Mast Cell Tumors Flashcards by Kait Esson

What markers are MCT positive for?

vimentin, tryptase, and CD117 (KIT) positive

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Treatment of choice for MCT localized to the skin in areas amenable to wide excision

surgery

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Surgical margins for MCT

Historically, surgical excision to include a 3-cm margin
Metric approach uses a prescribed metric distance, with lateral margins of 1 cm and 2 cm for low- and intermediate-grade MCTs
Proportional approach uses lateral margins proportional to the maximum dimension of the MCT.
For both approaches, deep margins include removal of one uninvolved fascial plane in continuity with the tumor.

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Treatment options of MCT if primary closure is not possible regardless of the width of the lateral margins

Wide excision +/-chemotherapy depending on histologic grading
Marginal excision followed by adjuvant therapy

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Two-year control rates for stage 0 tumors of low- or intermediate-grade MCTs treated with surgery followed by RT

85% to 95%

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Treatment options after curative excision surgery is unsuccessful and histologic margins are incomplete

Scar revision surgery
RT

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% of regrowth in MCTs with histologically confirmed incomplete margins

10-30%

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Treatment for poorly differentiated and metastatic MCT

Surgery (if possible) followed by systemic chemotherapy for best response

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Corticosteroids role in MCT treatment

Inhibit canine MCT proliferation and induce tumor cell apoptosis
May also contribute to apparent antitumor response by decreasing peritumoral edema and inflammation

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Cytotoxic chemotherapy protocols for MCT

Vinblastine + pred
CCNU + Vinblastine + pred
Vinblastine + cyclophosphamide + pred

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ORR to toceranib in dogs with recurrent or metastatic intermediate- or high-grade MCTs

~45%

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C-kit mutation correlation to toceranib response

Dogs with mutations in the c-kit gene were roughly twice as likely to respond to TOC than those with wild-type c-kit

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Tyrosine kinase inhibitors used for MCT

Toceranib, masitinib, imatinib

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ORR and MST of toceranib, pred, and hypofractionated RT in dogs with unresectable and/or metastatic MCTs

~80%
CR - 60%
PR 20%
MST not reached (follow up 1 year)

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Ancillary treatment to minimize the
effects of histamine release

H1 blockers diphenhydramine or chlorpheniramine
H2 blockers cimetidine, famotidine, or ranitidine
Proton pump inhibitor omeprazole

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Dog mast cell tumors in which locations carry worse prognosis?

Subungual (nail bed)
Oral
Other mucous membrane sites
Preputial
Scrotal
Visceral & bone marrow = grave

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Which cell proliferation indexes are prognostic for canine mast cell tumors?

Mitotic index
Relative frequency of AgNORs
Percent PCNA
Percent Ki-67

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Which breeds of dogs with MCTs have a better prognosis?

boxers and potentially other brachycephalic breeds

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What is the difference between the composition of mast cell granules in the GI and skin?

GI MCs express primarily chymase
Skin MCs express both chymase and tryptase

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The presence of which molecule is required for the differentiation of human and canine bone marrow derived mast cells?

Stem cell factor (SCF)

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Why dogs exhibit such a high degree of hypersensitivity to several chemical agents including polysorbate 80, cremophor EL, and doxorubicin?

BONUS QUESTION: Do you remember what polysorbate 80 and cremaphor EL are?

Canine bone marrow derived mast cells (cBMMCs) are exteremely sensitive to chemical degranulation.

Polysorbate 80 and Cremophor EL are both non-ionic surfactants commonly used in pharmaceutical formulations, particularly as solubilizers for poorly water-soluble drugs, but they are different brand names for essentially the same type of chemical compound - a polyethoxylated castor oil

Cremaphor EL: paclitaxel
Polysorbate 80: docetaxel, etoposide
That’s why IV administration of these drugs causes severe hypersensitivity.

Which genes are risk factors for the development of MCTs in golden retrievers?

Polymorphisms in the GNAI2 gene and multiple genes associated with hyaluronic acid synthesis.

How do estrogen and progesterone influence canine MCTs?

Their role is unclear, but European studies suggest female dogs may have better chemotherapy outcomes. US studies did not find the same effect probably because of the higher number of intact dogs in Europe.

What angiogenic growth factors are linked to canine MCTs?

VEGF and its receptor VEGFR2; VEGFR2 activation may be linked to worse post-surgical outcomes.

Which exons are commonly mutated in the c-kit gene? ## Footnote AH

Exons 8–9 (extracellular) and 11–12 (juxtamembrane).

How does micro-RNA-9 impact canine MCTs? ## Footnote AH

Its overexpression is linked to metastasis by promoting an invasive tumor phenotype.

What are the most common anatomical locations for cutaneous MCTs? ## Footnote AH

50% on the trunk and perineal region 40% on the limbs 10% on the head and neck

What is the prognosis for dogs with primary GI MCT? ## Footnote AH

40% alive at 30 days Less than 10% alive at 6 months

What substances released by mast cells contribute to hypotension in human MCT cases? ## Footnote AH

Prostaglandins (D-series) and other vasoactive substances.

How does KIT staining correlate with prognosis? ## Footnote AH

Diffuse cytoplasmic KIT staining may indicate shorter survival. c-kit mutations are linked to higher recurrence, metastasis, and mortality.

How does metastasis in muzzle MCTs affect prognosis?

50%-60% present with regional lymph node (LN) metastasis, but it does not affect px. and MST remains ~14 months.

Three distinct syndromes of MCT in cats?

1. cutaneous 2. splenic/visceral 3. intestinal

% of splenic/cutaneous MCT with c-kit mutation in cats?

67% (42/62)

Most common site of cutaneous MCT in cats?

head and neck

Two distinct histologic types of MCT in cats?

1. mastocytic (typical) 2. histiocytic (may regress spontaneously)

Which breed of cat is more predisposed to histiocytic type of MCT?

siamese

What are prognostic factors for cat cutaneous MCT?

MI KIT immunoreactivity

Definitive treatment for cat cutaneous MCT?

surgical excision

Local recurrence rate of feline cutaneous MCT?

0-24%

Frequency of systemic spread after surgical excision in feline MCT?

0-22% (more likely to be anaplastic tumors)

Control rate with Strontium 90 for feline cutaneous MCT?

98%, MST >3 years

Use of chemotherapy for cutaneous MCT in cats?

Generally limited Lomustine in one paper was used in 20 cats CR 2 PR 8

Most common site of dissemination for splenic MCT in cats?

1. liver (90%) 2. visceral LN (73%) 3. bone marrow (40%)

Rate of peripheral blood mastoytosis in cats with splenic MCT?

40-100%

Treatment of choice for splenic MCT in cats?

surgery (even if involvement of other organs is noted)

MST following splenectomy for cats with splenic MCT?

12-19 months

What part of the intestine is most commonly effected with intestinal MCT in cat?

1. small intestines 2. Colon (<15%)

Prognosis for intestinal MCT in cats?

-poor, metastasis common at diagnosis -two reports of better outcomes following surgical and/or medical management with MST ~1.5 years

Prognostic indicators for intestinal MCT in cats?

histologic differentiation (undifferentiated) MI (>2)

Treatment of choice for intestinal MCT in cats?

surgery with wide surgical margins (5-10cm)

Describe sclerosing MCT in cats?

variant of feline intestinal MCT metastatic disease to LN and/or liver in 23/36 cats 25 cases available for follow up, 23 died or euthanized within 2 months of diagnosis