MCT Flashcards
What’s the best-described genetic abnormality for canine MCT?
c-kit mutation.
- Kit = tyrosine kinase
- ligand = SCF
- mutation will lead to autophosphorylation.
- in the juxta membrane domain (exons 11-12) or the extracellular domain (exons 8-9)
What % of dogs will have multiple MCT on presentation?
11-14%
What’s the % of GI ulceration in dogs with MCT on necropsy?
35-83%
What mediator is thought to be responsible for hypotension during MCT degranulation?
Prostaglandin D
What’s AgNOR and how does that influence outcome in canine cutaneous MCT?
It’s a measure of the speed of cell cycle progression.
- Average AgNORs per cell < 1.7: No dogs died due to MCT-associated disease
- Average AgNORs per cell > 2.25: Significantly decreased survival
- Average AgNORs per cell > 4: Significantly decreased survival:
– 66.7% of dogs died from MCT-associated disease
– MST 17 weeks
What’s ki67 and how does that influence outcome in canine cutaneous MCT?
It’s a measure of numbers of cells that are actively dividing.
- >23 per grid area = shorter survival time
What’s Ag67
it’s the product of AgNOR and ki67
- if it’s >54 = shorter DFI
- increased risk of MCT mortality and metastasis
- significantly associated with an increased incidence and
rate of MCT recurrence at the original surgical site:
– 40% of dogs died due to MCT before 12 months postdiagnosis
What’s the metastatic rate of undifferentiated canine MCT?
55-90%; most will die of MCT within a year
What’s the outcome with MI < 5 vs > 5 for canine MCT?
< 5: MST = 80 months
> 5: MST = 3 months
What are 3 negative prognostic indicators for canine SQ MCT?
- MI > 4
- infiltrative pattern
- presence of multi-nucleation
What’s the LN metastatic rate of muzzle MCT in dogs?
50%, but can still live for 14 months
In what scenario is LN metastasis going in limit the survival time for canine MCT?
if the primary tumour is undifferentiated, then if there is also LN met, the MST = 194d compared to 503d. Treatment of the LN improves survival (240 vs 42 days).
Describe the MCT staging system.
Stage 0: microscopic, incompletely removed, no mets
Stage 1: single cutaneous mass, no LN mets
Stage 2: single cutaneous mass with regional LN metastasis
Stage 3: multiple cutaneous masses; large infiltrating tumours with or without regional LN mets
Stage 4: distant met
What classifies as Kiupel high grade canine cMCT?
- MI >7/ 10hpf
- at least 3 bizzare nuclei in 10 hpf
- at least 3 multinucleation in 10 hpf
- karyomegaly (>10% of nucleus)
What’s the % of normal sized LN that will still be metastatic in canine MCT?
50%
What factor is significantly associated with a HN>0 LN?
primary mass >3cm.
What are some minimum histological margins that did not show recurrence/ metastasis in canine cutaneous MCT?
lateral margins ≥ 10 mm and deep margins ≥ 4 mm.
What’s the accuracy of pre-tx biopsy for canine cutaneous MCT regarding the grade?
Fairly accurate!
overall concordance rate of 96% based on the Patnaik grading system, and an overall concordance rate of 92% based on the Kiupel grading system.
All discrepancies underestimated the grade of the MCT.
In this 2011 study, they found needle core to be the most accurate- but could be due to lower numbers in each case, and there was no statistical significance between the different sampling procedures (wedge, punch, needle core).
What’s the 2 year control rate of stage 0 canine MCT with adjuvant radiation therapy?
85-95% control rate
What’s the utility or re-excision or RT of incomplete/ close margin MCT
Either modality (Sx, RT) can significantly improve survival time compared to no treatment (2930d vs 2194 vs 710). Local recurrence occurred in 13% of the re-excision group, 8% of the radiation therapy group, and 38% of the comparison group.
What’s the prognostic value of removing HN2 & HN3 lymph nodes?
On multivariable analysis, the risk of tumour progression and tumour-related death were 5.47 and 3.61 times higher in the LNS group, respectively (P < 0.001)
Marconato et al 2018.
What’s the false-negative rate for LNs FNA vs Sx?
In one study in 2017:
High proportions of false-negative results were found in mesenteric T-cell lymphoma (22/35, 63%, mainly cats), metastatic sarcoma (8/14, 57%) and metastatic mast cell tumour (15/48, 31%, mainly dogs).
Report data on MCT discrepancies = 10-50%
What’s the recurrence rate for incompletely low/ intermediate grade canine MCT?
10-30%
(but studies still showed increased local recurrence and/or decreased ST in dogs with incompletely removed MCT)
What are the reported the local recurrence rate post surgery for canine MCT?
local recurrence rate ranging from 19% to 35.9% after surgery, regardless of histological margins
What’s the impact on neoadjuvant chemotherapy on surgical margin, tumour grade, and nodal grade in canine MCT?
- It is possible to downgrade the primary mass and nodal disease.
- the new surgical margin can be used,
- incomplete removal in about 31% of cases (historically should be closer to 5% without adjuvant), but previously study reported 53.3% (Ossowska, 2023)
- but recurrence rate was about 9% (2024 study), much higher in previous studies ( 20.8% [Ossowska] and 23.8%).
How does a 10-14 day course of prednisone as neoadjuvant treatment affect the mitotic index, Ki67, AgNOR, or Ki67xAgNOR in canine MCT?
no significant effects
Generally, what’s the RR for canine MCT (macroscopic) treated with vinblastine and pred?
just a bit less than 50%
(43, 47%)
Generally, what’s the RR for canine MCT (macroscopic) treated with TKI?
50-80%
Generally, what’s the best chemo for neoadjuvant therapy for canine MCT in terms of RR?
it appears that multi-agent protocol may result in higher RR
What are some general outcome for high grade/ incompletely removed high risk canine MCT treated with adjuvant vinblastine and pred?
Survival 2-3.7 years
What are some general outcome for incompletely removed high risk canine MCT treated with adjuvant vinblastine combination protocol?
VBL/Pred/CCNU: DFI = 35 weeks (8m) MST = 48 weeks (11m)
VBL/Pred/CYC: DFI 865 days (2.3y), MST = > 2029 days (5y)
What % of canine MCT have the c-kit mutation?
20-40%
What’s the response rate of toceranib for canine MCT?
42.8%, and if adding the ones that had placebo then switched to toceranib = 60%
Duration of response is around 12 weeks, with time to progression of 18 weeks
What’s the response rate of masitinib for canine MCT?
similar to toceranib
What are some TKI that have been used for canine MCT?
- toceranib
- masitinib
- imatinib
What’s the outcome of toceranib, prednisone and PRT?
- RR = 76.4% (58.8% CR, 17.6% PR).
- overall MST not reach; median follow-up 374 days
What’s gilvetmab and it’s utility in canine MCT?
- caninized monoclonal antibody targeting check point inhibitor, PD-1
- 46% ORR (majority PR): A total of 12 dogs (46%) had an objective response with 2 dogs having a complete response and 10 dogs having a partial response. A total of 7 dogs (27%) had stable disease and 6 dogs (23%) had progressive disease
What are the 3 anatomical forms of feline MCT?
- cutaneous
- splenic/ visceral
- intestinal
What are the 2 distinct forms of cutaneous MCT?
Mastocytic vs histiocytic
(mastocytic is more common)
Histiocytic form can regress in 4-24 months (mostly seen in young cats)
Which breed of cats is predisposed to MCT?
Siamese
What are the 2 sub-categories of mastocytic cutaneoius MCT in cats?
Compact (well differentiated, better prognosis) and diffuse (anaplastic, worse prognosis)
- but the prognostic value was not held in a 2002 study
What’s the most common anatomical site for cutaneous MCT in the cat vs dog?
Cat: head and neck
Dog: trunk
What’s the reported rate of splenic involvement for feline cutaneous MCT?
3/41 (7%)
What’s the recurrence rate of feline cutaneous MCT treated with surgery?
0-24%
What’s the outcome of feline eyelid MCT?
majority will not recur and will not have systemic disease.
- 83% local control, MST = 945 days (Sx +/- RT +/- cryo)
What’s the outcome of Sr90 for feline cutaneous MCT?
- 98% control rate
- MST > 3y
What’s the outcome for feline cutaneous MCT treated with CCNU?
2/20 = CR (10%)
8/20 = PR (40%)
Median response duration 168 days
What’s the dissemination rate to to other organs in feline splenic MCT on necropsy?
- liver 90%
- LN: 73%
- bone marrow: 40%
- lungs: 20%
- intestine: 17%
How likely is neoplastic effusion with feline splenic MCT?
up to 1/3 cats will have peritoneal and pleural effusion rich in eosinophils and mast cells
What are the 2 forms of feline splenic MCT?
- diffuse (more common)
- nodular
What’s the mainstay of treatment for feline splenic MCT?
- Splenectomy
- benefit of adjuvant chemotherapy is unclear
What’s the general outcome of feline splenic MCT treated with splenectomy?
Even with significant bone marrow or peripheral blood involvement, MST of 12-19m is reported (though one study only found 132 days)
- a 2018 paper reported MST of 856 days (28m; ~2y)
Which are the top 3 primary intestinal tumours in the cat?
- LSA
- adenocarcinoma
- MCT
What are some prognostic factors that have been reported for cats undergoing splenectomy for splenic MCT?
- male
- pre-op hyporexia
- pre-op weight loss
What’s the main presenting signs for cats with intestinal MCT?
- diarrhea, +/- fever.
- could be present for months
- can also have hx of vomiting, and hyporexia
- solitary abdominal mass is often palpable
Anatomically, where along the intestines is MCT most commonly found in the cat?
- small intestine (equal distribution)
- only 15% involves the colon
Where are some metastatic sites for feline intestinal MCT?
- liver/spleen
- LN
- peritoneal effusion
What’s the outcome of feline intestinal MCT?
poor, generally found with metastasis so euthanized shortly after diagnosis
What’s the outcome with surgery for feline intestinal MCT?
historically bad, but more recently found MST ~1.5y for Sx +/- TKI.
Where were some histological prognostic factors for feline intestinal MCT?
- Mitotic count > 2 = bad
- undifferentiated tumours = bad
- kit mutation was not prognostic
What kind of surgical margin should be planned for feline intestinal MCT?
5-10cm!
What’s the outcome of sclerosing form of feline intestinal MCT?
- 23/36 (64%) cats had mets to LN and/or liver
- 23/25 euthanized within 2 months
What’s the likelihood of nodal metastasis for low grade primary cutaneous feline MCT?
10/17 (59%); 12 were classified as HN2 or HN3.
What’s the nodal metastatic rate of canine cutaneous MCT?
18-68%
What’s the percentage of metastasis for canine cutaneous MCT based on the Patnaik grading system?
- Grade 1 = 3/52 (5.8%) –> all nodal mets
- Grade 2 = 48/291 (16.5%) –> mostly nodal mets
- Grade 3 = 21/43 (48.8%) –> still mostly nodal, then nodal + distant
only 1 dog from each grade 2 and 3 had distant met
What’s the percentage of metastasis for canine cutaneous MCT based on the Kiupel grading system?
- Low grade = 44/295 (14.9%) –> majority nodal
- High grade = 28/91 (30.8%) –> slighlty more than is nodal only, then nodal
only 1 dog from each grade had distant met
How many grade II/low grade vs. grade II/ high grade had metastasis?
- grade II/low: 41/243 (16.9%)
- grade II/high: 7/48 (14.6%)
not significant different
What are 2 prognostic factors for cats undergoing splenecotmy?
anemia and metastasis
In a 2023 study of cats receiving splenectomy for various causes, what was the metastatic rate for splenic MCT?
33.3% (7/21)
When is c-kit assessment most useulf?
c-kitgene mutations may be most informative in the identification of tumours that are histologically low grade, but are likely to be biologically aggressive, while membrane KIT localization is most likely to identify tumours that are less likely to have progressive disease
Is mutation in exon 8 and 11 prognostic?
only mutation in exon 11 is, not exon 8
Which breeds are most likely/ least likely to have high grade MCT?
Most likely: Shar-pei
Least likely: Golden and Pug
What’s the % of canine SQ MCT that are high grade?
About 33% of deep SQ MCT are high grade
What’s the utility of using CT to detect metastatic LN in canine MCT?
Not good.
- sensitivity of CT for nodal metastasis was 35.7%
- specificity was 96.6%
- overall accuracy was 60.5%, indicating that CT alone is not sufficient for assessing metastasis.
What’s the outcome of cutaneous mastocytosis treated with steroids?
8/11 dogs had tumour improvement (median 4yo)
What’s the utility of CT for staging for canine MCT?
CT identified the sentinel lymph node in 90-97% of cases, and 32% of dogs had additional or incidental MCTs detected.
- 32% of the time the SNL did not correspond with the regional LN
What factors are associated with high grade nodal metastasis?
- Kiupel high grade
- increasing number of SLN
- increased number of lymphocentres
Which antacid can change neutrophil to lymphocyte ratio?
Famotidine (vs. omeprazole vs. control), can significantly increase the NLR
What’s the recurrence and metastatic rate of canine SQ MCT?
The recurrence rate was 15% (17.8% in another study), and 63% (26.7% in another) of evaluated lymph nodes showed early or overt metastasis.
- the majority of the tumours that recurred had an infiltrative pattern
What’s the success rate of indirect radiographic lymphography?
- 90% success rate
- the SLN differed from regional lymph nodes in 57% of cases.
- 26% of cases had multiple SLNs
- 31% had multiple lymph centers
What’s the outcome of canine cutaneous MCT on the pinna?
- 22/39 (56.4%) had lymph node (LN) metastases, with the superficial cervical LN involved in all cases.
- 19/39 (48.8%) = high grade
- high grade MCT had a worse TTP and ST (270 days and 370 days), compared to not reached in low grade.
What’s the outcome of infrared fluorescence vs indirect CT lymphography?
Technique agreement was observed in 16 out of 20 dogs (80%), with lymph node metastases detected in 19 out of 20 dogs (95%).
What’s the outcome difference between Kiupel high grade MCT that did or did not have lymphadenectomy?
- No lymphadenectomy, median time to progression =150 days; MST = 250 dayys
- Yes lymphadenectomy, mTT = 229 days and MST = 371 days
What’s the outcome of Palladia with vinblastine for canine high grade, LN met, or stage IV MCT?
PFI = 310 days
MST = 373 days
What’s the outcome of canine MCT treated with alternating CCNU and vinblastine?
Macroscopic:
RR = 57%
PFI = 30 weeks; OST = 35 weeks
Microscopic
PFI = 35 weeks; OST = 48 weeks
What’s the MST of completely excised canine high grade MCT treated with adjuvant CCNU and pred?
MST ~ 900 days
Which has a better outcome: CCNU/vinblastine or Palladia for canine systemic mastocytosis?
CCNU/vinblastine
What’s the response rate of escalating vinblastine with prednisone for canine MCT?
ORR = 30.8%, PFI = 53 days
In the same study, some also had PRT, and the ORR = 75%, but it was not statistically significant
Up what % can be expected to respond to chemo in gross disease setting for canine MCT?
up to 64%
(pred, vinblastine, CCNU)
What’s the outcome of canine MCT treated with hydroxyurea in the gross disease setting?
4% CR, 24% PR, 28% ORR
- TPP = 46 days (for PRs)
What’s the outcome of feline GI MCT?
Metastatic rate ~50%
LN, liver, spleen
- MST = 531d (~1.5y)
What’s the metastatic rate of grade II/ low grade canine MCT?
15% (5-22%) chance of metastasis (lymph nodes), and a 2-3% chance of distant metastasis (liver and spleen).
What’s the recurrence rate of canine MCT?
high grade: 35.9% (that’s with complete excision!)
low grade: 3.9% (29% had margins <3mm and none recurred)
What’s the most important predictor of recurrence of canine MCT?
grade
What’s the metastatic rate of grade I/ low grade canine MCT?
< 10%
What’s the metastatic rate of high grade/ grade III canine MCT?
55-95%
