Conference 14 - 2016 Case: 1 20170111

Signalment:

11-year-old, castrated male, Labrador retriever, (Canis familiaris).The patient presented six months prior to euthanasia for evaluation of a cardiac arrhythmia and a several month history of intermittent coughing which had become more severe in the two days before initial presentation. An intermittent split P wave was noted on the ECG. Thoracic radiographs revealed a markedly enlarged heart, right atrial enlargement, enlarged pulmonary vessels, and a diffuse broncho-alveolar pattern. Echocardiography showed a space-occupying mass in the left atrium with mitral and tricuspid valve regurgitation. The patient was discharged with furosemide and returned six months later with exercise intolerance and respiratory distress. At that time due to the patients declining condition the owner elected euthanasia.

Gross Description:

A 5 x 6 x 8 cm, firm, multinodular mass is present on the proximocaudal aspect of the heart base, resting on the left atrium. On cross section, the mass is highly vascular and has a mottled red-to-brown mosaic pattern. The mass surrounds the pulmonary arteries, compressing the left pulmonary artery, but it is still patent. The mass is proximal to the pulmonary veins that are not compressed. Tumor invasion into the left atrial lumen is characterized by numerous nodular small projections, up to 0.5 cm, covered by intact endocardium. Left atrial luminal size is decreased due to compression by the mass. Mild endocardiosis of the mitral and tricuspid valves is evident. The right ventricle is distended and dilated in addition to an overall enlarged heart. The abdomen contains 4 liters of sero-sanguinous clear fluid, with another 2 liters of clear creamy yellowish fluid in the thoracic cavity. The spleen has multiple firm white and hemorrhagic masses ranging from 1 mm to 3 cm in size. The consistencies of the splenic masses are similar to the heart mass. The left anterior lung is very pale, soft, and slightly decreased in size due to compression by the left atrial mass. Mediastinal lymph nodes are enlarged with effacement of normal architecture.

Histopathologic Description:

Spleen: There are multiple variably-sized solid nodules effacing and replacing the splenic parenchyma. The neoplastic nodules are well demarcated and expansile. They are composed of large islands of polygonal cells separated by large connective tissue branches and supported by fine fibro-vascular stroma that subdivide the cells in small ribbons. The tumor cells are cuboidal to polyhedral in shape with a round nucleus and a moderate amount of granular lightly amphophilic cytoplasm. The cells are aligned along the small capillaries forming small packets where the cells show polarity with the cytoplasm towards the vessels. Mitotic activity is 11 mitotic figures in 10 hpf. There are areas of marked aniso-karyosis and occasional megalokaryosis (polymorphism) with prominent nucleoli. The large cells show a round eosinophilic prominent nucleolus. The adjacent splenic parenchyma is compressed and attenuated. There are small multiple aggregates of macrophages filled with large granulated golden pigment (hemosiderin- previous hemorrhages). The smooth muscle trabeculae are closer than expected due to collapse of the parenchyma with very few follicles.

Morphologic Diagnosis:

1. Heart: Chemodectoma

2. Heart: Mild diffuse mitral and tricuspid valve myxomatous degeneration

3. Spleen: Chemodectoma, metastasis

4. Liver: Chronic severe congestive hepatopathy

5. Lymph Nodes: Chemodectoma, metastasis

Lab Results:

Upon initial presentation, NOVA results are as follows:

Glucose: 118 mg/dL (60-115)

Ca++: 1.35 mmol/L (2.2-3.0)

Mg++: 0.49 mmol/L (1.5-2.5)

PCO2: 26.1 mmHg (34-40)

PO2: 49.1 mmHg (85-100)

PO2: 49.1 mmHg (85-100)

SO2: 85.4 % (>90)

BEecf: -7.3 mmol/L ([0]-[+6])

nCa: 1.37 mmol/L (1.13-1.33)

nMg: 0.50 mmol/L (0.26-0.41)

Condition:

Neuroendocrine carcinoma

Contributor Comment:

Spleen is the only tissue submitted. Chemodectomas are primary neuroendocrine tumors arising most commonly from the chemoreceptor organs of the aortic and carotid bodies.^1,2,4,12 Other chemoreceptors that rarely develop neoplasia include the nodose ganglion of the vagus nerve, ciliary ganglion in the orbit, the pancreas, and the glomus jugulare along the recurrent branch of the glossopharyngeal nerve.¹¹ They are synonymous with heart base tumors or non-chromaffin, extra-adrenal, paragangliomas in veterinary medicine.^3,4

Chemodectomas are uncommon neoplasms most often described in canines where they have an incidence of 0.19%.¹⁴ Chemo-dectomas are the second most common cardiac tumor, behind hemangiosarcomas, representing 8% of cardiac tumors.¹⁴ Contrary to humans, aortic body tumors are the more common form of chemodectoma in animals with carotid body tumors being less common and more malignant.⁴ In dogs, aortic body tumors are encountered up to four times more frequently than carotid body tumors.¹² The aortic body is located adjacent to the adventitia of the aortic arch at the bifurcation of the subclavian artery while the carotid body is located at the bifurcation of the common carotid artery.^1,4,14 Paren-chymal cells of neuroectodermal origin and sustentacular or stellate cells are the primary cell types that make up the chemoreceptor organs.^4,11 The function of the aortic and carotid bodies is to sense fluctuations in the carbon dioxide, pH, and oxygen tension in blood, which helps to regulate respiration and circulation.^4,7 The aortic and carotid bodies can increase heart rate and elevate arterial blood pressure through the sympathetic nervous system and alter the depth, minute volume, and rate of respiration through the parasympathetic nervous system.⁴ The chemoreceptor system is considered part of the parasympathetic nervous system, as it does not secrete catecholamines; however, the presence of secretory granules in the cytoplasm of the glomus cells, the functional cells of chemoreceptors, is inconsistent with this finding.^1,11,12

Due to the lack of catecholamine production, the tumors clinical manifestations are the result of being a space-occupying lesion. Smaller adenomas may go undetected, as they can be too small to cause clinical signs, while larger adenomas may press on the atria or displace the trachea and partially surround the major vessels at the base of the heart. Aortic body tumors can also be locally invasive and invade the lumen of the surrounding great vessels or heart chambers hindering blood flow.⁴ Common clinical manifestation of aortic body tumors include ascites, pulmonary edema, nutmeg liver, hemothorax, hemopericardium, anasarca, dyspnea, cyanosis, splenomegaly, and arrhythmias.^6,10,12,15 Many of these clinical manifestations are consistent with right-sided congestive heart failure brought on by the tumor acting as a space occupying lesion or by local invasion of vessels resulting in the obstruction of blood flow.¹⁵ Another way aortic body tumors cause lesions is through metastasis to other parts of the body. It is rare for an aortic body tumor to metastasize, with the most common locations being the lungs and liver.⁴ However, other locations have been identified including lymph nodes, myocardium, kidney, adrenal gland, bladder, spleen, and even bone.^4,5,7,12,14 Immuno-histochemistry has been valuable to definitively confirm the diagnosis of chemodectomas.^8,12,15

JPC Diagnosis:

Spleen: Neuroendocrine carcinoma, metastatic, Labrador retriever, Canis familiaris.

Conference Comment:

The contributor provides an excellent summary of the key features of chemodectomas in dogs. As is the tradition at the Joint Pathology Center, conference participants are not provided the full signalment, history, gross necropsy findings, or results of additional histo-chemical and immunohistochemical stains prior to the conference. Conference participants described nests and packets of neoplastic polygonal cells with small, round, hypochromatic nuclei separated and supported by a delicate fibrovascular stroma, and aptly determined the neoplasm to be of neuroendocrine origin; however, without the additional clinicopathologic information, the site of origin could not be definitively determined from histopathologic evaluation alone. As a result, participants discussed the most likely sites of origin for neuro-endocrine chemoreceptor paragangliomas (also known as chemodectomas and glomus tumors) in animals.

Chemoreceptor organs are present in several sites of the body, such as the cartotid body, aortic body, nodose ganglion of the vagus nerve, ciliary ganglion of the orbit, pancreas, jugular vein, middle ear, and glomus jugulare near the glossopharyngeal nerve.¹³ As mentioned by the contributor, they are all highly sensitive to changes in blood pH, oxygen tension, and temperature, and can rapidly change respiratory and heart rate via the autonomic nervous system.¹³ Metastasis occurs in about 1/3^rd of cases of chemodectomas arising from the carotid body, and multicentric neoplastic trans-formation has been frequently reported in brachiocephalic dogs, possibly because of breed-associated anatomic malformations in the upper respiratory tract resulting in chronic hypoxia.¹³

Neoplastic cells in neuroendocrine tumors contain variable numbers of cytoplasmic secretory granules, best visualized by electron microscopy. Additionally, the number of granules is used to distinguish adenomas, which contain more numerous granules, from carcinomas. In addition, neoplastic cells typically will be immunopositive for chromogranin-A, neuron-specific enolase (NSE), synapto-physin, and S100 protein. Prior to the conference, the JPC performed tissue immunohistochemistry for chromogranin-A, NSE, and synaptophysin. Unfortunately neoplastic cells were immunonegative for all three stains; however, participants speculated the results may be due to suboptimal tissue fixation.¹³

References:

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