Canine Pheochromocytoma
Pheochromocytoma is a rare endocrine tumor derived
from chromaffin cells. It is the most common neoplasm of the adrenal medulla
and develops often in dogs and cattle. The tumor can be unilateral or
bilateral, infrequently functional and has no reported breed or sex
predilection. Pheochromocytomas in dogs are usually benign, however, with
potential for local invasion. Occasionally, they are malignant with metastasis
to distant organs, especially the liver, regional lymph nodes or lungs. This
neoplasm is considered malignant when metastasis is present in non-chromaffin
cells. Affected dogs are usually older, with a mean age of 11 years.
Pheochromocytomas are of neuroectodermal origin, arising from chromaffin
cells, which produce and secrete catecholamines. Epinephrine and nor-epinephrine
are the catecholamines most commonly produced, with dopamine produced less
frequently. Catecholamine release in functional pheochromocytomas is usually
paroxysmal. This may be attributed to changes in blood flow, chemicals, or
drugs, or direct pressures on the tumor (abdominal palpation) since the tumors
have no innervation.
Clinical signs associated with pheochromo-cytoma are
often vague and intermittent, and may mimic more common disorders such as
hyperadrenocortisism, diabetes mellitus, hepatic or renal disease, or other
neoplasms. Clinical signs frequently observed include weakness, collapse,
lethargy, anorexia, vomiting, panting, weight loss, anxiety, restlessness,
polyuria, polydipsia, diarrhea, abdominal distention, hind limb edema,
epistaxis, seizures or acute blindness. The clinical signs are generally
associated with catecholamine excess and systemic hypertension. Elevation of
blood pressure induced by sudden release of catecholamines can precipitate
acute congestive heart failure, pulmonary edema, myocardial infarction, ventricular
fibrillation and cerebral hemorrhage. Nonfunctional tumors can also produce
clinical signs by their space occupying nature.
Pheochromocytomas occasionally result in secondary
conditions including invasion and thrombosis of the caudal vena cava, aortic
thromboembolism, spontaneous rupture of the tumor, paresis secondary to spinal
cord compression, arrhythmias, cardiac hyper-trophy, arteriolar sclerosis,
systemic hyper-tension, or hyperadrenocortisism. About 15-38% of
pheochromocytomas invade the caudal vena cava, causing clinical signs of
ascites, hind limb edema, or distention of the caudal epigastric veins.
Ultrasound and Doppler imaging can be used to identify obstruction of the
caudal vena cava. Aortic thrombo-embolism is fairly uncommon in dogs, and
occurs due to endothelial damage, vascular stasis, and hypercoagulable states.
Rarely, pheochromocytomas may rupture spon-taneously and cause retroperitoneal
hemorrhage or periumbilical ecchymoses (Cullen's sign). Systemic hypertension
occurs in 43-70% of canine patients with pheo-chromocytoma, and concurrent
hyperadreno-cortism has been found in 12% of reported cases.
Antemortem diagnosis of pheochromocytoma can be
difficult because the tumors are often non-functional or episodic in nature. Abnormalities
in routine laboratory testing are often non-specific, but may be useful to rule
out concurrent disease. The CBC may reveal anemia (from chronic disease or
blood loss) or a transient thrombocytopenia if the patient has platelet
consumption from episodic hemorrhage. The leukogram often reveals leukocytosis
characterized by a mature neutrophilia due to either catecholamine induced by
demargination of neutrophils or necrosis/inflammation within the tumor. Serum
blood chemistry occasionally reveals a mild azotemia, hypercholesterolemia,
hypoalbumi-nemia, and elevated ALT and ALP. Abdominal radiographs and
ultrasound can be used to detect abdominal masses, and thoracic radiographs
should be taken to detect distant metastasis. A pneumoperitoneogram may aid in
tumor visualization. Caudal abdominal venography can be useful to diagnose
local tumor invasion or tumor related thrombosis, and contrast urography can
identify invasion into the cranial pole of the kidney. Human medicine
frequently uses advanced imaging techniques (CT, MRI, or metaiodo-benzylguanidine
scanning) and serum or urine catecholamine metabolite assays to obtain a
diagnosis. These methods are of limited use in veterinary medicine because of
their unavailability, expense, the need for general anesthesia, and lack of
reference ranges. A definitive diagnosis of pheochromocytoma can only be
obtained through histopathology; therefore, the diagnosis is often obtained
post-mortem.
Grossly, pheochromocytomas are often large (10 cm or
greater in diameter), multilobular, firm, and encapsulated, and typically
replace most of the affected adrenal gland. A thin rim of adrenal cortex may
surround smaller neoplasms. Large tumors are often locally invasive into the
tissues surrounding the affected adrenal gland, most notably the caudal vena
cava where they may form a thrombus. Pheochromocytomas may also be located at
extra-adrenal sites where they are called paragangliomas. On cross section,
the tumors are often red-brown to yellow (as a result of areas of hemorrhage
and necrosis), and are calcified in approximately 10% of cases.
Histologically, the cells vary from small, round or polyhedral cells to large
pleomorphic cells with multiple hyperchromatic nuclei. Tumor cells are often
arranged in irregular cords that are separated by fine fibrovascular septae.
The cytoplasm is usually pale eosinophilic and finely granular. Cytoplasmic
granules can be observed by techniques using Muller, Zenker, Orth, or other
dichromate-containing fixatives. A valuable diagnostic aid is the Henle
chromoreaction, which can be performed by applying Zenker's solution to the
flat-cut surface of a freshly resected tumor. In a pheochromocytoma, the
catecholamines will be oxidized, forming a dark brown pigment within 20 minutes
of application.
The treatment of choice for canine pheochromocytoma
is surgical removal. Medical therapy can be used for nonresectable or
metastatic disease, or to stabilize the patient prior to surgical excision.
Medical therapy is generally aimed at correcting systemic hypertension and
cardiac arrhythmias. The prognosis is guarded; however, survival of up to one
year has been reported in 50% of dogs with uncomplicated cases following
surgical removal of the tumor. Pheochromo-cytoma should be considered in cases
which have vague clinical signs and concurrent hypertension. Perhaps with more
awareness of this condition, it can be diagnosed and managed more successfully.
-by Dr. Kelly Baete, Class of 2004
-edited by Dr. Gopa Gopalakrishnan, ADDL Graduate
Student
References:
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Jones TC, BD Hunt and NW King: 1997. Veterinary
Pathology. Baltimore: Williams and Wilkens
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Jubb KVF, PC Kennedy, N Palmer (Eds): 1993.
Pathology of Domestic Animals, 4th ed. San Diego: Academic Press, 1993.
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Locke-Bohannon LG and GE Mauldin: 2001. Canine
Pheochromocytoma: diagnosis and management. Compendium on Continuing Education
for the Practicing Veterinarian 23: 807-814.
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McGavin MD, WW Carlton, JF Zachary: 2001.
Thompson's Special Veterinary Pathology, 3rd ed. St. Louis: Mosby
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Santamarina et al: 2003. Aortic Thromboembolism
and Retroperitoneal Hemorrhage Associated with a Pheochromo-cytoma in a Dog. J
Vet Int Med. 17(6): 917-922.
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Williams JE and SG Hackner: 2001.
Pheochromocytoma Presenting as Acute Retroperitoneal Hemorrhage in a Dog. J
Vet Emerg and Critical Care. 11(3): 221-227
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