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A Practical Approach to Canine Splenic Masses
I’ve got a dog with a splenic mass lesion. What are the chances of it being a haemangiosarcoma?
The “double two-thirds rule” states that approximately 2/3 of canine splenic tumours are malignant, and out of those a further 2/3 are haemangiosarcomas. So, in other words about 44% are haemangiosarcomas. The dog’s breed can significantly affect the likelihood of a splenic mass lesion being a haemangiosarcoma, with German Shepherds and Retriever breeds being more likely to have a haemangiosarcoma (or any splenic malignancy) than Poodles, Spaniels and small Terriers. In the context of a haemoabdomen however, haemangiosarcoma accounts for approximately 2/3 of the cases (“triple two-thirds rule!”).
Ultimately the only ways of ascertaining if an aggressive, malignant process is going on is to demonstrate disseminated metastatic disease with imaging (and of course the absence of metastases doesn’t exclude the possibility of an aggressive malignancy), or to obtain tissue for histopathological analysis. A large primary mass in the absence of metastasis is suggestive of a benign lesion or low-grade malignancy however we can’t rely on this alone! The occurrence of haemoabdomen makes a malignant tumour more likely although any kind of splenic lesion can rupture.
Some of the other malignant differential diagnoses for a splenic mass can have good survival times with splenectomy alone, for example marginal zone lymphoma (not to be confused with a “normal” multicentric lymphoma) or some sarcomas. Histiocytic sarcoma or haemangiosarcoma represent the two most aggressive malignancies of the spleen, and chemotherapy is routinely indicated for these.
The dog has a metastastic splenic tumour. There’s no hope - right ?
In some studies the survival time for metastatic haemangiosarcoma cases has been shown to be no different from non-metastatic cases, providing they are treated appropriately with chemotherapy post surgery. The reported median survival time for surgery + chemo is in the region of 6 months, versus 6-8 weeks for surgery alone. In the case of splenic histiocytic sarcoma however (a much rarer diagnosis), the existence of metastasis at diagnosis will always negatively affect the prognosis.
The most important consideration in dealing with a haemangiosarcoma (of any location other than dermal, or perhaps lingual) is that it should be considered a systemic, medically-treated disease. It develops from malignant transformation of circulating blood vessel precursor cells (produced in the bone marrow); although the cancer cells are often found in a discrete mass lesion, the fact that malignant transformation has occurred elsewhere underlines that the cells are mobile and disease is systemic. In metastatic cases there is often debate about whether one tumour is “primary” and the others represent metastasis, or whether the disease is simply multicentric in nature. Owing to a large proportion of cells actively dividing, haemangiosarcoma is equivalently chemosensitive and should expect a similar overall survival time to many cases of multicentric T cell high-grade lymphoma. Surgery does not directly treat the disease, it is simply a “first-aid” measure to address catastrophic haemorrhage or to address “ticking time-bombs” (lesions about to rupture), and is also necessary to conirm the diagnosis. Splenic or right-auricular lesions are frequently considered good surgical candidates (in the latter case this is because the lesions are usually well-pendunculated).
Can haemangiosarcoma occur in other locations than the spleen ?
Yes – it can occur anywhere with blood vessels ! However visceral locations are the most common. The localisation of the disease will affect the metastatic propensity and survival times. Most visceral locations will expect a metastatic rate of at least 90% (kidney slightly less), whereas the subcutaneous or intramuscular masses have a varied rate of metastasis between 30-80%. Dermal lesions have a metastatic rate of 0-30% and are often cured with surgical excision. Lingual lesions (rare in the UK) behave similarly. A small number of primary lymph node haemangiosarcomas (among other locations) have been described and their course of disease has been aggressive.
What chemotherapy treatments are recommended for haemangiosarcoma?
The standard-of-care is one injection of doxorubicin every 2 weeks for up to 6 doses. Other chemotherapy drugs can be given in between doxorubicin doses to intensify the treatment if desired but few studies have shown survival times beyond 6-9 months for the majority of dogs. Metronomic chemotherapy has been shown to produce survival times of approximately 6 months post surgery in non-metastatic cases (exactly how they fare when disease is widely-metastatic is unknown). Continuous administration of thalidomide too has been shown to extend survival to six months in non-metastatic cases following splenectomy. Tyrosine kinase inhibitors are sometimes used as well, although current evidence does not support their use.
After 6 cycles of doxorubicin-based chemotherapy, tradition has involved stopping all treatment. In the face of an unwaveringly aggressive disease this is a peculiar practice. Although we are right to be concerned about making dogs unwell with an extended course of chemotherapy, consideration should be given to trying to maintain the disease control using, for example metronomic chemotherapy or thalidomide rather than “submitting” to the disease. Current evidence has shown benefit of this practice in one study, but not in another. Further, prospective evaluation is required, but it is the choice of the author to transition dogs onto a metronomic chemotherapy protocol as well as thalidomide after six cycles of doxorubicin-based treatment. Regular imaging to assess for disease recurrence is performed. When disease recurs, rescue agents like dacarbazine have been used with varying, but usually low, success.
Use of doxorubicin is a subject that courses much concern to many vets, but often for the wrong reasons. It is certainly a highly-vesicant drug, but providing a perfectly-placed first-stick IV catheter is used, and the infusion given with diligent monitoring, the risk of extravasation can be successfully controlled. Doxorubicin is certainly cardiotoxic too and pre-treatment echocardiography is advisable, however the risk of cardiotoxicity is often over-shadowed by rapid and aggressive dissemination of cancer which will occur if doxorubicin is not given, making the balance of risk and benefit clear. Providing doxorubicin is given over 20-30 minutes, continuous monitoring with ECG is not necessary.
The most common and often the dose-limiting toxicity of doxorubicin is gastrointestinal; typically diarrhoea and vomiting occurring 2-4 days post dosing. In some cases this can be serious and necessitate hospitalisation of the dog for intravenous fluids and supportive care. When the author uses doxorubicin, an initial dose of 27mg/m2 (a 10% reduction from the normal starting dose of 30mg/m2) is used for cases with pre-existing GI disease (or a history of poor dietary tolerance of many foods). Maropitant is given before the procedure (either IV or oral) and then for 3-4 days afterwards at home. Omeprazole and metronidazole are used to treat mild to moderate gastrointestinal upsets as an outpatient. Most cases of doxorubicin treatment are without severe adverse event however, and the benefit of the drug clearly outweighs the attendant risk.
What about haemangiosarcoma in cats ?
In cats, haemangiosarcoma lesions are equally-distributed between skin/subcutis and visceral sites. The cutaneous / subcutaneous tumours are extremely invasive (a 60-80% rate of local recurrence has been reported) but the rate of metastasis is considered to be low (owing to the rarity of these tumours a metastatic rate has not been established). Complete excision could therefore cure cats with local disease only, however high rates of recurrence are reported. Feline visceral haemangiosarcomas have a metastatic rate similar to their canine counterparts.
Further Reading:
• Davies O, Taylor AJ. Refining the “double two-thirds” rule: Genotype-based breed grouping and clinical presentation help predict the diagnosis of canine splenic mass lesions in 288 dogs. Vet Comp Oncol. 2020;1–11.
• Treggiari E, Borrego JF, Gramer I, et al. Retrospective comparison of first-line adjuvantanthracycline vs metronomic-based chemotherapy protocols in the treatment of stage I and II canine splenic haemangiosarcoma. Vet Comp Oncol. 2020;18:43–51.
• Marconato L, Chalfon C, Finotello R, et al. Adjuvant anthracycline-based vs metronomic chemotherapy vs no medical treatment for dogs with metastatic splenic hemangiosarcoma: A multi-institutional retrospective study of the Italian Society of Veterinary Oncology. Vet Comp Oncol. 2019;17:537–544.
• The addition of metronomic chemotherapy does not improve outcome for canine splenic haemangiosarcoma. C. K. Alexander1,*, K. L. Cronin*, M. Silver†, H. L. Gardner‡ and C. London; Journal of Small Animal Practice • Vol 60 • January 2019 •
• VAC Protocol for Treatment of Dogs with Stage III Hemangiosarcoma; Alvarez, Hosoya, Lara-Garcia et.al; J Am Anim Hosp Assoc 2013; 49:
• Evaluation of outcome associated with subcutaneous and intramuscular hemangiosarcoma treated with adjuvant doxorubicin in dogs: 21 cases (2001–2006); Bulakowski, Philibert, Siegel et.al; J Am Vet Med Assoc 2008;233:122–128
• Survival time of dogs with splenic hemangiosarcoma treated by splenectomy with or without adjuvant chemotherapy: 208 cases (2001–2012); Wendelburg, Price, Burgess et.al ; J Am Vet Med Assoc 2015;247:393–403
• Continuous Low-Dose Oral Chemotherapy for Adjuvant Therapy of Splenic Hemangiosarcoma in Dogs; J Vet Intern Med 2007;21:764–769
