History

A 15-year-old 377.0-kg (829.4-lb) American Quarter Horse mare (Equus caballus) was evaluated because of progressive weight loss and muscle wasting of approximately 1 year's duration despite the owner changing the horse's diet to include a high-fat concentrate mix. The wasting had become more dramatic several months prior to presentation, with partial anorexia and limb edema developing during the preceding several weeks.

Clinical and Gross Findings

On physical examination, the mare was quiet, alert, and responsive; rectal temperature, heart rate, and respiratory rate were considered normal. The mare was thin (body condition score,¹ 2/9). A CBC revealed mild normocytic normochromic anemia. Results of a plasma biochemical panel included mildly high aspartate aminotransferase activity, high γ-glutamyltransferase activity, high BUN concentration, mild hyperbilirubinemia, and mild hypoalbuminemia; creatinine and total protein concentrations were within reference ranges. Rectal palpation revealed that the left dorsal colon, left ventral colon, and pelvic flexure were displaced cranially and to the right of midline, but a mass was not palpated. Abdominal ultrasonography revealed an irregular, space-occupying mass predominantly in the left ventral area of the abdominal cavity, along with peritoneal effusion and thickening of small intestinal loops. The liver and spleen were enlarged, and both had multifocal hyperechoic areas. Pleural and mild pericardial effusion were evident with bilateral pulmonary collapse. Abdominocentesis revealed serosanguineous peritoneal fluid with mononuclear pleocytosis consisting predominantly of macrophages. An exploratory celiotomy was declined by the owner because of the horse's long-term clinical signs and poor prognosis for full recovery; thus, the horse was euthanized by IV injection of 100 mL of pentobarbital sodium and phenytoin sodium.^a

At necropsy, the horse was thin with minimal postmortem autolysis. The abdominal cavity contained numerous nodules and masses, which occupied approximately 70% of the entire cavity (Figure 1). The left side of the liver had a large, multinodular, cavitated, mottled, dark to pale tan mass (weighing 68.0 kg [149.6 lb]) that markedly extended and compressed the parenchyma. On cut surface, the mass was mottled dark red to yellow or tan and gelatinous. Smaller but similar nodules were observed throughout the abdominal cavity, and several organs including the liver were affected. The spleen was mottled purple to tan and had several similar 1- to 7-cm-diameter nodules that variably extended into the parenchyma. The serosal surface of the small and large intestines had multiple small similar nodules. Mucosal erosion and severe ulceration were noted in the nonglandular mucosa at the margo plicatus and terminal portion of the esophagus. The ulcers had a maximum dimension of 2 to 30 cm and were likely secondary to the horse's overall debilitated condition and gastric reflux.

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Photographs of intra-abdominal masses in a 15-year-old American Quarter Horse mare (Equus caballus) that had a 1-year history of clinical signs including progressive weight loss and muscle wasting. Approximately 70% of the abdominal cavity is occupied by numerous well-demarcated masses (A–C). On cut surface, the masses were gelatinous, mottled dark red to pale tan, and compressing the liver and multiple other organs (D; arrows).

Citation: Journal of the American Veterinary Medical Association 258, 7; 10.2460/javma.258.7.717

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Histopathologic, Immunohistochemical, and Laboratory Findings

In the abdominal cavity, the masses represented a multinodular, well-demarcated, markedly expansile neoplasm surrounded by a variably thick fibrous collagen capsule (Figure 2). The neoplasm was a loose proliferation of spindle-shaped cells in streaming bundles separated by an abundant myxomatous matrix that frequently formed large mucinous lakes. The neoplastic cells were spindle shaped to stellate with variably distinct borders and light eosinophilic cytoplasm. Each cell had a centrally located elongated nucleus with finely to coarsely stippled chromatin and an inconspicuous nucleolus. The mitotic index was < 1 mitotic figure/10 hpf (400X [2.37 mm²]). There were necrotic and hemorrhagic foci throughout the tumor with moderate numbers of hemosiderin-laden macrophages. Neoplastic cell cytoplasm was strongly immunopositive for CD117.

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Photomicrographs of sections of the intra-abdominal masses in the horse. A—The mesenchymal neoplasm is encapsulated and markedly compressing the splenic parenchyma. H&E stain; bar = 1 mm. B—There is a loose proliferation of neoplastic spindle-shaped cells arranged in streaming bundles and disorganized solid sheets with an abundant intercellular myxomatous matrix forming mucinous lakes. H&E stain; bar = 200 μm. C—The matrix is alcian blue stain positive. Alcian blue stain (pH, 2.5); bar = 1 mm. D—Neoplastic cells are strongly cytoplasmic immunoreactive for CD117 (c-KIT). Polyclonal anti-CD117 (c-KIT) antibody with 3-3′-diaminobenzene and hematoxylin counterstain; bar = 100 μm.

Citation: Journal of the American Veterinary Medical Association 258, 7; 10.2460/javma.258.7.717

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Morphologic Diagnosis and Case Summary

Morphologic diagnosis: spindle-shaped cell sarcoma (consistent with gastrointestinal stromal tumor [GIST]) in multiple abdominal organs and the peritoneum.

Case summary: malignant GIST with transplantation metastasis in a horse.

Comments

On the basis of the clinical findings for the horse of the present report, differential diagnoses included abdominal abscess, abdominal neoplasia, right displaced colon, and small intestine inflammatory disease. Necropsy revealed the large, multinodular, cavitated mass on the left side of the liver and masses in other organs. Histologic findings for the intra-abdominal neoplasm along with the neoplasm's positive cytoplasmic immunohistochemical staining for CD117 (c-KIT) were most consistent with a GIST.

The scattered nodules of tumor growth in the abdomen of the horse of the present report were indicative of transplantation metastasis. The primary site of the tumor was undetermined, but it likely originated from the gastrointestinal wall; however, no definitive origination site of the tumor within the gastrointestinal serosa or mucosa was grossly identified. Although the largest tumor was associated with the liver, this lesion was considered metastatic. The clinical signs of weight loss, poor body condition, and partial anorexia were likely secondary to the large size of the GIST. The cranial and right displacements of the pelvic flexure and left dorsal and ventral colons were likely attributable to the size of the tumor, and the severe esophageal erosions and ulcerations were likely secondary to gastric reflux as a result of severe abdominal compression and delayed gastric emptying.

Gastrointestinal stromal tumors in humans,² nonhuman primates,^3,4,5 dogs,^2,6 horses,^2,7,8,9 ponies,^7,10 donkeys,¹¹ and rats¹² have been described. This tumor is thought to be derived from the interstitial cells of Cajal present in the myenteric plexus and between the inner and outer tunica muscularis.^2,8,13 In horses, the tumor cells are composed of undifferentiated mesenchymal cells mixed with myogenic and neural spindle-shaped cells.^7,8 Immunohistochemical staining of neoplastic cell cytoplasm for c-KIT is a requirement for the diagnosis of GIST.^2,5,13 However, factors such as autolysis and duration of fixation of tissue samples might lead to negative results of immunostaining of sections.¹³ In humans, GISTs originating outside the tubular gastrointestinal tract are known as extragastrointestinal stromal tumors and are found in the retroperitoneum, mesentery, omentum, pancreas, and pelvis. Extragastrointestinal stromal tumors and GISTs are associated with similar clinical signs, pathological features, and immunohistochemical findings.^14,15,16

Among horses, GISTs have been reported as more commonly affecting older females with unclear breed predisposition.⁷ The most common locations are the cecum and colon; however, the stomach and small intestine may also be affected.^2,7,8,13 The neoplasms can arise from the subserosal, serosal, or intramural layers.^2,7 Tumor size usually varies from 1 to 10 cm in diameter; however, large masses, as described for the horse of the present report, have been documented.^9,10,17 These neoplasms can also be solitary or multiple with or without criteria of malignancy.^2,7,8,13

In humans, high mitotic activity and large size of GISTs are indicative of a poor prognosis; however, the prognosis for domestic animals with GISTs as it relates to tumor size is not known.¹³ In horses, GISTs have been reported as having a benign nature without metastasis.^7,8,13,17 However, in the horse of the present report, suspected intra-abdominal transplantation metastasis was observed. Reported microscopic patterns include loosely to densely proliferating spindle-shaped cells that are separated by myxoid matrix.^2,7,8,13 Myxoid matrix was markedly prominent in the tumor of this horse. Many GISTs in old horses have been considered to be incidental findings during surgical procedures, meat inspections, or necropsies.^7,8,13 However, intermittent colic, weight loss, and poor body condition may develop in horses with GISTs and become more frequent findings over time.^9,13,17 Rarely, GISTs have been associated with cecal impaction, intestinal displacement, and strangulation of the distal portion of the ileum.^2,7 The cranial and right displacement of the colon and pelvic flexure palpated during rectal examination of the horse of the present report was likely due to the size of the tumor.

In dogs and horses with GISTs, associated findings commonly include paraneoplastic hypoglycemia as a result of the production of insulin-like growth factors as well as the production of erythropoietin leading to erythrocytosis. Therefore, hypoglycemia and anemia might be used as crude indicators of these neoplasms in live animals with progressive weight loss, muscle wasting, and the presence of an abdominal mass.^10,13 As illustrated by the case described in the present report, GISTs may develop in relatively young horses.