Tumors involving the heart occur relatively infrequently

Transcription

1 J Vet Intern Med 1999;13: Cardiac Tumors in Dogs: Wendy A. Ware and David L. Hopper A Veterinary Medical Database search from 1982 to 1995 identified 1,383 dogs with tumors of the heart from a total population of 729,265 dogs (0.19% incidence). Hemangiosarcoma (HSA) was the most common cardiac tumor identified. In the subset of dogs with specific histologic diagnoses, the number with HSA was almost 10-fold that of the 2nd most common tumor, aortic body tumor. Primary heart tumors were more common than cardiac metastases. When biologic behavior was noted, most heart tumors were classified as malignant. Cardiac tumors (excluding lymphoma) occurred most often in dogs between the ages of 7 and 15 years. In very old dogs ( 15 years), the frequency of cardiac tumors was the same or lower than that of the youngest age group. Tumors occurred with similar frequency in males and females, but the relative risk for spayed females was 4 times that for intact females. For HSA, spayed females had 5 times greater relative risk than did intact females. The risk for castrated males was slightly greater than that for intact males, which had 2.4 times the relative risk of intact females. Thus, neutering appeared to increase the risk of cardiac tumor in both sexes. Intact females were least likely to develop a cardiac tumor, whereas spayed females were most likely to develop a tumor. Twelve breeds had greater than average risk of developing a cardiac tumor, whereas 17 had lower risk. Key words: Aortic body tumor; Breeds; Cardiac; Dog; Heart; Hemangiosarcoma. Tumors involving the heart occur relatively infrequently in both animals and humans. 1 6 Primary heart tumors were recognized in humans as early as the 16th century, although the first recorded antemortem diagnosis was made in the 1930s. 5 Development of angiocardiography, echocardiography, and other imaging modalities has markedly increased the detection of cardiac tumors in people and animals. 5,7 11 Cardiac tumors occur both as primary and as metastatic lesions. In humans, the frequency of metastatic heart tumors has been estimated to be times that of primary cardiac tumors, which have a reported incidence of between and 0.19%. 5,12 14 This preponderance of metastatic over primary heart tumors also has been reported in the veterinary literature. 6 The true proportion of dogs with metastatic as compared with primary cardiac tumors is unknown, but reports describing primary cardiac tumors in dogs 4,7 11,15 49 are more numerous than those describing metastatic disease. 16,17,22,40,49 56 The most common histologic types of cardiac tumors in dogs are different from those in humans. About 75% of primary cardiac tumors in humans are benign and nearly 50% of these are myxomas (usually involving the left atrium). Other fairly common benign types of cardiac tumors in humans include lipoma, papillary fibroelastoma, and rhabdomyoma in children. 5,12 Only about 25% of primary cardiac tumors in people are malignant, and these usually are sarcomas (eg, angiosarcoma, rhabdomyosarcoma, fibrosarcoma). 5 In contrast, malignant hemangiosarcoma (HSA) is reported to be the most common cardiac tumor in dogs. 2,4,6,8,30,41,46,48,51,58 61 Almost all primary cardiac tumors in dogs involve the right side of the heart, especially the right atrium. 2,4,8,33 Aortic body tumors (ABT) also have been reported relatively frequently in From the Departments of Veterinary Clinical Sciences and Biomedical Sciences (Ware) and the Veterinary Diagnostic Laboratory (Hopper), College of Veterinary Medicine, Iowa State University, Ames, IA. Reprint requests: Wendy A. Ware, DVM, MS, Department of Veterinary Clinical Sciences, College of Veterinary Medicine, Iowa State University, Ames, IA Received February 3, 1998; Accepted April 27, Copyright 1999 by the American College of Veterinary Internal Medicine /99/ /$3.00/0 dogs. 7,22,25,31,32,34,37,42,43,45,47,49,57,62 69 ABT are tumors of chemoreceptor tissue located at the aortic root or heart base. Only sporadic cases of cardiac myxoma have been reported in dogs. 19,20,24,26 Occasional cases of ectopic thyroid or parathyroid tumors at the heart base, 7,11,26,40,44 pericardial mesotheliomas, 61,70 72 or other neoplasms 8 10,24,26 29,35,36,39,73 76 also have been reported. Some histologic types of cardiac tumors have been associated with certain breeds of dogs. 2,22,23,30,37,41,47,77,78 Depending on their anatomical location and associated hemodynamic disturbances, cardiac tumors cause a variety of clinical signs. Tumors that cause pericardial effusion and cardiac tamponade have been reported most often, and HSA of the right auricle, atrium, or ventricle and ABT account for the majority of these cases. 3,4,7,22,30,38,46,48,59,60,71,73,79,80 Associated clinical signs generally result from hemodynamic consequences of cardiac tamponade: restricted ventricular filling secondary to external cardiac compression, venous congestion (especially behind the right heart), and poor cardiac output. Arrhythmias also can contribute to hemodynamic compromise. 30,38,59 Some cardiac tumors do not cause pericardial effusion and these tumors include a variety of histologic types. 8 11,19,24 27,29,33,35,39,43,54 59,75 Such tumors can cause signs of congestive heart failure or low cardiac output by obstructing blood flow within the heart or proximal great vessels and by inducing arrhythmias. Neoplasms that extensively infiltrate the myocardium also can interfere with contractile function. 33,56 This study was undertaken to determine the incidence of cardiac tumors of all types in a large population of dogs and to characterize any associations between tumor occurrence and age, gender, reproductive status, or breed. In addition, the relative frequency of occurrence of common cardiac tumor types was examined for the subpopulation in which specific histologic diagnoses were reported. We also sought to identify any age, breed, or gender predilections for the most common tumors. The yearly occurrence rates of all cardiac tumors and common histologic tumor types also was evaluated for changes over time. Materials and Methods The Veterinary Medical Database (VMDB) at Purdue University was searched for accessions from January 1, 1982, through December

2 96 Ware and Hopper Fig 1. Approximate percentage distribution of the most common histologic types of cardiac tumors identified by a VMDB search. For 34% of heart tumors, a histologic diagnosis was not reported. 31, 1995, to determine the number of cardiac tumors of all types reported in dogs. The age, breed, gender, and reproductive status (intact, spayed, castrated) of affected animals was identified. Not all dogs diagnosed with cardiac tumors had specific histologic diagnoses reported to the VMDB, and such animals were given the generic diagnosis of tumor heart. Others had a more specific histologic diagnosis listed. All dogs identified with a cardiac tumor, regardless of whether a specific diagnosis was reported, are referred to here as the total tumor group. The relationships between the parameters listed above and tumor incidence were evaluated for the total tumor group and for the subgroups diagnosed with cardiac HSA, ABT, ectopic thyroid carcinoma (TCA), and cardiac lymphoma (LSA). A preliminary VMDB search done for the years also listed a summary of all diagnostic codes recorded for the dogs with cardiac tumors, in addition to the specific diagnoses indicated above. From this list, the percentage of benign compared with malignant and primary compared with metastatic heart tumors was estimated. The age groups used in this study were those defined by the VMDB with the exception that the 6 youngest age categories of puppies and dogs were combined into 1 group. Six nonoverlapping categories were used 4 years, 4 to 7 years, 7 to 10 years, 10 to 15 years, and 15 years. A small number of dogs were of unknown age. The reported incidences of total tumors, HSA, ABT, TCA, and LSA were evaluated by year to detect changes in incidence rate over time. The SAS statistical analysis programs (1990, version 6, 4th ed., SAS Institute, Cary, NC) were used to complete all data analyses. Comparisons of the relative distribution of tumors among the various groups were made using the FREQ procedure. The Pearson chi-square test 81 was used to evaluate the relative distribution of tumor incidence across age groups of dogs and years of the study. Within breeds, the Fisher exact test 81 (2-sided) was applied to 2 2 tables of counts to compare incidence rates of all (total) tumors in intact as compared with castrated or spayed dogs. The Mantel Haenzel estimator 81 was used to combine information across breeds and to compare the overall relative risk of developing a cardiac tumor between intact and castrated males and between intact and spayed females. Breeds with at least 6 reported cases of HSA or ABT were similarly evaluated. The Fisher exact test was used to compare tumor incidence rates for each breed (all sexes together) with the overall incidence rate for the remaining breeds. A statistically significant difference was defined as P.05. Results Fig 2. The percentage distribution of histologic types of cardiac tumors for the 66% of cases where a histologic diagnosis was reported to the VMDB. A variety of tumors with more specific diagnostic codes are grouped within the categories: epithelial-glandular, connective tissue, nerve tissue, muscle tissue, and epithelial-nonglandular. Cardiac tumors were diagnosed in 90 of the 194 breeds in the VMDB (729,265 dogs evaluated). This analysis included mixed-breed dogs. There were 1,383 dogs in the total tumor group (overall incidence 0.19%). Cardiac HSA was identified in 633 dogs, ABT in 69, cardiac LSA in 34, and TCA in 13. Small numbers of many other histologic types also were reported (Figs 1, 2) and accounted for about 12% of the total number of tumors. The specific histologic diagnosis was unknown in about 34% of cases. Based on review of the diagnostic codes from the earlier search ( ), 84% of 1,077 heart tumors were given behavioral codes indicating that the heart was the primary organ affected. Only 16% of cardiac tumors were coded as metastatic lesions. Of the primary cardiac tumors, 39% were coded tumor heart, and in almost all of these cases the presence or absence of malignancy was not determined. HSA was diagnosed in 46% of primary heart tumor cases and in almost all of these cases the behavioral codes indicated malignancy. ABT was diagnosed in 7%, LSA in 3%, and TCA in 1% of primary heart tumor cases. Fibrosarcomas accounted for about 1% and unspecified sarcomas for another 1% of primary heart tumor cases. Other primary cardiac tumors included occasional adenocarcinomas, mesotheliomas, and chondrosarcomas. Overall, 56% of primary heart tumors were identified as malignant and 2% as benign, but the presence or absence of malignancy was not established in 42%. Of all the metastatic heart tumors, 24% were coded tumor heart and were not further described. HSA originating in an organ outside the heart accounted for 34% of metastatic heart tumors, and LSA accounted for 3%. Metastatic adenocarcinoma was reported in 21% of dogs with secondary heart tumors. Other metastatic cancers included osteosarcoma (6%), mastocytoma ( 5%), and various other sarcomas ( 5%). It is unclear how many of the dogs with cardiac tumors also had pericardial effusion. In a preliminary VMDB search of dogs with cardiac tumors ( ), additional diagnostic codes also were listed. Based on review of these codes, at least 16% of the dogs with cardiac tumors also had pericardial effusion that was coded by the attending clinician. Cardiac tumors were not equally distributed across age groups. Figure 3 illustrates the percentage distribution of total tumors and the 4 most common histologic types. The relative age distribution was not the same for all tumor types evaluated. LSA occurred at an early age, whereas

3 Cardiac Tumors in Dogs 97 Fig 3. Age group distributions for all heart tumors together and for the 4 most common tumor types. HSA, ABT, and TCA occurred more frequently in dogs between 7 and 15 years of age. This age distribution pattern did not change when the data were subclassified by gender and reproductive status. There was no significant difference in the relative age distribution of HSA, ABT, TCA, and total tumor groups, but dogs in the total tumor group tended to be slightly younger than dogs in the other 3 groups. Dogs 15 years of age had a lower incidence of all tumor types. Slightly 49% of dogs with cardiac tumors were female (683), 50% were male (693), and 7 dogs with tumors were of unspecified gender. Gender distribution in the VMDB at the time of the search was 50.5% female, 47.6% male, 1.2% unknown gender, and 0.7% designated, as in litters. Using 2 2 tables and the Fisher exact test to compare total tumor rates for intact and spayed females within each breed, significant differences were found for the Australian Shepherd Dog, Boxer, English Setter, German Shepherd Dog, Golden Retriever, Labrador Retriever, Mastiff, Rottweiler, Scottish Terrier, Siberian Huskey, and mixed-breed dogs. The overall measurement of relative risk, adjusting for different tumor rates in different breeds (Mantel Haenzel), was 4.38 (95% confidence interval [CI] ) for spayed females, indicating that spayed females had a 338% greater risk of developing a tumor than did intact females. The comparison of tumor rates for intact and castrated males within each affected breed identified significant differences for the American Staffordshire Terrier, Bulldog, Collie, German Shepherd Dog, Rottweiler, Siberian Husky, and mixed-breed dogs. The Mantel Haenzel estimator of the overall relative risk was 1.63 ( CI) for castrated males, indicating that castrated males had a 63% greater risk of developing a tumor than did intact males. Results of marginal analyses that summed across all breeds agreed closely with these results for both genders. When the tumor rate of castrated males was compared with that of spayed females, there were differences found for the American Staffordshire Terrier and Collie, but the overall relative risk adjusting for different tumor rates in different breeds (0.91, CI) was not different between castrated and spayed animals. For intact dogs, significant differences were identified in the American Cocker Spaniel, Bulldog, Golden Retriever, and mixed breeds. The relative risk of a tumor in intact males was 2.44 times the risk in intact females ( CI). Separate analyses were done for HSA and ABT in breeds that had at least 6 tumor cases reported. Based on sample size, this number of tumor cases was sufficient to obtain reliable statistics. The numbers of TCA and LSA within individual breeds were too low to identify any significant differences. Breeds included in the analysis for HSA were Afghan Hound, American Cocker Spaniel, Boxer, Doberman Pinscher, English Setter, German Shepherd Dog, Golden Retriever, Irish Setter, Labrador Retriever, Miniature Poodle, Scottish Terrier, Shetland Sheepdog, Siberian Husky, and mixed breed. Using 2 2 contingency tables and the Fisher exact test to compare tumor rates for intact and spayed females, significant differences were found for the Afghan Hound, English Setter, German Shepherd Dog, Golden Retriever, Labrador Retriever, Siberian Huskey, and mixed-breed dogs. The overall measurement of relative risk, adjusting for different tumor rates in different breeds (Mantel Haenzel), was 5.33 ( CI) for spayed females. Using 2 2 tables and the Fisher exact test, no significant differences were found between intact and castrated males within any breed. Summary statistics yielded an overall relative risk of 1.55 ( CI) for castrated compared with intact males. A marginal analysis for each gender was in agreement with the above findings. Comparison of castrated males and spayed females with HSA indicated no overall difference in risk of HSA for castrated males and spayed females (0.84, CI). However, when intact dogs with HSA were compared, differences were found in several breeds: English Setter, Golden Retriever, Shetland Sheepdog, and mixed breeds. For intact dogs with HSA, the relative risk of tumor occurrence was 2.82 ( CI) for males compared with females. The analysis for ABT included Boxers, Bulldogs, German Shepherd Dogs, and mixed-breed dogs. Comparing spayed and intact females, the overall measurement of relative risk was 3.80 ( CI) for spayed females. There was no significant difference in risk of ABT for castrated and intact males (overall risk was 0.85, CI). There was no difference in risk between castrated males and spayed females, but for intact males the relative risk of ABT was 3.52 ( CI) times that for intact females. The incidence rate for all cardiac tumors taken together (total tumors) was evaluated across breeds. The rate for each affected breed was compared with the overall incidence rate for the remaining breeds using the Fisher exact test. Twenty-nine breeds had a significantly different incidence rate; the rate was higher in 12 breeds and lower in 17 breeds (Tables 1, 2). For breeds with higher tumor incidence rates, the reported tumor types are listed in Table 1, but the histologic type of tumor was not recorded in many cases and the actual prevalence of these specific tumors is unclear. Many of the breeds for which no cardiac tumors were reported had very few individuals entered into the VMDB. Breeds with at least 500 individual dogs entered into the VMDB but with no heart tumors reported are listed in Table 3. The incidence rates of HSA also were compared using the Fisher exact test (2-sided) among the 14 breeds in which at least 6 cases of HSA were specifically identified. This subset of 14 breeds contained 541 cases of HSA out of 413,750 dogs. Within this group, the Afghan Hound, American Cocker Spaniel, Doberman Pinscher, English Setter, German Shepherd Dog, Golden Retriever, Labrador Re-

4 98 Ware and Hopper Table 1. Dog breeds with high cardiac tumor incidence. Breed Saluki French Bulldog Irish Water Spaniel Flat Coated Retreiver Golden Retriever Boxer Afghan Hound English Setter Scottish Terrier Boston Terrier Bulldog German Shepherd Dog Incidence (SE) a (0.0060) b (0.0080) c (0.0084) c (0.0037) d (0.0004) d (0.0008) b (0.0017) d (0.0012) b (0.0012) d (0.0010) a (0.0009) d Tumors Total HSA ABT TCA LSA No. Dogs Relative Risk 95% CI , , , , , , , , HSA, hemangiosarcoma; ABT, aortic body tumor; TCA, thyroid carcinoma; LSA, lymphoma; CI, confidence interval. a P.001. b P.01. c P.05. d P triever, Miniature Poodle, and mixed-breed dogs had significantly higher incidence rates of HSA compared with the other breeds in this subset combined. Conversely, breeds with no significant difference in HSA incidence were Boxer, Irish Setter, Scottish Terrier, Shetland Sheepdog, and Siberian Husky. There were too few ABT to complete a similar subgroup analysis. Tumor occurrence rates for the total tumor group and for HSA, ABT, TCA, and LSA were evaluated over the years of reporting ( ) using the Pearson chi-square test. The rates for total tumors and HSA show a significant increasing linear trend across time (Fig 4). The rate for HSA appeared to decrease in after being relatively stable from 1987 to The rates of ABT also differed across years, being relatively higher between 1984 and 1987 and then declining. Cross-tabulation did not show significant nonhomogeneity of reported rates for LSA, although the rates of LSA tended to be slightly higher in , followed by a very low rate thereafter. The reporting rates for TCA were very low and did not change over time. Discussion Hemangiosarcoma (angiosarcoma, malignant hemangioendothelioma) is a highly malignant tumor reported to be more common in the dog than in other species. 4,17,30,77,78,82 The heart (especially the right auricle) is one of the most common sites for this tumor. Other common locations include the spleen, subcutaneous tissues, and liver. 4,16 18,30,51,77 Our results agree with other reports in which HSA was identified as the most common primary cardiac tumor in dogs. 2,8,58 HSA was the cardiac tumor most commonly reported to the VMDB, occurring almost 10 times as often as ABT. Although 34% of all the canine heart tumor cases did not have a specific histologic diagnosis reported to the VMDB, the proportion of HSA, ABT, and other tumors within this group probably was similar to that in the group with a histologic diagnosis reported. ABTs arise from chemoreceptor cells, which are sensitive to blood oxygen and carbon dioxide tensions and other factors. Chemoreceptor cells are involved in the regulation of respiration and heart rate. 22,47 Clusters of these cells are located near the aortic root (aortic bodies), carotid bifurcations (carotid bodies), and elsewhere (glomus pulmonale, glomus jugulare). 22 Neoplasms of chemoreceptor tissue (chemodectomas, nonchromaffin paragangliomas) in dogs most often develop in the aortic bodies rather than at other sites. 22,23,47 These tumors usually are locally invasive but sometimes metastasize. 23,25,32,34,37,49,57 Unless symptomatic pericardial effusion or dysfunction of surrounding structures results, they may be only an incidental finding. 42,45,49,58 Multiple chemodectomas in the same animal and an association with other endocrine tumors may occur. 23,31 There were few cases of TCA reported to the VMDB.

5 Cardiac Tumors in Dogs 99 Table 2. Dog breeds with low cardiac tumor incidence. Breed Shar Pei Chow Chow Maltese Dalmatian Toy Poodle Samoyed Chihuahua American Cocker Spaniel Collie Shih Tzu Dachshund English Springer Spaniel Pekingese Yorkshire Terrier Rottweiler Beagle Miniature Poodle Incidence (SE) No. Tumors No. Dogs a b c a d a a d (0.0001) b a d a c (0.0004) c a c a Relative Risk 95% CI 1 4, , , , , , , , , , , , , , , , , CI, confidence interval. a P.01. b P.001. c P.05. d P This finding is consistent with the existence of only sporadic literature reports describing these tumors. 7,11,26,40,44 Nevertheless, ectopic thyroid tissue within the mediastinum is reported to occur frequently in the dog. 83 The majority of heart tumors in people are reported to be metastatic. 5,13,14 This observation also has been made in the veterinary literature, 6,8,10,84 but convincing support for such a statement is lacking. The present study suggests that primary cardiac tumors are more common than metastatic tumors in dogs probably because of the prevalence of cardiac HSA in this species. Many different clinicians were responsible for assigning the diagnostic codes reported to the VMDB, and it is impossible to be certain that all HSA coded as primary cardiac tumors in this survey did actually originate in the heart rather than being metastatic. Furthermore, if cardiac metastases from other neoplasms were not specifically diagnosed and coded by the various clinicians, those cases would not have been detected in this VMDB search and the number of metastatic cardiac tumors would be underestimated. Most primary cardiac tumors were malignant, and this finding is consistent with previous veterinary reports and the preponderance of HSA. Based on the preliminary VMDB search, an estimated 16% of all cases had codes consistent with some type of pericardial effusion. This estimate is thought to be low in view of the prevalence of HSA and the common clinical association of pericardial effusion with HSA and ABT. Many clinicians may simply have not listed a diagnostic code for pericardial effusion, even if it was present, and instead only listed the code for the underlying tumor. The finding that HSA, ABT, and TCA occurred more commonly in dogs 7 years of age was expected. The middle-age to older distribution for all dogs with cardiac tumor taken together is reflective of the large percentage of HSA and other tumors that occur in older animals. This age distribution is in agreement with previous reports of cardiac tumors in dogs 4,16,17,23,47 and is consistent with the increased prevalence of many tumors types in older animals. How-

6 100 Ware and Hopper Table 3. Dog breeds with no reported cardiac tumors. More than 500 individuals in database Basenji Belgian Tervuren Bloodhound Blue Tick Coonhound Black and Tan Coonhound Toy Fox Terrier Giant Schnauzer Manchester Terrier Minature Pinscher Long Haired Dachshund More than 1,000 individuals in database English Cocker Spaniel Jack Russell Terrier More than 2,000 individuals in database Pug More than 5,000 individuals in database Pomeranian Fig 4. The yearly incidence rates for all heart tumors together and for the 4 most common tumor types across the years of the study. Linear trend lines for all tumors together (y 8E 05x ; R ) and for hemangiosarcoma (y 3E 05x ; R ) are shown. VMDB entries for 1995 and possibly 1994 were incomplete. HSA, hemangiosarcoma; ABT, aortic body tumor; LSA, lymphoma; TCA, thyroid carcinoma. ever, dogs 15 years of age were much less likely to be diagnosed with a cardiac tumor. Tumor occurrence in this very old group was less than or similar to (for HSA) the rate of occurrence in dogs 4 years of age. It is unclear from this study what genetic, environmental, or other factors tended to protect these geriatric survivors from the development of cardiac tumors (or other diseases), thus allowing them to reach an advanced age. LSA involving the heart occurred more often in younger dogs. In general, canine LSA has been reported to occur more commonly in middleaged to slightly older animals (median years of age). 85 In some previous reports, no differences were noted between males and females in the occurrence of cardiac tumors or specifically HSA. 4,30,41,60 In others, an increased incidence was noted in males 16 18,77 or at least there was a male bias. 22,23,37,47 In this study, when reproductive status (ie, neutered compared with intact) was not considered, the occurrence of total cardiac tumors and HSA was the same for males and females. Clear differences in tumor incidence were found however when intact and neutered animals of each gender were compared. The difference was especially pronounced in females. When all heart tumors were considered together across breeds, spayed females had 4 times the risk of developing a heart tumor as did intact females. This difference in risk also reached significance in 11 individual breeds, all except one of which had an increased (5 breeds) or average (5 breeds) risk of cardiac tumors and larger numbers of HSA cases reported. When HSA cases were evaluated separately across breeds, the relative risk for HSA in spayed females was 5 times that for intact females. In addition, the relative risk for developing ABT also was greater (by almost 4-fold) in spayed females than in intact females. Castrated males had only a slightly greater risk (1.6 times) of developing a heart tumor than did intact males. Likewise, most of the individual breeds in which differences were identified had an increased or average tumor incidence. The overall relative risk of cardiac tumor development was not different between spayed females and neutered males. Intact males however had 2.4 times greater relative risk than did intact females. Of the 4 breeds in which gender difference reached significance, Golden Retrievers had a high rate of HSA and Bulldogs had more ABTs. In both of these tumor types, the relative risk for intact males compared with intact females was even greater (below). We are unaware of any other reports identifying an effect of reproductive status on the incidence of cardiac tumors. In a previous report of splenic HSA in dogs however, an increased odds ratio in spayed compared with intact females was found. 82 It is unclear why intact dogs, especially females, had lower risk for cardiac tumors than neutered dogs. A protective effect of sex hormones, especially in females, may exist. The comparisons of gender and reproductive status for HSA cases were done in the 14 breeds with at least 6 cases identified. Six of these breeds also had a significantly higher overall incidence rate of cardiac tumors. Two of these breeds (American Cocker Spaniel, Miniature Poodle) had a lower incidence overall, but because of their popularity had sufficient numbers of HSA cases reported to be included in the study, as did the 6 breeds with average overall incidence rates. The increased relative risk associated with neutered status in females was greater than that in the total tumor group. This risk was apparent not only in 4 breeds with a significantly higher overall tumor incidence rate, but also in 3 breeds with an average incidence rate. For males, no individual breed differences were found across all breeds, but there was a slightly increased risk for castrated males. The relative risk of HSA was not different between castrated males and spayed females, but intact males were almost 3 times as likely as intact females to develop cardiac HSA. Neutering may increase the risk of cardiac HSA development in either gender. Conversely, intact reproductive status appears to provide some protective effect in females. Reproductive status was important for females but not for males in dogs with ABT. Spayed females had a 3.8 times greater relative risk of ABT than did intact females. There was no difference in risk between intact and castrated males or between castrated males and spayed females. Intact males however had 3.5 times the risk of intact fe-

7 Cardiac Tumors in Dogs 101 males. Several literature reports of ABT identify increased risk for male as compared with female dogs. 22,23,47 Our report indicates that the risk of ABT is similar for spayed females and all males, with intact females enjoying some protection. In this survey, 12 breeds were identified as having a significantly higher tumor incidence rate compared with all other breeds in the total tumor group. Several of these have been reported as prone to either HSA or ABT in previous studies. The German Shepherd Dog has been identified often as having increased risk for HSA, not only of the heart but also at other sites. 2 4,16 18,30,41,60,61,77,78,82 Previous reports of HSA (not limited to the heart) also have identified the Golden Retriever 30,61,78 and Poodle 17,30 as having an increased incidence. The Golden Retriever had a higher incidence rate of cardiac tumors than the German Shepherd Dog in this study; but Miniature and Toy Poodles had significantly lower than average incidence rates for all cardiac tumors together. Despite this, Miniature Poodles had a higher incidence of HSA alone (see below). The present study also indicates that other breeds have an even higher relative risk of cardiac tumors. The fact that some of these breeds are less popular (as indicated by the number of individuals in the VMDB) may account for their infrequent appearance in literature reports. For example, there were only 168 Irish Water Spaniels, 215 French Bulldogs, and 401 Salukis in the VMDB at the time of the search; but there were 32,940 Golden Retrievers and 37,872 German Shepherd Dogs. The majority of canine ABT reported in the literature have been in brachycephalic breeds, specifically Boxers and Boston Terriers. 22,23,31,34,37,42,47,57,63,64,67 69 In 1 study, a nonsignificant trend was identified toward increased risk of ABT in English bulldogs 22, an ancestral breed of Boxers and Boston Terriers. The present study determined these breeds to have a higher occurrence of all cardiac tumors evaluated together. The proportion of dogs of these breeds with a specific diagnosis of ABT, HSA, LSA, or TCA was fairly small compared to the total number of tumors in the breed (Table 1). Four of 4 Bulldogs but only 7 of 16 Boxers and 2 of 4 Boston Terriers were identified with ABT. Unfortunately, it cannot be determined how many of the dogs given the diagnosis tumor heart actually had ABT. Chronic hypoxia may stimulate development of chemoreceptor tumors in both dogs and humans, and this factor could explain the increased occurrence of ABT in brachycephalic breeds. 22,23,73 Not all dogs diagnosed with ABT however are brachycephalic. Conversely, 17 breeds in which cardiac tumors were reported to the VMDB had a significantly lower overall tumor incidence rate (Table 2). Many of these breeds were very popular and were well represented in the VMDB. The reason for the lower tumor incidence in these breeds is unknown. Over 104 breeds had no reported cardiac tumors. The majority of these breeds were represented by very few individuals in the VMDB. Thus, it is not certain that they truly had decreased risk. However, 14 breeds with no reported cardiac tumors (Table 3) had at least 500 individuals in the VMDB. These breeds probably do have reduced risk of cardiac tumor development. Although most of the breeds that did have cardiac tumors reported were represented by many individuals in the VMDB, 5 breeds (Bearded Collie, French Bulldog, Puli, Saluki, Irish Water Spaniel) were represented by 500 individuals. HSA accounted for a large proportion (69%) of the tumors with a histologic diagnosis. Consequently, it was of interest to further compare the incidence rates of breeds with at least 6 of these tumors identified. Analysis was limited to these breeds because statistical accuracy is uncertain with contingency table cells containing 5 animals. The test controlled for the number of dogs in the sample set, which was a select subset of the total number of dogs and tumors. Therefore, there were differences in the breeds identified with significantly increased HSA incidence compared with total tumor incidence. Breeds that had higher rates of HSA and total tumors included the Afghan Hound, English Setter, German Shepherd Dog, and Golden Retriever. Doberman Pinschers, Labrador Retrievers, and mixedbreed dogs had higher incidence rates of HSA but only average total tumor incidence rates. In the subset of breeds with 6 HSA cases, American Cocker Spaniels and Miniature Poodles had significantly higher HSA incidence despite having lower total tumor incidence. Likewise, the Boxer and Scottish Terrier had higher total tumor rates but nonsignificant HSA rates. These differences are related to the fact that the HSA subgroup represented only a portion of the whole population with heart tumors. It is unclear how much error was introduced into the HSA subset due to the fact that 34% of the total number of heart tumors did not receive a specific histologic diagnosis; these cases probably were not equally distributed among breeds. However, we suspect that the proportion of HSA cases in this 34% of total tumors is approximately 69% (as shown in Fig 2). During the years included in the study, there was a fairly significant increase in the reported incidence rate of all cardiac tumors together (Fig 4). There was a more modest increase in the HSA subset alone. Whether there was truly an increase in tumor incidence rates, especially during the earlier years of the study, or whether there was only increased recognition of these tumors is not known. In view of the fairly stable occurrence rate for the other histologic tumor types evaluated, the increase in rates for HSA and all tumors together may be real. An increase in incidence of HSA (hemangioendothelioma) of all body sites during the early to mid-1980s also was noted in a previous report. 16 The tumor rates for the last 2 years included in the present study must be viewed cautiously because data entry for 1995 and possibly 1994 was not complete at the time of the final VMDB search. The VMDB is only as complete and accurate as the information provided by individual clinicians whose cases are included. For example, many of the cardiac tumor cases in this survey did not have a histologic diagnosis. Thus, a smaller population was available for analysis of the different tumor types. The group of cases with no histologic diagnosis, is suspected to have been similar to that with specific diagnoses, but this assumption is not necessarily accurate. If a diagnosis or clinical finding was not coded, it was not retrievable from the VMDB. Thus, although some cases had additional information coded, such as presence of pericardial effusion, congestive heart failure, or arrhythmias, it cannot be assumed that cases without this information were not similarly affected. It would have been use-

8 102 Ware and Hopper ful to evaluate and summarize the clinical abnormalities accompanying various cardiac tumors in this large population. This task however would require review of the actual clinical records. The animals recorded in the VMDB were primarily from teaching hospitals and referral practices. As such, they may not accurately represent the entire population for each breed. In summary, the overall incidence of cardiac tumors in this large population of dogs was relatively small (0.19%). Most tumors involved the heart primarily, and only a small number were identified as metastatic lesions. Furthermore, of the heart tumors in which presence or absence of malignancy was determined, the great majority were malignant. About one third of the cardiac tumors in this study were not identified by histologic diagnosis. Of the two thirds with histologic diagnoses coded, HSA was the most common heart tumor. The next most common tumor was ABT, occurring at about 10% the rate of HSA. Most cardiac tumors occurred in dogs between the ages of 7 and 15 years, but dogs 15 years of age were affected less frequently than expected. Although the numbers of male and female dogs with heart tumors were similar, differences associated with reproductive status were found. For all tumors and for HSA and ABT evaluated separately, spayed females, castrated males, and intact males all were at greater risk than were intact females. For all tumors and HSA, castrated males had only slightly more risk than intact males. Twelve breeds had significantly greater risk for the development of heart tumors. Conversely, at least 17 breeds had lower risk. Acknowledgments We thank Alan Warble for assistance with Veterinary Medical Database searches and Haiyan Shu for assistance with statistical evaluation. References 1. Luginbühl H, Detweiler DK. Cardiovascular lesions in dogs. Ann NY Acad Sci 1968;127: Zook BC. Some spontaneous cardiovascular lesions in dogs and cats. 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