Evaluation of prognostic factors associated with outcome in dogs with multiple cutaneous mast cell tumors treated with surgery with and without adjuvant treatment: 54 cases (1998-2004)

OBJECTIVE: To evaluate prognostic factors associated with outcome of dogs with multiple cutaneous mast cell tumors (MCTs) treated with surgery with or without adjuvant treatment. DESIGN: Retrospective case series. ANIMALS: 54 dogs with a minimum of 2 simultaneous, histologically confirmed cutaneous MCTs that had been excised and had adequate staging and follow-up data. PROCEDURE: Medical records from 1998 to 2004 were examined. Outcome was assessed with the Kaplan-Meier product-limit method and log-rank analysis. Prognostic factors evaluated included signalment; number, histologic grade, location, size, local recurrence, and de novo development of MCTs; quality of surgical margins; clinical signs at the time of diagnosis; and use of adjuvant treatment. RESULTS: Medical records of 54 dogs with 153 tumors were included. Median follow-up time was 658 days. Median disease-free interval (1,917 days; range, 11 to 1,917 days) and median survival time (1,917 days; range, 14 to 1,917 days) were not yet reached. The 1- year and 2- to 5-year survival rates were 87% and 85%, respectively. The overall rate of metastasis was 15%. Factors that negatively influenced survival time in the univariate analysis included incomplete excision, local recurrence, size > 3 cm, clinical signs at the time of diagnosis, and use of adjuvant treatment. Presence of clinical signs at the time of diagnosis was the only negative prognostic factor for disease-free interval detected in the multivariate analysis. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggested that multiple cutaneous MCTs in dogs are associated with a low rate of metastasis and a good prognosis for long-term survival with adequate excision of all MCTs.     

Evaluation of prognostic indicators in dogs with multiple,simultaneously occurring cutaneous mast cell tumours: 63 cases

Sixty‐three dogs with multiple contemporaneous cutaneous mast cell tumours (MCTs) were identified. The aim of this study was to determine the significance of breed, concurrent dermatological condition; number of cutaneous MCTs, size, location, histological grade and mitotic index; completeness of excision (complete, close or incomplete); local recurrence, metastasis and adjuvant therapy for the prognostic evaluation of dogs with a unique disease presentation of multiple, simultaneously occurring cutaneous MCTs. On the basis of multivariable survival analysis, dogs with one recorded grade 3 MCT had shorter progression‐free survival (PFS) times (18.7 versus 2.2 months) and median survival times (MSTs) (24 versus 3 months). Dogs treated with adjuvant vinblastine/lomustine had a 16 times increased risk of dying. MSTs were found to be significantly longer in dogs with one recorded MCT on an extremity. For all dogs, the PFS (range 14–1835 days) and MSTs (range 28–1835 days) were not reached.     

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.     

Cellular proliferation in canine cutaneous mast cell tumors: associations with c-KIT and its role in prognostication

Canine cutaneous mast cell tumor (MCT) is a common neoplastic disease in dogs. Due to the prevalence of canine MCTs and the variable biologic behavior of this disease, accurate prognostication and a thorough understanding of MCT biology are critical for the treatment of this disease. The goals of this study were to evaluate and compare the utility of the proliferation markers Ki67, proliferating cell nuclear antigen (PCNA), and argyrophilic nucleolar organizing region (AgNOR) as independent prognostic markers for canine MCTs and to evaluate the use of these markers in combination, as each marker assesses different aspects of cellular proliferation. An additional goal of this study was to evaluate the associations between cellular proliferation and c-KIT mutations and between cellular proliferation and aberrant KIT protein localization in canine MCTs. Fifty-six MCTs treated with surgical excision alone were included in this study. Each MCT was evaluated for Ki67 expression, PCNA expression, and KIT protein localization using immunohistochemistry; for AgNOR counts using histochemical staining; and for the presence of internal tandem duplication c-KIT mutations using polymerase chain reaction amplification. In this study, increased Ki67 and AgNOR counts were both associated with significantly decreased survival. On the basis of these results, we recommend that the evaluation of cellular proliferation, including evaluations of both Ki67 expression and AgNORs, should be routinely used in the prognostication of canine MCTs. Additionally, the results of this study show that MCTs with aberrant KIT protein localization or internal tandem duplication c-KIT mutations are associated with increased cellular proliferation, further suggesting a role for c-KIT in the progression of canine MCTs.     

Evaluation of a two-centimeter lateral surgical margin for excision of grade I and grade II cutaneous mast cell tumors in dogs

OBJECTIVE: To evaluate completeness of excision and clinical outcome in dogs with cutaneous mast cell tumors (MCTs) excised with a lateral margin of 2 cm and a deep margin of 1 fascial plane. DESIGN: Prospective study. ANIMALS: 16 client-owned dogs with 1 or more cutaneous MCTs. PROCEDURE: Excision of MCTs was performed with a 2-cm lateral margin and a deep margin of 1 fascial plane. Histologic tumor grading was performed; surgical margins were categorized as complete or incomplete. Follow-up information was obtained via repeat examination of the dogs by veterinarians or client-completed questionnaires. RESULTS: 4 grade I and 19 grade II cutaneous MCTs were evaluated. Overall, 21 (91%) MCTs were completely excised; 2 grade II tumors had foci of mast cells at the 2-cm margin. Two dogs received adjunctive treatments following surgery. Follow-up information was available for all dogs (median follow-up period, 379 days; range, 51 to 538 days); no local recurrence was detected during this time. De novo MCTs were detected in 3 of 16 dogs at 37, 54, and 154 days after surgery. Via Kaplan-Meier analysis, median survival time and disease-free interval were both > 538 days (medians not yet reached). No prognostic variables were identified. CONCLUSIONS AND CLINICAL RELEVANCE: Excision with a 2-cm lateral margin and a deep margin of 1 fascial plane may result in satisfactory excision of grades I and II MCTs in dogs, with recurrence rates similar to those reported previously. Use of these margins may minimize complications associated with larger local tumor resection.     

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.     

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.     

Retrospective outcome evaluation for dogs with surgically excised,solitary Kiupel high‐grade,cutaneous mast cell tumours

Published outcomes for dogs with specifically high‐grade mast cell tumours (MCTs), controlled for clinical stage, are few. Clinical outcomes for 49 dogs with Kiupel high‐grade, clinical stage I, cutaneous MCTs were evaluated. Median survival time (MST) was 1046 days; 1 and 2‐year survival rates were 79.3% and 72.9%, respectively. At study end 24 dogs had died, 23 dogs were alive (median follow‐up 980 days) and 2 dogs were lost to follow‐up. Death was considered MCT‐related in 14 of 20 dogs with a known cause of death. Local tumour recurrence developed in nine dogs (18.4%); regional lymph node metastasis occurred in six dogs (12.2%); and a new MCT developed in 15 dogs (30.1%). Tumour location, histologic margin size and use of chemotherapy did not affect MST; increasing mitotic count (P = .001) and increasing tumour diameter (P = .024) were independently negatively prognostic. Six dogs that developed lymph node metastasis after surgery had worse MST (451 days) than 42 dogs that did not develop metastasis (1645 days); (P < .001). Our study suggests that dogs with local surgical control of clinical stage I histologically high Kiupel grade cutaneous MCT may have a long survival time; especially those with smaller tumours and a lower mitotic count. Our results suggest that evaluation of staging information and mitotic count may be equally helpful as histologic grading when making a prognosis; and highlight the importance of not relying on histologic grade alone when predicting survival for dogs with MCT.     

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.     

Impact of tumour depth, tumour location and multiple synchronous masses on the prognosis of canine cutaneous mast cell tumours

The goal of this study was to determine the significance of tumour depth, tumour location and multiple synchronous tumour masses for the prognostic evaluation of canine cutaneous mast cell tumours (MCTs). The study population consisted of 100 formalin-fixed, paraffin-embedded cutaneous MCTs that had been surgically removed from 100 dogs and submitted to the Diagnostic Center of Population and Animal Health at Michigan State University between 1998 and 2001. None of the dogs had received chemotherapy or radiation therapy. For each case the following data were obtained from the referring veterinarians: sex, breed, weight, age at diagnosis, diagnostics performed, adjunct medications given at the time of surgery, tumour location, number of tumour masses, tumour recurrence (development of MCTs at the surgical site), development of additional MCTs at distant sites (outside the surgical margins), tumour duration before removal, survival time and cause of death, if applicable. Tumour depth was determined through microscopic evaluation of 5 microm sections stained with haematoxylin and eosin. Based on univariable and multivariable survival analysis, dogs with multiple synchronous cutaneous MCTs at the time of diagnosis have a worse prognosis compared with dogs with single tumours. Additional treatment beyond surgical excision alone should be considered for these animals. Older dogs and Boxers with cutaneous MCTs were at higher risk to develop additional MCTs at distant sites (outside the surgical margins), and older and male dogs with cutaneous MCTs had significantly shorter survival times. Univariable analysis also determined that dogs with cutaneous MCTs located on the head and neck had an increased risk of additional MCT development at distant sites and that sterilized dogs with cutaneous MCTs had shorter survival times. However, these findings were not confirmed by multivariable analysis. Tumour depth was of no prognostic significance for dogs with cutaneous MCTs.     

Immunohistochemical detection of proliferating cell nuclear antigen and Ki-67 in mast cell tumors from dogs

OBJECTIVE: To determine whether immunohistochemical detection of proliferating cell nuclear antigen (PCNA) and Ki-67 correlated with prognosis for dogs with cutaneous mast cell tumors (MCT). DESIGN: Case series. ANIMALS: 120 dogs with solitary cutaneous MCT that were excised. PROCEDURE: Information on signalment, history, and outcome was obtained by sending a questionnaire to referring veterinarians. Tumors were graded histologically, and immunohistochemical staining for Ki-67 and PCNA was performed. RESULTS: Survival rates 12, 18, and 24 months after surgery were significantly different among groups when dogs were grouped on the basis of histologic grade. Although mean number of PCNA-positive nuclei/1,000 tumor nuclei was significantly higher for dogs that died of MCT than for those that survived, there was great overlap in values. Mean number of Ki-67-positive nuclei/1,000 tumor nuclei was significantly higher for dogs that died of MCT than for those that survived, without any overlap in values between groups, and number of Ki-67-positive nuclei/1,000 tumor nuclei was significantly different among groups when tumors were grouped on the basis of histologic grades. For dogs with grade-II tumors, number of Ki-67-positive nuclei/1,000 tumor nuclei (< 93 vs > or = 93) was significantly associated with outcome (survived vs died). CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that for dogs with solitary cutaneous MCT, determining number of Ki-67-positive nuclei may be useful in predicting prognosis, particularly for dogs with grade-II tumors.     

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.     

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.     

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.     

Prognostic factors for survival of dogs with inguinal and perineal mast cell tumors treated surgically with or without adjunctive treatment: 68 cases (1994-2002)

OBJECTIVE: To determine the prognostic factors for survival and tumor recurrence in dogs with cutaneous mast cell tumors (MCTs) in the perineal and inguinal regions treated surgically with or without adjunctive radiation therapy, chemotherapy, or both. DESIGN: Retrospective study. ANIMALS: 68 dogs. PROCEDURE: Medical records of dogs with histologically confirmed MCTs in the perineal region, inguinal region, or both treated surgically with or without adjunctive radiation therapy, chemotherapy, or both were reviewed. RESULTS: Mean tumor-free interval was 1,635 days (median not reached), and 1- and 2-year tumor-free rates were 79% and 71%, respectively. Median survival time was 1,111 days (mean, 1,223 days), and 1- and 2-year survival rates were 79% and 61%, respectively. Factors that negatively influenced survival time were age at diagnosis, tumor recurrence, and treatment with lomustine. CONCLUSIONS AND CLINICAL RELEVANCE: Results indicated that dogs with MCTs in the inguinal and perineal regions, if appropriately treated, may have survival times and tumor-free intervals similar to dogs with MCTs in other locations.     

The use of KIT and tryptase expression patterns as prognostic tools for canine cutaneous mast cell tumors

Cutaneous mast cell tumors (MCTs) are one of the most common tumors in dogs. Currently, prognostic and therapeutic determinations for MCTs are primarily based on the histologic grade of the tumor, but a vast majority of MCTs are of an intermediate grade, and the prognostic relevance is highly questioned. A more detailed prognostic evaluation, especially of grade 2 canine MCTs, is greatly needed. To evaluate the prognostic significance of KIT and tryptase expression patterns in canine cutaneous MCTs, we studied 100 cutaneous MCTs from 100 dogs that had been treated with surgery only. The total survival and disease-free survival time and the time to local or distant recurrence of MCTs were recorded for all dogs. Using immunohistochemistry, 98 of these MCTs were stained with anti-KIT and antitryptase antibodies. Three KIT- and three tryptase-staining patterns were identified. The KIT-staining patterns were identified as 1) membrane-associated staining, 2) focal to stippled cytoplasmic staining with decreased membrane-associated staining, and 3) diffuse cytoplasmic staining. The tryptase-staining patterns were identified as 1) diffuse cytoplasmic staining, 2) stippled cytoplasmic staining, and 3) little to no cytoplasmic staining. Based on univariate and multivariate survival analysis, increased cytoplasmic KIT staining was significantly associated with an increased rate of local recurrence and a decreased survival rate. The tryptase-staining patterns were not significantly associated with any survival parameter. On the basis of these results, we propose a new prognostic classification of canine cutaneous MCTs, according to their KIT-staining pattern, that can be used for the routine prognostic evaluation of canine cutaneous MCTs.     

Long-term postsurgical outcomes of mast cell tumors resected with a margin proportional to the tumor diameter in 23 dogs

We evaluated the postsurgical outcomes of cutaneous or subcutaneous mast cell tumors (MCTs, n=25) in 23 dogs, resected with lateral surgical margins proportional to the widest tumor diameter, including at least one facial plane. The tumor diameter range was 0.3–2.6 cm (median: 0.9 cm), and all were histologically diagnosed as Kiupel’s low-grade MCT. Resection was histologically complete in 20, close (deep margin) in three, and incomplete (deep margin) in two. No dogs developed local recurrence at the site of initial surgery during follow-up of 161–2,219 days (median: 976 days). These results suggest that resection of low-grade, relatively small MCTs with surgical margins proportional to the tumor diameter is a practical procedure with high success rates.     

Canine subcutaneous mast cell tumor: characterization and prognostic indices

Histologic grading schemes for canine cutaneous mast cell tumors (MCTs) were not developed for subcutaneous MCTs. Despite this, subcutaneous MCTs are currently categorized by many as grade II or higher. The aim of this investigation was to assess the pathology and clinical outcome for subcutaneous MCTs to provide a more accurate prognosis. Information on clinical outcome for 306 dogs was obtained from veterinarians and correlated with histologic features. Mean and median follow-up was 842 and 891 days, respectively (range, 3-2,305 days). Only 27 (9%) were confirmed as mast cell-related deaths. Metastasis occurred in 13 (4%), and 24 (8%) had local reoccurrence, even though 171 (56%) cases had incomplete surgical margins. Median survival time was not reached, and the estimated 6-month, 1-, 2-, and 5-year survival probabilities were 95%, 93%, 92%, and 86%, respectively. Dogs were euthanized or died as a result of local tumor reoccurrence, additional MCT development distant to the surgical site, or metastasis. Decreased survival time was linked to mitotic index (number of mitotic figures per 10 high-power fields), infiltrative growth pattern, and presence of multinucleation. Both univariable and multivariable analysis showed mitotic index to be strongly predictive of survival, local reoccurrence, and metastasis. The results of the study indicate that the majority of subcutaneous MCTs have a favorable prognosis, with extended survival times and low rates of reoccurrence and metastasis.     

Prednisone and Vinblastine Chemotherapy for Canine Mast Cell Tumor—41 Cases (1992–1997)

Forty-one dogs with mast cell tumors (MCTs) were treated with oral prednisone and injectable vinblastine (VBL), both in the adjuvant setting (23 dogs) and in dogs with gross disease (18 dogs). Adverse effects were noted in 20% (8/41) of the patients, usually after the 1st dose of VBL. Adverse effects were considered mild in 6, and severe, necessitating treatment discontinuation, in 2 (5%). Overall response rate in the evaluable dogs with gross disease was 47% (7/15), consisting of 5 complete responses and 2 partial responses. Median response duration was 154 days (24 to >645 days). As adjuvant therapy to incomplete surgical resection, prednisone and VBL conferred a 57% 1- and 2-year disease-free rate. Median survival time (MST) for the entire patient population was not reached with a median follow-up of 573 days; however, the MST for dogs with grade III MCT was 331 days, with 45% of dogs alive at 1 and 2 years. This is an apparent improvement over historical survival data employing surgery alone. Upon univariate analysis, significant prognostic factors (P < .05) for survival included presence of a locally recurrent tumor, presence of gross disease, argyrophilic nucleolar organizer region frequency, lymph node status, histologic grade, previous chemotherapy, and ulceration of the tumor. Similar criteria were significant when analyzed for time to treatment failure. Response to therapy was also predictive of survival in the gross disease group. Upon multivariate analysis, histologic grade (P = .012) and presence of a locally recurrent tumor (P < .001) were significant factors for survival.     

Principles of treatment for mast cell tumors

Mast cell tumors (MCT) are the most common malignant cutaneous tumors that occur in dogs. They are most commonly found on the trunk, accounting for approximately 50% to 60% of all sites. MCTs associated with the limbs account for approximately 25% of all sites. Cutaneous MCTs have a wide variety of clinical appearances. Histologic grade is the most consistent prognostic factor available for dogs. MCTs located at 'nail bed' (subungual), inguinal/preputial area, and any mucocutaneous area like perineum or oral cavity carry a guarded prognosis and tend to metastasize. MCTs usually exfoliate well and are cytologically distinct. The extent of staging procedures following fine-needle aspirate cytologic diagnosis is based on the presence or absence of negative prognostic indicators. Surgery is the treatment of choice for solitary MCTs with no evidence of metastasis. Reponses rates to chemotherapy, (partial response) as high as 78% have been reported, and preliminary evidence suggests that multiagent (prednisone and vinblastine) protocols may confer a higher response rate than single-agent therapy. MCTs are the second most common cutaneous tumor in the cat. There are two distinct forms of cutaneous MCTs in the cat. The more common form is the mastocytic form, and the less common is the histiocytic form. Unlike in the dog, the head and neck are the most common sites for MCTs in the cat followed by the trunk and limbs. Cats with disseminated forms of MCT often present with systemic signs of illness, which include depression, anorexia, weight loss, and vomiting. The diagnosis and staging of MCTs in cats is similar to that in the dog. As with dogs with cutaneous MCTs, surgery is the treatment of choice. Little is known about the effectiveness of adjunctive chemotherapy options for cutaneous MCTs. Adjunctive chemotherapy does not appear to increase survival times.