produce carcinogens and initiate carcinogenesis
ability to promote carcinogenesis in an initiated epithelium
ability to metabolise procarcinogens
ability to modify the microenv and induce chronic inflammation
actinic cheilitis - definition
chronic inflammatory process, affects mainly L lip, due to a chronic UV exposure
actinic cheilitis - significant and independent risk factors
age 60 or above
Fitzpatrick skin phototype 2
outdoor working for >25 years
prev history of non-melanoma skin cancer
actinic cheilitis - clinical features
dryness, scaliness, colour variation
can be associated with atrophy, swelling, erythema, ulceration and diminished demarcation of vermillion border
vertical folds of lip can become more pronounced
grey-white discolouration
fissures
actinic cheilitis - tx
biopsy
surgical tx 1st line
laser therapy appears best option among non-surgical approaches
heterogeneous, photodynamic therapy and imiquimod application are promising
no evidence of effective tx in preventing malignant transformations
actinic cheilitis - clinical diagnosis
painless thickening and whitish discolouration at borders of lips, may gradually become scaly and indurated
actinic cheilitis - histopathological diagnosis
epithelial atrophy hyperkeratosis solar elastosis - loss of eosin staining, accumulation of thick irregular elastic fibres and tangled fibrillin - elastin replaces collagen perivascular inflammation \+/- dysplasia
actinic cheilitis - why is biopsy mandatory?
some are found to be severe dysplasia or OSCC on 1st biopsy
actinic cheilitis - prevention
sunscreen and UV protective clothing
wide-brimmed hats
lip balm containing UVA and B
sunscreen/zinc
proposed classification of cheilitis categories
mostly reversible
mostly persistent
in association with dermatoses and systemic diseases (common conditions)
modified WHO criteria for OLP and OLL - clinical
bilateral, more or less symmetrical lesions
reticular pattern: lace-like network of slightly raised grey-white lines
erosive, atrophic, bullous and plaque-type lesions only accepted as a subtype in the presence of reticular lesions elsewhere in the oral mucosa
= in all other lesions that resemble OLP but don’t complete above criteria, use term ‘clinically compatible with’
modified WHO criteria for OLP and OLL - histopathological
well-defined band-like zone of cellular infiltration confined to superficial part of CT (LP), consisting mainly of lymphocytes
‘liquefaction degeneration’ in basal layer
absence of epithelial dysplasia
= when histopathological features are less obvious, use term ‘histopathologically compatible with’
modified WHO criteria for OLP and OLL - final diagnosis
OLP - fulfilment of both clinical and histopathologic criteria
OLL - clinically/histopathologically ‘compatible’ with either or both
LP proposed criteria - clinical
multifocal symmetric distribution white and red lesions exhibiting 1 or more of the following forms: - reticular/papular - atrophic (erythematous) - erosive (ulcerative) - plaque - bullous lesions not localised exclusively: - to the sites of smokeless tobacco placement - adjacent to and in contact with Rxs lesion onset does not correlate with the: - start of a medication - use of cinnamon containing products
LP proposed criteria - histopathological
band-like or patchy, predominantly lymphocytic infiltrate in the LP confined to the epithelium-LP interface
basal cell liquefactive (hydropic) degeneration
lymphocytic exocytosis
absence of epithelial dysplasia
absence of verrucous epithelial architectural change
leukoplakia - definition
clinical term to describe a white plaque (that can’t be rubbed off) of questionable risk having excluded (other) known diseases/disorders that carry no increased risk of cancer
- doesn’t indicate what kind of white plaque lesion
leukoplakia - clinical parameters
site size homogeneity multifocality duration > or < 5yrs dysplasia smoking habit drinking habit
leukoplakia - predictive risk factors for malignant transformation - pt characteristics
F non-smoker >60yrs drinker chronic alcohol MW use history of H and N cancer
leukoplakia - predictive risk factors for malignant transformation - lesion characteristics
dysplasia <5yrs since diagnosis lat tongue, FOM, RM trigone/SP >200mm2 multifocal non-homogeneous infection with c albicans DNA aneuploidy
leukoplakia - clinical types (surface colour and morphology)
homogeneous
- uniform colour, flat, thin, with/without a slightly corrugated surface
non-homogeneous
- speckled: white plaque mixed in w red areas
- nodular: small polypoid outgrowth, white or red
- verrucous: white plaque with a warty surface
- mixed lesions: red and white plaque
leukoplakia - differential diagnosis
white sponge naevus frictional keratosis morsicatio buccarum chemical injury acute pseudomembranous candidosis leukoedema LP (plaque type) lichenoid reaction discoid lupus erythematosus skin graft hairy leukoplakia leukokeratosis nicotina palate
leukoplakia - initial mandatory management
biopsy
make definitive diagnosis when any aetiological cause other than tobacco/areca nut use has been excluded and histopathology has not confirmed any other specific disorder
leukoplakia - results of biopsy
most histologically benign
- usually hyperkeratosis or chronic inflammation
up to 20% may show changes - dysplasia/carcinoma
- high risk sites tongue and FOM
KUS
a histopathological term: just indicates hyperkeratosis with minimal/no atypia i.e. hyperkeratosis without epithelial dysplasia
what may KUS transform into?
OSCC
KUS histological features
can have parakeratosis, epithelial atrophy/acanthosis +/- inflammation
histologically different from frictional and reactive keratoses
KUS aetiology
unclear
don’t appear to be reactive
not obviously dysplastic
unclear what the biologic behaviour of these lesions is
KUS location
many occur at sites that are high risk for epithelial dysplasia and OSCC - tongue, FOM, SP
why might KUS be a more appropriate term than “benign hyperkeratosis”?
significance is unknown
some may be reactive and some may progress to dysplasia and OSCC
non-reactive keratoses (true leukoplakia)
KUS
dysplasia
cancer OSCC
PVL features
disease of unknown origin
clinically often begins as single white lesion, over time tends to become multifocal
grows slowly and progressively, harder to control
elderly women
high recurrence rate after tx
v high rate of malignant change
all sites in oral cavity can be affected, doesn’t show any preference for specific oral subsites
PVL modified diagnostic criteria
1 - leukoplakia showing verrucous/wartlike areas, involving >2 oral subsites
2 - add all involved sites ≥3cm
3 - disease evolution at least 5yrs, spreading and enlarging and ≥1 recurrences in a prev treated area
4 - at least 1 biopsy to rule out verrucous carcinoma/SCC
= all 4 criteria should be met
PVL tx
surgical resection
PVL major criteria
A - leukoplakia lesion with >2 oral sites
- most freq gingiva, alveolar process and palate
B - verrucous area
C - spread/engrossed during disease development
D - recurrence in a prev txed area
E - histopathology
- from simple epithelial hyperkeratosis to verrucous hyperplasia, verrucous carcinoma or oral SCC (in situ/infiltrating)
PVL minor criteria
A - ≥3cm when adding all affected areas
B - F
C - pt (M/F) non-smoker
D - disease evolution >5yrs
PVL final diagnosis
3 major criteria (inc E)
2 major criteria (inc E) and 2 minor criteria
proliferative leukoplakia
NOT a form of non-homogeneous leukoplakia
may be a more appropriate term than PVL because 18% are fissured and 22% erythematous
proliferative erythroleukoplakia PEL
better describes PL with prominent erythema
has highest malignant transformation rate similar to erythroleukoplakia
clinical diagnostic criteria PL
white/keratotic lesions - smooth/fissured/verrucous/erythematous +/- ulcer
multifocal non-contiguous lesions or one lesion >4cm involving one site, or one lesion >3cm involving contiguous sites
expand in size/develop multifocality over time
histopathology diagnostic criteria PL
if doesn’t show dysplasia/carcinoma shows hyperkeratosis, parakeratosis, atrophy or acanthosis with min to no cytologic atypia (KUS)
+/- lymphocytic band or verrucous hyperplasia
these features must not support a diagnosis of frictional or reactive keratosis
leukoplakia management
photos every visit - submit to pathologist with biopsy
follow-up every 3-6m
- depends on histopathological diagnosis
periodic biopsies esp when change in character of lesion
biopsies that show only KUS can be followed only
- tx gingival leukoplakias on a case-by-case basis as many other factors impact tx - age, health, degree of involvement, bone loss, tooth mobility, appearance/behaviour of lesion
leukoplakia result of biopsy - mild/mod dysplasia
can likely be observed if it is felt that complete removal not possible due to extent/location of lesion
if area discrete excision can be attempted
leukoplakia result of biopsy - severe dysplasia/CIS
excise esp if discrete with the understanding that the margin will likely show KUS or mild/mod dysplasia
what should pathology reports for excisional biopsies always report on?
margins, eben if they show KUS
tx of leukoplakia to prevent cancer
surgical interventions non-surgical - vit A/retinoids - beta carotene or carotenoids - NSIADs (ketorolac and celecoxib) - herbal extracts - bleomycin - Bowman-Birk inhibitor
currently no evidence of a tx that is effective for preventing development of oral cancer
classification of OLLs
oral lichenoid contact lesions (OLCLs)
oral lichenoid drug reactions (OLDRs)
OLLs in GvHD (OLL-GvHD)
OLL unclassified
Van der Waals OLLs classification
amalgam Rx
drug-related
cGvHD
unclassified
OLCLs - when is histological confirmation recommended?
in clinically atypical cases (exclude dysplasia/malignancy)
- but histopathology alone can’t reliably distinguish between OLP and OLCL
OLCLs tx
may do skin patch testing - take readings at days 3,7,14 or even later to avoid missing delayed reactions
removal/replacement/coverage of Rxs that are in direct physical contact with mucosal lesions and are thought to be playing a causative role
why can it be difficult to establish a diagnosis in OLDRs?
lack of specific features that distinguish it from OLP
may be hazardous to replace/withdraw drug
may take several months to see clinical change after withdrawing drug
OLL-GvHD - when is histological confirmation indicated?
in absence of S+S of involvement of other systems/organs
when investigations of other sites provide only negative/non-specific results
cases of atypical clinical presentation to exclude dysplasia/malignancy
OLL-GvHD tx
1st line - topical CS (+/- topical antimycotics) as an adjunct to systemic therapy or for isolated lesions
2nd line tx - topical calcineurin inhibitors as an adjunct to systemic therapy or for isolated lesions
PUVA not recommended - oncogenic potential
potential histologic difference between LP and LTR
perivascular cuffing/infiltrate in LTR - inflammatory cells round blood vessels
indicates delayed hypersensitivity reaction
OSF definition
debilitating, progressive, irreversible, collagen metabolic disorder induced by the chronic chewing of areca nut and its commercial preparations, affecting the oral mucosa and occasionally the pharynx and oesophagus, leading to mucosal stiffness and fct morbidity, has a potential risk of malignant transformation
OSF epidemiology
about 10-20% world pop chew betel quid
about 600m areca nut chewers globally
recently noticed in children and adolescents
- similar clinical presentation to adults: burning sensation and blanching of buccal mucosa
OSF pathogenesis
chewing betel quid is main cause of OSF
betel quid interferes with collagen metabolism
- increases collagen synthesis
- reduces collagen clearance
the thick fibres injure the oral mucosa
- causes inflammation of epidermal cells and activates macrophages to secrete cytokines
changes in cytokines and GFs cause fibroblast proliferation and collagen synthesis near the site of injury - fibrosis
OSF S+S
mucosal blanching
stiffness
fibrous bands with a gradual inability to open the mouth
shrunken and everted uvula
depapillated tongue
fibrosis of palate with subsequent nasal intonation
OSF prodromal symptoms
*burning sensation in mouth on eating spicy food
*ulceration/recurrent stomatitis
excessive salivation
defective gustatory sensation
occ dryness with painful vesicles
OSF late S+S
fibrosis of laryngopharynx, oesophagus, Eustachian tubes, dysphagia and even hearing impairment
OSF malignant transformation to OSCC
OSF pathogenesis is quite varied which makes its transformation to malignancy open to many varied mechanisms areca nut as a potent carcinogen - arecoline, major alkaloid of areca nut, with its cytotoxic and genotoxic properties mediates carcinogenesis by many pathways hypoxia cell cycle alterations angiogenesis sensecence alterations in oncosuppressor genes
= early diagnosis and tx only best possible way to control progression towards malignancy
OSF Grade 1 clinical
involves <1/3 oral cavity
mild blanching, burning sensation, recurrent ulceration and stomatitis, dryness
OSF Grade 1 fct
mouth opening up to 35mm
OSF Grade 1 histopathological
stage of inflammation
OSF Grade 1 tx
habit cessation
nutritional supplement
antioxidants
topical steroid ointment
excellent prognosis
OSF Grade 2 clinical
1/3-2/3 involved
blanching with mottled and marble-like appearance, fibrotic bands palpable and involvement of SP and premolar area
OSF Grade 2 fct
mouth opening 25-35mm
cheek flexibility reduced by 33%
OSF Grade 2 histopathological
stage of hyalinisation
OSF Grade 2 tx
habit cessation nutritional supplement intralesional injection of placental extracts hyaluronidase steroid therapy physio
prognosis good, recurrence rate low
OSF Grade 3 clinical
> 2/3 of oral cavity
severe blanching
broad thick fibrous palpable bands at cheeks, lips and rigid mucosa
depapillated tongue and restricted tongue movement
shrunken bud like uvula
FOM involvement and lymphadenopathy
OSF Grade 3 fct
mouth opening 15-25mm
cheek flexibility reduced by 66%
OSF Grade 3 histopathological
stage of fibrosis
OSF Grade 3 tx
surgical
prognosis fair, recurrence rate high
OSF Grade 4 clinical
leukoplakia changes, erythroplakia
ulcerating and suspicious malignant lesion
OSF Grade 4 fct
mouth opening <15mm or nil
OSF Grade 4 histopathological
stages of malignant transformation: erythroplakia changes into SCC
OSF Grade 4 tx
surgical and biopsy of suspicious lesion
prognosis poor, malignant transformation
OSF tx
depends on degree of clinical involvement
early stage - habit cessation sufficient
medical tx is symptomatic and predominantly aimed at improving mouth movements
- steroids
- enzymes
- drugs
- nutritional interventions
advanced stage - surgical tx - where restricted mouth opening due to heavy fibrous bands in buccal mucosa
no reliable evidence for effectiveness of any interventions
GvHD definition
post-allogenic transplant
develops when non-identical donor immune cells recognise the recipient tissue antigens (the host) as foreign, and the donated cells/bone marrow attack the body
GvHD risk factors
genetic factors older donor and recipient age multiparous F donor advanced malignant condition at transplantation donor type donor haematopoietic cell source
aGvHD pathogenesis
activation of APCs
donor T cell activation, proliferation, differentiation and migration
target tissue destruction
2 forms of GvHD
acute or chronic
can get 1 form, both forms or neither
historically - time post-transplant (< or > 100 days)
now clinical manifestations guide whether the S+S of GvHD are acute or chronic
major organs affected by aGvHD
skin (erythema)
GI (secretory)
liver
aGvHD - 1st episode
classic acute
aGvHD - subsequent episode
recurrent
persistent
new onset or late acute
major organs affected by cGvHD
skin (lichenoid, sclerotic) mouth nails and hair - loss eyes - dry lung - restrictive/obstructive MS - myositis haematopoietic - anaemia, neutropenia GI (oesophageal) - strictures liver - jaundice other
cGvHD with no sign of acute
classic chronic
cGvHD with signs of acute
overlap syndrome
where there are mixed features of both acute and chronic
associated with adverse prognosis and increased disease burden
acute GvHD skin
maculopapular skin rash
- most freq affected and usually first organ
aGvHD GIT
nausea, diarrhoea, abdo pain
aGvHD liver
cholestatic hyperbilirubinaemia
aGvHD oral cavity
diffuse ulcerative and erythematous lesions +/- lip crusting
aGvHD grading
1 mild
2 mod
3 severe
4 v severe
chronic GvHD
by definition after day 100 but usually 3-18m post-BMT
major cause of late non-relapse death following allogenic BMT
no effective prophylaxis regimen
cGvHD risk factors
prior acute GvHD
older recipient age
F donor (multiparous in particular) with a M recipient
use of peripheral blood SCs
oral complications of cGvHD
OSCC
rampant caries
fibrosis
oral manifestations (main ones) of cGvHD
oral mucosal cGvHD - lichen type features - hyperkeratotic plaques salivary gland cGvHD sclerotic cGvHD
NIH oral cGvHD clinical scoring
score mucosal changes: erythema, lichenoid, ulcers
- no evidence, mild, mod, severe
GvHD tx
oral mucosal - steroid solutions - lips - tacrolimus ointment salivary gland - xerostomia - stimulants, moisturising agents - caries - OH, F, diet - candidiasis - fluconazole sclerotic - physical therapy - intralesional steroid therapy - surgery to disrupt mucosal bands
GvHD - oral cavity may be only clinical site affected in a subset of pts
initial activation of APCs may occur via a respiratory infection or other inflammatory insult to oral cavity
once APCs activate CD4 and CD8 T cells, they initiate a strong cytokine response and migrate into oral mucosa, causing tissue damage and a reactive hyperkeratosis
once cellular mediators (T cells, activated macrophages and NK cells) have chemotaxed into target tissues, their production of chemokine and cytokine mediators acts synergistically to enhance target tissue destruction - oral ulcerations
potentially malignant lesion
altered tissue in which cancer is more likely to form
potentially malignant condition
generalised state with increased cancer risk
why should the term “potentially malignant disorder” be used rather than premalignant/precancerous/preneoplastic?
malignant change won’t definitely happen
molecular markers in oral epithelial dysplasia
signalling pathways EGFR cell cycle Ki67, p53, pRB immortalisation telomerase apoptosis p53, 21 angiogenesis VEGF COX 1 and 2 enzymes proliferation and differentiation markers viruses - HPV loss of heterozygosity 3p 9p 13q (retinoblastoma) 17p
no markers, whether single or in combination, have been identified to help determine progression
where do most oral carcinomas arise in the UK vs high incidence areas e.g. India?
UK - most in clinically normal mucosa
high incidence areas - from potentially malignant lesions
how much more likely is leukoplakia to progress to cancer than clinically normal mucosa?
50-100x
- but not every leukoplakia will progress into cancer
leukoplakia clinical predictors of malignancy
age and gender
idiopathic (non-smoker, low alcohol)
site - buccal mucosa low risk, FOM and tongue high risk
clinical appearance - non-homogeneous - verrucous, ulcerated leukoerythroplakia
leukoplakia histopathological indicators of malignant change - gold standard
dysplasia
atrophy (esp if red lesion)
candida infection
biological marker - why could the DNA content in leukoplakia be a potential future prognostic indicator?
DNA content in nuclei of dysplastic epithelial cells is higher than in normal epithelial cells
dysplasia
disordered/abnormal maturation (growth) in a tissue
- has to show this to be considered potentially malignany
atypia
changes in cells
- fct, appearance, arrangement to other cells
criteria for diagnosis of dysplasia
assess architectural changes then cytology
boundaries between categories not well defined
architectural changes
- abnormal maturation and stratification
- how many layers
- rete pegs
cytological abnormalities
- cellular atypia
grading of epithelial dysplasia - WHO 2005
hyperplastic mild mod severe carcinoma in situ
hyperplastic (basal hyperplasia)
increased basal cell numbers rest of epithelium normal architecture - regular stratification - basal compartment larger no cellular atypia
mild dysplasia
architecture: changes in lower 1/3
cytology: mild atypia (few cells)
- pleomorphism
- hyperchromatism
- foci of slight irregularity in the stratification of the epithelium as it matures towards surface
- occ superficial mitoses
- basal cells hyperplasia, crowding - slight dip to accommodate increase
- not high numbers of cells abnormal
most cases will regress esp if can identify a causative factor and address it e.g. smoking often a reactive change
hyperchromatism
increased DNA in nuclei so they take up more stain
mod dysplasia
changes extend into middle 1/3
cytology - mod atypia
- pleomorphism
- hyperchromatism
severe dysplasia
architecture - changes extend to upper 1/3
cytology - severe atypia and numerous mitoses, abnormally high
- loss of polarity
- hyperchromatism
- pleomorphism
- most cells involved
- severe immune inflammatory reaction against changed epithelial cells/ulcer - change in antigenicity
- mitoses should only occur in basal cell layer, not high up in epithelium
high risk of malignant change
keratinised - clinically leukoplakia
areas where epithelium thin - erythroplakia
ulceration
= non-homogeneous
carcinogenesis components
genetic
env (carcinogens)
CIS
theoretic concept
malignant but not invasive
abnormal architecture
- full thickness (or almost full) of viable cell layers
- large rete pegs
pronounced cytological atypia
- mitotic abnormalities frequent
still located in epithelium - why not invasive SCC
inflammation in LP
- immune response larger in more severe dysplasia
- due to genetic changes happening in epithelial cells
molecular basis of cancer
damage
altered gene expression - affects formation of protein (increased/silenced)
altered cell fct
changes to genes may inc:
changes to chromosomes
- aneuploidy - abnormal number of chromosomes
- translocations - a part breaks off and may attach to another
- amplifications
genes
- mutations
- deletions
- amplifications
epigenetic changes
- chemical changes in DNA, such as methylation and modification of the histones that package DNA
- DNA itself isn’t changing but makes it more likely to be/not be silenced
oral cancer genes involved
oncogenes TSGs Tp53 genes that regulate apoptosis genes involved in DNA repair miRNA - micro RNA viral component HPV16 and 18
oncogenes
have normal roles within the cells, produce GFs, differing oncogenes activated
TSGs
suppress the growth of cells
Tp53 (a TSG)
checks cells - sends irreparable cells for apoptosis to prevent mutations being passed on
a TSG and an apoptosis gene
mutation or inactivation
miRNA - microRNA
strands of non-coding RNA - don’t produce proteins
some can act as oncogenes/TSGs - can play a part in neoplastic transformation
viral component - HPV16 and 18 (oncogenic types)
oropharyngeal and cervical
produce proteins which deactivate proteins produced by TSGs e.g. p53
Knudson’s 2 hit hypothesis of carcinogenesis
TSGs - both alleles need to be inactivated before malignancy
field change theory (field cancerisation)
all of area may be susceptible to developing oral cancer
- if they have oral cancer the rest of the oral cavity is at risk
genetic instability increases possibility of developing cancer
clinically may appear normal
difficult to estimate extent of field
multiple primaries 15-20%
- inc larynx, pharynx and resp tract
6 hallmarks of cancer
evading apoptosis self-sufficiency in growth signals insensitivity to anti-growth signals limitless replicative potential (immortality) sustained angiogenesis tissue invasion and metastasis
process of carcinogenesis
“multistep” - initiation, promotion, progression
sum of genetic changes (not order/number) important
cancer cell interacts with its env - gets other cells to produce factors to help it grow and metastasise
features predicting LN involvement
non-cohesive front
perineural infiltration
malignant cells in lymphatic vessels and bv’s
oral cancer pathology report points
diagnosis: SCC 90%
differentiation and grading
pattern of invasive front
local extension of disease
what is the pattern of invasive front related to?
nodal spread
differentiation and grading
how well tissue resembles normal and how much of its fct it can perform
well-differentiated
can tell they are epithelial cells and produce keratin
better response, less recurrence, better prognosis
moderately differentiated
80% can tell epithelial cells but no keratin production
poorly differentiated
hard to tell whether epithelial cells
need tests
anaplastic differentiated
virtually impossible (related to metastatic tumours)
pattern of invasive front
related to nodal spread
cohesive front
non-cohesive front
cohesive front
all cells advancing together at same rate, like a wave
non-cohesive front
strands/individual malignant cells breaking off from main front
associated with LN spread (micrometastasis)
OSCC subtypes
verrucous carcinoma - better prognosis, slow growing, rarely recurs basaloid squamous - HPV association - aggressive spindle cell - aggressive
causes of pigmentation
physiological/natural/racial mucosal melanoma smoking post-surgical pigmentation inflammatory e.g. LP medications (prolonged CHX MW) Addisons
spread of oral cancer
local extension of disease
lymphatic spread
haematogenous spread
local extension of disease
varies according to site mucosal extension muscle (tongue etc) bone - edentulous: gaps in cortex - dentate: via PDL nerve
lymphatic spread
*embolism - in lymphatics to get to LNs
permeation - tumour grows through lymphatic system
tumour involved node with EC spread
sentinal node biopsy
see if cancer has spread to LNs
identify principal LNs by special techniques
- remove and study under microscope for micrometastasis
- if clear don’t need to remove chain, if not remove
haematogenous spread
late feature (lymphatic first)
? enter veins in neck
- veins more susceptible as thinner walls
metastasis to lungs, spine etc
metastatic cascade
intravasation survive in circulation arrest in organ/tissue extravasation survive extravasation initial proliferation established growth
oral cancer histopathology
invasion - cells beyond usual boundary into CT and even muscle (likely LN spread) - hard/induration
individual cells and nuclei vary size and shape
LN - epithelium cells present - 2 reasons - either due to metastatic tumour or developmental anomaly
LN appears as dark lymphoid tissue - organised pattern and peripheral CT capsule (FNAB)
immune reaction with every malignancy
- non-self cells
- malignant cells: influence other immune cells to produce things which help them
palatal lesions in reverse smokers
white and/or red patches affecting the HP in reverse smokers
freq stained w nicotine
OLE
AI CT disease
may affect lip and oral cavity
erythematous area surrounded by whitish striae, freq with a target configuration
often palate
dyskeratosis congenita
rare cancer-prone inherited bone marrow failure syndrome caused by aberrant telomere biology
dyskeratosis congenita diagnostic triad
dysplastic nails
lacy reticular skin pigmentation
oral leukoplakia
