- Email: [email protected]
Periurethral Vascular Hamartoma in a 6-Month-Old Foal With Idiopathic Hematuria: New Differential Diagnosis
Accepted Manuscript Periurethral vascular hamartoma in a 6-month-old foal with idiopathic hematuria: new differential diagnosis Nicolas I. Busse, DVM, Enrique A. Paredes, DVM, Dr. Vet. Med., Hedie A. Bustamante, DVM, PhD, Nicolás Ansoleaga, DVM, Benjamín Uberti, DVM, MS PII:
S0737-0806(18)30004-2
DOI:
10.1016/j.jevs.2018.02.017
Reference:
YJEVS 2473
To appear in:
Journal of Equine Veterinary Science
Received Date: 4 January 2018 Revised Date:
22 February 2018
Accepted Date: 22 February 2018
Please cite this article as: Busse NI, Paredes EA, Bustamante HA, Ansoleaga N, Uberti B, Periurethral vascular hamartoma in a 6-month-old foal with idiopathic hematuria: new differential diagnosis, Journal of Equine Veterinary Science (2018), doi: 10.1016/j.jevs.2018.02.017. 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.
ACCEPTED MANUSCRIPT 1
Title:
2
Periurethral vascular hamartoma in a 6-month-old foal with idiopathic hematuria: new
3
differential diagnosis
Nicolas I. Busse, DVMa
6
Enrique A. Paredes, DVM, Dr. Vet. Med.b
7
Hedie A. Bustamante, DVM, PhDa
8
Nicolás Ansoleaga, DVMa
9
Benjamín Uberti, DVM, MSa
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From the aInstitute of Veterinary Clinical Sciences, bInstitute of Animal Pathology, College of
12
Veterinary Sciences, Universidad Austral de Chile, Valdivia, Chile, 5090000
13
Address: Universidad Austral de Chile, Independencia 641, Valdivia, Chile, 5090000
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Corresponding author: Dr. Benjamin Uberti ([email protected]).
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ACCEPTED MANUSCRIPT Abstract:
17
Hamartomas are non-malignant masses of normal tissue organized in a chaotic manner. Here,
18
we describe a 6-month-old 120 kg Chilean Criollo foal that manifested chronic hematuria
19
observed since birth. Severe anemia and lack of development were the main complaints of
20
this referral. The foal was depressed, in poor body condition, had lagged development and a
21
coarse haircoat. Mucous membranes were pale and numerous blood clots were observed
22
towards the end of micturition. Severe normocytic normochromic anemia was confirmed by
23
hematological analysis; there were no significant findings in serum biochemistry or
24
coagulation tests. Transabdominal ultrasonography and urinary tract endoscopy yielded no
25
clinically relevant results. Empirical treatment was initiated on a tentative diagnosis of
26
idiopathic renal hematuria (dexamethasone 0.1 mg/kg [0.045 mg/lb], q 24 h, IV, sodium
27
ceftiofur 2.2 mg/kg [0.99 mg/lb], IM, q 24 h, blood transfusions), but the foal’s condition
28
further deteriorated, warranting euthanasia. Necropsy revealed a vascular malformation on the
29
extraluminal portion of the proximal urethra at the bladder junction, with a 3 mm urethral
30
communication. Histopathologic examination confirmed this mass to be a hamartoma of
31
vascular origin, which incidentally communicated with the urethral lumen and led to
32
progressive blood loss. In this case, the location of this malformation impeded its discovery
33
and ultimately an accurate diagnosis. Hamartomas are currently not listed as a differential
34
diagnosis for bleeding-related urinary tract disorders in the modern literature, thus we propose
35
that they should be considered as a differential diagnosis in cases of unexplained or refractory
36
idiopathic hematuria.
37
Keywords: Hematuria, Hamartoma, Foal
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ACCEPTED MANUSCRIPT 1. Introduction
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Hamartomas are non-malignant growths composed of normal tissues grouped in an unorderly
40
distribution, and their composition is dependent on the organ in which they are located. These
41
structures grow according to the normal development of the surrounding tissues, and rarely
42
develop malignant behavior; clinical relevance depends almost exclusively on the location
43
and size of the mass. They are reported frequently in humans, but seldom in domestic animals
44
[1]. The first report of hamartoma on an equine subject was made in 1981 and affected
45
ovarian tissues in a mare [2]. Other notable reports of this particular kind of lesion in equines
46
include hamartomatous myelodysplasia of the spinal cord [3], vascular hamartoma in a foal´s
47
brain [4], mesenchymal hamartoma of the liver [5], vascular hamartoma of the tongue [6],
48
subcutaneous hamartoma [7], and ovarian vascular hamartoma [8]. These previous case
49
reports stress the importance of mass location regarding clinical manifestation. The following
50
report states a previously undescribed location and clinical presentation of a vascular
51
hamartoma.
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2. Materials and methods
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2.1 Case description
55
A 6-month-old Chilean Criollo foal was referred for evaluation of chronic hematuria and ill
56
thrift. The referring veterinarian stated that the foal presented hematuria and poor weight gain
57
since birth. No other animals were reported sick. The foal was recently weaned, kept on
58
pasture with other animals and supplemented with complete pelleted feed. The foal was not
59
dewormed nor vaccinated. The foal’s mother was reportedly healthy and had been dewormed
60
prior to parturition; the deworming product was not recorded.
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ACCEPTED MANUSCRIPT On physical examination, the patient was standing but depressed and unresponsive to external
62
stimuli. The horse had a dull and rough haircoat with abundant scaling, reddish stains on hind
63
hooves and pasterns, poor body condition (body condition score of 2 out of 9 and a body
64
weight of 120 kilograms), tachycardia (91 BPM), a grade 3/6 soft holosystolic murmur and
65
very pale mucous membranes with delayed capillary refill time (3 seconds). PCV was 9% and
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total solids 63 g/L. Rectal temperature was 38°C and respiratory rate was 12 breaths/minute.
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Abdominal sounds were reduced in the upper left quadrant, the rest presenting normal
68
borboygmi. Upon examination of the urinary tract, the foal was observed to urinate freely,
69
without signs of stranguria nor dysuria, and frank blood was observed throughout all stages of
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micturition; fresh blood clots were expelled towards the end of urination. No evident lesions
71
were identified in prepuce or penis, and no active bleeding was observed. Due to the severity
72
of anemia and prior to performing further diagnostics, a decision was made to perform a
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blood transfusion. After major and minor cross-matching blood compatibility testing, 3 liters
74
of whole blood were transfused. This procedure increased the foal’s PCV to 24% and
75
corrected most of the altered physiological constants, also eliminating the systolic murmur.
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After initial stabilization, and in order to explore the cause of hematuria, a battery of
77
diagnostic tests was ordered. Blood coagulation tests (PT, PTT) ruled out current
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coagulopathies. Hematologic and serum biochemical examination were performed to evaluate
79
the foal´s systemic status, revealing severe normochromic microcytic anemia prior to the
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blood transfusion: red blood cell count was markedly reduced (2.25x10^6µL; reference range
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5.9-9.4 x10^6µL), with minimal microcytosis (40 fL; reference range 40-61 fL) and severe
82
reduction of hemoglobin (30 g/L; reference range 107-167 g/L). Serum proteins were
83
moderately reduced (56 g/L; reference range 68-84 g/L). Serum fibrinogen results were
84
mildly increased (7 g/L; reference range <5 g/L). The leukogram revealed mild leukopenia
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(4300 cells/µL; reference range 5000-11000 cells/ µL) with normal neutrophil count (3225
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ACCEPTED MANUSCRIPT cells/ µL; reference range 2200-6100 cells/ µL) and marked lymphopenia (774 cells/ µL;
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reference range 1500-6500 cells/ µL). There were no significant findings in serum
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biochemistry analyses; urea and creatinine were within normal ranges. A spontaneously-
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occurring midstream urine sample was obtained. Urinalysis revealed a specific gravity of
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1.032 possibly due to mild dehydration, with abundant presence of red blood cells (>100 per
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field), proteins (1 g/L), and a pH value of 5.
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2.3 Diagnostic Imaging
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Transabdominal urinary tract ultrasonography revealed no visible abnormalities of the urethra
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or the explorable portion of the bladder. Transrectal ultrasonography was not feasible on
95
account of the foal’s size. Renal ultrasonography revealed mild size increase of both kidneys
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(approximately 5%) compared to a healthy foal of the same age, size and breed which was
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examined at the same time for comparison purposes. The cranio-caudal length of the left
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kidney was 10.5 cm, and the right kidney measured 12 cm. These dimensions were relatively
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similar to published information from 6-month-old foals of other, larger breeds (Quarter
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horse, Thoroughbred and Standardbred) (left kidney length reference range 14.79-16.87 cm;
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right kidney length reference range 10.7-11.77 cm) [9]. Subjective evaluation of the right
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renal parenchyma suggested a hyperechogenic interphase between the renal cortex and
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medulla. The left renal parenchyma had no visible abnormalities. Doppler examination of
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both kidneys revealed no obvious vascular abnormalities such as enlarged/varicose vessels,
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sinuses, or blood-filled cavities.
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Lower urinary tract endoscopy was performed with a 4 mm fiberendoscopea, under standing
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sedation, to locate and visualize the site of bleeding. There were visible clots of blood in the
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bladder lumen and intermittently throughout the urethra, which demanded bladder lavage with
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sterile saline solution to clean the urinary tract and facilitate its exploration. There were no
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ACCEPTED MANUSCRIPT obvious lesions in the visible lateral and dorsal bladder walls, nor along the urethra. The
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ureteral openings were not directly observable during standing endoscopy due to limited
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maneuverability of the small diameter endoscope used, but no clots or blood were detected on
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the dorsal aspect of the bladder. This procedure was performed on two different occasions, 7
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days apart, with the same results.
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2.4 Treatment and Outcome
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Given the lack of a clear diagnosis, no noticeable distal urinary tract lesions, and persistent
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hematuria, a tentative diagnosis of idiopathic renal hematuria was made. Therefore, an
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empirical treatment course of dexamethasone (0.1 mg/kg [0.045 mg/lb], IV, q 24 h) was
119
initiated [10] to rule out an autoimmune component of disease. Ancillary treatment included
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sodium ceftiofur (2.2 mg/kg [0.99 mg/lb], IM, q 24 h), formalin (10%, 5 Ml, IV, q 24 h) and a
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commercial enteral multi-mineral and iron supplement. However, the foal did not improve
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and hematuria did not change its frequency or volume. Due to the lack of response to
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treatment in the successive days, a second blood transfusion was warranted, raising the PCV
124
from 14% to 28% (day 7 after admission). A definitive antemortem diagnosis of the cause of
125
hematuria could not be reached, and humane euthanasia was decided due to continued
126
worsening; the foal was euthanized on day 18 with a PCV of 10%.
127
3. Results:
128
3.1 Postmortem Findings
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A full necropsy was performed. The urinary tract was fully inspected and sampled routinely.
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A multinodular, 1.5 cm in diameter, reddish growth was observed on the dorso-lateral region
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of the proximal urethra, immediately distal to the vesical trigone and connected with a small
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area of bleeding in the urethral mucosa of approximately 3 mm in length (Figures 1 and 2).
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Microscopic examination of the mass showed multiple blood-filled vascular vessels of
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ACCEPTED MANUSCRIPT different sizes and lined by a single layer of endothelial cells. The blood vessels were
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separated by abundant connective tissue stroma (Figure 3). Abundant acute hemorrhage was
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visible adjacent to some vessels.
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No other significant findings were identified on the remaining systems.
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ACCEPTED MANUSCRIPT 4. Discussion:
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This report characterizes an infrequent and previously unreported urinary tract lesion, with a
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relevant clinical presentation and eventually fatal clinical outcome. The cardinal clinical sign
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of this case was ill thrift and hematuria, evidenced macroscopically as urine discoloration.
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Urine discoloration can be diagnostically challenging for equine clinicians (especially in field
144
practice), and may be classified in categories according to, for example, the molecules
145
involved (myoglobin, hemoglobin, bilirubin), the presence and amount of red blood cells
146
present in the urine (microscopic or macroscopic hematuria), or moment of discoloration
147
within micturition (initial, mid-, or terminal hematuria). Visible strands of blood in the urine
148
stream suggest a bleeding point in the urethra, thus not allowing blood to fully mix with urine,
149
as opposed to hematuria originated from lesions in the kidneys, ureters, or bladder, in which
150
blood is homogenously mixed with urine. Hematuria in the equine patient is a clinical sign
151
associated with well described disorders such as congenital malformations, urolithiasis,
152
neoplasia, intoxications (such as cantharidin), trauma, or urinary tract infections.
153
Hemospermia caused by rents communicating the urethral wall with the corpus spongiosum
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penis also involves a connection between a vascular structure and the urethral lumen [11, 12].
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Urethral rents are attributed to the anatomical distribution of the urethra in ischial arch, where
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a narrowing of the diameter may influence a strain on urethral tissues, leading to a rupture and
157
communication with the corpus spongiosum penis. Hematuria is more often presented in
158
geldings than in stallions due to increased intracavernosal pressure [11]. In the case reported
159
here, although fiberendoscopic evaluation was performed twice following current
160
examination protocols, no diagnostic images were obtained on either occasion. This suggests
161
that some defects are not readily identifiable depending on the diameter of the lesion,
162
equipment limitations (such resolution, display size), and/or operator experience. In this case,
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the communication between the hamartoma and the urethral lumen was very small (3 mm),
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ACCEPTED MANUSCRIPT which impeded its visualization during urethral endoscopy. Moreover, the case was
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particularly difficult to explore endoscopically due to the size of the foal, which impeded the
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use of a 12 mm video endoscope with two-dimensional guidewires, situation that also made
167
the distension of the bladder more troublesome. Therefore, ancillary imaging techniques
168
would be necessary in these rare cases to pinpoint such a focalized lesion.
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Periurethral structures are difficult to evaluate, especially the proximal and middle portions of
170
the urethra located inside the pelvic cavity. Transrectal ultrasonography could offer insight
171
into the status of proximal urethral structures and peripheral tissues in male patients, although
172
patients´ size may impede this maneuver. In this pediatric case, the foal´s size impeded
173
transrectal ultrasonography which could well have evidenced a periurethral mass. Previous
174
reports of bladder growths in humans have also described diagnostic difficulties, and even
175
cases of diagnosis at surgery [13]. In human medicine, bladder hamartomas are considered
176
rare entities, but have been described in pediatric and adult patients [14-18]. Clinical signs
177
may vary from painless hematuria to dysuria, and treatments have included transurethral
178
resection or partial cystectomy [15]. Similar surgical approaches may potentially be useful in
179
equine cases depending on mass size, location and patient size.
180
In conclusion, we propose that the presence of vascular hamartomas in the periphery of the
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urinary tract should be considered as a differential diagnosis for refractory hematuria of
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unknown/indeterminate origin.
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ACCEPTED MANUSCRIPT 186
Acknowledgments:
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The authors declare no conflicts of interest.
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Footnotes:
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a. Broncho-Fiberscope 60003VB1, KARL STORZ GmbH, Tuttlingen, Germany.
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References:
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[1] Bartyzel BJ, Max A, Gruszczyńska J, et al. Hamartoma: a rare developmental disorder.
194
Med Weter 2017;73:202–207.
195
[2] Rhyan JC, D’Andrea GH, Smith LS. Congenital ovarian vascular hamartoma in a horse.
196
Vet Pathol 1981;18:131.
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[3] Taylor KR, MacKay RJ, Nelson EA, et al. Spinal cord hamartomatous myelodysplasia in
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2 horses with clinical neurologic deficits. Vet Pathol 2016;53:844–846.
199
[4] Borel N, Grest P, Junge H, Wehrli Eser M. Vascular hamartoma in the central nervous
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system of a foal. J Vet Diagn Invest 2014; 26:805-809.
201
[5] Brown DL, Anderson M, Cullen JM. Mesenchymal hamartoma of the liver in a late-term
202
equine fetus. Vet Pathol 2007;44:100–102.
203
[6] Brunson BL, Taintor J, Newton J, et al. Vascular hamartoma in the tongue of a horse. J
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Equine Vet Sci 2006;26:275–277.
205
[7] Saifzadeh S, Derakhshanfar A, Shokouhi F, et al. Vascular hamartoma as the cause of
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hind limb lameness in a horse. J Vet Med Ser A Physiol Pathol Clin Med 2006;53:202–204.
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ACCEPTED MANUSCRIPT [8] Foley GL, Johnson R. A congenital interstitial cell hamartoma of the equine ovary. Vet
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Pathol 1990;27:364–366.
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[9] Aleman M, Gillis CL, Nieto JE, Renaudin CD, Bea J. Ultrasonographic anatomy and
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biometric analysis of the thoracic and abdominal organs in healthy foals from birth to age 6
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months. Equine Vet J 2002;34:649-55.
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[10] Vits L, Araya O, Bustamante H, et al. Idiopathic renal haematuria in a 15-year-old
213
Arabian mare. Vet Rec 2008;162:251–252.
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[11] Schumacher J, Schumacher J, Schmitz D. Macroscopic haematuria of horses. Equine Vet
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Educ 2002;14:201–210.
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[12] Schott HC. Hematuria. In: Reed SM, Bayly WM, Sellon DC, editors. Equine Internal
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Medicine, 3rd ed. St. Louis: Saunders Elsevier, 2012, p. 1209–1213.
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[13] Susset J, Korzinstone C, Masse S. Cavernous Hemangioma Of Vesical Neck. Urology
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1981;17:75–76.
220
[14] Brancatelli G, Midiri M, Sparacia G, Martino R, Rizzo G, Lagalla R. Hamartoma of the
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urinary bladder: case report and review of the literature. Eur Radiol 1999;9:42–4.
222
[15] Ota T, Kawai K, Hattori K, Uchida K, Akaza H, Harada M. Hamartoma of the urinary
223
bladder. Int J Urol 1999;6:211–214.
224
[16] Al Shahwani N, Alnaimi AR, Ammar A, Al-Ahdal EM. Hamartoma of the urinary
225
bladder in a 15-year-old boy. Turk J Urol 2016;42:101-3.
226
[17] Adam A, Gayaparsad K, Engelbrecht MJ, Moshokoa EM. Bladder hamartoma: a unique
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cause of urinary retention in a child with Goldenhar syndrome. Saudi J Kidney Dis Transpl
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2013;24:89-92.
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[18] Murray C, Marchan J, Özel B, Özel B. Bladder wall hamartoma: an unusual cause of
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urinary urgency and frequency. Female Pelvic Med Reconstr Surg 2015;21:e8-e10.
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ACCEPTED MANUSCRIPT Figures (in color):
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Fig. 1 - Ventral view of the bladder and proximal urethra. Bladder (white arrowhead), urethra
237
(black arrowhead), vascular hamartoma (white arrow), opening of vascular hamartoma to the
238
urethral lumen (black arrow). Opening is approximately 3 mm wide.
239
Fig. 2 - Caudo-dorsal view of the urethra: close-up view of the lesion. Vascular hamartoma
240
(white arrow), opening to the urethral lumen (black arrow), blood clot (white arrowhead).
241
Bar = 1 cm.
242
Fig. 3 - Vascular hamartoma in the proximal urethra, horse. There are numerous blood vessels
243
of different sizes in the submucosa (arrows) separated by a connective tissue stroma (star).
244
100x; Bar = 200 µm.
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Highlights: •
Unexplained chronic hematuria and anemia in a 6-month-old Chilean Criollo foal with ill thrift. Progressive blood loss led to humane destruction and necropsy, which revealed a
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•
single vascular malformation with a small communication with the urethral lumen. The infrequent etiology and location of this congenital malformation hindered
diagnostic efforts; this is the first description of a periurethral vascular hamartoma in
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horses.
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Animal welfare/ethical statement: The case described in this manuscript received the best available quality of medical care according to Universidad Austral de Chile´s School of Veterinary Sciences. Humane euthanasia was decided in order to avoid animal suffering. Publication was pursued with the owner´s consent.
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Conflict of interest statement: The authors declare no conflicts of interest.
S0737-0806(18)30004-2
DOI:
10.1016/j.jevs.2018.02.017
Reference:
YJEVS 2473
To appear in:
Journal of Equine Veterinary Science
Received Date: 4 January 2018 Revised Date:
22 February 2018
Accepted Date: 22 February 2018
Please cite this article as: Busse NI, Paredes EA, Bustamante HA, Ansoleaga N, Uberti B, Periurethral vascular hamartoma in a 6-month-old foal with idiopathic hematuria: new differential diagnosis, Journal of Equine Veterinary Science (2018), doi: 10.1016/j.jevs.2018.02.017. 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.
ACCEPTED MANUSCRIPT 1
Title:
2
Periurethral vascular hamartoma in a 6-month-old foal with idiopathic hematuria: new
3
differential diagnosis
Nicolas I. Busse, DVMa
6
Enrique A. Paredes, DVM, Dr. Vet. Med.b
7
Hedie A. Bustamante, DVM, PhDa
8
Nicolás Ansoleaga, DVMa
9
Benjamín Uberti, DVM, MSa
M AN U
10
SC
5
RI PT
4
From the aInstitute of Veterinary Clinical Sciences, bInstitute of Animal Pathology, College of
12
Veterinary Sciences, Universidad Austral de Chile, Valdivia, Chile, 5090000
13
Address: Universidad Austral de Chile, Independencia 641, Valdivia, Chile, 5090000
EP
15
Corresponding author: Dr. Benjamin Uberti ([email protected]).
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ACCEPTED MANUSCRIPT Abstract:
17
Hamartomas are non-malignant masses of normal tissue organized in a chaotic manner. Here,
18
we describe a 6-month-old 120 kg Chilean Criollo foal that manifested chronic hematuria
19
observed since birth. Severe anemia and lack of development were the main complaints of
20
this referral. The foal was depressed, in poor body condition, had lagged development and a
21
coarse haircoat. Mucous membranes were pale and numerous blood clots were observed
22
towards the end of micturition. Severe normocytic normochromic anemia was confirmed by
23
hematological analysis; there were no significant findings in serum biochemistry or
24
coagulation tests. Transabdominal ultrasonography and urinary tract endoscopy yielded no
25
clinically relevant results. Empirical treatment was initiated on a tentative diagnosis of
26
idiopathic renal hematuria (dexamethasone 0.1 mg/kg [0.045 mg/lb], q 24 h, IV, sodium
27
ceftiofur 2.2 mg/kg [0.99 mg/lb], IM, q 24 h, blood transfusions), but the foal’s condition
28
further deteriorated, warranting euthanasia. Necropsy revealed a vascular malformation on the
29
extraluminal portion of the proximal urethra at the bladder junction, with a 3 mm urethral
30
communication. Histopathologic examination confirmed this mass to be a hamartoma of
31
vascular origin, which incidentally communicated with the urethral lumen and led to
32
progressive blood loss. In this case, the location of this malformation impeded its discovery
33
and ultimately an accurate diagnosis. Hamartomas are currently not listed as a differential
34
diagnosis for bleeding-related urinary tract disorders in the modern literature, thus we propose
35
that they should be considered as a differential diagnosis in cases of unexplained or refractory
36
idiopathic hematuria.
37
Keywords: Hematuria, Hamartoma, Foal
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ACCEPTED MANUSCRIPT 1. Introduction
39
Hamartomas are non-malignant growths composed of normal tissues grouped in an unorderly
40
distribution, and their composition is dependent on the organ in which they are located. These
41
structures grow according to the normal development of the surrounding tissues, and rarely
42
develop malignant behavior; clinical relevance depends almost exclusively on the location
43
and size of the mass. They are reported frequently in humans, but seldom in domestic animals
44
[1]. The first report of hamartoma on an equine subject was made in 1981 and affected
45
ovarian tissues in a mare [2]. Other notable reports of this particular kind of lesion in equines
46
include hamartomatous myelodysplasia of the spinal cord [3], vascular hamartoma in a foal´s
47
brain [4], mesenchymal hamartoma of the liver [5], vascular hamartoma of the tongue [6],
48
subcutaneous hamartoma [7], and ovarian vascular hamartoma [8]. These previous case
49
reports stress the importance of mass location regarding clinical manifestation. The following
50
report states a previously undescribed location and clinical presentation of a vascular
51
hamartoma.
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SC
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38
52
2. Materials and methods
54
2.1 Case description
55
A 6-month-old Chilean Criollo foal was referred for evaluation of chronic hematuria and ill
56
thrift. The referring veterinarian stated that the foal presented hematuria and poor weight gain
57
since birth. No other animals were reported sick. The foal was recently weaned, kept on
58
pasture with other animals and supplemented with complete pelleted feed. The foal was not
59
dewormed nor vaccinated. The foal’s mother was reportedly healthy and had been dewormed
60
prior to parturition; the deworming product was not recorded.
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ACCEPTED MANUSCRIPT On physical examination, the patient was standing but depressed and unresponsive to external
62
stimuli. The horse had a dull and rough haircoat with abundant scaling, reddish stains on hind
63
hooves and pasterns, poor body condition (body condition score of 2 out of 9 and a body
64
weight of 120 kilograms), tachycardia (91 BPM), a grade 3/6 soft holosystolic murmur and
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very pale mucous membranes with delayed capillary refill time (3 seconds). PCV was 9% and
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total solids 63 g/L. Rectal temperature was 38°C and respiratory rate was 12 breaths/minute.
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Abdominal sounds were reduced in the upper left quadrant, the rest presenting normal
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borboygmi. Upon examination of the urinary tract, the foal was observed to urinate freely,
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without signs of stranguria nor dysuria, and frank blood was observed throughout all stages of
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micturition; fresh blood clots were expelled towards the end of urination. No evident lesions
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were identified in prepuce or penis, and no active bleeding was observed. Due to the severity
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of anemia and prior to performing further diagnostics, a decision was made to perform a
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blood transfusion. After major and minor cross-matching blood compatibility testing, 3 liters
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of whole blood were transfused. This procedure increased the foal’s PCV to 24% and
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corrected most of the altered physiological constants, also eliminating the systolic murmur.
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After initial stabilization, and in order to explore the cause of hematuria, a battery of
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diagnostic tests was ordered. Blood coagulation tests (PT, PTT) ruled out current
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coagulopathies. Hematologic and serum biochemical examination were performed to evaluate
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the foal´s systemic status, revealing severe normochromic microcytic anemia prior to the
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blood transfusion: red blood cell count was markedly reduced (2.25x10^6µL; reference range
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5.9-9.4 x10^6µL), with minimal microcytosis (40 fL; reference range 40-61 fL) and severe
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reduction of hemoglobin (30 g/L; reference range 107-167 g/L). Serum proteins were
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moderately reduced (56 g/L; reference range 68-84 g/L). Serum fibrinogen results were
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mildly increased (7 g/L; reference range <5 g/L). The leukogram revealed mild leukopenia
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(4300 cells/µL; reference range 5000-11000 cells/ µL) with normal neutrophil count (3225
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reference range 1500-6500 cells/ µL). There were no significant findings in serum
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biochemistry analyses; urea and creatinine were within normal ranges. A spontaneously-
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occurring midstream urine sample was obtained. Urinalysis revealed a specific gravity of
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1.032 possibly due to mild dehydration, with abundant presence of red blood cells (>100 per
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field), proteins (1 g/L), and a pH value of 5.
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2.3 Diagnostic Imaging
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Transabdominal urinary tract ultrasonography revealed no visible abnormalities of the urethra
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or the explorable portion of the bladder. Transrectal ultrasonography was not feasible on
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account of the foal’s size. Renal ultrasonography revealed mild size increase of both kidneys
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(approximately 5%) compared to a healthy foal of the same age, size and breed which was
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examined at the same time for comparison purposes. The cranio-caudal length of the left
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kidney was 10.5 cm, and the right kidney measured 12 cm. These dimensions were relatively
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similar to published information from 6-month-old foals of other, larger breeds (Quarter
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horse, Thoroughbred and Standardbred) (left kidney length reference range 14.79-16.87 cm;
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right kidney length reference range 10.7-11.77 cm) [9]. Subjective evaluation of the right
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renal parenchyma suggested a hyperechogenic interphase between the renal cortex and
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medulla. The left renal parenchyma had no visible abnormalities. Doppler examination of
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both kidneys revealed no obvious vascular abnormalities such as enlarged/varicose vessels,
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sinuses, or blood-filled cavities.
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Lower urinary tract endoscopy was performed with a 4 mm fiberendoscopea, under standing
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sedation, to locate and visualize the site of bleeding. There were visible clots of blood in the
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bladder lumen and intermittently throughout the urethra, which demanded bladder lavage with
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sterile saline solution to clean the urinary tract and facilitate its exploration. There were no
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ureteral openings were not directly observable during standing endoscopy due to limited
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maneuverability of the small diameter endoscope used, but no clots or blood were detected on
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the dorsal aspect of the bladder. This procedure was performed on two different occasions, 7
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days apart, with the same results.
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2.4 Treatment and Outcome
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Given the lack of a clear diagnosis, no noticeable distal urinary tract lesions, and persistent
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hematuria, a tentative diagnosis of idiopathic renal hematuria was made. Therefore, an
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empirical treatment course of dexamethasone (0.1 mg/kg [0.045 mg/lb], IV, q 24 h) was
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initiated [10] to rule out an autoimmune component of disease. Ancillary treatment included
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sodium ceftiofur (2.2 mg/kg [0.99 mg/lb], IM, q 24 h), formalin (10%, 5 Ml, IV, q 24 h) and a
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commercial enteral multi-mineral and iron supplement. However, the foal did not improve
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and hematuria did not change its frequency or volume. Due to the lack of response to
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treatment in the successive days, a second blood transfusion was warranted, raising the PCV
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from 14% to 28% (day 7 after admission). A definitive antemortem diagnosis of the cause of
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hematuria could not be reached, and humane euthanasia was decided due to continued
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worsening; the foal was euthanized on day 18 with a PCV of 10%.
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3. Results:
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3.1 Postmortem Findings
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A full necropsy was performed. The urinary tract was fully inspected and sampled routinely.
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A multinodular, 1.5 cm in diameter, reddish growth was observed on the dorso-lateral region
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of the proximal urethra, immediately distal to the vesical trigone and connected with a small
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area of bleeding in the urethral mucosa of approximately 3 mm in length (Figures 1 and 2).
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Microscopic examination of the mass showed multiple blood-filled vascular vessels of
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separated by abundant connective tissue stroma (Figure 3). Abundant acute hemorrhage was
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visible adjacent to some vessels.
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No other significant findings were identified on the remaining systems.
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This report characterizes an infrequent and previously unreported urinary tract lesion, with a
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relevant clinical presentation and eventually fatal clinical outcome. The cardinal clinical sign
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of this case was ill thrift and hematuria, evidenced macroscopically as urine discoloration.
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Urine discoloration can be diagnostically challenging for equine clinicians (especially in field
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practice), and may be classified in categories according to, for example, the molecules
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involved (myoglobin, hemoglobin, bilirubin), the presence and amount of red blood cells
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present in the urine (microscopic or macroscopic hematuria), or moment of discoloration
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within micturition (initial, mid-, or terminal hematuria). Visible strands of blood in the urine
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stream suggest a bleeding point in the urethra, thus not allowing blood to fully mix with urine,
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as opposed to hematuria originated from lesions in the kidneys, ureters, or bladder, in which
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blood is homogenously mixed with urine. Hematuria in the equine patient is a clinical sign
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associated with well described disorders such as congenital malformations, urolithiasis,
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neoplasia, intoxications (such as cantharidin), trauma, or urinary tract infections.
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Hemospermia caused by rents communicating the urethral wall with the corpus spongiosum
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penis also involves a connection between a vascular structure and the urethral lumen [11, 12].
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Urethral rents are attributed to the anatomical distribution of the urethra in ischial arch, where
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a narrowing of the diameter may influence a strain on urethral tissues, leading to a rupture and
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communication with the corpus spongiosum penis. Hematuria is more often presented in
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geldings than in stallions due to increased intracavernosal pressure [11]. In the case reported
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here, although fiberendoscopic evaluation was performed twice following current
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examination protocols, no diagnostic images were obtained on either occasion. This suggests
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that some defects are not readily identifiable depending on the diameter of the lesion,
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equipment limitations (such resolution, display size), and/or operator experience. In this case,
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the communication between the hamartoma and the urethral lumen was very small (3 mm),
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ACCEPTED MANUSCRIPT which impeded its visualization during urethral endoscopy. Moreover, the case was
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particularly difficult to explore endoscopically due to the size of the foal, which impeded the
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use of a 12 mm video endoscope with two-dimensional guidewires, situation that also made
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the distension of the bladder more troublesome. Therefore, ancillary imaging techniques
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would be necessary in these rare cases to pinpoint such a focalized lesion.
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Periurethral structures are difficult to evaluate, especially the proximal and middle portions of
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the urethra located inside the pelvic cavity. Transrectal ultrasonography could offer insight
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into the status of proximal urethral structures and peripheral tissues in male patients, although
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patients´ size may impede this maneuver. In this pediatric case, the foal´s size impeded
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transrectal ultrasonography which could well have evidenced a periurethral mass. Previous
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reports of bladder growths in humans have also described diagnostic difficulties, and even
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cases of diagnosis at surgery [13]. In human medicine, bladder hamartomas are considered
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rare entities, but have been described in pediatric and adult patients [14-18]. Clinical signs
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may vary from painless hematuria to dysuria, and treatments have included transurethral
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resection or partial cystectomy [15]. Similar surgical approaches may potentially be useful in
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equine cases depending on mass size, location and patient size.
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In conclusion, we propose that the presence of vascular hamartomas in the periphery of the
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urinary tract should be considered as a differential diagnosis for refractory hematuria of
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unknown/indeterminate origin.
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Acknowledgments:
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The authors declare no conflicts of interest.
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Footnotes:
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a. Broncho-Fiberscope 60003VB1, KARL STORZ GmbH, Tuttlingen, Germany.
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References:
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[1] Bartyzel BJ, Max A, Gruszczyńska J, et al. Hamartoma: a rare developmental disorder.
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Med Weter 2017;73:202–207.
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[2] Rhyan JC, D’Andrea GH, Smith LS. Congenital ovarian vascular hamartoma in a horse.
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Vet Pathol 1981;18:131.
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[3] Taylor KR, MacKay RJ, Nelson EA, et al. Spinal cord hamartomatous myelodysplasia in
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2 horses with clinical neurologic deficits. Vet Pathol 2016;53:844–846.
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[4] Borel N, Grest P, Junge H, Wehrli Eser M. Vascular hamartoma in the central nervous
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system of a foal. J Vet Diagn Invest 2014; 26:805-809.
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[5] Brown DL, Anderson M, Cullen JM. Mesenchymal hamartoma of the liver in a late-term
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equine fetus. Vet Pathol 2007;44:100–102.
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[6] Brunson BL, Taintor J, Newton J, et al. Vascular hamartoma in the tongue of a horse. J
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Equine Vet Sci 2006;26:275–277.
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[7] Saifzadeh S, Derakhshanfar A, Shokouhi F, et al. Vascular hamartoma as the cause of
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hind limb lameness in a horse. J Vet Med Ser A Physiol Pathol Clin Med 2006;53:202–204.
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Pathol 1990;27:364–366.
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[9] Aleman M, Gillis CL, Nieto JE, Renaudin CD, Bea J. Ultrasonographic anatomy and
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biometric analysis of the thoracic and abdominal organs in healthy foals from birth to age 6
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months. Equine Vet J 2002;34:649-55.
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[10] Vits L, Araya O, Bustamante H, et al. Idiopathic renal haematuria in a 15-year-old
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Arabian mare. Vet Rec 2008;162:251–252.
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[11] Schumacher J, Schumacher J, Schmitz D. Macroscopic haematuria of horses. Equine Vet
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Educ 2002;14:201–210.
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[12] Schott HC. Hematuria. In: Reed SM, Bayly WM, Sellon DC, editors. Equine Internal
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Medicine, 3rd ed. St. Louis: Saunders Elsevier, 2012, p. 1209–1213.
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[13] Susset J, Korzinstone C, Masse S. Cavernous Hemangioma Of Vesical Neck. Urology
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1981;17:75–76.
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[14] Brancatelli G, Midiri M, Sparacia G, Martino R, Rizzo G, Lagalla R. Hamartoma of the
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urinary bladder: case report and review of the literature. Eur Radiol 1999;9:42–4.
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[15] Ota T, Kawai K, Hattori K, Uchida K, Akaza H, Harada M. Hamartoma of the urinary
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bladder. Int J Urol 1999;6:211–214.
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[16] Al Shahwani N, Alnaimi AR, Ammar A, Al-Ahdal EM. Hamartoma of the urinary
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bladder in a 15-year-old boy. Turk J Urol 2016;42:101-3.
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[17] Adam A, Gayaparsad K, Engelbrecht MJ, Moshokoa EM. Bladder hamartoma: a unique
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cause of urinary retention in a child with Goldenhar syndrome. Saudi J Kidney Dis Transpl
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2013;24:89-92.
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[18] Murray C, Marchan J, Özel B, Özel B. Bladder wall hamartoma: an unusual cause of
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urinary urgency and frequency. Female Pelvic Med Reconstr Surg 2015;21:e8-e10.
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Fig. 1 - Ventral view of the bladder and proximal urethra. Bladder (white arrowhead), urethra
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(black arrowhead), vascular hamartoma (white arrow), opening of vascular hamartoma to the
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urethral lumen (black arrow). Opening is approximately 3 mm wide.
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Fig. 2 - Caudo-dorsal view of the urethra: close-up view of the lesion. Vascular hamartoma
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(white arrow), opening to the urethral lumen (black arrow), blood clot (white arrowhead).
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Bar = 1 cm.
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Fig. 3 - Vascular hamartoma in the proximal urethra, horse. There are numerous blood vessels
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of different sizes in the submucosa (arrows) separated by a connective tissue stroma (star).
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100x; Bar = 200 µm.
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Highlights: •
Unexplained chronic hematuria and anemia in a 6-month-old Chilean Criollo foal with ill thrift. Progressive blood loss led to humane destruction and necropsy, which revealed a
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•
single vascular malformation with a small communication with the urethral lumen. The infrequent etiology and location of this congenital malformation hindered
diagnostic efforts; this is the first description of a periurethral vascular hamartoma in
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horses.
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Animal welfare/ethical statement: The case described in this manuscript received the best available quality of medical care according to Universidad Austral de Chile´s School of Veterinary Sciences. Humane euthanasia was decided in order to avoid animal suffering. Publication was pursued with the owner´s consent.
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Conflict of interest statement: The authors declare no conflicts of interest.