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Mast Cell Tumour Flashcards

1
Q

What is the most common skin cancer in the dog?

A

mast cell tumour (16-21% of all cutaneous tumours)

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2
Q

What bioactive substance does MCT granules contain?

A
  • heparin
  • histamine
  • Cytokines: tumour necrosis factor alpha (TNF-alpha). IL-6
  • Protease: chymase, tryptase
  • chemokines: CCL2, CXCL1
  • growth factors: VEGF, bFGF
  • lipid mediators: prostgalndin D2, leukotriene C4
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3
Q

Which breeds are at increased risk for MCT?

A
  • dogs of bulldogs descend
  • Labrador
  • Golden
  • Cockers
  • Schnauzers
  • Staffordshire terriers
  • beagles
  • Rhodesian ridgeback
  • Weimaraners
  • Chinese shar-pei
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4
Q

What are the genetic factors for MCT in Goldens?

A

GNAI2 gene and multiple genes associated with hyaluronic acid synthesis

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5
Q

What are some genetic changes that can predispose a dog to MCT?

A
  • p53 pathway
  • changes in proteins p21 and p27 (cyclin-dependent kinase inhibitors – regulation of cell cycle)
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6
Q

What’s the best-described molecular abnormality in canine MCT?

A
  • receptor tyrosine kinase (RTK) KIT
  • expressed normally on a variety of cells
  • ligand = somatic cell factor (SCF)
  • SCF + RTK –> dimerization –> phosphorylation –> intracellular signaling promoting proliferation, differentiation, and maturation of MCT from CD34+ stem cells
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7
Q

What’s the proportion of canine MCT that has the c-kit mutaiton?

A

significant minority (~30% of intermediate to high grade MCT)
- mutation in juxtamembrane domain (exons 11-12)
- mutation in extracellular domain (exons 8-9)
- result in ligand (SCF) independent activation – subsequent unregulated KIT signal transduction
- linked to increased risk of local recurrence, metastasis, and a worse prognosis

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8
Q

When a MCT is incompletely excised, if possible, a second excision of the surgical scar with additional wide margins should be performed . However, not all MCTs with surgically incomplete margins will recur. What __% of MCTs with histologically confirmed incomplete margins tend to recur?

A

10 – 30%

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9
Q

You have a dog with a high-grade mast cell tumor. After removal of the primary tumor with complete margins, you decided to start an adjuvant Vinblastine – Prednisone protocol. Further staging found no evidence of additional regional or distant metastasis. What do you expect the median survival time to be?

A

1374 days)

Thamm DH, Turek MM, Vail DM: Outcome and prognostic fac- tors following adjuvant prednisone/vinblastine chemotherapy for high-risk canine mast cell tumour: 61 cases, J Vet Med Sci 68:581– 587, 2006.

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10
Q

You have a dog with inoperable mast cell disease. As such, you decide to start the dog on Palladia. What would be reasonable expectations with regards to response rate (CR / PR) and median duration of response?

A

40-50% for 3months
London CA, Malpas PB, Wood-Follis SL, et al.: Multi-center, pla- cebo-controlled, double-blind, randomized study of oral toceranib phosphate (SU11654), a receptor tyrosine kinase inhibitor, for the treatment of dogs with recurrent (either local or distant) mast cell tumor following surgical excision, Clin Cancer Res 15:3856–3865, 2009.

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11
Q

Which of the following statements regarding Palladia is most accurate?
A) MCTs with mutated c-kit does not respond to Palladia better than those with wild type c-kit.​

B) Leukopenia is the most common adverse effect associated with Palladia​

C) In the gross disease setting, up to 80% of patients with MCT responded to Palladia​

D) There has been case reports of SARDs associated with the use of Palladia

A

A
B - GI
C - 40-60%

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12
Q

Vertigo is a 8 y/o Mc DSH who presents to you with a swollen eyelid. FNAs are suggestive of mast cell disease. Which of the following statements are the most accurate?​
A) Surgical excision should be performed with the goal of getting good margins, even if this would involve a flap or enucleation.​

B) This is a mucocutaneous junction MCT, and has a more aggressive disease process, full staging should be performed before making a plan.​

C) If the owner has financial difficulties, even a debulking surgery has been shown to have good long term prognosis.​

D) Refuse to see the cat because the owners will not do anything except pester you every other week for three months and still end up euthanizing the cat. ​

A

C). 50% of the tumors were completely excised, no cats developed either local tumor recurrence or metastatic disease

and only one cat (1/19) developed disseminated cutaneous tumors

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13
Q

Elsa is Labrador currently being managed with Palladia for a low grade but inoperable MCT on her head. When she presents to you, she has marked edema of her limbs but has otherwise been doing well at home. Which of the following tests is most useful to investigate the cause of the edema? ​
A) CT- suspect widespread metastasis and degranulation​

B) Urinalysis with UPC- proteinuria as a side effect from the Palladia causing secondary edema​

C) CBC- symptoms are most likely due to inflammation which will be evident on the CBC​

D) Endoscopy- occult loss of protein in the feces from Palladia side effects ​

A

b

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14
Q

Timone is a 7 yo Mastiff with a suspected high grade cutaneous MCT that is currently causing discomfort and suspected systemic signs His owners are unable to pursue surgery, RT, or chemo, which of the following is true regarding Prednisone in the palliative setting for Timone?​
A) Has the potential for benefit if his tumor expresses high levels of glucocorticoid receptors​

B) Statistically there is less than 50% chance of any benefit​

C) Complete response is expected for 2-3 months​

D) Doses of at least 2mg/kg are needed to see any response​

A

a

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15
Q

What’s the typical anatomical distribution of cutaneous canine MCT?

A

50% = trunk and perineal
40% = limbs
10% = head and neck

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16
Q

What’s the % of dogs presenting with multiple MCT?

A

11-14%

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17
Q

What’s the typical presenting signs for dogs with GI MCT?

A

vomiting, diarrhea, melena

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18
Q

What’s the prognosis for dogs with GI MCT?

A

40% alive @ 30 days
10% @ 6months

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19
Q

What’s the % of dogs with well-differentiated MCT?

A

80-90%

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20
Q

What’s the % of dogs with intermediate grade MCT that can experience long term survival?

A

75%

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21
Q

What’s the metastatic rate of high grade canine MCT?

A

55-96%
most will die of their disease in a year

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22
Q

Where does canine MCT metastasize to?

A

Local LNs, spleen, and liver
bone marrow, peripheral blood

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23
Q

What’s Darier’s sign?

A

mechanical manipulation - degranulation - erythema and wheal formation

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24
Q

What are the clinical signs associated with substantial MCT burden in the dog?

A

vomiting, diarrhea, fever, peripheral edema, and rarely, collapse

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25
Q

What’s the level of plasma histamine and gastrin in dogs with gross high grade MCT?

A

plasma histamine concentration = high
plasma gastrin concentration = low (released by antral G cells as a negative feedback loop for increased HCl secretion)

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26
Q

What causes the hypotension in MCT?

A

prostaglandin D (seen in human med)

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27
Q

What’s the cause of coagulopathy in MCT?

A

heparin secretion
more of a local hemorrhage

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28
Q

What are the major prognostic factors for canine MCT?

A
  • grade
  • clinical stage
  • location
  • cell proliferation rate
  • growth rate
  • microvessel density
  • recurrence
  • systemic signs
  • age
  • breed
  • sex (M<F)
  • tumour size
  • c-kit mutation (worse prognosis)
  • DNA CNV (worse prognosis)
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29
Q

What’s the most consistent and reliable prognostic factor for canine MCT?

A

histological grade

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30
Q

What are some (4) criteria of high grade canine MCT?

A
  1. > 7 mitotic figure / 10HPF
  2. at least 3 multinucleated cells / 10 HPF
  3. at least 3 bizarre nuclei / 10 HPF
  4. karyomegaly
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31
Q

What’s the importance of ki-67 in canine MCT?

A

it’s a marker of proliferation is correlated with patient survival

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32
Q

What’s the significance of argyrophlic nucleolar organzier regions (AgNOR)?

A

it’s a surrogate of cell proliferation
has been correlated with histologic grade and post-op outcome

33
Q

What’s the cutoff for MI for canine MCT?

A

5
MI < 5, MST = 80m
MI >5, MST = 3m
strong predictor of overall survival for dogs with MCT

34
Q

What’s the prognostication of DNA copy number variation on canine MCT?

A

increased DNA CNV is associated with higher grade and shorter post-op ST

35
Q

What’s the relationship between proliferating indices and grade?

A

increases in those indices increases grade (high ki-67, PCNA, AgNOR)

36
Q

Which locations have a worse prognosis?

A
  • preputial/inguinal
  • subungual (nail bed) region
  • mucocutaneous junction (oral cavity, perineum)
37
Q

What’s the metastatic rate for dogs with MCT on the muzzle?

A

50-60% of affected dogs present with regional LN metastasis

38
Q

What’s the prognosis of canine MCT on the muzzle with regional LN metastasis?

A

good! 14m

Hillman LA, Garrett LD, de Lorimier LP, et al.: Biological behavior
of oral and perioral mast cell tumors in dogs: 44 cases (1996-
2006), J Am Vet Med Assoc 237:936–942, 2010.

39
Q

What’s the prognosis for canine visceral or bone marrow MCT?

A

grave prognosis

40
Q

What’s the prognosis of canine SQ MCT?

A

likely better than cutaneous
in 306 dogs with SQ MCT
- 4% had metastasis
- 8% had recurrence
- 2 year survival = 92%, 5y survival = 86%

Thompson JJ, Pearl DL, Yager JA, et al.: Canine subcutaneous
mast cell tumor: characterization and prognostic indices, Vet Pathol
48:156–168, 2011

41
Q

What’s the prognosis of canine conjunctival MCT?

A

good!
15/32 disease free at mean of 21.4m post-op
no dogs died of MCT related disease

Fife M, Blocker T, Fife T, et al.: Canine conjunctival mast cell
tumors: a retrospective study, Vet Ophthalmol 14:153–160, 2011.

42
Q

What’s the MST for dogs with high grade MCT with and without LN metastasis?

A

With LN met = 194d
Without LN met = 503d

Hume CT, Kiupel M, Rigatti L, et al.: Outcomes of dogs with
grade 3 mast cell tumors: 43 cases (1997-2007), J Am Anim Hosp
Assoc 47:37–44, 2011.

43
Q

Does treatment of the affect LN for dogs with high grade MCT effect outomce?

A

Yes
with treatment = MST 240d
no treatment = MST 42d

44
Q

What IHC are typically used for MCT?

A

vimentin (+)
tryptase (+), CD117 (KIT) (+)
potentially useful marker - chymase, MCP-1, IL-8

45
Q

What’s the significance of “histological node” score?

A

High HN score (HN2/HN3) = poor prognosis

Weishaar KM, Thamm DH, Worley DR, et al.: Correlation
of nodal mast cells with clinical outcome in dogs with mast cell
tumour and a proposed classification system for the evaluation of
node metastasis, J Comp Pathol 151:329–338, 2014.

46
Q

What’s the outcome for cyclophosphamide, VBL, and prednisone for high grade canine MCT?

A

PFI - 865 days
OST >2092 days

Camps-Palau MA, Leibman NF, Elmslie R, et al.: Treatment of
canine mast cell tumours with vinblastine, cyclophosphamide and
prednisone: 35 cases (1997-2004), Vet Comp Oncol 5:156–167,
2007.

47
Q

What’s the response rate of canine MCT to single agent corticosteroid?

A
  • Corticosteroids can inhibit canine MCT proliferation and induce cell apoptosis in vitro, but can also contribute to apparent anti-tumour response by decreasing peritumoral edema and inflammation
  • response rate 70-75%
    CR (1/21) PR (4/21) were noted, but short lived @ 1mg/kg
  • response rate is dependent on tumour expression of glucocorticoid receptors
48
Q

What’s the objective response rate of Palladia against recurrent of metastatic intermediate- or high- grade MCT?

A
  • 42.8% (21/145 CR, 41/145 PR)
    Overall RR (including stable disease n = 16) = 60%
  • median duration of objective response = 12 weeks (3m)
  • median time to tumour progression = 18weeks (4.5m)
  • those with c-kit mutation was twice as likely to respond (69% vs 37%), but more recent data failed to confirm

London CA, Malpas PB, Wood-Follis SL, et al.: Multi-center, placebo-
controlled, double-blind, randomized study of oral toceranib
phosphate (SU11654), a receptor tyrosine kinase inhibitor, for the
treatment of dogs with recurrent (either local or distant) mast cell
tumor following surgical excision, Clin Cancer Res 15:3856–3865,
2009

49
Q

What are the most common AE of Palladia?

A
  • most common = GI - decreased appetite, weight loss, diarrhea, occasional vomiting or melena
    Generally manageable with supportive therapy, drug holidays, and dose reduction
  • hypertension
50
Q

What’s the outcome for canine recurrent or unresectable MCT treated with masitinib?

A

40% alive @ 2 years
- those with c-kit mutation had improved outcome

51
Q

What are some side effects of masitinib?

A

most common = GI - vomiting, diarrhea. Generally mild and self-limiting
- myelosuppression, also mild in most cases
- small % = PLN
- rare = hemolytic anemia

52
Q

What’s the outcome for TOC, pred, and hpofrationated RT?

A

overall RR = 76.4%
58.8% CR, 17.6% PR
overall MST not reached with median follow-up time of 374 days

Carlsten KS, London CA, Haney S, et al.: Multicenter prospective
trial of hypofractionated radiation treatment, toceranib, and prednisone
for measurable canine mast cell tumors, J Vet Intern Med
26:135–141, 2012.

53
Q

What are the 3 distinct forms of feline MCT?

A
  1. Cutaneous
  2. Splenic/ visceral
  3. Intestinal
54
Q

What are the 2 distinct histo types of feline cutaneous MCT?

A
  1. Mastocytic
    - compact – similar to canine MCT, 50-90% of cases
    - diffuse/ anaplastic – high MI, marked cellular and nuclear pleomorphism, infiltrates SQ
  2. Histiocytic – less common, morphologically similar to histiocytic MC, may spontaneous regress
55
Q

Do cats also have c-kit mutation?

A

yes!
42/62 (67%) cutaneous and splenic MCT
mostly exon 8 (28/62) and 9 (15/62)

56
Q

What’s the % of cats presenting with multiple MCT?

A

20%

57
Q

What’s the more typical signalment for cats with histiocytic form of MCT?

A

Young (<4y), Siamese cats

58
Q

What are the most common anatomical location for feline MCT?

A

head (pinnae, near base of ear commonly) & neck (unlike the dog!)
trunk, limbs, and others

59
Q

What IHC markers are usually (+) for feline MCT?

A

vimentin
alpha-1 antitrypsin
kit

60
Q

What’s the cutoff for MI for feline MCT?

A

5/ 10 HPF (just like the dog)

61
Q

What’s the definitive tx for feline cutaneous MCT?

A

Surgery
- completeness of excision, histo factors (nuclear pleomorphism, MI) not associated with tumour recurrence

Molander-McCrary H, Henry CJ, Potter K, et al.: Cutaneous mast
cell tumors in cats: 32 cases (1991-1994), J Am Anim Hosp Assoc
34:281–284, 1998.

62
Q

What’s the tx and px for feline eyelid MCT?

A

Surgery alone - local tumour control achieved in 83% (19/23), MST = 945d/ Only 50% of the tumour was completely excised - no cats developed local recurrence or metastasis

Montgomery KW, van der Woerdt A, Aquino SM, et al.: Periocular
cutaneous mast cell tumors in cats: evaluation of surgical excision
(33 cases), Vet Ophthalmol 13:26–30, 2010.

63
Q

What’s the treatment approach to feline cutaneous MCT?

A

they tend to be more benign in behaviour and wide surgical margin may not be as critical as in the dog

64
Q

What’s the outcome for cutaneous feline MCT treated with Strontium 90?

A

98% control, MST >3y

65
Q

How well does feline MCT respond to prednisone?

A

not as good as the dog

66
Q

What’s the efficacy of imatinib with feline cutaneous MCT?

A

all were partial response
- need to monitor closely for neutropenia, proteinuria, and increases in creatinine (masitinib)

67
Q

What’s the most common differential for feline splenic disease?

A

MCT

68
Q

What are some of metastatic sites for feline splenic MCT?

A

liver (90%), visceral LN (73%), bone marrow (40%), lung (20%), and intestine (17%)
up to 1/3 has peritoneal/ pleural effusion
Peripheral blood mastocyosis in 40-100% of cats
23% had bone marrow invovlement

69
Q

What are the clinical signs typically noted with feline splenic MCT?

A
  • systemic illness - rarely associated with cutaneous MCT
  • abdominal palpation = organomegaly
  • ddx = LSA, myeloproliferative disease, accessory spleen, HSA, hyperpalsia, splenitis
  • Gi ulcer, hemorrahge, hypotensive shock, labored breathing
  • coagulopathy (90%) but no clinical significance
70
Q

What’s the treatment of choice for feline splenic MCT?

A

splenectomy, even when there are other organ involvement
MST = 12-19m

71
Q

What are some negative prognostic factors for feline splenic MCT?

A
  • decreased appetite, significant weight loss, male
72
Q

Can post-op chemo improve outcome for feline splenic MCT?

A

unclear

73
Q

What’s the most common GI tumour in the cat?

A

LSA,
#2 = adenocarcinoma, #3 = MCT

74
Q

What’s the typical clinical signs of cats with intestinal MCT?

A

vomiting, diarrhea, hyporexia
solitary palpable abdominal mass
- metastasis is common

75
Q

What’s the predilection site for feline intestinal MCT?

A

small intestines, colon less common (<15%)

76
Q

How frequent is peripheral mastocytosis with feline intestinal MCT?

A

rare

77
Q

What’s the prognosis of feline intestinal MCT?

A

poor, metastasis in common at time of diagnosis
- However, surgical and/or TKI – MST 1.5 years
- undifferentiated and those with MI >2 had worse outcome

Halsey CH, Powers BE, Kamstock DA: Feline intestinal sclerosing
mast cell tumour: 50 cases (1997-2008), Vet Comp Oncol 8:72–79,
2010

78
Q

What’s sclerosing MCT?

A

it’s a variant of feline intestinal MCT
metastasis to LN and/or liver was noted in 23/36 cats, 23 died within 2m of diagnosis

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