Page 407 - Withrow and MacEwen's Small Animal Clinical Oncology, 6th Edition

CHAPTER 21 Mast Cell Tumors 385

TABLE 21.1 Prognostic Factors for Mast Cell Tumors in Dogs
Factor Comment
VetBooks.ir Histologic grade Strongly predictive of outcome. Dogs with undifferentiated tumors typically die of their disease after local therapy alone, whereas those
with well-differentiated tumors are usually cured with appropriate local therapy.
Clinical stage Stages 0 and 1, confined to the skin without local lymph node or distant metastasis, have a better prognosis than higher-stage disease.
Location Subungual, oral, and other mucous membrane sites are associated with more high-grade tumors and worse prognosis. Preputial and
scrotal tumors are also associated with a worse prognosis. Subcutaneous tumors have a better prognosis. Visceral or bone marrow
disease usually carries a grave prognosis.
Cell proliferation Mitotic index, relative frequency of AgNORs, and percent PCNA or Ki-67 immunopositivity are predictive of postsurgical outcome.
rate
Growth rate MCTs that remain localized and are present for prolonged periods of time (months or years) without significant change are usually benign.
Microvessel Increased microvessel density is associated with higher grade, a higher degree of invasiveness, and a worse prognosis.
density
Recurrence Local recurrence after surgical excision may carry a more guarded prognosis.

Systemic signs The presence of systemic illness (e.g., hyporexia, vomiting, melena, GI ulceration) may be associated with a higher stage of disease.
Age Older dogs may have shorter median disease-free intervals when treated with radiation therapy than younger dogs.
Breed MCTs in boxers (and potentially other brachycephalic breeds) tend to be of low or intermediate grade and are thus associated with a
better prognosis.
Sex Male dogs had a shorter survival time than female dogs when treated with chemotherapy.
Tumor size Large tumors may be associated with a worse prognosis after surgical removal and/or radiation therapy.
c-kit mutation The presence of an activating mutation in the c-kit gene is associated with a worse prognosis.
DNA copy num- Higher CNVs are observed in tumors of higher grade and those with a worse prognosis.
ber variation

AgNORs, Argyrophilic nucleolar organizer regions; CNV, copy number variation; GI, gastrointestinal; MCTs, mast cell tumors; PCNA, proliferating cell nuclear antigen.

TABLE 21.2 Histologic Classification of Mast Cell Tumors in Dogs
Grade Bostock Grading Patnaik Grading Microscopic Description

Anaplastic, undifferentiated 1 3 Highly cellular, undifferentiated cytoplasmic boundaries, irregular size and shape of
(high grade) nuclei; frequent mitoses, sparse cytoplasmic granules
Intermediate grade 2 2 Cells closely packed with indistinct cytoplasmic boundaries; nucleus-to-cytoplasmic
ratio lower than anaplastic; infrequent mitoses; more granules than anaplastic
Well differentiated (low 3 1 Clearly defined cytoplasmic boundaries with regular, spherical or ovoid nuclei, mito-
grade) ses rare or absent; cytoplasmic granules large, deep staining, and abundant

87
TABLE 21.3 Relative Frequency of Canine Mast Cell information. In this setting, tumors were classified as high grade
if they possessed (1) at least 7 mitotic figures/10 HPF, (2) at least
Tumors by Histologic Grade
3 multinucleated cells/10 HPF, (3) at least 3 bizarre nuclei/10
Number of High Grade Intermediate Low Grade HPF, or (4) karyomegaly. In a series of 95 dogs evaluated by both
Investigator Dogs (%) Grade (%) (%) the Patnaik and this alternative system, the alternative system was
somewhat better at predicting which dogs would be more likely
Hottendorf 21 300 19 27 54 to die of disease ; at least one follow-up study has confirmed
87
88
Bostock 59 114 39 26 34 the utility of this two-tiered system. There remains incomplete
Patnaik 14 83 20 43 36 information to confirm whether two-tiered system is truly better
than the Patnaik three-tiered system for predicting the biologic
Simoes 85 87 22 40 38 behavior of MCTs. The authors prefer to receive grades according
to both schemes on MCT histopathology reports.
Several markers of proliferation have been evaluated to assist
in determining whether an MCT is likely to behave in a more
made to develop a new grading system that would separate tumors aggressive manner. 49,79,89–97 Ki-67 is a protein found in the
into “high” or “low” grade based on one of four features iden- nucleus, the levels of which appear to correlate with cell prolifera-
tified on histopathologic evaluation, in an attempt to minimize tion and patient survival. 90,91 Silver colloid staining of paraffin-
interpathologist disagreement and still provide useful prognostic embedded sections can be used to determine the relative presence