Effects of stage and number of tumours on prognosis of dogs with cutaneous mast cell tumours

Between 1997 and 1999, 280 dogs with mast cell tumours were identified, of which 59 (21 per cent) had multiple tumours. Follow-up data for survival analysis were available for 145 dogs with single tumours and 50 dogs with multiple tumours. There was no significant difference between the survival times of the two groups; the survival rates after 12 and 24 months were 88 per cent and 83 per cent, respectively, for the dogs with single tumours, and 86 per cent at both intervals for the dogs with multiple tumours. Eight of the dogs with single tumours had lymph node metastases (stage II disease) and these dogs had a median survival time of 431 days, whereas the 50 dogs with multiple tumours (classified as stage III disease) and the dogs with single tumours (classified as stage I disease) had not reached their median survival times. Golden retrievers appeared to be predisposed to developing multiple tumours in the population studied, with an odds ratio of 3.8. This study found no evidence that dogs with multiple tumours had different survival times than those with single tumours, although there was evidence that the presence of lymph node metastasis generally carried a poorer prognosis.     

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.     

Evaluation of minichromosome maintenance protein 7 as a prognostic marker in canine cutaneous mast cell tumours

Minichromosome maintenance proteins (MCMs) are sensitive markers of cellular proliferation and have been shown to be significant predictors of survival in several human malignancies. MCM7 was evaluated as a prognostic marker in canine cutaneous mast cell tumours (MCTs). MCM7 immunohistochemistry was performed and an index of MCM7-positive cells calculated in dogs with known outcome. The Receiver Operating Characteristics method was used to individuate the best cut-off value of MCM7 score as predictor of survival. Survival analysis and prognostic variables were analysed with statistical methods. Ninety-five dogs were included with 31 dying of MCTs. A value of 0.18 was used as cut-off value of MCM7 score as a binary variable. The median survival time for MCM7 score ≤0.18 was not reached at 3668 days, whereas for MCM7 score >0.18 was 187 days (log-rank test; P < 0.0001). In the multivariable analysis, MCM7 was significantly associated with survival after controlling for age, surgical margins and histological grade (hazard ratio 9.2; P = 0.001).     

Outcome following removal of canine spindle cell tumours in first opinion practice: 104 cases

O bjectives : To define the outcome of a cohort of canine patients with a histological diagnosis of spindle cell tumour of soft tissue managed solely by surgery in first opinion practice.
M ethods : Clinical details of 104 spindle cell sarcomas submitted to Finn Pathologists during the year 2000 were reviewed. Questionnaires were sent to the submitting veterinarians, requesting details about the tumour, surgery performed and ultimate outcome of the patient.
R esults : The method of surgical resection was described as marginal in 45 dogs (44·2 per cent). Excision margins of 3 cm or more were described in less than 10 per cent of cases. Tumours recurred locally in 29 dogs (27·9 per cent). Eighteen dogs (21·7 per cent) died of tumour-related causes. Most deaths were unrelated to sarcoma (50 dogs, 60·2 per cent) or unknown (15 dogs, 18 per cent). The median survival time was 1013 days. Tumour size, location or degree of surgical resection were not significantly related to survival or tumour recurrence. A palpable assessment of tumour invasion into underlying tissues was significantly associated with decreased disease-free interval (P<0·0001) and survival time (P = 0·0070).
C linical S ignificance : The results of this retrospective study indicate that many spindle cell tumours managed in first opinion practice exhibit a low-grade biological behaviour and may respond well to more conservative surgery than current recommendations advise.     

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.     

Deionised water as an adjunct to surgery for the treatment of canine cutaneous mast cell tumours

Medical records of 55 dogs with a diagnosis of cutaneous mast cell tumour were reviewed. Twenty-seven of the dogs were treated with surgery plus deionised water and the remaining 28 with surgery alone. A survival analysis was performed to determine whether deionised water, as an adjunct to surgery for cutaneous mast cell tumour, affected survival time or time to tumour recurrence. Dogs in which mast cell tumour recurred had a significantly shorter survival time compared with dogs with no recurrence (P=0.05), regardless of the method of treatment. A significant negative association between tumour recurrence and method of treatment (P=0.0097) and clinical stage (P=0.0223) was observed. Dogs treated with surgery and deionised water had a significantly shorter time to recurrence of their mast cell tumour (P=0.0113). Based on these results, deionised water does not appear to be beneficial in prolonging survival time or time to tumour recurrence for dogs with cutaneous mast cell tumours.     

Chlorambucil and prednisolone chemotherapy for dogs with inoperable mast cell tumours: 21 cases

O bjectives : To evaluate the response of measurable canine mast cell tumours unsuitable for other treatment modalities to a chemotherapy protocol comprising chlorambucil and prednisolone.
M ethods : Dogs bearing measurable mast cell tumours, unsuitable for treatment by surgery or radiotherapy, were treated with orally administered prednisolone and chlorambucil, and their responses assessed.
R esults : Twenty-one dogs were enrolled in the study; 13 had intermediate-grade mast cell tumour, six were high grade and two were diagnosed by cytology alone. Eight dogs had multiple tumours and 13 dogs had single tumours, and six dogs had lymph node metastases and no dogs had visceral metastases detected. Three dogs achieved complete remission, five achieved partial remission (overall response rate 38 per cent), nine had static disease and four dogs had progressive disease. Median progression-free interval for the eight responders was 533 days, and median survival time for all dogs in the study was 140 days. Progression-free interval and median survival time were not influenced by the age, sex, weight or neutering status of the patient, by the grade or stage of the tumour or whether the patient had single or multiple tumours. No toxicity was detected.
C linical S ignificance : Response and survival rates of inoperable canine MCT to chlorambucil and prednisolone are comparable to previously described protocols, with no apparent toxicity.     

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.     

Canine cutaneous neoplasms: prevalence and influence of age, sex and site on the presence and potential malignancy of cutaneous neoplasms in dogs from Zimbabwe

Histopathological examination was performed on cutaneous biopsies from 900 dogs with skin lesions from Zimbabwe, collected from 1996 to 2000. Clinical data were collected from medical records. Sixty per cent (540/900) of the cases were tumours and 40% (360/900) were non-neoplastic inflammatory or degenerative diseases. Thirty different histological types of tumour were diagnosed. The prevalence of epithelial, mesenchymal, lymphohistiocytic and melanocytic tumours was 39.4%, 44.4%, 7.4% and 8.7%, respectively. The 10 most common tumours, comprising 73.7% of all cutaneous neoplasms, were mast cell tumours, squamous cell carcinomas, perianal gland adenomas, lymphomas, benign melanomas, haemangiosarcomas, sebaceous gland adenomas, fibrosarcomas, lipomas and malignant melanomas. The prevalence of various neoplasms, age of affected dogs and sites of occurrence were similar to surveys in other countries, except that in Zimbabwe there was a greater prevalence of lymphomas and of tumours associated with increased exposure to ultraviolet light (squamous cell carcinomas, haemangiosarcomas and melanomas). For all classes of tumours the sex of the dog did not have any significant influence on the likelihood of developing a tumour. For a dog diagnosed with a tumour located on the trunk, the tumour was significantly more likely to be an epithelial tumour than a non-epithelial tumour The occurrence of melanocytic tumours on the trunk was significantly lower than at other sites. Lymphohistiocytic tumours were 10 times more likely to occur at multiple locations as opposed to single locations.     

Mandibulectomy and maxillectomy in the dog: long term survival in 100 cases

Mandibulectomy or maxillectomy was performed in dogs for the removal of 100 bone-involved oral tumours of varying histological type. These techniques provided excellent results when used for the excision of carcinomas achieving one year survival rates for basal cell carcinomas (acanthomatous epulides) and squamous cell carcinomas of 100 and 84 per cent, respectively. Mandibulectomy and maxillectomy were, therefore, considered to achieve good wide local excision and to be the techniques of choice for the management of oral carcinomas. Prognoses for sarcomas were, however, considerably poorer. There was a high incidence of local recurrence (32 per cent) and distant metastasis (27 per cent) and one year survival rates for fibrosarcomas, osteosarcomas and malignant melanomas were 50, 42 and 0 per cent, respectively. Mandibulectomy and maxillectomy were not considered to achieve radical local excisional margins in all cases and were inadequate as the sole form of treatment for sarcomas of the oral cavity. Mandibulectomy and maxillectomy may be useful, however, as part of a combined modality approach to oral sarcomas or may be justified as the sole therapy where adjuvant modalities are not available.     

Soft tissue sarcomas and mast cell tumours in dogs; clinical behaviour and response to surgery

OBJECTIVE: To characterise the types of canine soft tissue sarcoma and mast cell tumour treated surgically at the University Veterinary Centre, Sydney. To evaluate the success of surgical treatment of these tumours and identify variables predictive of local recurrence and survival. To establish whether conclusions drawn from previous international studies are applicable to the University Veterinary Centre, Sydney, dog population and vice versa. DESIGN: Clinical presentation and results of surgical excision of 54 soft tissue sarcomas and 70 mast cell tumours affecting the trunk and limbs of dogs at the University Veterinary Centre, Sydney, between 1989 and 2001 were reviewed retrospectively. RESULTS: Cross-bred dogs and Rhodesian Ridgebacks were at significantly greater risk of developing soft tissue sarcomas, and Boxers, Australian Cattle Dogs and Staffordshire Bull Terriers were at significantly greater risk of developing mast cell tumours than other breeds. Fine needle aspiration biopsy yielded a correct diagnosis in 62.5% of soft tissue sarcomas and 96% of mast cell tumours. Local recurrence was encountered after surgical excision in 7.4% of soft tissue sarcomas and 7.3% of mast cell tumours. Metastasis occurred in 6% of soft tissue sarcomas and 12% of mast cell tumours. The most significant risk factors for local recurrence were contaminated surgical margins (soft tissue sarcomas) and histological grade (mast cell tumours). Due to the low number of animals experiencing metastasis, no conclusions could be drawn about significant risk factors. CONCLUSIONS: Aggressive surgical management of soft tissue sarcomas and mast cell tumours is associated with a low incidence of local recurrence. The type, location and behaviour of mast cell tumours and soft tissue sarcomas in the population of dogs presented to the University Veterinary Centre, Sydney are similar to those reported by others.     

Vinblastine and prednisolone chemotherapy for surgically excised grade III canine cutaneous mast cell tumours

The effect of treatment with vinblastine and prednisolone chemotherapy in dogs undergoing only surgical excision of Patnaik grade III cutaneous mast cell tumours is reported. Potential explanatory variables were explored using Kaplan–Meier survival analysis with log‐rank tests. During a median follow‐up period of 429 days, the overall median survival time (MST) was not reached (lower 95% CI = 322 days). The 1‐year survival probability was 0.71 (standard error 0.1), remaining unchanged at 2 years. Secondary disease at presentation was an independent risk factor for survival (P= 0.045). The MST of dogs presenting with secondary disease was 322 days, with a lower 95% confidence interval of 142 days and a 1‐year survival of probability of 0.47 (standard error 0.19). Adverse effects were recorded in 6 of the 108 (5.6%) vinblastine doses given. This chemotherapy regimen is a well‐tolerated adjunct to surgery for grade III mast cell tumours and appears to prolong survival compared with that expected with surgery alone.     

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.     

Cytological comparison of fine-needle aspirates of liver and spleen of normal dogs and of dogs with cutaneous mast cell tumours and an ultrasonographically normal appearing liver and spleen

Staging of dogs with cutaneous mast cell tumours (MCTs) is an important diagnostic step. Aspiration of the liver and the spleen is often part of routine staging. This study cytologically compared mast cell numbers in fine‐needle aspirates of liver and spleen of clinically normal unaffected dogs with those of dogs with cutaneous MCT and an ultrasonographically normal appearing liver and spleen. The unaffected dogs (n = 32) were selected from humane society dogs, and the affected dogs (n = 51) were selected from hospital cases. There were no statistically significant differences in each of the parameters evaluated for the liver aspirates. For splenic aspirates, affected dogs showed significantly more mast cells per cluster (P = 0.04) and more isolated mast cells per slide (P = 0.03) compared with unaffected dogs. However, no clinically important difference existed between the unaffected and affected dogs; thus, routine aspiration of an ultrasonographically normal appearing liver and spleen of dogs with cutaneous MCT does not appear to be a clinically useful staging tool.     

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.     

Orthovoltage radiation and weekly low dose of doxorubicin for the treatment of incompletely excised soft-tissue sarcomas in 39 dogs

The efficacy and toxicity of orthovoltage radiation therapy and concurrent low doses of doxorubicin for the treatment of incompletely excised soft-tissue sarcomas in 39 dogs was investigated retrospectively. The 39 dogs had 40 soft-tissue sarcomas and received 51 Gy orthovoltage radiation in 17 daily 3 Gy fractions; they also received 10 mg/m(2) doxorubicin once a week administered intravenously one hour before the dose of radiation. The median follow-up time was 910 days. The tumours recurred locally in seven of the dogs, in five of them within the radiation field; the median time to their recurrence was 213 days (range 63 to 555 days). Six of the dogs developed a distant metastasis after a median time of 276 days (range eight to 826 days). The one-year and two- to four-year tumour control rates were 84 per cent and 81 per cent, respectively, and the one-, two- and three- to four-year survival rates were 85 per cent, 79 per cent and 72 per cent, respectively. Tumours with a mitotic rate of more than 9 per 10 high-power fields were significantly more likely to recur, and the dogs with such tumours survived for significantly shorter periods.     

Clinical staging for oropharyngeal malignancies in the dog

One hundred dogs bearing malignancies of the oropharyngeal region were examined over a three-year period and prospectively staged using the World Health Organisation TNM Classification of Tumours of Domestic Animals. Primary tumours were characterized by their large size or local infiltration (71 per cent, T3 status) and invasion into adjacent bone (60 per cent, Tb status). Regional lymph node metastasis was less common (17 per cent, N1b, N2b or N3 status) and distant metastasis was an unusual presenting feature (5 per cent, M1 status). The early Stage I and II tumours together accounted for 8 per cent of the total series whilst the more advanced Stage III group were by far the most frequent, representing 84 per cent. The remaining 8 per cent being classified as Stage IV because of extensive regional or distance metastatic deposits. Prognoses by stage showed actuarial survival rates at 12 months of 100 per cent for Stage I, 71 per cent for Stage II, 31 per cent for Stage III with no survivors in the Stage IV group. Survival rates for the major histological types were 44 per cent for the non-tonsillar squamous cell carcinoma, 22 per cent for the tonsillar squamous cell carcinoma and fibrosarcomas, 17 per cent for mastocytomas whilst none of the malignant melanomata survived 12 months.     

Comparison of mitotic index and Ki67 index in the prognostication of canine cutaneous mast cell tumours

Proliferation markers are commonly used for prognostication of mast cell tumours. The aim of the study is to compare the relative abilities of Ki67 and mitotic index to predict survival in the same cohort of dogs with cutaneous MCTs. Histological grade, mitotic index and Ki67 index were performed in all samples and clinical information was obtained by a follow‐up questionnaire. Ninety‐five dogs were included in the study with a median follow‐up of 1145 days. Survival times varied significantly between categories of histological grade, mitotic index and Ki67 index. Multivariable analyses showed that the risk of dying due to MCT was similar in dogs with increased Ki67 index [hazard ratio, HR: 3.0 (95% CI 1.3–6.8)] or increased mitotic index [HR: 2.7 (95% CI 1.1–6.5)]. In conclusion, both mitotic index and Ki67 index were able to independently differentiate MCTs with worse prognosis. This distinction is particularly meaningful in selecting intermediate grade MCTs that may benefit from more aggressive local or systemic treatment.     

Histological and immunohistochemical features of cutaneous mast cell tumor in six captive four-toed hedgehogs (Atelerix albiventris)

This report described the histopathological and immunohistochemical features of cutaneous mast cell tumor (MCT) in six hedgehogs. The hedgehogs presented single cutaneous mass with ulcer and crusting. Histologically, the neoplastic lesions were characterized by the proliferation of well-differentiated mast cells (3 cases), and atypical mast cells (3 cases) with one atypical histiocytic morphology. Immunohistochemically, tumor cells were positive for KIT and mast cell tryptase, and were negative for Iba-1. In well-differentiated MCT, all patients were clinically improved and survived more than 365 days after surgical excision, whereas an atypical histiocytic MCT showed aggressive behavior with re-recurrence, and the animal died 115 days after surgery. These findings suggest that, compatible with other animals, well-differentiated MCT has a better prognosis in hedgehogs.     

Imprint and brush cytology in the diagnosis of canine intranasal tumours

Fifty-four dogs with nasal tumours were included in this study. Based on histopathology, 52 tumours were malignant (36 epithelial and 16 mesenchymal) and two were benign (one oncocytoma and one pleiomorphic adenoma). Malignancy was significantly more frequently diagnosed by imprint cytology (81 per cent of the cases) than by brush cytology (56 per cent). Brush cytology was a significantly more sensitive technique in epithelial than in mesenchymal tumours, while the sensitivity of imprint cytology was not affected by the histological type. Brush cytology determined an epithelial origin in 88 per cent of epithelial tumours, and imprint cytology in 90 per cent. In mesenchymal tumours, the scores were significantly lower, the histological type being determined in only 20 per cent and 50 per cent, using brush and imprint cytology, respectively.