Abstract
A case of peripheral arterial tumor embolization in a cat is described. The cat presented with signs of aortic thromboembolism, including decreased peripheral pulse quality, pallor, and coolness of the distal limbs, as well as proprioceptive deficits. Thoracic radiographs revealed a cavitary lung mass; echocardiography was unremarkable. Cytologic evaluation of aspirates of the mass suggested malignancy. The left hindlimb was amputated, and histopathology confirmed embolization of an adenocarcinoma. Although rare, peripheral arterial tumor embolization should be considered as a differential in cats presenting with signs of thromboembolic disease.
Embolization of a malignant tumor in a peripheral artery is rare in human beings and poorly documented in animals. Most human cases are associated with primary or secondary lung cancer, following tumor invasion of the pulmonary vein (Starr et al 1981, Singh et al 2000, Xiromeritis et al 2000). In cats, almost all cases of ischemic neuromyopathy result from arterial embolization of a fragment of an intracardiac thrombus, formed as a consequence of underlying cardiac disease (Laste and Harpster 1995). This paper describes ischemic neuromyopathy in a cat due to peripheral arterial tumor embolization.
A 14-year-old male neutered Abyssinian presented with a 1-day history of right carpal hyperextension, and pallor and coolness of the footpads of the right forefoot. Historical illnesses included feline asthma of 12 years duration, for which the cat was being treated with prednisone (2.5 mg q72h PO). One month prior to presentation, at an annual examination, the owner reported that the cat had been coughing with increased frequency for the last 2 months. Lateral and ventrodorsal thoracic radiographs revealed a cavitary mass in the left caudal lung lobe, which was absent on radiographs performed a year earlier, and a persistent moderate bronchial pattern. A CBC, serum biochemistry profile, and urinalysis revealed renal failure, characterized by azotemia (creatinine 2.5 mg/dl, reference range [RR]=0.1–2.1 mg/dl; BUN 39 mg/dl, RR=13–35 mg/dl) and a urine specific gravity of 1.018. Hyperglobulinemia was also present (total protein 8.6 g/dl, RR=5.6–7.6 g/dl; albumin 2.6 g/dl, RR=2.3–3.5 g/dl; globulin 6.0 g/dl, RR=2.9–5.6 g/dl). The owner declined further evaluation at that time.
Upon presentation, abnormalities noted on clinical examination were tachypnea (52 breaths/min), tachycardia (240 beats/min), right carpal hyperextension, and pallor of the right front footpads. No musculoskeletal pain was detected. Pulsatile flow was decreased using Doppler measurement of blood flow to the right distal forelimb. The owner was advised to monitor the cat for further problems.
The following day, the cat re-presented because of recumbency, increased vocalization, two episodes of vomiting, and inappetence. Heart rate was 260 beats/min and respiratory rate was 60 breaths/min. The distal hindlimbs were cool, but femoral pulses were palpable proximally. A region of purple discoloration was noted on the left tarsal pad and the claw beds of the left hindlimb were cyanotic. The left gastrocnemius muscle was firm but both gastrocnemius muscles were painful. Neurologic examination of the left hindlimb revealed absence of deep pain distally, withdrawal reflexes, and conscious proprioception but a normal patellar reflex. No neurologic abnormalities were detected in the remaining limbs. Doppler signals were absent distally in both hindlimbs.
Abnormalities noted on the CBC were mature neutrophilia (15,520 cells/μl, RR=1200–13,200 cells/μl) and monocytosis (3450 cells/μl, RR=0–800 cells/μl). A microcytic, normochromic anemia was also noted (HCT 24.9%, RR=26.1–46.7; MCV 37 UM3, RR=39.5–50.6). A serum biochemistry profile revealed hyperamylasemia (2028 U/l, RR=170–1250 U/l), elevated AST (112 U/l, RR=9–53), mild azotemia (BUN 35 mg/dl, creatinine 1.7 mg/dl), and hyperproteinemia (total protein 7.7 g/dl, albumin 2.5 g/dl). Creatine kinase was 4770 U/l (RR=55–382 U/l). Urinalysis revealed a specific gravity of 1.019, 3+ occult blood, a pH of 6, 2+ protein, and a benign sediment. The urine protein:creatinine ratio was 1.7.
The clinical signs and clinicopathologic abnormalities suggested distal aortic thromboembolism. Thrombin, activated partial thromboplastin, and prothrombin times were normal, but fibrin split products (FSPs) and fibrinogen were increased (FSPs 5–20 μg/ml, RR=0–5 μg/ml; fibrinogen 0.4 g/dl, RR=0.1–0.3 g/dl). Thoracic radiographs showed enlargement of the lung mass with an interstitial infiltrate in the caudodorsal lung tip (Fig 1). An echocardiogram was normal. Using abdominal ultrasound, no mass could be detected within the distal aorta.
00049-4/unzip/10.1016_S1098-612X(03)00049-4-fig1.png)
Right lateral thoracic radiograph from a cat with distal aortic embolism of metastatic adenocarcinoma. Note the large, cavitary mass in the distal portion of the left caudal lung lobe.
Fine needle aspirates were obtained from the lung mass using fluoroscopic guidance and examined cytologically. Cytology revealed many phagocytic macrophages, neutrophils, and occasional atypical cells, surrounded by granular proteinaceous material and extracellular debris consistent with necrosis. Malignancy was suspected, but because of profound inflammation, could not be concluded.
The cat was hospitalized and treated with cage rest, oxymorphone (0.03 mg/kg SC q4h), heparin (780 U SC q8h), and fluids (Normosol-M, 10 ml/h IV). The cat was discharged 3 days later with instructions to administer aspirin (5 mg PO q 72h). Although the cat could ambulate, the left hind paw was more discolored and lacked deep pain. Limb amputation was recommended but the owner declined.
Two weeks later (day 15), the cat re-presented with a 1-day history of anorexia and one episode of vomiting. Depression, pyrexia (103.1F), tachycardia (210 beats/min), and dehydration were noted. The distal left rear limb was cold and firm, and the skin had begun to slough on its lateral aspect. A CBC revealed leukocytosis, with 13,270 segmented neutrophils/μl, 13,420 band neutrophils/μl (RR=0–160 cells/μl), toxic change, and 2130 monocytes/μl. Serum biochemistry revealed hyperamylasemia (1587 U/l) and azotemia (BUN 43 mg/dl, creatinine 2.8 mg/dl). Treatment with fluids (Lactated Ringer's Solution with 16 mEq/l of KCl, 40 ml/h IV) and ampicillin (75 mg IV q8h) was initiated, and the following morning, the gangrenous limb was amputated. The cat was later discharged with instructions to give clavulanic acid–amoxicillin for 10 days (62.5 mg PO q12h).
Several sections of muscular arteries and adjacent skeletal muscle from the limb were stained with hematoxylin and eosin for histopathological examination. Obturating thrombi were noted in the lumen of many arteries. Clusters of anaplastic polyhedral epithelial cells, consistent with tumor emboli, were located within many thrombi(Fig 2). Within the skeletal muscle were extensive areas of acute coagulation necrosis. The tumor cells stained positive with cytokeratin, consistent with metastatic carcinoma.
00049-4/unzip/10.1016_S1098-612X(03)00049-4-fig2.png)
Clusters of anaplastic polyhedral epithelial cells within the lumen of two arterial sections from the amputated hindlimb of a cat. These cells stained positive for cytokeratin. Tumor cells were admixed with thrombi in other arterial sections, and within skeletal muscle, there were extensive areas of acute coagulation necrosis (hematoxylin and eosin stain).
Five days after discharge, the cat was euthanized after acute onset of increased vocalization, collapse, and respiratory distress. The distal left forelimb was cool and the entire limb lacked voluntary motor activity. Necropsy was notpermitted.
Peripheral arterial embolism resulting from a metastatic tumor is a rare cause of acute arterial embolism in humans and other animals, and, to the author's knowledge, this represents the first report of the condition in cats. In cats, decreased peripheral pulse pressure, pallor, and coolness of the distal limbs, and accompanying neurologic deficits almost always result from aortic thromboembolism secondary to underlying cardiac disease, most commonly hypertrophic cardiomyopathy (Laste and Harpster 1995, Schoeman 1999). The distal aorta is affected in over 90% of cases, but brachial (especially right brachial), renal, pulmonary, and mesenteric embolizations may also occur. In addition toaortic embolization, tumor embolization of the right then left brachial artery was likely in the cat described in this report.
In human patients, most cases of tumor embolism involve atrial myxomas, which are rare, but frequently embolize (Durgut et al 2002). Remaining cases of tumor embolism are usually associated with pulmonary neoplasia, as was likely in the cat in this report (Starr et al 1981, Singh et al 2000, Xiromeritis et al 2000). A recent retrospective study of 104 cases of tumor embolism in humans found that nearly 90% were associated with lung tumors (44% primary and 32% secondary) and 13% were associated with primary aortic tumors (Xiromeritis et al 2000). Fewer cases were associated with other neoplasms. The most common sites of embolization were the middle cerebral artery (24% of arteries), aortic bifurcation (20%), and the common femoral artery (17%). As reported for the cat in this study, approximately 20% of patients suffer recurrent or multiple embolizations. Although macroscopic invasion of pulmonary veins by lung neoplasms is common in human patients, spontaneous detachment of fragments large enough to occlude peripheral arteries is extremely rare (Spencer et al 1993). Approximately half of the embolic episodes occur after pneumonectomy, and in less than 5% of cases, the embolic event is the first manifestation of underlying pulmonary neoplasia(Xiromeritis et al 2000). Because a postmortem was not permitted in the cat in this report, it remains possible that both the pulmonary mass and tumor embolus represented metastases from an undetected neoplasm located elsewhere, although this seems unlikely given the otherwise unremarkable radiographic and ultrasonographic findings.
Interestingly, in a retrospective study of 100 cats with aortic thromboembolism, thoracicradiography revealed solitary lung masses in two cats, although cardiac disease was present on echocardiographic evaluation (Laste and Harpster 1995). Another three cases had caudodorsal lung consolidation, speculated to be due to concurrent pulmonary thromboembolism. The authors also described an additional cat with a lung mass, aortic thromboembolism, and no evidence of cardiac disease. Tumor emboli may have been the cause of presenting signs in these cases. Alternatively, thromboembolism may have been associated with a hypercoagulable state resulting from underlying neoplasia. This was suggested as the underlying mechanism in a cat with aortic thromboembolism, multiple bronchoalveolar carcinomas, and marked thrombocytosis (Hogan et al 1999). Histopathology of the thromboembolus was not reported in that study, and so tumor embolization remained another possible cause.
The treatment of choice in human patients is surgical embolectomy, which has a success rate (with return of end organ function) of 84% (Chandler 1993). Although success has beenreported (Robins et al 1982), embolectomy has not been widely adopted in cats, due to the high risk of anesthetizing affected cats and the small vessel sizes encountered.
In conclusion, although rare, peripheral arterial tumor embolization should be considered in cats presenting with signs consistent with feline aortic thromboembolism, especially in older cats lacking evidence of underlying cardiac disease. In addition to an evaluation for underlying neoplastic disease, histopathologic examination ofarterial emboli should be performed where possible, such as following limb amputation or at necropsy. This will lead to consideration of appropriate further therapy for affected cats, and further our understanding of this phenomenon.
Acknowledgements
The author would like to thank Drs Rita Miller, Kristin Jacob, Kenneth Bell, Jacob Odders and Heather Chalfant for their assistance with this case, and Dr Timothy O'Brien for interpretation of the histopathology.