Exam 2 - Malignant White and Red Lesions Flashcards
Because 90% of oral cancers arise from the surface epithelium (ex. SCC), the term “oral cancer” generally denotes SCC.
True
What % of oral cancers arise from the surface epithelium?
90
90% of oral cancers arise from what?
surface epithelium
Oral cancer generally denotes ________, because 90% of cancers arise from the surface epithelium.
SCC (squamous cell carcinoma)
Epidemiology of oral cancer:
___% of all cancers in the US
Most common cancer in ______
More common in (male/female) _______ 2:1
Higher risk for white ____ that are >____ yrs old and middle aged _____ _____.
Increasing overall if oropharynx is included
No significant improvement has been made in the _______ __________ (more at a lower stage) of oral/oropharyngeal cancer in last 30 yrs.
Incidence rates have increased ____% since mid 2000s.
2% of all cancers in the US
Most common cancer in India
More common in (male/female) male 2:1
Higher risk for white males that are >65 yrs old and middle aged black men.
Increasing overall if oropharynx is included.
No significant improvement has been made in the early diagnosis (more at a lower stage) of oral/oropharyngeal cancer in last 30 yrs.
Incidence rates have increased 1% since mid 2000s.
Why has incidence rate of oral cancer increased?
Mostly due to oropharyngeal cases increasing
What percentage of oral cancers are associated with tobacco (cigarettes), with or without alcohol.?
80%
______% of oral cancers have no identifiable risk factors - lateral tongue young adult (especially women) or gingiva (older women).
20-25%
T/F Heredity appears to play a major causative role in oral cancer.
Falseee
Heredity does not appear to play a major causative role
Clinical Description of Oral Cancer
Irregular shape, mix of red and white
Often ulcerated center with “rolled” border
Exophytic (growing out) or endophytic (growing in) growth pattern
Often much firmer (indurated) than surrounding tissues
Early lesions- asymptomatic, pain is usually a late feature
Ragged RL is characteristic of bone involvement
T/F Pain is usually an early feature of oral cancer.
False its a late feature
Keywords used to describe the clinical appearance of oral cancer
Irregular Shape
Ulcerated with rolled border
Exophytic or Endophytic
Indurated (firmer than surrounding tissues)
Ragged RL is characteristic of bone involvement
Early lesions- asymptomatic, pain is usually a late feature
SSC LIP is one of the more common site not really intraoral. Secondary to ____ _____ exposure.
Arises in the setting of ______ ________.
UV light; actinic cheilitis
T/F Upper lip is more likely to have SSC than lower lip.
False - lower lip more likely (90% lower lip)
T/F Upon discovery of a lip SCC, usually the lesion is >3 cm.;
False usually <1cm upon discovery
T/F Lip SCC is usually slow-growing, well-differentiated lesion. WIth a relatively good prognosis.
True!
What is the most common intraoral site for SCC?
Lateroventral tongue (>50%)
What is the second most common intraoral site for SCC?
Floor of mouth
When oral SCC is seen in younger pt (<40 yrs of age), it almost always develops at what site?
Lateroventral tongue
Which is more common the anterior or posterior lateroventral tongue for SCC?
Posterior
Dorsal tongue SCC is uncommon ~___%.
4%
What is the most likely location to develop SCC from pre-existing white/red lesion?
Floor of the mouth
Which intraoral location is often associated with 2nd primary malignancy?
Floor of the mouth
What is an intermediate risk site to find an oral SCC or leukoplakia?
Gingiva/Alveolar Mucosa
What is the third most common site to find oral SCC?
Gingiva/Alveolar Mucosa
What is the most likely site for misdiagnosis of an oral SCC as it may mimic benign/reactive gingival lesions (ex. Pyogenic granuloma) or periodontal disease?
Gingiva/alveolar mucosa
What intraoral site is it most common to find an oral SCC in women?
Gingiva/Alveolar Mucosa
2:1 and those w/out identifiable risks factors
Oral SCC found on hard palate is rare unless _______ _______.
reverse smoking
How do you differentiate between Perio ds and SCC?
Perio - inflammatory so it will be red NO white there is edema and the texture is smooth
SCC- more of a granular pebbly look with white areas
What is one of the ways you can get oral SCC of the hard palate?
SCC May develop in the maxillary sinus and invade through the sinus floor
Most SSCs affecting the palate arise on the _________ ________ palate. They likely show a visible premalignant lesion .
lateral soft
In most oropharyngeal carcinomas (____% arise) from the ______ region without a visible precursor lesion.
In most oropharyngeal carcinomas (70% arise) from the tonsillar region without a visible precursor lesion
T/F Most SSC affecting the palate have a visible precursor lesion (leukoplakia/erythroplakia) where as oropharyngeal lesions usually do not.
TRUE
tonsillar cancers usually form down in the crypts
T/F Oropharyngeal cancers are going to be more likely diagnosed based on their symptoms.
True
Oropharyngeal cancers are going to be more likely diagnosed based on their ________.
symptoms
What are some symptoms of oropharyngeal SCC?
Dysphagia (difficulty swallowing)
persistent sore throat
dull/sharp pain may referred to ear note toothaches happen so check to make sure teeth are good
odynophagia (pain on swallowing)
cachexia
What is a low risk site for oral SCC in the western world except in the setting of betel quid use?
Buccal Mucosa
What are the Clinical diff for oral SCC?
Non-specific ulcer (traumatic ulcer)
Specific infections (very uncommon)
* TB, deep fungal - symptoms in lungs
* Syphilis
Immune-mediated condition
*Granulomatosis with polyangiitis
*Crohn’s disease
Clinical Differential of SCC can be immune mediated conditions. What are the two we talked about?
- Granulomatosis with polyangiitis
- Crohn’s disease
Clinical Differential of SCC can be Specific infections (very uncommon). What are the two we talked about?
- TB, Deep fungal infection
- Syphilis
Describe radiographically Oral SCC bone invasion.
usually a late phenomenon; causes a “moth-eaten” RL with ragged/ill-defined borders
pathologic fracture is possible
could look like osteomyelitis need clinical correlation
What other pathology can Oral SCC look like radiographically?
Osteomyelitis
Describe the histopathology of SSC
Invasive cords past basement membrane and nests of malignant squamous epithelial cells arising from, but not connected to, dysplastic surface epithelium
Tumor cells show an increased nuclear/cytoplasmic ratio
Pleomorphism - a lot of variation in the field
Mitotic activity
Varying degrees of keratin production (ex. Keratin pearls) and dyskeratosis
Desmoplasia - tumor-induced fibrosis why the tissue feel firm
Keratin pearls
When giving a grade to oral SCC what do you call very early lesions?
“Superficial invasive” or “microinvasive”
There are multiple classification schemes for grading oral SCC. Somewhat subjective interpretation of histologic differentiation”
_______ differentiated (grade I; ____ grade)
__________ differentiated (grade II; _________ grade)
_________ differentiated (grade III, IV; _______ grade)
Well differentiated (grade I; low grade)
Moderately differentiated (grade II; intermediate grade)
Poorly differentiated (grade III, IV; high grade)
T/F Differentiation does not influence staging of oral SCC.
TRUE!
The stage is its clinical spread
What are the two microscopic feature that influence the stage and prognosis of oral SCC?
- Depth of invasion (>5mm) correlates with increased risk for nodal metastasis
- Extracapsular spread outside a lymph node, “extranodal extension” (ENE), is associated with a worse prognosis
Extracapsular spread outside a lymph node = ______ _________
“extranodal extension” (ENE)
All oropharyngeal SSCs require high risk HPV (HRHPV) testing because affects the ______.
Stage
All oropharyngeal SSCs require what type of testing?
high risk HPV (HRHPV) testing because affects staging
Presence of HPV ___, ____ indicates transcriptionally active (clinically relevant) HPV infection so the gold standard is to test for this. More expensive.
Presence of HPV E6, E7 indicates transcriptionally active (clinically relevant) HPV infection so the gold standard is to test for this. More expensive.
What is the less expensive/routine HPV test to use for oropharyngeal SCC?
P16 Immunohistochemistry (inexpensive, sensitive surrogate marker for HRHPV) is the routine test
After biopsy proven oral SCC (or other H/N cancer), what do you do next?
Complete head and neck exam (by surgical oncologist, usually ENT) - fiberoptic exam of upper aerodigestive tract; include examination under anesthesia (EUA) if esophageal or lung disease
Dental exam - PANX (maybe CBCT) will need to treat any unresolved dental disease
Imaging to evaluate the primary tumor, any second primaries, and nodal disease
*MRI or CT with contrast from skull base to base of neck
*Chest CT any enlarged mediastinal LN
* If >N1 nodes, PET/CT to check for distant metastases
Multidisciplinary consultations as needed:
Oncologist: surgical, medical, and radiation
Nutrition, speech/swallowing eval, counseling (ex. Smoking, repro)
Head and Neck Cancer Work-up:
If greater than N1 nodes what imaging should you do?
PET/CT to check for distant metastases
What Treatment is done for an early SSC lesion (T1,T2) ?
Wide surgical excision (1 cm margin) or radiation if pt cant have surgery
What Treatment is done for a Moderately advanced SCC tumor?
Surgery + adjuvant radiation (try to avoid the mandible) or combined chemoradiation
What Treatment is done for an Advanced SCC (recurrent, mets, or or inoperable cases)?
radiation and/or chemo
Describe these surgical aspects:
Selective neck dissection
Selective neck dissection - only select group of LN
Describe these surgical aspects:
Radical neck dissection
Radical neck dissection - removal of lymphatics of lateral triangle of neck and associated structures (IJV, SMG, SCM, SAN)
Describe these surgical aspects:
Modified radical neck dissection
Modified radical neck dissection - just remove LN, preserve associated structures
What types of radiation are used to tx SCC?
- Intensity-modulated radiation therapy (IMRT) targets the tumor site and minimized damage to surrounding tissue
- Brachytherapy (placement of tiny, radioactive seeds) used from small intraoral tumors or with IMRT to increase dosage (Not usually used for intraoral cancer)
Which type of chemotherapy should be used for head and neck cancers neoadjuvant or post adjuvant?
post adjuvant
Post-op concurrent chemoradiation therapy
What type of tx is given for Stage III, IVa, IVb with no distant mets?
Convention fractionated radiation 70 gy (2.0Gy/fraction 5 day/wk over 7 weeks) + Cisplatin (given every 3 weeks up to 3 doses)
What are the other drugs besides cisplatin used for chemotx?
Carboplatin
5-fluorouracil
Taxanes (paclitaxel and docetaxel)
Basically drugs that just kill fast growing cells
What tx route would you take for distant metastasis?
Single/multi agent chemo (NOT Radtx)
If cisplatin is not working well you may think about using targeted therapies. Give an example
Immunotherapy - uses antibodies to block checkpoints
EGFR monoclonal antibody used for head and neck cancers - Cetuximab
What is the term used to describe this process?
antibodies used to block checkpoints (PD-1, CTLA-4) from being activated and thereby allow the immune response to occur
Immunotherapy
What is the EGFR monoclonal antibody used for head and neck cancers?
Cetuximab
What type of therapy is used for recurrent or metastatic head and neck SSC who have progressed on or following platinum-based chemotherapy?
Immunotherapy
Immunotherapy has a good response to what cancers?
Melanoma and lung cancer
What are the other two approved immunotherapy drugs?
nivolumab and pembrolizumab
Mnemonic: Never poop
Regular pathogenesis: Dendritic cells recognize when cell has gone bad will phagocytose them and then present to a CTL.
Cancer Pathogenesis: In normal setting there is a marker CTL-4 on T cell that bind to dendritic cell preventing MHC complex which prevents the CTL cell from becoming active. So essentially the cell does not respond to the bad signal.
Immunotherapy mechanism 1:
Giving ____________ allows a different receptor to bind to the dendritic cell. Now alerting there is a tumor cell over here that is making peptides and is a bad cell. Goes find the cell that had bad peptide and destroys it.
anti CTLA-4
Cancer Pathogenesis:
When PD-1 (on CTL) Bind to PD-1 Ligand (on
tumor cell) it prevents activation of the
CTL. NO TUMOR CELL DEATH.
Describe the immunotherapy mechanism 2:
Antibodies have been developed to bind to either PD-1 or the PD-1 Ligand either one prevent the interaction stimulating the CTL to release granules and kill tumor cell
When do most recurrences of oral SCC recur?
Within 2 years
T/F All mucosa exposed to carcinogen has the potential for cancer development.
True
What do you call mucosa exposed to carcinogen has the potential for cancer development?
condemned mucosa
Field effect/cancerization: Up to _____% will develop new upper aerodigestive tract malignancies, particularly if carcinogenic habits are continued
25%
Overall 5 yr survival (oral and oropharyngeal SCC) is about ___%
67%
What is the most important prognostic indicator for oral SCC =
stage (tumor size, extent of metastatic spread)
What is the most important prognostic indicator for oropharyngeal SCC =
HPV status (not noted on survival data)
T/F HPV + tumors have a better prognosis.
True - think related to virus blocking normal suppressor genes but tumor suppressor genes where not mutated so when you treat you dont get field effect
Oropharyngeal carcinoma - prognosis
Based on HPV status
Often poorly differentiated and non keratinizing. But HPV + tumors respond better to chemo and/or rad tx. Why? They lack TP53 mutation and field cancerization
think related to virus blocking normal suppressor genes but tumor suppressor genes where not mutated so when you treat you dont get field effect
Oral SCC Prognosis
Generally poor b/c about 2/3rd of pt present with stage III or IV disease
T/F Once there is LN spread it is at least a stage III
True
T/F Oral SCC - While prognosis has improved a little it is still one of the worst prognosis of any major cancer. Even with tx significant disfigurement, disability, and pain.
True
What is a variant of SCC?
Verrucous Carcinoma
What can give rise to verrucous carcinoma (SCC variant)?
Proliferative verrucous leukoplakia
Name the lesion: Less aggressive form of squamous cell carcinoma
Verrucous Carcinoma
T/F Verrucous Carcinoma: large lesion can develop regular SCC in them.
True
Where does Verrucous Carcinoma tend to grow?
Low risk sites - buccal mucosa, alveolar gingiva, and hard palate
Name the lesion:
White or mixed red and white, papillary/verrucous plaque or mass
Tends to grow laterally, invades with a pushing margin but does not infiltrate
Verrucous Carcinoma
Describe the histology of Verrucous Carcinoma
Microscopically bland can cause misdiagnosis as hyperplasia
How do you tx Verrucous Carcinoma?
Surgical excision is recommended. Not as aggressive surgery is needed as for SCC because not very invasive
Radiation can be used as adjunctive tx but is less effective than surgery
What can Verrucous Carcinoma be misdiagnosed as?
Hyperplasia
T/F Radiation is more effective than surgery in treating verrucous carcinoma.
FALSE
not as aggressive surgery is needed as for SCC because not very invasive
How does Verrucous Carcinoma grow?
Laterally and exophytic it does push down into margin but DOES NOT infiltrate
Differentiation influences stage or grade?
Grade
Stage is determined by its clinical spread
T/F Can also do a stain to test for oropharyngeal SCC
True
