JPC SYSTEMIC PATHOLOGY
Signalment (JPC #1965139): 11-year-old castrated male German shorthair pointer
HISTORY: None provided
HISTOPATHOLOGIC DESCRIPTION: Slide A: Fibroadipose tissue: Extending to all borders and compressing adjacent adipose tissue is a multilobular, densely cellular, infiltrative neoplasm composed of polygonal cells arranged in nests and packets supported by a thin rim of sustentacular cells and a fine fibrovascular stroma, with lobules separated by dense bands of fibrovascular connective tissue. Neoplastic cells have variably distinct borders, a moderate amount of pale eosinophilic, frequently vacuolated, granular cytoplasm, and round nuclei with stippled chromatin and 1-2 variably distinct nucleoli. There is moderate anisocytosis and anisokaryosis, with occasional neoplastic cells having large, multilobed nuclei (ancient change). Mitoses average 1 per 10 HPF. There are scattered areas of necrosis characterized by loss of tissue architecture and replacement by eosinophilic cellular and karyorrhectic debris, and individual cell necrosis characterized by hypereosinophilic cytoplasm, pyknosis, karyorrhexis and karyolysis, with variably sized foci of mineralization and acicular (cholesterol) cleft formation. Multifocally neoplastic cells impinge on vessel walls. There are multifocal peripheral infiltrates of lymphocytes, plasma cells, macrophages (often hemosiderin-laden), scattered hemorrhage, congestion, and accumulations of hematoidin pigment.
Slide B (Churukian-Schenk): The cytoplasm of neoplastic cells contains many discrete, brown to black, argyrophilic granules.
MORPHOLOGIC DIAGNOSIS: Fibroadipose tissue: Chemodectoma, German shorthair pointer, canine.
SYNONYMS: Aortic/carotid body tumor, paraganglioma, nonchromaffin paraganglionoma, extra-adrenal paraganglionoma, glomus cell tumor
- Chemodectoma/paraganglioma is a tumor of nonchromaffin extra-adrenal paraglangia cells (chemoreceptor cells) and may occur throughout the body ( where there are sympathetic and parasympathetic ganglia (i.e. head, neck, thorax, abdomen);
- Brachycephalic breeds appear predisposed
- Chemoreceptors are composed of parenchymal (chemoreceptor and glomus) cells and sustentacular/stellate cells (i.e. support cells)
- Chemoreceptor organs: – responsible for detecting and responding to changes in CO2, pH, and oxygen tension
- Carotid and aortic bodies are a subset of chemoreceptor organs, and also regulate respiration, heart rate and blood pressure
- In animals, aortic body tumors are more common than carotid body tumors
- Carotid body tumors are more likely to be malignant than are aortic body tumors
- There is a distinction between tumors of chromaffin (ganglia of the sympathetic trunk) and non-chromaffin paraganglia; paragangliomas of chromaffin origin may be referred to as extra-adrenal pheochromocytomas
- Unknown etiology; suggested genetic predisposition that is aggravated by chronic oxygen hypotension (brachycephalic dog breeds, humans and animals living at high altitude)
- Genetic pathogenesis is similar to pheochromacytomas – HIF1 pathway, MAPK/mTOR pathway, and hypermethylation/mutation of SDHx genes
- Nonfunctional neoplasm acts as a space-occupying lesion à cardiac decompensation
TYPICAL CLINICAL FINDINGS:
- Signs result from pressure on atria and/or vena cava:
- Hydropericardium, hydrothorax, edema
- Dyspnea, cyanosis, coughing
- Compression on esophagus may cause dysphagia
- Slow-growing palpable mass near angle of mandible may be present in dogs with carotid body tumors
- Dyspnea and cough reported in dogs with multiple pulmonary metastases of malignant carotid body tumors
TYPICAL GROSS FINDINGS:
- Aortic body tumors most often single masses within pericardial sac near heart base; often more benign than carotid body tumors:
- Adenoma: Single or multiple nodules, smooth, white, mottled with red-brown hemorrhage
- Carcinoma: Larger than adenoma, locally invades heart and great vessels at heart base; can form papillary projections into lumen of pulmonary artery, metastasis to lung and liver
- Carotid body tumors arise near bifurcation of common carotid artery in cranial cervical area; more often malignant with more frequent metastasis:
- Adenoma: Unilateral, single, smooth, firm, encapsulated, white mottled with red-brown hemorrhage; attached to the carotid artery adventitia and can entrap the glossopharyngeal nerve
- Carcinoma: Larger than adenoma, multinodular, hemorrhagic, cystic; may incorporate external jugular vein and cranial nerves; may deviate trachea; metastasis to lung, bronchial and mediastinal lymph nodes, liver, pancreas, kidney
- Multicentric neoplastic transformation of chemoreceptor tissue is common in brachycephalic breeds; 65% of carotid body tumor cases also have aortic body tumors
TYPICAL LIGHT MICROSCOPIC FINDINGS:
- Multiple lobules of polygonal cells divided by connective tissue trabeculae originating from the capsule with further subdivision into nests and packets by fine fibrovascular septae
- Uniform round to oval, central nuclei with finely granular chromatin
- Mitoses infrequent; little cellular pleomorphism
- Tumor invasion through the capsule into walls of large muscular arteries, atria, tracheal bifurcation, and/or pericardium
- Arranged in broad sheets with less distinctive nesting and packeting
- Pleomorphic, hyperchromatic cells with frequent mitoses
- Mononuclear tumor giant cells with bizarre, multilobed nuclei are more common in carcinomas, but may be found in adenomas as well
- Abundant eosinophilic, granular to vacuolated cytoplasm and indistinct cell borders
- Cells undergo rapid autolysis
- Well-vascularized; frequent hemorrhage, coagulative necrosis, cholesterol clefts, and mineralization
- Clusters of polyhedral cells that lack normal orientation to sustentacular, neural and vascular elements
- Variable cytoplasmic density depends on number of electron dense, membrane-bound secretory granules (granules more numerous in adenomas than in carcinomas); the granules in chemodetomas are endocrine secretory granules and NOT chromaffin granules (as seen in pheochromocytoma)
- Stellate (sustentacular cells) have long cytoplasmic processes that surround tumor cells and terminate near perivascular spaces
ADDITIONAL DIAGNOSTIC TESTS:
- Argyrophilic cytoplasmic granules (positive Churukian-Schenk or Grimelius)
- In contrast to pheochromocytomas, chemodectomas lack chromaffin granules
- IHC: inconsistently positive for synaptophysin, S-100, and neuron specific enolase; positive for chromogranin A
For gross finding of heart base tumor:
- Ectopic thyroid adenoma (white-tan, solid nodules) or carcinoma (multinodular, necrotic and hemorrhagic) (differentiate with IHC [positive for TTF-1 and thyroglobulin] or EM [lack secretory granules and have numerous microvilli on luminal surfaces]); cells are smaller with darker cytoplasm and hyperchromatic nuclei, follicles with colloid may be present and positive with thyroglobulin IHC
- Ectopic parathyroid chief cell adenoma: Light brown to red, encapsulated (differentiate with IHC [positive for calcitonin])
- Malignant lymphoma: Usually involves right atrium, either nodular with a pale, flesh-like appearance or diffuse causing an irregular, thickened and gray myocardium
- Hemangiosarcoma: Usually involves right auricle and atrium; gray to red-black
- Thymoma: Cranial mediastinum
- Carotid body tumors have been reported in dogs, cats, cattle and mink
- Aortic body tumors have been reported in dogs, cats, cattle and birds
- Horses: Unique orbital paraganglioma where neoplastic cells locally invade retrobulbar tissue causing exophthalmos
- Humans: Carotid body tumors are more common than aortic body tumors
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- Romanucci M, Malatesta D. Cytological, histological and ultrastructural nuclear features of monster cells in canine carotid body carcinoma. J Comp Path. 2014; 151:57-62.
- Rosol T, Grone A. Endocrine glands. In: Maxie MG, ed. Jubb, Kennedy, and Palmer’s Pathology of Domestic Animals. Vol 3. 6th ed. St. Louis, MO: Elsevier; 2016:354-356.
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