RETROSPECTIVE ANALYSIS OF 104 CASES
Nancy O. Brown, VMD; Amiya K. Patnaik, MVSc; E. Gregory MacEwen, VMD
Hemangiosarcoma was diagnosed in 104 dogs. The mean age was 10 years. Twenty-two breeds were represented. The most common were the German Shephard Dog and Poodle. Most tumors were in the spleen (65/104). Other primary sites included the soft tissues of the trunk and extremities (18), liver (6), heart (3), and lung (2). Sixty of the dogs were examined because of rupture of the primary tumor or metastatic disease. Of the 104 dogs, 4 are alive and 100 are dead: 35 were euthanatized at the time of diagnosis, and the remaining 65 had a mean survival time of 123 days. The mean survival time of the 4 living dogs was 360 days. Forty-seven of the 65 dogs with splenic hemangiosarcoma were treated with surgery alone, surgery and immunotherapy, or surgery, immunotherapy, and combination chemotherapy. The same 47 dogs were clinically staged. There was no difference in survival time according to therapy or stage of disease.
HEMANGIOSARCOMA, also referred to as angiosarcoma and malignant hemangioendothelioma, is a malignant tumor composed of endothelial cells that develops more frequently in the dog than in any other species.1,2 There are several reports of canine hemangiosarcoma in the veterinary literature3-6; prevalence has been reported as 39/12,635 (0.3%),1 25/1,262 (1.98%),7 and 23/1,168 (1.97%).3 Prevalence in man is much lower than in the dog.4 Development of these tumors in adult human beings has been related to thorium dioxide, exposure to arsenicals, and exposure to vinyl chloride. 8,9
Dogs with hemangiosarcoma are usually older than 8 years1,10; mean ages of 9.0,10 9.5,1 10.0,4 and 10.5a years have been reported. Most investigators report no breed or sex predilection,1,10,11 although some report a higher prevalence in the German Shepherd Dog6,7,12 and male dog.3,7,12
The sire of primary involvement in usually the spleen, although many other locations have been reported. Other sites include the liver, heart, lungs, kidneys, skin, oral cavity, muscle, and peritoneum.2,3,13
Clinical signs include weakness, depression, pale mucous membranes, splenic, enlargement, abdominal distention, increased pulse and respiration, and weight loss.1,6,10 Hematologic findings include low values for Hb, PCV, and RBC count, high reticulocyte count, and neutrophilic leukocytosis.5
Hemangiosarcomas are poorly circumscribed, nonencapsulated, and often adherent to adjacent organds.1,10 Hemorrhage and necrosis are common. Diagnosis is based on clinical, laboratory, and radiographic findings and abdominal paracentesis when indicated. Diagnosis is confirmed by histology.
Metastasis is rapid and widespread and occurs via hematogenous routes.3 The most frequently reported sites are the liver and lungs; other sites include the kidneys, skeletal muscle, peritoneum, omentum, lymph nodes, mesentery, adrenal glands, and diaphragm.1,2,6,10,12,13
Dogs with hemangiosarcoma have a poor prognosis regardless of location. Duration of signs before diagnosis is short and many die suddenly from rupture of the primary or metastatic tumors. Surgery is the only effective therapy. In 2 reports of dogs that underwent splenectomy, 54% (22/40) had angiogenic tumors12 and 50% (41/82) had tumors of which 32% (26/82) were confirmed as sarcomas.11 Mean survival time in one series of cases (n=7) was 8 months,5 whereas only 7 of 26 dogs in another series lived more than 1 year.11
The purpose of this report is to describe the epidemiology and response to therapy in 104 dogs with hemangiosarcoma.
MATERIALS AND METHODS
The case records of dogs with hemangiosarcoma diagnosed between Jan 1, 1975 and June 30, 1980, were reviewed. Diagnosis and classification were confirmed in each case by histologic examination of neoplastic tissue. The extent of disease and presence of concurrent illness, if any, were determined at the time of diagnosis.
The dogs were allotted to 1 of 4 groups: (1) no treatment, (2) surgery alone, (3) surgery and immunotherapy, and (4) surgery, immunotherapy, and chemotherapy. Immunotherapy consisted of administration of a mexed bacterial vaccine* (MBV, 0.025 ml, IM, initially, then slowly increased by 0.025 to 0.05 ml once weekly until toxicosis was observed; maximal dose, 0.25 ml). Chemotherapy consisted of vincristine† (0.0125 mg/kg, SID, orally), and methotrexate§ (0.4 to 0.6 mg/kg, once weekly, IV)
*Mixed bacterial Vaccine, Fabenfabriken, Bayer, Wuppertal, Germany. Streptococcus pyogenes culture, 16.66 mg (10⁸ to 10⁹ organisms per ml), was mixed with 5.0 ml of Serratia spp. Suspension (protein content, 12.5 mg per ml) in 40-ml flasks and heated for 1 hour at 75° C. The flasks were frozen at -60°C and subsequently lyophilized. This material will be reconstituted by the addition of 3.33 ml glycerol and 25 ml distilled water per flask.
†Oncovin. Eli Lilly and Company, Indianapolis, Indiana.
‡Cytoxan. Mean Johnson & Company, Evansville, Indiana.
§Methotrexate. Lederle Laboratories, Wayne, New Jersey
Immunotherapy and/or chemotherapy was initiated at the time of suture removal. A physical examination and hematologic testing were performed weekly to detect adverse reactions, if any. If the WBC count dropped below 4,000 cells/mm,3 chemotherapy was discontinued for 1 week to allow the bone marrow to “rebound” and the WBC count to return to the normal range. (7,000 to 9,000 cells/mm3). Therapy was continued for 3 months following surgery.
The therapeutic response was measured in terms of survival time. Survival time was defined as the time from the date of diagnosis to death. Cause of death was determined in each case.
Hemangiosarcoma was diagnosed in 104 dogs in a 5 1/2-year period (Jan 1, 1975 to June 1, 1980). The mean age was 10 years (range, 2 to 16 years). There were 59 males (57%) and 45 females (43%). Twenty-two breeds were represented; the mose common were the German Shephard Dog (34, 33%) and Poodle (9, 9%). There were 26 (25%) dogs of mixed breeding.
Of the 104 dogs with hemangiosarcoma, 60 (58%) were examined because of rupture of the primary tumor or metastatic disease. The primary tumor was located in the following sires: spleen, 65 dogs (62%); soft tissues of the trunk and extremities, 18 (17%); liver, 6 (6%); head, 4 (4%); heart, 3 (3%); long bones, 3 (3%); lungs, 2 (2%); and bladder, aorta, and prostate gland, 1 each (1%).
One hundred of the 104 dogs died. Thirty-five received no treatment and died at the time of diagnosis; they were dead on arrival at the hospital, were euthanatized because of poor prognosis, or died during surgery. Of the 69 dogs treated, the mean survival time was 123 days. Four dogs are alive with a mean survival time of 360 days.
Of the 65 dogs treated that have died, 34 were necropsied. Twenty-three (67%) had evidence of metastatic disease. In these 23 dogs, the most common sites of metastasis were the lungs (15, 65%), liver (12, 52%), heart (9, 39%), kidneys (6, 26%), mesentery (6, 26%), intestines (6, 26%), adrenal glands (5, 22%), omentum (5, 22%), and peritoneum (2, 9%).
The dogs with splenic hemangiosarcoma comprised the largest group. Of the 65 dogs with primary splenic hemangiosarcoma, 50 (77%) were examined initially because of rupture of the primary or metastatic tumor(s). The liver (15), omentum (9), peritoneum (4), kidneys (3), lungs (3), mesentery (2), and heart (1) were the sites of metastasis for the dogs with splenic hemangiosarcoma. Eighteen were euthanatized at the time od diagnosis.
Forty-seven of the 65 dogs with splenic hemangiosarcoma were clinically staged (Table 1) at surgery; a splenectomy was performed in all 47 dogs. Eight dogs (17%) had stage I disease (primary only), 15 dogs (32%) had stage II disease (rupture), and 24 dogs (51%) had stage III disease (metastasis). Table 2 shows the correlation of survival time and clinical stage of disease in the 47 dogs with splenic hemangiosarcoma. The median survival time of the dogs with stage I disease was 151 days; of the dogs with stage II disease, 107 days; and of the dogs with stage III disease, 73 days. There was no statistical difference between these survival times.
Table 3 shows the correlation of survival time and treatment in 47 dogs with splenic hemangiosarcoma. Twenty-one dogs (5, stage I; 8, stage II; 8, stage III) were treated with surgery alone; 10 dogs (1 stage I; 4 stage II; 5 stage III) were treated with splenectomy and MBV; and 16 dogs (2 stage I; 3 stage II; 11 stage III) were treated with splenectomy, MBV, and combination chemotherapy. The median survival time for the surgery group was 65 days; for the surgery and MBV group, 91 days; and for the surgery, MBV, and chemotherapy group, 117 days. It appears that splenectomy, MBV, and combination chemotherapy was the preferred treatment; most of the dogs so treated (11/16) had more advanced disease, and as a group they had a longer median survival time.
The results of this and other studies indicate that hemangiosarcoma usually develops in dogs between 8 and 10 years of age.1,4,10 We found a slight predominance in males (57%), which some other investigators also have reported,3,7,12 although we were unable to compare this figure with the percentage of males in the hospital population at large. In this and in some other studies, the German Shepherd Dog was the most commonly affected breed.6,7,12 The spleen is by far the most common sire of the primary tumor in dogs with hemangiosarcoma; in this study the spleen was the primary sire in 65 of 104 (62%) of dogs. The next most common site was the soft tissues of the trunk or extremities, which illustrates the variety of sites from which this tumor can arise. The cases of this study also illustrate the rapid, uncontrolled course of the disease. Many of the dogs were beyond medical help at the time of examination. On the basis of our findings, we conclude that even if surgery is performed to remove primary hemangiosarcoma, most dogs so affected will die in less than 4 months.
- Moulton JE, Tumors in domestic animals, 2nd Berkeley Calif: University of California Press, 1978;35-36.
- Waller T, Rubarth S. Haemangioendothelioma in domestic animals. Acta Vet Scand 1967;8:234-261.
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- Ishmael J, McC Howell J. Neoplasia of the spleen of the dog with a note on nodular hyperplasia. J Comp Pathol 1968;78:59-67.
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- Kleine LJ, Zook BC, Munson TO. Primary cardiac hemangiosarcomas in dogs. J Am Vet Assoc 1970;157:326-337.
- Ludwig J, Hoffman HN. Hemangiosarcoma of the liver: spectrum of morphologic changes and clinical findings. Mayo Clin Proc 1975;50:255-263.
- Adam YG, Huvos AG, Hajdu SI. Malignant vascular tumors of the liver. Ann Surg 1972;175:375-383.
- Champman WL. Disease of the lymph nodes and spleen. In: Ettinger SJ, ed. Textbook of veterinary internal medicine.Philadelphia: WB Saunders Co, 1975;1675
- Bartels P. Indications for splenectomy and the post-operative survival rate. J Small Anim Pract 1970;10:781-785.
- Frey AJ, Betts CW. A retrospective survey of splenectomy in the dog. J Am Anim Hosp Assoc 1977;13:730-734.
- Jubb KVF, Kennedy PC. Pathology of domestic animals. New York: Academic Press Inc, 1963;370-373.
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