key points OSCC Flashcards
benign nomenclature
-oma
except epithelial neoplasms classified on their microscopic or macroscopic pattern
malignant nomenclature
- carcinoma for epithelial origin
- sarcoma for CT
most common types of oral cancer
SCC
NHL
mucoepidermoid carcinoma
which area has highest prevalence?
southern asia
high risk sites
tonsils (HPV)
tongue (smoking)
base of tongue
FOM
what does OSCC arise from?
oral keratinocytes
high risk sites for OSCC
tongue
FOM
gingiva
high risk sites for OSCC if betel quid chewing
buccal mucosa and gingiva
characteristics of benign tumours
expansive growth rare and typical mitoses no metastasis local consequences variable - compressions no recurrences general consequences none except secretory tumours/particular sites freq stabilisation typical structure
characteristics of malignant tumours
infiltrating growth atypical structure numerous and atypical mitoses metastasis severe local consequences - infiltration, destruction, necrosis constant and severe general consequences always fatal common recurrences
clinical appearance
OPMDs
ulceration
- solitary lesion not healing/responding to conservative
management
- irregular and indurated margins usually
speckled
- ill-defined mixed white red lesions with granular aspects
exophytic growth
- irregular outgrowth with a smooth or verrucopapillary
surface above normal mucosa
- verrucopapillary surface - verrucous carcinoma
subtypes of OSCC
verrucous carcinoma basal SCC papillary SCC spindle cell SCC adenosquamous carcinoma lymphoepithelial carcinoma acantholytic SCC carcinoma cuniculatum
which subtypes have exophytic verruco-papillary component?
verrucous carcinoma
carcinoma cuniculatum
papillary SCC
late clinical features
pain - mostly if ulcerated
trismus (buccal mucosa and infratemporal fossa)
FOM - restriction of tongue mobility, progressive difficulty in mastication and speech, drooling of saliva
gingiva - excessive mobility of involved teeth
tongue base - fullness in throat sensation, dysphagia, lump in neck sensation, voice changes, ear pain
diagnostic pathway
history and exam
histopathology and clinical adjuncts
radiologic imaging
= then grading and staging
predictors of prognosis
grading and staging
grading
cytologic differentiation of cells
how bad do the cells look?
how much do they look like healthy cells under microscope?
staging
where has the cancer spread?
size of primary lesion, LNs, metastases
morphologic features for grading
degree of keratinisation (ideally high)
nuclear polymorphism (ideally little)
number of mitoses (ideally low) - excluded from Bryne system
pattern of invasion (ideally pushing, well-delineated, infiltrating borders)
host response (ideally marked - lymphoplasmacytic infiltrate)
Grade X
differentiation can’t be assessed
Grade 1
well-differentiated
Grade 2
moderately differentiated
Grade 3
poorly differentiated
Grade 4
undifferentiated/anaplastic
how does the grade affect prognosis?
lower grade = better prognosis
predicts how quickly the cancer will spread
staging (TNM)
Tumour T0-4
Node N0-3
Metastasis M0-1
8th edition cancer staging
Tumour thickness TT
DOI
ENE
TT
perpendicular from mucosal surface of tumour to deepest point of tissue invasion
DOI
level of basement membrane adjacent to normal mucosa to deepest point of tumour invasion
>10mm sig increased risk of recurrence and nodal metastasis
elective neck dissection should be consideration for tumours <5mm deep
ENE
extension of metastatic cells through the nodal capsule into the perinodal tissue
what is CT used for?
detecting primary tumour and local bone infiltration
MDCT
precisely determine tumour boundaries
CECT
accurately determine LN metastases
what can’t CT do?
differentiate between recurrences, surgical scars and adverse reactions after radio
imaging without ionising radiation
MRI
US
MRI
good for STs, bone marrow, vessels and nerves
can detect local LN and distant metastases
US
evaluate superficial lesions, LNs and to guide FNAB
with colour doppler can use US to determine type of blood vascularity in a lesion, often increasing the specificity of diagnosis
PET-CT
can use to look for primary tumour site when metastases are found earlier (CUP)
may detect malignancy in structures which appear normal/difficult to assess on CT/MRI e.g. small vol LN metastases
routinely used to detect recurrence and distant metastasis of known primary tumours, as well as 2nd primary tumours
recommended in advanced cancer stages and the whole body imaging improves analysis of TMN
cTMN
estimate of cancer based on results of physical exams, imaging, endoscopy, biopsy, done before tx starts
pTNM
relies on results of exams and tests before surgery, as well as what is learned about cancer during surgery
gives more precise info, can be used to help determine what other txs might be needed, as well as to help predict tx response and outcomes (prognosis)
first stage before imaging
establish primary site and any neck metastases clinically and have histological diagnosis
role of radiology
accurately stage full extent and distant spread with TNM
T groupings
TX Tis T1 T2 T3 T4a T4b
N groupings
NX N0 N1 N2a N2b N2c N3a N3b
what are involved LNs initially?
soft, mobile, non-tender
advanced stage LNs
enlarged
firm/hard texture
usually non-tender fixation of nodes to adjacent tissue due to invasion of cells through the capsule
M groupings
cM0
cM1
pM1 - microscopically confirmed
what increases the chance of bilateral cervical nodal spread?
the closer to the midline the primary tumour is
prognostic overall staging groups
0 1 2 3 4a 4b 4c
oropharynx includes:
inferior (anterior) surface of SP and uvula base of tongue anterior and posterior tonsillar pillars pharyngeal tonsils lat and posterior pharyngeal walls
overall tx modalities
surgery
chemo
radio
multimodal approach
OSCC stage 1 and 2 tx
surgery or RT
OSCC stage 3 and 4 tx
concomitant radio/chemo with surgery best outcome
what are definitive RT, concurrent CRT and sequential therapy typically reserved for?
medically inoperable pts
unresectable disease
resectable disease where surgical resection cannot be accomplished with acceptable long-term fct consequences
contraindications to open resection
T4b - invasion of masticator space, pterygoid plates, skull base or carotid encasement
pt perception of QOL
goal of surgery
completely resect primary tumour and any neck deposit to prevent recurrence and high survival rate
attempt to ensure negative resection margins - increased risk of tx failure in pts with positive surgical margins
- specimen examined and margins checked
surgical techniques
open resection
TORS
TLM
minimally invasive surgery: TORS and TLM
may provide improved fct outcomes with min surgical morbidity and enhance the pathologic staging
surgeon distant from pt controlling robotic unit
indications for minimally invasive surgery
T1-2 tumours of oropharynx but only if surgeon has good oral access
contraindications for minimally invasive surgery
retrognathia
class 2 occlusion
limited cervical extension
SP tumour: higher rate of rhinolalia, velopharyngeal insufficiency and nasopharyngeal reflux
pros of minimally invasive surgery
no external incision reduced immediate post-op toxicity shorter post-op hospitalisation time faster fct recovery enhanced visualisation: 3D and magnification of field elimination of physiologic tremors movements can be scaled fatigue reduction
cons of minimally invasive surgery
absence of tactile sensation: unable to feel resistance or how tight a knot is
equipment size and weight
cost - installation and annual maintenance
surgery - neck dissection types
comprehensive
selective
superselective
elective
neck dissection - comprehensive
all LN levels of the neck are removed +/- 3 non-lymphatic structures (SCM, IJV, CN11)
neck dissection - selective
not all neck LN levels are dissected
e.g. OSCC at least level 1-3, oropharynx SCC at least level 2-4
neck dissection - superselective
dissection of only one or two contiguous LN levels to further reduce the morbidity of neck dissection
neck dissection - elective
dissection of the appropriate nodal level, based on the risk of occult microscopic metastases
for OSCC SLNB or DOI currently best predictors
DOI ≥ 4mm accurate cut off value for preforming an elective neck dissection in early stage OSCC
SLNB
identifying and harvesting the initial node to which the primary tumour drains
indications for a SLNB
assess pts with biopsy-proven OSCC staged as early tumours with clinically (palpation) and radiologically (US, CT, MRI) N0 neck
assess bilateral N0 necks in primary tumours close to or crossing the midline
accuracy of SLNB
high
using immunohistochemistry can increase SLNB diagnostic accuracy
how does RT work?
uses high energy ionising radiation to disrupt the integrity of malignant cells through focal DNA damage, while doing as little harm as possible to normal cells
uses of RT
exclusive tx of primary cancer
adjuvant therapy after surgery
adjuvant therapy before surgery
palliative
uses of RT - exclusive tx of primary cancer
early stage or unresectable/advanced stage in combination with chemo
uses of RT - adjuvant therapy after surgery
+/- chemo to control positive neck nodes and/or kill remaining cancer cells in positive margins
uses of RT - adjuvant therapy before surgery
+/- chemo to shrink tumour
uses of RT - palliative
control symptoms of advanced OSCC e.g. pain, bleeding, dysphagia, and problems caused by bone metastases, and to give pt a better QOL
types of RT
EBRT
brachytherapy
EBRT
machine used to aim high energy rays/beams from outside the body into the tumour
- focus on exact location to spare normal tissues as much as possible
EBRT usual radiation schedule
tx usually 5 days a week for 6-7wks
other EBRT schedules
hyperfractionation
accelerated fractionation
may reduce risk of cancer coming back in or near place it started (local recurrence) but tend to have more severe SEs
hyperfractionation
total radiation dose in a larger number of doses e.g. 2 smaller doses per day
accelerated fractionation
≥ 2 doses each day so tx completed faster e.g. 3 wks instead
simulation technique
determine areas that will be radiated through a stimulator, scan to identify target vols
mark with tattoos
types of EBRT
intensity-modulated (IMRT) - most common 3D conformal (3D-CRT) image guided (IGRT) volumetric modulated arc therapy (VMAT/Rapid Arc) intensity modulated proton therapy (IMPT) stereotactic radiosurgery (SRS) stereotactic body (SBRT) intraoperative (IORT)
IMRT
a high precision RT that uses computer-controlled linear accelerators to deliver precise radiation doses to a malignant tumour or specific areas within a tumour
- dose to target usually proportional to estimated tumour burden
+ allows higher radiation doses to be focused on tumour
+ spare OAR
internal radiation therapy (brachytherapy)
hollow catheters placed into/around tumour during surgery
left in place for several days while pt stays in hospital
radioactive material put into tubes for short time each day
small radioactive pellets (rice) put right into tumour
give off low levels of radioactivity for several weeks and over time lose strength
pellets just left in place and rarely cause problems
short term RT SEs
visible during/immediately after RT and may last for 2-3wks after tx oral mucositis dental pain taste loss trismus (due to pain) odynophagia dysphagia candidiasis radiation dermatitis (RD) ORN
long term RT SEs
visible several weeks after RT and may last long time/permanently after tx
salivary gland hypofct
trismus - muscle fibrosis
extensive dentition breakdown due to radiation caries
ORN can develop months/years after completion of RT
ORN
irradiated bone becomes devitalised and exposed through the overlying skin or mucosa without healing for 3m, without recurrence of tumour
why is the mandible more affected by ORN?
only supplied by inferior alveolar artery, whereas maxilla supplied by anterior, middle and posterior superior alveolar arteries
ORN classification
no universally used staging classification
- Marx, Epstein et al
what % of ORN cases develop within 3yrs after RT?
70-94%
risk factors for ORN
hyperfractionated irradiation regimen - high total dose
literature suggests chemo coupled with radio increases incidence
pre- irradiation and post-irradiation dental extractions
poor OH and PDD
tobacco and alcohol use
ORN conservative tx
improve OH ABs minimal surgical debridement hyperbaric O2 therapy medical management: pentoifylline, tocopherol
chemo
a drug tx to kill fast growing cancer cells that multiply much more quickly than host cells in body
indications for chemo
can be used as primary/sole tx for cancer
adjuvant therapy after surgery (+/- RT to kill any residual cancer cells)
adjuvant therapy before surgery (+/- radio to shrink size of tumour)
palliative therapy (to relieve S+S of advanced OSCC and give pt a better QOL)
types of chemo
adjuvant
induction
concomitant
adjuvant chemo
given after surgery for reducing the incidence of distant metastatic recurrence
induction chemo
given before definitive tx (radio/surgery) in order to potentially reduce the risk of distant metastasis and the size of the primary tumour to improve locoregional control
concomitant chemo
given with surgery/radio to achieve radiosensitisation
CRT
chemo is given as a radiation sensitiser with the goal of reducing radiation resistance
chemo oral side effects
mucositis infection oral lichenoid reactions hyperpigmentations hyposalivation altered taste bleeding MRONJ SJS/TEN
RFs for cancer
predisposing factors
genetic susceptibility
OPMDs
oral microbiome
predisposing factors - synergistic effect
social - alcohol and tobacco
diet - low fruit and veg intake
physical agents - UV light, radiation
chemicals (env and occupational exposures) - arsenic, benzene, asbestos
one way alcohol causes cancer
ethanol broken down into acetaldehyde then acetate
if too much alcohol drunk - body can’t process it fast enough so get build up of acetaldehyde - toxic and causes DNA damage
diet and oral cancer
fruit and veg reduce risk
fish and omega 3 fatty acids may reduce risk
high consumption of processed meat increases risk
no significant association between total/red/white meat and risk
dietary supplements don’t have same effect on risk reduction
oral hygiene and oral cancer
risk factor
may also be a prognostic factor
increases carcinogenity of other known carcinogens e.g. tobacco and alcohol
oral microbiome and oral cancer
candida associated with increased risk
HPV
oral HPV manifestations
verruca - verruca vulgaris or common wart
condyloma - condyloma acuminatum
papilloma
NOT OPMDs
why can’t early diagnosis of HPV-related OSCC be accurately established?
because the clinical lesions of early HPV-related OSCC are unknown
infection with high risk HPV
16 or 18
typically lasts 12-18m and is cleared eventually by the immune system
if host immune system fails to clear and it persists for long time - get overexpression of main viral oncoproteins E6 and E7, inhibition of TSPs, p53, pRb
dysplasia
epigenetic events
DNA methylation
histone modifications
miRNAs
