Chapter 22 - Oral Tumors Flashcards
1
Q
Oral cancer accounts for what percentage of all cancer in dogs and cats?
A
6 to 7% - dogs, 4th most common cancer overall
3% - cats
2
Q
Oropharyngeal cancer is how many times more common in dogs than cats? Is there a sex predisposition in dogs?
A
2.6x more common in male dogs
Male sex predisposition for OMM and tonsillar SCC
3
Q
Whar are the most common malignant tumors in the oral cavity in dogs and cats?
A
Dogs:
- Melanoma
- Squamous cell carcinoma
- Fibrosarcoma
Cats:
- Squamous cell carcinoma
- Fibrosarcoma - 13% of al oral tumors
4
Q
In what size of dogs is malignant melanoma more common?
A
Small breeds
5
Q
How many of oral malignant melanomas are amelanotic melanomas?
A
1/3
6
Q
Which IHC markers can differentiate an amelanotic melanoma from other oral tumors (4)?
A
Melan A, S100, PNL2, tyrosinase (TRP1/2)
93% sensitive
100% specific
7
Q
What is the metastatic rate of oral malignant melanomas?
To which places does it most commonly metastasize?
Metastatic rate is dependent on what (3)?
Death due to pulmonary metastasis occurs in what % of dogs?
A
80%
RegionalLN (75%), lungs (90%)
Site, size, WHO stage
Up to 70%
8
Q
What can increase the risk of SCC development in cats (4)?
A
Flea collars 5x
Canned food 3x
Canned tuna 4.7x
Household smoke 2.5x
9
Q
What gene is thought to be possibly mutated in cats with oral SCC that are exposed to environmental smoke?
A
p53
10
Q
What paraneoplastic syndrome has been associated with cats with oral SCC?
A
Hypercalcemia - PTH-rp mediated
11
Q
What is the metastatic rate to LN and lungs in cats with oral SCC?
A
30% mandibular LN mets
10% pulmonary mets
Rare and infrequent
12
Q
What is the metastatic rate for dogs with non-tonsillar vs tonsillar/tongue oral SCC? Most common metastatic site?
A
Non-tonsillar: 20%
Tonsillar/tongue: 70%
13
Q
What percentage of dogs with oral SCC have bone involvement?
A
80%
14
Q
What percentage of dogs with oral malignant melanoma have bone involvement?
A
90%
15
Q
What percentage of dogs with oral fibrosarcoma have bone involvement?
A
60-70%
16
Q
What percentage of dogs with oral acanthomatous ameloblastomas have bone involvement?
A
80-100%
17
Q
How commonly do cats with oral SCC and fibrosarcoma have bone involvement?
A
Common
18
Q
Oral fibrosarcoma in dogs tends to occur in what size, breed, and age?
A
Large sized
Goldens and Labradors; Goldens especially for hi-low FSA
7.3 - 8.6 (young adults)
19
Q
Most common location in dogs with oral SCC?
A
Rostral
20
Q
Most common location for oral high-low fibrosarcoma?
A
Hard palate and maxillary arcade - between the canine and carnassial teeth
21
Q
What is the treatment of choice for biopsy results that suggest fibromas or low grade fibrosarcoma?
A
Aggressive surgery and/or RT
22
Q
What is the metastatic rate of oral fibrosarcomas in dogs and where does it metastasize? Hi-low FSA met rate?
A
FSA - up to 30% met rate
Lungs and regional LNs (equally)
High low FSA 12-20% met rate
23
Q
What are epulides and what were the three types? What is the new term for these lesions?
A
Benign gingival proliferations arising from the periodontal ligament that appear similar to gingival hyperplasia
Old terminology: epulides
- Acanthomatous
- Fibromatous
- Ossifying
New terminology:
Acanthomatous ameloblastoma
Peripheral odontogenic fibroma = included ossifying and firbous epulides
24
Q
What are peripheral odontogenic fibromas?
___% of feline peripheral odontogenic fibromas occur in cats less than ___ yrs.
What is the mean age at presentation for dogs?
Metastatic rate?
A
Slow growing, firm masses that are usually covered by intact epithelium
50% occur in cats less than 3 yrs
Dogs - 8 to 9 years
0%
25
Most common site for peripheral odontogenic fibromas?
Maxilla, rostral to the third premolar teeth
26
Recurrence rate in dogs?
3-yr PFS with RT in dogs?
0-17% (even if bone not removed)
86%
27
What dog breeds (2) are predisposed to acanthomatous ameloblastoma development?
What is the site of predilection?
Do they metastasize?
Shetland Sheepdog and Old English sheepdogs
7 to 10 years
Rostral mandible
Out of the epulides, this is the ONLY ONE that invades bone in 80-100% of cases
0% metastatic rate
28
What paraneoplastic syndrome has been associated in a cat ith gingival vascular hamartroma?
Hyperglycemia
29
In px with oral tumors, bone lysis is not radiographically evident until ___ % or more of the cortex is destroyed.
40%
30
Except for _____, the majority of oral tumors invade the bone.
Peripheral odontogenic fibromas
31
What are the minimum margins needed for malignant oral tumors in dogs? What about cats?
2cm - dogs
| >2cm in cats because of high chance of recurrence with SCC
32
What are the most common intraoperative and post operative complications of oral tumors when treated with sx?
Intraoperative - blood loss and hypotension
Post operative - incisional dehisence, epistaxis, increased salivation, mandibular drift and malocclusion, difficulty prehending food
33
Are enteral tubes recommended for dogs and cats after oral surgery?
Only for cats with any type of mandibulectomy because eating can be difficult for 2 to 4 months following surgery
34
What oral tumors are known to be responsive to RT (3)?
Malignant melanoma
Canine oral SCC
Acanthomatous ameloblastoma
35
What oral tumors are considered to be RT resistant?
Feline SCC
| Fibrosarcoma
36
What radiosensitizers have been used in cats (3) with oral SCC and dogs (1) with oral melanoma?
Cats - etanidazole, gemcitabine (not recommended because of significant hematologic and local tissue toxicities)
Dogs - platinum drugs
37
Late complications in oral tumors treated with full fractionation RT occur in less than ___% of the cases.
<5%
38
For which oral tumors is chemotherapy potentially indicated (2)?
Oral melanoma in dogs
Tonsillar SCC in dogs and cats
Bulky dz, metastatic dz present
39
ORR of piroxicam in dogs with oral SCC?
17% (1 CR, 2 PR)
40
ORR and MST in dogs with oral SCC when treated with piroxicam and cisplatin? Nephrotoxicity?
ORR of piroxicam and carboplatin?
Piroxicam and cisplatin:
56% ORR
MST 8m
41% nephrotoxicity
Piroxicam and carbo:
ORR 57%
Sustained in all dogs at median follow up of 534d
41
Palladia ORR and clinical benefit in dogs with oral SCC?
ORR 75%
| Clinical benefit 88%
42
Recently, ___ was shown to decrease SCC growth in vitro in tumors that over-expressed ___.
```
YM 155 (a survivin inhibitor)
Survivin
```
43
Which oral tumor has an unacceptable recurrance rate despite complete resection and needs to be addressed with wider resections or other adjuvant therapies such as RT?
Oral fibrosarcomas
44
With surgery for oral melanomas, the disease is usually controlled in ___% of the cases.
75%
45
Most common cause of death in dogs with OMM? Time to metastasis?
Metastasis
| 10m
46
What factors affect prognosis in dogs with oral melanoma when treated with sx (3)?
Tumor size: <2cm vs >2cm
Stage - mets vs no mets
Ability of the first sx to achieve local control
47
What is the reported ORR and MST of hypofractionated RT in cats with OMM?
60% ORR
| MST 146 days (4.8m)
48
What is the MST for dogs melanoma in the tongue, lip, hard palate, and maxilla, when treated with a combination of treatments?
Tongue - MST > 551 d
Lip - MST 580d
Hard palate - MST 330d
Maxillary - MST 320d
Lowe met rates for tongue and lip*
49
Although most small intestinal neoplasia is ___ in dogs, most rectal tumors are ____. Examples of the second blank?
Malignant
| Benign: rectal polyps, adenomas, carcinoma in situ
50
What are the most common intestinal tumors in dogs and cats?
```
Dogs:
* Lymphoma
* Adenocarcinoma
* GIST/leiomyosarcomas
Cats:
* Lymphoma
* Adenocarcinoma
* Mast cell tumor
```
51
What breeds of dogs are associated with predisposition of intestinal tumors? (2)In what breed of dogs are MCT overrepresented?
Collies and GSDMaltese
52
Infection with what bacteria is associated with an increased risk of gastric cancer in humans? Association of this bacteria an lymphoma has been reported in which spp?
Helicobacter pylori Cat
53
What type of intestinal cancer has been reported in a dof 4 weeks after initiation of cyclosporine and ketaconazole for anal furunculosis?
Lymphoma There is an association between cyclosporin and lymphoma in patients with transplants
54
Sensitivity of CT for identifying metastatic LN in px with oral tumors?
Poor
| 10-12%
55
What % of dogs and cats with facial/oral tumors have metastasis to the mandibular LN vs other regional LN?
When retropharyngeal LN metastasis is present, what LNs are also ALWAYS involved according to one study?
What % has ipsilateral vs contralateral metastasis?
55%
Mandibular LN
Ipsilateral 90%
Contralateral 60%
56
What is the most common complication in dogs with oral tumors undergoing a partial maxillectomy? With what was it significantly associated with (4)?
Intraoperative bleeding - 53%
43% required blood transfusion
BOTH significantly associated with:
- tumor size
- location (caudal)
- maxillectomy type (complete, caudal, and if involving orbit or complete)
- surgical approach (dorsolateral combined with intraoral)
57
What are the 3 most common short-term complications in dogs with oral tumors undergoing a partial maxillectomy?
Lip trauma 13%
| Dehiscence and fistula 11%
58
Cats undergoing surgery for oral tumors can experience difficulty eating for how long post op?
2-4m
59
What oral tumors are considered RT responsive and therefore radiation can be considered as primary treatment (3)?
OMM
Canine OSCC
Acanthomatous ameloblastoma
60
What oral tumors are considered to be RT resistant (2)?
Canine FSA
| Feline OSCC
61
In a study of 234 dogs with oral tumors undergoing curative-intent surgery, complete surgical margins were obtained in what % of cases? Local recurrence and metastatic rate higher in what tumor types? Shortest ST in which tumors?
Complication rate?
85%
FSA - 55% recurrence rate
Melanoma - 30% met rate
Shortest ST: melanoma and OSA
Complication rate: 16% - dehiscence, oronasal fistula, nasal discharge
62
Overall, what % of dogs with oral tumors treated with RT experience late side effects?
<5%
63
Overall, what oral tumor types in dogs have low rates of recurrence and the best survival times vs the opposite?
Low RR and best ST:
- Acanthomatous ameloblastoma
- OSCC
High RR and worse ST:
- FSA
- OMM
64
Favorable prognostic factors associated with surgery in px with oral tumors (3)?
- Small tumor diameter
- Rostral location
- Complete margins
65
Negative prognostic factors associated with surgery in px with oral tumors (4)?
- Tumors caudal to canines 5x RR
- Incompletely excised tumors 2-4x RR
- Maxillary tumors between canines and PM3 4.6x death risk
- Maxillary tumors caudal to PM3 5.1x death risk
66
Overall recurrence rate in dogs with oral tumors when treated with sx? Recurrence rate ranges in incompletely vs completely excised tumors?
Recurrence is dependent on?
Overall 30%
Incomplete - 60 to 65%
Complete - 15 to 20%
Size
67
Identified prognostic indicators for RT in oral tumors (2)?
Overall recurrence rate and risk?
Size and type
30% RR
3x more likely for T2
8x more likely for T3
(compared to T1)
68
MST of dogs with oral SCC w/o treatment?
2m
69
MST of dogs with SCC when treated with mandibulectomy and maxillectomy? Recurrence rates?
Mandibulectomy 9-26m; up to 20% RR
| Maxillectomy 19m; up to 50% RR
70
MST of dogs with oral SCC when treated with definitive RT alone?
15m
71
MST of dogs with oral SCC when treated with sx and definitive RT vs hypofractionated RT?
Sx + definitive RT - 3yrs
Sx + hypofractionated RT - 5.6yrs
Addition of RT prolongs ST!!!
72
The risk of tonsillar SCC is ___x higher in dogs living in urban areas.
10x
73
What % of dogs and cats with tonsillar SCC have systemic dz at diagnosis?
What % of dogs have pulmonary mets at dx?
90%
10-20%
74
What % of dogs with tonsillar SCC have bilateral dz as per CT?
50%
75
Canine tonsillar SCC and surgery?
Rarely curative and if performed, it should be bilateral due to high % of dogs with bilateral dz
76
Control rate with radiation therapy alone and 1-yr SR in dogs with tonsillar SCC?
Can this be improved?
75% control rate
<10% 1-yr survival
Yes; with chemotherapy - improved RR and ST
77
Overall MST of dogs with tonsillar SCC treated with sx, RT, and/or chemotherapy? Negative PI?
6m
| Anorexia, lethargy
78
Canine papillary oral SCC:
- Age of dogs?
- What % have T2 or T3 dz at diagnosis?
- Overexpression of what protein?
- Met rate?
- Therapy, prognosis, and MST?
Very young dogs; 2-5m, but in 1 study 75% were >6yrs
Arise from the gingiva of the dentate jaws; 67% rostral
92% are advanced; T2-T3 at dx
0% metastatic rate
Complete excision or reduction + RT: all dz-free at >4yr
Excellent prognosis
Histopath:
- Exophytic superficial papillary portion that lacks criteria of malignancy and can be confused with papilloma
- Deep invasive portion extends into gingival stroma or bone can be confused with SCC or ameloblastoma
- Papillomavirus has not been detected
79
What are identified risk factors in cats with oral SCC (4)?
- Flea collars 5x increased risk
- Canned tunna 4.7 increased risk
- Canned food 3x increased risk
- Household smoke 2.5x increased risk
80
As opposed to high COX2 expression in dogs with oral SCC, what % of oral SCC in cats express COX2?
18% - therefore COX2 likely not beneficial
81
What was recently published about intratumoral T cells in cats with oral SCC (3)?
- CD3+ T cell infiltrates in 92% of samples
- T-regs within the neoplastic epithelium and stroma in 60%
- Increased total frequency of circulating Tregs compared to healthy controls (but proportion of T regs compared to other lymphocytes unchanged)
-Weak COX2 expression
82
MST in cats with mandibular SCC treated with rostral mandibulectomy vs hemimandibulectomy alone? Overall median DFI?
Rostrally 2.5yrs
Hemi 7m
DFI 11m
83
MST, recurrence rate, and 1-yr ST in cats with oral SCC treated with mandibulectomy and RT?
MST 14m
86% recurrence
1-yr SR 57%
84
Palladia ORR/biological response and MST in cats with SCC? Prognostic indicators?
ORR 57% (biological response rate)
MST 4m
Anorexia at dx
85
Negative PI in cats with oral SCC (6)?
```
Anorexia at dx
Location: tongue, mandible, or maxilla
Tonsillar/cheek - improved prognosis
Mandible with sx -improved
Male cats - shorter PFI and MST with stereotactic RT
High bmi-1% expression
High MVD
More keratinized SCC
```
86
Recent literature suggest an improved overall MST for oral FSA in dogs of what?
250d to 2 years
Likely due to improved sx technique
87
Overall MST, recurrence rate, and 1-yr SR of dogs with oral FSA treated with surgery?
MST 10-12m
RR 20-50%
1-yr SR of
20-50%
88
DFI and MST of incompletely excised oral FSA in dogs?
DFI 13m
MST 19m
50% of maxillary tumors incompletely excised
89
MST of dogs with oral FSA when tx with RT alone?
7m
90
MST, recurrence rate, and 1-yr PFS in dogs with oral FSA when treated with sx and adjuvant RT?
What is prognostic (1)?
MST 18-26m (1.5 to 2.2yrs)
30-60% recurrence
1-yr PFS of 76%
Tumor size: T1 and T2 improved PFS and ST vs T3
91
Prognostic factors in dogs with oral FSA (7)?
- Location: mandibular shorter PFS and MST vs maxillary
- Size: T1 MST not reached vs T2 and T3
- Grade
- Tx with any type of RT longer PFS and MST, but definitive RT protocol better than palliative
- Type of sx performed: no sx vs conservative vs aggressive
- Complete sx excision
- Sx + RT longer PFS and ST
92
What % of lingual masses in dogs and cats are neoplastic and what % are malignant?
54% neoplastic
| 64% malignant
93
Most common tumor, location, and and metastatic rate in both dogs and cats?
SCC
19% overall
Dogs - midline
Cats - ventral surface/frenulum
94
Up to what % of normal tongue can be removed in dogs?
60%
95
Recurrence rate post sx in dogs with lingual tumors?
28% at median of 4m
Only 56% incompletely excised
96
Overall MST in dogs with lingual tumors when treated with sx? Prognostic indicators (1)?
483d
Tumor size; T1 longer MST vs T2+
97
Prognosis in dogs with lingual SCC is dependent on what?
Grade
98
MST in dogs with grade I, II, and III lingual SCC when treated with surgery?
I - 16m
II - 4m
III - 3m
Overall 7m
99
Grade on lingual SCC is dependent on what (6)?
```
Degree of differentiation
Degree of keratinization
MI
Tissue and vascular invasion
Nuclear pleomorphism
Schirrous reaction
```
100
1 yr survival in dogs with lingual SCC vs cats?
Dogs 50% if complete margins, 80% if low grade
| Cats <25%
101
Median OST and metastatic rate in dogs with lingual HSA? Most commonly seen in what breed? Prognostic indicators (2)?
OST 1.5yr
45% metastatic rate
41% recurrence rate
30% Border Collies
PI:
presence of clinical signs (MST 160d vs 630d)
T2+ tumors (MST 150d vs 630d)
Majority are low to intermediate grade
102
Possible predilection of lingual T-zone lingual lymphoma has been noted in what breed?
Golden Retriever
103
How does lingual T-zone lymphoma look grossly?
Multifocal to coalescing, raised, red, nodular mases
RARELY ulcerated
104
What % of dogs with lingual T zone lymphoma have concurrent lymphadenopathy and lymphocytosis?
70% lymphadenopathy
| 60% lymphocytosis
105
Immunophenotype of lingual T zone lymphoma?
Majority are CD8+
CD45-
Lack epitheliotropism
Expand within superficial submucosa and are separated from the dermis
106
CR and SD responses in dogs with lingual T zone lymphoma to any treatment?
Survival time?
CR 60%
SD 30%
10/12 still alive 27 to 893d post diagnosis
107
What is the 4th most common tumor in the oral cavity of dogs?
OSA
108
What % of canine OSA is oral or maxillofacial?
12%
109
What % of canine oral or maxillofacial OSA involves the mandible vs the maxilla?
Mandible 27%
| Maxilla 16-22%
110
What is the overall metastatic rate of dogs with oral/maxillofacial OSA?
What % of dogs have mets at diagnosis?
Is the rate higher for the mandible or maxilla and if so, what is the metastatic rate?
Time to metastasis?
35-40% overall
6% at diagnosis
58% mandibular
17-20 months
111
What breed of dogs is predisposed to flat bone OSA?
Boxers
112
What type of OSA is most commonly seen in the mandible vs maxilla?
Mandible - osteoblastic
| Maxilla - osteoclastic
113
What is the MST, recurrence rate, and 1-yr SR in dogs with MAXILLARY OSA tx with maxillectomy alone? Most common cause of death?
MST 5-10m
30-100% recurrence
17-27% alive at 1 year
Local recurrence; no mets reported
114
What is the MST, recurrence rate, MFI, metastatic rate, and 1-yr SR in dogs with MANDIBULAR OSA tx with maxillectomy and +/- chemo? Most common cause of death?
```
MST 17.5m
Recurrence rate 15-45%
MFI 20m
Metastatic rate 58%
1-yr SR 35-70%
Metastasis most common cause of death in 35%
```
115
Prognostic factors in dogs with mandibular OSA for metastasis and ST?
- Grade II/III tumors 2.4x increased risk of mets and shorter MST
- No adjuvant chemotherapy 2.6x increased risk of mets and shorter MST
116
What OSA location in the canine head is most likely to recur after sx?
Calvarium
117
Overall MST in dogs with OSA of the calvarium, mandible, and maxilla tx with sx?
MST 11m
118
What is the MST of dogs with OSA of the head when treated with definitive or SRT vs palliative RT?
Definitive/SRT - 4m
| Palliative - 3m
119
Chemotherapy has been shown to be beneficial in OSA of the head in which location?
Mandibular; prolongs MFI and ST
120
Identified prognostic indicators in dogs with OSA of the head? Positive (4) and negative (5)
Positive:
- mandibular location
- smaller body weight
- grade I
- pure-bred dogs
Negative:
- Incomplete surgical margins
- Grade II/III tumors
- Lack of adjuvant chemo post op
- Every 1,000-cell increase in monocyte count associated with a 76% increased hazard of death
- MI >40 on univariate
121
Tx of choice for canine MLO?
Sx; poor responses to RT and chemo
122
Overall RR and RR for grade I, II, and III MLO in dogs?
What is it dependent on (2)?
47-58% overall; grade and margins
I - 30%
II - 47%
III - 78%
123
DFI in dogs with completely vs incompletely excised MLO?
Complete - 3.6 yrs
| Incomplete - 11m
124
Overall metastatic rate and metastatic rate in grade I, II, and III MLO in dogs? Incompletely vs completely excised tumors? When does it occur?
What is it dependent on (2)?
60% - overall to lungs late in dz; grade and margins
I - 30%
II - 60%
III - 78%
Complete - 25%
Incomplete - 75%
Slow growing tumor so can consider metastasectomy (>12m survival)
125
Overall MST and MST in grade I, II, and III MLO in dogs?
What is it dependent on (2)?
Overall MST 21m; location and grade
I - 50m
II - 22m
III - 11m
126
What is the MST in dogs with MLO of the mandible vs other locations?
Mandibular MST 4yrs vs 590d if other locations
127
What are the 2 types of feline epulides?
Fibromatous - 60%
Giant cell epulis - 30%
128
How does GCE differentiate from fibromatous epulis in cats?
Which IHC markers can be used to identify them and what origin is it suggestive of?
Significantly different and more aggressive behavior
Rapid growth, ulcerative changes, rapid recurrence after sx
IHC suggestive of osteoclastic origin
Positive for: vimentin, TRAP, RANK
Negative for: SMA, MIB-1, factor VIII
In dogs, these behave like fibromatous epulis and rarely recur post sx
129
What 2 proteins do dogs with AA express?
MMP9
| TIMP1
130
MST and recurrence rate for mandibular AA treated with mandibulectomy? 1yr SR?
MST not reached; >28-64m
0-3% recurrence
98-100% 1-yr SR
131
MST and recurrence rate for maxillary AA treated with maxillectomy? 1yr SR?
MST not reached; >26-30m
0-11% recurrence
71-100% 1-yr SR
132
When hypofractionated RT is used to treat AA, what is the 3-yr PFS? Recurrence rate? Complications (2)?
80% 3-yr SR
8-18% recurrence; 8x higher risk in T3 tumors
Malignant transformation in 5-18%
Bone necrosis 6%
133
Response rate of IL bleomycin in dogs with AA?
100% CR for > 1 yr in 4 dogs
