Submitted by: Patricia Shea, DVM
Vet Pathol 2019;56:43-49.
Grading cutaneous mast cell tumors in cats.
Sabattini S, Bettini G.
Cutaneous mast cell tumors (cMCTs) are the second most common skin neoplasm in cats; approximately 20% of skin tumors in cats are cMCTs. While validated histopathologic grading systems for canine cMCTs, such as the Patnaik 3-tier and the Kiupel 2-tier, have been available for years, grading of feline cMCTs has hitherto eluded pathologists. Most cMCTs in cats are benign and curable by complete surgical excision, but a minority of these tumors are aggressive and can metastasize to local lymph nodes, be associated with visceral mast cell neoplasia, or become a part of disseminated cutaneous disease. The goal of these authors was to create a basic grading system for feline cMCTs that would assist in the identification of those neoplasms that are likely to demonstrate aggressive biological behavior.
In this retrospective study, cases of surgically excised feline cMCTs in which the patient had available clinical and follow-up information were obtained from the medical database of a veterinary medical teaching hospital. Those animals with multiple cMCTs were only included in the study if all nodules had been removed surgically and were available for histopathologic evaluation. The 63 cases that were ultimately included in the study were divided into two groups: Group 1 (n = 48; 76% of animals) and Group 2 (n = 15; 24%). Group 1 comprised those cats who were alive and free of MCT-related diseases 1000 days after surgery. The second group of 15 cats had at least one of the following criteria associated with their cMT disease: (1) lymph node metastasis confirmed histologically or cytologically; (2) microscopically confirmed visceral mast cell neoplasia following removal of the cMCT; (3) onset of microscopically confirmed disseminated cutaneous mast cell disease, represented by > 10 nodules. Those cats whose cause of death was uncertain or who died from causes unrelated to mast cell neoplasia prior to 1000 days post-surgery were excluded from the study.
Group 1 cats included 40 domestic shorthairs, 3 domestic longhairs, and one each of Ragdoll, Siamese, Persian, Maine Coon, and Chartreux breeds. Males accounted for 26 of these animals, and there were 22 females. Mean age of the group 1 cats was 8.5 +/- 3.8 years, and in 88% of these animals, the MCTs were single nodules. The majority of the cMCTs in Group 1 were on the head (n= 30); 20 were on the trunk, and 7 were found on the limbs. Median diameter of the largest cMCT on the animal was 1 cm, and clean surgical margins were found in 39/48 (81%) of the animals, while infiltrated surgical margins were present in 9 (19%). Almost all of the Group 1 patients (44/48; 92%) were treated with surgery only, while 3 of the cats also received corticosteroids and one was given toceranib.
In Group 2, there were 11 domestic shorthairs, 2 Siamese, one Turkish Angora, and one Chartreux; there were 4 males and 11 females. The mean age in Group 2 was 10.6 +/- 3.5 years. Single nodules were present in 12 of the cats, while the other three had 2 nodules. In this group, 2 of the tumors were present on the head, 11 on the trunk, and 5 on the limbs. Median tumor diameter was 2.5 cm, and surgical margins were clean in 11 cases (73%) and infiltrated in 4 animals (27%). Three of the cats in this group had histologically confirmed regional lymph node metastases at the time of diagnosis, and two more were found to have nodal metastasis later on. More of these cats (n =8; 53%) received additional treatment than did Group 1 patients: mastinib, toceranib, lomustine, vincristine, each in one patient, and corticosteroids in 6 animals. Over half of the Group 2 cats (n =8; 53%) developed cutaneous disseminated MCT neoplasia subsequent to initial cMCT excision (median 141 days post-initial surgery). Splenic MCT was ultimately diagnosed in 9 Group 2 cats (60%) within a median time of 340 days post-initial surgery).
Of the 15 group 2 cats, 14 either died or were euthanized due to mast cell neoplasia. Median overall survival time in this group was 349 days. n the case of Group 1, 34/48 (71%) were alive with a median follow-up time of 1317 days. Fourteen (29%) of the group 1 animals died of causes unrelated to mast cell neoplasia, after median overall survival time of 1412 days.
Histologic parameters evaluated in the 63 cases of feline cMCTs were growth pattern (compact nodular or diffuse), subcutaneous invasion, histologic subtype (well-differentiated, pleomorphic/well-differentiated, or atypical/poorly granulated), nuclear: cytoplasmic ratio, nuclear pleomorphism, nucleolar prominence/chromatin clusters, anisokaryosis, multinucleated cells, pyknosis/karyorrhexis, mitotic count, neoplastic emboli, eosinophils, lymphoid aggregates, and margin status.
Results of the study demonstrated that those tumors with aggressive biological behavior were more likely to be larger (> 1.5 cm) and were rarely located on the head. Group 2 (biologically aggressive) tumors had histological characteristics such as subcutaneous invasion, irregular nuclear shapes, prominent nucleoli or chromatin clusters, presence of pyknosis or karyorrhexis, higher mitotic counts (>5 mitotic figures per 10 high-power microscopic fields), and presence of vascular emboli and lymphoid aggregates.
The grading system developed by the study classifies feline cMCTs as high-grade if they had more than 5 mitotic figures per 10 high-power fields on histology, and also met at least two of the following three criteria: tumor diameter > 1.5 cm, irregular nuclear shape, and nucleolar prominence/chromatin clusters. All of these parameters were found to have statistically significant odds ratios supporting a diagnosis of high grade MCT in a cat. In those study subjects having multiple cMCTs (n = 9; 14%), tumors from the same animal all had similar morphology and the same grade. Based on the grading system proposed in this paper, 48 (76%) of the cats had low-grade cMCTs and 15 (24%) had high-grade cMCTs.
Only one of the Group 1 cats had a high grade cMCT based on the proposed grading system. In Group 2, only one patient did not have a high grade cMCT. The latter cat was the only Group 2 patient still alive at the end of the study, all of the rest having died or been euthanized due to mast cell neoplasia.
Limitations of the study were noted by the authors. Their proposed grading system for feline cMCTs predicted survival time but not progression-free interval based on histologic grade. As some cats can develop multiple cMCTs throughout life, it cannot be assumed that subsequent tumors are of the same grade as the initial one(s), and these newer nodules need to be graded as well. Also, because uniform staging criteria for feline MCTs do not exist, splenic MCT or other visceral involvement at the time of surgical excision of the cMCT(s) in the 9 study cats who were later found to have splenic MCTs, cannot be excluded. Only a small number (n = 6) of atypical cMCTs, 4 in Group 1 and 2 in Group 2, although correctly graded in the presently proposed system, were available for evaluation in this study, and more of these atypical feline cMCTs would need to be studied in order to draw conclusions as to the applicability of this grading system to atypical and pleomorphic subtypes of cMCTs in cats.
J Vet Cardiol 2020;30:77-91.
Atenolol use in cats with subclinical hypertrophic cardiomyopathy: a double-blind, placebo-controlled, randomized clinical trial of effect on the quality of life, activity, and cardiac biomarkers.
Coleman AE, DeFrancesco TC, et al.
When hypertrophic cardiomyopathy (HCM) is detected in a feline patient with no clinical signs, there is always a concern that the condition will progress into clinically significant heart disease and eventually into congestive heart failure. Therefore, although subclinical HCM does not always progress to significant disease, interest in therapies that may control or resolve it is warranted. However, medicating cats on a consistent daily basis for life without sufficient evidence-based rationale is needlessly stressful for both owner and patient.
The use of atenolol in HCM, the most common primary cardiomyopathy in cats, is characterized by echocardiographic evidence of left ventricular concentric hypertrophy and fibrosis, which in turn impairs ventricular filling during diastole. Up to 30% of cats may have HCM. The average age at diagnosis of HCM is 6 years, but HCM can be first identified in cats as young as 6 months of age. The diagnosis of HCM excludes other diseases or conditions that may be associated with left ventricular wall thickening, such as hyperthyroidism, systemic hypertension, subaortic stenosis, acromegaly, and dehydration.
In this study of 59 client-owned cats, 32 of whom had subclinical HCM and 27 of whom were enrolled as healthy controls, quality of life (QOL) and quantitative accelerometer-based activity measurements, as well as cardiac biomarker (cardiac troponin I and N-terminal proBNP) concentrations, were evaluated prospectively in all subjects. The QOL measurements were derived from a questionnaire completed by the cats’ owners. Following treatment with atenolol on 16 of the cats with subclinical HCM and placebo on the other 16 asymptomatic HCM patients, the effects of atenolol therapy or placebo on the same parameters was recorded.
No difference in accelerometer-based activity scores was found between the healthy controls and the cats with subclinical HCM, but the owner-assessed activity of daily living scores for the HCM cats was lower than in the control group. The cats with subclinical HCM also had significantly higher cardiac troponin I and NT-proBNP levels, and significantly more cardiac arrhythmias than those in the healthy control group.
The cats with HCM received either oral atenolol at 6.25 mg/cat q 12 hours or a placebo for 6 months. No variability of atenolol dosing was attempted based on the severity of echocardiographic findings, body condition, or weight. When the HCM patients were rechecked 6 months after beginning treatment, those cats receiving atenolol demonstrated no significant change in their echocardiographic findings, QOL scores, accelerometry activity measurements, or systemic blood pressure. This subgroup did, however, have lower heart rates and less intense heart murmur grades than the HCM cats receiving placebo.
At the dosage used in this study, atenolol therapy had no effect on the owner-assessed QOL or activity levels of cats with subclinical HCM, and the authors concluded that atenolol therapy showed no benefit in symptom reduction in cats with subclinical HCM.