Essential information for veterinary practitioners about hemangiosarcoma

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Hemangiosarcoma is often the first thing that comes to mind when a splenic mass is found in a dog. Although it is the most common malignant splenic tumor, it is not the only differential. Unfortunately, obtaining a definitive diagnosis and prognosis for the patient requires histopathology, which must be obtained surgically. The decision to go forward with surgery in the face of a potentially poor prognosis can be a difficult one for clients, especially in an emergency situation when the tumor has ruptured and is actively hemorrhaging.

During a session at the American Veterinary Medical Association Virtual Convention, Sue Ettinger, DVM, DACVIM (oncology), a veterinary oncologist at the VCA Veterinary Referral and Emergency Center in Norwalk, Connecticut, discussed key facts that practitioners need to know about hemangiosarcoma to help their clients make the best decision for their pet and family.

How does hemangiosarcoma present?

Clinical signs of hemangiosarcoma vary greatly depending on tumor location and how advanced the disease is at diagnosis. Tumor location can vary from the skin to subcutaneous tissue to visceral organs. The most common primary visceral sites are the spleen, heart, and liver. Because it is a cancer of blood vessels, it metastasizes quickly, with the liver and lungs being the most common targets.

Some patients with splenic hemangiosarcoma present with nonspecific signs such as decreased appetite, lethargy, or gastrointestinal distress, and other patients present in hypovolemic shock after an acute collapse. It is also possible for patients to have no clinical signs, with the mass being found by accident.

Ettinger reminded clinicians that although large breed dogs are generally at increased risk, any dog can present with hemangiosarcoma. Golden retrievers, German shepherds, and Labrador retrievers are thought to be at highest risk, and a genetic predisposition is suspected.

The double two-thirds rule

Ettinger noted that only approximately 45% of splenic masses are hemangiosarcoma, based on what she referred to as the “double two-thirds rule”: Two-thirds of patients presenting with a splenic mass have a malignant tumor, and of these malignancies, two-thirds are hemangiosarcoma. According to Dr Ettinger, published literature reports between 45% to 65% of splenic masses in dogs to be hemangiosarcoma.

Differentials for the one-third of dogs with benign masses include nonneoplastic masses like hematomas, abscesses or nodular hyperplasia, or a benign hemangioma. Differentials for the remaining malignancies include lymphoma, histiocytic sarcoma, and osteosarcoma.

In Ettinger’s experience, emergency clinicians have a higher suspicion of hemangiosarcoma when a splenic mass is identified, despite the double two-thirds rule. This is likely because patients presenting with a splenic mass in the emergency setting often have ruptured tumors and hemoabdomen, which both increase the index of suspicion for malignancy. In one study that evaluated dogs presenting with nontraumatic hemoabdomens, 80% of the splenic masses were neoplastic, with 88% of those diagnosed as hemangiosarcoma.¹

Another exception to this rule is that nonruptured splenic masses found incidentally, which Ettinger nicknamed “incidentalomas,” are less likely to be malignant. In a 2016 study, only 30% of these masses were malignant.²

Preoperative diagnostics

Ultimately, the definitive diagnosis of any splenic mass is through histopathology. However, several diagnostics should be performed prior to surgery to assess patient risk and stability.

Blood work is an essential part of the preoperative work-up and should include, at a minimum, a complete blood count (CBC) and a chemistry panel. CBC results may raise the suspicion of malignancy if anemia, nucleated red blood cells, abnormal red blood cell morphology, or thrombocytopenia are present. CBC results can also help assess risk of perioperative mortality. Patients with marked preoperative thrombocytopenia or anemia (hematocrit levels<30%) have an increased risk of death.³

Coagulation status should be assessed with a prothrombin time or partial thromboplastin time blood test, in house if available. If these tests are not available in house, perform a buccal mucosal bleeding time evaluation or toenail clip to assess clotting. Half of patients with hemangiosarcoma will present with a coagulopathy.

Chest radiographs should be performed prior to surgery to assess for gross metastatic disease. Taking 3 views of the chest is essential to maximize the chances of detecting a lung nodule if one is present.

If available, abdominal ultrasound can be a helpful tool because it is less affected by effusion than radiographs. It allows the clinician to confirm the presence of any splenic tumors and assess the degree of effusion and for gross metastasis to other abdominal organs. Additionally, the architecture of the mass can be evaluated, which guides the decision to perform fine needle aspiration (FNA). FNAs are not recommended on cavitated splenic masses. Generally, cytology is low yield and inaccurate for hemangiosarcoma, and obtaining the sample has a high risk of hemorrhage due to the friable nature of the mass. If a solid splenic mass is visualized, an aspirate may be helpful to aid in the diagnosis.

Although some textbooks recommend echocardiography prior to surgery to screen for right atrial masses, it is not necessary in most cases, according to Ettinger. A better use of the client’s money is an electrocardiogram, monitoring during and after surgery because arrhythmias are common in patients regardless of whether the mass is benign or malignant. The presence of intraoperative ventricular arrhythmias doubles the risk of perioperative mortality.³

Traditional treatment options

Hemangiosarcoma is a treatable cancer, and when treated, dogs do live longer. However, according to Ettinger, the 1-year survival is less than 10% no matter how aggressive treatment is. The best prognosis is seen with non-ruptured, low-grade splenic tumors.

Surgery is the first-line treatment for splenic masses. During surgery, the abdomen should be fully explored. The gross appearance and size of the primary mass at the time of surgery does not correlate with malignancy. Suspected metastatic lesions on other abdominal organs, such as the liver, may actually be hematomas, extramedullary hematopoiesis, or another benign process. Thus, all suspicious lesions should be biopsied and submitted for histopathology along with the entire spleen. Surgeons must remember that hemangiosarcoma can only be diagnosed definitively by histopathology and should not make intraoperative assumptions about malignancy.

Ettinger cautioned that iatrogenic spread of neoplastic cells is possible due to the highly friable nature of the tissue. To minimize seeding of neoplastic cells during surgery, the abdomen should be thoroughly lavaged prior to closure, and fresh gloves and instruments should be used for closure.

Surgery alone is considered a palliative treatment, which controls local disease and reduces risks of acute hemorrhage in the future. Average survival time following palliative surgery is 1 to 3 months.⁴

Average survival time can be extended to 6 months when surgery is followed by systemic chemotherapy.⁵ Doxorubicin-based protocols are the most common, but the number of treatments that a patient can receive are limited by the accumulated cardiotoxicity. Other protocols, including the use of metronomic chemotherapy, are being investigated to maximize survival times and quality of life following surgery.

There is also new, ongoing research into therapeutic options for hemangiosarcoma, but limited data are available at this time. Ettinger said that a new drug called eBAT is being studied at the University of Minnesota as both a treatment and preventative option, but it is not commercially available. Losartan, an angiotensin subtype II receptor blocker in dogs, is also being studied as a possible palliative option due to its antitumor effects. Ettinger expressed excitement about the possibility of new therapies but noted that more research is needed.

The role of supplements

Ettinger also discussed the use of supplements as a part of both palliative and curative-intent treatment protocols. Polysaccharopeptides are derived from Asian mushrooms and are thought to have antitumor activities through several different mechanisms of action. Several blends are available, but many are proprietary, which makes comparing brands difficult. Ettinger recommended I’m-Yunity, the product used in a small study of 15 dogs that showed a slight increase in survival times beyond surgery alone, though the study lacked a placebo group.⁶ However, because this product can be expensive, she offered K9 Immunity Plus as an alternative, with the reminder that this blend has not been studied.

Yunnan Baiyao, a Chinese herbal mixture commonly used in patients with hemorrhage, may also be helpful for patients with hemangiosarcoma. Ettinger suggested this product as a palliative measure for patients with metastatic nodules that could rupture and bleed or for patients with a splenic tumor that has ruptured and the client declines surgery.

Key talking points

When discussing hemangiosarcoma with clients, Ettinger described it as an “aggressive and malignant cancer of blood vessels” that can occur in many locations in the body. She stresses to clients that noninvasive tests will not tell us if a splenic mass is hemangiosarcoma and that we must wait for biopsy results to give accurate diagnosis and prognosis. Treatment of hemangiosarcoma is fought on 2 battlefronts: locally and distantly. Locally is where the cancer is growing, and distantly is to control metastatic disease.

Despite the poor long-term prognosis, Ettinger noted that “a lot of my clients who treat are very happy they did, even with surgery alone, because the quality of life they get is good.”

Kate Boatright, VMD, a 2013 graduate of the University of Pennsylvania, is an associate veterinarian and freelance speaker and author in western Pennsylvania. She is actively involved in organized veterinary medicine at the local, state, and national levels and is a former national officer of the Veterinary Business Management Association.

References

1. Pintar J, Breitschwerdt EB, Hardie EM, Spaulding KA. Acute nontraumatic hemoabdomen in the dog: a retrospective analysis of 39 cases (1987-2001). J Am Anim Hosp Assoc. 2003;39(6):518-522. doi:10.5326/0390518
2. Cleveland MJ, Casale S. Incidence of malignancy and outcomes for dogs undergoing splenectomy for incidentally detected nonruptured splenic nodules of 105 cases (2009-2013). J Am Vet Med Assoc. 2016;248(11):1267-1273. doi:10.2460/javma.248.11.1267
3. Wendelburg KM, O'Toole TE, McCobb E, Price LL, Lyons JA, Berg J. Risk factors for perioperative death in dogs undergoing splenectomy for splenic masses: 539 cases (2001-2012). J Am Vet Med Assoc. 2014;245(12):1382-1390. doi:10.2460/javma.245.12.1382
4. Wendelburg KM, Price LL, Burgess KE, Lyons JA, Lew FH, Berg K. Survival time of dogs with splenic hemangiosarcoma treated by splenectomy with or without adjuvant chemotherapy: 208 cases (2001-2012). 2015;247(4):393-403. doi:10.2460/javma.247.4.393
5. Chun R. Hemangiosarcoma. In: Clinical Veterinary Advisor Dogs and Cats. 2nd ed. St. Louis, MO: Elsevier Mosby;2017:483-486.
6. Brown DC, Reetz J. Single agent polysaccharopeptide delays metastases and improves survival in naturally occurring hemangiosarcoma. Evid Based Complement Alternat Med. 2012;2012:384301. doi:10.1155/2012/384301