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Mast cell tumors Flashcards

1
Q

MCT are the most common cutaneous tumors in the dog, T/F?

A

True

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2
Q

MCTs are the most common cutaneous tumor in the cat, T/F?

A

False, second most common

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3
Q

What substances make up the cytoplasmic granules of mast cells?

A

Heparin, histamine, TNF-a, and several proteases

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4
Q

MCT make up what percentage of cutaneous tumors in dogs?

A

16-21% of all cutaneous tumors

Most common cutaneous tumors in dogs

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5
Q

Average age of dogs that get MCT?

Sex predilection?

A

Primarily a disease of older dogs (8-9yr) but also been reported in younger dogs with no sex predilection

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6
Q

12 dog breeds at increase risk for MCTs?

A

Boxer, Boston, English bulldog, pug, golden, cocker spaniels, schnauzers, Staffordshire terriers, beagles, Rhodesian ridgebacks, Weimaraners and Chinese Shar-Pei.

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7
Q

Dog breed that gets less aggressive MCT?

Dog breed that gets most aggressive MCT?

A

Bulldog (less aggressive) vs Shar-pei (aggressive) anecdotally

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8
Q

Expression of ____ and ___ has been demonstrated in many canine MCT and may be associated with inferior postsurgical outcomes?

A

VEGF, VEGFR2

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9
Q

A significant minority of canine MCT possess the somatic mutation in the c-kit gene involving either exon ___ or exon ___.

These are linked to?

A

Juxtamembrane domain (11-12), extra cellular domain (8-9)

Mutation present in 25-30% of intermediate and high grade

Ultimately linked to increased risk of local recurrence, metastasis, and a worse prognosis

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10
Q

Aberrant cytoplasmic localization and increased phosphorylation of ____ expression in MCT may be associated with dysregulated ____?

A

KIT, dyregulated KIT function

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11
Q

Overexpression of _____ was associated with MCT metastasis and induction of an invasive phenotype?

A

micro-RNA-9

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12
Q

Majority of MCT in dogs occur in ____ the and ____ and are solitary

Percentage for multiple MCT occurence in dogs?

A

dermis, subcutaneous tissue

11-14% multiple

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13
Q

___% cutaneous MCT occur on the trunk and perineal region, ___% on the limbs and ___% on the head and neck

A

50%, 40%, 10%

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14
Q

conjunctiva, salivary gland, nasopharynx, larynx, oral cavity, ureter, and spine

A
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15
Q

Infiltration of which 4 organs are commonly observed in visceral disease?

A

LNs, spleen, liver and bone marrow

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16
Q

l A case series of dogs with GI MCT only 40% of dogs were alive at 30 days after the first admission and <10% were alive at 6 months

A
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17
Q

Well-differentiated MCT appearance?

Undifferentiated MCT appearance?

A

Solitary, small, slow-growing tumors with some hair loss

Rapidly growing, ulcerated, and edematous.

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18
Q

What is darier’s sign?

A

Erythema and wheal formation in surrounding skin after manipulating MCT - release of vasoactive amines

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19
Q

Histamine released from MCT granules is thought to act on _____ cells via ____ receptors, which leads to _____

A

Parietal cells, H2 receptors, increased HCL secretion

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20
Q

Grade as prognostic indication - most important

l The histological grade is considered the most consistent and reliable prognostic factor available

l Recently an attempt was made to develop anew grading system that would separate tumors into “high” or “low” grade based on one of four features identified on histo evaluation. To minimize interpathologist disagreement (on grading schemes) H

l High grade if (1) at least 7 mitotic figures /10HPF, (2) at least 3 multinucleated cell/10HPF (3) at least 3 bizarre nuclei/10HPF or (4)karyomegaly

l 95 dogs both evaluated with Patnaik and Kiupel system and Kiupel system was somewhat better at predicting which dogs would be more likely to die of the disease.

l The author prefers to receive grades according to both schemes on the MCT histopathology report.

A
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21
Q

Location as prognostic factor

3 locations associated with aggressive behaivour for MCT?

A

l Tumors in preputial/inguinal area, subungual region, and other mucocutaneous sites historically have been associated with aggressive behavior.

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22
Q

What percentage of dogs with MCTs located in the muzzle present with regional LN metastasis?

A

50-60%

Does not necessarily indicate a worse long-term prognosis. (MST 14 months with these mets to LN)

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23
Q

Porgnosis with visceral or bone marrow MCT?

A

Grave prognosis noted from visceral or bone marrow MCT

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24
Q

In 306 dogs with subcutaneous MCT, mets occurred in ___ and __ experienced local recurrence. 2-5 year survival probability was ___ and ___ respectively

Decreased survival linked to?

A

4%, 8%

92% and 86%

MI>4, infiltration growth pattern, presence of multinucleation

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25
Q

Conjunctival MCT was found to have a good prognosis 15/32 disease-free at the mean of 21.4 months post-surgery

A
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26
Q

For poorly differentiated tumors, LN mets result in MST of 194d (6.5 mo) compared with 503d (16.7 mo) for dogs with no mets. for these dogs, treatment of LN improved MST to 240d (8 mo) vs 42 days

A
27
Q

What 3 breeds are associated with benign MCT?

A

Boxers and pugs and dogs of bulldog descent appear to develop MCT that often act more benign fashion

28
Q

Is recent rapid growth associated with worse prognosis?

A

Yes

29
Q

What 4 clinical signs have been associated with worse pronosis?

A

Systemic signs, local tumor ulceration, erythema or pruritus has been associated with worse prognosis

30
Q

Recently, in 100 dogs with 115 resectable MCT (primarily low and intermediate-grade) no local or mets was noted from more than 2 years after excision with lateral histological margins 1cm or greater and deep histological margins 4mm or greater. * Just remember that tissue shrinkage can occur up to 30% for cutaneous tissue with formalin-fix*

A
31
Q

Marginal excision of low to intermediate MCT is also an acceptable approach if followed by RT.

A

(Two-year control rates of 85%-95% can be expected for stage 0 of low to intermediate grade MCT

32
Q

Corticosteroid has been reported for many years in preclinical or anecdotal settings to be of some benefit (apoptosis and anti-inflammation effect): anti-tumor effect, 70%-75% response rate but short term (few weeks)

A
33
Q

“high risk” MCT (LN positive, mucous membrane origin or high histological grade)

Post-op pred and vinblastine(VBL) MST of 1374 days

70% 1 and 2-year disease-free survival rates after pred and VBL

post-op pred, VBL and lomustine DFI 35 weeks and overall ST 48 weeks

Post-op pred, VBL and cyclophosphamide PFI 865 days and ST >2092 days

A
34
Q

What percentage of MCT possess the c-kit mutation?

A

20-40%

35
Q

Objective response rate to palladia on intermediate to high-grade MCT?

A

Objective response rate of Palladia (n=86) on intermediate to high grade MCT was 37.2% vs 7.9% (placebo)

36
Q

MCT with a mutation in the c-kit gene showed a higher response rate (69% vs 37%) however, more recent studies have failed to confirm it. (Also shorter PFS compared to c-kit wild type )

A
37
Q

3 syndromes associated with feline MCT?

A

cutaneous, splenic/visceral and intestinal MCT

38
Q

Do feline MCT posses the c-kit mutation?

What exons?

What percentage?

A

It is evident that feline MCT also possesses somatic activating mutations in c-kit (exon 8 and 9) and (67%) in cutaneous and visceral form.

39
Q

Feline cutaneous MCT is the second most common cutaneous MCT, T/F?

What percentage US? UK?

A

True

20% of cutaneous tumors of cats in the US (8% in the UK)

40
Q

What are the 2 distinct type of feline cutenaous MCT?

A

Two distinct types of cutaneous MCT in the cat: 1) mastocytic (dog-like) and 2) histiocytic type

41
Q

Mean age for cats that develop feline cutaneous MCT?

Mastocytic?

Histiocytic?

A

Mean age of 8-9y however (10y mastocytic and 2.4y histiocytic)

42
Q

What are the 2 subtypes of feline mastocytic MCT?

Behaivour?

A

Two subtypes for Mastocytic forms are (compact 50-90%) and diffuse-type with prognostic significance

Compact type tends to behave benignly. In CONTRAST, Mastocytic - diffuse-type may behave in a more malignant manner.

43
Q

Common location for feline cutanoeus MCT?

A

Location wise, head and neck masses are most common followed by trunk, limb (unlike dog). Also affected cats are usually healthy other than intermittent pruritis and erythema.

44
Q

How does the feline histiocytic form of cuetanoeus MCT present?

A

Multiple nonpruritic, firm, hairless, pink and sometimes ulcerated sq nodules

45
Q

Feline cutanoeus MCTs are positive for what markers?

A

vimentin, a-1antitrypsin, and KIT

46
Q

Histological grading system for canine MCT does not provide any prognostic information for cats, T/F?

A

(except maybe be high MI index such as MI >5)

47
Q

Definitive treatment for feline MCT?

A

Surgical excision

Stage for lymphadenopathy, visceral MCT, and other cutaneous MCT

48
Q

What is the local recurrece rate for feline cutaneous MCT? Systemic spread?

A

Local recurrence rate is 0-24%, systemic spread after sx varies from 0-22%

49
Q

Mean age for cats with visceral/splenic MCT?

A

10 years

50
Q

List the 5 most common metastatic sites for feline visceral/splenic MCT?

A

The spleen is the primary site however necropsy of 30 cats with splenic MCT revealed dissemination in liver (90%), visceral LN (73%), bone marrow (40%), lung (20%) and intestine (17%). Peripheral blood mastocytosis 40-100%

51
Q

MST for cats with splenic MCT following splenectomy?

A

12-19 months

52
Q

What is the most common diffeential for cats with splenic disease?

A

Splenic MCT

53
Q

What is the third most common primary intestinal tumor?

A

MCT followed by LSA and adenocarcinoma

54
Q

Mean age of cats with intestinal MCT?

A

13y however as young as 3y reported

55
Q

Clinical signs associated with feline intestinal MCT?

A

Vomiting, diarrhea and hyporexia and solitary palpable abdominal mass

56
Q

Most common site for feline intestinal MCT?

A

More common in the small intestine and colonic involvement is less than 15%

57
Q

Metastatic is uncommon with feline intestinal MCT, T/F?

A

Metastasis is common with intestines MCT (abdominal LN and hepatomegaly)

58
Q

Peripheral masctocytosis is common with feline MCT?

A

Common with splenic/visceral, uncommon with intestinal MCT

59
Q

Prognosis for feline intestinal MCT?

A

l Carries poor prognosis due to the metastasis and often euthanized soon after the diagnosis. However, two recent reports showed MST after sx or medical management was approximately 1.5 years. And MI was found to be prognostic whereas c-kit mutation was not prognostic.

60
Q

Treatment for feline intestinal MCT?

A

A wide margin (5-10cm) is required also undifferentiated tumors with MI >2 May have a worse prognosis.

61
Q

What is sclerosing feline MCT?

A

In a variant of feline intestinal MCT, termed sclerosing MCT, (mets to LN or liver present) 23/25 was euthanized within 2 months

Limited information exists regarding the use of chemotherapy or TKIs.

62
Q

Metastatic rate for undifferentiated canine MCT?

A

55-96% and most dogs will die within 1 year

63
Q

IHC markers for canine MCT

Vimentin +, and majority are tryptase and CD117 (KIT) positive

Other markers: chymase, MCP-1, IL-8

A

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