Abstract
A 14-yr-old, male African warthog (Phacochoerus aethiopicus) with a chronic history of unilateral epistaxis, degenerative osteoarthritis, and intermittent weakness in the distal lumbar trunk was evaluated under general anesthesia. The animal was housed singly and fed a commercial pelleted diet (Mazuri PMI Feeds, St. Louis, MO, USA), alfalfa hay, and small amounts of fresh produce.
The warthog was anesthetized with detomidine (Domitor, Pfizer Animal Health, New York, NY, USA), butorphanol (Torbugesic, Fort Dodge Laboratories, Fort Dodge, IA, USA), and midazolam hydrochloride (Abbott Laboratories, North Chicago, IL, USA) via blowdart. Indirect oscillometric blood pressure readings (Cardell, CAS Medical Systems, Inc., Branford, CT, USA) averaged 162 mm Hg (systolic), 72 mm Hg (diastolic), and 107 mm Hg (mean arterial pressure), with a mean heart rate of 93 bpm. Rigid laparoscopic evaluation of the nasal meatus of both nares demonstrated no abnormalities. Radiographs of thoracic and pelvic limbs demonstrated severe osteoarthritis in all four carpi and tarsi. Cardiothoracic evaluation demonstrated a grade III/VI holosystolic murmur with the point of maximal intensity over the left intercostal space 4 to 5, above the sternal border.
The combination of progressive degenerative osteoarthritis, epistaxis, and cardiac murmur precluded resolution and the warthog was euthanatized. Gross necropsy demonstrated severe chronic osteoarthritis, hemorrhage in the ethmoid region, and firm mass on the left antebrachium that was later identified as a fibroma. The heart was grossly normal, but weights and measurements were not obtained. Mild endocardiosis of the mitral valve was observed. Although the left adrenal was normal in size, the right adrenal contained a circumscribed tan mass about 1 cm in diameter within the medulla. Representative tissues from all internal organs were placed in 10% neutral buffered formalin, embedded in paraffin, sectioned, and stained with hematoxylin and eosin.
Histopathologically, the right adrenal medulla contained a unilateral medullary tumor that circumferentially displaced the cortex and compressed the remaining normal medulla. The mass was well defined but not encapsulated and consisted of sheets and nests of medium-sized round to somewhat elongate cells immersed in fibrovascular stroma. The cells had pink homogeneous cytoplasm. The nuclei were eccentric and anisomorphic, and relatively large, with stippled chromatin and small nucleoli. Mitoses were uncommon. Irregular areas of degeneration and necrosis were present in the mass. Immunohistochemical staining detected finely granular cytoplasmic expression of chromogranin, which was less intense than in cells of the normal adrenal medulla, and non-existent in the cells of the adrenal cortex. Neoplastic cells did not express neurofilament protein H chain. These findings are characteristic of pheochromocytoma (PC). The adrenal medulla was normal except for brown pigment of some of the cells. In the heart, myocardial fibers were separated slightly by pale interstitium. Elastin fibers of the heart were mineralized and collections of golden perinuclear granules consistent with lipofuscin were frequent in myocardial fibers. Severe atrophy of peripheral nerve fibers with fiber loss and increased pale ground substance between and around fibers within the nerve sheath was also noted. Testicular tubules were disorganized and collapsed, producing few sperm cells. The interstitium contained increased fibrous tissue and hemosiderin-rich macrophages. No pathologic insult was observed in either nasal cavity.
Pheochromocytomas are known to cause constant or intermittent hypertension and have been associated with systolic heart murmurs in humans.3 Repeated nasal hemorrhage is certainly characteristic of hypertension,2 but was not observed in this warthog when compared to other warthogs anesthetized with similar drugs. Recent hemorrhage of the mass could have resulted in massive catecholamine release and instituted acute hypertension and epistaxis. This mass was rounded and benign in character. Pheochromocytomas have been reported in all domestic species, as well as a hippopotamus, sea otter, rat, wolfdog, and ring-tailed lemur.1,5-7,9
Pheochromocytomas are uncommon in pigs. A review of over 10,000 necropsy specimens of domestic swine (USDA/FSIS eastern Laboratory, Athens, GA USA, pers. com., 2004) did not find PC in any swine. However, these market hogs were generally less than 2 yr old. Of 3.7 million swine surveyed in 1965 in Great Britain, one 2.5-yr-old female had a PC diagnosed postmortem in an abattoir survey. Only one other adrenal neoplasm in swine was observed; an adrenal cortical adenoma in a 6-mo-old gilt.8
Pheochromocytomas produce noradrenaline and adrenaline leading to hypertensive states in domestic animals. Documentation of elevated indirect BP readings, compared to a conspecific (66/40) immobilized with similar anesthetic induction agents (Jackie Gai, pers. com., 2004) is compatible with a PC, though reference values for blood pressures in anesthetized warthogs are not reported and mean values obtained here are within generally acceptable limits for other domestic and exotic mammals. Plasma norepinephrine values in this warthog were elevated when compared to three other male African warthogs under anesthesia, but lower than one additional, clinically healthy male. Values were compatible with PC; however, no reference values exist for norepinephrine values in African warthogs and should be interpreted with caution. Tissue norepinephrine values were not performed.1 Chronic intermittent epistaxis, without underlying site-specific pathology, is also compatible with hypertension. Surgery is the treatment of choice for dogs with pheochromocytomas. Medical therapy permits metabolic and cardiovascular stabilization of patients before surgery and is used to treat intraoperative arrhythmia and episodes of hypertension.4 Surgical intervention or medical treatment in this case would be impractical owing to difficulty in direct monitoring, acceptance of oral medications, and superceding degenerative conditions.
Clinicians should consider pheochromocytoma when evaluating aged swine with episodic weakness and epistaxis.
Acknowledgments
We wish to thank Drs. Danielle Okeson, Jackie Gai, Ned Gentz, Zoli Gyimesi, Pat Morris, and Julia Napier for their assistance and submittal of comparative data.
Literature Cited
1. Duncan, M., B.H. Grahn, B.P. Wilcock, H. Boermans, L.K. Johnson, and D.A. Smith. 1994. Pheochromocytoma associated with hypertensive lesions in a river hippopotamus. J. Zoo Wildl. Med. 25:575– 579.
2. Labianca N.J.F., F.D. Fuchs, S.R. Facco, M. Gus, L. Fasolo, R. Mafessoni, and A.L. Gleissner. 1999. Is epistaxis evidence of end-organ damage in patients with hypertension? Laryngoscope. 109:1111–1115.
3. Lenz, T., J. Gossmann, K.L. Schulte, L. Salewski, and H. Geiger. 2002. Diagnosis of pheochromocytoma. Clin. Lab. 48:5–18.
4. Locke-Bohannon, L.G., and G.E. Mauldin. 2001. Canine pheochromocytoma: diagnosis and management. Compendium. 23:807–815.
5. Martinez, M.J., and S.R. Mog. Spontaneous complex pheochromocytoma in a Fischer 344 Rat. 2001. Vet. Pathol. 38:470–473.
6. Reichard, T.A., P.K. Ensley, and M.J. Henrick. 1981. Pheochromocytoma in a ring-tailed lemur (Lemur catta). Proc. Am. Assoc. Zoo Vet. Annu. Meet. 44.
7. Sako, T., N. Kitamura, Y. Kagawa, K. Hirayama, M. Morita, T. Kurosawa, T. Yoshino, and H. Taniyama. 2001. Immunohistochemical evaluation of a malignant pheochromocytoma in a wolfdog. Vet. Pathol. 38:447–450.
8. Sandison, A.T., and L.T. Anderson. 1968. Tumors of the endocrine glands in cattle, sheep and pigs found in a British abattoir survey. J. Comp. Pathol. 78:435–444.
9. Stetzer, E., T.D. Williams, and J. W. Nightingale. Cholangiocellular adenocarcinoma, leiomyoma, and pheochromocytoma in a sea otter. 1981. J. Am. Vet. Med. Assoc. 179:1283–1284.