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<article xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:mml="http://www.w3.org/1998/Math/MathML" article-type="research-article" xml:lang="en">
<front>
<journal-meta>
<journal-id journal-id-type="publisher-id">JSAVA</journal-id>
<journal-title-group>
<journal-title>Journal of the South African Veterinary Association</journal-title>
</journal-title-group>
<issn pub-type="ppub">1019-9128</issn>
<issn pub-type="epub">2224-9435</issn>
<publisher>
<publisher-name>AOSIS</publisher-name>
</publisher>
</journal-meta>
<article-meta>
<article-id pub-id-type="publisher-id">JSAVA-89-1636</article-id>
<article-id pub-id-type="doi">10.4102/jsava.v89i0.1636</article-id>
<article-categories>
<subj-group subj-group-type="heading">
<subject>Case Report</subject>
</subj-group>
</article-categories>
<title-group>
<article-title>Unilateral subcutaneous fibroma in the distal femoral region of a 5-year-old Nooitgedacht mare</article-title>
</title-group>
<contrib-group>
<contrib contrib-type="author" corresp="yes">
<contrib-id contrib-id-type="orcid">https://orcid.org/0000-0001-9895-6702</contrib-id>
<name>
<surname>Poore</surname>
<given-names>Luke A.</given-names>
</name>
<xref ref-type="aff" rid="AF0001">1</xref>
</contrib>
<contrib contrib-type="author">
<contrib-id contrib-id-type="orcid">https://orcid.org/0000-0002-5604-9976</contrib-id>
<name>
<surname>Duncan</surname>
<given-names>Neil</given-names>
</name>
<xref ref-type="aff" rid="AF0002">2</xref>
</contrib>
<contrib contrib-type="author">
<contrib-id contrib-id-type="orcid">https://orcid.org/0000-0002-8542-6451</contrib-id>
<name>
<surname>Williams</surname>
<given-names>June</given-names>
</name>
<xref ref-type="aff" rid="AF0002">2</xref>
</contrib>
<aff id="AF0001"><label>1</label>Department of Companion Animal Clinical Studies, University of Pretoria, South Africa</aff>
<aff id="AF0002"><label>2</label>Department of Paraclinical Studies, University of Pretoria, South Africa</aff>
</contrib-group>
<author-notes>
<corresp id="cor1"><bold>Corresponding author:</bold> Luke Poore, <email xlink:href="vicandluke@hotmail.com">vicandluke@hotmail.com</email></corresp>
</author-notes>
<pub-date pub-type="epub"><day>05</day><month>12</month><year>2018</year></pub-date>
<pub-date pub-type="collection"><year>2018</year></pub-date>
<volume>89</volume>
<issue>0</issue>
<elocation-id>1636</elocation-id>
<history>
<date date-type="received"><day>17</day><month>11</month><year>2017</year></date>
<date date-type="accepted"><day>09</day><month>10</month><year>2018</year></date>
</history>
<permissions>
<copyright-statement>&#x00A9; 2018. The Authors</copyright-statement>
<copyright-year>2018</copyright-year>
<license license-type="open-access" xlink:href="https://creativecommons.org/licenses/by/4.0/">
<license-p>Licensee: AOSIS. This work is licensed under the Creative Commons Attribution License.</license-p>
</license>
</permissions>
<abstract>
<p>A non-ossified unilateral subcutaneous fibroma was diagnosed in the distal femoral region of a 5-year-old Nooitgedacht mare. Histopathological examination of the excised mass revealed long interweaving bundles of semi-mature monotonous collagenous connective tissue with fusiform nuclei without mitotic figures. The mare made an uneventful recovery following surgical removal of the neoplasm. Subcutaneous fibromas should be considered in the differential diagnosis of skin swellings associated with the limbs of horses.</p>
</abstract>
</article-meta>
</front>
<body>
<sec id="s0001">
<title>Introduction</title>
<p>Neoplasia of the appendicular skeleton in the horse is unusual (Schooley &#x0026; Hendrickson <xref ref-type="bibr" rid="CIT0029">1998</xref>), with the axial skeleton and head being more commonly affected (Collins <xref ref-type="bibr" rid="CIT0007">1998</xref>; Gibbs <xref ref-type="bibr" rid="CIT0010">1994</xref>; Hance &#x0026; Bertone <xref ref-type="bibr" rid="CIT0012">1993</xref>; Kidd &#x0026; Bradshaw <xref ref-type="bibr" rid="CIT0017">2002</xref>). Cutaneous fibromas have rarely been reported in domestic animals, although they are common in humans (Jacobson <xref ref-type="bibr" rid="CIT0016">1971</xref>). By contrast, the tumour often confused with fibroma, and often called fibroma, is bovine papilloma virus&#x2013;associated equine sarcoid, which is the most common tumour of horses and accounts for over half of all equine skin tumours (Taylor &#x0026; Haldorson <xref ref-type="bibr" rid="CIT0035">2013</xref>). There are a small number of previous reports of non-sarcoid cutaneous or subcutaneous fibroma in the horse (Attenburrow &#x0026; Heyse-Moore <xref ref-type="bibr" rid="CIT0002">1982</xref>; Kidd &#x0026; Bradshaw <xref ref-type="bibr" rid="CIT0017">2002</xref>). This, to the authors&#x2019; knowledge, is the first report of a confirmed non-ossifying subcutaneous fibroma on the limb of a horse.</p>
</sec>
<sec id="s0002">
<title>Ethical considerations</title>
<p>No approval was required as this case report describes a clinical case and the mare was part of the teaching herd of the Onderstepoort Veterinary Academic Hospital, University of Pretoria.</p>
</sec>
<sec id="s0003">
<title>Case presentation</title>
<p>A 5-year-old Nooitgedacht mare was presented to the Onderstepoort Veterinary Academic Hospital, University of Pretoria, South Africa for evaluation of a mass overlying the right distolateral femoral region. It was reported that the mass had been present for approximately 3 months and had slowly increased in size during this period. In addition, the mare had shown evidence of right hind limb lameness of increasing severity over this period. Clinical examination revealed a firm, single smooth nodular subcutaneous mass measuring 4 cm &#x00D7; 5 cm below but adherent to the skin at the distolateral aspect of the right femur. The mare resented local palpation. No other abnormalities were evident on a general physical examination. A dynamic gait evaluation performed in hand at a trot on a straight line on a hard surface revealed a 3/5 right hind limb lameness (American Association of Equine Practitioners Scale 1&#x2013;5).</p>
<p>A radiographic examination of the distal right femur was unremarkable and ultrasonographic evaluation revealed a well-defined subcutaneous homogenous mass with moderate echodensity. No abnormalities were palpable or visualised ultrasonographically at the local or regional lymph nodes to indicate metastasis.</p>
<p>The mass, which was of firm consistency and grey to white on cut surface as previously reported (Hendrick <xref ref-type="bibr" rid="CIT0013">2002</xref>), was surgically excised. Histopathological examination, using routine haematoxylin and eosin staining on sections cut from formalin-fixed, paraffin wax-embedded tissue, revealed long interweaving bundles of semi-mature monotonous collagenous connective tissue. Mitotic figures were absent and the nuclei were fusiform and regular to wavy. Occasional blood vessels showed a mild perivascular round cell infiltrate. A diagnosis of fibroma was made (<xref ref-type="fig" rid="F0001">Figures 1</xref> and <xref ref-type="fig" rid="F0002">2</xref>).</p>
<fig id="F0001">
<label>FIGURE 1</label>
<caption><p>A photomicrograph showing the fibrous connective tissue of the mass in longitudinal section with elongated wavy collagen fibrils and nuclei. (H&#x0026;E &#x00D7;400).</p></caption>
<graphic xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="JSAVA-89-1636-g001.tif"/>
</fig>
<fig id="F0002">
<label>FIGURE 2</label>
<caption><p>A photomicrograph showing the fibroma exhibiting interweaving regions of fairly well-differentiated but monotonous collagenous tissue. (H&#x0026;E &#x00D7;200).</p></caption>
<graphic xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="JSAVA-89-1636-g002.tif"/>
</fig>
<p>Immunohistochemical examination was performed by the avidin&#x2013;biotin complex technique (Haines &#x0026; Chelack <xref ref-type="bibr" rid="CIT0011">1991</xref>) using Polyclonal Rabbit Anti-S100 (Dako Code No. Z0311; Dako, California, United Stated) at the dilution of 1:32 000, after antigen retrieval at pH6, antibody incubation time of 1 hour, and using the Dako Real En Vision Detection System (Ref K5007), to exclude spindle cells of neural origin. The result was diffusely negative when compared with the labelling of a section of spinal cord in which glial cells labelled correctly. This was specifically done to exclude the differential diagnosis of cutaneous schwannoma, which is a benign spindle cell variant of the four subtypes of peripheral nerve sheath tumours, and occasionally seen in the dermis of horses (Higgins et al. <xref ref-type="bibr" rid="CIT0015">2017</xref>; Sch&#x00F6;niger et al. <xref ref-type="bibr" rid="CIT0028">2011</xref>).</p>
<p>The mare was re-examined as an outpatient 14 days later when skin staples and sutures were removed. She was clinically unremarkable, the swelling of the surgical site had resolved and the area was non-painful on palpation. The mare was sound and comfortable when trotted on a straight line on a hard surface. She was maintained in a small paddock and the surgical site monitored for swelling or discharge for 6 weeks. At examination 12 months post-surgery the mare was clinically healthy, the surgical site had healed without tumour recurrence and she remained sound.</p>
</sec>
<sec id="s0004">
<title>Discussion</title>
<p>Fibromas are benign neoplasms composed of fibrous tissue or fully developed connective tissue (Kidd &#x0026; Bradshaw <xref ref-type="bibr" rid="CIT0017">2002</xref>). Fibromas account for between 2.1&#x0025; and 17.1&#x0025; of all equine skin neoplasms (Scott <xref ref-type="bibr" rid="CIT0031">2007</xref>). There has been significant controversy differentiating fibromas from equine sarcoids (Baker &#x0026; Leyland <xref ref-type="bibr" rid="CIT0003">1975</xref>; Valentine <xref ref-type="bibr" rid="CIT0036">2006</xref>) and no breed or sex predilection has been reported (Baker &#x0026; Leyland <xref ref-type="bibr" rid="CIT0003">1975</xref>; De Meyer et al. <xref ref-type="bibr" rid="CIT0008">2017</xref>).</p>
<p>Fibromas have been predominantly reported to be associated with the equine head with affected regions, including the guttural pouch (Merriam <xref ref-type="bibr" rid="CIT0023">1972</xref>), orbit (Colitz et al. 2000), mandible (Morse et al. <xref ref-type="bibr" rid="CIT0024">1988</xref>; Robbins, Arighi &#x0026; Ottewell <xref ref-type="bibr" rid="CIT0027">1996</xref>; Sponseller et al. <xref ref-type="bibr" rid="CIT0033">2006</xref>), maxilla (Kodaira et al. <xref ref-type="bibr" rid="CIT0019">2010</xref>), nasal cavity (Puff et al. <xref ref-type="bibr" rid="CIT0026">2006</xref>) and paranasal sinuses (Cilliers et al. <xref ref-type="bibr" rid="CIT0006">2008</xref>; Dixon &#x0026; Head <xref ref-type="bibr" rid="CIT0009">1999</xref>). These have frequently been ossifying fibromas (Cilliers et al. <xref ref-type="bibr" rid="CIT0006">2008</xref>; Kodaira et al. <xref ref-type="bibr" rid="CIT0019">2010</xref>; Morse et al. <xref ref-type="bibr" rid="CIT0024">1988</xref>; Puff et al. <xref ref-type="bibr" rid="CIT0026">2006</xref>; Robbins et al. <xref ref-type="bibr" rid="CIT0027">1996</xref>; Sponseller et al. <xref ref-type="bibr" rid="CIT0033">2006</xref>).</p>
<p>There are two reports of fibroma associated with the equine abdomen (Tafti, Oryna &#x0026; Maleki <xref ref-type="bibr" rid="CIT0034">1998</xref>; Wilson &#x0026; Sykes <xref ref-type="bibr" rid="CIT0037">1981</xref>), one with the neck (McCauley et al. <xref ref-type="bibr" rid="CIT0022">2002</xref>) and one with the prepuce (De Meyer et al. <xref ref-type="bibr" rid="CIT0008">2017</xref>).</p>
<p>Fibromas associated with the appendicular skeleton have been reported infrequently. These include ossifying fibroma of the proximal tibia (Collins <xref ref-type="bibr" rid="CIT0007">1998</xref>), non-ossifying fibroma of the proximal tibia (Kidd &#x0026; Bradshaw <xref ref-type="bibr" rid="CIT0017">2002</xref>), fibroma of the tendons (Adams, Fessler &#x0026; Thacker <xref ref-type="bibr" rid="CIT0001">1982</xref>) and non-ossifying fibroma of the proximal phalanx (Attenburrow &#x0026; Heyse-Moore <xref ref-type="bibr" rid="CIT0002">1982</xref>). No reports were found of cutaneous or subcutaneous fibroma associated with the limbs.</p>
<p>Fibromas in large animals have been described as solitary, slow growing, well-defined, progressive, round to oval intradermal or subcutaneous masses (Scott <xref ref-type="bibr" rid="CIT0030">1988</xref>). They are usually firm, white to tan on cut surface and well demarcated but not encapsulated in horses (Knottenbelt, Patterson Kane &#x0026; Snalune <xref ref-type="bibr" rid="CIT0018">2015</xref>). Although classified as benign lesions, surgical resection has been recommended and recurrence has been reported with incomplete excision (Colitz et al. 2000). With complete resection, recurrence is rare (Knottenbelt et al. <xref ref-type="bibr" rid="CIT0018">2015</xref>).</p>
<p>Palpation, radiographic examination and ultrasonographic examination of the mass in this case report showed it to be well defined in the subcutaneous tissue overlying the right lateral distal femoral region. The overlying epidermis was intact, was dissected away from the mass and there was no evidence of alopecia, hypopigmentation or ulceration, which have been reportedly associated with fibromas (Scott <xref ref-type="bibr" rid="CIT0031">2007</xref>; Scott &#x0026; Miller <xref ref-type="bibr" rid="CIT0032">2003</xref>).</p>
<p>Histologically, fibroma is characterised by a low number of fibroblasts with interwoven collagen fibres (De Meyer et al. <xref ref-type="bibr" rid="CIT0008">2017</xref>). These fibroblasts are fusiform with a low mitotic index (De Meyer et al. <xref ref-type="bibr" rid="CIT0008">2017</xref>). Collagenous fibres are variable in maturation and have a haphazard orientation (De Meyer et al. <xref ref-type="bibr" rid="CIT0008">2017</xref>).</p>
<p>Essential characteristics of equine sarcoid that differentiate it from fibroma include the hyperplastic, hyperkeratotic epithelial component with typical long, slender extensions (rete pegs) into the proliferating immature dermal fibroblasts (Martens et al. <xref ref-type="bibr" rid="CIT0020">2000</xref>; Taylor &#x0026; Haldorson <xref ref-type="bibr" rid="CIT0035">2013</xref>), which show mitotic figures in a roughly whorled fibrocellular mass (Taylor &#x0026; Haldorson <xref ref-type="bibr" rid="CIT0035">2013</xref>). These were not evident in the current case. Fibromas do not usually have an epithelial component, whereas, below the epithelium in sarcoids, except in nodular or early occult varieties (Mauldin &#x0026; Peters-Kennedy <xref ref-type="bibr" rid="CIT0021">2017</xref>), the superficial fibroblasts classically are orientated perpendicularly to the basement membrane (Bogaert et al. <xref ref-type="bibr" rid="CIT0005">2008</xref>; Bogaert et al. <xref ref-type="bibr" rid="CIT0004">2010</xref>; Martens et al. <xref ref-type="bibr" rid="CIT0020">2000</xref>). Six variants of sarcoid are described, and they are commonly found in various sites on the head, neck, extremities and the ventrum, including the groin. They may occur singly or multifocally (Mauldin &#x0026; Peters-Kennedy <xref ref-type="bibr" rid="CIT0021">2017</xref>). The epidemiology of sarcoid, in contrast to fibroma, is also specific and unique, being associated with bovine papillomavirus (BPV-1, BPV-2 and BPV-13) (Mauldin &#x0026; Peters-Kennedy <xref ref-type="bibr" rid="CIT0021">2017</xref>), with potential risks being genetic haplotype of the horse, the presence of fly vectors and skin trauma (Taylor &#x0026; Haldoson <xref ref-type="bibr" rid="CIT0035">2013</xref>). For this reason, the difference between sarcoid and fibroma can be made based on PCR for BPV.</p>
<p>Schwannomas, a recently recognised and reported differential diagnosis for fibroma and sarcoid, are now classified as a subtype of peripheral nerve sheath tumours (PNST) (Higgins et al. <xref ref-type="bibr" rid="CIT0015">2017</xref>). They are uncommonly recognised in horses, and are solitary, well-demarcated, expansile, usually dermal, spindle cell masses which may be multinodular or single; all 22 cases in one series labelled positively with anti-S100 antibody (Sch&#x00F6;niger et al. <xref ref-type="bibr" rid="CIT0028">2011</xref>). Occasional cutaneous spindle cell tumours in horses that appear histologically to overlap between sarcoid and PNST may variably label with S100 antibody (Drs J. Steyl and S. Clift, Onderstepoort, South Africa, pers. comm., 04 January 2018). The fibroma in the current case was clearly immunohistochemically negative for S100.</p>
<p>Various options have been proposed for the treatment of fibroma in the horse with surgical curettage (Attenburrow &#x0026; Heyse-Moore <xref ref-type="bibr" rid="CIT0002">1982</xref>), radiotherapy (Orsini, Baird &#x0026; Ruggles <xref ref-type="bibr" rid="CIT0025">2004</xref>; Robbins et al. <xref ref-type="bibr" rid="CIT0027">1996</xref>; Wyn-Jones <xref ref-type="bibr" rid="CIT0038">1983</xref>), carbon dioxide laser (McCauley et al. <xref ref-type="bibr" rid="CIT0022">2002</xref>) and cisplatin-containing biodegradable beads (Hewes &#x0026; Sullins <xref ref-type="bibr" rid="CIT0014">2006</xref>) suggested.</p>
<p>To our knowledge, there are no previous reports of limb-associated subcutaneous fibromas (non-ossifying) in the horse. Subcutaneous fibromas should be considered in the differential diagnosis of skin swellings associated with the limbs of horses. Surgical excision of the mass in this case report resulted in a full resolution of the clinical signs and is recommended in the treatment of this form of benign neoplastic mass in horses.</p>
</sec>
</body>
<back>
<ack>
<title>Acknowledgements</title>
<sec id="s20005" sec-type="COI-statement">
<title>Competing interests</title>
<p>The authors declare that they have no financial or personal relationships that may have inappropriately influenced them in writing this article.</p>
</sec>
<sec id="s20006">
<title>Authors&#x2019; contributions</title>
<p>L.A.P. was responsible for the surgical aspects of the case. N.D. and J.W. were responsible for the histological and immunohistochemical examinations.</p>
</sec>
</ack>
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<fn><p><bold>How to cite this article:</bold> Poore, L.A., Duncan, N. &#x0026; Williams, J., 2018, &#x2018;Unilateral subcutaneous fibroma in the distal femoral region of a 5-year-old Nooitgedacht mare&#x2019;, <italic>Journal of the South African Veterinary Association</italic> 89(0), a1636. <ext-link ext-link-type="uri" xlink:href="https://doi.org/10.4102/jsava.v89i0.1636">https://doi.org/10.4102/jsava.v89i0.1636</ext-link></p></fn>
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