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Tumors of chemoreceptor organs are called chemodectomas or paragangliomas. These chemoreceptor organs are responsible for detecting changes in blood oxygen and carbon dioxide levels, and in blood pH. The aortic and carotid bodies are the most common sites for the development of paragangliomas in dogs (1,2) and cats (3). The aortic body is located in the aortic arch at the bifurcation of the subclavian artery and the carotic body is located at the bifurcation of the common carotid artery.
Aortic body tumors are reported to occur 4 to 5 times more frequently than carotid body tumors in dogs (2,4). These tumors usually express neuroendocrine markers that can be detected by using immunohistochemical staining, such as neuron specific enolase (NSE), synaptophysin, and chromogranin A (4–6). Ultrastructurally, the cytoplasm of the tumor cells contains neurosecretory dense core granules (7).
We diagnosed a carotid body tumor in an 8-year-old, female, white puli dog. The owners observed that the dog became moody and inactive, and developed hoarseness. The dog was given long-acting antibiotics and a combined vitamin (A + D3 + E) injection. After this treatment, the dog’s physical status slightly improved. The dog was returned to the clinic after 37 d with the following signs: distress, hyperpnea, dyspnea, increased intra-ocular pressure (glaucoma) of the left eye, and bilateral dilation of the pupils. At the beginning of the clinical examination, the dog collapsed and was given oxygen after intubation. On physical examination, an extensive, firm mass surrounding the larynx was found, but the parotid, mandibular, and the retropharyngeal lymph nodes were normal. The owners opted for euthanasia.
Necropsy disclosed a 105- × 30-mm, firm, and multilobulated tumor in the left lateral laryngeal region (Figure 1). The swelling extended to the Y-shaped fusion of the linguofacial and maxillary veins forming the external jugular vein, but it was not associated with these veins. Medial to this branching, the tumor masked the bifurcation of the common carotid artery, the origin of the occipital, lingual, and facial arteries, and the vagosympathetic trunk. The tumor was not associated with the neighboring salivary glands. Caudal to the tumor, the common carotid artery was distended. The tumor was dark tan to purple, well circumscribed, and encapsulated. The cut surface revealed a greyish-red septate mass around the internal carotid artery, with multiple areas of hemorrhage and cystic degeneration (Figure 2).
Histologically, the tumor tissue was divided into lobules by prominent branching trabeculae of connective tissue contiguous with the fibrous capsule, and many blood vessels were present. The cells were polygonal or oval, and they contained variable amounts of granular, slightly basophilic cytoplasm. Areas of spindle cells and giant cells with bizarre-shaped, double, and enlarged nuclei with prominent nucleoli were encountered (Figure 3). Nuclear anaplasia and hyperchromatism were seen, but mitotic figures were rare. Immunohistochemical evaluation utilized 4-μm paraffinembedded tissue sections and standard streptavidin-biotin indirect immunoperoxidase methods with a panel of commercially available mouse and rabbit anti-human primary monoclonal antibodies recognizing alpha-smooth muscle actin (DAKO Corp.), vimentin (HRP, DAKO Corp.), cytokeratin (MNF116, DAKO Corp.), desmin (DAKO Corp.), neuron-specific enolase (NSE, DAKO Corp.), synaptophysin (SYN, Biogenics Corp.), S-100 (DAKO Corp.), and Ki-67 (DAKO Corp.). The positive controls were feline pancreas (NSE, SYN) and canine skin (S-100). Negative controls included staining reactions in which the primary antibody was omitted.
All tumor cells were negative for cytokeratin (MNF 116), desmin, S-100, and smooth muscle actin, and strongly positive for vimentin and synaptophysin. Some tumor cells also stained positively for neuron-specific enolase, and the number of Ki-67 positive cells was low. By electron microscopy, the neoplastic cells contained neurosecretory dense core granules (Figure 4). The location of the tumor and its morphological and immunohistochemical features pointed to the diagnosis of paraganglioma (carotid body tumor).
Having the pathological diagnosis, the clinical signs can be explained in a coherent way. The hoarse voice can be explained by the compression of the laryngeal nerves. Hyperpnea and dyspnea can be explained on the basis of the dysregulation of the chemoreceptors of the carotid body. In human patients with hypertonia or arteriosclerosis, collapse may result from volume changes of the carotid sinus, with activation of the stretch receptors and consequential downregulation of the blood pressure (12). Compression of the internal carotid artery also affects the tissues perfused by this artery on the same side, including the eye. The majority of the retinal blood supply arrives from the internal ophthalmic artery via the central retinal artery; therefore, the unilateral ocular signs were probably the result of retinal ischemia rather than glaucoma. The phenomenon is referred to as amaurosis fugax in human medicine (13).
Carotid body tumors are rare neoplasms that tend to splay the carotid bifurcation as they enlarge, and can extend along the internal carotid to the base of the skull. The paraganglioma is histologically similar to the normal carotid body, except that cell clusters tend to be larger and contain vascular areas and giant cells with bizarre-shaped nuclei, binucleation, and karyomegaly with prominent nucleoli. Nuclear pleomorphism and cellular hyperchromatism are common and should not be considered as the only indicator of malignancy (14). In fact, there are no clear histologic characteristics of malignancy, except for the presence of metastases, which were absent in the present case.
Dr. Deim’s current address is Central Veterinary Institute, Department of Mammalian Pathology, Budapest Tabornok u.2 1149 Hungary.