Unilateral ovarian leiomyoma and its management in a Friesian mare.
Leiomyomas in the horse are described arising from smooth muscles from all over the body; in the dermis (Bailey 2003), the duodenum (Kasper and Doran 1993), the colon (Watt et al., 2001), the tunica albuginea (Johnson and Steinberg 1989), the cervix (Romagnoli et al., 1987) and especially in the myometrium (Hoffsis et al., 1986, Broome et al., 1992, Berezowski 2002, Janicek et al., 2004).
A neoplastic enlargement of the ovary can be caused either by tumoural changes of follicle or corpus luteum components (granulosa-theca cell tumour, teratoma, dysgerminoma, cystadenoma, cystadenocarcinoma, arrhenoblastoma), or of mesodermal tissue (fibroma, leiomyoma) or the condition can develop after metastasis (lymphoma, melanoma) (Bosu and Smith 1992, Chassy et al., 2002, Westermann et al., 2003, McCue et al., 2006, Schlafer and Miller 2007, Vanhaesebrouck et al., 2010). In extremely rare cases, a congenital hamartoma is diagnosed (Westermann et al., 2003). However, the most common neoplasia of the ovary by far is the granulosa-theca cell tumour, which represents 2.5% of all equine tumours (McCue 1998). Ovarian tumours originating in nongonadal tissues are rare in domestic animals, with the exception of the sow. Hemangiosarcomas are infrequently described (Gruys et al., 1976), but leiomyomas which develop from smooth muscles in the mesovarium have only been reported in the bitch, the queen, the sow, the human and the rat (Chassey et al., 2002) and mare are considered to be exceptional (Zorlu et al., 1993, Kohno et al., 1999, Eker et al., 2006, Moore et al., 2006). Recently, Carstanjen et al. (2008) described a primary fibroleiomyoma of the ovary in the mare. To our knowledge, the present article is the first to present a histologically and immunohistologically confirmed leiomyoma of the ovary in the mare.
An uniparous, thirteen year old Friesian mare was presented with intermittent moderate colic symptoms and an enlarged left ovary. The mare had a foal in the previous year and had not been bred in the current year. The owner had noted some moderate character changes in the mare during the previous year (prolonged oestrus periods and nymphomania during oestrus). During spring of the current year after weaning, she exhibited obvious and extended oestrus periods (up to 10 days long) and on ultrasound examination, an enlarged left ovary due to a large cyst-like structure (>11 cm diameter) was seen. Fourteen days later, the cyst-like structure was still in place and was observed to be causing a displacement of the left ovary to medio ventral. At that time, the mare was injected with 3000 I.U. chorion gonadotrophine (hCG) Chorulon (a) with the intention to stimulate an ovulation of the presumed follicular cyst. Five days later it was clear that the therapy had not worked and she was put on allyltrenbolone for three weeks (30 mg altrenogest SID, Regumate Equine (a)).
In mid summer, the mare was presented at the clinic. She was in good health and good body condition and she had a normal rectal temperature (37.9[degrees]C), pulse frequency (40b/min) and respiration rate (24/min). The capillary refill time was within normal limits (<2 sec) and no enlarged lymph nodes were noted. Abdominal auscultation revealed normal borborygmi on both sides. Ultrasound examination revealed a normal sized right, active ovary (some follicles between 15 and 25 mm, but no corpus luteum) and an enlarged left ovary containing a large anechogenic cystic structure. The cystic wall was rather thin (less than 4 mm) and no obvious vascularisation within the wall and the surrounding stroma could be seen (Power Doppler, 7.5 MHz, Esaote Pie Medical MayLab30). Within the cyst, no specking, fibrin or organisation of the tissue could be visualized by ultrasound. Profound rectal palpation and ultrasound examination revealed no abnormalities either in the other parts of the genital tract or in the remaining abdominal organs.
A left standing flank laparoscopic ovariectomy was performed. Before ligation of the left ovary, the cystic structures were aspirated (550 ml). The ovary was then removed easily. Apart from the large cyst, the macroscopic aspect of the rest of the ovary was of normal size and rather solid without a marked ovulation fossa.
The mare was then given NSAID's (50 mg/ml meglumine, Finadynea) and broad spectrum antibiotics for 5 days. Two months after the operation, the mare was healthy, but still exhibiting long-lasting and excessive oestrus behaviour (up to 10 days) and rather short inter-oestrusintervals (only 10 days). Four months after the operation, the mare was cycling regularly with pronounced oestrus behaviour and normalized inter-oestrus intervals.
Samples of the tumour were fixed in 4% phosphate buffered formalin for 24h and embedded in paraffin wax using standard protocols. Sections of 4 mm tick were stained with haematoxylin and eosin. On histological examination, the biopsies consisted of highly cell dense tissue with interlacing bundles of spindle shaped cells. In between these bundles, moderately high numbers of small blood vessels were present. The spindle shaped tumour cells occasionally formed whorls around some of the small blood vessels. The tumour cells had a fibrilla reosinophylic not well demarcated cytoplasm and an oval or cigar shaped medium-sized nucleus. The chromatin was finely granular and only occasionally a fairly small nucleolus was observed. Very little extracellular matrix was present between the tumour cells. Scattered in the tumour, small areas of necrosis were observed. At the margin of the tumour, there was no capsule. At one side of the tumour, multiple layers of granulosa cells intermingled with some luteinized cells were found. Immunohistochemical staining was done for S100 protein (polyclonal rabbit anti-S100, 1/ 3200, Dakocytomation, Glostrup, Denmark), smooth muscle actin (SMA) (monoclonal mouse anti-human smooth muscle actin, 1/200, Dakocytomation) and Ki-67 (monoclonal mouse antibody Ki67, 1/2, Prosan, Merelbeke, Belgium), using the Envision+ System-HRP (Dakocytomation) and haematoxylin counterstaining for visualisation.
The staining for S-100 was negative, whereas all tumour cells stained intensely positive for SMA (Fig.1). Only 1 to 5 tumour cells per high power field stained positive for Ki-67. On the basis of these observations, the tumour was classified as a leiomyoma.
[FIGURE 1 OMITTED]
The clinical appearance and the cystic nature of the left ovary in this mare, with an active collateral right ovary, could have been caused by an anovulatory follicle or a haematoma (Meinecke 1986), although if this were the case then the ultrasound appearance would have changed over time (McCue 1998, Curtin 2003). Another possibility is that it was caused by a granulosa cell tumour, though this is less plausible with an active collateral ovary present (Bartmann et al., 2001, McCue et al., 2006). Other possible causes include a teratoma (Catone et al., 2004), a cystadenoma (Hinrichs et al., 1989) and apparently, a leiomyoma as well. Normally, a leiomyoma is described as being solid, but in the literature cystic appearances in leiomyomas are described in woman (Kim et al., 2000, Thamboo and Lee 2003, Lerwill et al., 2004). On the other hand, the cyst-like structure in the present case can be independent of the tumour, since it is not discernable from an atretic, anovulatory follicle.
Most ovarian tumours do not produce any hormones, except for the granulosa cell tumour (GCT) and, to a lesser extent the cystadenoma (Hinrichs et al., 1989, McCue et al., 2006). In human medicine, a case of a testosterone producing ovarian leiomyoma due to hilus hyperplasia has been described (Parish et al., 1984), but in horses no similar leiomyo-mashave been described to compare with. The inhibin production of the GCT, which induces the characteristic collateral ovarian atrophy, makes the GCT rather easy to discern from other tumour enlargements of the ovary (McCue et al., 2006, Schlafer and Miller, 2007). All other cystic changes in the ovary are more difficult to distinguish on rectal palpation and ultrasound alone, especially at a given moment in time.
Most of the time, leiomyomas of the ovary in other species are incidental findings without any specific symptomatology, although symptoms can appear as a result of expansive growth of the ovarian tumour, which results in pressure symptoms, abdominal pain and adhesions of the tumour to surrounding structures, for which reason even fertility could indirectly be affected. In the leiomyoma described in this article, as in the ovarian fibroleiomyoma described by Carstanjen et al. (2008), the diagnosis was only determined because the mare was suffering from moderate intermittent colic. Most probably, the leiomyoma cannot be blamed for the irregularity of the oestrus cycle in this case. In the review of Meinecke (1986), a regular cycling mare with a leiomyoma is mentioned. Other ovarian tumours may result in irregular endometrial differentiation and thus endometrial biopsy might have been a possible aid in differentiating the tumour prior to surgery (Bartmann et al., 2001).
In felids, 32% of all genital tract leiomyomas are characterized by a low mitotic rate. In the present case, a moderate to low mitotic rate was determined (1 to 5 tumour cells per hpf stained for the Ki-67). The generalized positive staining for SMA is similar to what was described for the fibroleiomyoma (Carstanjen et al., 2009).
Chassey et al. (2002) saw an increasing incidence of leiomyomas with increasing age. There was no protective effect of parity in the cat as seen in uterine leiomyomas in women (Houston et al., 2001), nor was there a correlation with long-lasting progestin medication as seen in rats (Yamate et al., 1998) and women (Rein et al., 1995). For uterine leiomyomas, there seems to be a familial predisposition in humans (Vikhlyaeva et al., 1995). In horses, there is one report of uterocer-vical leiomyomas having occurred in two half-sibling fillies, which might suggest a hereditary component (Romagnoli et al., 1987). Furthermore, the long-term negative effects of so-called endocrine disrupters have been said to influence the incidence of leiomyomas in mice (Newbold et al., 2007).
In other species, ovarian leiomyomas are often found in combination with an affected contralateral ovary (Boss et al., 1999), with uterine leiomyomas (Norris et al., 1969, Lerwill et al., 2004) or another endometrial pathology (Boss et al., 1999) and in women, with other ovarian tumours (Doss et al., 1999, Lerwill et al., 2004). In the present case, no other pathologies besides endometritis could be found.
In conclusion, ovarian leiomyomas are rare tumours in the mare. The diagnosis of left ovarian leiomyoma in this case was based on histological and immunohistochemical analysis. Unilateral ovariectomy of the affected ovary is the treatment of choice and prognosis as a future broodmare is good with due regard to proper treatment of the endometritis occurring.
The authors would like to thank Dr Ann Martens for her critical review of the article.
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J. Govaere (1), R. Ducatelle (2), J. Declercq (3), M. Hoogewijs (1), A.de Kruif (1)
Faculty of Veterinary Medicine
(1) Department of Reproduction, Obstetrics and Herd Health, e-mail:email@example.com
(2) Department of Pathology, Bacteriology and Poultry Diseases
(3) Department of Surgery and Anaesthesiology of Domestic Animals
(a)-Brand of MSD Ltd., Boxmeer, Netherlands
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|Title Annotation:||Short Communication|
|Author:||Govaere, J.; Ducatelle, R.; Declercq, J.; Hoogewijs, M.; Kruif, A. de|
|Date:||Jan 1, 2012|
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