Imaging features of retroperitoneal extra-adrenal paragangliomas in 10 dogs.

Retroperitoneal paragangliomas are rare tumors of the neuroendocrine system. Only a few canine case reports are available with rare descriptions of their imaging features. The objectives of this multi-center, retrospective case series study were to describe the diagnostic imaging features of confirmed retroperitoneal paragangliomas and specify their location. Medical records and imaging studies of 10 affected dogs with cytological or histopathologic results concordant with retroperitoneal paragangliomas were evaluated. Dogs had a median age of 9 years. Four of them had clinical signs and laboratory reports compatible with excessive production of catecholamines. Six ultrasound, four CT, four radiographic, and one MRI studies were included. The paragangliomas did not have a specific location along the aorta. They were of various sizes (median 33 mm, range: 9-85 mm of length). Masses had heterogeneous parenchyma in six of 10 dogs, regardless of the imaging modality. Strong contrast enhancement was found in all CT studies. Encircling of at least one vessel was detected in six of 10 masses, clear invasion of a vessel was identified in one of 10 masses. In five of 10 cases, the masses were initially misconstrued as lymph nodes by the on-site radiologist. Retroperitoneal paragangliomas appear along the abdominal aorta, often presenting heterogeneous parenchyma, possibly affecting the local vasculature, and displaying strong contrast enhancement on CT. Clinical signs can be secondary to mass effects or excessive catecholamine production. Underdiagnosis and misdiagnosis of this tumor are suspected as they can be silent, of small size, or confused with other structures.

Intracardiac malignant nonchromaffin paraganglioma (chemodectoma) in a cat.

A 5-year-old male castrated Domestic Shorthair cat was presented to a veterinary specialty hospital for evaluation of large-volume pleural effusion. Echocardiography revealed a large intracardiac mass at the level of the interatrial septum impairing right atrial inflow resulting in lymphocytic pleural effusion and ascites. Differential diagnoses included lymphoma, hemangiosarcoma, rhabdomyosarcoma, chemodectoma, neurofibrosarcoma, myxoma, metastatic carcinoma or intracardiac thrombus, abscess or granuloma. Due to poor long-term prognosis and recurrent, large-volume pleural effusion, the cat was humanely euthanized. The heart was submitted for histopathologic evaluation. The mass was subsequently determined to be a malignant extra-adrenal nonchromaffin paraganglioma (chemodectoma) arising from the pulmonary trunk near its bifurcation in the region of the glomus pulmonale. Chemodectomas are rare in cats and to the authors' knowledge, there are no reports of one originating from the glomus pulmonale.

Choroidal neuroendocrine neoplasia in a dog.

OBJECTIVE: To report onset and progression of clinical signs of a neuroendocrine neoplasm (NEN) presumed metastatic to the choroid in a dog. ANIMALS STUDIED: A 7.5-year-old female spayed German shepherd dog mix referred for advanced imaging and evaluation of a subretinal mass in the right eye. PROCEDURES: Procedures performed included general physical and ophthalmic examinations; ocular, orbital, and abdominal ultrasonography; thoracic radiographs; cranial magnetic resonance imaging; serologic testing for infectious agents; analysis of hematologic as well as serum and urine biochemical parameters; echocardiography; electrocardiography; cytologic assessment of lymph nodes; and histopathology and immunohistochemistry of the enucleated globe. RESULTS: Examination and imaging identified a pigmented mass within and expanding the superior choroid. Following enucleation, a choroidal NEN with tumor emboli in scleral blood vessels was diagnosed by histopathologic assessment and confirmed by immunohistochemical labelling. Despite extensive and repeated diagnostic testing over many months, a putative primary site was not identified until 19 months after the initial ocular signs were noted. At that time, a heart-base mass and congestive heart failure were highly suggestive of a chemodectoma. CONCLUSION: This comprehensive report of a NEN presumed metastatic to the choroid in a dog suggests that ocular disease can be a very early and solitary sign of NEN in the dog.

An aortic body carcinoma with sarcomatoid morphology and chondroid metaplasia in a French Bulldog.

An 11-year-old female French Bulldog was presented with a mass at the base of the heart, detected by X-ray and echocardiography. Clinical abnormality included abdominal retention by ascites. Radiation therapy was performed for 5 weeks. The mass volume didn't change during the radiotherapy. The condition became worse and the dog died 6 months after the initial presentation and necropsy was performed. Grossly, the mass, 12.5 × 6.5 × 6.0 cm in size, was found at the base of the heart. Histopathological examination revealed that cardiac mass was composed of alveolar, bundle and diffuse proliferation of neoplastic cells. Most of the neoplastic cells showed a spindle morphology; in some areas small round or polyhedral neoplastic cells were observed. Occasional cartilage metaplasia was seen multifocal in the mass, and it was surrounded by the sarcomatoid proliferation. Electron microscopy revealed a few neuroendocrine granules in the cytoplasm of spindle and polyhedral neoplastic cells. Metastatic cells in the lungs which had not irradiated demonstrated typical morphology of aortic body tumors. Based on these findings, the case was diagnosed as an aortic body carcinoma with sarcomatoid morphology and chondroid metaplasia.

Stereotactic body radiation therapy for heart-base tumors in six dogs.

INTRODUCTION: Heart-base tumors are increasingly treated with radiotherapy, yet safety and efficacy are incompletely understood. This case series describes outcomes after stereotactic body radiation therapy (SBRT) for presumed chemodectoma. ANIMALS: Six pet dogs. METHODS: A retrospective study was performed, including dogs with a clinical diagnosis of chemodectoma and treatment with three-fraction SBRT (30 Gy total). RESULTS: Heart-base tumors, presumed or confirmed to be chemodectomas, were diagnosed via histopathology or imaging. Treatment was delivered with intensity modulation and cone-beam computed tomography-based image guidance, using a linear accelerator and robotic couchtop. Intrafraction respiratory motion was managed with either neuromuscular blockade and breath-holding (n = 3) or high-frequency jet ventilation (n = 3); mean total anesthesia times for each technique were 165 and 91 min per fraction, respectively. Four tumors were assessed after SBRT; tumor volume decreased by 30-76%. Possible treatment-related complications included cough, tachyarrhythmias, and congestive heart failure. Two dogs experienced sudden death 150 and 294 days after SBRT. Three dogs are alive 408-751 days after SBRT, and one dog died of unrelated disease 1,228 days after SBRT. CONCLUSIONS: This SBRT protocol resulted in rapid tumor volume reduction, and jet ventilation effectively reduced treatment delivery times. However, cardiac arrhythmias (presumably tumor or treatment associated) and sudden death were common after SBRT. Therefore, SBRT is a potentially useful treatment but may not be appropriate for dogs with incidentally diagnosed, slowly growing tumors, which are not causing cardiovascular disturbances. Longer follow-up and larger case numbers are needed to more completely define safety and impact of treatment on long-term survivability.

Orbital paraganglioma in a dog.

A 10-year-old Rottweiler presented with right-sided moderately painful exophthalmia, blindness, absence of dazzle and pupillary light reflexes, a swollen optic nerve head and ventrolateral indentation of the globe. On magnetic resonance imaging, a 3 x 2 x 2 cm mass with a fluid filled center and contrast-enhancing periphery was noted posteriolateral of the globe. Orbital ultrasound was used for a guided fine needle aspirate of the mass. Cytology revealed moderate numbers of polygonal cells with lightly basophilic cytoplasm. Several cells showed nuclear pseudoinclusions. Histopathology following exenteration of the orbit revealed an infiltrative, extradural neoplasm surrounding the optic nerve. Cells were arranged in packets. Neoplastic cells were immunopositive for neuron specific enolase, synaptophysin and chromogranin A and immunonegative for cytokeratin. Findings were consistent with an extra-adrenal paraganglioma (neuroendocrine tumour). Although complete excision could not be confirmed on histopathology, the owners reported no apparent tumour recurrence 25 months after surgery. In conclusion a paraganglioma should be considered as a differential diagnosis of an orbital mass.

Succinate dehydrogenase subunit D and succinate dehydrogenase subunit B mutation analysis in canine phaeochromocytoma and paraganglioma.

Phaeochromocytomas (PCs) are tumours of the adrenal medulla chromaffin cells. Paragangliomas (PGLs) arise in sympathetic ganglia (previously called extra-adrenal PCs) or in non-chromaffin parasympathetic ganglia cells that are usually non-secretory. Parenchymal cells from these tumours have a common embryological origin from neural crest ectoderm. Several case series of canine PCs and PGLs have been published and a link between the increased incidence of chemoreceptor neoplasia in brachycephalic dog breeds and chronic hypoxia has been postulated. A similar link to hypoxia in man led to the identification of germline heterozygous mutations in the gene encoding succinate dehydrogenase subunit D (SDHD) and subsequently SDHA, SDHB and SDHC in similar tumours. We investigated canine PCs (n = 6) and PGLs (n = 2) for SDHD and SDHB mutations and in one PGL found a somatic SDHD mutation c.365A>G (p.Lys122Arg) in exon 4, which was not present in normal tissue from this brachycephalic dog. Two PCs were heterozygous for both c.365A>G (p.Lys122Arg) mutation and an exon 3 silent variant c.291G>A. We also identified the heterozygous SDHB exon 2 mutation c.113G>A (p.Arg38Gln) in a PC. These results illustrate that genetic mutations may underlie tumourigenesis in canine PCs and PGLs. The spontaneous nature of these canine diseases and possible association of PGLs with hypoxia in brachycephalic breeds may make them an attractive model for studying the corresponding human tumours.

Cytological, histological and ultrastructural nuclear features of monster cells in a canine carotid body carcinoma.

A 7-year-old female Shih-tzu dog was presented with severe dyspnoea. A large mass was palpated in the left cranial neck. Cytological examination of an aspirate sample revealed cells with marked anisokaryosis, giant elements and many bare nuclei. Scattered intact giant cells showed scant, granular cytoplasm and intranuclear inclusions. Histologically, neoplastic cells were subdivided into lobules by fine collagenous trabeculae. Numerous pleomorphic giant, or 'monster', cells were observed, showing a highly indented nuclear envelope, intranuclear cytoplasmic pseudoinclusions (ICPs) and 'ground-glass' nuclear appearance. Neoplastic emboli were present, but no distant metastases were detected grossly. Immunohistochemically, the neoplastic cells expressed synaptophysin and had variable expression of neuron-specific enolase and vimentin. The cells were negative for pan-cytokeratin, CAM 5.2, glial fibrillary acidic protein and S100. Nuclear abnormalities and cytoplasmic neurosecretory granules were noted ultrastructurally. These features were consistent with a diagnosis of carotid body carcinoma (chemodectoma). Monster cells with ICPs have not been documented previously in canine chemodectoma.

Malignant paraganglioma in a cougar (Puma concolor).

A 7½-yr-old male cougar (Puma concolor) was presented with a 2-wk history of progressive hindlimb abnormalities. An abdominal mass was palpated on physical examination. Computed tomography of the abdomen showed a mass surrounding the left ureter. A postmortem diagnosis of paraganglioma was established.

Extra-adrenal retroperitoneal paraganglioma in a dog.

An extra-adrenal retroperitoneal paraganglioma was observed in a 10.5-year-old male Boxer dog. Additionally, the dog had an aortic base tumor, multiple thyroid adenomas, multiple testicular interstitial cell tumors, bilateral nodular adrenal cortical hyperplasia, and parathyroid gland hyperplasia. The hypothesis that the retroperitoneal mass represents a primary extra-adrenal paraganglioma rather than metastatic mass from the aortic body tumor is considered. Either primary or metastatic extra-adrenal retroperitoneal paragangliomas are rarely reported in dogs.

Comparison of presumptive echocardiographic and definitive diagnoses of cardiac tumors in dogs.

BACKGROUND: Echocardiography is used for identification of cardiac tumors and presumptive diagnoses often are made based on the location of identified masses. OBJECTIVES: To determine the accuracy of echocardiographically based presumptive diagnoses of cardiac tumors when compared with clinicopathologic or histopathologic definitive diagnoses. ANIMALS: A total of 24 client-owned dogs having a cardiac mass on echocardiogram that was subsequently definitively diagnosed by cytology or histopathology. METHODS: Retrospective study. A Cardiac Veterinary Database search of animals seen at the University of Tennessee John and Ann Tickle Small Animal Hospital from 2006 to 2012 identified 24 dogs that fit the inclusion criteria. RESULTS: The presumptive diagnosis of chemodectoma, ectopic thyroid carcinoma, or lymphoma in cases with heart base masses was correct in 7/9 cases. The presumptive diagnosis of hemangiosarcoma in cases with right atrial masses was correct in 4/8 cases. Seven cases had an open diagnosis because of the unusual presentation on echocardiogram (ECG); various neoplasms were diagnosed in these animals, but hemangiosarcoma, chemodectoma, ectopic thyroid carcinoma, and lymphoma accounted for 6 of them. Pericardial effusion was seen in 10/24 cases. ECG abnormalities were seen in 8/24 cases. Survival ranged from <1 to >150 days. CONCLUSIONS AND CLINICAL IMPORTANCE: In this retrospective study, the presumptive diagnosis based on echocardiographic tumor location was only moderately accurate. Cardiac tumors that were considered unusual on echocardiogram were nonetheless frequently found to be the common cardiac tumor types seen in dogs.

Use of three-dimensional conformal radiation therapy for treatment of a heart base chemodectoma in a dog.

CASE DESCRIPTION: A 9-year-old spayed female mixed-breed dog was evaluated because of a progressively worsening, nonproductive cough and gagging of 1 year's duration. CLINICAL FINDINGS: Physical examination results were unremarkable. A cranial mediastinal mass was identified at the heart base with 3-view thoracic radiography. A CT scan of the thorax revealed an invasive mass surrounding major vessels at the heart base that was not considered surgically resectable. Thoracoscopic biopsy specimens of the cranial mediastinal mass were obtained, and histologic evaluation revealed that the tumor was a chemodectoma. TREATMENT AND OUTCOME: On the basis of results of the CT scan, a 3-D conformal radiation therapy plan was generated with computer treatment-planning software. The patient was treated with external beam radiation therapy; a 6-MV linear accelerator was used to deliver a prescribed dose of 57.5 Gy in twenty-three 2.5-Gy fractions. The cough improved following radiation therapy. Prior to treatment, the tumor volume was calculated to be 126.69 cm(3). Twenty-five months following radiation therapy, a follow-up CT scan was performed and there was a >50% reduction in tumor volume at that time. Disease progression causing pericardial, pleural, and peritoneal effusion and syncopal episodes occurred 32 months following radiation therapy, which were treated with pericardectomy and additional radiation therapy. The dog was still alive and doing well 42 months following initial radiation treatment. CLINICAL RELEVANCE: Conformal radiation therapy provided an additional treatment option for a nonresectable heart base chemodectoma in the dog of this report; conformal radiation therapy was reasonably tolerable and safe.

Right atrial chromaffin paraganglioma in a dog.

Cardiac neoplasia is relatively uncommon in canine patients, with the most common neoplasms including right atrial hemangiosarcoma and paragangliomas occurring at the heart base (i.e. chemodectomas or aortic body tumors). Intracardiac paragangliomas are rare neoplasms in humans and have seldom been documented in the veterinary literature. This report describes the clinical course and histopathological findings in an adult canine patient with an intracardiac chromaffin paraganglioma (non-adrenal pheochromocytoma) of the right atrium.

A case of synchronous hepatocellular carcinoma and aortic body chemodectoma in a dog - pathological case report.

The authors describe a case of synchronously occurring (double) tumours, i.e. primary hepatocellular carcinoma and aortic body chemodectoma in a 14-year-old mixed-breed male dog. The tumours were identified during necropsy, following euthanasia. In the last months of its life, the dog showed signs of weakness, anorexia, apathy, inactivity, and abdominal palpation elicited a painful reaction. The primary liver cancer emerged in the left lateral lobe without evidence of any distant metastases. Histopathological and immunohistochemical investigations revealed a well-differentiated, trabecular, claudin-7-, claudin-5- and pancytokeratin-negative hepatocellular carcinoma. The Ki-67 proliferation index was 33%. During necropsy, a synchronously occurring benign, grade I type aortic body chemodectoma was also detected in the dog. This neuroendocrine tumour showed chromogranin-, synaptophysin-, neuron-specific enolase- and S100 protein-positivity, and the Ki-67 proliferation index was 2%. The authors believe that this is the first description of synchronously occurring hepatocellular carcinoma and aortic body chemodectoma in a dog.

Cases with manifestation of chemodectoma diagnosed in dogs in Department of Internal Diseases with Horses, Dogs and Cats Clinic, Veterinary Medicine Faculty, University of Environmental and Life Sciences, Wroclaw, Poland.

In the period of 3 years, 9 tumours of chemodectoma were supravitally diagnosed and histopathologically verified in dogs. In this period 15 351 dogs were admitted to the Clinic of Dogs and Cats and 2 145 dogs were examined in the cardiological outpatient clinic for dogs. This tumour is located in a typical place--at the base of the heart. Most frequently the tumour manifested in older boxers. Only in one case such a tumour was diagnosed in another breed of dogs. The tumours ranged in size between 3 and 16 cm in diameter. The principal sign accompanying tumours of cardiac base involved dyspnoea but in 3 cases the tumours yielded no clinical signs. All the diagnoses were additionally verified using immunohistochemical examination. We used antibodies to chromogranin A (clone DAK-A3 1:100), synaptophysin (clone SY38 1:20) and neuron-specific enolase (clone BBS/NC/VI-H14 1:150). An immunohistochemical examination is vital for the diagnosis since it allows to differentiate histologically distinct types of neoplasia which may locate in the same site and may manifest a similar histological pattern.

Metastatic extra-adrenal sympathetic paraganglioma in a horse.

Post-mortem examination was performed on a horse that died after exhibiting signs of colic. Gross findings included haemoperitoneum and a large round encapsulated mass located in the sublumbar area cranial to the left kidney. On sectioning the mass was solid red to brown and small nodules of similar tissue were noted at the periphery of the mass. The spleen was firm and three nodules were found in one thyroid gland. Microscopically, the abdominal mass, adjacent nodules, the spleen and one thyroid nodule consisted of clusters and cords of round to oval neoplastic cells, separated by a fine collagen and reticulin fibre network. Immunohistochemically, tumour cells expressed chromogranin A, synaptophysin and neuron-specific enolase, but did not express cytokeratin. The findings were consistent with a metastatic extra-adrenal sympathetic paraganglioma.