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Mediastinal Paraganglioma as a Cause of Hemothorax and Thoracic Spinal Cord Compression in a Quarter Horse Gelding
Accepted Manuscript Mediastinal paraganglioma as a cause of hemothorax and thoracic spinal cord compression in a Quarter Horse gelding Nicholas J. Parkinson, Katherine E. Wilson, Geoffrey K. Saunders, Virginia A. Buechner-Maxwell, W. Kent Scarratt, R Scott Pleasant, Rebecca A. Funk PII:
S0737-0806(17)30099-0
DOI:
10.1016/j.jevs.2017.10.001
Reference:
YJEVS 2391
To appear in:
Journal of Equine Veterinary Science
Received Date: 3 March 2017 Revised Date:
28 September 2017
Accepted Date: 2 October 2017
Please cite this article as: Parkinson NJ, Wilson KE, Saunders GK, Buechner-Maxwell VA, Scarratt WK, Pleasant RS, Funk RA, Mediastinal paraganglioma as a cause of hemothorax and thoracic spinal cord compression in a Quarter Horse gelding, Journal of Equine Veterinary Science (2017), doi: 10.1016/ j.jevs.2017.10.001. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
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Mediastinal paraganglioma as a cause of hemothorax and thoracic spinal cord compression
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in a Quarter Horse gelding
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Nicholas J Parkinsona1, Katherine E Wilsona, Geoffrey K Saundersb, Virginia A. Buechner-
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Maxwella, W. Kent Scarratta, R Scott Pleasanta, Rebecca A Funka
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Author institutions and affiliations:
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a. Department of Large Animal Clinical Sciences, Virginia-Maryland College of Veterinary
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Medicine, Virginia Polytechnic and State University, Blacksburg, VA.
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b. Department of Biomedical Sciences and Pathobiology (Saunders), Virginia-Maryland College
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of Veterinary Medicine, Virginia Polytechnic and State University, Blacksburg, VA.
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Author email addresses: Parkinson: [email protected] ; Wilson: [email protected] ;
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Saunders: [email protected] ; Buechner-Maxwell: [email protected] ; Scarratt: [email protected] ;
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Pleasant: [email protected] ; Funk: [email protected]
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Bush Campus, Midlothian, EH25 9RG, United Kingdom.
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Present address: Royal (Dick) School of Veterinary Studies, University of Edinburgh, Easter
Corresponding author: Nicholas J Parkinson, [email protected]
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Abstract
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Neuroendocrine tumors are rarely diagnosed in horses. This report describes a case of a
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neuroendocrine tumor with strong similarities to descriptions of posterior mediastinal
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paragangliomas in humans and dogs. A 12-year-old Quarter Horse gelding was presented
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initially for management of hemothorax of unknown origin that responded to medical
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management. 19 months later, the horse was presented again with acute-onset hindlimb ataxia, at
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which time a thoracic mass adjacent to the vertebral bodies was detected on radiography. The
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gelding was euthanized after failing to respond to anti-inflammatory therapy, and on necropsy
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the mass was identified as a paraganglioma invading the spinal canal. Despite its locally invasive
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behavior, the tumor showed no evidence of metastasis, and its apparent slow progression was in
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sharp contrast to more common thoracic neoplasms such as hemangiosarcoma. Combined with
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the reported success of surgical excision in human mediastinal paragangliomas, this suggests that
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early diagnosis of such tumors could provide the opportunity for successful treatment.
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Keywords: equine, neuroendocrine tumor, chemodectoma
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This research did not receive any specific grant from funding agencies in the public, commercial,
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or not-for-profit sectors.
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The authors declare no conflicts of interest.
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1. Introduction
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Neuroendocrine tumors are a diverse group of neoplasms that are uncommonly diagnosed in
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horses. The clinical signs associated with such tumors depend on both endocrine functionality
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and anatomic location. Paragangliomas are tumors derived from the paraganglia, accumulations
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of neural crest-derived cells associated with autonomic ganglia, which are widely distributed
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throughout the body. As a consequence of their tissue of origin, they can occur in a particularly
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wide variety of anatomic locations compared to other neuroendocrine tumors. They have been
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reported infrequently in horses, at anatomical sites including the orbit, heart base and sublumbar
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region. [1-8] Paragangliomas in the dorsal mediastinum have been described as a cause of spinal
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cord compression in humans and dogs, but to the best of the authors knowledge, the case
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presented here represents the first report of a comparable syndrome in a horse. [9-13] This case
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differed from those described in other species, however, in that the anatomical associations of the
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tumor, with both the wall of a major artery and the spinal column, led to the development of two
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temporally distinct clinical manifestations, presenting an additional diagnostic challenge.
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2. Case Details
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2.1 First Presentation
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A 12-year-old Quarter Horse gelding presented to the Virginia-Maryland College of Veterinary
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Medicine for evaluation of lethargy and reluctance to move of 24 hours’ duration. These clinical
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signs had been refractory to analgesia with flunixin meglumine (1 mg/kg PO q12h). There had
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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
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tachycardia (88 beats per minute) and moderate tachypnea (32 breaths per minute). Lung sounds
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were absent cranioventrally. Moderate pectoral ventral edema was present. Mucous membranes
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were pink and moist with a capillary refill time of less than two seconds. Gastrointestinal
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borborygmi were within normal limits and normal feces were passed. Ultrasonography of the
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thorax (Figure 1) revealed a large-volume bilateral pleural effusion extending to the dorsal lung
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fields. The fluid had a variable echogenicity with visible fibrin strands and a ‘swirling’
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appearance suggestive of hemorrhage. No masses or evidence of rib fractures could be detected.
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No pericardial or peritoneal effusion was present, and all abdominal viscera had a normal
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ultrasonographic appearance.
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Complete blood count and chemistry (Table 1) showed a mild normocytic, normochromic
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anemia, with no evidence of inflammation. There was a mild to moderate thrombocytopenia,
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confirmed by examination of a blood smear. Coagulation times were mildly prolonged.
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Abnormalities on chemistry were consistent with acute blood loss and reduced tissue perfusion.
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Thoracocentesis yielded hemorrhagic fluid from both hemithoraces, with a PCV of 36% and total
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protein of 48 g/L. Cytological examination was consistent with hemorrhagic effusion, with rare
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erythrophagia and leukophagia within macrophages. No evidence of inflammation or neoplasia
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was observed.
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The most likely differential diagnoses for hemothorax in this case were considered to be trauma,
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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
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increases in coagulation times were thought to be secondary to consumption of platelets and
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clotting factors. No evidence of trauma or neoplasia could be detected on physical or
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ultrasonographic examination. Thoracic radiography was considered, but the volume of pleural
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fluid was deemed likely to limit the diagnostic yield.
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Initial management comprised conservative fluid therapy (lactated ringer’s solution at 2 ml/kg/hr
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with supplementary calcium gluconate) and prophylactic antimicrobial therapy (ceftiofur
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sodiuma, 2.2 mg/kg IV q12h). Given the lack of respiratory distress and to facilitate erythrocyte
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autotransfusion, thoracic drainage was not performed.[14] After initiation of fluid therapy, the
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gelding’s demeanor improved and blood lactate decreased to 1.8 mmol/L within 12 hours.
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However, PCV and total protein continued to fall (to 17% and 30 g/L respectively in 18 hours),
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rendering a blood transfusion necessary. PCV continued to fall despite administration of 8L
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cross-matched whole blood, and a second transfusion was initiated 24 hours later when the PCV
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reached 13%. This was discontinued due to development of severe urticaria and facial edema,
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both of which were responsive to dexamethasoneb administration (0.08 mg/kg IV). The
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transfusions increased the total protein to 50 g/L, but PCV continued to fall to 12%. Marked
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pectoral edema and jugular distension developed, most likely resulting from reduced venous
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return due to elevated intrathoracic pressure. Three days after presentation, the PCV began to
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improve, coinciding with improvements in demeanor and heart rate. By day nine of
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hospitalization the PCV had increased to 29% and total protein to 80 g/L, and heart rate had
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reduced to 44 beats per minute. Marked pleural effusion was however still evident on ultrasound.
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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
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confirmed complete resolution of the hemothorax with only mild comet-tail artifacts (indicating
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pleural roughening) in the cranioventral lung fields.
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2.2 Second Presentation
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Nineteen months after initial presentation, the horse re-presented with acute onset hindlimb
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ataxia of 24 hours’ duration.
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Bilaterally symmetrical grade 4/5 ataxia was present in the hindlimbs. Gait deficits included
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inconsistent foot placement, marked circumduction when turning and toe dragging when
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backing, and the horse frequently came close to falling. Lower motor neuron strength appeared
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normal, and no proprioceptive deficits were detected in the forelimbs. Mentation, cranial nerve
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reflexes, cervical and panniculus reflexes, and tail and anal tone were all normal. On the basis of
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this assessment, the lesion was localized to the thoracolumbar spinal cord. Differential diagnoses
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for a focal lesion at this site included equine protozoal myeloencephalitis, trauma,
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discospondylitis, fibrocartilaginous embolism, or neoplasia. The animal was in good body
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condition, and no further abnormalities were detected on general physical examination, complete
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blood count or chemistry. Initial treatment, pending the results of diagnostic testing, consisted of
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ponazurilc (5 mg/kg PO q24h) for suspected equine protozoal myeloencephalitis, and anti-
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inflammatory treatment with dimethyl sulfoxided (0.5 g/kg IV q12h) and flunixin megluminee
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(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
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(reference interval 0 – 6 / mm3), 10 erythrocytes/mm3, and total protein of 787 mg/L (reference
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interval 50-1000 mg/L). The nucleated cell population consisted of 71.4% small lymphocytes
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and 28.6% large mononuclear cells. A single phagocytosed erythrocyte was observed within one
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large mononuclear cell, but no evidence of inflammation or neoplasia was observed. Titers
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against Sarcocystis neurona antigens SnSAG 2 and 4/3 were positive in both serum (1:4000) and
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CSF (1:20), but the high serum:CSF titer ratio (200:1) was not consistent with intrathecal
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antibody production, and therefore did not support a diagnosis of equine protozoal
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myeloencephalitis.[15] Additionally, serum titers for Neospora hughesii (by immunofluorescent
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antibody test) and Borrelia burgdorferi antigens OspA, OspC and OspF (by multiplex enzyme-
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linked immunosorbent assay) were negative.
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Radiographs of the thoracolumbar spine showed a 17.6 cm x 10.1 cm broad-based smoothly
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marginated mass of soft tissue to mineral opacity at the ventral surface of the vertebral bodies of
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the fourth to sixth thoracic vertebrae (T4 - T6), superimposed on the craniodorsal margin of the
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aortic arch (Figure 2). Two clearly demarcated radiolucencies were present within the body of
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T5. Laterality of the mass could not be determined from the images. Mild modeling of the
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articular facets of the caudal cervical, caudal thoracic and cranial lumbar vertebrae was present
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but considered unlikely to be of clinical significance. Thoracic ultrasonography showed only
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minor pleural irregularities in the cranioventral lung fields, presumed to be secondary to the
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previous hemothorax. The mass could not be imaged ultrasonographically, indicating a deeper
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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
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lesion. Differential diagnoses included neoplasia (e.g. hemangiosarcoma or osteosarcoma),
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abscess, or granuloma. Abscess was considered unlikely given the normal complete blood count
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and fibrinogen concentration. Due to its deep location, the mass was not accessible for
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percutaneous biopsy. Thoracoscopy was offered to visualize the lesion and attempt to obtain a
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biopsy, but was declined due to its invasive nature and limited chance of improving outcome.
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Despite medical management, the horse showed a slight increase in hindlimb weakness after
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seven days of hospitalization. The owners elected to continue palliative treatment at home.
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Euthanasia was performed on humane grounds 24 hours later when the horse became recumbent
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and unable to rise.
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On post mortem examination, a 12 x 7 x 9 cm mass was attached to the ventral aspect of the fifth
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thoracic vertebra, extending into the vertebral body with loss of 50% of the bone (Figure 3). The
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mass was a homogeneous tan color with multifocal red nodules on the surface and contained red
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hemorrhagic necrotic foci. The tumor was protruding into the spinal canal but did not penetrate
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the ventral longitudinal ligament. There was no evidence of metastasis or neoplasia at other sites.
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Short fibrous tags were present on the pleural surfaces, most likely as a sequela of the
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hemothorax. There were no relevant gross abnormalities in other organs. Histologically, the
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tumor arose from the wall of an artery and was composed of nests of cuboidal cells separated by
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fine fibrovascular septae (Figure 4). The cells had vacuolated, pale eosinophilic cytoplasm. Two-
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fold anisokaryosis and rare mitoses were present. Immunohistochemical staining was positive for
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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
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the aortic arch or spinal artery branch of the aorta. Bilateral, symmetrical axonal degeneration
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and myelin swelling were noted in the ventral and lateral white matter at the level of T7, with
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occasional mild lymphocytic-plasmacytic perivascular cuffing. These findings were consistent
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with spinal cord compression by the neoplasm.
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3. Discussion
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The cause of the neurologic disease in this horse was confirmed to be a dorsal mediastinal
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neuroendocrine tumor associated with an artery wall, most likely a paraganglioma. The location
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and arterial association suggest a causal link with the prior hemothorax.
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The nomenclature and diagnostic criteria of paragangliomas and related neuroendocrine tumors
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are subject to some inconsistency in the published human and veterinary literature.
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Paragangliomas have been subdivided historically into chromaffin and non-chromaffin types.
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The former are associated with sympathetic ganglia (e.g. sympathetic trunk and celiac ganglion)
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and tend to secrete catecholamines. Chromaffin paragangliomas may also be referred to as intra-
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adrenal or extra-adrenal pheochromocytomas, with the adrenal medulla considered by some
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authors to be an extreme example of a paraganglion. Non-chromaffin paraganglia are clusters of
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glomus cells with chemoreceptor function, especially in the aortic and carotid bodies but also at
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other sites including the inner ear and along the vagus nerve. Tumors of these tissues have been
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previously termed ‘glomus cell tumors’ or ‘chemodectomas’. These parasympathetic
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paragangliomas occur most commonly in the head and neck. It is now recognized that
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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
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types (with the exception of intra-adrenal pheochromocytoma) in humans.[16] Malignancy in
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these tumors is defined by distant metastasis and not by local invasion. [17]
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The anatomic location of the paraganglioma in this horse, in the craniodorsal mediastinum
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immediately ventral to the thoracic vertebral bodies, was consistent with reports in humans and
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in dogs.[9-13] These tumors typically originate from the costovertebral sulcus, and are
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considered to arise from the aorticosympathetic paraganglia. Clinical signs attributable to
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cathecholamine secretion are reported in 19 to 48% of cases of mediastinal paraganglioma in
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humans.[9, 11, 18] They can be locally invasive and are often reported to invade the spinal canal,
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but hemorrhage is not a typical feature. Hemorrhage from intra-adrenal pheochromocytomas is,
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however, more commonly reported in horses than in humans[19], so it is possible that
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paragangliomas display similar species-related differences in clinical behavior. Although
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catecholamines were not measured in this case, no physiological evidence of increased
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production (such as tachycardia, hyperglycemia or sweating) could be detected on the second
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presentation, and all such abnormalities on the first presentation could be attributed to the
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hemothorax.
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There are only a small number of case reports of paragangliomas at other sites in horses, most
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commonly in the orbit (11 cases).[1-4] These tumors are believed to arise from the ciliary
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ganglion. It is unclear if non-chromaffin paraganglion tissue is present at this site in normal
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animals. Other reported cases include two heart base tumors (reported as chemodectoma or aortic
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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
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extra-adrenal paragangliomas with extensive distant metastasis have been reported in horses.[7,
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8] Ten to fifteen percent of human cases are familial, often associated with mutations in the
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succinate dehydrogenase subunit genes SDHD, SDHB and SDHC, which lead to mitochondrial
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respiratory chain dysfunction and activation of the hypoxia-inducible pathway.[16] Little is yet
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known regarding the underlying genetic basis of paragangliomas in veterinary species, but a
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study of two carotid body paragangliomas and six pheochromocytomas in dogs found potentially
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pathogenic SHDB or SDHD mutations in four cases. Three were germline mutations, indicating
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potential heritability. This suggests that the underlying aetiopathogenesis could be similar
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between species, in at least a proportion of cases.[21, 22] The small number of reported equine
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cases appear to be sporadic, across a range of breeds, and the underlying genetic changes have
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not yet been investigated.
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The diagnosis of a neuroendocrine tumor in this case was supported by immunohistochemistry,
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with positive staining for NSE and synaptophysin, but negative CgA staining. This pattern is
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consistent with two canine cases of posterior mediastinal paraganglioma [12, 13] but differs from
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other equine paragangliomas, which have been positive for CgA in all seven cases for which
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immunostaining for this marker has been reported.[3, 7] These three markers cannot distinguish
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paragangliomas from pheochromocytomas, which are histologically identical.[23] Prognostic
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significance of the immunostaining pattern has not yet been investigated in horses. Weak CgA
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staining has been suggested to reflect poor differentiation or parasympathetic origin in human
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paragangliomas [24, 25], or more malignant behavior in canine chemodectomas.[26] However,
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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
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circulating biomarker in humans, at least for tumors of sympathetic origin [27, 28], but this has
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not been investigated in horses. Similarly, urine and plasma metanephrines (catecholamine
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metabolites) are useful diagnostically in humans, but are not well characterized in horses;
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although they may have some utility in detecting mediastinal or abdominal paragangliomas of
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sympathetic origin, it is not currently known what proportion of equine tumors are functional,
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and sensitivity will likely be lower for detection of parasympathetic paragangliomas at other
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locations such as the head and neck.. Diagnosis in the horse therefore relies on a combination of
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imaging and histopathology, both of which may be challenging ante mortem depending on
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anatomic location.
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The diagnosis in this case may have been accelerated by earlier radiography after resolution of
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the initial hemothorax. The index of suspicion of neoplasia was, however, reduced initially by
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the rapid recovery and subsequent prolonged clinical remission. This is in stark contrast to the
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expected clinical behavior of hemangiosarcoma, the most commonly reported neoplastic cause of
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hemothorax in horses, which carries a poor prognosis. Most cases of disseminated
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hemangiosarcoma progress rapidly, with a median survival of 17 days from onset of signs.[29]
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Diagnosis of neoplastic causes of hemothorax is complicated by lack of shedding of
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hemangiosarcoma cells into pleural effusion, ultrasonographic findings that are often non-
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specific, and limited diagnostic accuracy of radiographs.[29] Pleuroscopy can be useful in
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selected cases.[30]
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The neuroendocrine tumor in this case caused local tissue destruction and ultimately severe
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clinical disease, but was classified as benign (based on human guidelines) and had an apparent
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slow, insidious progression. Metastasis in humans is not common, and posterior mediastinal
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paragangliomas have been cured by local resection. It is conceivable that, if appropriate
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resources are available and sufficient surgical access can be achieved, an early diagnosis in a
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horse could lead to a positive outcome. Paraganglioma should therefore be considered as a
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possible differential diagnosis for suspected neoplastic conditions not just in the thorax but in
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any location where paraganglion tissue is present, and obtaining a tissue sample for
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histopathologic diagnosis should be considered a priority.
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Manufacturer’s details
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a. Naxcel; Zoetis, Kalamazoo, MI.
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b. Dexamethasone Solution; VetOne Pharmaceuticals, Boise, ID
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c. Marquis®; Merial, Duluth, GA
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d. DMSO 90% Solution; Neogen, Lexington, KY
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e. Banamine; Merck Animal Health, Madison, NJ
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[19] Luethy D, Habecker P, Murphy B, Nolen-Walston R. Clinical and Pathological Features of
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[21] Galac S, Korpershoek E. Pheochromocytomas and paragangliomas in humans and dogs.
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Veterinary and comparative oncology. 2017.
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[22] Holt DE, Henthorn P, Howell VM, Robinson BG, Benn DE. Succinate dehydrogenase
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subunit D and succinate dehydrogenase subunit B mutation analysis in canine
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phaeochromocytoma and paraganglioma. J Comp Pathol. 2014;151:25-34.
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[23] Fraga M, Garcia-Caballero T, Antunez J, Couce M, Beiras A, Forteza J. A comparative
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immunohistochemical study of phaeochromocytomas and paragangliomas. Histol Histopathol.
348
1993;8:429-36.
349
[24] Kliewer KE, Wen DR, Cancilla PA, Cochran AJ. Paragangliomas: assessment of prognosis
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by histologic, immunohistochemical, and ultrastructural techniques. Hum Pathol. 1989;20:29-39.
351
[25] Schmid KW, Schroder S, Dockhorn-Dworniczak B, Kirchmair R, Totsch M, Bocker W, et
352
al. Immunohistochemical demonstration of chromogranin A, chromogranin B, and secretogranin
353
II in extra-adrenal paragangliomas. Mod Pathol. 1994;7:347-53.
354
[26] Noszczyk-Nowak A, Nowak M, Paslawska U, Atamaniuk W, Nicpon J. Cases with
355
manifestation of chemodectoma diagnosed in dogs in Department of Internal Diseases with
356
Horses, Dogs and Cats Clinic, Veterinary Medicine Faculty, University of Environmental and
357
Life Sciences, Wroclaw, Poland. Acta Vet Scand. 2010;52:35.
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[27] Baudin E, Gigliotti A, Ducreux M, Ropers J, Comoy E, Sabourin JC, et al. Neuron-specific
359
enolase and chromogranin A as markers of neuroendocrine tumours. Br J Cancer. 1998;78:1102-
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7.
361
[28] Vinik AI, Woltering EA, Warner RR, Caplin M, O'Dorisio TM, Wiseman GA, et al.
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NANETS consensus guidelines for the diagnosis of neuroendocrine tumor. Pancreas.
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2010;39:713-34.
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[29] Southwood LL, Schott HC, 2nd, Henry CJ, Kennedy FA, Hines MT, Geor RJ, et al.
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Disseminated hemangiosarcoma in the horse: 35 cases. J Vet Intern Med. 2000;14:105-9.
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[30] Rossier Y, Sweeney CR, Heyer G, Hamir AN. Pleuroscopic diagnosis of disseminated
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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
371
presentation
372 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
Globulin
18 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
Prothrombin time
373 374 375 376
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thromboplastin time
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23 – 41 g/L
4.9 mmol/L
< 2.0 mmol/L
13.4 s
9.9 – 12.5 s
57.2 s
32.0 – 46.5 s
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32 – 40 g/L
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Blood lactate
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377
Figure legends
378
Figure 1. Ultrasonograms of hemothorax on initial presentation. Dorsal is to the left. Note
380
the atelectasis of the ventral lung tip and the variable echotexture of the fluid. Key: D,
381
diaphragm. L, lung. PE, pleural effusion.
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Figure 2. Thoracic radiograph after onset of ataxia. The subvertebral mass is delineated by
384
the white arrowheads. Note areas of lucency in T5 (black arrows).
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Figure 3. Post mortem specimen showing invasion of T5 by a soft tissue tumor. Cranial is to
387
the left. The defects in the vertebral body (white arrows) correspond to the radiolucencies in Fig
388
2.
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Figure 4. Histopathological appearance of the paraganglioma. A: Low magnification view,
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(40X) hematoxylin and eosin staining. The tumor is associated with the wall of a large muscular
392
artery. B: High magnification view (200X) showing nests of cuboidal cells separated by a fine
393
fibrovascular stroma, consistent with a neuroendocrine tumor. Hematoxylin and eosin staining.
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Paragangliomas are uncommonly diagnosed neuroendocrine neoplasms in horses. The case report presents the first description of a dorsal mediastinal paraganglioma in a horse. The neoplasm was benign but locally invasive, presenting first as hemothorax and later with ataxia after extension through the adjacent vertebral body. Surgical excision of comparable tumors in humans is often curative, so early diagnosis may improve prognosis.
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S0737-0806(17)30099-0
DOI:
10.1016/j.jevs.2017.10.001
Reference:
YJEVS 2391
To appear in:
Journal of Equine Veterinary Science
Received Date: 3 March 2017 Revised Date:
28 September 2017
Accepted Date: 2 October 2017
Please cite this article as: Parkinson NJ, Wilson KE, Saunders GK, Buechner-Maxwell VA, Scarratt WK, Pleasant RS, Funk RA, Mediastinal paraganglioma as a cause of hemothorax and thoracic spinal cord compression in a Quarter Horse gelding, Journal of Equine Veterinary Science (2017), doi: 10.1016/ j.jevs.2017.10.001. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
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Mediastinal paraganglioma as a cause of hemothorax and thoracic spinal cord compression
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in a Quarter Horse gelding
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Nicholas J Parkinsona1, Katherine E Wilsona, Geoffrey K Saundersb, Virginia A. Buechner-
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Maxwella, W. Kent Scarratta, R Scott Pleasanta, Rebecca A Funka
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Author institutions and affiliations:
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a. Department of Large Animal Clinical Sciences, Virginia-Maryland College of Veterinary
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Medicine, Virginia Polytechnic and State University, Blacksburg, VA.
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b. Department of Biomedical Sciences and Pathobiology (Saunders), Virginia-Maryland College
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of Veterinary Medicine, Virginia Polytechnic and State University, Blacksburg, VA.
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Author email addresses: Parkinson: [email protected] ; Wilson: [email protected] ;
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Saunders: [email protected] ; Buechner-Maxwell: [email protected] ; Scarratt: [email protected] ;
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Pleasant: [email protected] ; Funk: [email protected]
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Bush Campus, Midlothian, EH25 9RG, United Kingdom.
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Present address: Royal (Dick) School of Veterinary Studies, University of Edinburgh, Easter
Corresponding author: Nicholas J Parkinson, [email protected]
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Abstract
25
Neuroendocrine tumors are rarely diagnosed in horses. This report describes a case of a
26
neuroendocrine tumor with strong similarities to descriptions of posterior mediastinal
27
paragangliomas in humans and dogs. A 12-year-old Quarter Horse gelding was presented
28
initially for management of hemothorax of unknown origin that responded to medical
29
management. 19 months later, the horse was presented again with acute-onset hindlimb ataxia, at
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which time a thoracic mass adjacent to the vertebral bodies was detected on radiography. The
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gelding was euthanized after failing to respond to anti-inflammatory therapy, and on necropsy
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the mass was identified as a paraganglioma invading the spinal canal. Despite its locally invasive
33
behavior, the tumor showed no evidence of metastasis, and its apparent slow progression was in
34
sharp contrast to more common thoracic neoplasms such as hemangiosarcoma. Combined with
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the reported success of surgical excision in human mediastinal paragangliomas, this suggests that
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early diagnosis of such tumors could provide the opportunity for successful treatment.
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Keywords: equine, neuroendocrine tumor, chemodectoma
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This research did not receive any specific grant from funding agencies in the public, commercial,
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or not-for-profit sectors.
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The authors declare no conflicts of interest.
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1. Introduction
49
Neuroendocrine tumors are a diverse group of neoplasms that are uncommonly diagnosed in
50
horses. The clinical signs associated with such tumors depend on both endocrine functionality
51
and anatomic location. Paragangliomas are tumors derived from the paraganglia, accumulations
52
of neural crest-derived cells associated with autonomic ganglia, which are widely distributed
53
throughout the body. As a consequence of their tissue of origin, they can occur in a particularly
54
wide variety of anatomic locations compared to other neuroendocrine tumors. They have been
55
reported infrequently in horses, at anatomical sites including the orbit, heart base and sublumbar
56
region. [1-8] Paragangliomas in the dorsal mediastinum have been described as a cause of spinal
57
cord compression in humans and dogs, but to the best of the authors knowledge, the case
58
presented here represents the first report of a comparable syndrome in a horse. [9-13] This case
59
differed from those described in other species, however, in that the anatomical associations of the
60
tumor, with both the wall of a major artery and the spinal column, led to the development of two
61
temporally distinct clinical manifestations, presenting an additional diagnostic challenge.
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2. Case Details
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2.1 First Presentation
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A 12-year-old Quarter Horse gelding presented to the Virginia-Maryland College of Veterinary
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Medicine for evaluation of lethargy and reluctance to move of 24 hours’ duration. These clinical
67
signs had been refractory to analgesia with flunixin meglumine (1 mg/kg PO q12h). There had
68
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
71
tachycardia (88 beats per minute) and moderate tachypnea (32 breaths per minute). Lung sounds
72
were absent cranioventrally. Moderate pectoral ventral edema was present. Mucous membranes
73
were pink and moist with a capillary refill time of less than two seconds. Gastrointestinal
74
borborygmi were within normal limits and normal feces were passed. Ultrasonography of the
75
thorax (Figure 1) revealed a large-volume bilateral pleural effusion extending to the dorsal lung
76
fields. The fluid had a variable echogenicity with visible fibrin strands and a ‘swirling’
77
appearance suggestive of hemorrhage. No masses or evidence of rib fractures could be detected.
78
No pericardial or peritoneal effusion was present, and all abdominal viscera had a normal
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ultrasonographic appearance.
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Complete blood count and chemistry (Table 1) showed a mild normocytic, normochromic
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anemia, with no evidence of inflammation. There was a mild to moderate thrombocytopenia,
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confirmed by examination of a blood smear. Coagulation times were mildly prolonged.
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Abnormalities on chemistry were consistent with acute blood loss and reduced tissue perfusion.
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Thoracocentesis yielded hemorrhagic fluid from both hemithoraces, with a PCV of 36% and total
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protein of 48 g/L. Cytological examination was consistent with hemorrhagic effusion, with rare
88
erythrophagia and leukophagia within macrophages. No evidence of inflammation or neoplasia
89
was observed.
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The most likely differential diagnoses for hemothorax in this case were considered to be trauma,
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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
94
increases in coagulation times were thought to be secondary to consumption of platelets and
95
clotting factors. No evidence of trauma or neoplasia could be detected on physical or
96
ultrasonographic examination. Thoracic radiography was considered, but the volume of pleural
97
fluid was deemed likely to limit the diagnostic yield.
98
Initial management comprised conservative fluid therapy (lactated ringer’s solution at 2 ml/kg/hr
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with supplementary calcium gluconate) and prophylactic antimicrobial therapy (ceftiofur
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sodiuma, 2.2 mg/kg IV q12h). Given the lack of respiratory distress and to facilitate erythrocyte
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autotransfusion, thoracic drainage was not performed.[14] After initiation of fluid therapy, the
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gelding’s demeanor improved and blood lactate decreased to 1.8 mmol/L within 12 hours.
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However, PCV and total protein continued to fall (to 17% and 30 g/L respectively in 18 hours),
105
rendering a blood transfusion necessary. PCV continued to fall despite administration of 8L
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cross-matched whole blood, and a second transfusion was initiated 24 hours later when the PCV
107
reached 13%. This was discontinued due to development of severe urticaria and facial edema,
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both of which were responsive to dexamethasoneb administration (0.08 mg/kg IV). The
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transfusions increased the total protein to 50 g/L, but PCV continued to fall to 12%. Marked
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pectoral edema and jugular distension developed, most likely resulting from reduced venous
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return due to elevated intrathoracic pressure. Three days after presentation, the PCV began to
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improve, coinciding with improvements in demeanor and heart rate. By day nine of
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hospitalization the PCV had increased to 29% and total protein to 80 g/L, and heart rate had
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reduced to 44 beats per minute. Marked pleural effusion was however still evident on ultrasound.
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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
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confirmed complete resolution of the hemothorax with only mild comet-tail artifacts (indicating
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pleural roughening) in the cranioventral lung fields.
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2.2 Second Presentation
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Nineteen months after initial presentation, the horse re-presented with acute onset hindlimb
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ataxia of 24 hours’ duration.
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Bilaterally symmetrical grade 4/5 ataxia was present in the hindlimbs. Gait deficits included
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inconsistent foot placement, marked circumduction when turning and toe dragging when
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backing, and the horse frequently came close to falling. Lower motor neuron strength appeared
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normal, and no proprioceptive deficits were detected in the forelimbs. Mentation, cranial nerve
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reflexes, cervical and panniculus reflexes, and tail and anal tone were all normal. On the basis of
129
this assessment, the lesion was localized to the thoracolumbar spinal cord. Differential diagnoses
130
for a focal lesion at this site included equine protozoal myeloencephalitis, trauma,
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discospondylitis, fibrocartilaginous embolism, or neoplasia. The animal was in good body
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condition, and no further abnormalities were detected on general physical examination, complete
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blood count or chemistry. Initial treatment, pending the results of diagnostic testing, consisted of
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ponazurilc (5 mg/kg PO q24h) for suspected equine protozoal myeloencephalitis, and anti-
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inflammatory treatment with dimethyl sulfoxided (0.5 g/kg IV q12h) and flunixin megluminee
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(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
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(reference interval 0 – 6 / mm3), 10 erythrocytes/mm3, and total protein of 787 mg/L (reference
140
interval 50-1000 mg/L). The nucleated cell population consisted of 71.4% small lymphocytes
141
and 28.6% large mononuclear cells. A single phagocytosed erythrocyte was observed within one
142
large mononuclear cell, but no evidence of inflammation or neoplasia was observed. Titers
143
against Sarcocystis neurona antigens SnSAG 2 and 4/3 were positive in both serum (1:4000) and
144
CSF (1:20), but the high serum:CSF titer ratio (200:1) was not consistent with intrathecal
145
antibody production, and therefore did not support a diagnosis of equine protozoal
146
myeloencephalitis.[15] Additionally, serum titers for Neospora hughesii (by immunofluorescent
147
antibody test) and Borrelia burgdorferi antigens OspA, OspC and OspF (by multiplex enzyme-
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linked immunosorbent assay) were negative.
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Radiographs of the thoracolumbar spine showed a 17.6 cm x 10.1 cm broad-based smoothly
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marginated mass of soft tissue to mineral opacity at the ventral surface of the vertebral bodies of
152
the fourth to sixth thoracic vertebrae (T4 - T6), superimposed on the craniodorsal margin of the
153
aortic arch (Figure 2). Two clearly demarcated radiolucencies were present within the body of
154
T5. Laterality of the mass could not be determined from the images. Mild modeling of the
155
articular facets of the caudal cervical, caudal thoracic and cranial lumbar vertebrae was present
156
but considered unlikely to be of clinical significance. Thoracic ultrasonography showed only
157
minor pleural irregularities in the cranioventral lung fields, presumed to be secondary to the
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previous hemothorax. The mass could not be imaged ultrasonographically, indicating a deeper
159
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
162
lesion. Differential diagnoses included neoplasia (e.g. hemangiosarcoma or osteosarcoma),
163
abscess, or granuloma. Abscess was considered unlikely given the normal complete blood count
164
and fibrinogen concentration. Due to its deep location, the mass was not accessible for
165
percutaneous biopsy. Thoracoscopy was offered to visualize the lesion and attempt to obtain a
166
biopsy, but was declined due to its invasive nature and limited chance of improving outcome.
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Despite medical management, the horse showed a slight increase in hindlimb weakness after
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seven days of hospitalization. The owners elected to continue palliative treatment at home.
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Euthanasia was performed on humane grounds 24 hours later when the horse became recumbent
171
and unable to rise.
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On post mortem examination, a 12 x 7 x 9 cm mass was attached to the ventral aspect of the fifth
174
thoracic vertebra, extending into the vertebral body with loss of 50% of the bone (Figure 3). The
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mass was a homogeneous tan color with multifocal red nodules on the surface and contained red
176
hemorrhagic necrotic foci. The tumor was protruding into the spinal canal but did not penetrate
177
the ventral longitudinal ligament. There was no evidence of metastasis or neoplasia at other sites.
178
Short fibrous tags were present on the pleural surfaces, most likely as a sequela of the
179
hemothorax. There were no relevant gross abnormalities in other organs. Histologically, the
180
tumor arose from the wall of an artery and was composed of nests of cuboidal cells separated by
181
fine fibrovascular septae (Figure 4). The cells had vacuolated, pale eosinophilic cytoplasm. Two-
182
fold anisokaryosis and rare mitoses were present. Immunohistochemical staining was positive for
183
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
185
the aortic arch or spinal artery branch of the aorta. Bilateral, symmetrical axonal degeneration
186
and myelin swelling were noted in the ventral and lateral white matter at the level of T7, with
187
occasional mild lymphocytic-plasmacytic perivascular cuffing. These findings were consistent
188
with spinal cord compression by the neoplasm.
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3. Discussion
191
The cause of the neurologic disease in this horse was confirmed to be a dorsal mediastinal
192
neuroendocrine tumor associated with an artery wall, most likely a paraganglioma. The location
193
and arterial association suggest a causal link with the prior hemothorax.
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The nomenclature and diagnostic criteria of paragangliomas and related neuroendocrine tumors
196
are subject to some inconsistency in the published human and veterinary literature.
197
Paragangliomas have been subdivided historically into chromaffin and non-chromaffin types.
198
The former are associated with sympathetic ganglia (e.g. sympathetic trunk and celiac ganglion)
199
and tend to secrete catecholamines. Chromaffin paragangliomas may also be referred to as intra-
200
adrenal or extra-adrenal pheochromocytomas, with the adrenal medulla considered by some
201
authors to be an extreme example of a paraganglion. Non-chromaffin paraganglia are clusters of
202
glomus cells with chemoreceptor function, especially in the aortic and carotid bodies but also at
203
other sites including the inner ear and along the vagus nerve. Tumors of these tissues have been
204
previously termed ‘glomus cell tumors’ or ‘chemodectomas’. These parasympathetic
205
paragangliomas occur most commonly in the head and neck. It is now recognized that
206
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
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types (with the exception of intra-adrenal pheochromocytoma) in humans.[16] Malignancy in
209
these tumors is defined by distant metastasis and not by local invasion. [17]
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The anatomic location of the paraganglioma in this horse, in the craniodorsal mediastinum
212
immediately ventral to the thoracic vertebral bodies, was consistent with reports in humans and
213
in dogs.[9-13] These tumors typically originate from the costovertebral sulcus, and are
214
considered to arise from the aorticosympathetic paraganglia. Clinical signs attributable to
215
cathecholamine secretion are reported in 19 to 48% of cases of mediastinal paraganglioma in
216
humans.[9, 11, 18] They can be locally invasive and are often reported to invade the spinal canal,
217
but hemorrhage is not a typical feature. Hemorrhage from intra-adrenal pheochromocytomas is,
218
however, more commonly reported in horses than in humans[19], so it is possible that
219
paragangliomas display similar species-related differences in clinical behavior. Although
220
catecholamines were not measured in this case, no physiological evidence of increased
221
production (such as tachycardia, hyperglycemia or sweating) could be detected on the second
222
presentation, and all such abnormalities on the first presentation could be attributed to the
223
hemothorax.
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There are only a small number of case reports of paragangliomas at other sites in horses, most
226
commonly in the orbit (11 cases).[1-4] These tumors are believed to arise from the ciliary
227
ganglion. It is unclear if non-chromaffin paraganglion tissue is present at this site in normal
228
animals. Other reported cases include two heart base tumors (reported as chemodectoma or aortic
229
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
231
extra-adrenal paragangliomas with extensive distant metastasis have been reported in horses.[7,
232
8] Ten to fifteen percent of human cases are familial, often associated with mutations in the
233
succinate dehydrogenase subunit genes SDHD, SDHB and SDHC, which lead to mitochondrial
234
respiratory chain dysfunction and activation of the hypoxia-inducible pathway.[16] Little is yet
235
known regarding the underlying genetic basis of paragangliomas in veterinary species, but a
236
study of two carotid body paragangliomas and six pheochromocytomas in dogs found potentially
237
pathogenic SHDB or SDHD mutations in four cases. Three were germline mutations, indicating
238
potential heritability. This suggests that the underlying aetiopathogenesis could be similar
239
between species, in at least a proportion of cases.[21, 22] The small number of reported equine
240
cases appear to be sporadic, across a range of breeds, and the underlying genetic changes have
241
not yet been investigated.
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The diagnosis of a neuroendocrine tumor in this case was supported by immunohistochemistry,
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with positive staining for NSE and synaptophysin, but negative CgA staining. This pattern is
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consistent with two canine cases of posterior mediastinal paraganglioma [12, 13] but differs from
246
other equine paragangliomas, which have been positive for CgA in all seven cases for which
247
immunostaining for this marker has been reported.[3, 7] These three markers cannot distinguish
248
paragangliomas from pheochromocytomas, which are histologically identical.[23] Prognostic
249
significance of the immunostaining pattern has not yet been investigated in horses. Weak CgA
250
staining has been suggested to reflect poor differentiation or parasympathetic origin in human
251
paragangliomas [24, 25], or more malignant behavior in canine chemodectomas.[26] However,
252
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
254
circulating biomarker in humans, at least for tumors of sympathetic origin [27, 28], but this has
255
not been investigated in horses. Similarly, urine and plasma metanephrines (catecholamine
256
metabolites) are useful diagnostically in humans, but are not well characterized in horses;
257
although they may have some utility in detecting mediastinal or abdominal paragangliomas of
258
sympathetic origin, it is not currently known what proportion of equine tumors are functional,
259
and sensitivity will likely be lower for detection of parasympathetic paragangliomas at other
260
locations such as the head and neck.. Diagnosis in the horse therefore relies on a combination of
261
imaging and histopathology, both of which may be challenging ante mortem depending on
262
anatomic location.
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The diagnosis in this case may have been accelerated by earlier radiography after resolution of
265
the initial hemothorax. The index of suspicion of neoplasia was, however, reduced initially by
266
the rapid recovery and subsequent prolonged clinical remission. This is in stark contrast to the
267
expected clinical behavior of hemangiosarcoma, the most commonly reported neoplastic cause of
268
hemothorax in horses, which carries a poor prognosis. Most cases of disseminated
269
hemangiosarcoma progress rapidly, with a median survival of 17 days from onset of signs.[29]
270
Diagnosis of neoplastic causes of hemothorax is complicated by lack of shedding of
271
hemangiosarcoma cells into pleural effusion, ultrasonographic findings that are often non-
272
specific, and limited diagnostic accuracy of radiographs.[29] Pleuroscopy can be useful in
273
selected cases.[30]
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The neuroendocrine tumor in this case caused local tissue destruction and ultimately severe
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clinical disease, but was classified as benign (based on human guidelines) and had an apparent
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slow, insidious progression. Metastasis in humans is not common, and posterior mediastinal
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paragangliomas have been cured by local resection. It is conceivable that, if appropriate
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resources are available and sufficient surgical access can be achieved, an early diagnosis in a
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horse could lead to a positive outcome. Paraganglioma should therefore be considered as a
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possible differential diagnosis for suspected neoplastic conditions not just in the thorax but in
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any location where paraganglion tissue is present, and obtaining a tissue sample for
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histopathologic diagnosis should be considered a priority.
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Manufacturer’s details
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a. Naxcel; Zoetis, Kalamazoo, MI.
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b. Dexamethasone Solution; VetOne Pharmaceuticals, Boise, ID
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c. Marquis®; Merial, Duluth, GA
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d. DMSO 90% Solution; Neogen, Lexington, KY
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e. Banamine; Merck Animal Health, Madison, NJ
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References
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[1] Basher AWP, Severin GA, Chavkin MJ, Frank AA. Orbital neuroendocrine tumors in three
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[2] Goodhead AD, Venter IJ, Nesbit JW. Retrobulbar extra-adrenal paraganglioma in a horse and
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its surgical removal by orbitotomy. Veterinary & Comparative Ophthalmology. 1997;7:96-100.
301
[3] Miesner T, Wilkie D, Gemensky-Metzler A, Weisbrode S, Colitz C. Extra-adrenal
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paraganglioma of the equine orbit: six cases. Vet Ophthalmol. 2009;12:263-8.
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[4] Theuss T, Brandt K, Jäger K, Schoon HA. An orbital paraganglioma as the cause of unilateral
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exophthalmus in a horse. Pferdeheilkunde. 2013;29:708-11.
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[5] de Barros CS, dos Santos MN. Aortic body adenoma in a horse. Aust Vet J. 1983;60:61.
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[6] Levy M, Stegelmeier BL, Hudson LM, Sandusky GE, Blevins WE, Christian JA.
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Chemodectoma in a horse. Can Vet J. 1990;31:776-7.
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[7] Herbach N, Breuer W, Hermanns W. Metastatic extra-adrenal sympathetic paraganglioma in
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[8] Kim DY, Hodgin EC, Lopez MK, Nasarre C. Malignant retroperitoneal paraganglioma in a
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[9] Moran CA, Suster S, Fishback N, Koss MN. Mediastinal paragangliomas. A
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clinicopathologic and immunohistochemical study of 16 cases. Cancer. 1993;72:2358-64.
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[10] Ramos R, Moya J, Villalonga R, Morera R, Ferrer G. Mediastinal aortosympathetic
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paraganglioma: report of two cases. Asian Cardiovasc Thorac Ann. 2007;15:e49-51.
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[11] Spector JA, Willis DN, Ginsburg HB. Paraganglioma (pheochromocytoma) of the posterior
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mediastinum: a case report and review of the literature. J Pediatr Surg. 2003;38:1114-6.
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[12] Mascort J, Pumarola M. Posterior mediastinal paraganglioma involving the spinal cord of a
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[13] Rizzo SA, Newman SJ, Hecht S, Thomas WB. Malignant mediastinal extra-adrenal
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paraganglioma with spinal cord invasion in a dog. J Vet Diagn Invest. 2008;20:372-5.
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[14] Groover ES, Wooldridge AA. Equine haemothorax. Equine Veterinary Education.
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[15] Reed SM, Howe DK, Morrow JK, Graves A, Yeargan MR, Johnson AL, et al. Accurate
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management of neuroendocrine tumors: pheochromocytoma, paraganglioma, and medullary
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paraganglioma. Arch Pathol Lab Med. 1980;104:46-51.
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[19] Luethy D, Habecker P, Murphy B, Nolen-Walston R. Clinical and Pathological Features of
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[22] Holt DE, Henthorn P, Howell VM, Robinson BG, Benn DE. Succinate dehydrogenase
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[23] Fraga M, Garcia-Caballero T, Antunez J, Couce M, Beiras A, Forteza J. A comparative
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by histologic, immunohistochemical, and ultrastructural techniques. Hum Pathol. 1989;20:29-39.
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[26] Noszczyk-Nowak A, Nowak M, Paslawska U, Atamaniuk W, Nicpon J. Cases with
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manifestation of chemodectoma diagnosed in dogs in Department of Internal Diseases with
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[27] Baudin E, Gigliotti A, Ducreux M, Ropers J, Comoy E, Sabourin JC, et al. Neuron-specific
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NANETS consensus guidelines for the diagnosis of neuroendocrine tumor. Pancreas.
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[30] Rossier Y, Sweeney CR, Heyer G, Hamir AN. Pleuroscopic diagnosis of disseminated
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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
371
presentation
372 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
Globulin
18 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
Prothrombin time
373 374 375 376
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thromboplastin time
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23 – 41 g/L
4.9 mmol/L
< 2.0 mmol/L
13.4 s
9.9 – 12.5 s
57.2 s
32.0 – 46.5 s
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32 – 40 g/L
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Blood lactate
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Figure legends
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Figure 1. Ultrasonograms of hemothorax on initial presentation. Dorsal is to the left. Note
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the atelectasis of the ventral lung tip and the variable echotexture of the fluid. Key: D,
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diaphragm. L, lung. PE, pleural effusion.
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Figure 2. Thoracic radiograph after onset of ataxia. The subvertebral mass is delineated by
384
the white arrowheads. Note areas of lucency in T5 (black arrows).
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Figure 3. Post mortem specimen showing invasion of T5 by a soft tissue tumor. Cranial is to
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the left. The defects in the vertebral body (white arrows) correspond to the radiolucencies in Fig
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2.
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Figure 4. Histopathological appearance of the paraganglioma. A: Low magnification view,
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(40X) hematoxylin and eosin staining. The tumor is associated with the wall of a large muscular
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artery. B: High magnification view (200X) showing nests of cuboidal cells separated by a fine
393
fibrovascular stroma, consistent with a neuroendocrine tumor. Hematoxylin and eosin staining.
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Paragangliomas are uncommonly diagnosed neuroendocrine neoplasms in horses. The case report presents the first description of a dorsal mediastinal paraganglioma in a horse. The neoplasm was benign but locally invasive, presenting first as hemothorax and later with ataxia after extension through the adjacent vertebral body. Surgical excision of comparable tumors in humans is often curative, so early diagnosis may improve prognosis.
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