Page 406 - Withrow and MacEwen's Small Animal Clinical Oncology, 6th Edition

384 PART IV Specific Malignancies in the Small Animal Patient

shown to be high in dogs with measurable high-grade MCTs, and
there is preliminary information that monitoring of plasma his-
tamine concentrations may be useful in assessing disease progres-
VetBooks.ir sion. These dogs also have decreased concentrations of plasma
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gastrin, which is normally released by antral G cells in response
to increased gastric hydrochloric acid concentrations, acting as a
negative feedback loop. Dogs with substantial MCT burden (i.e.,
large tumors, metastatic disease, systemic disease) are much more
likely to present with clinical signs related to the release of MC
mediators. These may include vomiting, diarrhea, fever, peripheral
edema, and rarely collapse.
Perioperative degranulation of MCTs and subsequent release of
histamine and other less characterized vasoactive substances may
also result in potentially life-threatening hypotensive events during
surgery. It is thought that prostaglandins in the D series secreted
by tumor cells may mediate the hypotensive effects observed in
humans with MC diseases. 75,76 Coagulation abnormalities, also
reported in dogs with MCTs, are likely due to heparin release from
• Fig. 21.1 Subcutaneous mast cell tumor from the shoulder of a dog. This 68,77
mass was originally misdiagnosed as a lipoma based on palpation alone. MC granules. Although clinical evidence of systemic hemor-
Wide surgical excision to include the deep muscle layer was necessary to rhage is not typically associated with this phenomenon, localized
achieve complete surgical margins. excessive bleeding at the time of biopsy or surgery due to degranu-
lation after tumor manipulation can be a complication, even in
the presence of normal presurgical coagulation parameters.

Prognostic Factors
A discussion of prognostic factors associated with canine MCTs
will precede sections on diagnosis and treatment, as steps followed
in those sections are predicated on the presence or absence of these
prognostic factors. Table 21.1 lists factors known to be predictive
of biologic behavior and clinical outcome in dogs with MCTs. It
is important to note that no one factor is entirely predictive of
biologic behavior and, as such, all prognostic indicators should be
taken into consideration when evaluating a patient.
Histologic grade is considered the most consistent and reli-
able prognostic factor available for dogs with MCTs, although
it will not predict the behavior of every tumor. 13,57,78,79 Several
investigators have applied histologic grading systems to canine
MCTs based on degree of differentiation (Table 21.2). The num-
ber grades used in these studies are at odds. Therefore for the
sake of clarity, the three differentiation groups should be simply
referred to as undifferentiated (high) grade, intermediate grade,
and well-differentiated (low) grade. Table 21.3 lists the relative
distribution of MCT grades encountered in larger series. STs after
surgical excision based on histologic grade are presented in Table
21.4. The vast majority of dogs with well-differentiated MCTs
(80%–90%) and approximately 75% of dogs with intermediate-
grade MCTs experience long-term survival after complete surgi-
cal excision. 58,78,80–83 Metastatic rates for undifferentiated MCT
• Fig. 21.2 Erythema and wheal formation occurred in surrounding skin after range from 55% to 96%, and most dogs with these tumors die
manipulation of this cutaneous mast cell tumor. This phenomenon result- of their disease within 1 year. 57,84 The majority disseminate first
ing from release of vasoactive amines from mast cell granules is known as to local LNs, then to spleen and liver. Other visceral organs may
Darier’s sign. (Courtesy D. Vail, University of Wisconsin–Madison.) be involved; however, lung involvement is rare. Neoplastic MCs
may be observed in the bone marrow and peripheral blood in
“Darier’s sign” (Fig. 21.2). This can also occur spontaneously, and cases of widespread systemic dissemination. 68
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dog owners may describe the tumor as periodically increasing and The current histopathologic grading system does not detect a
decreasing in size. GI ulceration has been documented in 35% to small percentage of those well- or intermediately differentiated
83% of dogs with MCTs that underwent necropsy. 72,73 The inci- MCTs that result in death of affected dogs, and this is complicated
dence of GI ulceration may be overrepresented owing to the fact by the fact that there is disagreement in tumor grading schemes
that more aggressive forms of the disease likely end up in necropsy among pathologists. In one study, there was significant variation
surveys. Histamine released from MCT granules is thought to act among pathologists in grading a specific set of MCTs, although
on parietal cells via H receptors, resulting in increased hydro- this was found to be less so if all pathologists strictly employed
2
chloric acid secretion. Plasma histamine concentrations have been the system described by Patnaik. 13,85,86 Recently, an attempt was