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- 2. Megan 13yo Female Border Collie Presentation: worsening lethargy. With a history of intermittent anemia over the last few weeks. Clinical Findings: QAR Slightly pale MM, Normal CRT Fluid thrill noted on abdominal palpation HR 120 bpm, Temperature and RR wnl.
- 3. Investigations Abdominal Ultrasound: revealed large volume of free fluid. Small cavitated mass adjacent to the spleen, and a larger mass arising in cd abdomen. Abdomenocentesis: Blood (PCV 32%) Orthogonal thoracic radiographs: unremarkable Cardiac scan: No obvious masses Hematology: Moderate Anemia (HCT 28%) (ref 37-55%) Neutrophilia (15x10^9/L) (ref 6-12x10^9/L) Thrombocytopenia (60x10^9/L) (ref 200-500x10^9/L) Mildly prolonged APTT (37 seconds) (ref 17-24sec)
- 4. Diagnosis Haemoabdomen, likely secondary to abdominal neoplasia. Non Traumatic/Spontaneous Causes of Haemoabdomen • Neoplasia*** • Splenic hematoma • Splenic torsion • Coagulopathies • Vena caval syndrome secondary to Dirofilariasis
- 5. Plan Referred to Soft Tissue service for an emergency exploratory laparotomy. Findings of Exlap: Small mass on falciform fat Larger caudal abdominal mass 800ml of free blood Grossly abnormal liver Both masses, and a liver biopsy were sent for histopathology.
- 6. Histopathology The histological appearance of the two masses was consistent with an haemangiosarcoma. No normal tissue is present in the examined sections to suggest a site of origin.
- 7. Haemangiosarcoma (HSA) Highly malignant tumor of endothelial cells. Occurs more frequently in dogs than in any other species and is characterized by a high fatality rate (1) The overall prevalence is reported to be 0.3% to 2.0% of all tumors in dogs; German shepherds, golden retrievers, and Labrador retrievers are overrepresented (2). The etiology of HSA is still unknown, although the strong breed association suggests an inherited or familial predisposition.
- 8. Haemangiosarcoma (HSA) cont. The 3 most common primary sites of HSA are the spleen (28% to 50%), right atrium/auricle (up to 50%), and skin or subcutaneous tissue (13%) (1,3). Most common sites of metastasis of HSA: Lungs (65%) Spleen (36-60%) Kidneys (55%) Liver (41-55%) which can occur via haematogenous spread or by local seeding after tumor rupture (1).
- 9. Common Laboratory Findings Hematology: Anemia morphological changes to red blood cells: nucleated erythrocytes Polychromasia poikilocytes, anisocytes, shistocytes, and reticulocytes Neutrophilia due to either stress or tumor rupture and necrosis thrombocytopenia
- 10. Common Diagnostic Imaging Findings Thoracic Radiographs Metastatic patterns in dogs with HSA: widely disseminated nodular pattern (common) diffuse interstitial pattern (uncommon) Abdominal US primary HSA: mixed pattern of anechoic and hyperechoic regions metastatic HSA: diffusely anechoic or hypoechoic appearance Echocardiography Helps detect structural abnormalities, presence of tumours, clots or fluid. Electrocardiography ventricular arrhythmias are commonly associated with HSA due to hypoxia, anemia, or hypovolemia
- 11. Treatment of HSA Usually a combination of: Chemotherapy: Doxorubicin +/- Cyclophosphamide (AC) +/-Vincristine (VAC) Metronomic Chemotherapy Continuous low dose oral cyclophosphamide. Surgical: Try to remove the primary tumour. Ex: SPLENECTOMY: Historically the treatment of SPLENIC HSA.
- 12. HSA Staging Clinical Stage Tumour Node Metastasis I T0-1 N0 M0 II T1-2 N0-1 M0 III T2-3 N0-2 M1 T (Primary Tumour) T0 No evidence of neoplasia T1 <5cm diameter, confined to primary site T2 >5cm diameter, ruptured, or invading subcutaneous tissue T3 Invading adjacent structures including muscle Node N0 No evidence N1 Regional LN involvement N2 Distant LN involvement Metastasis M0 No evidence of metastasis M1 Evidence of distance metastasis
- 13. Prognosis Relatively Poor MST (Mean survival times) Surgery alone: 2-3 months Surgery followed by Chemotherapy: 4-6 months
- 14. Back to Megan… Post Operatively: Due to her loss of blood and thrombocytopenia she required fresh frozen plasma and Packed red cell transfusion (post operative PCV 6%, Hg 2 g/dl) with good response over the following 24h. She was sent home on strict cage rest, pain medications, antibiotics, and antiemetics. With a recheck in 10 days to remove the sutures and talk about chemotherapy treatment options.
- 15. Megan’s Treatment Plan Pre Chemotherapy: Heart Scan Showed adequate contractility Abdominal scan Revealed a nodule on the left kidney that should be monitored Start Doxorubicin therapy. One dose every 3 weeks, for 4-6 doses. She received her first dose this week. If protocol not tolerated, discussed switching to metronomic chemotherapy.
- 16. Questions?
- 17. References Canine hemangiosarcoma: retrospective analysis of 104 cases.Brown NO, Patnaik AK, MacEwen EG J Am Vet Med Assoc. 1985 Jan 1; 186(1):56-8. Kahn, S. Anthony, et al. "Doxorubicin and deracoxib adjuvant therapy for canine splenic hemangiosarcoma: A pilot study." The Canadian Veterinary Journal 54.3 (2013): 237. Sorenmo, K. U., Baez, J. L., Clifford, C. A., Mauldin, E., Overley, B., Skorupski, K., Bachman, R., Samluk, M. and Shofer, F. (2004), Efficacy and Toxicity of a Dose-Intensified Doxorubicin Protocol in Canine Hemangiosarcoma. Journal of Veterinary Internal Medicine, 18: 209– 213. doi: 10.1111/j.1939-1676.2004.tb00162.x Thamm DH. Hemangiosarcoma. In: Withrow SW, Vail DM, editors. Small Animal Clinical Oncology. 4th ed. St Louis, Missouri: Saunders/Elsevier; 2007. pp. 785–795.
Editor's Notes
- - Presented as a emergency to the SAH for worsening lethargy- occurring over a course of several weeks, along with intermittent anemia that was dx by her regular vet. - On clinical exam: the most significant clinical findings included slightly pale MM, and a fluid thrill that was noted on abdominal palpation. She also had an audible grade 1 heart murmur. No petechial haemorrhage or scleral haemorrhage was noted and her pulse quality was reasonable. **Hx: Dog previously diagnosed with idiopathic epilepsy
- -Further diagnostic investigation revealed… -A large volume of free fluid in the abdomen, along with a small cavitated mass sitting adjacent to the spleen, and a larger mass arising in the caudal abdomen. -Blood was obtained from Abdomenocentesis -Hematology revealed a moderate anemia, neutrophilia, and marked thrombocytopenia, as well as a mildly prolonged Activated Partial Thromboplastin Time -Thoracic radiographs were clear, and a cardiac scan revealed no obvious masses. Additional info: Abdominal US: to look for amount of fluid present, to look for masses, to assist in sampling. Ddx for abdominal masses: Neoplasia, cysts, hematomas. - Abdomenocentesis- PCV of abdominal fluid will be > than peripheral blood if active bleeding is occurring. - Orthogonal thoracic radiographs to look for- metastasis (or if trauma possible- look for concurrent thoracic injury or diaphragmatic rupture) Cardiac scan to look for HSA (most common sites- Spleen and commonly the RIGHT ATRIUM) Hematology: Anemia- results of the abdominal bleed. Leukocytosis is often noted in associated with stress, trauma, or NEOPLASIA. The thrombocytopenia is likely due to PLT consumption. Significance with haematology and coagulation tests and parameters***
- At this point a diagnosis of hemoabdomen was made. Using the information gathered from our hx, clinical exam, diagnostic imaging and hematology- the most likley cause of the hemoabdomen is secondary to abdominal neoplasia, however there are several other possible causes of non traumatic hemoabdomen including: Splenic hematoma Splenic torsion Coagulopathies. For example: rodenticide poisoning, hepatic disease and hemophilia -In one study I found, up to 80% of intra-abdominal neoplasia in dogs was malignant, and of those 88% were hemangiosarcomas. Other malignant tumors (of spleen, or abdomen): mesotheliomas, lymphosarcomas, various other sarcomas and possibly metastatic carcinomas Additional information: •neoplastic effusion can be differentiated from non-neoplastic as neoplastic effusions have: •significantly lower glucose concentrations (72.6 mg/dL v 110.0 mg/dL) •significantly higher lactate concentrations (3.81 mmol/L v 1.68 mmol/L)
- -Megan was referred to Soft tissue service for an emergency exploratory lapartomy, where a small mass was found on falciform fat and removed. Another larger mass in the caudal abdomen was consistent with a large blood clot adherent to omentum and mesentery, the bladder and abdominal wall although not originating from any of these organs. The mass was dissected and removed without causing further haemorrhage.
- -on histopath, the masses were found to be hemangiosarcomas, and the changes in the liver were mild and consistent with degeneration likely secondary to hypoxia. -Before continuing on with Megan’s case, I’m now going to talk to you a bit more in depth about Hemangiosarcoma in dogs. Additional Information: ***POST OP INFORMATION: Due to Megan's loss of blood and thrombocytopenia she required a FFP (fresh frozen plasma) and PRCs (packed red cells) transfusion (post operative PCV 6%, Hg 2 g/dl) with good response over the following 24h (current PCV 23% with TS 52 g/dl). Her aPTT was very increased following surgery as well (170s). Her HR and BP have remained stable and within normal and she has been more mobile and alert although with no appetite. **look up transfusion information
- -Hemangiosarcomas are highly malignant tumors of endothelial cells (so of the linings of the body’s blood vessels). Sarcomas- arise from transformed cells of mesenchymal origin. HSA occurs most frequently in dogs, and is often characterized by its: High fatality rate There is a strong breed association, suggesting there is likely an inherited or familial predisposition. - There is also a higher reported incidence in male dogs. References: Thamm DH. Hemangiosarcoma. In: Withrow SW, Vail DM, editors. Small Animal Clinical Oncology. 4th ed. St Louis, Missouri: Saunders/Elsevier; 2007. pp. 785–795. 2. Canine hemangiosarcoma: retrospective analysis of 104 cases.Brown NO, Patnaik AK, MacEwen EG J Am Vet Med Assoc. 1985 Jan 1; 186(1):56-8.
- -The most common primary sites include : -the spleen -and the right atrium of the heart -and less commonly- the skin or subcutaneous tissue. Metastasis and local infiltration occur early in the disease progression. And the most common sites for metastasis include: The lungs The spleen The kidneys and The liver Other less common sites of metastasis: brain (20%), intestines (20%), adrenal glands (20%), skeletal muscle (20%), visceral lymph nodes (15%), skin and subcutaneous tissue (15%), left ventricle (10%), and mesentery and omentum (10%) Reference: 3. Cutaneous hemangiosarcoma in 25 dogs: a retrospective study.Ward H, Fox LE, Calderwood-Mays MB, Hammer AS, Couto CG J Vet Intern Med. 1994 Sep-Oct; 8(5):345-8.
- Common laboratory findings associated with HSA include: regenerative anemia with morphological changes to the red blood cells that can be due to iron loss, or DIC and sluggish flow through abnormal vascular channels resulting in increased membrane fragility Neutrophilia- due to stress or tumor rupture and necrosis and a Thrombocytopenia. Additional Information: Thrombocytopenia can be associated with--- --Kasabach-Merritt syndrome is characterized by an enlarging vascular tumor, thrombocytopenia, anemia, prolonged PT and APTT, decreased FDP, and increased fibrin split products
- - Thoracic radiographs- useful to check for metastatic spread to the lungs. Abdominal Ultrasound- highly useful in finding the primary tumor, and also for evaluating the spleen and other abdominal organs for metastasis. Echo- helps detect the presence of tumors, or structural abnormalities ECG- can detect ventricular arrhythmias commonly associated with HSA. These can be due to hypoxia, anemia or hypovolemia Additional information: Thoracic Rads: •false-negative results are high: 22% from splenic HSA and > 50% for right atrial HAS US: •ultrasound-guided FNA or needle-core biopsy contraindicated due to risk of seeding and low diagnostic yield
- -Doxorubicin is usually the chemotherpeutic of choice. It is often used in a single agent protocol, but occasionally is seen in combination protocols with Cyclophosphamide and Vincristine. -Doxorubicin treatment can result in cardiotoxicity and the common side effects of chemotherapy in general can include: myelosuppression, and GI upset. So some dogs may not tolerate treatments well. -Another option is Continuous Low-Dose Oral Chemotherapy -One study I read showed similar mean survival times to conventional doxorubin single agent treatment, and this may be tolerated better by some dogs. Additional Info: complications of chemo: neutropenia (common), severe gastroenteritis, cardiotoxicity, hemorrhagic cystitis and sepsis ( for Adjuvant Therapy of Splenic Hemangiosarcoma in Dogs- alternating cycles of low dose cyclophosphamide, etoposide,and piroxicam was used as adjuvant therapy for dogs with stage II HAS- showing similar mean survival times to conventional doxorubicin single agent treatment. Immunotherapy •immunotherapy aims at altering host-tumor response •mixed bacterial vaccination and liposome-encapsulated muramyl tripeptide phosphatidylethanolamine (L-MTPE) have been investigated with mixed results Other Treatments •angiogenesis inhibitors and gene therapy
- -You will approach staging HSA like you approach any other cancer case- using the TNM system. -Metastasis and local infiltration occur early in the disease progression, so often cases of HSA are not detected until later stages.
- The prognosis for canine HSA is relatively poor. Surgery mean survival time is based off of splenic HSA, and refers to total splenectomies - It should be noted that dog’s with splenic HSA that have ruptured, have a poorer prognosis.
- -Post operatively Megan received a FFP and PRC transfusion. Her PCV continued to increase, coagulation times reduced, and PLT count returned to normal after a few days. -She was given another abdominal ultrasound where they found a degree of inflammation around the site of the larger mass and a suspicious area in the kidney, which they were concerned may represent spread of the tumour.
- -after discussion with the owner, they were keen to proceed with Doxorubicin therapy every 3 weeks for 4-6 doses to optimize her survival prospects. -before doxorubicin treatment started she received a heart scan (which showed her heart had adequate contractility to begin treatment). She will receive another heart scan after receiving 4 doses of Doxorubicin since it is associated with DCM. Her abdominal US revealed a nodule on her left kidney that could potentially be an indication of tumor spread. This will be closely monitored. She received her first dose of Doxorucin this week (with Chlorphenamine IV and Maropitant SC), and was sent home with cerenia tablets.