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    A Descriptive Review of Cardiac Tumours in Dogs and Cats - Enhanced Reader

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    Keywords cardio tumours ats chematharapy. dogs. radiotherapy, surgery Conespondence address: ETreggi Small ima Teaching Hospital School of Veterinary Science University of Liverpool Neon Uc ema ‘etreggiriegmsileom Review Article DOK: 10.1111/ve0.12167 A descriptive review of cardiac tumours in dogs and cats E. Treggiari, B. Pedro, J. Dukes-McEwan, A. R. Gelzer and L. Blackwood Small Animal Teaching Hospital, School of Veterinary Science, University of Liverpool, Neston, UK Abstract Cardiac tumours are uncommon in the canine and feline population and often an incidental finding, Common types include haemangiosarcoma (HSA), aortic body tumours (chemodectoma and pparaganglioma) and lymphoma, These neoplasms can cause mild to severe life threatening clinical signs that are independent ofthe histological type and may be related to altered cardiovascular function or local haemorthage/effusion into the pericardial space. Cardiac tumours may require symptomatic treatment aimed at controling tumour bleeding and potential arrhythmias, and other signs caused by the mass effect. Additional treatment options include surgery, chemotherapy and radiotherapy. For all medical therapies, complete remission is unlikely and medical management, beyond adjunctive chemotherapy in HSA, requires further investigation but combination chemotherapy is recommended for lymphoma. The im of this report isto summarize and critically appraise the current literature in a descriptive review. However, interpretation is limited by the lack of definitive diagnosis and retrospective nature of most studies. Introduction Cardiac tumours are uncommon inthe canine pop: ‘lation. Several small studies report an incidence between 0,12! and 4.339%? while a larger retrospec: y* reported 1383 dogs with tumours of the heart from a total population of 729.265 dogs (0.19% incidence) in a veterinary medical database tive stu ‘These neoplasms occur most frequently in middle age to older dogs, with the exception of lymphoma, which may also affect younger patients. ‘The aim of this report is to summarize and criti= cally appraise the current literature in a descriptive review. However, interpretation is limited by the lack of definitive diagnosis and retrospective nature fof most studies. ‘The most common type of cardiac tumour is hhaemangiosarcoma (HSA, 69%). In addition to HSA, the following tumours are commonly reported: aortic body tumours (chemodectoma and paraganglioma),** Iymphoma® and ectopic 247-* Less frequently, sev eral other types of tumours are documented: thyroid carcinoma, (2015 Jo key Sons ted melanoma, mast cell granular cell tumous!! coma! undilferentiated sarcoma of presumptive myofbroblastic origin. fibroma fibrosarcoma rhabdomyoma.® rhabdomyosarcoma,” leiomyoma adenoma," blastoma,* thyroid tumour mesothelioma,2-# myxosar- smesenchymoma! leiomyosar- coma." chondrosarcoma,*®* osteosarcoma,’ paraganglioma,™ peripheral nerve sheat tumour.” hamartoma!” and lipoma.‘!~® Furthermore, single cases of valvular osteosarcoma, valvular yxosarcoma'® and valvular metastasis of dissem- inated histiocytic sarcoma® are deseribed in the Iiterature Cardiac tumours ean be either benign or malig- nant (and primary or secondary).’* Reports regarding the rate of primary versus secondary tumours in canine patients are contradictory: when retrospectively reviewing a veterinary medical database, Ware and Hopper reported that most of the tumours identified in the canine heart were primary (84%) and only a 16% were thought to be a 274 E Tieggiarietat ietastaic.\” On the other hand, when Aupperle ct al, reviewed necropsy findings with histological analysis, they reported cardiac tumours in 41% of the study population, and of these most were metastatic (69% metastases, 31% primary)” In this study, metastases were found in the heart in 346% ofthe dogs with malignant neoplastic disease, which is comparable to. humans where cardiac retaslases are more common than primary car diac tumours?” The difference between the two \eterinary studs likely reflects the diferent study populations the Ware study® cases were identified from a database search for cardiac tumours’ and only two-thirds ofthe included cases had histolog ical casification. Additionally, metastatic disease ‘may have been coded in the database asthe primary diagnosis, not asa cardiac tumour In the necropsy study.” clinically silent cardiac metastases are likely to have been identified, and in fact reports that cardiac metastases were not suspected based oon clinical signs in any case {A study assessing location of cardiac neoplasms dlocuments that most primary cardi tumours are located in the right atrium/right atrial appendage (63%), followed by heart base (18%) and let ventricle (9%)7 However, the data are derived mainly from post-mortem evaluations, thus pos- sibly reflecting a bias towards the more aggressive or malignant types of cardiac tumours, includ- ing those that cause pericardial effusion or more severe clinical signs and patient death, Most right striafauricularmasses, likely HSA, show malignant tumour characteristics including the tendeney to ietastasze, regardless of whether they occur with or without pericardial effusion. In contrast, heart base masses such as chemodectomas often display more benign behaviour, with a low incidence of metastasis and variable occurrence of pericardial effusion; indeed some dogs may be completely asymptomatic. Thus tumours ofthis type are likely to be underestimated by post-mortem-based stud ies, Other reported heart base tumours include adenomas and adenocarcinomas, with adenomas most common: these would similarly tend to be underrepresented in a necropsy study: Unlike primary tumours, most metastatic lesions reported by post-mortem (75%) are found in the inner third of the left ventricular free wall, the 102015 Jon Wty & Sons, Veternary and Comparative Onooay interventricular septum, or both. Only 25% of ‘metastatic tumours are found in the right atrium, right ventricular wall or both 7° ‘Ware et a, reported that the breeds with higher incidence of cardiac tumours re German Shepherd dogs (GSD), Golden Retrievers, Boxers, Bulldogs, Boston Terriers, Scottish Terriers, English Setters, Afghan Hounds, Flat-Coated Retriever, Irish Water Spaniels, French Bulldogs and Salukis.® Breeds specifically recognized to be at increased risk of developing cardiac HSA (as well as splenic HSA) are GSD and Golden Retrievers Brachycephalic dogs are predisposed to aortic body tumours, in particular Boxers; this was thought to be associ- ated with chemoreceptors stimulation caused by chronic hypoxia*™, however, this hypothesis has never been proved and instead a genetic compo- nent is more likely." Secondary cardiac tumours can affect any bred. ‘Most common canine tumour types HSA HSA is the most common cardiae tumour in dogs Diagnosis is often presumptive, and relies fon imaging findings and anatomical location HSA commonly presents as a mass involving the right atrium (Fig. 1C) and the right ateial appendage. In the authors’ experience, HSA also presents infrequently as a ditlse infiltrative tumour (Figs. 1D and 2B). Atrial HSA can present as a solitary tumour, or occur concurrently with a splenic mass." The rate of concurrent right atrial masses in dogs that present to the veterinarian for investigations of splenic HSA varies between 8.7 and 25%," therofore echocardiography may be indicated in these cases as part of the staging process. On the other hand, the rate of concurrent splenic HSA in dogs that present tothe hospital for cardiac HSA has been reported as 29%, Interest- ingly, 42% of these dogs had non-splenic metastases at presentation: it is therefore unclear whether these patients have two primary tumours, or one primary and a metastatic lesion in the spleen. In addition, the risk for non-splenic metastasis appears to decrease with age, but an age-related reduction in the frequency of concurrent splenic and cardiac HSA is not documented. 15,2, 273-208 Cardiac tumoursin dogs andcats 275 Figure 1. Eshocand anceof cat aphic ap aed chem unde heart b ‘optimize the small an mass. Most Ii roan. Calo Showing 3 smal and milly heer this mass revealed fine-needle aspirates of thi ms Diagnosis is very rarely attempted by means of biopsy and/or cytology, because of the perceived risks of non-representative sampli complications. Su ant chemother apy have been described in the management of atrial HSA, with adjuvant chemotherapy. being considered the most effective treatment in these Lymphoma Lymphoma involving the heart and surround. ing structures is infrequently reported in dogs Primary’ cardiac Iymphoma is defined in human medicine a affecting the heart, the Iymphor pericardium or both. According to the World ealth Organization (WHO) criteria for staging of in dogs, cardiac lymphoma with peri cardial effusion is classified as stage V (extranodal ted dost the base ofthe i ight parasternal ong axis four chamber view, modified to oma. (3) right parasternal short axis view at the level of the heart bas, mealfed to sp iferetial diagnosis ch ight trim and ght ventricle shoving amass arising fom the atm and extending int the ight atro-ventriculse inano sulbstage b n other than liver or spleen (with clinical signs). This stage of lymphoma may be subject to worse prognosis overall, but there is no specific daa for the cardiac form. The largest study on cardiac lymphoma evaluated outcome in 12 dogs, of which 5 were treat with multi-drug chemotherapy. In that report, eardiae lymphom, ‘was diagnosed using cytology of the pericardial effusion in eight dogs; immunohistochemistry was available for just three dogs, confirming T-cell ot and B-cell origin in os chemotherapy either P followed by partial pericardiectomy:® but median ardiocentesis alone or afer pericardiocentesis survival times (MST) were short (157 days). One of the five dogs also received adjunctive radiation therapy, Seven dogs did not receive any treatment. 276. E-Tieggiatietal A Figure 2. (A) Post-mortem appearance Aortic body tumours (chemodectoma/paraganglioma) Aortic body tumours can potentially arise from any anatomical site, although chemodectomas set to be the most common type, occurring in the wall of the ascending aorta at the level of the heart base. Chemodectomas are non-functional tumours of paraganglial cells and therefore believed to be essentially benign with low metastatic potential (Figs. 14,B and 2A). Conversely, paragangliomas arise from paraganglil cell located within the atria along the root of the great v sels and derive from the visceral autonomic ganglia. Extra-adrenal paragangliomas that are functional and secr catecholamines are usually omaffin positive and have been termed chrom fin paragangliomas or -ochromocytomas."* The current veterinary literature on this type of neoplasn limited to ease reports." 4 paraganglioma in an intracardiac location was identified at necropsy in the right atrium of a GSD which presented with signs of depression and anorexia."* Successful surgical excision is described, resulting in a survival time (ST) of a left atrial paraganglioma years with no adjuvant treatment. A functional chromaffin paraganglioma in the right atrium »chemodsctoms atthe eel ofthe heart hase and surrounding the sorta (8) Post mortem appearance of a cifise hasmangiosaroms, Roth timour types have been confirmed om histo thology was reported in a S-year-old Labrador that pre sented with ascites secondary to caudal vena cava obstruction: biopsies obtained through a left jugular venotomy were consistent with a new: roendocrine tumour, most likely chemodectoma However, due to the dog’ clinical signs at the time of biopsies (transient hypertension and atrial fibrillation), a functional paraganglioma was sus- pected, This dog was euthanized hence no further ‘outcome information was available, but electron microscopy showed granules within the cytoplasm of the neoplastic cells, hence supporting the suspicion of functional tumour. A similar report has described a case of a functional para glioma which stained positive for chromogranin indicating a neuroendocrine origin, Intracardiac metastases of an aortic body tumour have also been described in one dog,® but metastases from these lesions seem uncommon. Rhabdomyoma and rhabdomyosarcoma ‘The exact histogenesis of rhabdomyoma is and whether cardiac rhabdomy- coma is a true neoplasm or a hamartoma is still a controversial issue in the medical literature, In humans, cardiac rhabdomyomas are reported to regress spontaneously* Interestingly, a cardiac shabdlomyoma has been reported ina young Beagle (© months old," in which no signs of cardiac com promise were founds inthis case the tumour was an incidental finding on necropsy and stained positive for Periodic Acid Schiff (PAS) and desmin. The same tumour type has been reported in an older dog (6 years old), associated with chylothorax.” Malignant muscle tumours are also described. A shabdlomyosarcoma was described ina GSD involv: ing the right atrium and the right ventricle, causing right-sided heart failure (pleural, pericardial and abdominal effusions):* The dog was euthanized after the mass was found on echocardiography and diagnosis confirmed at the time of necropsy. Another rhabdomyosarcoma was diagnosed in a Labrador Retriever with pericardial effusion. on biopsies obtained using thoracotomy.® One case report in a Great Dane witha primary cardi rhab- domyosarcoma, demonstrated involvement of the heart, lungs, diaphragm, liver, kidney and greater ‘omentum, confirming that this tumour type has the potential to metastasise Clinical signs Cardiac tumours can cause mild to severe, life-threatening clinical signs, or just bean inciden- tal finding* The clinical signs caused by cardiac tumours are independent of the histological typet and may be related to altered cardiovascu- lar funetion caused by the mass effect ox, more commonly, local haemorrhage/effusion into the pericardial space. Cardiac or pericardial tumours are responsible for most of the pericardial effu- sions documented in dogs (up to 60%), with HSA being the most common cause, followed by ‘mesothelioma and aortic body tumours.” Clinical signs associated with pericardial effusion secondary to cardiac neoplasia are not specific, but similar to those caused by idiopathic pericardial effusion. Pericardial effusion can result in right atrial or even right ventricular tamponade and therefore cause decreased pre-load and compromised car- diac output andor right-sided congestive heart failure! Clinical signs may include acute collapse, exercise intolerance or lethargy, and on physical examination there may be muifled heart Cardiac tumoursin dogs and cats 277 sounds, tachycardia, pulse deficits, pale mucous membranes, weak femoral pulses ascites, tachyp- noea/dyspnoea or increased abdominal effort, subcutaneous oedema, jugular venous distension, jugular pulsations, positive hepatojugular refluy, ‘weight loss and even vomiting.” Dogs can also present with chylous effusions, citherin the pleural? or pericardial space.” Cranial vena cava syndrome can be observed in cases of heart base masses compressing the cranial. vena. cava. Syncopal episodes can also occur in cases of right ventricular outflow tract obstruction”! Occasionally, signs of left-sided congestive heart failure can be present due to the location ofthe tumous, which can obstruct left ven: tricular inflow. Sudden death is also reported, not only most likely related to rupture of the tumour with haemorrhage and/or cardiac tampon- ade, butalso potentially secondary to arrhythmias? Tachyarrhythmias (mainly ventricular arthyth- mias either due to the primary cardiac mass or associated with splenic/hepatic masses) oF brad= yarthythmias [eg. third degree atrio-ventricular block (AVB}"4) have been described. Aupperle etal. reported that in dogs with metastatic cardiac tumours, the clinical presen- tation and symptoms cortelated mainly with the primary extea-cardiac tumour: cardiac metastases ‘were not suspected ante-mortem in any case. Diagnosis History and physical examination may help in the diagnostic process, although cardiac tumours may produce no vert abnormalities on routine clini- cal examination, unless associated with pericardial effusion (as detailed above) Cardiac masses can be difficult to detect and even aller detection obtaining definitive diagnosis ‘may be challenging. In the clinical setting, masses from extra-cardiac locations are routinely sampled to achieve a cytological or histological diagnosis fr as part of the staging of an oncologic condition, ‘Whenever feasible, cardiac masses may also be aspi- tated as this will provide more prognostic informa tion and allow specific treatment (Fig. 3). Sampling of cardiac masses is not a routine procedure, mainly given the potential risk of arrhythmias and (©2015 Jon Wey & Sons Li Veterinary and Compraine Oncology 18.2, 273-288 278 E Tieggiaretat. ane e Le ES] Figure 3. Cytological features of cantie tumours obtained by fine needle aspiration, Diff quick stan. A, Bs chemodectoma, [Note the naked nucle suggesting a neuroendocrine origin. Marked anysokariosis sao visible (magnification, 10030)-C, De oemangiosarcoma, Numerous mesenchymal alls on a background of eythrocytes are visible in gure C (magnifiation 20 >A detl of the mesenchymal clls with basophilic and vacuolated ytoplasm i shown in figure D (magnification, 100) hhaemorthage. However: in the authors’ experience, this procedure is relatively safe and fine-needle aspirates seem to have a reasonable diagnostic accuracy (unpublished data; manuscript under review). Transvenous endomyocardial biopsies?" ”* and open chest or thoracoscopic biopsies” can also be performed in selected patients and can provide a histopathological diagnosis (Fig. 4). ‘An electrocardiogram may be used as a diag- nostic tool, Cardiac tumours can cause pericar- dial effusions and be associated with low-voltage QRS and electrical alternans. In addition, conduc- tion disturbances" or arrhythmias (either tachy- or bradyarshythmnias) can also be detected **”? How- ever these findings are not specific for the presence of a cardiac neoplasm. ‘When pericardial effusion is present, cytology should be performed to try to distinguish benign from malignant pericardial effusions, or identify what type of cardiac neoplasia is present. A study evaluating the diagnostic utility of pericardial fluid analysis reported frequent false-positive (13%) and false-negative (749) results.” Its utility is variable {©2015 Jot Wily & Sons, eteinaryond Comparative Oncology. depending on the tumour type, and there is an improved diagnostic yield from effusions with a packed cell volume (PCV) of less than 109%. Mac- Gregor et al diagnosed cardiac lymphoma in 7/12 cases by means of pericardial fluid analysis pos- sibly because samples of lymphoid tumours are usually associated with a higher cellolaity and ‘more likely to be exfoliative and less haemorrhagic. ‘The pH of the pericardial effusion has also been evaluated” as a mean to distinguish between idio- pathic or neoplastic effusion; however, due toa si nificant overlap between the two groups, this isnot currently recommended as a diagnostic test." ‘The utility of serum concentrations of Troponin and Troponin T to diagnose cardiac neoplasia and to differentiate benign from malignant pericardial effusions has been investigated. Serum troponin 1 was shown to be higher in dogs with cardiac HSA than in dogs with extra-cardiae HSA, dogs with extra-cardiac neoplasia other than HSA and dogs with pericardial effusion not caused by HSA." In cases of pericardial effusion, Troponin 1 increases not only in the plasma but also in the pericardial 15,2, 273-208 Figure 4. Histopatholgical features of cardia tumours, (A) Haemangiosarcoma, Spindle to polygonal cls with inistinet eytoplasmc ints arranged in interacing bundles enclosing blood-flled spaces (H&E original magnification 100°). (B) Chemodectoma, Tumour pelygonal els are ranged in nests and packets supported bya fine and Achat brovascular stroma (HSE original magnification 10030, fluid, but the concentration of Troponin T in the effusion does not appear to help differentiating between aetiologies Troponin T was not signit- cantly different between dogs with idiopathic peri- cardial effusion and dogs with pericardial effusion caused by acandiac HSA"? ‘Thoracic radiographs can raise the suspicion for cardiac tumours or pericardial effusion, if there isa Visible change inthe cardiac silhouette. For staging purposes, lung metastases can also be identified. Echocardiography has been shown to have a high specificity (100%) and sensitivity (82%) for the detection and characterization of masses in dogs with pericardial effusion. The location and size ofthe tumour may help predict the diagnosis! (for example HSA appears to be more common in the right atrium/right atrial appendage) but a presumptive diagnosis based on the anatomical Cardiac tumoursin dogs and cats 279 location is only moderately accurate“ with an accuracy ranging from 50 to 78% depending on the tumour type (Fig 1). In addition, reports of valvu- Jar primary or secondary tumours! highlight the fact that such lesions have been misdiagnosed as endocarditis by less experienced ultrasonogra- phers, and therefore a neoplastic process should be considered asa differential diagnosis in some cases of valvular abnormalities. Advanced imaging modalities such as com- puted tomography (CT), positron emission tomography (PET) scans (Fig. 5) and magnetic resonance imaging (MRI) are useful diagnostic tools for the detection of cardiac tumours.®”4#-* Pneumopericardiography:” angiography”! and gated radionuclide imaging are also reported. Multidetector CT was not superior to echocar- ography in detecting cardiac masses in dogs with pericardial effusions despite its benefits in the ‘denttication of pulmonary metastases" Cardiac MRI was used to diferentiate neoplastic from non-neoplastic pericardial effusions, but this ‘modality did not improve the accuracy of a final diagnosis of cardiac tumours when compared to echocardiography.” Treatment and prognosis Multiple treatment options exist for cardiac tumours including surgery, chemotherapy and radiotherapy (RT), in addition to. symptomatic treatment, which may be necessary to stabilize patients that present with cardiac tamponade (e.g pericardiocentesis). Adequate control of the pri- rary tumour is often difficult to achieve and this limits survival, particularly in cases with severe clinical signs. The lack of a definitive diagnosis in most cases may also mean that some patients do not receive the most appropriate treatment: this is most relevant if a chemosensitive tumour (e.g Iymphoma) is present but goes undiagnosed, Without treatment, the prognosis for cardiac tumours is variable but generally poor. A study of 51 dogs diagnosed with histologically confirmed HSA reported MST of 7.1 days (range, 1 -26days) for dogs that received no treatment” Pericardio- centesis as palliative monotherapy is aso associated with a poor outcome.*##82-5* (©2015 Jon Wey & Sons Li Veterinary and Compraine Oncology 18.2, 273-288 260 E Tieggiaretal Figure 5. CTappearance ofa chemodectoms. Oblique) and transverse (B) post contrast thoraie C1 ot the lve ofthe sti rot. There large, well narginted ireglaly shaped, heterogeneous and hypoatenuating mass dora to the sortie toot, displacing the het ventrally The image B shows the mass inthe pane ofthe aortic oot. Noe the ventral an et-sided Adsplacerent ofthe aorta Right Surgery Pericardiectomy for dogs with cardiac tumour associated pericardial disease conveyed a MST of S2days in 9 dogs” compared to pericardic tomy for non-neoplastic pericardial disease (MST 792 days in 13 dogs)”® While this study included only a small numberof dogs cases with confirmed cardiac neoplasia, it suggests that pericardice: tomy is advantageous over just pericardiocentesis, given recurrence of clinical signs associated with pericardial effusion is one of the main causes of death/euthanasia. Pericardiectomy does inerea the potential risk of severe and acute haemor shage into the pleural space (instead of a contained haemorrhage into the pericardial space), but overall appears to confer a survival advantage. Pericardiee tomy and tumour resection resulted in a MST of Bodays (range, 10-202 days) in a group of 12 dogs? in this case ST was found tobe significantly longer when compared to dogs that received no treatment (8) or medical management alone (26). However, in another study on 143 dogs, MST and recurrence of pericardial effusion did not seem to be alfected by pericardiectomny in patients with cardiac HSA. However, these results have to be interpreted With caution, as the tumour diagnosis was only pre suumptive in the majority of eases included in that study: lef: Ao aorta: Cseardae house: T trachess Me mass Surgical excision is the treatment of choice for HSA, and is desirable as longas anatomical location permits (Fig. 6). There are a number of case series reporting successful surgery of cardiac tumours, though mosbidity and mortality are high. In a study on 51 dogs using traditional tho racotomy for HSA resection.”" MST was 86days (range, 10-202days) for dogs that had peri- cardiectomy and surgical resection of the HSA y e, 118-241 days) for dogs that had surgical excision of the HSA and adju- vant chemotherapy. This compares favourably to palliative pericardiocentesis with no additional treatment (MST, 7.1 days; range, 1-26days) oF with non-chemotherapeutic medical management only (MST, 27 days: range, 1-188 days”), However, another study on 23 dogs* reported shorter MST after surgery: MST was 42 days (range, 0-138 days) for dogs treated with surgery alone, and 175 days (range, 36-229 days) for the dogs treated with surgery and chemotherapy. In this study, peri- cardiectomy was also performed in 21 (919%) dogs, while the pericardium was closed in 2 (995) dogs ‘he two dogsin that study in which the pericardium was closed did not receive chemotherapy and lived 23 and 138days after surgery: In both studies, ST ‘was significantly longer for dogs that received adju- vant chemotherapy after surgery compared to those that received surgery alone; however, the role of 15,2, 273-208 Cardiac tumoursin dogs and cats 281 Figure 6. (A) Inaoperative view of right tial haemangiosarcoma (HSA). (B) Right auricular appendage HSA before surgical excision, adjuvant chemotherapy cannot be further clarified due tothe retrospective nature (and potential bias inadvising treatment and timing of enthanasia due to owners decisions) ofthe study. Thoracoscopic resection has been described in 9 cases* Fight HSA and 1 pyogranulomatous lesion were resected, mainly from the right atrial sppondage (8 dogs). One dog with a mass located at the base ofthe right auricle died during surgery, bat no other post-operative complications were noted in the remaining patients. However, masses close to the base of the right atrial appendage may not be amenable to resection with thoracoscopy. Another report describes successful removal of a high right atrial HSA via subtotal thoracoscopic pericardiectomy* achieving a ST of 177 days in combination with chemotherapy. ‘There isa single case report describing. pericar- dial patch graft to repair the defect after resection of aright atrial HSA; this dog also received adjune tive carboplatin and recurrence was documented 7 months later. A palliative RT protocol was started at that point and ST was 260 days after diagnosis, Aortic body and heart base masses that are not locally inv “Malignant heart base masses tend to invade local rmphatics* making resection dificult. For aortic body tumours!” the recommended treatment includes pericardicctomy in order to better control clinical signs (e.g, pericardial eff sion) In one case series of 25 heart base masses. mean ST for dogs that underwent pericardiec- tomy (661 170days)_ was significantly longer than mean ST for dogs that were treated medically e may be more amenable to surgery. vessels oF (pricandiocentesis, diuretics oF chemotherapy), achieving a survival of 129 4 51 days. There was no final diagnosis for any of the dogs in this study. Chemotherapy Surgical excision of HSA is the treatment of choice, bout when this isnot feasible, chemotherapy options include cyclophosphamide-based_ chemotherapy, single-agent anthracyclines or anthracyeline-based combination therapy, but data are limited and lim: ited efficacy is expected in a gross disease setting Conventional chemotherapy is most effective in the minimal residual disease setting, and for splenic HSA is used as post-operative adjunctive therapy to try to delay development of elincaly significant metastatic disease. A doxorubicin-based combina: tion protocol (VAC protocol) for HSA has been shown to result in a MST of 172days although no control group was included in the study and historical controls were used for comparison. Three dogs had concurrent right atrial as well as splenic involvement in this study, and this protocol has not been specifically evaluated for dogs with confirmed primary cardiac HSA. In cardiac HSA, chemotherapy may offer @ survival advantage when compared to pericardio- centesis alone, but without the ability to achieve « compartmental excision ofthe primary tumour, as is achieved by splenectomy, the impact on survival will likely be less than asan adjunct in splenic HSA. 1n 23 dogs with cardiac HSA, treated surgically” by means of pericardiectomy and mass resection, mean ST after surgery without chemotherapy ranged between 43 and 46 days, whereas mean ST (©2015 Jon Wey & Sons Li Veterinary and Compraine Oncology 18.2, 273-288 282 E Tieggiaretat was 164 days for dogs that also received adjuvant chemotherapy. Only 8 of the 23 dogs received chemotherapy and protocols were doxorubicin alone in 3 dogs (ST 12, 36 and 188 days), doxoru- bicin and cyclophosphamide in 3 dogs (ST 118, 162 and 228days) and doxorubicin, cyclophos- phamide, and vineristine in 1 dog (ST 205 days). The chemotherapy protocol for the remaining dog was not specified. Time to initiation of treatment, cycles received and stage also varied between groups (with 7 [28%] dogs with docu mented metastatic disease at presentation). Thus the study lacks the power to demonstrate any dilference between protocols. An individual case report in a dog receiving single agent doxoru- bicin after surgery reports similar survival time (177 days)" Doxorubicin was also used in a study” on pre sumptive cardiac HSA identified using echocar- diography in 16 dogs, treated with chemotherapy alone. Histopathological diagnosis was performed afer post-mortem examination in only one case, confirming HSA. These authors used doxorubicin either alone or in combination in a multi-agent pro- tocol as already described in previous studies and achieved a MST of 139 days, A recent larger study!" compared the outcome of 64 dogs with a presumptive diagnosis of cardiac HSA on echocardiography, treated with doxoru- bicin asa first line treatment, versus 76 untreated patients. Although median progression-free sur Vival (PFS) and MST were of short duration (66 and 119 days respectively) in those dogs receiving chemotherapy, the authors found an improved survival when compared to the untreated group, whose MST was 12 days only. None of the dogs received pericardiocentesis or surgery before receiving chemotherapy, with the responders expe- riencing either complete response (CR) or stable disease (SD). Following the completion of the oxorubicin-based protocol, 1 dog was treated with vineristine and cyclophosphamide, whereas 20 dogs that showed no response to doxoru bicin received rescue chemotherapies (including vincristine, cyclophosphamide and carboplatin). Hleven dogs within the responders’ group also received metronomic cyclophosphamide, but this did not seem to affect the outcome significantly. 102015 Jon Wty & Sons, Veternary and Comparative Onooay Interestingly, metastatic disease at diagnosis was detected more frequently in the group receiving chemotherapy and this may have biased the clni- cian advice and subsequently the owners decision of pursuing further treatment, This study again Jacks a histopathological confirmation of HSA but reflects « common situation encountered in clinical practice, where dogs are treated based on a presumptive diagnosis. Although suffering the lim- itations of a retrospective study, the results suggest a potential advantage in using chemotherapy alone in such cases. Cyclophosphamide-based metronomic chemo: therapy has been used as a post-operative adjune- tive treatment in splenic HSA,!" showing a similar efficacy when compared to anthracycline-based protocols Potential cardiac HSA may be sensitive to the same type of treatment, but again the gross disease setting isnot comparable. The authors have treated 2 dogs with cytologically confirmed atrial HSA with a cyclophosphamide-based metronomic protocol, achieving survivals of 20 and 66 days, respectively, with both dogs being euthanized because of recurrence of clinical signs associated with pericardial effusion (unpublished data). Chemotherapy is the treatment of choice for cardiac lymphoma, as is recommended for other anatomic locations of lymphoma. A small study con 12 dogs showed that the MST of 5 patients that received combination chemotherapy (includ: ing prednisone, vincristine, cyclophosphamide, Leasparaginase, doxorubicin, mechlorethamine, procarbazine, lomustine) was 157days. OF the 7 dogs that did not receive any treatment, MST for 6/7 dogs was only 15days.® In this study, 1 dog treated with pericardiocentesis only sur- vived >1169 days, making the original diagnosis uestionable. This study also suggested that the prognosis for cardiac lymphoma was not as poor as for other stage V, substage b lymphomas.® This was a very small study, and may also be influ: enced by clinician/owner bias in advising/declining any further treatment, hence dogs with a worse clinical presentation or more severe clinical signs may not have been treated and had a shorter survival Future prospective studies may include new tar: geted therapies such as tyrosine-kinase inhibitors, 15,2, 273-208 which may have a rationale if used as antiangio- sgenetic agents, especially in HSA cases." For all medical therapies, complete remission (CR) is unlikely. Whatever the diagnosis, treat- ‘ment may also require symptomatic management aimed at controlling tumour bleeding and poten- tial arrhythmias, and other signs caused by themass effect. Unlike other solid tumours, achieving par- tial response (PR) or SD may not lead to adequate control of the associated clinical signs to enhance survival. Radiotherapy A single case report! described the use of con- formal radiation therapy in a dog with chemod- ctoma this resulted in a partial response (more than 50% reduction in tumour volume). The dog ‘was symptom-free for 32 months, followed by adi- tional 42months subsequent to further RT and pericardiectomy, RT remains an interesting treat- ‘ment option to treat heart base masses that are not easily accessible surgically, but more studies are needed to confirm the efficacy of this, and intensty-modulated RT or other highly conformal techniques may be most appropriate Cardiac tumours in cats Cardiac tumours are much less common in cats than in dogs, and tend to be malignant.” One of the largest retrospective studies” reporting 30 cardiac tumours found lymphoma to be the most common. “Thirteen cas, four of which were FeLV positive, ad ‘malignant lymphoma (12 B- and 1 T-cell). Metas- tases ofextracandiae tumours occurred in the heart in 5 cases. As in dogs, cardiac metastases were pre- dominantly locate in the interventricular septum and the left ventricular wall.” Cardiac metastases of a solid adenocarcinoma of the lungs and of mam- mary adenocarcinomas have also been reported in the same study. A case of a primary pericardial HSA in a 13-year-old domestic shorthair cat with metastases tothe liver as also been deseribed.!™ Recently pericardial lymphoma has been reported in 7 cats! (1 non-classifed, 3 T-cell and 3 B-cell), Diagnosis was confirmed using cytol ogy with fine-needle aspirates of the pericardium Cardiac tumoursin dogs and cats 283, and cytology of the pericardial and pleural effu- sions. Clinical findings at presentation may include poor body condition, dehydration and dyspnoea, In most cases, there was echocardiographic evi- dence of diffuse thickening of the pericardium, ‘Survival time ranged between 7 and 11 days when untreated oF receiving single-agent drugs (doxoru- bicin or prednisolone alone), except for one cat that received a multi-drug chemotherapy protocol (CHOP protocol) and was still alive 750 days after dliagnosis, The long survival time in this case was associated with complete remission confirmed on thoracic radiographs and echocardiography, but the real efficacy of chemotherapy in these cases ‘warrants further investigations. Achieving SD, as in dogs, may not be beneficial for those tumours causing life-threatening clinical signs. Conclusions Cardiac tumours are rare in dogs and cats and can be challenging to detect. Frequently, entified using echocardiog- raphy; however, a definitive diagnosis is usually acquired only in post-mortem. Sampling of acces- sible cardiac masses should be considered as this dige mass can by ‘may influence prognosis and treatment, as well as outcome, ‘Most ofthe studies reported here are retrospec tive in nature, limiting the information that can be inferred, A significant sample selection bias has to be suspected, both on the side of veterinarians ma ing treatment recommendations and dog owners Retrospective studies generally require large sample sizes, in order to yield meaningfal results, and many ‘ofthe studiesare on small numbers of cases, Cardiac neoplasms are uncommon in veterina and prospective studies are therefore likely to be limited by the slow accrual of cases unless these are y medicine, very large multicentre studies, Treatment options are limited, but in cases of HSA best outcomes are achieved with a combina- tion of surgery and chemotherapy (most commonly. anthracycline-based). Cardiac lymphoma may respond to multiagent chemotherapy protocols, However, regardless of diagnosis, treatment often requires symptomatic management of tumour (©2015 Jon Wey & Sons Li Veterinary and Compraine Oncology 18.2, 273-288 284, E Tieggiar etal bleeding and potential arrhythmias other than signs caused by the mass effect, as achieving CR is ‘uncommon, Unlike other solid tumours, achieving PR or SD may not lead to adequate control of the associated clinical signs to enhance survival. RT is an interesting but not readily accessible option for heart base tumours. Medical management, beyond adjunctive chemotherapy in HSA, requires further investigation but combination chemotherapy is recommended for lymphoma, Acknowledgements ‘The authors would like to acknowledge Dr Jeremy Mortier (Small Animal Teaching Hospital, Uni versity of Liverpool, UK) for providing the CT scan images and their description; Dr Ana Canadas (Instituto de Ciencias Biomedicas de Abel Salazar, Universidade do Porto, Portugal) for providing the histopathology pictures and their description; Dr Giorgio Romanelli (Clinica Veterinaria Nerviano, Milan, Maly) for providing the post-mortem and intra-operative pictures. Brigite Pedro’ cardiology residency training programme was supported in part by Boehringer Ingelheim Vetmedica References 1. Detwiler DK and Patterson DF. The prevalence and types of cardiovascular disease in dogs. Arals ofthe New York Academy of Sciences 1965: 127 481-516, 2 Prange H, Pall-junge G, Katenkamp D, Schneider and Zieger M. 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