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Page 1: file · Web viewMediastinal paraganglioma as a cause of hemothorax and thoracic spinal cord compression in a Quarter Horse gelding. Nicholas J Parkinsona1, Katherine E Wilsona

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Mediastinal paraganglioma as a cause of hemothorax and thoracic spinal cord compression

in a Quarter Horse gelding

Nicholas J Parkinsona1, Katherine E Wilsona, Geoffrey K Saundersb, Virginia A. Buechner-

Maxwella, W. Kent Scarratta, R Scott Pleasanta, Rebecca A Funka

Author institutions and affiliations:

a. Department of Large Animal Clinical Sciences, Virginia-Maryland College of Veterinary

Medicine, Virginia Polytechnic and State University, Blacksburg, VA.

b. Department of Biomedical Sciences and Pathobiology (Saunders), Virginia-Maryland College

of Veterinary Medicine, Virginia Polytechnic and State University, Blacksburg, VA.

Author email addresses: Parkinson: [email protected] ; Wilson: [email protected] ;

Saunders: [email protected] ; Buechner-Maxwell: [email protected] ; Scarratt: [email protected] ;

Pleasant: [email protected] ; Funk: [email protected]

1 Present address: Royal (Dick) School of Veterinary Studies, University of Edinburgh, Easter

Bush Campus, Midlothian, EH25 9RG, United Kingdom.

Corresponding author: Nicholas J Parkinson, [email protected]

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Abstract

Neuroendocrine tumors are rarely diagnosed in horses. This report describes a case of a

neuroendocrine tumor with strong similarities to descriptions of posterior mediastinal

paragangliomas in humans and dogs. A 12-year-old Quarter Horse gelding was presented

initially for management of hemothorax of unknown origin that responded to medical

management. 19 months later, the horse was presented again with acute-onset hindlimb ataxia, at

which time a thoracic mass adjacent to the vertebral bodies was detected on radiography. The

gelding was euthanized after failing to respond to anti-inflammatory therapy, and on necropsy

the mass was identified as a paraganglioma invading the spinal canal. Despite its locally invasive

behavior, the tumor showed no evidence of metastasis, and its apparent slow progression was in

sharp contrast to more common thoracic neoplasms such as hemangiosarcoma. Combined with

the reported success of surgical excision in human mediastinal paragangliomas, this suggests that

early diagnosis of such tumors could provide the opportunity for successful treatment.

Keywords: equine, neuroendocrine tumor, chemodectoma

This research did not receive any specific grant from funding agencies in the public, commercial,

or not-for-profit sectors.

The authors declare no conflicts of interest.

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1. Introduction

Neuroendocrine tumors are a diverse group of neoplasms that are uncommonly diagnosed in

horses. The clinical signs associated with such tumors depend on both endocrine functionality

and anatomic location. Paragangliomas are tumors derived from the paraganglia, accumulations

of neural crest-derived cells associated with autonomic ganglia, which are widely distributed

throughout the body. As a consequence of their tissue of origin, they can occur in a particularly

wide variety of anatomic locations compared to other neuroendocrine tumors. They have been

reported infrequently in horses, at anatomical sites including the orbit, heart base and sublumbar

region. [1-8] Paragangliomas in the dorsal mediastinum have been described as a cause of spinal

cord compression in humans and dogs, but to the best of the authors knowledge, the case

presented here represents the first report of a comparable syndrome in a horse. [9-13] This case

differed from those described in other species, however, in that the anatomical associations of the

tumor, with both the wall of a major artery and the spinal column, led to the development of two

temporally distinct clinical manifestations, presenting an additional diagnostic challenge.

2. Case Details

2.1 First Presentation

A 12-year-old Quarter Horse gelding presented to the Virginia-Maryland College of Veterinary

Medicine for evaluation of lethargy and reluctance to move of 24 hours’ duration. These clinical

signs had been refractory to analgesia with flunixin meglumine (1 mg/kg PO q12h). There had

been no management change or observed trauma prior to the onset of clinical signs.

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On presentation, the gelding was obtunded, with normal body temperature (37.1°C) but marked

tachycardia (88 beats per minute) and moderate tachypnea (32 breaths per minute). Lung sounds

were absent cranioventrally. Moderate pectoral ventral edema was present. Mucous membranes

were pink and moist with a capillary refill time of less than two seconds. Gastrointestinal

borborygmi were within normal limits and normal feces were passed. Ultrasonography of the

thorax (Figure 1) revealed a large-volume bilateral pleural effusion extending to the dorsal lung

fields. The fluid had a variable echogenicity with visible fibrin strands and a ‘swirling’

appearance suggestive of hemorrhage. No masses or evidence of rib fractures could be detected.

No pericardial or peritoneal effusion was present, and all abdominal viscera had a normal

ultrasonographic appearance.

Complete blood count and chemistry (Table 1) showed a mild normocytic, normochromic

anemia, with no evidence of inflammation. There was a mild to moderate thrombocytopenia,

confirmed by examination of a blood smear. Coagulation times were mildly prolonged.

Abnormalities on chemistry were consistent with acute blood loss and reduced tissue perfusion.

Thoracocentesis yielded hemorrhagic fluid from both hemithoraces, with a PCV of 36% and total

protein of 48 g/L. Cytological examination was consistent with hemorrhagic effusion, with rare

erythrophagia and leukophagia within macrophages. No evidence of inflammation or neoplasia

was observed.

The most likely differential diagnoses for hemothorax in this case were considered to be trauma,

neoplasia, spontaneous or exercise-induced vessel rupture, or coagulopathy.[14] In the absence

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of other history or clinical signs to implicate coagulopathy, the thrombocytopenia and moderate

increases in coagulation times were thought to be secondary to consumption of platelets and

clotting factors. No evidence of trauma or neoplasia could be detected on physical or

ultrasonographic examination. Thoracic radiography was considered, but the volume of pleural

fluid was deemed likely to limit the diagnostic yield.

Initial management comprised conservative fluid therapy (lactated ringer’s solution at 2 ml/kg/hr

with supplementary calcium gluconate) and prophylactic antimicrobial therapy (ceftiofur

sodiuma, 2.2 mg/kg IV q12h). Given the lack of respiratory distress and to facilitate erythrocyte

autotransfusion, thoracic drainage was not performed.[14] After initiation of fluid therapy, the

gelding’s demeanor improved and blood lactate decreased to 1.8 mmol/L within 12 hours.

However, PCV and total protein continued to fall (to 17% and 30 g/L respectively in 18 hours),

rendering a blood transfusion necessary. PCV continued to fall despite administration of 8L

cross-matched whole blood, and a second transfusion was initiated 24 hours later when the PCV

reached 13%. This was discontinued due to development of severe urticaria and facial edema,

both of which were responsive to dexamethasoneb administration (0.08 mg/kg IV). The

transfusions increased the total protein to 50 g/L, but PCV continued to fall to 12%. Marked

pectoral edema and jugular distension developed, most likely resulting from reduced venous

return due to elevated intrathoracic pressure. Three days after presentation, the PCV began to

improve, coinciding with improvements in demeanor and heart rate. By day nine of

hospitalization the PCV had increased to 29% and total protein to 80 g/L, and heart rate had

reduced to 44 beats per minute. Marked pleural effusion was however still evident on ultrasound.

The gelding was discharged for monitoring at home with instructions for strict stall rest. On re-

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examination after six weeks, the horse was clinically normal, and thoracic ultrasonography

confirmed complete resolution of the hemothorax with only mild comet-tail artifacts (indicating

pleural roughening) in the cranioventral lung fields.

2.2 Second Presentation

Nineteen months after initial presentation, the horse re-presented with acute onset hindlimb

ataxia of 24 hours’ duration.

Bilaterally symmetrical grade 4/5 ataxia was present in the hindlimbs. Gait deficits included

inconsistent foot placement, marked circumduction when turning and toe dragging when

backing, and the horse frequently came close to falling. Lower motor neuron strength appeared

normal, and no proprioceptive deficits were detected in the forelimbs. Mentation, cranial nerve

reflexes, cervical and panniculus reflexes, and tail and anal tone were all normal. On the basis of

this assessment, the lesion was localized to the thoracolumbar spinal cord. Differential diagnoses

for a focal lesion at this site included equine protozoal myeloencephalitis, trauma,

discospondylitis, fibrocartilaginous embolism, or neoplasia. The animal was in good body

condition, and no further abnormalities were detected on general physical examination, complete

blood count or chemistry. Initial treatment, pending the results of diagnostic testing, consisted of

ponazurilc (5 mg/kg PO q24h) for suspected equine protozoal myeloencephalitis, and anti-

inflammatory treatment with dimethyl sulfoxided (0.5 g/kg IV q12h) and flunixin megluminee

(1.1 mg/kg IV q12h).

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Lumbosacral cerebrospinal fluid (CSF) had a nucleated cell count of less than 1 cell/mm3

(reference interval 0 – 6 / mm3), 10 erythrocytes/mm3, and total protein of 787 mg/L (reference

interval 50-1000 mg/L). The nucleated cell population consisted of 71.4% small lymphocytes

and 28.6% large mononuclear cells. A single phagocytosed erythrocyte was observed within one

large mononuclear cell, but no evidence of inflammation or neoplasia was observed. Titers

against Sarcocystis neurona antigens SnSAG 2 and 4/3 were positive in both serum (1:4000) and

CSF (1:20), but the high serum:CSF titer ratio (200:1) was not consistent with intrathecal

antibody production, and therefore did not support a diagnosis of equine protozoal

myeloencephalitis.[15] Additionally, serum titers for Neospora hughesii (by immunofluorescent

antibody test) and Borrelia burgdorferi antigens OspA, OspC and OspF (by multiplex enzyme-

linked immunosorbent assay) were negative.

Radiographs of the thoracolumbar spine showed a 17.6 cm x 10.1 cm broad-based smoothly

marginated mass of soft tissue to mineral opacity at the ventral surface of the vertebral bodies of

the fourth to sixth thoracic vertebrae (T4 - T6), superimposed on the craniodorsal margin of the

aortic arch (Figure 2). Two clearly demarcated radiolucencies were present within the body of

T5. Laterality of the mass could not be determined from the images. Mild modeling of the

articular facets of the caudal cervical, caudal thoracic and cranial lumbar vertebrae was present

but considered unlikely to be of clinical significance. Thoracic ultrasonography showed only

minor pleural irregularities in the cranioventral lung fields, presumed to be secondary to the

previous hemothorax. The mass could not be imaged ultrasonographically, indicating a deeper

location within the lung parenchyma or mediastinum.

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The location of the thoracic mass was consistent with the neuroanatomic localization of the

lesion. Differential diagnoses included neoplasia (e.g. hemangiosarcoma or osteosarcoma),

abscess, or granuloma. Abscess was considered unlikely given the normal complete blood count

and fibrinogen concentration. Due to its deep location, the mass was not accessible for

percutaneous biopsy. Thoracoscopy was offered to visualize the lesion and attempt to obtain a

biopsy, but was declined due to its invasive nature and limited chance of improving outcome.

Despite medical management, the horse showed a slight increase in hindlimb weakness after

seven days of hospitalization. The owners elected to continue palliative treatment at home.

Euthanasia was performed on humane grounds 24 hours later when the horse became recumbent

and unable to rise.

On post mortem examination, a 12 x 7 x 9 cm mass was attached to the ventral aspect of the fifth

thoracic vertebra, extending into the vertebral body with loss of 50% of the bone (Figure 3). The

mass was a homogeneous tan color with multifocal red nodules on the surface and contained red

hemorrhagic necrotic foci. The tumor was protruding into the spinal canal but did not penetrate

the ventral longitudinal ligament. There was no evidence of metastasis or neoplasia at other sites.

Short fibrous tags were present on the pleural surfaces, most likely as a sequela of the

hemothorax. There were no relevant gross abnormalities in other organs. Histologically, the

tumor arose from the wall of an artery and was composed of nests of cuboidal cells separated by

fine fibrovascular septae (Figure 4). The cells had vacuolated, pale eosinophilic cytoplasm. Two-

fold anisokaryosis and rare mitoses were present. Immunohistochemical staining was positive for

synaptophysin and neuron-specific enolase (NSE), but negative for chromogranin A (CgA). The

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neoplasm was identified as a neuroendocrine tumor, most likely a paraganglioma arising from

the aortic arch or spinal artery branch of the aorta. Bilateral, symmetrical axonal degeneration

and myelin swelling were noted in the ventral and lateral white matter at the level of T7, with

occasional mild lymphocytic-plasmacytic perivascular cuffing. These findings were consistent

with spinal cord compression by the neoplasm.

3. Discussion

The cause of the neurologic disease in this horse was confirmed to be a dorsal mediastinal

neuroendocrine tumor associated with an artery wall, most likely a paraganglioma. The location

and arterial association suggest a causal link with the prior hemothorax.

The nomenclature and diagnostic criteria of paragangliomas and related neuroendocrine tumors

are subject to some inconsistency in the published human and veterinary literature.

Paragangliomas have been subdivided historically into chromaffin and non-chromaffin types.

The former are associated with sympathetic ganglia (e.g. sympathetic trunk and celiac ganglion)

and tend to secrete catecholamines. Chromaffin paragangliomas may also be referred to as intra-

adrenal or extra-adrenal pheochromocytomas, with the adrenal medulla considered by some

authors to be an extreme example of a paraganglion. Non-chromaffin paraganglia are clusters of

glomus cells with chemoreceptor function, especially in the aortic and carotid bodies but also at

other sites including the inner ear and along the vagus nerve. Tumors of these tissues have been

previously termed ‘glomus cell tumors’ or ‘chemodectomas’. These parasympathetic

paragangliomas occur most commonly in the head and neck. It is now recognized that

chromaffin staining of paragangliomas does not reliably reflect function, and according to World

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Health Organization guidelines, ‘paraganglioma’ is the current preferred term for both tumor

types (with the exception of intra-adrenal pheochromocytoma) in humans.[16] Malignancy in

these tumors is defined by distant metastasis and not by local invasion. [17]

The anatomic location of the paraganglioma in this horse, in the craniodorsal mediastinum

immediately ventral to the thoracic vertebral bodies, was consistent with reports in humans and

in dogs.[9-13] These tumors typically originate from the costovertebral sulcus, and are

considered to arise from the aorticosympathetic paraganglia. Clinical signs attributable to

cathecholamine secretion are reported in 19 to 48% of cases of mediastinal paraganglioma in

humans.[9, 11, 18] They can be locally invasive and are often reported to invade the spinal canal,

but hemorrhage is not a typical feature. Hemorrhage from intra-adrenal pheochromocytomas is,

however, more commonly reported in horses than in humans[19], so it is possible that

paragangliomas display similar species-related differences in clinical behavior. Although

catecholamines were not measured in this case, no physiological evidence of increased

production (such as tachycardia, hyperglycemia or sweating) could be detected on the second

presentation, and all such abnormalities on the first presentation could be attributed to the

hemothorax.

There are only a small number of case reports of paragangliomas at other sites in horses, most

commonly in the orbit (11 cases).[1-4] These tumors are believed to arise from the ciliary

ganglion. It is unclear if non-chromaffin paraganglion tissue is present at this site in normal

animals. Other reported cases include two heart base tumors (reported as chemodectoma or aortic

body adenoma)[5, 6], and a laryngeal neuroendocrine tumor.[20] As in humans, the majority of

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tumors are benign (although this does not preclude local invasion). However, two sublumbar

extra-adrenal paragangliomas with extensive distant metastasis have been reported in horses.[7,

8] Ten to fifteen percent of human cases are familial, often associated with mutations in the

succinate dehydrogenase subunit genes SDHD, SDHB and SDHC, which lead to mitochondrial

respiratory chain dysfunction and activation of the hypoxia-inducible pathway.[16] Little is yet

known regarding the underlying genetic basis of paragangliomas in veterinary species, but a

study of two carotid body paragangliomas and six pheochromocytomas in dogs found potentially

pathogenic SHDB or SDHD mutations in four cases. Three were germline mutations, indicating

potential heritability. This suggests that the underlying aetiopathogenesis could be similar

between species, in at least a proportion of cases.[21, 22] The small number of reported equine

cases appear to be sporadic, across a range of breeds, and the underlying genetic changes have

not yet been investigated.

The diagnosis of a neuroendocrine tumor in this case was supported by immunohistochemistry,

with positive staining for NSE and synaptophysin, but negative CgA staining. This pattern is

consistent with two canine cases of posterior mediastinal paraganglioma [12, 13] but differs from

other equine paragangliomas, which have been positive for CgA in all seven cases for which

immunostaining for this marker has been reported.[3, 7] These three markers cannot distinguish

paragangliomas from pheochromocytomas, which are histologically identical.[23] Prognostic

significance of the immunostaining pattern has not yet been investigated in horses. Weak CgA

staining has been suggested to reflect poor differentiation or parasympathetic origin in human

paragangliomas [24, 25], or more malignant behavior in canine chemodectomas.[26] However,

no immunohistochemical marker was helpful in predicting aggressive clinical behavior in a study

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of ten human mediastinal paragangliomas.[9] Chromogranin A also has diagnostic utility as a

circulating biomarker in humans, at least for tumors of sympathetic origin [27, 28], but this has

not been investigated in horses. Similarly, urine and plasma metanephrines (catecholamine

metabolites) are useful diagnostically in humans, but are not well characterized in horses;

although they may have some utility in detecting mediastinal or abdominal paragangliomas of

sympathetic origin, it is not currently known what proportion of equine tumors are functional,

and sensitivity will likely be lower for detection of parasympathetic paragangliomas at other

locations such as the head and neck.. Diagnosis in the horse therefore relies on a combination of

imaging and histopathology, both of which may be challenging ante mortem depending on

anatomic location.

The diagnosis in this case may have been accelerated by earlier radiography after resolution of

the initial hemothorax. The index of suspicion of neoplasia was, however, reduced initially by

the rapid recovery and subsequent prolonged clinical remission. This is in stark contrast to the

expected clinical behavior of hemangiosarcoma, the most commonly reported neoplastic cause of

hemothorax in horses, which carries a poor prognosis. Most cases of disseminated

hemangiosarcoma progress rapidly, with a median survival of 17 days from onset of signs.[29]

Diagnosis of neoplastic causes of hemothorax is complicated by lack of shedding of

hemangiosarcoma cells into pleural effusion, ultrasonographic findings that are often non-

specific, and limited diagnostic accuracy of radiographs.[29] Pleuroscopy can be useful in

selected cases.[30]

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The neuroendocrine tumor in this case caused local tissue destruction and ultimately severe

clinical disease, but was classified as benign (based on human guidelines) and had an apparent

slow, insidious progression. Metastasis in humans is not common, and posterior mediastinal

paragangliomas have been cured by local resection. It is conceivable that, if appropriate

resources are available and sufficient surgical access can be achieved, an early diagnosis in a

horse could lead to a positive outcome. Paraganglioma should therefore be considered as a

possible differential diagnosis for suspected neoplastic conditions not just in the thorax but in

any location where paraganglion tissue is present, and obtaining a tissue sample for

histopathologic diagnosis should be considered a priority.

Manufacturer’s details

a. Naxcel; Zoetis, Kalamazoo, MI.

b. Dexamethasone Solution; VetOne Pharmaceuticals, Boise, ID

c. Marquis®; Merial, Duluth, GA

d. DMSO 90% Solution; Neogen, Lexington, KY

e. Banamine; Merck Animal Health, Madison, NJ

References

[1] Basher AWP, Severin GA, Chavkin MJ, Frank AA. Orbital neuroendocrine tumors in three horses. Journal of the American Veterinary Medical Association. 1997;210:668-71.

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[2] Goodhead AD, Venter IJ, Nesbit JW. Retrobulbar extra-adrenal paraganglioma in a horse and its surgical removal by orbitotomy. Veterinary & Comparative Ophthalmology. 1997;7:96-100.[3] Miesner T, Wilkie D, Gemensky-Metzler A, Weisbrode S, Colitz C. Extra-adrenal paraganglioma of the equine orbit: six cases. Vet Ophthalmol. 2009;12:263-8.[4] Theuss T, Brandt K, Jäger K, Schoon HA. An orbital paraganglioma as the cause of unilateral exophthalmus in a horse. Pferdeheilkunde. 2013;29:708-11.[5] de Barros CS, dos Santos MN. Aortic body adenoma in a horse. Aust Vet J. 1983;60:61.[6] Levy M, Stegelmeier BL, Hudson LM, Sandusky GE, Blevins WE, Christian JA. Chemodectoma in a horse. Can Vet J. 1990;31:776-7.[7] Herbach N, Breuer W, Hermanns W. Metastatic extra-adrenal sympathetic paraganglioma in a horse. J Comp Pathol. 2010;143:199-202.[8] Kim DY, Hodgin EC, Lopez MK, Nasarre C. Malignant retroperitoneal paraganglioma in a horse. J Comp Pathol. 1994;110:407-11.[9] Moran CA, Suster S, Fishback N, Koss MN. Mediastinal paragangliomas. A clinicopathologic and immunohistochemical study of 16 cases. Cancer. 1993;72:2358-64.[10] Ramos R, Moya J, Villalonga R, Morera R, Ferrer G. Mediastinal aortosympathetic paraganglioma: report of two cases. Asian Cardiovasc Thorac Ann. 2007;15:e49-51.[11] Spector JA, Willis DN, Ginsburg HB. Paraganglioma (pheochromocytoma) of the posterior mediastinum: a case report and review of the literature. J Pediatr Surg. 2003;38:1114-6.[12] Mascort J, Pumarola M. Posterior mediastinal paraganglioma involving the spinal cord of a dog. J Small Anim Pract. 1995;36:274-8.[13] Rizzo SA, Newman SJ, Hecht S, Thomas WB. Malignant mediastinal extra-adrenal paraganglioma with spinal cord invasion in a dog. J Vet Diagn Invest. 2008;20:372-5.[14] Groover ES, Wooldridge AA. Equine haemothorax. Equine Veterinary Education. 2013;25:536-41.[15] Reed SM, Howe DK, Morrow JK, Graves A, Yeargan MR, Johnson AL, et al. Accurate antemortem diagnosis of equine protozoal myeloencephalitis (EPM) based on detecting intrathecal antibodies against Sarcocystis neurona using the SnSAG2 and SnSAG4/3 ELISAs. J Vet Intern Med. 2013;27:1193-200.[16] Pathology and genetics of tumours of endocrine organs / edited by Ronald A. DeLellis .. [et al.]. Lyon: IARC Press; 2004.[17] Chen H, Sippel RS, O'Dorisio MS, Vinik AI, Lloyd RV, Pacak K, et al. The North American Neuroendocrine Tumor Society consensus guideline for the diagnosis and management of neuroendocrine tumors: pheochromocytoma, paraganglioma, and medullary thyroid cancer. Pancreas. 2010;39:775-83.[18] Gallivan MV, Chun B, Rowden G, Lack EE. Intrathoracic paravertebral malignant paraganglioma. Arch Pathol Lab Med. 1980;104:46-51.[19] Luethy D, Habecker P, Murphy B, Nolen-Walston R. Clinical and Pathological Features of Pheochromocytoma in the Horse: A Multi-Center Retrospective Study of 37 Cases (2007-2014). J Vet Intern Med. 2016;30:309-13.[20] Koenig J, Silveira A, Chalmers H, Buenviaje G, Lillie BN. Laryngeal neuroendocrine tumour in a horse. Equine Veterinary Education. 2012;24:12-6.[21] Galac S, Korpershoek E. Pheochromocytomas and paragangliomas in humans and dogs. Veterinary and comparative oncology. 2017.

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[22] Holt DE, Henthorn P, Howell VM, Robinson BG, Benn DE. Succinate dehydrogenase subunit D and succinate dehydrogenase subunit B mutation analysis in canine phaeochromocytoma and paraganglioma. J Comp Pathol. 2014;151:25-34.[23] Fraga M, Garcia-Caballero T, Antunez J, Couce M, Beiras A, Forteza J. A comparative immunohistochemical study of phaeochromocytomas and paragangliomas. Histol Histopathol. 1993;8:429-36.[24] Kliewer KE, Wen DR, Cancilla PA, Cochran AJ. Paragangliomas: assessment of prognosis by histologic, immunohistochemical, and ultrastructural techniques. Hum Pathol. 1989;20:29-39.[25] Schmid KW, Schroder S, Dockhorn-Dworniczak B, Kirchmair R, Totsch M, Bocker W, et al. Immunohistochemical demonstration of chromogranin A, chromogranin B, and secretogranin II in extra-adrenal paragangliomas. Mod Pathol. 1994;7:347-53.[26] Noszczyk-Nowak A, Nowak M, Paslawska U, Atamaniuk W, Nicpon J. 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. Acta Vet Scand. 2010;52:35.[27] Baudin E, Gigliotti A, Ducreux M, Ropers J, Comoy E, Sabourin JC, et al. Neuron-specific enolase and chromogranin A as markers of neuroendocrine tumours. Br J Cancer. 1998;78:1102-7.[28] Vinik AI, Woltering EA, Warner RR, Caplin M, O'Dorisio TM, Wiseman GA, et al. NANETS consensus guidelines for the diagnosis of neuroendocrine tumor. Pancreas. 2010;39:713-34.[29] Southwood LL, Schott HC, 2nd, Henry CJ, Kennedy FA, Hines MT, Geor RJ, et al. Disseminated hemangiosarcoma in the horse: 35 cases. J Vet Intern Med. 2000;14:105-9.[30] Rossier Y, Sweeney CR, Heyer G, Hamir AN. Pleuroscopic diagnosis of disseminated hemangiosarcoma in a horse. J Am Vet Med Assoc. 1990;196:1639-40.

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Table 1. Pertinent data from complete blood count, chemistry and coagulation panel on

presentation

Value on presentation Reference interval

Packed cell volume (PCV) 29% 32 – 53%

White blood cell count 5.53 x 109/L 5.4 – 14.3 x 109/L

Platelet count 74 x 109/L 100 – 350 x 109/L

Fibrinogen 3 g/L 1 – 4 g/L

Albumin 23 g/L 32 – 40 g/L

Globulin 18 g/L 23 – 41 g/L

Blood urea nitrogen 15.7 mmol/L 6 – 10 mmol/L

Creatinine 194 µmol/L 62 - 133– 1.5 µmol/L

Sodium 126 mmol/L 132 – 138 mmol/L

Chloride 85 mmol/L 98 – 106 mmol/L

Calcium 2.1 mmol/L 2.85 – 3.35 mmol/L

Blood lactate 4.9 mmol/L < 2.0 mmol/L

Prothrombin time 13.4 s 9.9 – 12.5 s

Activated partial

thromboplastin time

57.2 s 32.0 – 46.5 s

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Figure legends

Figure 1. Ultrasonograms of hemothorax on initial presentation. Dorsal is to the left. Note

the atelectasis of the ventral lung tip and the variable echotexture of the fluid. Key: D,

diaphragm. L, lung. PE, pleural effusion.

Figure 2. Thoracic radiograph after onset of ataxia. The subvertebral mass is delineated by

the white arrowheads. Note areas of lucency in T5 (black arrows).

Figure 3. Post mortem specimen showing invasion of T5 by a soft tissue tumor. Cranial is to

the left. The defects in the vertebral body (white arrows) correspond to the radiolucencies in Fig

2.

Figure 4. Histopathological appearance of the paraganglioma. A: Low magnification view,

(40X) hematoxylin and eosin staining. The tumor is associated with the wall of a large muscular

artery. B: High magnification view (200X) showing nests of cuboidal cells separated by a fine

fibrovascular stroma, consistent with a neuroendocrine tumor. Hematoxylin and eosin staining.

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