Recurrence rate, clinical outcome, and cellular proliferation indices as prognostic indicators after incomplete surgical excision of cutaneous grade II mast cell tumors: 28 dogs (1994-2002)

The objectives of this study were to determine local recurrence rate, clinical outcome, and prognostic value of the number of argyrophylic nucleolar organizer regions (AgNORs), presence of proliferating cell nuclear antigen (PCNA), and number of Ki-67-positive nuclei after incomplete surgical excision of canine cutaneous grade II mast cell tumors (MCTs). This retrospective study included 30 MCTs in 28 dogs. Medical records were examined and follow-up information was obtained from owners and referring veterinarians. Only cases in which excision was incomplete and no anvcillary therapy (other than prednisone) for MCT was given were included. Paraffin-embedded tumor tissues were retrieved for AgNORs, PCNA, and Ki-67 staining. Median follow-up time was 811.5 days. Seven (23.3%) tumors recurred locally. Median time to local recurrence was not reached with a mean of 1,713 days. The estimated proportions of tumors that recurred locally at 1, 2, and 5 years were 17.3, 22.1, and 33.3%, respectively. Eleven (39.3%) dogs developed MCTs at other cutaneous locations. Median progression-free survival was 1,044 days. Median overall survival was 1,426 days. The combination of Ki-67 and PCNA scores was prognostic for local recurrence (P = .03) and development of local recurrence was prognostic for decreased overall survival (P = .04). Results suggest that a minority of incompletely excised MCTs recur. Therefore, ancillary local therapies may not always be necessary. However, local recurrence can negatively affect survival of the affected dogs. Cellular proliferation indices may indicate the likelihood of MCT recurrence after incomplete excision.     

Correlation of histologic grading of canine mast cell tumors with Ki67/PCNA/AgNOR/c‐Kit scores: 38 cases (2002–2003)

Introduction: The Patnaik grading system for canine cutaneous MCT is currently one of the best determinants of prognosis; however, clinical outcome does not always correlate with histologic grade. The development of molecular markers offers a potential advantage and may complement subjective grading. The primary purpose of this study was to correlate histologic grading to Ki67/PCNA/AgNOR/c‐Kit scores. Methods: Thirty‐eight dogs with cutaneous MCT underwent surgical resection. Tumors were graded, with expansion of grade II MCT to low, medium (or II only) and high. For statistical purposes, MCT grade I, II (low, medium, high) and III were assigned a score of 1, 2, 3, 4, or 5, respectively. Sections were processed for AgNOR staining and expression of PCNA, Ki67 and c‐Kit as previously described (modified biotin‐strepavidin with DAB substrate). Paraffin‐embedded canine tissue arrays were used as positive and negative controls (primary antibody replaced with pre‐immune sera). Parametric statistical testing was performed using Statview statistical software with P ≤ .05 as significant. Results: There were 12, 20, 5 and 1 grade II low, grade II medium, grade II high and grade III MCT, respectively. The mean Ki67 score was 9.114 (median 8.0, range 1–28), mean PCNA score was 26.25 (median 24.0, range 5–65), mean AgNOR score was 1.499 (median 1.35, range 1.02–2.76) and c‐Kit scores were +1 (9/37), +2 (19/37) and +3 (9/37). With parametric statistical testing, significantly positive correlations were found for Ki67/Grade, PCNA/Grade, AgNOR/Grade, Ki67/PCNA, Ki67/AgNOR and PCNA/AgNOR (all P < .0001). No significant correlation was found for c‐Kit and grade; however, +3 c‐Kit scores had statistically significantly higher grades than +2 c‐Kit scores (P = .0458). Conclusions: Ki67/PCNA/AgNOR scores are positively correlated to grade in dogs with MCT. Further studies to correlate Ki67/PCNA/AgNOR/c‐Kit scores with clinical variables are ongoing.     

Evaluation of surgical margins required for complete excision of cutaneous mast cell tumors in dogs

OBJECTIVE: To determine whether neoplastic mast cells extended into tissue 1, 2, or 3 cm laterally or deeper than 1 fascial plane from the visible edge of cutaneous mast cell tumors (MCTs) in dogs. DESIGN: Prospective study. ANIMALS: 21 client-owned dogs with > or = 1 cutaneous MCT PROCEDURES: After preparation for surgery, each dog's skin was marked 1, 2, and 3 cm from the tumor edge at 0 degrees, 90 degrees, 180 degrees, and 270 degrees. At each 3-cm mark, deep fascia was exposed and sutured to the skin; the tumor was excised in routine fashion and fixed in formalin. Tumors were graded; margins were examined histologically for neoplastic mast cells. RESULTS: 23 cutaneous MCTs in 21 dogs were included in this study. Fifteen (65%) tumors were located on the trunk, 5 (22%) on the hind limbs, and 3 (13%) on the head and neck. There were 3 (13%) grade-I and 20 (87%) grade-II tumors. All grade-I tumors were completely excised at all margins. Seventy-five percent of the grade-II tumors were completely excised at the 1-cm margin, and 100% were completely excised at the 2-cm margin. Two grade-II MCTs located on the hind limbs of dogs were excised with a complete but close (within 1 mm) deep margin. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that a 2-cm lateral margin and a deep margin of 1 fascial plane appear to be adequate for complete excision of grade-I and -II MCTs in dogs.     

Production of stem cell factor in canine mast cell tumors

Mast cell tumor (MCT) is the most common cutaneous tumor in dogs. We recently revealed that production of stem cell factor (SCF) contributes to the proliferation of neoplastic mast cells in an autocrine/paracrine manner. The aim of the present study was to determine the contribution of the mechanism in clinical MCTs. In consequence, high SCF expression (>10 times compared to HRMC cells) was observed in 5 of 7 MCT samples used in the study regardless of KIT mutation, which was confirmed in immunohistochemical analysis. In addition, production of SCF was observed in Ki-67-positive cells in the MCT xenograft. These results indicate the broad contribution of SCF autocrine/paracrine mechanism on clinical MCTs, providing the rationale for the clinical use of KIT inhibitors regardless of KIT mutation.     

Canine mast cell tumors: correlation of apoptosis and proliferation markers with prognosis

The Patnaik histologic grading system is commonly used to predict the behavior of cutaneous mast cell tumors (MCTs) in dogs, but it is less useful for grade 2 MCTs because they exhibit considerable variation in biological behavior. In this retrospective study, immunohistochemical staining for Ki-67, proliferating cell nuclear antigen (PCNA), and survivin and a standardized argyrophilic staining of nucleolar organizer regions (AgNOR) protocol were performed on 121 archived paraffin-embedded specimens of canine cutaneous MCTs, for which clinical follow-up data were available. Cox regression models indicated that the Ki-67 score (hazard ratio, 1.92; P < .001) and mean AgNOR score (hazard ratio, 2.57; P < .001) were significantly associated with Patnaik grade and survival time. A binary Ki-67 variable (cutoff point Ki-67 score = 1.8) was a significant predictor of survival for dogs with grade 2 MCTs. The estimated 1-, 2-, and 3-year survival probabilities for dogs with grade 2 MCTs and Ki-67 scores less than 1.8 were 0.92, 0.86, and 0.77, respectively (SEs, 0.08, 0.14, and 0.23, respectively; median not estimable). The corresponding survival probabilities for dogs with grade 2 MCTs and Ki-67 scores higher than 1.8 were 0.43, 0.21, and 0.21, respectively (SEs, 0.19, 0.18, and 0.18, respectively; median survival time, 395 days). No significant association was identified between survival and survivin score or PCNA score. This study shows that both mean AgNOR score and Ki-67 score are prognostic markers for canine MCTs. The Ki-67 score can be used to divide Patnaik grade 2 MCTs into 2 groups with markedly different expected survival times.     

Vinblastine and prednisolone as adjunctive therapy for canine cutaneous mast cell tumors

Twenty-seven dogs with inadequately excised, cutaneous mast cell tumors (MCT; 20 residual microscopic disease, seven marginal excision) were treated with a vinblastine and prednisolone chemotherapeutic protocol. Twenty dogs were available for follow-up examination after 12 months. One dog suffered local recurrence of the tumor, four dogs developed new cutaneous tumors, and one dog had both events. Fourteen dogs were free of MCT. There was no confirmed tumor-related mortality. Although toxicity from the chemotherapy was generally mild, one dog died of sepsis during treatment.     

Canine subcutaneous mast cell tumors: cellular proliferation and KIT expression as prognostic indices

Molecular assays are widely used to prognosticate canine cutaneous mast cell tumors (MCT). There is limited information about these prognostic assays used on MCT that arise in the subcutis. The aims of this study were to evaluate the utility of KIT immunohistochemical labeling pattern, c-KIT mutational status (presence of internal tandem duplications in exon 11), and proliferation markers--including mitotic index, Ki67, and argyrophilic nucleolar organizing regions (AgNOR)--as independent prognostic markers for local recurrence and/or metastasis in canine subcutaneous MCT. A case-control design was used to analyze 60 subcutaneous MCT from 60 dogs, consisting of 24 dogs with subsequent local recurrence and 12 dogs with metastasis, as compared to dogs matched by breed, age, and sex with subcutaneous MCT that did not experience these events. Mitotic index, Ki67, the combination of Ki67 and AgNOR, and KIT cellular localization pattern were significantly associated with local recurrence and metastasis, thereby demonstrating their prognostic value for subcutaneous MCT. No internal tandem duplication mutations were detected in exon 11 of c-KIT in any tumors. Because c-KIT mutations have been demonstrated in only 20 to 30% of cutaneous MCT and primarily in tumors of higher grade, the number of subcutaneous MCT analyzed in this study may be insufficient to draw conclusions on the role c-KIT mutations in these tumors.     

Usefulness of Ki-67 proliferation marker in the cytologic identification of liver tumors in dogs

BACKGROUND: Performing a biopsy is currently the best method of diagnosing liver disease. To reduce possible risk factors resulting from a biopsy, liver cytology can provide an alternative technique. The diagnostic accuracy of cytology for identifying liver tumors is, however, limited. The results of cytology might be improved by using immunochemistry for Ki-67, a proliferation marker, on liver cytology specimens. OBJECTIVES: The purpose of this study was to investigate the value of Ki-67 immunochemistry on liver cytologic specimens from dogs for identifying neoplastic diseases of the liver, by comparing the results to histologic findings. METHODS: Liver biopsy and cytology samples were obtained from 30 dogs with hepatic disease. All samples were evaluated by an anatomic pathologist and a cytopathologist. Parallel Ki-67 immunochemistry of histologic and cytologic samples was performed. The gradation of Ki-67 expression in histologic and cytologic samples was assessed. RESULTS: Cytologic specimens of liver tumors (n = 9) showed <50% Ki-67-positive cells. Twenty of 21 cases of non-neoplastic liver disease had no or few single Ki-67-positive cells. Using Ki-67, the diagnostic accuracy of cytologic evaluation was increased from 78% to 100% for malignant neoplasia. CONCLUSIONS: Based on the results of this study, the cytologic evaluation of liver together with Ki-67 immunochemistry can improve the diagnostic accuracy of cytology for liver neoplasia.     

Clinical outcome of dogs with grade-II mast cell tumors treated with surgery alone: 55 cases (1996-1999)

OBJECTIVE: To determine outcome for dogs with grade-II mast cell tumors treated with surgery alone. DESIGN: Retrospective study. ANIMALS: 55 dogs. PROCEDURES: Medical records were examined, and signalment; location and size of tumor; staging status; dates of local recurrence, metastasis, death, or last follow-up examination; status of surgical margins; previous surgery; postoperative complications; and cause of death were recorded. Follow-up information was obtained via reexamination or telephone conversations with owners or referring veterinarians. Univariate analysis was performed to identify prognostic factors. RESULTS: 60 tumors in 55 dogs were included. Median follow-up time was 540 days. Three (5%) mast cell tumors recurred locally; median time to local recurrence was 62 days. Six (11%) dogs developed another mast cell tumor at a different cutaneous location; median time to a different location was 240 days. Three (5%) dogs developed metastases; median time to metastasis was 158 days. Fourteen dogs died; 3 deaths were related to mast cell tumor, and 7 were unrelated. The relationship with mast cell tumor was not known for 4. Median survival times were 151, 841, and 827 days, respectively, for these 3 groups. Forty-six (84%) dogs were free of mast cell tumors during the study period. A reliable prognostic factor could not be identified. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that additional local treatment may not be required after complete excision of grade-II mast cell tumors and that most dogs do not require systemic treatment.     

Hypotonic water as adjuvant therapy for incompletely resected canine mast cell tumors: a randomized, double-blind, placebo-controlled study

Objective— To evaluate efficacy of hypotonic water as adjuvant therapy after marginal resection of canine mast cell tumors (MCT).
Study Design— Double-blinded, placebo-controlled, prospective, randomized study.
Animals— Dogs (n=30) with spontaneous, cutaneous, solitary MCT.
Methods— The wound bed of MCT, resected with margins <0.5 cm, was injected with either hypotonic or isotonic water according to a standardized protocol. Follow-up was obtained by clinical examination at 1, 2, 3, 6, and 12 months and annual telephone contact with the owner.
Results— Eighteen dogs were treated with isotonic lactated Ringer's solution and 12 dogs with hypotonic distilled water. All MCT were stage 0 tumors and most grade II. Six tumors (4 isotonic, 2 hypotonic) recurred locally, 3 of these dogs died from disease-related reasons within 4 months. The surviving 3 dogs were alive with a median survival time (ST) of 1092 days. The calculated 2-year recurrence-free rate was 92.7%; the 2-year disease-free rate 79.1%; and the 2-year survival rate 89.5%. No significant differences in local recurrence and ST were observed between treatment groups. Histologic grading was the only significant prognosticator for ST and recurrence-free periods.
Conclusion— No significant differences in local recurrence and ST were observed between adjunctive hypotonic water and placebo treatment after marginal resection of solitary MCT.
Clinical Relevance— Hypotonic water does not decrease the rate of local recurrence in dogs with solitary MCT after marginal surgical excision.     

The effect of prednisone on histologic and gross characteristics in canine mast cell tumors

The objective of the study was to determine whether neoadjuvant prednisone therapy affects histological features of cutaneous and subcutaneous mast cell tumors. Twenty-eight dogs with a treatment naïve > 1-cm diameter mast cell tumor (MCT) were randomly assigned (Random number generator; Random.org, Dublin, Ireland) in a blinded fashion to receive either prednisone or placebo (Quality Food Center Pharmacy, Kirkland, Washington, USA). Volumes of mast cell tumors were calculated before incisional and excisional biopsies. Following incisional biopsy, patients received either prednisone (1 mg/kg body weight) daily or a placebo for 7 to 14 days leading up to excisional biopsy. Tumor grade for cutaneous MCT, and mitotic count and atypia for all tumors were reported. Perioperative treatment with prednisone had no significant effect on tumor grade, atypia, or mitotic count. Tumor volume was significantly decreased with prednisone treatment. The use of neoadjuvant prednisone to decrease MCT volume in order to facilitate tumor excision, can be considered without significant concern for change of tumor histologic features in the common population of low- to intermediate-grade MCT.     

Association of argyrophilic nucleolar organizing regions, Ki-67, and proliferating cell nuclear antigen scores with histologic grade and survival in dogs with soft tissue sarcomas: 60 cases (1996-2002)

OBJECTIVE: To determine whether argyrophilic nucleolar organizing regions (AgNORs), Ki-67, and proliferating cell nuclear antigen (PCNA) scores were associated with histologic grade and survival in dogs with soft tissue sarcomas (STSs). DESIGN: Retrospective study. ANIMALS: 60 dogs with STSs. PROCEDURE: Medical records were examined and histologic specimens were reviewed. Tissue specimens obtained from archival materials were used to prepare sections for histologic staining for AgNOR and immunohistochemical staining for Ki-67 and PCNA labeling. Follow-up monitoring was obtained by reevaluation or telephone conversations with referring veterinarians or owners. RESULTS: 27 (45%) STSs were grade 1, 23 (38%) were grade 2, and 10 (17%) were grade 3. The mean and median AgNOR, Ki-67, and PCNA scores were determined, and significant positive associations among AgNOR and Ki-67 scores with histologic grade and mitotic score were detected. Fifty-four dogs had adequate follow-up examinations and were included in survival analysis and evaluation of prognostic factors. Overall median survival time was > 1,306 days. Twelve of 54 (22%) dogs died of tumor-related causes. Metastatic disease developed in 8 of 54 (15%) dogs. Results of univariate analysis indicated that increased mitotic score, increased AgNOR score, increased Ki-67 score, incomplete surgical margins, noncurative intent surgery, Ki-67 score greater than the median Ki-67 score, and AgNOR score greater than the median AgNOR score were prognostic factors for decreased survival time. Results of multivariate analysis indicated that increased AgNOR score was the only prognostic factor for decreased survival time. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggested that AgNORs and possibly Ki-67 should be routinely evaluated with histologic grading for STSs in dogs.     

Recurrence rates and clinical outcome for dogs with grade II mast cell tumours with a low AgNOR count and Ki67 index treated with surgery alone

Grade II mast cell tumours (MCT) are tumours with variable biologic behaviour. Multiple factors have been associated with outcome, including proliferation markers. The purpose of this study was to determine if extent of surgical excision affects recurrence rate in dogs with grade II MCT with low proliferation activity, determined by Ki67 and argyrophilic nucleolar organising regions (AgNOR). Eighty‐six dogs with cutaneous MCT were evaluated. All dogs had surgical excision of their MCT with a low Ki67 index and combined AgNORxKi67 (Ag67) values. Twenty‐three (27%) dogs developed local or distant recurrence during the median follow‐up time. Of these dogs, six (7%) had local recurrence, one had complete and five had incomplete histologic margins. This difference in recurrence rates between dogs with complete and incomplete histologic margins was not significant. On the basis of this study, ancillary therapy may not be necessary for patients with incompletely excised grade II MCT with low proliferation activity.     

Mast cell tumor destruction by deionized water

In a controlled study, malignant murine P815 mastocytoma cells exposed in vitro to distilled and deionized water died as a result of progressive swelling, degranulation, and membrane rupture. A 90% mean cell death occurred when cells obtained directly from culture were exposed to deionized water for 2 minutes. Of 6 cryopreserved malignant murine cell lines, which included Cloudman S91 melanoma, CMT-93 rectum carcinoma, MMT-06052 mammary carcinoma, and S-180 Sarcoma, only P815 mastocytoma and YAC-1 lymphoma were significantly (P less than 0.05) affected by hypotonic shock; Cloudman S91 melanoma cells were the most resistant. Mastocytoma cells were selectively killed by hypotonic solution, and lymphoma cells were also killed by isotonic saline solution. Local mast cell tumor (MCT) recurrence and percentage survival were evaluated in 12 cats (21 MCT) and 54 dogs (85 MCT) subjected to surgery alone or local infiltration of deionized water as an adjunct to surgery. Of all 16 incompletely excised MCT in cats, there was no local recurrence following injection. Four mast cell tumors (2 cats) regressed after being injected in situ. In dogs with clinical stage-I MCT, local recurrence was detected in 50% (5/10), but with injection after incomplete excision, local MCT recurrence was significantly (P less than 0.05) less (6.6%, 1/15). Percentage recurrence was significantly (P less than 0.05) less and survival significantly greater when incompletely excised grade-II MCT were injected. Mean follow-up period after surgery in cats and dogs was 35 and 23.4 months, respectively.     

Visceral mast cell tumors in dogs: 10 cases (1982-1997)

OBJECTIVE: To characterize the clinical features of visceral mast cell tumors (MCT) without associated cutaneous involvement in dogs. DESIGN: Retrospective study. ANIMALS: 10 dogs with histologically confirmed MCT without associated cutaneous lesions. PROCEDURE: Information on signalment, clinical signs, laboratory examinations, and time from first admission to death was obtained from the medical record of each dog. RESULTS: Purebred male dogs of miniature breeds appeared to have a higher prevalence of visceral MCT. Clinical signs included anorexia, lethargy, vomiting, and diarrhea. Anemia (n = 7), hypoproteinemia (5), and mastocythemia (5) were detected. Treatments, including glucocorticoids, were not successful. Primary sites of tumors were the gastrointestinal tract (n = 6) and the spleen or liver (1); the primary site was not confirmed in the remaining 3 dogs. In 7 dogs, tumors were categorized as grade II or III, on the basis of histologic findings. The prognoses were poor, and all dogs died within 2 months after first admission. CONCLUSIONS AND CLINICAL RELEVANCE: Visceral MCT is uncommon in dogs, and the prognosis is extremely poor. Biological behavior and drug susceptibility of visceral MCT may be different from cutaneous MCT. The lack of specific clinical signs may result in delay of a definitive diagnosis. The rapid progression of clinical signs and difficulty in diagnosis contributes to a short survival time.     

Evaluation of risk and clinical outcome of mast cell tumours in pug dogs

Mast cell tumours (MCT) are common in dogs and characterized by diverse biologic behaviour. Our objective was to evaluate the risk of MCT in pugs and to describe the clinical behaviour of MCT in this breed. Data obtained from the Veterinary Medicine Database demonstrate significantly increased frequency of MCT in pugs compared with other dogs (OR = 2.28, 95% CI = 1.81–2.86). The medical records for 25 purebred pugs with a histologic diagnosis of MCT were reviewed. Multiple cutaneous tumours were documented in 14 (56 %) of the dogs. Histologic review of 64 tumours from these dogs confirmed that most tumours (94%) were low to intermediate grade. Sixty‐four per cent of these dogs are still living, while only three dogs (12%) have died due to mast cell disease. A median survival time has not been reached. The median follow‐up time is 660 days from the diagnosis of the first MCT. We conclude that MCT in pugs are relatively benign, despite the presence of multiple cutaneous tumours in most cases. Multiple tumours in breeds with predisposition to MCT may indicate separate primaries rather than advanced stage disease.     

Prognostic significance of surgical margin, Ki-67 and cyclin D1 protein expression in grade II canine cutaneous mast cell tumor

The prognosis for canine cutaneous mast cell tumor (CCMT) is thought to be correlated with histopathological grading. However, the wide variety of histopathologic types of grade II is one of the most troublesome and difficult points for prognosis. The objective of this study is to determine the prognostic value of surgical margin, ki-67 and cyclin D1 protein expression in grade II tumor. Surgically resected specimens of solitary grade II CCMT from 48 dogs with follow-up periods over 360 days (median was 1080 days) were used in this study. The expression of cyclin D1 and ki-67 proteins was determined by morphometrically using slides stained immunocytochemically, and the correlations among the results, survival rate, and recurrence and/or metastasis rate of each dog were analyzed statistically. The recurrence and/or metastasis and mortality rate in the incomplete surgical excision group within 30 months postoperatively were higher than that of the complete surgical excision group. In the incomplete surgical excision group, dogs with low positive staining of ki-67 had a significantly better survival, but the recurrence and metastasis rate and ki-67 positivity failed to show a significant correlation. Only a small number of cases showed cyclin D1-positive tumor cells, but most of them had a poor outcome with a high recurrence rate. In grade II CCMT, incomplete excision induced a relatively high metastasis rate and poor prognosis. Ki-67 positivity is a marker for the estimation of overall survival in incomplete surgical excision cases. Cyclin D1 positivity was low and may not have a prognostic role.     

Use of kit internal tandem duplications to establish mast cell tumor clonality in 2 dogs

Mast cell tumor (MCT) is one of the most common tumors of dogs. Some affected dogs develop multiple cutaneous tumors in various locations over months to years. In these cases, it is not clear whether the tumors have arisen de novo, or if each tumor represents a recurrence of the previously excised original tumor (ie, distant metastasis). We used the presence of an internal tandem duplication (ITD) in c-kit to demonstrate that in 2 dogs with recurrent cutaneous MCT that had developed over 1-2 years, each recurrent MCT tumor possessed an identical ITD when compared to the original MCT, indicating that the multiple tumors were clonal in origin. This study demonstrates that similar to the situation in humans, specific somatic mutations identified in oncogenes found in canine neoplasms can be used to provide evidence of tumor clonality.     

The Biologic Behavior of Mast Cell Tumors in Pug Dogs

Introduction:  The purpose of this study was to quantitate the risk and to describe the behavior of mast cell tumors (MCT) in Pugs.
Methods and Materials:  Using the Veterinary Medicine Database, the frequency of MCT in Pugs was compared to the frequency in other dogs using a Chi‐square test. To describe the biologic behavior of MCT in pugs, cases with histologically confirmed diagnosis were identified through the University of Minnesota (UMN) Diagnostic Laboratory and Veterinary Medical Center. Histology was reviewed by a single pathologist. Survival analysis was performed to determine the impact of clinical and histologic data on survival.
Results:  The frequency of MCT diagnosis in Pugs was significantly increased compared to other dogs (OR = 2.28, 95% CI = 1.81–2.86). Twenty‐five purebred Pugs with a diagnosis of MCT were identified through UMN. Multiple cutaneous tumors were documented in 14 (56%) of the dogs. Most tumors were low to intermediate grade. Only three dogs have died of their disease. Sixteen are still living (median follow‐up = 660 days). The only factors predicting survival were grade, mitotic index and tumor size.
Discussion:  Our data confirms MCT predisposition in Pugs and suggests that mast cell tumors in Pugs are relatively benign, despite the presence of multiple cutaneous tumors in most cases. Multiple tumors in breeds with predisposition to MCT may indicate separate primaries rather than advanced stage disease.
This work was supported in part by NCI grants R03‐CA101030 and K08‐CA89530.