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Consultant on Call ONCOLOGY

Peer Reviewed Laura Garrett, DVM, DACVIM (Oncology)


University of Illinois

Diagnosis & Management of


Canine Mast Cell Tumors

PROFILE circulating histamine, which may


lead to GI ulcers and allergic reac-
Definition tions.
Mast cell tumors (MCTs) arise from malig- Local release of heparin may slow
nantly transformed mast cells. In dogs, most blood clotting in the tumor area.
of these tumors arise as primary tumors in the MCTs have extremely variable biologic
skin. They are the most common skin tumor behavior; they range from relatively
in dogs, accounting for roughly 20% of all benign and curable with local excision to
reported skin tumors. very aggressive, rapidly metastatic, and
fatal (See Negative Prognostic Factors,
Signalment page 56).
Breed predilection Sites for metastasis include regional lymph
Any breed may be affected but certain nodes, spleen, liver, bone marrow, and skin;
breeds are predisposed, including golden metastasis to the lungs is very rare.
retrievers, Labrador retrievers, Boston ter-
riers, boxers, and pugs. Signs
Pugs are more likely to have multiple History
MCTs at diagnosis (56% of dogs in 1 Duration of tumor presence and rate of MCTs have
study), but these tumors demonstrate more growth are importantsome dogs may have highly variable
benign behavior and rarely lead to death. recent, rapid tumor growth while others may
biologic behavior,
Age & range have a tumor that has been present and
MCTs can affect dogs of any age but typi- unchanged for months to sometimes years. ranging from
cally affect middle-aged to older dogs. Owners may report seeing the mass grow and benign and
However, MCTs are a common tumor shrink repeatedly; this is due to local histamine curable to
identified in young animals. release that leads to intermittent swelling.
GI signs (eg, vomiting, anorexia, tarry stools)
aggressive
Causes may result from histamine release and gastric and fatal.
Causes are mostly unknown. ulceration.
Breed predilections support some component
of underlying genetic cause. Examination
Mutations in the c-kit tyrosine kinase recep- Examination most often reveals single, firm
tor are found in roughly 33% of these tumors. nodules without a characteristic appearance;
multiple lesions are possible. The nodules may
Pathophysiology/Biologic Behavior be cutaneous or subcutaneous.
MCTs contain histamine and heparin. Cutaneous tumors may or may not be
Dogs with MCTs have increased levels of haired, ulcerated, reddened, or painful.

MCT = mast cell tumor CONTINUES

Consultant on Call / NAVC Clinicians Brief / January 2012 ..................................................................................................................................................................55


Consultant on Call CONTINUED

Subcutaneous tumors often feel like a Biopsy with histopathologic testing is


lipoma. Both cutaneous and subcuta- needed for tumor grading, assessment
neous lesions may be freely movable or of mitotic index, and if needed special
fixed and invasive. stains (c-kit, Ki-67 [a proliferation
Regional lymph node size does not deter- marker]) (for a staff handout go to
mine presence or absence of metastasis. cliniciansbrief.com/journal/oncology-
Nodes may be large due to local inflamma- mct-staff-handout).
tion and reactive hyperplasia, while nodes
with metastasis may be normal in size. Differentials
Lipoma
DIAGNOSIS Inclusion cyst
Bacterial or fungal abscess
Definitive Severe flea allergy dermatitis or other allergic
Definitive diagnosis is made with cytologic dermatopathy
testing of fine-needle aspirate. Other neoplasia (soft tissue sarcoma, heman-
Rare tumors do not stain well with giosarcoma, cutaneous lymphoma, plasma cell
Diff-Quik; these slides need to be tumor, histiocytic sarcoma)
stained with a Romanowsky-type stain
(requiring submission to a clinical Laboratory Findings
pathology laboratory) (Figures 2 and 3). MCTs rarely cause changes to the CBC,
 Many theories exist as to why rare serum biochemical profile, and urinalysis.
MCTs will not uptake Diff-Quik Buffy-coat preparation to assess for circulating
stain (including varying chemical mast cells has little utility in evaluating canine
MCT = mast cell tumor
compositions of the mast cells), but MCTs due to low specificity.
none has been proven.

NEGATIVE PROGNOSTIC FACTORS


Recent, rapid growth

Deep, fixed mass

Systemic signs (eg, vomiting, tarry stools)

Tumor location: Mucocutaneous (mouth, nail bed, eyelid margin), haired


muzzle (Figure 1), pinnae, and possibly inguinal and preputial regions

Regional lymph node metastasis

1 Internal spread

Muzzle MCT in a Boston terrier; Histologic features: High-grade (grade 3) tumor, high mitotic index (>5
note the marked enlargement of mitotic figures in 10 high-power fields), presence of c-kit mutation, high
the left mandibular lymph node.
Metastatic MCT was confirmed
Ki-67 score (>1.8); the latter 2 require special testing on biopsy specimens
via cytologic testing.

All factors must be considered when attempting to predict how an individual MCT will act.
Evidence of lymph node or internal metastasis signifies aggressive behavior, although some
dogs with lymph node metastasis can live for years. In cases without metastasis, the histo-
logic features listed are the gold standard of behavior prediction, but even they may be
inaccurate at times.

56 ..................................................................................................................................................................NAVC Clinicians Brief / January 2012 / Consultant on Call


2 3
Cutaneous MCT stained with Diff-Quik stain; Same tumor as in Figure 2, stained with a
note the presence of round cells but absence of Romanowsky-type stain; the granules are easily
granules. visualized.

Imaging TREATMENT
Conducting staging tests before tumor
removal is recommended when negative Treatment is based on prognostic factors
prognostic indicators are present. Staging tests (tumor grade, mitotic index, and stage) and
may be conducted after tumor removal if his- potential for systemic disease:
tologic evaluation reveals a high-grade MCT Surgical excision (2- to 3-cm margins) is
or high mitotic index. the mainstay of therapy for low- to inter-
mediate-grade tumors (grade 1 or 2) with a
Abdominal Ultrasonography low mitotic index.
When MCTs are present caudally, abdominal Radiation can be used in cases with
ultrasonography is used to assess the spleen incomplete margins to help prevent local
(Figure 4) and liver. Fine-needle aspiration of recurrence. FIND MORE
these organs may be useful, especially when a Systemic adjuvant therapy should be con- For step-by-step
lesion is visible. sidered for tumors with negative prognostic instructions on how to
Abdominal ultrasonography is also critical for factors and if the potential for systemic perform fine-needle
assessing sublumbar lymph nodes when an MCT disease exists. aspiration, see
is present on the caudal aspect of a patient. Procedures Pro:
A cytologist needs to assess whether the Surgical Fine-Needle Aspiration
appearance, number, and clustering of mast Wide (23 cm around, 1 tissue plane deep to in the June 2010
cells suggest metastasis. tumor) surgical excision should be performed. issue of Clinicians
If wide margins are not achievable, narrow Brief, available at
Thoracic Radiography debulking surgery may be used, followed by cliniciansbrief.com/
MCTs rarely metastasize to the lungs; how- radiation therapy. journal.
ever, thoracic radiographs may be helpful in
evaluating sternal lymph nodes if the tumor is Radiation
on the ventral abdomen or if visceral disease Radiation therapy has good efficacy in
exists. preventing local regrowth after incomplete
resection.
Additional Diagnostics It also may be used against bulky disease as
Fine-needle aspiration of regional lymph palliative therapy, with potential to shrink a
nodes is critical even if the lymph nodes are bulky mass substantially.
not enlarged.
CONTINUES

Consultant on Call / NAVC Clinicians Brief / January 2012 ..................................................................................................................................................................57


Consultant on Call CONTINUED

Adjunct Medication
Antihistamines and GI mucosal protectants
should be used as needed.
All dogs with bulky MCTs should begin
receiving histamine-1 (diphenhydramine) and
histamine-2 (famotidine) blockers for life or
until disease remission.
Omeprazole may be used for refractory gastric
ulcers.
NSAIDs must be used with caution in dogs
with MCTs because these patients are predis-
posed to gastric ulceration. Do not use
NSAIDs if the dog is receiving prednisone or
a targeted therapy drug.

Client Education
4 It is important to explain the unpredictable
nature of MCTs (despite assessment of prog-
Ultrasound image of MCTs in the spleen of a dog with systemic mast cell
disease. The patients primary tumor was located on the muzzle and controlled nostic factors) to clients.
for 1 year until systemic progression occurred. Some patients without negative prognostic
factors will develop systemic, aggressive dis-
Medical ease, while others with negative factors will
Chemotherapy may be beneficial for bulky,
not relapse or have metastasis.
Even local recurrence is unpredictable, with
nonexcisable local disease or for treatment or
prevention of systemic disease in dogs with reported recurrence rate of 70% for incom-
negative prognostic factors. pletely resected tumors.
Vinblastine and lomustine have shown
efficacy. FOLLOW-UP
Prednisone has some antitumor effects; it
also helps decrease local swelling, which Patient Monitoring
may be confused with an antitumor If treating bulky disease, monitor response to
response. therapy and adjust treatment as needed.
Prednisone is often combined with If patient has finished therapy with no
other chemotherapy agents. remaining evidence of disease, check for
Targeted therapy includes tyrosine kinase recurrence or new tumors at 1 month, every
inhibitors, which block c-kit signaling; 3 months for 1.5 years, and every 6 months
toceranib phosphate, which is approved in thereafter.
the United States; and masitinib, which
recently received conditional approval. Future
Indications for these drugs are the same as Some dogs are prone to developing MCTs,
for chemotherapy. Safety and efficacy of regardless of whether it is a new tumor or
combining targeted drugs with chemother- systemic disease from a previous tumor.
apy are under investigation. Any new mass should be aspirated and evalu-
As with chemotherapy agents, adverse ated, then staged and treated as described
effects also occur with targeted therapy. previously.
MCT = mast cell tumor The most common adverse effects of
toceranib phosphate are diarrhea, anorexia,
and weight loss. Concurrent medications
may be beneficial and include omeprazole,
famotidine, and diphenoxylateatropine.

58 ..................................................................................................................................................................NAVC Clinicians Brief / January 2012 / Consultant on Call


IN GENERAL Future Considerations
Ongoing evaluations of targeted therapies
Relative Cost combined with chemotherapy may show
High costs may reflect the need for surgery; if improved response and survival rates in dogs
adjuvant treatments are needed, costs are even with aggressive MCT.
higher: $$$$ to $$$$$
See Aids & Resources, back page, for references
& suggested reading.
Cost Key
$ = up to $100 $$$$ = $501$1000
$$ = $101$250 $$$$$ = more than $1000
$$$ = $251$500
FOR MORE

For a convenient staff handout, see Classifying Systems


Prognosis
for Mast Cell Tumors at cliniciansbrief.com/journal/
Varies considerably; most dogs will be cured
oncology-mct-staff-handout.
with appropriate local therapy.
Dogs with negative prognostic factors may
still live for years with multimodal therapy.

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Consultant on Call / NAVC Clinicians Brief / January 2012 ..................................................................................................................................................................59