+ Biologic Behavior

• HSA is a highly metastatic tumor with microscopic or macroscopic metastatic disease at diagnosis
• HSA arises from vascular endothelial cells
• HSA is the most common splenic tumor in dogs and accounts for 24%-50% dogs with splenic masses
• Splenic hemangioma and hematoma occur in 3%-34% dogs with splenic masses
• Other primary HSA sites include right atrium, liver, integument, urinary bladder, prostate, kidney, muscle, bone, CNS, and oral cavity
• Median age 9.0-10.5 years
• Sex predisposition: males
• Breed predisposition: GSD, Golden Retriever, Labrador Retriever, and Schnauzer
• Cause is unknown although linked with exposure to thorium dioxide, arsenical or vinyl chloride compounds, ultraviolet light, and local radiation therapy in humans
• 25% of dogs with splenic HSA have concurrent right atrial HSA
• HSA is highly metastatic: > 50% metastatic rate for splenic HSA
• Lungs are the most common metastatic site (64%-67%), followed by spleen (36%-60%), kidneys (55%), liver (41%-55%), 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%)
• Tumor rupture or erosion through blood vessels is common and results in seeding of peritoneum or omentum with tumor cells
• Splenic tumors other than HSA include LSA (4%), various sarcomas (i.e., undifferentiated sarcoma, FSA, leiomyosarcoma, mesenchymoma, myxosarcoma, histiocytic sarcoma, OSA, and liposarcoma), and metastatic carcinomas

+ General Considerations

• Splenic HSA and hemangioma have similar ultrasonographic and gross appearance and are difficult to differentiate
• HSA is significantly more likely to have increased VEGF levels
• Hemoabdomen is more common in dogs with HSA (76.4%) compared to hemangioma (29.6%)
• Neoplastic disease accounts for 80% of non-traumatic hemoabdomen cases in dogs and HSA for 88% of these cases
• 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)

+ Laboratory Findings

• Hematology: anemia and morphological changes to red blood cells such as nucleated erythrocytes, polychromasia, poikilocytes, anisocytes, shistocytes, and reticulocytes
• Morphologic changes due to iron loss, altered hepatic lipoprotein metabolism, microangiopathic disease, or DIC and sluggish flow through abnormal vascular channels resulting in increased membrane fragility
• Neutrophilic leukocytosis is common due to either stress or tumor rupture and necrosis
• Thrombocytopenia due to DIC, but may form part of Kasabach-Merritt syndrome
• Kasabach-Merritt syndrome is characterized by an enlarging vascular tumor, thrombocytopenia, anemia, prolonged PT and APTT, decreased FDP, and increased fibrin split products
• Thrombocytopenia (75%-90%), fragmented red blood cells (80%), and DIC (50%) are common findings
• Anemia and DIC associated with blood loss is common in cats with visceral HSA

+ Survey Radiographs

• 2 metastatic patterns in dogs with HSA:
• Widely disseminated nodular pattern (common)
• Diffuse interstitial pattern (uncommon)
• False-negative results are high: 22% from splenic HSA and > 50% for right atrial HSA

+ Ultrasonography

• Abdominal ultrasonography is a highly accurate and sensitive tool for splenic evaluation
• Primary HSA: mixed pattern of anechoic and hyperechoic regions
• Metastatic HSA: diffusely anechoic or hypoechoic appearance
• Ultrasound-guided FNA or needle-core biopsy contraindicated due to risk of seeding and low diagnostic yield

+ Electrocardiography

Ventricular arrhythmias are commonly associated with HSA due to hypoxia, anemia, or hypovolemia

+ Surgical Management

• Total splenectomy recommended
• Total splenectomy is considered a palliative procedure to reduce the risk of hemorrhage

+ Chemotherapy

• Doxorubicin 30 mg/m2 q 2-3 weeks for 5 doses
• ± cyclophosphamide 100-150 mg/m2
• Complications: neutropenia (common), severe gastroenteritis, cardiotoxicity, and sepsis

+ 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

+ Hemorrhage

• Hemorrhage is caused by tumor rupture, manipulation of the spleen or liver, and inadequate ligation
• Treatment: intravenous fluids and fresh whole blood (preferred as thrombocytopenia common in HSA)
• Autotransfusion contraindicated due to neoplastic cells and low clotting factors and platelets

+ Coagulopathy

• Fragmentation anemia and thrombocytopenia are common ± DIC
• Treatment: intravenous fluids (to maintain circulating volume) and fresh whole blood transfusions

+ Cardiac Arrhythmias

• Ventricular extrasystole and ventricular tachycardia
• Possible causes of cardiac arrhythmias include release of emboli during splenic manipulation, transient ischemic episodes, and release of toxic factors from abdominal viscera into the splanchnic circulation
• Treatment: correct underlying cause, correct acid-base and electrolyte abnormalities, intravenous fluids ± anti-arrhythmic drugs (lidocaine)
• Continuous ECG monitoring is recommended for 12-36 hours post-splenectomy

+ Prognosis

• Poor prognosis
• MST 19-86 days with surgery alone, with 12-month survival rate 6.25%
• MST 172-202 days with surgery and chemotherapy with 12-month survival rate up to 20%
• MST 257-273 days for stage I HSA
• MST 156-210 days for stage II HSA
• MST 107-136 days for stage III HSA
• Prognostic factors include clinical stage and addition of immunotherapy:
• Stage III disease (i.e., metastasis) significantly decreases MST (60-107 days v 172-273 days) and 12-month survival rate (0% v 20%)
• L-MTPE combined with surgery and chemotherapy significantly improves MST compared to surgery and chemotherapy only (277 days v 143 days)