History

A 22-year-old Warmblood gelding was referred to the North Carolina State University Large Animal Emergency Service for evaluation of anemia. The horse was treated for signs of colic and fever (38.9 °C)suspected to be secondary to a large colon impaction the day before the referral. Treatment consisted of administration of an unknown dose of flunixin meglumine and enteral fluids administered via nasogastric intubation.

Clinical and Gross Findings

On physical examination, the horse was quiet and alert, with mild tachycardia (52 beats/min), tachypnea (28 beats/min), and pale pink mucous membranes. Complete blood count showed marked macrocytic, normochromic, regenerative anemia with a mean corpuscular volume of 55.1 fL (reference interval, 36 to 52 fL), mean corpuscular hemoglobin concentration of 38.5 g/dL (reference interval, 34 to 39 g/dL), and HCT of 11% (reference interval, 32% to 52%) associated with mild leukopenia (4,000 cells/µL; reference interval, 5.50 X 10³ to 12.50 X 10³ cells/µL) and thrombocytopenia (26 X 10³/platelets/µL; reference interval: 100 X 10³ to 600 X 10³/platelets/µL). Manual PCV was 15%. Serum biochemistry showed mild hypocalcemia (calcium, 11.0 mg/dL; reference interval, 11.50 to 14.20 mg/dL), hyperbilirubinemia (bilirubin, 4.70 mg/dL; reference interval, 0.50 to 2.30 mg/dL), and hypoproteinemia (protein, 4.80 g/dL; reference interval, 5.70 to 8.00 g/dL). Venous blood gas analysis showed metabolic alkalosis (pH, 7.59; Hco₃, 35.5 mmol/L) without respiratory compensation (Pco₂, 37 mm Hg). Abdominal palpation per rectum was unremarkable aside from multiple nodules palpable in the caudal edge of the spleen. Abdominal ultrasonography revealed moderate free hypoechoic peritoneal fluid. The spleen was diffusely hyperechoic with rounded edges and had multifocal cavitations with a large, rounded mass measuring approximately 10 cm in in maximum dimension. An abdominocentesis revealed frank blood. Given the clinical presentation and poor prognosis, the horse was euthanized.

Gross postmortem examination revealed 3 L of frank blood in the peritoneal space. The spleen had multifocal to coalescing, semifirm, dark red masses ranging from 0.2 cm in diameter to 14.5 X 14.0 X 8.7 cm with multiple cavitations filled with blood and yellow friable necrotic material on cut surface (Figure 1). Extending from the capsular surface of the left kidney and severely compressing the subjacent renal cortex was a nonencapsulated similar mass associated with a subcapsular hematoma measuring 23.0 X 7.0 X 21.0 cm and weighing 1.1 kg. Similar masses ranging from 0.2 cm in diameter up to 6 X 4 X 3 cm were noted in the serosal surface of the peritoneum, omentum, mesentery, intestines, stomach, esophagus, liver, adrenal glands, diaphragm, kidneys, lymph nodes, extraocular muscles, epaxial muscle, thoracic pleura, lungs, pericardial sac, and heart. Colonic impaction was not observed during the postmortem evaluation.

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Photograph of the spleen of a 22-year-old Warmblood gelding that had a 1-day history of fever, pale pink oral and ocular mucous membranes, and marked macrocytic, normochromic regenerative anemia. Note the prominent multifocal to coalescing, markedly raised, tan to red, semifirm masses ranging from 1 cm in diameter to 14.5 X 14 X 8.7 cm.

Citation: Journal of the American Veterinary Medical Association 260, 11; 10.2460/javma.22.03.0100

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Histopathologic Findings

Histologically, the splenic masses consisted of a nonencapsulated, poorly demarcated, infiltrative, densely cellular mesenchymal neoplasm composed of plump spindle cells haphazardly arranged in broad streams, poorly formed blood-filled vascular clefts, and channels separated within a fibrous stroma. Neoplastic endothelial cells had variably distinct cell borders, a mild to moderate amount of eosinophilic fibrillar cytoplasm, and oval to elongated nuclei with coarsely stippled chromatin containing up to 2 distinct nucleoli (Figure 2). Anisocytosis and anisokaryosis were moderated; 50 mitotic figures were noted in 10 hpf (2.37 mm²). Within the neoplasm, there were multifocal areas of necrosis, hemorrhage, organizing thrombus, and a moderate number of hemosiderophages and hematoidin-laden macrophages. The peritoneum, omentum, mesentery, intestines, stomach, esophagus, liver, adrenal glands, diaphragm, kidneys, lymph nodes, extraocular muscles, epaxial muscle, thoracic pleura, lungs, pericardial sac, and heart had neoplastic cells with similar morphological features as those described within the spleen. The left renal capsule had an area of rupture resulting from the multifocal proliferation of neoplastic cells similarly described in the spleen. Furthermore, the renal tubules were undergoing degeneration and necrosis with intratubular hyaline casts and intratubular erythrocytes.

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Photomicrograph of sections of the spleen of the horse in Figure 1. A—The masses consisted of a nonencapsulated, poorly demarcated, infiltrative, densely cellular mesenchymal neoplasm forming vascular clefts and poorly defined, irregular, variably sized vascular channels lined by a discontinuous layer of neoplastic cells. H&E stain; bar = 100 µm. B—Neoplastic endothelial cells had variably distinct cell borders, a mild to moderate amount of eosinophilic fibrillar cytoplasm, and oval to elongated nuclei with coarsely stippled chromatin. Anisocytosis and anisokaryosis were moderated, with evidence of high mitotic activity (arrowheads). H&E stain; bar = 25 μm.

Citation: Journal of the American Veterinary Medical Association 260, 11; 10.2460/javma.22.03.0100

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Morphologic Diagnosis and Case Summary

Morphologic diagnosis and case summary: disseminated hemangiosarcoma with hemoabdomen in a horse.

Comments

The clinical, ultrasonographic, macroscopic, and histopathologic findings confirmed disseminated hemangiosarcoma with secondary hemoabdomen. Hemangiosarcoma is a malignant neoplasm arising from the vascular endothelium and most commonly presents as a multicentric form with primary involvement in the spleen, liver, and subcutis.^1,2 In horses, visceral hemangiosarcomas are considered rare, with a prevalence of 0% to 0.7% among the evaluated horses, often with a poor prognosis.^1,3 No breed or sex predispositions are reported.³ Affected horses are between 3 years to 27 years, with an average age of 12 years.⁴ In horses, the final diagnosis is usually based on postmortem and histological examination.⁴

Clinical findings typically associated with hemangiosarcomas in horses include apathy, difficulty breathing, pale mucous membranes, poor body condition, anemia, tachycardia, tachypnea, fever, abdominal distension, and pain.⁴ Given the nonspecific clinical findings of colic and anemia as seen in this case, differential diagnoses included infectious diseases (eg, babesiosis and ehrlichiosis), gastrointestinal diseases (eg, gastric ulcer, colic, and parasites), and neoplasia (eg, malignant melanocytic tumor, lymphoma, and carcinoma). Complete blood count revealed regenerative macrocytic normochromic anemia with leukopenia and thrombocytopenia, which are findings reported in horses with hemangiosarcoma as similarly described in dogs.^3–5 The hematological alterations are consequences of the hemorrhagic episodes secondary to neoplastic proliferation. In this case, CBC alterations were attributed to the rupture of the renal capsule leading to severe hemoabdomen. Histological findings in the renal tubules were likely secondary to extensive subcapsular hemorrhage and ischemic injury. The colic clinically observed in this case may be secondary to decreased water intake, dehydration, anemia, or gastrointestinal stasis from pain.⁶ In addition, it is believed that the hemoabdomen secondary to a neoplastic mass rupture had increased the intra-abdominal pressure and/or caused irritation of the intestinal wall, contributing to the colic syndrome.^7,8 Ultrasound examination was extremely important to detect the free fluid in the abdominal cavity, the hyperechogenicity of the spleen with rounded edges, multifocal cavitations, and a large mass that altogether was clinically compatible with a splenic abscess or hemangiosarcoma.⁹ Due to the critical condition of the horse associated with the risk of rupture of the mass, euthanasia was elected.

Macroscopically, hemangiosarcomas have a semifirm consistency and a color ranging from yellow- brown to red, with multiple cavitations and an abundant amount of blood oozing on cut surface.² Disseminated hemangiosarcomas in horses are commonly reported to primarily affect the lungs, pleura, skeletal muscle, spleen, heart, kidney, and brain. The most common metastatic sites are the gastrointestinal tract, mesentery, liver, adrenal glands, diaphragm, ovary, larynx, and mandible.^4,10 In this case, in addition to splenic masses, other multiple neoplastic masses were seen in different organs previously mentioned. All masses had similar gross features as observed in the spleen but with variable smaller sizes, most likely indicating metastatic sites and not the primary neoplastic origin. Therefore, it is highly speculated that the primary origin of the hemangiosarcoma of the case reported was the spleen based on the largest observed mass.

Histologically, the characteristics of hemangiosarcomas are the endothelial neoplastic proliferation arranged in channels and vascular clefts filled with blood with multiple hemorrhagic foci.² The moderate anisocytosis and anisokaryosis associated with a high number of mitotic figures indicated important criteria of cellular malignancy.^2,3 Although this neoplasm had histologic features consistent with a high-grade hemangiosarcoma based on the canine grading system,¹¹ histologic grade has not been correlated with prognosis in either dogs¹¹ or horses.² Other features, such as infiltration and mitotic rate, are better predictors of prognosis in horses.²

Definitive diagnosis of hemangiosarcomas is confirmed by microscopic examination. Immunohistochemistry is usually not needed for the final diagnosis.² When helpful to identify poorly differentiated neoplasms, von Willebrand antibody-antigen has been described as exhibiting a variable degree of cytoplasmic binding with neoplastic hemangiosarcoma cells in horses.¹² Treatment options in horses are limited based on the location of the primary tumor, with complete surgical removal being possible only when it occurs in the cutaneous and/or ocular forms.⁵ In cases of disseminated hemangiosarcoma as observed herein, effective therapy is not reported to this date and the prognosis is often grave.¹