Page 404 - Withrow and MacEwen's Small Animal Clinical Oncology, 6th Edition

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Mast Cell Tumors

CHERYL A. LONDON AND DOUGLAS H. THAMM

The neoplastic proliferation of mast cells (MCs) referred to as Interestingly, the cBMMCs are extremely sensitive to chemical
mast cell tumor (MCT; mastocytoma, MC sarcoma) represents degranulation, which may help explain why dogs exhibit such a
the most commonly encountered cutaneous tumor in the dog and high degree of hypersensitivity to several chemical agents includ-
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the second most common cutaneous tumor in the cat. 1–5 Systemic ing polysorbate 80, cremaphor EL, and doxorubicin. The func-
forms of the disease are often referred to as mastocytosis. Canine tion of cBMMCs can be modulated by cytokines, steroids, and
and feline forms of the disease are considered separately in this nonsteroidal antiinflammatory drugs. 9–11
chapter, as many differences exist with regard to histologic type,
biologic behavior, therapy, and prognosis. Incidence and Risk Factors

Canine Mast Cell Tumors MCT is the most common cutaneous tumor in the dog, account-
ing for between 16% and 21% of all cutaneous tumors.
1,3,5,12
Biology of Canine Mast Cells Although MCTs are primarily a disease of older dogs (mean
age approximately 8–9 years), they have also been reported in
MC precursors leave the bone marrow and migrate to various tis- younger dogs and there is no apparent sex predilection. 1,3,5 Most
sues throughout the body where they undergo differentiation into occur in mixed breeds; however, several breeds are at increased
mature MCs with their characteristic cytoplasmic granules, which risk for MCTs, including dogs of bulldog descent (boxer, Bos-
stain metochromatically with Geimsa and toluidine blue. These ton terrier, English bulldog, pug), Labrador and golden retrievers,
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granules contain a number of bioactive substances including hepa- cocker spaniels, schnauzers, Staffordshire terriers, beagles, Rhode-
rin, histamine, preformed tumor necrosis factor-alpha (TNF-α), sian ridgebacks, Weimaraners, and Chinese shar-pei. 1,5,13–15 The
and several proteases. The nature and composition of MC gran- increased incidence of MCTs in certain breeds suggests the pos-
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ules is highly influenced by the microenvironment in which the sibility of an underlying genetic cause. A recent genome-wide
MC mature. For example, in dogs, MCs in the gastrointestinal association study in golden retrievers identified polymorphisms
(GI) tract express primarily chymase whereas MCs in the skin in the GNAI2 gene and multiple genes associated with hyaluronic
express both chymase and tryptase. On stimulation, MCs can rap- acid synthesis as risk factors for MCT development. Interest-
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idly produce a variety of proteases (chymase, tryptase), cytokines ingly, although dogs of bulldog ancestry are at higher risk for
(TNF-α, interleukin-6 [IL-6]), chemokines (CCL2, CXCL1), MCT development, it is generally accepted that MCTs in these
growth factors (vascular endothelial growth factor [VEGF], basic dogs are likely to be less aggressive. 1,17 In contrast, anecdotal evi-
fibroblast factor [bFGF]), and lipid mediators (prostaglandin D dence suggests that Chinese shar-pei develop MCTs that may be
2
[PGD ], leukotriene C [LTC ]). Through this process, MCs more biologically aggressive (A. Avery, personal communication).
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2
4
4
participate in several biologic activities, including wound healing, Spontaneously regressing MCTs in young animals have been
induction of innate immune responses, antiparasite activity, and described in cats, pigs, horses, and humans. Multiple cutaneous
modulation of reaction to insect and spider venoms. 6,8 MCT that all regressed within 27 weeks was reported in a 3-week-
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Normal canine MCs can be generated from bone marrow old Jack Russell terrier. This syndrome of spontaneous regres-
derived hematopoietic precursors. 9,10 These cells, known as canine sion in young animals may indicate a hyperplastic or dysplastic
bone marrow derived MCs (cBMMCs), have been used to char- syndrome rather than a true neoplastic lesion.
acterize the functional properties of MCs in this species. As with The etiology of MCTs in dogs is for the most part unknown.
normal human MCs, their differentiation requires the presence Historically, MCTs have been associated with chronic inflamma-
of the growth factor stem cell factor (SCF), and can be influ- tion or the application of skin irritants; however, the epidemiology
enced by the presence of other cytokines. 9,10 On stimulation, of disease in dogs does not support the role of a topical carcino-
these cells rapidly release histamine, monocyte chemoattractant gen. 19–21 Unequivocal evidence is lacking for a viral etiology,
protein-1 (MCP-1), TNF-α, and tryptase, and they produce sev- although MCTs have been transplanted to very young or immu-
eral additional cytokines and chemokines including IL-3, IL-13, nocompromised laboratory dogs using tumor cell tissues and rarely
granulocyte-macrophage colony-stimulating factor (GM-CSF), by cell-free extracts. 22–24 No C-type or other identifiable virus par-
and macrophage inflammatory protein-1 alpha (MIP-1α). 9,10 ticles have been observed, and no epidemiologic evidence exists to

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