key points OPMDs Flashcards
1
Q
OPMD definition
A
morphological alterations with an increased potential for malignant transformation
indicate a risk of likely future malignancies elsewhere in (clinically normal appearing) mucosa
2
Q
what are OPMDs generally higher in?
A
Asians and males
3
Q
major risk factors
A
tobacco (smoked and smokeless)
excessive alcohol consumption
chewing betel quid containing areca nut
HPV role still unclear
4
Q
clinical features associated with an increased risk of malignant progression
A
size >200mm2 texture non-homogeneous red/speckled tongue and FOM F >50yrs non-smoker
5
Q
histologic features associated with an increased risk of malignant progression
A
severe dysplasia
HPV16+
DNA aneuploidy
many genes involved
6
Q
progression from dysplasia to cancer over what time frame
A
usually 2.5 - 8yrs (av 5yrs)
7
Q
primary prevention
A
eliminate modifiable risk factors
8
Q
secondary prevention
A
oral screening and periodic follow up
9
Q
diagnostic tools
A
COE histopathology adjunctive diagnostic tools - vital staining - light-based detection systems - optical diagnostic technologies - salivary biomarkers
10
Q
describe LP
A
chronic, inflammatory, mucocutaneous immuno-mediated disorder of unknown aetiology
11
Q
LP etiopathogenesis
A
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
12
Q
LP potential triggers
A
viral infections bacterial products food allergens mechanical trauma systemic drugs locally delivered drugs contact sensitivity dysplasia
13
Q
LP epidemiology
A
1-2% pop
mostly middle-aged adults
- slight F predominance
- no apparent racial predilection
14
Q
LP oral sites involved
A
any
common - buccal mucosa bilaterally, borders and dorsum of tongue, gingiva
rarer - palate (hard/soft), lips, FOM
15
Q
LP EO manifestations
A
genital lesions - 20% of those with oral
cutaneous lesions - rosy, papular, scaly, itchy, regress and recur, flexor surfaces - 15% of those with oral
16
Q
which LP lesions tend to be most persistent and difficult to tx?
A
oral
17
Q
clinical types of LP
A
reticular papular plaque atrophic erosive (ulcerative) bullous desquamative gingivitis
18
Q
3 conditions desquamative gingivitis is seen in
A
LP
pemphigus
pemphigoid
19
Q
symptoms of LP
A
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
20
Q
T lymphocytes in LP
A
accumulate beneath epithelium of oral mucosa and increase rate of differentiation of SSE, resulting in hyperkeratosis and erythema +/- ulceration
21
Q
LP - which clinical types have the highest malignant potential?
A
atrophic and ulcerative
22
Q
LP histopathology
A
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
23
Q
LP clinical appearance
A
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
24
Q
desquamative gingivitis
A
clinical - descriptive term
whole thickness of gingiva can be affected
most often LP - can be pemphigus or pemphigoid
SLS, flavour or preservatives
25
when should you biopsy LP?
smoker
symptomatic
erosive type
26
LP tx
```
CS - topical/systemic
retinoids - topical/systemic
vit A
homeopathic/herbal
immunosuppressive agents
- azathioprine
- methotrexate
calcineurin inhibitors
- cyclosporin
- tacrolimus
biological agents
```
27
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
28
erythroplakia definition
clinically descriptive term
| a fiery red patch that cannot be characterised clinically or pathologically as any other definable disease
29
risk factors for erythroplakia
tobacco chewing
tobacco smoking
betel quid chewing
+/- tobacco and alcohol usage
30
erythroplakia epidemiology
much rarer than leukoplakia
| varies 0.2-0.7%?
31
erythroplakia pathogenesis
unknown
| indications that it may be related to lichenoid lesions, which would constitute precursors of erythroplakia
32
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
33
histopathological predictors of malignancy
architectural changes - abnormal maturation and stratification
cytological abnormalities - cellular atypia
34
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
```
35
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
```
36
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
37
chronic multifocal candidiasis
```
tetrad
CHC
denture stomatitis
angular cheilitis
MRG and oval/circular erythematous lesion on palate corresponding (kissing lesion)
```
38
CHC risk/predisposing factors
```
tobacco smoking and chewing
alcohol consumption
betel quid chewing
Fe deficiency
diabetes
immunocompromised
```
39
CHC management
biopsy
smoking cessation
fluconazole and follow up
surgical excision if persistent and dysplasia
tx of concomitant staph infection - topical mupirocin 2% cream
40
CHC clinical diagnosis
homogeneous/non-homogeneous leukokeratotic plaque-type lesions localised in the retrocommissural area, +/- involvement of the commissure (fissure) and pericommissural area
41
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
42
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
43
actinic cheilitis - definition
chronic inflammatory process, affects mainly L lip, due to a chronic UV exposure
44
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
45
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
46
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
47
actinic cheilitis - clinical diagnosis
painless thickening and whitish discolouration at borders of lips, may gradually become scaly and indurated
48
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
```
49
actinic cheilitis - why is biopsy mandatory?
some are found to be severe dysplasia or OSCC on 1st biopsy
50
actinic cheilitis - prevention
sunscreen and UV protective clothing
wide-brimmed hats
lip balm containing UVA and B
sunscreen/zinc
51
proposed classification of cheilitis categories
mostly reversible
mostly persistent
in association with dermatoses and systemic diseases (common conditions)
52
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'
53
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'
54
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
55
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
```
56
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
57
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
58
leukoplakia - clinical parameters
```
site
size
homogeneity
multifocality
duration > or < 5yrs
dysplasia
smoking habit
drinking habit
```
59
leukoplakia - predictive risk factors for malignant transformation - pt characteristics
```
F
non-smoker
>60yrs
drinker
chronic alcohol MW use
history of H and N cancer
```
60
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
```
61
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
62
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
```
63
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
64
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
65
KUS
a histopathological term: just indicates hyperkeratosis with minimal/no atypia i.e. hyperkeratosis without epithelial dysplasia
66
what may KUS transform into?
OSCC
67
KUS histological features
can have parakeratosis, epithelial atrophy/acanthosis +/- inflammation
histologically different from frictional and reactive keratoses
68
KUS aetiology
unclear
don't appear to be reactive
not obviously dysplastic
unclear what the biologic behaviour of these lesions is
69
KUS location
many occur at sites that are high risk for epithelial dysplasia and OSCC - tongue, FOM, SP
70
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
71
non-reactive keratoses (true leukoplakia)
KUS
dysplasia
cancer OSCC
72
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
73
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
74
PVL tx
surgical resection
75
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)
76
PVL minor criteria
A - ≥3cm when adding all affected areas
B - F
C - pt (M/F) non-smoker
D - disease evolution >5yrs
77
PVL final diagnosis
3 major criteria (inc E)
| 2 major criteria (inc E) and 2 minor criteria
78
proliferative leukoplakia
NOT a form of non-homogeneous leukoplakia
| may be a more appropriate term than PVL because 18% are fissured and 22% erythematous
79
proliferative erythroleukoplakia PEL
better describes PL with prominent erythema
| has highest malignant transformation rate similar to erythroleukoplakia
80
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
81
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
82
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
83
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
84
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
85
what should pathology reports for excisional biopsies always report on?
margins, eben if they show KUS
86
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
87
classification of OLLs
oral lichenoid contact lesions (OLCLs)
oral lichenoid drug reactions (OLDRs)
OLLs in GvHD (OLL-GvHD)
OLL unclassified
88
Van der Waals OLLs classification
amalgam Rx
drug-related
cGvHD
unclassified
89
OLCLs - when is histological confirmation recommended?
in clinically atypical cases (exclude dysplasia/malignancy)
| - but histopathology alone can't reliably distinguish between OLP and OLCL
90
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
91
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
92
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
93
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
94
potential histologic difference between LP and LTR
perivascular cuffing/infiltrate in LTR - inflammatory cells round blood vessels
indicates delayed hypersensitivity reaction
95
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
96
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
97
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
98
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
99
OSF prodromal symptoms
*burning sensation in mouth on eating spicy food
*ulceration/recurrent stomatitis
excessive salivation
defective gustatory sensation
occ dryness with painful vesicles
100
OSF late S+S
fibrosis of laryngopharynx, oesophagus, Eustachian tubes, dysphagia and even hearing impairment
101
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
102
OSF Grade 1 clinical
involves <1/3 oral cavity
| mild blanching, burning sensation, recurrent ulceration and stomatitis, dryness
103
OSF Grade 1 fct
mouth opening up to 35mm
104
OSF Grade 1 histopathological
stage of inflammation
105
OSF Grade 1 tx
habit cessation
nutritional supplement
antioxidants
topical steroid ointment
excellent prognosis
106
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
107
OSF Grade 2 fct
mouth opening 25-35mm
| cheek flexibility reduced by 33%
108
OSF Grade 2 histopathological
stage of hyalinisation
109
OSF Grade 2 tx
```
habit cessation
nutritional supplement
intralesional injection of placental extracts
hyaluronidase
steroid therapy
physio
```
prognosis good, recurrence rate low
110
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
111
OSF Grade 3 fct
mouth opening 15-25mm
| cheek flexibility reduced by 66%
112
OSF Grade 3 histopathological
stage of fibrosis
113
OSF Grade 3 tx
surgical
prognosis fair, recurrence rate high
114
OSF Grade 4 clinical
leukoplakia changes, erythroplakia
| ulcerating and suspicious malignant lesion
115
OSF Grade 4 fct
mouth opening <15mm or nil
116
OSF Grade 4 histopathological
stages of malignant transformation: erythroplakia changes into SCC
117
OSF Grade 4 tx
surgical and biopsy of suspicious lesion
prognosis poor, malignant transformation
118
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
119
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
120
GvHD risk factors
```
genetic factors
older donor and recipient age
multiparous F donor
advanced malignant condition at transplantation
donor type
donor haematopoietic cell source
```
121
aGvHD pathogenesis
activation of APCs
donor T cell activation, proliferation, differentiation and migration
target tissue destruction
122
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
123
major organs affected by aGvHD
skin (erythema)
GI (secretory)
liver
124
aGvHD - 1st episode
classic acute
125
aGvHD - subsequent episode
recurrent
persistent
new onset or late acute
126
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
```
127
cGvHD with no sign of acute
classic chronic
128
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
129
acute GvHD skin
maculopapular skin rash
| - most freq affected and usually first organ
130
aGvHD GIT
nausea, diarrhoea, abdo pain
131
aGvHD liver
cholestatic hyperbilirubinaemia
132
aGvHD oral cavity
diffuse ulcerative and erythematous lesions +/- lip crusting
133
aGvHD grading
1 mild
2 mod
3 severe
4 v severe
134
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
135
cGvHD risk factors
prior acute GvHD
older recipient age
F donor (multiparous in particular) with a M recipient
use of peripheral blood SCs
136
oral complications of cGvHD
OSCC
rampant caries
fibrosis
137
oral manifestations (main ones) of cGvHD
```
oral mucosal cGvHD
- lichen type features
- hyperkeratotic plaques
salivary gland cGvHD
sclerotic cGvHD
```
138
NIH oral cGvHD clinical scoring
score mucosal changes: erythema, lichenoid, ulcers
| - no evidence, mild, mod, severe
139
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
```
140
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
141
potentially malignant lesion
altered tissue in which cancer is more likely to form
142
potentially malignant condition
generalised state with increased cancer risk
143
why should the term "potentially malignant disorder" be used rather than premalignant/precancerous/preneoplastic?
malignant change won't definitely happen
144
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
145
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
146
how much more likely is leukoplakia to progress to cancer than clinically normal mucosa?
50-100x
| - but not every leukoplakia will progress into cancer
147
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
148
leukoplakia histopathological indicators of malignant change - gold standard
dysplasia
atrophy (esp if red lesion)
candida infection
149
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
150
dysplasia
disordered/abnormal maturation (growth) in a tissue
| - has to show this to be considered potentially malignany
151
atypia
changes in cells
| - fct, appearance, arrangement to other cells
152
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
153
grading of epithelial dysplasia - WHO 2005
```
hyperplastic
mild
mod
severe
carcinoma in situ
```
154
hyperplastic (basal hyperplasia)
```
increased basal cell numbers
rest of epithelium normal
architecture
- regular stratification
- basal compartment larger
no cellular atypia
```
155
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
156
hyperchromatism
increased DNA in nuclei so they take up more stain
157
mod dysplasia
changes extend into middle 1/3
cytology - mod atypia
- pleomorphism
- hyperchromatism
158
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
159
carcinogenesis components
genetic
| env (carcinogens)
160
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
161
molecular basis of cancer
damage
altered gene expression - affects formation of protein (increased/silenced)
altered cell fct
162
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
163
oral cancer genes involved
```
oncogenes
TSGs
Tp53
genes that regulate apoptosis
genes involved in DNA repair
miRNA - micro RNA
viral component HPV16 and 18
```
164
oncogenes
have normal roles within the cells, produce GFs, differing oncogenes activated
165
TSGs
suppress the growth of cells
166
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
167
miRNA - microRNA
strands of non-coding RNA - don't produce proteins
| some can act as oncogenes/TSGs - can play a part in neoplastic transformation
168
viral component - HPV16 and 18 (oncogenic types)
oropharyngeal and cervical
| produce proteins which deactivate proteins produced by TSGs e.g. p53
169
Knudson's 2 hit hypothesis of carcinogenesis
TSGs - both alleles need to be inactivated before malignancy
170
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
171
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
```
172
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
173
features predicting LN involvement
non-cohesive front
perineural infiltration
malignant cells in lymphatic vessels and bv's
174
oral cancer pathology report points
diagnosis: SCC 90%
differentiation and grading
pattern of invasive front
local extension of disease
175
what is the pattern of invasive front related to?
nodal spread
176
differentiation and grading
how well tissue resembles normal and how much of its fct it can perform
177
well-differentiated
can tell they are epithelial cells and produce keratin
| better response, less recurrence, better prognosis
178
moderately differentiated
80% can tell epithelial cells but no keratin production
179
poorly differentiated
hard to tell whether epithelial cells
| need tests
180
anaplastic differentiated
virtually impossible (related to metastatic tumours)
181
pattern of invasive front
related to nodal spread
cohesive front
non-cohesive front
182
cohesive front
all cells advancing together at same rate, like a wave
183
non-cohesive front
strands/individual malignant cells breaking off from main front
associated with LN spread (micrometastasis)
184
OSCC subtypes
```
verrucous carcinoma
- better prognosis, slow growing, rarely recurs
basaloid squamous
- HPV association
- aggressive
spindle cell
- aggressive
```
185
causes of pigmentation
```
physiological/natural/racial
mucosal melanoma
smoking
post-surgical pigmentation
inflammatory e.g. LP
medications (prolonged CHX MW)
Addisons
```
186
spread of oral cancer
local extension of disease
lymphatic spread
haematogenous spread
187
local extension of disease
```
varies according to site
mucosal extension
muscle (tongue etc)
bone
- edentulous: gaps in cortex
- dentate: via PDL
nerve
```
188
lymphatic spread
*embolism - in lymphatics to get to LNs
permeation - tumour grows through lymphatic system
tumour involved node with EC spread
189
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
190
haematogenous spread
late feature (lymphatic first)
? enter veins in neck
- veins more susceptible as thinner walls
metastasis to lungs, spine etc
191
metastatic cascade
```
intravasation
survive in circulation
arrest in organ/tissue
extravasation
survive extravasation
initial proliferation
established growth
```
192
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
193
palatal lesions in reverse smokers
white and/or red patches affecting the HP in reverse smokers
| freq stained w nicotine
194
OLE
AI CT disease
may affect lip and oral cavity
erythematous area surrounded by whitish striae, freq with a target configuration
often palate
195
dyskeratosis congenita
rare cancer-prone inherited bone marrow failure syndrome caused by aberrant telomere biology
196
dyskeratosis congenita diagnostic triad
dysplastic nails
lacy reticular skin pigmentation
oral leukoplakia
