file · Web viewMediastinal paraganglioma as a cause of hemothorax and thoracic spinal cord...
Click here to load reader
-
Upload
hoanghuong -
Category
Documents
-
view
212 -
download
0
Transcript of file · Web viewMediastinal paraganglioma as a cause of hemothorax and thoracic spinal cord...
1
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]
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
2
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.
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
3
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.
48
49
50
51
52
53
54
55
56
57
58
59
60
61
62
63
64
65
66
67
68
69
4
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
70
71
72
73
74
75
76
77
78
79
80
81
82
83
84
85
86
87
88
89
90
91
92
5
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-
93
94
95
96
97
98
99
100
101
102
103
104
105
106
107
108
109
110
111
112
113
114
115
6
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).
116
117
118
119
120
121
122
123
124
125
126
127
128
129
130
131
132
133
134
135
136
137
7
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.
138
139
140
141
142
143
144
145
146
147
148
149
150
151
152
153
154
155
156
157
158
159
160
8
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
161
162
163
164
165
166
167
168
169
170
171
172
173
174
175
176
177
178
179
180
181
182
183
9
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
184
185
186
187
188
189
190
191
192
193
194
195
196
197
198
199
200
201
202
203
204
205
206
10
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
207
208
209
210
211
212
213
214
215
216
217
218
219
220
221
222
223
224
225
226
227
228
229
11
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
230
231
232
233
234
235
236
237
238
239
240
241
242
243
244
245
246
247
248
249
250
251
252
12
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]
253
254
255
256
257
258
259
260
261
262
263
264
265
266
267
268
269
270
271
272
273
274
13
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.
275
276
277
278
279
280
281
282
283
284
285
286
287
288
289
290
291
292
293
294
295
296
297298
14
[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.
299300301302303304305306307308309310311312313314315316317318319320321322323324325326327328329330331332333334335336337338339340341342
15
[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.
343344345346347348349350351352353354355356357358359360361362363364365366367
368
369
16
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
370
371
372
373374375
17
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.
376
377
378
379
380
381
382
383
384
385
386
387
388
389
390
391
392
393394