Pathology in Practice

Colleen F. Monahan Department of Biomedical and Diagnostic Sciences, College of Veterinary Medicine, University of Tennessee, Knoxville, TN 37996.

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Linden E. Craig Department of Biomedical and Diagnostic Sciences, College of Veterinary Medicine, University of Tennessee, Knoxville, TN 37996.

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History

A 30-year-old 468-kg (1,030-lb) American Paint gelding was evaluated at the University of Tennessee Veterinary Medical Center because of signs of colic. The horse had no previous history of colic. The owner reported that the horse had no clinical signs the night before, but was found sweating and shaking in its stall the next morning. There were signs that the horse had been rolling on the ground and had inflicted head trauma. The owner had administered flunixin megluminea (10 mL, IV), but when the horse's condition failed to improve, it was brought to the hospital.

Clinical and Gross Findings

On initial physical examination, the horse was hypothermic and tachycardic with pale mucous membranes and a slow capillary refill time (2.5 seconds). It had decreased gastrointestinal sounds and cold extremities. The horse's PCV was 48% (reference interval, 28% to 44%), and serum total protein concentration was 8.0 g/dL (reference interval, 6.1 to 8.0 g/dL). A nasogastric tube was inserted, and < 1 L of reflux was obtained. Abdominal ultrasonography revealed distended small intestinal loops with decreased motility. Findings on rectal palpation suggested right dorsal displacement of the large colon. Abdominocentesis was performed and no fluid was aspirated; however, a gritty sensation was detected, consistent with gravel in the ventral colon. Owing to the horse's age and surgical risk, the owner elected euthanasia (by means of IV injection of pentobarbital solution). On necropsy, there was an 11 × 11 × 8-cm, partially encapsulated mass that was soft, ovoid, and mottled red, tan, and purple and that originated from the medulla of the right adrenal gland (Figure 1). There was no evidence of metastasis. The small and large intestines had no notable gross findings. Other findings included an adenoma (most likely C-cell type) of the left thyroid gland and a pars intermedia adenoma of the pituitary gland. The left adrenal gland was grossly normal.

Figure 1—
Figure 1—

Photograph of a mass within the right adrenal gland of a 30-year-old horse with signs of colic. Arrowheads indicate the remaining adrenal cortex.

Citation: Journal of the American Veterinary Medical Association 248, 3; 10.2460/javma.248.3.271

Formulate differential diagnoses from the history, clinical findings, and Figure 1—then turn the page →

Histopathologic Findings

On histologic examination, the right adrenal gland had an encapsulated neoplastic proliferation of columnar to polygonal cells arranged in trabeculae along a fine fibrovascular stroma; the neoplasm completely replaced and enlarged the medulla (Figure 2). The neoplastic mass markedly distorted and compressed the adrenal cortex. The mass contained multifocal necrosis. The neoplastic cells had moderately distinct borders, finely granular gray-blue cytoplasm, and ovoid nuclei. Chromatin was coarsely stippled, and nucleoli were variably prominent. There was moderate anisocytosis and 2-fold anisokaryosis (ie, some of the nuclei were twice the size of others). Mitotic figures were rare. Hemorrhage and siderophages were within the stroma. Cytoplasmic granules were argyrophilic (as determined by use of Churukian-Schenk stain; Figure 3). Sections of the small and large intestines had no important histopathologic findings. The microscopic characteristics of the left adrenal gland were considered normal.

Figure 2—
Figure 2—

Photomicrograph of a section of the adrenal mass from the horse in Figure 1. The mass is composed of a proliferation of columnar to polygonal cells arranged in trabeculae along a fine fibrovascular stroma. H&E stain; bar = 100 μm.

Citation: Journal of the American Veterinary Medical Association 248, 3; 10.2460/javma.248.3.271

Figure 3—
Figure 3—

Photomicrograph of a section of the adrenal mass from the horse in Figure 1. The cytoplasmic granules of the neoplastic cells stain brown with Churukian-Schenk stain, indicating a neuroendocrine origin. Churukian-Schenk stain; bar = 100 μm.

Citation: Journal of the American Veterinary Medical Association 248, 3; 10.2460/javma.248.3.271

Morphologic Diagnosis and Case Summary

Morphologic diagnosis and case summary: pheochromocytoma of the right adrenal gland in a horse.

Comments

Pheochromocytomas are rare in horses. In horses, these neoplasms can cause clinical signs that are similar to more commonly occurring conditions, such as colic, acute laminitis, and rhabdomyolysis, and pheochromocytoma is an important differential diagnosis to consider in such cases.1 Pheochromocytomas are tumors that originate from the chromaffin cells of the medulla of the adrenal gland. On gross examination, they are often large and red as a result of hemorrhage. The tumors can grow rapidly and rupture, leading to hemoabdomen.2 In horses, they are usually unilateral and well encapsulated with benign biological behavior.3,4 There is no known breed or sex predilection for pheochromocytoma among horses4; affected horses are typically middle-aged, most commonly > 12 years of age.5

Pheochromocytomas can be functional or nonfunctional; functional tumors produce excessive amounts of catecholamines (epinephrine and norepinephrine), which lead to clinical signs such as anxiety, tachycardia, tachypnea, excess sweating, muscle tremors, and mydriasis in horses.4 Often, signs of abdominal pain can develop secondary to hematomas or ileus caused by the increased intestinal adrenergic receptor stimulation.5 Other clinical signs associated with pheochromocytomas in horses are hyperthermia, dry and pale mucous membranes, prolonged capillary refill time, urinary bladder paralysis, and ataxia. Paroxysmal clinical signs may develop owing to intermittent production of catecholamines by the tumor cells.6 Clinical pathological findings can include hemoconcentration, stress leukogram, or leukopenia with neutropenia.5 Horses with functional pheochromocytomas usually have nonspecific biochemical findings, such as azotemia, metabolic acidosis, hyperkalemia, and hyperglycemia.4 These clinical signs and clinicopathologic findings can easily be interpreted as signs of gastrointestinal tract or other nonadrenal gland disease, as illustrated by the case described in this report.

Functional pheochromocytomas are diagnosed on the basis of high serum catecholamine concentrations or high concentrations of catecholamine metabolites in the urine. Diagnosis can be difficult because catecholamines are labile and many laboratories do not perform catecholamine-specific assays.4,5,7 Often, a presumptive diagnosis is based on ultrasonographic findings and results of blood pressure assessments along with the appropriate clinical signs, such as colic, tachycardia, excess sweating, and muscle tremors. Pheochromocytomas are often diagnosed at necropsy rather than in the living animals, as occurred in the case of this report. Most nonfunctional pheochromocytomas remain undiagnosed because they fail to produce catecholamines and induce the associated clinical signs.2 However, nonfunctional pheochromocytomas are still capable of rupture and can result in hemoabdomen and signs of abdominal pain.2,4

In horses with functional pheochromocytomas, prognosis is poor because of the complications associated with surgical treatment. Fatal arrhythmias can be induced by the interaction of anesthetic agents and high circulating concentrations of catecholamines.2 Also, the anatomic location of the adrenal glands in horses makes surgical removal difficult. The adrenal glands are located deep within the abdomen and close to large vessels, such as the caudal vena cava and the abdominal aorta.

Multiple endocrine neoplasia (MEN) syndrome encompasses several different syndromes, each related to specific endocrine tumors. Multiple forms of MEN syndrome have been described for several species, including humans and cattle. In cattle, MEN typically includes C-cell adenoma of the thyroid gland, bilateral pheochromocytomas, and pituitary adenoma.8 In humans, it often includes C-cell adenoma of the thyroid gland, pheochromocytoma, and multicentric bilateral nodular hyperplasia of the adrenal medulla.9,10 In horses, MEN syndrome has been reported3; by definition, the horse of the present report represented a case of MEN syndrome because of the presence of a pheochromocytoma, thyroid C-cell adenoma, and pituitary adenoma of the pars intermedia. However, owing to the high incidence of thyroid C-cell adenomas and pituitary pars intermedia adenomas in older horses, it is unlikely that their development was related to the development of the much rarer pheochromocytoma in the case described in this report.

Certain stains can be used to help identify cells of neuroendocrine origin in tissue sections. For the horse of this report, Churukian-Schenk stain (a histochemical stain) was used. Churukian-Schenk stain is silver based and stains the intracytoplasmic hormonal secretory granules that characterize neuroendocrine tumors; the positive cells appear black or brown owing to their argyrophilic nature.11 Neuroendocrine-specific immunohistochemical stains include those that identify synaptophysin and chromogranin A. Synaptophysin is an integral membrane glycoprotein found in both normal and neoplastic neuroendocrine cells of neural type, including pheochromocytomas and paragangliomas.12 Chromogranin A is an acidic glycoprotein that is widely expressed in neuroendocrine cells and is a major component of secretory granules. Staining for chromogranin A is often used to identify endocrine tumors, such as pheochromocytomas, pancreatic islet cell tumors, and medullary thyroid carcinomas.13

Footnotes

a.

Banamine, Merck Animal Health, Madison, NJ.

References

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