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Pathology in Practice

Figure 1—Photograph of the right thoracic wall at the level of the fifth and sixth ribs in a 27.25-year-old Arabian mare examined because of weight loss and intermittent anorexia during the preceding several weeks that subsequently collapsed and died. Notice that the intercostal muscles and rib bones are effaced by multiple, well-demarcated, raised to flat, slightly firm, dark red to black nodules (white arrows). The fifth rib is fractured (black arrowhead).

History A 27.25-year-old 394-kg (866.8-lb) sexually intact female Arabian was examined because of several weeks of weight loss and intermittent anorexia. The horse’s body condition score was 4 of 9. Gastroscopy was performed, and findings were considered normal. However, the horse suddenly collapsed and died at the time of discharge from the hospital; necropsy was performed at the University of Illinois Veterinary Diagnostic Laboratory. Clinical and Gross Findings At necropsy, the horse was in poor nutritional condition, characterized by decreased skeletal muscle and adipose tissue overlying the ribs and prominences of the vertebral column. The pleural cavity contained approxiThis report was submitted by Rommel Max Tan, DVM, PhD; Adam W. Stern, DVM; and Eva-Christina Schliewert, DVM; from the Department of Animal Biotechnology and Conservation, Delaware Valley College, Doylestown, PA 18901 (Tan); and the Department of Pathobiology and Veterinary Diagnostic Laboratory (Stern) and the Department of Clinical Medicine (Schliewert), College of Veterinary Medicine, University of Illinois, Urbana, IL 61802. Address correspondence to Dr. Tan ([email protected]). JAVMA, Vol 244, No. 8, April 15, 2014

mately 10 to 15 L of blood (hemothorax). Disseminated throughout the left and right lung lobes were numerous, 1- to 5-mm-diameter, slightly firm, dark red to black nodules. When cut, the nodules oozed blood. The right wall of the thorax, at the level of the fifth and sixth ribs, had several dozen nodules (1 mm to 3 cm in diameter) similar to those within the lungs (Figure 1). The cut surfaces of these nodules also oozed blood. The right fifth rib was fractured and focally effaced by an approximately 5 X 5-cm, 15-cm-diameter, red to black, friable neoplasm. Within this neoplasm were fragments of bone. The dorsal aspect of the right sixth rib was also fractured. The peritoneal cavity contained approximately 10 L of blood (hemoabdomen). The body of the spleen had a single nodule (2 X 1 X 1.5 cm) similar to those within the lungs. The root of the mesentery had an 18 X 23 X 14-cm, red, friable mass of clotted blood (hematoma). The perirenal fat was filled by approximately 5-cm-thick clotted blood that partially effaced a portion of the left kidney. There was a pedunculated lipoma within the mesentery. Formulate differential diagnoses from the history, clinical findings, and Figure 1—then turn the page → Vet Med Today: Pathology in Practice


Histopathologic Findings

Figure 2—Photomicrograph of a section of the right thoracic wall of the horse in Figure 1. The neoplasm is composed of blood filled-vascular channels that are supported by collagenous stroma containing hemosiderophages (arrowhead). H&E stain; bar = 100 µm.

Samples of the affected tissues underwent histologic examination. Within the fifth rib and the internal intercostal muscle between the fifth and sixth ribs, there was an infiltrative, unencapsulated, moderately cellular neoplasm mixed with marked amounts of necrosis. Neoplastic cells were arranged in blood-filled channels, supported by scant mild to moderate collagenous stroma (Figure 2). The neoplastic cells lining these channels were polygonal, with indistinct cell borders, and scant eosinophilic homogeneous cytoplasm. The neoplastic cells each had a round to ovoid nucleus, with finely stippled chromatin and 1 to 3 nucleoli. Moderate anisocytosis and anisokaryosis were present, and there were 7 mitotic figures/10 randomly selected hpfs (400X). The neoplastic tissues within the spleen and lungs were similar to the neoplasm within the thoracic wall. The tissue surrounding the kidneys was composed of extravasated erythrocytes, fibrin, and marked amounts of necrotic debris. Following immunohistochemical staining for factor VIII–related antigen (an endothelial cell marker), the neoplastic cells had strong diffuse cytoplasmic stain uptake (Figure 3). Morphologic Diagnosis and Case Summary Morphologic diagnosis: hemangiosarcoma of the intercostal muscles and ribs, metastatic hemangiosarcoma of the lungs and spleen, perirenal hemorrhage and necrosis, and mesenteric hematoma. Case summary: thoracic hemangiosarcoma with visceral metastases in a horse. Discussion

Figure 3—Photomicrograph of a section of the right thoracic wall of the horse in Figure 1. Following immunohistochemical staining, the neoplastic cells have diffuse, strong, intracytoplasmic staining for factor VIII–related antigen (arrowhead). Nonvascular connective tissue on the left is not stained. Factor VIII– related antigen-specific immunohistochemical stain with hematoxylin counterstain; bar = 100 µm. 910

Vet Med Today: Pathology in Practice

Based on the location of the largest lesional focus (ie, the affected intercostal muscle and rib), differential diagnoses included hemangiosarcoma, telangiectatic osteosarcoma, and localized trauma. Telangiectatic osteosarcoma was ruled out because of the positive immunohistochemical staining for factor VIII–related antigen and the absence of osteoid. The histologic and immunohistochemical findings were consistent with hemangiosarcoma originating from the thoracic wall, most likely from the skeletal muscle. There was no history of traumatic injury to this horse. Main differential diagnoses for hemothorax are hydrothorax, chylothorax, and pleuropneumonia.1 Possible causes for hemothorax include complications of lung biopsy, pulmonary hemorrhage induced by strenuous exercise, traumatic injury (fractured rib), pulmonary infarction, lung lobe torsion, laceration of the heart, laceration or rupture of great vessels, rupture of a pulmoJAVMA, Vol 244, No. 8, April 15, 2014

nary abscess, aneurysm, neoplasia, and coagulopathy.1,2 Main differential diagnoses for hemoperitoneum include colic and dystocia.1 Possible causes of hemoperitoneum include rupture of a splenic hematoma, splenic or hepatic rupture secondary to systemic amyloidosis, bleeding secondary to torsion or rupture of portions of the reproductive tract, ovarian hemorrhage, mesenteric vessel rupture (verminous arteritis), aneurysm, abdominal abscess, neoplasia, and coagulopathy.2,3 Hemangiosarcoma is a malignant neoplasm of vascular endothelial cells. Hemangiosarcoma in dogs and cats has been commonly reported, but this type of neoplasm appears to be rare in horses, cattle, sheep, goats, and pigs.4–6 Dogs with hemangiosarcoma commonly have signs of disseminated visceral disease, often involving the spleen, liver, lungs, and right auricle.4 Hemangiosarcoma commonly develops in the skin and soft tissue of the eyelids, distal aspect of the limbs, and paws in cats.4 In horses, although hemangiosarcoma is uncommon, it is most often reported to develop within the lungs and pleura (thoracic wall), spleen, and skeletal muscle in adults and in the skin and limbs of juveniles.7,8 Other reported locations of hemangiosarcomas in horses are the vertebrae, pelvic bone, spinal cord, cerebrum, medulla oblongata, heart, kidneys, liver, ovaries, adrenal glands, lymph nodes, mediastinum, mesentery, diaphragm, vulva, prepuce, oral cavity, mandible, larynx, gastrointestinal tract, eyes, frontal sinus, tarsal sheaths, and limbs.8–12 Thoroughbreds were the most common breed in 2 case series.7,8 There is no reported sex predilection.8 Congenital or juvenile hemangiosarcoma in horses has been reported and can be either locally invasive or disseminated.7,8,12 In dogs with hemangiosarcoma, the right auricle and the spleen are considered primary sites, whereas lesions within the lungs and liver are considered metastatic.4 In 1 case series8 of equine disseminated hemangiosarcoma, the suspected primary site was determined as the site of the tumor with the largest size, with the spleen and skeletal muscle being the most common primary sites. On the basis of this criterion, the skeletal muscle was the likely candidate as the primary site for the horse of the present report, with metastasis to the lungs and the spleen. The left kidney was partially effaced, and it is suspected that there was a malignancy at this site; however, neoplastic tissue was not present in the examined hemorrhage and necrosis. This is a common problem in the diagnosis of hemangiosarcoma. Multiple samples from the edge of the hemorrhage including the zone at which there is transition to surrounding tissue of normal appearance should be collected for histologic examination to increase the yield of diagnostically useful information. Rupture of the presumed perirenal neoplasm was the most likely cause of the hemoabdomen in the case described in this report. Clinical signs in horses with hemangiosarcoma can include dyspnea, lethargy, cutaneous or muscular swelling anywhere in the body, limb swelling, epistaxis, and lameness. Common physical examination findings can include high heart and respiratory rates, joint effusion, pale mucous membranes, and fever.7,8 None of these clinical findings were evident in the horse of the present report, suggesting that sudden rupture of the thoracic neoplasm resulted in hemothorax and the death of this animal. Clinical pathological changes associated with hemangiosarcoma typically include anemia, thrombocytopenia, and neutrophilic leukocytosis.7,8 Reticulocytes are never present in the blood of horses, even during diseased states; thus, the regenerative nature of anemia could not be determined in the horses described in the published case series.7,8 Grossly, hemangiosarcoma appears as JAVMA, Vol 244, No. 8, April 15, 2014

friable, red to black masses either embedded within or bulging from the surface of organs.8,12 Associated gross findings include intramuscular hemorrhage, hemothorax, and hemoperitoneum.8 Histologically, the neoplasm appears as anastomosing blood-filled channels lined by spindle to polygonal to ovoid cells and supported by fibrous connective tissue.8 In domestic animals, results of immunohistochemical staining have indicated that hemangiosarcoma tissues are positive for vimentin, CD31, lectins, factor VIII–related antigen, CD34, CD44, podocalyxin, type IV collagen, and laminin.5,13 Among horses, an epithelioid variant, which can be misdiagnosed as an epithelial neoplasm, can develop, and is similar to an epithelioid variant reported for other domestic animal species.8,14 In some dogs and cats, hemangiosarcomas have been associated with solar exposure.13 A single case of hemangiosarcoma in a cat was associated with an intra-abdominal steel surgical staple.15 Hemangiosarcoma in humans have been associated with thorium dioxide, arsenicals, and vinyl chloride.5 Treatment for horses with hemangiosarcoma is usually palliative. Attempts to surgically remove the tumors in combination with cryo- or chemotherapy may be successful, but recurrence is common.7 Supportive care treatment with NSAIDs or steroidal anti-inflammatory drugs, antimicrobials, furosemide, and IV fluid therapy is initiated in many cases. Generally, the prognosis for affected horses is very guarded; horses with hemangiosarcoma typically deteriorate rather quickly and are usually euthanized because of poor response to treatment.8 References 1.

2. 3. 4. 5. 6. 7. 8. 9. 10. 11. 12. 13. 14. 15.

Hewson J, Arroyo L, Slater J. Medical conditions of the lower respiratory tract. In: Munroe GA, Weese JS, eds. Equine clinical medicine, surgery, and reproduction. London: Manson Publishing Ltd, 2011;477. Perkins G, Ainsworth DM, Yeager A. Hemothorax in 2 horses. J Vet Intern Med 1999;13:375–378. Pusterla N, Fecteau M-E, Madigan JE, et al. Acute hemoperitoneum in horses: a review of 19 cases (1992–2003). J Vet Intern Med 2005;19:344–347. Goldschmidt MH, Hendrick MJ. Tumors of skin and soft tissue. In: Meuten DJ, ed. Tumors in domestic animals. 4th ed. Ames, Iowa: Blackwell Publishing, 2002;99–101,292–294,504–505. Scott DW, Miller WH. Neoplasms, cysts, hamartomas and keratosis. In: Scott DW, Miller WH, eds. Equine dermatology. 2nd ed. St Louis: Elsevier Inc, 2011;493. Bildfell RJ, Valentine BA, Whitney KM. Cutaneous vasoproliferative lesions in goats. Vet Pathol 2002;39:273–277. Johns I, Stephen JO, Del Piero F, et al. Hemangiosarcoma in young horses. J Vet Intern Med 2005;19:564–570. Southwood LL, Schott HC II, Henry CJ, et al. Disseminated hemangiosarcoma in the horse: 35 cases. J Vet Intern Med 2000;14:105–109. Gumber S, Baia P, Wakamatsu N. Vulvar epithelioid hemangiosarcoma with solar elastosis in a mare. J Vet Diagn Invest 2011;23:1033–1036. Kiupel M, Frank N, Stevenson GW, et al. Intrapelvic hemangiosarcoma in a horse. J Vet Diagn Invest 2000;12:91–95. Ladd SM, Crisman MV, Duncan R, et al. Central nervous system hemangiosarcoma in a horse. J Vet Intern Med 2005;19:914–916. Dunkel BM, Del Piero F, Kraus BM, et al. Congenital cutaneous, oral and periarticular hemangiosarcoma in a 9-day old Rocky Mountain horse. J Vet Intern Med 2004;18:252–255. Gross TL, Ihrke PJ, Walder EJ, et al. Vascular tumors. In: Gross TL, Ihrke PJ, Walder EJ, et al, eds. Skin diseases of dogs and cats. 2nd ed. Ames, Iowa: Blackwell Publishing, 2005;749–753. Warren AL, Summers BA. Epithelioid variant of hemangioma and hemangiosarcoma in the dog, horse, and cow. Vet Pathol 2007;44:15–24. Tan RM, Singh K, Sandman K. Subcutaneous hemangiosarcoma induced by a foreign body (steel staple) in a cat. Can Vet J 2013:54:377–380. Vet Med Today: Pathology in Practice


Pathology in practice. Hemangiosarcoma.

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