Mares with ovarian diseases can have a variety of clinical signs (or not). Behavioural abnormalities are one. One should not assume that a mare with abnormal estrous behaviour or aggression has an ovarian disorder.
Huggins et al (2024) found that of 2914 hormone profile samples of mares with behaviour issues, 2506 (84%) did not have hormonal changes to suggest a granulosa cell tumor. Mares with stallion like behaviour are highly likely to have a sex cord stromal tumor based on hormone profile.
Crabtree J. Can ovariectomy be justified on grounds of behaviour? Equine Vet Edu 2015; 28: 58-59.
Huggins L, Norris J, Conley A, Dini P. Abnormal mare behaviour is rarely associated with changes in hormonal markers of granulosa cell tumours: A retrospective study. Equine Vet J. 2024; 56: 759-767.
The dogma is that mares dont develop cystic ovarian disease or folliclular cysts. They are called anovulatory follicles. They can be extremely large!
Anovulatory follicles are follicles that develop but fail to ovulate. They are also called transition follicles.
One of the big conundrums is the presence of many anovulatory follicles and differentiating them from a sex cord stromal tumor - granulosa cell predominent (AKA granulosa cell tumor). This is discussed further in neoplasia below.
Anovulatory follicles are just like regular ovarian follicles, but they fail to ovulate. It is usually a bilateral disease and the ovaries are of a similar size. The hormone profile should be similar to ovarian follicles. A dyssymmetry in size and elevated AMH (>10 ng/ml, highest sensitivity), inhibin and or testosterone would indicate a sex cord stromal tumor.
HAF are anovulatory follicles that develop hemorrhage and become partially luteinised, There is a layer of luteal cells around the periphery and supposedly a thin layer of fibrous tissue internally at the junction of the hemorrhage and the luteal cells. They are also called luteinised unruptured follicles.
The development of HAF can be induced by using prostaglandin inhibitors (COX-2 inhibitors) such as flunixin meglumine when given in conjunction with hCG. (Bashir et al 2016).
Bashir ST, Gastal MO, Tazawa SP1, Tarso SG, Hales DB1, Cuervo-Arango J1, Baerwald AR1, Gastal EL. The mare as a model for luteinized unruptured follicle syndrome: intrafollicular endocrine milieu. Reproduction. 2016; 151: 271-283.
Ellenberger C, Müller K, Schoon HA, Wilsher S, Allen WR.Histological and immunohistochemical characterization of equine anovulatory haemorrhagic follicles (AHFs). Reprod Domest Anim. 2009; 44: 395-405.
Oophoritis is unusual in mares. Here are some exceptions.
Abscessation
Randleff-Rasmussen and Gray (2018) reported on a mare with an abscess of the right ovary. Within the abscess was a wire foreign body.
Randleff-Rasmussen PK, Gray AS. Metallic foreign body in the ovary of a broodmare. Equine Vet Education 2018; 30: 237-240
It is my experience based on years of providing opinions on ovarian changes in different species that the majority of pathologists do no know what a normal ovary in a mare looks like histologically, and with age, cyclicity and various non-neoplastic conditions, the vast majority make incorrect interpretations. I thus consider many reports on equine ovarian disease and especially neoplasia with great suspicion.
The majority of sex cord stromal tumours of the ovary of mares are reported as granulosa cell tumours. Because of this, the majority of reports are about granulosa cell tumours and these will be listed below. Other types of sex cord stromal tumours in the mare will be listed separately.
Kelmer et al (2013) published a surgical paper where 14 ovaries were removed from mares and the histological diagnosis was granulosa cell tumour in 9 cases, an ovarian cyst in 1 and no diagnosis for the others.
Hector and Cruz (2014) report on a single case of an ovarian tumor. This clinical paper had no details of the ovarian tumor apart from the diagnosis.
Sherlock et al (2016) reported on 52 cases of granulosa cell tumors. 60% of them had elevated serum inhibin. 27% were bilateral and those that were unilateral were about equally represented on each side. Only 11% of horses had long term complications and there was no indication of metastatic disease.
Castillo et al (2019) reported on a mare with bilateral granulosa cell tumors. I am unconvinced that this mare has ovarian neoplasia based on the photographs and photomicrographs presented.
Pinna et al (2019) reported on bilateral ovarian tumors - granulosa cell tumors. Their photomicrograph is somewhat believable.
Derick et al (2020) reported on 27 mares what underwent ovariohysterectomy for unwanted behaviour including "general disagreeable demeanour, aggression towards other horses, problems with training, and displaying constant estrus". 83% had an improvement in all specific unwanted behaviour. 90% had some improvement in behaviour. 18 of 27 (67%) had normal ovaries. Five of 27 had unilateral sex cord stromal tumor (granulosa cell tumor and granulosa theca cell tumor was not separated) and four of 27 had bilateral tumors.
Differentiating a sex cord stromal tumor from anovulatory follicles is a conundrum. If there is unilateral enlargement of one ovary and a small contralateral ovary, it is likely that the large ovary has a functional GCT. A multicystic (honeycomb) ovary, a solid mass or an ovary with a single large cyst may be a GCT. Elevated AMH (>10ng/ml) followed by inhibins and then testosterone is supportive (or confirmatory?).
Immunohistochemistry:
Nelissen and Miller reported on the staining of granulosa cell tumors with inhibin and antiMullerian hormone. They found that 18 of 18 tumors stained for AMH and Inhibin.
Granulosa cell type. Granulosa cells stain for vimentin, Ccalretinin, Moesin, P-Eqrin, Anti-Mullerian hormone.
Castillo JM, Tse MPY, Dockweiler JC, Cheong SH, de Amorim MD. Bilateral granulosa cell tumor in a cycling mare. Can Vet J. 2019; 60: 480-484.
Crabtree J. Review of seven cases of granulosa cell tumour of the equine ovary. Vet Rec. 2011; 169: 251.
Devick IF, Leise BS, McCue PM, Rao S, Hendrickson DA. Ovarian histopathology, pre- and post-operative endocrinological analysis and behavior alterations in 27 mares undergoing bilateral standing laparoscopic ovariectomy. Can Vet J. 2020 Feb;61(2):181-186.
Dolin A, Schweiger P, Waselau M, Egerbacher M,Walter I. Immunohistochemical markes for equine granulosa cell tumors: a pilot study. J Equine Sci 2023; 34 37-46
Hector RC, Cruz AM (2014) Ascites in a 13-year-old miniature horse mare with an ovarian granulosa theca-cell tumour: A manifestation of Meigs' syndrome? Equine Vet Educ 2014; 26: 237-241
Kelmer G, Raz T, Berlin D, Steinman A, Tatz AJ. (2013) Standing open-flank approach for removal of enlarged pathologic ovaries in mares. Vet Rec 2013, 172
Nelissen S, Miller AD. Comparison of anti-Müllerian hormone and inhibin immunolabeling in canine and equine granulosa cell tumors. J Vet Diagn Invest. 2022 Sep 14:10406387221124589. doi: 10.1177/10406387221124589. Epub ahead of print. PMID: 36113168.
Pinna AE, Okada CTC, Ferreira CSC, Campos DG, Possidente KS, de Cássia C L Morais R, Oliveira M, Salomão MC, Hataka A. Double ovarian tumour in the mare: Case report. Reprod Domest Anim. 2019; 54: 912-916.
Renaudin CD, Kelleman AA, Keel K, McCracken JL, Ball BA, Ferris RA, McCue PM, Dujovne G, Conley AJ. Equine granulosa cell tumours among other ovarian conditions: Diagnostic challenges. Equine Vet J. 2020.
Sherlock CE, Lott-Ellis K. Bergren KA , Wither JM, Fews D, Mair TS. Granulosa cell tumours in the mare: A review of 52 cases. Equine Veterinary Education 2016; 28: 75-82.
Luteoma
Combs et al reported on 2 mares with luteomas. Each was in a small ovary - the other was normal! They had stallion like behaviour and there was elevated inhibin B. One had increased AMH. One ovary had an 8 mm nodule and a high power photomicrograph was provided. The other mare had 2-16 mm follicles but not mass. They found a structure they considered to be a luteoma.
Combs E, Beachler T, Troy JR, Olds-Sanchez A, Howard JM, Fales-Williams A, Yaeger M, Tatarniuk DM. Luteoma in two mares treated by ovariectomy. Equine Vet Educ 2022: 34: e318-e322.
Epithelial tumours
Epithelial neoplasms of the mare are very rare. There are different types reported.
Son et al (2005) reported on a mare with what they believed to have a cystadenocarcinoma. No additional testing was done to confirm this.
Browne et al (2016) reported on a mare with metastatic carcinoma proportedly from the ovary. The left ovary was enlarged to 24cm and was 5kg in weight. The carcinoma of the ovary produced tubules and had a solid phenotype. They were PanCK postitive and vimentin and inhibin negative. The mare had hypertrophic osteopathy.
Browne NS, Scarratt WK, Robertson J. Hypertrophic osteopathy secondary to metastatic ovarian adenocarcinoma in a mare. Can Vet J. 2016; 57: 1237-1241.
Son YS, Lee CS, Jeong WI, Hong IH, Park SJ, Kim TH, Cho EM, Park TI, Jeong KS. Cystadenocarcinoma in the ovary of a Thoroughbred mare. Aust Vet J. 2005; 83: 283-284.
Dysgerminoma
Teratoma
All germ cell tumors are rare, however teratomas are the more common type.
Duarte et al (2022) reported 5 potential cases, 3 of which were confirmed.
Duarte L, Allen WR, Guime M, Lores M, Wilsher S. Equine ovarian teratomas: Diagnostic challenges illustrated by case reports. Equine Vet Educ 2022; 34: e393-e405
Teratocarcinoma
Charles (2020) reported a single case of ovarian teratocarcinoma. It was about 50 cm diameter, there were nodules in the surrounding fatty tissue. The anaplastic tissue was the epithelial tissue. The cartilage and respiratory tissue was well differentiated.
Charles LN. Metastatic Ovarian Teratocarcinoma in a Horse. J Comp Pathol. 2020; 181: 68-72.
Frazer GS, Robertson JT, Boyce RW. Teratocarcinoma of the ovary in a mare. J Am Vet Med Assoc. 1988; 193: 953-955.
I remain very sceptical about some of the reports of stromal tumors of the ovary of horses. Many pathologists unaware of the normal ovarian features misdiagnose normal as neoplasia. It is the most common second opinion I get about ovarian 'disease' in the mare, and the majority of times, the ovaries are normal. Normal ovarian stroma looks like a stromal neoplasm like a smooth muscle tumour.
Daniel et al (2015) reported bilateral leiomyomas in a mare with behavioural issues. No lesions were seen on ultrasound. The putiative neoplastic cells surrounded many follicles! I am not convinced this mare had a neoplasm. The photomicrographs looked like normal ovarian stroma. They used smooth muscle actin to confirm, but ovarian stroma contains SMA positive cells normally.
Daniel A, McCue P, Ferris R, Miller C, Leise B. Bilateral ovarian leiomyoma treated by standing laparoscopic ovariectomy Equ Vet Educ 2015; 27: 510-514