This page is part of the site called Surgical Pathology of the Canine Female Reproductive Tract by

Dr Rob Foster

Disease of the Canine Ovary and Mesovarium

Table of Contents

Ovarian diseases

The following are some of the ovarian diseases I have seen, to give you an indication of what to expect. These were mostly submitted because the practitioner saw something unusual at ovariohysterectomy. These cases are from YagerBest Surgical Pathology (now owned by Antech Canada Inc) and are up to 2009.

GENERAL SURVEYS

Maya-Pulgarin et al (2018) reported on lesions in the reproductive tracts of 76 bitches with macroscopic lesions of the reproductive tract selected from 3600 bitchs who had ovariohysterectomies in Colombia. They found hyperplasia of rete ovarii, follicular cysts, oophoritis, adenoma of the rete ovarii, cysts of superficial structures, and granulosa cell tumors in 10.5%, 10.5%, 7.9%, 4.0%, 2.6%, and 2.6%, respectively. 

Maya-Pulgarin D, Gonzalez-Dominguez MS, Aranzazu-Taborda D, Mendoza N, Maldonado-Estrada JG. Histopathologic findings in uteri and ovaries collected from clinically healthy dogs at elective ovariohysterectomy: a cross-sectional study. J Vet Sci 2017; 18: 407-414

CYSTS OF THE OVARY AND SURROUNDS

Intraovarian cysts

 

Defining what is a cyst and what is a normal structure (follicles are 'cysts') is problematic. This is especially the case with follicles and those unique structures of the bitch, the subsurface epithelial structures. If one uses the statistical basis for defining the reference range of normal, being 2 standard deviations above and below the mean, then we have a starting point. Abnormal cysts within the ovary are numerous - the most common are cystic rete ovarii. This is followed by cystic corpus luteum and then by follicular cysts and luteinised cysts.

Knauf et al 92014) examined ovarian cysts by macroscopic evaluation and aspiration of cysts to determine the concentration of hormones estrodiol 17B and progesterone and compare with serum concentration. The concentration in cyst fluid was related to serum levels, and varies from cyst to cyst, but could alter ovarian function.

Knauf Y, Bostedt H, Failing K, Knauf S, Wehrend A. (2014) Gross Pathology and Endocrinology of Ovarian Cysts in Bitches. Reprod Dom Anim 2014; 49: 463–468.

Cystic rete ovarii

McEntee (1990) defines these as dilation of the rete tubules (see normal) , and not of the mesonephric tubules (compare with normal development of the rete in the section on normal development), which have a smooth muscle wall. Because the rete tubules may communicate with the mesonephric tubules, both may dilate simultaneously. The rete tubules are within the medulla of the ovary at the hilus (where the vessels enter the ovary) and they can extend into the mesovarium. According to Anderson and Simpson (1973) cystic rete ovarii occur in up to 10% of older dogs.

It would seem reasonable that, in order to be consistent, those cysts of the medulla and hilus of the ovary with an epithelial lining and without a smooth muscle coat be termed 'cystic rete ovarii' whereas those with a smooth muscle wall be called cystic mesonephric tubules. This is what I use.

Cysts of the rete ovarii can become up to several centimeters in diameter. When large, they compress the ovarian cortex. There is almost always multiple variably sized cysts. Rarely do adenomas and carcinomas develop from these.

Dow (1960) reported seeing these cysts in 9 of 400 animals. They were unilateral.

Akihara et al (2007) evaluated different cystic structures in the ovary by immunohistochemistry for placental alkaline phosphatase (PLAP), S100, inhibin, Desmin and AE1/AE3 cytokeratin. Ther found 12 of 109 cysts to be cystic rete ovarii. The epithelium of cystic rete ovarii were all negative for PLAP and inhibin, all were positive for AE1/AE3, and variably stained for S100 and Desmin.

 

Subgross photograph of an ovary with multiple cystic rete ovarii

Compressed ovarian cortex of a dog with a large cystic rete ovarii (bottom). The ovarian surface epithelium is the upper line, epithelium of the rete cyst is at the bottom.

 

Akihara Y, Shimoyama Y, Kawasako K, Komine M, Hirayama K, Kagawa Y, Omachi T, Matsuda K, Okamoto M, Kadosawa T, Taniyama H. (2007). Immunohistochemical evaluation of canine ovarian cysts. J Vet Med Sci 2007 69(10): 1033-1037.

Anderson AC Simpson ME (1973) The ovary and reproductive cycle of the dog (Beagle). As quoted by McEntee K (1990) Reproductive Pathology of Domestic Mammals. Academic Press.

McEntee K (1990) Reproductive Pathology of Domestic Mammals. Academic Press p61

.

Cystic subsurface epithelial structures

Cysts of the subsurface epithelial structures in the dog are dilations of the normally occuring subsurface epithelial structures (for normal see here), thus they occur along the ovarian surface beneath the ovarian epithelium. They are similar to epithelial inclusion cysts of other species - except that the dog normally has 'downgrowths' of the surface epithelium. McEntee (1990) reports that they are not seen in young bitches but occur with increasing frequency in older dogs. They are seldom larger than 5 mm. They are lined by a single layer of cuboidal cells.

Dow (1960) reported seeing 20 bitches with ovarian changes that he called 'germinal cysts' that have the idential location and appearance as cystic SES. Some of his follicular cysts may also have been these too.

Akihara et al (2007) found these to be the most numerous cysts of the canine ovary. They found 57 in 109 cysts. They stained for desmin (96%), AE1/AE3 (93%) and placental alkaline phosphatase (19%). Inhibin was consistently negative.

We record only a low number of these, possibly because our population tended to be younger dogs.

Cysticly dilated subsurface epithelial structures. These would be barely visible grossly.

Cystic subsurface epithelial structures. This degree of cystic dilation was visible as multiple cysts.

Akihara Y, Shimoyama Y, Kawasako K, Komine M, Hirayama K, Kagawa Y, Omachi T, Matsuda K, Okamoto M, Kadosawa T, Taniyama H. (2007) Immunohistochemical evaluation of canine ovarian cysts. J Vet Med Sci. 2007 69(10):1033-1037.

Dow C, (1960) Ovarian abnormalities in the bitch. J Comp Path 1960, 70: 59-69

McEntee K (1990) Reproductive Pathology of Domestic Mammals. Academic Press p60-61

Follicular cysts

Surprisingly little is recorded about ovarian follicular cysts. Dow (1960) reports on the histology of follicular cysts. He reported them as having either a lining of granulosa cells, a single flattened layer or a sclerotic wall. McEntee (1990) reports some of the information and more recently, Akihara et al (2007) reports on the immunohistochemistry of ovarian cysts.

A follicular cyst is a cyst resembling a Graafian follicle that is larger than a normal follicle. One must know the size of a normal follicle before this diagnosis can be made (see normal female dog). I also feel comfortable calling a structure a follicular cyst if it is much larger than the surrounding follicles. 'Much larger' then becomes a subjective call! something that I hate to do. It is also important to correlate clinical parameters (signs of follicular cysts including prolonged estrus) with the histological.

Follicular cysts are lined by granulosa cells, or a Dow (1960) contends, larger cysts have a layer of cuboidal or flattened cells, and some only have a hyalinised wall.

Dow (1960) reported finding solitary follicular cysts in 41 and multiple in 22 of 400 dogs examined.

Akihara et al (2007) examined 109 ovarian cysts and found that 26 follicular cysts representing 24% intraovarian cysts.We found a much smaller number. follicular cysts were lined by granulosa cells that stained for inhibin, but not for other antigens like S100, placental alkaline phosphatase, desmin, and AE1/AE3.

Walter et al (2018) examined ovaries from 30 dogs with supposed ovarian disease. Supposed follicular cysts were found that were 0.2 to 5 cm. with an average of 1cm!

Knauf et al (2018) reported on a study of the ovaries of 21 female dogs with 'gynecopathies', mostly vaginal discharge. Their definition of an ovarian cyst was we defined an 'a fluid-filled cavity [25] of any size present outside the physiological estrus cycle and located within or on the ovary's surface'. Their definition does not include size. They report finding 61 follicular cysts, 13 lutein cysts and 9 nonclassifable cysts. They also found 72 cystic subsurface epithelial structures and 38 cystic rete ovarii.

Jisna et al (2021) reviewed ovarian cysts. They defined ovarian (follicular cysts) as "...fluid filled structures of variable size that are unilateral or bilateral ...". They considered they arise from a lack of LH surge or local deficiencies in homeostasis imparing receptivity to LH.

 

Large follicles. When they are larger than normal they are called follicular cysts.

Photomicrograph of cystic follicles. This bitch had many cystic follicles.

Akihara Y, Shimoyama Y, Kawasako K, Komine M, Hirayama K, Kagawa Y, Omachi T, Matsuda K, Okamoto M, Kadosawa T, Taniyama H. (2007) Immunohistochemical evaluation of canine ovarian cysts. J Vet Med Sci. 2007 69(10):1033-1037.

Dow (1960) abnormalites of the canine ovary. J Comp Pathol (1960) 70: 52-56

Jisna KS, Patra MK, Singh LK, Saxena AC, De UK, Singh V, Karikalan M, Kumar H, Krishnaswamy N. Ovarian cysts in the bitch: An update. Top Companion Anim Med. 2021

Knauf Y, Kohler K, Knauf S, Wehrend A. Histological classification of canine ovarian cyst types with reference to medical history. J Vet Sci 2018; 19: 725-734.

McEntee K (1990) Reproductive Pathology of Domestic Mammals. Academic Press p57

Walter B, Coelfen A, Jäger K, Reese S, Meyer-Lindenberg A, Aupperle-Lellbach H. Anti-Muellerian hormone concentration in bitches with histopathologically diagnosed ovarian tumours and cysts. Reprod Dom Anim 2018; 53: 784–792.

Luteinised cysts

A luteinised follicle is a cystic follicle that has luteinised. They are large follicles (too large for normal) have a cystic centre and a thin layer of luteal cells at the periphery. They are uncommon in the bitch. (McEntee 1990). I have only seen a couple convincing examples.

Dow (1960) found luteinised cysts in 9 of 400 bitches.

Marino et al (2009) in the proceedings of the ESVP/ECVP reports the results of examination of 462 female genital tracts. Cystic structures larger than 8 mm were considered cysts. They found 17 'stromal cysts' of which most were luteinised cysts. They expressed alfa inhibin. They considered separation of follicular and luteinised cysts of no use.

Walter et al (2018) reported finding 7 luteinised cysts in 63 abnormal ovaries. Their definition was difficult to justify.

Knauf reported on a study of the ovaries of 21 female dogs with 'gynecopathies', mostly vaginal discharge. Their definition of an ovarian cyst was we defined an 'a fluid-filled cavity [25] of any size present outside the physiological estrus cycle and located within or on the
ovary's surface'. Their definition does not include size. They report finding 61 follicular cysts, 13 lutein cysts and 9 nonclassifable cysts. They also found 72 cystic subsurface epithelial structures and 38 cystic rete ovarii.

 

photograph of a luteinised cyst. A follicular cyst fails to completely luteinise to produce this.

The histology of a luteinised cyst is the same as a cystic corpus luteum, except that the luteinised cyst is larger than normal..

Dow C, (1960) Ovarian abnormalities in the bitch. J Comp Path 1960, 70: 59-69

Knauf Y, Kohler K, Knauf S, Wehrend A. Histological classification of canine ovarian cyst types with reference to medical history. J Vet Sci 2018; 19: 725-734.

Marino G, Mannarino C, Di Prima ML, Rizzo S, Zanghì A. (2009) Stromal Cysts in the Canine Ovary J Comp Pathol (2009) 141: 297

Walter B, Coelfen A, Jäger K, Reese S, Meyer-Lindenberg A, Aupperle-Lellbach H. Anti-Muellerian hormone concentration in bitches with histopathologically diagnosed ovarian tumours and cysts. Reprod Dom Anim 2018; 53: 784–792.

Cystic corpora lutea

This is a somewhat controversial 'lesion'. A cystic corpus luteum is a corpus luteum that has failed to completely luteinise, and is formed by incomplete luteinisation of a follicle. The controversial nature of their existence is that in the dog, all corpora lutea, as they develop, have a cystic centre that eventually fills in, so some would say that all corpora lutea are cystic in the early phase! A cystic corpus luteum occurs then when one or more fail to completely luteinise. I have heard that these are anovulatory follicles that luteinise as they apparently have oocytes in the central cavity. They have no clinical significance. I have seen many ovaries where there is one follicle that fails to completely fill with luteal cells while the others do so. This is a histological diagnosis and a curiosity.

Normal ovary with corpora lutea with a cystic centre (cystic corpus luteum)

 

Dow (1960) reported that all corpora lutea have a central cystic region for a short time.

Dow C, (1960) Ovarian abnormalities in the bitch. J Comp Path 1960, 70: 59-69

Extraovarian (periovarian, paraovarian) cysts

There are 3 basic types of cysts within the structures around the ovary - paramesonephric duct cysts, mesonephric duct cysts and mesonephric tubule cysts. Although very rare, a bursal cyst can occur also (see below). If you want to drive yourself to distraction, try to separate extraovarian cysts into these 3 categories and repete, and see how many you recategorise the next day! Location is by far the best guide, but even then, be prepared to be humbled! These are embryonic structures and differentiation is based on environment and other factors.

Theoretically, the following table should help.

I have not seen this written anywhere, but those cysts derived from ducts should be solitary or in a chain. Those that are multiple in the location of the mesonephric tubules (mesovarium or hilus of the ovary) should be cystic mesonephric tubules. This is particularly likely if they are close to and even connected to the rete ovarii. The significance of cystic embryonic structures? They are benign and are a major differential diagnosis for cystadenomas and cystadenocarcinomas.

Kim et al (2012) reports on a single large distended cyst that had a structure of a distended uterus. They called this a parovarian cyst - a cystic remnant of the paramesonephric duct.

Here are some examples of periovarian cysts.

 

Solitary cystic mesonephric tubule

Photomicrograph of cystic mesonephric tubule with ciliated epithelial lining and smooth muscle wall.

Photomicrograph of multiple cysts of mesonephric tubules

Kim H, Choi H, Kim H, Choi J (2012) .A giant parovarian cyst in a dog with a granulosa cell tumor. J Vet Med Sci 2012, 74(3): 385-389

Unknown cysts

Sontas et al 2011 reported on a dog with a very large cyst in the region of the right ovary of a dog that was previously spayed but which had a contralateral ovary. The structure was muliloculated and epithelial lined. It had a smooth muscle wall. They called it an ovarian cyst. My thoughts after examining their photographs was that this was extreme hydrosalpynx in ovarian remnant syndrome.

Knauf reported on a study of the ovaries of 21 female dogs with 'gynecopathies', mostly vaginal discharge. Their definition of an ovarian cyst was we defined an 'a fluid-filled cavity [25] of any size present outside the physiological estrus cycle and located within or on the
ovary's surface'. Their definition does not include size. They report finding 61 follicular cysts, 13 lutein cysts and 9 nonclassifable cysts. They also found 72 cystic subsurface epithelial structures and 38 cystic rete ovarii.

 

Knauf Y, Kohler K, Knauf S, Wehrend A. Histological classification of canine ovarian cyst types with reference to medical history. J Vet Sci 2018; 19: 725-734.

Sontas BH, Milani C, Romagnoli S, Bertolini G, Caldin M, Caliari D, Zappulli V, Mollo A. (2011) A Huge Ovarian Cyst in a Hysterectomized Bitch. Reprod Dom Anim 2011, 46: 1107-1111

HYPERPLASIA of OVARIAN STRUCTURES

Granulosa cell hyperplasia

Granulosa cell hyperplasia is seen in 2 main situations - in ovarian remnants and in older dogs with low numbers of ovarian follicles, especially primordial and primary follicles. I will speak to the latter here. I suspect the pathogenesis is the same for ovarian remnants.

The granulosa cell hyperplasia I speak of here is in normal sized follicles. The lining cells of the follicles are of the granulosa cell type but they are hypertrophied in comparison to normal granulosa cells. The granulosa cell lining of the follicles is undulating and papillary. The formation of the papillary structures appears to be the result of increased numbers of cells yet throughout all of the follicle they maintain the same number of cells thick and roughly the same overall thickness of wall. I am even more convinced of this diagnosis considering you indicate there are multiple of these.

This is different to hyperplasia of the rete ovarii that occurs normally in older dogs

Hyperplasia of subsurface epithelial structures.

Subsurface epithelial structures are unique epithelial structures in the capsule of the ovary that appear to be downgrowths of the ovarian epithelium. They are present in every canine ovary. These can become cystic and when they do the lumen is clear and the cells lining them are either normal, attenuated, or larger than normal and cuboidal or even columnar. There appears to be transition towards structures that then develop papillae and these are lined by epithelial cells identical to those seen in the variations of subsurface epithelial structures including cystic change. Sometimes an eosinophilic matrix is present in the stroma just beneath the epithelium. There also appears to be a transition to marked hyperplasia with the formation of multiple nodules composed of well-differentiated epithelial cells that are either papillary or sometimes tubular. A transition to "adenoma" occurs but the separation between hyperplasia and adenoma is not known by me and it is not reported. My observation is that with epithelial proliferation the content of these structures becomes hypereosinophilic and I use this in part as a means of separating hyperplasia from adenoma. Distinct and unequivocal neoplasms have this content. Adenomas still have well differentiated epithelium although the nuclear to cytoplasmic ratio is different, the cell size is different and subtle nuclear features are different to the hyperplastic lesions. These structures can grow to a large size and when they fulfil my criteria of adenoma, one then considers whethe they could be carcinoma. After all, the sites of the genesis of carcinomas.

Hyperplasia of the Rete Ovarii

The normal rete ovarii causes considerable constination amongst pathologists who rarely see canine ovaries. Even in some, the enlargement in size of the rete ovarii is mistaken for neoplasia. For example, Matos et al (2019) reported on finding a large number of subclinical and microscopic granulosa cell tumors in the ovaries of a large number of bitches. I am unconvinced.

It is common to see hyperplastic changes in the rete ovarii of bitches as they age. Considering how rare Sex Cord Stromal Tumors of dogs is, I do not regard these as preneoplastic.

Matos ACHDS, Leite JDS, Consalter A, de Mello MFV, de Lourdes Gonçalves Ferreira M, Fosenca ABM, Ferreira AMR. Histopathological findings in the early diagnosis of granulosa cell tumour in bitches. Reprod Domest Anim. 2019; 54: 828-834.

 

OVARIAN NEOPLASIA

I once thought that identifying the phenotype of a mass or abnormal cell population in the ovary was simple and straight forward. I am now much more cautious. Some neoplasms of the ovary are simple, but others are very complex. The complexity is based on the potential for ovarian tumours to express whatever phenotype they wish. After all, the ovary begins embryologically as mesenchyme and mesothelium of the gonadal ridge, and is populated with 'germ' cells, and becomes epithelial tissue, stromal tissue, rete ovarii, endocrine tissue, blood vessels, and many other phenotypes. Neoplasms have traditionally been divided into groups based on phenotype, and now immunohistochemistry assists us, especially in those neoplasms where their phenotype is not obvious.One thing that is not specifically mentioned in ovarian neoplasia is the fact that in every case I have seen, the ovary expands, but remains, often completely, but always largely, within a stretched ovarian bursa. This is important in distinguishing ovarian neoplasia from neoplasia of the ovarian bursa or uterine tube and mesosalpynx.

This is the general rule that I currently use to separate out hyperplasia of subsurface epithelial structures, adenoma, intraovarian adenocarcinoma and extraovarian adenocarcinoma. This scheme is based on the human method for differentiating these.
Hyperplasia of subsurface epithelial structures is a circular noninvasive proliferation of epithelium that forms cysts, papillae and tubular forms. Mitoses are rare and there is minimal basement membrane material or secretion visible.
Adenoma has a single layer of epithelium lining tubules, papillae or the cysts. Anisokaryosis is minimal and there is usually basement membrane material or secretion present.
Intraovarian adenocarcinoma is when there is invasion, piling up of epithelial cells so they are more than one or two cells thick lining the tubules or papillae, and if the mitotic count is above six per 10 high-power fields.
Extraovarian adenocarcinoma is when the lesion within the ovary has broken through the capsule onto the surface of the ovary or is within the bursa.

'Clinical' Study Prevalence

Cotchin E. (1961) Canine ovarian neoplasms. Res Vet Sci 1961, 2: 113-142.

Dow C (1960) Ovarian abnormalities in the bitch. J Comp Path 1960 70: 59-69

Norris HJ, Garner FM, Taylor HB. (1970) Comparative pathology of ovarian neoplasms. IV Gonadal stromal tumors of canine species. J Comp Path 1970, 80: 399-405

Patniak AK, Greenlee PG (1987). Canine ovarian neoplasms: a clinicopathologic study of 71 cases, including histology of 12 granulosa cell tumors. Vet Pathol 1987, 24: 509-514.

Sforna M, Brachelente C, Lepri E, Mechelli L (2003) Canine Ovarian Tumours: a retrospective study of 49 cases. Vet Res Commun (2003) 27 Suppl 1: 359-361

Goto S, Iwasaki R, Sakai H, Mori T. A retrospective analysis on the outcome of 18 dogs with malignant ovarian tumours. Vet Comp Oncol. 2021; 19: 442-450.

 

Epithelial neoplasia of the ovary

Epithelial tissues of the ovary in the dog includes the surface 'germinal epithelium', which is modified mesothelium, subsurface epithelial structures derived from the surface epithelium, and the rete ovarii derived from mesonephric tubules and or cords. Many tumours obviously occur in subsurface epithelial structures and they are often multifocal. Others appear to only involve the germinal epithelium, but lets face it, few of us take multiple or serial sections of ovarian masses to completely characterise neoplasms.

According to the World Health Organisation publication, Tumours of the Genital System, the types of epithelial neoplasms of the ovary are (1) papillary adenoma and cystadenoma, (2) papillary adenocarcinoma and (3) rete adenoma. Papillary adenomas are smooth and nodular or papillary and are within distended subsurface epithelial structures, are often multiple and are composed of small cuboidal or cylindrical cells that may have cilia. Mitoses are rare. They may have a glandular or cystic appearance. Papillary carcinomas have a shaggy appearance, increased mitotic activity, invasion into the ovarian stroma and extension into the ovarian bursa. Most important is the statement 'distinguishing between them can be difficult". My observation is that epithelial tumours of the surface or SES progress from papillary hyperplasia to adenoma to carcinoma, and all 3 forms can sometimes be identified in the same ovary. It is no wonder that classification can be difficult.

As with most studies, the categorisation of epithelial tumours is based on their histological appearance, and not on their clinical behaviour. The separation of epithelial tumours into 'benign' and 'malignant' phenotype is therefore subjective. To add to this subjectivity is the separation of neoplasms into papillary and cystic types when most have a combination of both phenotypes, plus solid areas. Where available, I have included the published prognosis. There needs to be a detailed long term followup of epithelial ovarian tumors in dogs to accurately predict outcome for individual cases.

The normal staining patterns of the canine ovary is reviewed in 'the normal canine ovary'

 

Kennedy PC, Cullen JM, Edwards JF, Goldschmidt MH, Larsen S, Munson L, Nielsen S. (1998) Histological classification of Tumors of the Genital System of Domestic Animals. 2nd ed. 1998. Armed Forces Institute of Pathology, American Registry of Pathology, and The World Health Organization Collaborating center for Worldwide Reference on Comparative Oncology. Washington DC.

Immunohistochemistry

There are several studies that report immunohistochemical staining of ovarian neoplasms including epithelial tumours. For the immunohistochemical staining of normal ovarian structure, see normal ovary.

The staining pattern of normal epithelium includes positivity for cytokeratin 7, cytokeratin AE1/AE3, and for vimentin. The epithelium should not stain for inhibin. Thus epithelial tumours should have a similar staining pattern. Tissues with a sex cord stromal phenotype may be AE1/AE3 and vimentin positive also. Riccardi et al (2007) found interesting results. They had neoplasms diagnosed as carcinomas - examples that histologically were identified as carcinomas that did not stain for CK7 and were inhibin positive. They reclassified them as 'granulosa cell tumours'. This reclassification, based on immunohistochemistry, was not accompanied by any prognostic outcome or other verification. Almost all of their cases were cytokeratin AE1/AE3 positive, including granulosa cell tumours.

Akihara ete al (2007) also examined ovarian neoplasms immunohistochemically. They classified the tumours histologically and found that all or their carcinomas were positive for AE1AE3, desmin.and vimentin. 2 of the 6 were negative for CK7 and placental alkaline phosphatase (PLAP) - the others were positive. All were negative for inhibin. They had no sex cord stromal tumours with CK7 staining and they had 6 of 18 that did not stain for inhibin alpha.

Banco et al (2011) performed a study with a stained ovarian tumours for an antigen called Hector Battiflora mesothelial epitope (HBME)-1 which is a news epithelial marker. They found that normal ovarian surface epithelium and 17 of 18 epithelial tumours were positive. No gonadal stromal tumours were positive.all of their gonadal stromal tumours were positive for inhibin alpha, but no epithelial tumour stain with this antibody.

What do we do with this information. I suggest we use histology be our first guide. If it is CK7 positive, it is (probably) a carcinoma. If it is inhibin alpha positive it is a sex cord stromal neoplasm, and if it is negative for both, go by the histology!

Akihara Y, Shimoyama Y, Kawasako K, Komine M, Hirayama K, Terasawa A, Ohmachi T, Matsuda K, Okamoto M, Taniyama H. (2007) Histological and immunohistochemical evaluation of canine ovary. Reprod Domest Anim. 42(5): 495-501.

Banco B, Antuofermo E, Borzacchiello G, Cossu-Rocca P, Grieco V. (2011) Canine ovarian tumors: an immunohistochemical study with HBME-1 antibody. J Vet Diagn Invest 2011, 23: 977-981

Riccardi E, Greco V, Verganti S, Finazzi M. (2007) Immunohistochemical diagnosis of canine ovarian epithelial and granulosa cell tumors. J Vet Diagn Invest 19: 431-435

 

Adenoma

The classification of a neoplasm as an adenoma implies a benign behaviour and a well differentiated phenotype, lack of aggressive features such as invasion, and a low mitotic count. Cyst adenoma and papillary adenoma are the main types, but this is artificial as most have features of both. The names are arbitarily given based on the dominant appearance. The so-called papillary adenomas are located at the periphery of the ovary, and often in the SES. They are often multiple, vary in size from microscopic to macroscopic and should not spread/metastasise. There is an apparent gradation from hyperplasia to adenoma of the epithelium. This is problematic as seeding to the peritoneum should be easy given their peripheral location on the ovary - which is in almost direct contact with the abdominal cavity. The term cystadenoma is also used but most adenomas are a mixture of these and other phenotypes including solid tumours. There are many cases where the formation of neoplasms of the ovary are multifocal - multiple microscopic examples are seen in the same section.

All studies that report laterality indicate that these are unilateral tumours (Dow 1960, Patniak and Greenlee 1987, this series)

Dow (1960) found 10 of 11 epithelial tumours to be adenomas. They had one carcinoma. All were unilateral and many were multifocal. Two were called mucinous cystadenomas as they had goblet cells within the lining epithelium of the cysts.

Cotchin (1961) found 20 adenomas in 69 bitches. The largest was 17 cm diameter. 16 of the 20 were 'intracystic papillary adenomas'. 2 had large numbers of eosinophils. One looked very like a granulosa cell tumour.

Norris et al (1970) reports on 20 cystadenomas.

Patniak and Greenlee (1987) found 12 of 33 epithelial neoplasms to be adenomas. All were unilateral, and none were metastatic.

Sforna et al (2003) found 21 cases of adenoma. They were smaller than carcinomas and where not associated with abdominal effusion. Endocrine disorders consistent with hyperestrogenism were seen with some.Cotchin E. (1961) Canine ovarian neoplasms. Res Vet Sci 1961, 2: 113-142.

Cystadenoma of the ovary

Wall of cystadenoma of ovary. Well differentiated flattened epithelium lining fluid filled spaces (protein visible on left).

Papillary adenoma of the ovary arising in a subsurface epithelial structure.

Dow C, (1960) Ovarian abnormalities in the bitch. J Comp Path 1960, 70: 59-69

Norris HJ, Garner FM, Taylor HB. (1970) Comparative pathology of ovarian neoplasms. IV Gonadal stromal tumors of canine species. J Comp Path 1970, 80: 399-405

Patniak AK, Greenlee PG (1987). Canine ovarian neoplasms: a clinicopathologic study of 71 cases, including histology of 12 granulosa cell tumors. Vet Pathol 1987, 24: 509-514.

Sforna M, Brachelente C, Lepri E, Mechelli L (2003) Canine Ovarian Tumours: a retrospective study of 49 cases. Vet Res Commun (2003) 27 Suppl 1: 359-361

Ovarian Adenocarcinoma

Carcinomas are classified as such based on aggressive features such as invasion of the stroma, spread to the bursal tissues and abdomen. They have many mitoses, but noone has quantified this! The phenotype of cytic, papillary or solid subtypes is difficult to justify as most have components of all three but to varying degrees. My personal preference is to just call them ovarian carcinomas, as I see no trend or indication about differences in metastatic potential between the different subtypes. A good study with large numbers is desparately required. Carcinomas, expecially the more solid types, are sometimes impossible to differentiate from some sex cord stromal tumours (granulosa cell tumours). I have seen tumors that have the classical appearance of carcinoma but which did not stain with CK7 or AE1/AE3. Thus they should all be confirmed using immunohistochemistry for different cytokeratins and inhibin. This problem with confirmation makes one view publications with a more critical view.

Studies indicate that these can be bilateral. Patniak and Greenlee (1987) found 5 of 18 to be bilateral. Five of 40 in this series were reported by the submitting veterinarians to be bilateral.

One of 11 epithelial neoplasms found by Dow (1960) was a carcinoma. This carcinoma, was widely metastatic including peritoneal carcinomatosis.

Cotchin (1961) reported 5 of 69 ovarian tumours were carcinomas. Two bitches had metastasis. Both had peritoneal carcinomatosis and one had extensive lymph node involvement.

Norris et al (1970) reports on 3 adenocarcinomas. They also had a category of 'intermediate' with 10 cases. Cystadenomas numbered 20.

Patniak and Greenlee (1987) reported that 10 of 18 epithelial tumours were carcinomas . Most had peritoneal carcinomatosis.

Sforna et al (2003) found 7 cases of adenocarcinoma. Three of 7 cases had abdominal effusion suggesting peritoneal spread.

Goto et al (2021) reported on 4 adenocarcinomas. The numbers were very low and the median survival time was long - over 1000 days unless there was metastatic disease

In summary then, the number of carcinomas is any one study is low, and about half of those had some evidence of metastasis. The unfortunate thing is the lack of standardisation of clinical situation. Most studies are in referral or academic settings where the case load is biased toward the more severe or those with clinical signs of metastasis. Most of the ones I have seen were incidental findings are mature spay for other reasons such as mammary tumour removal. Quoting a 50% metastatic rate in these different scenarios could potentially be wrong. The answer is then 'dont know'.

 

Bilateral papillary carcinoma of ovary

Ovarian carcinoma replacing the ovary - mixed type

Ovarian cystadenocarcinoma

Photomicrograph of cystadenocarcinoma

Photomicrograph of papillary cystadenocarcinoma

Photomicrograph of solid ovarian carcinoma

Dow C, (1960) Ovarian abnormalities in the bitch. J Comp Path 1960, 70: 59-69

Goto S, Iwasaki R, Sakai H, Mori T. A retrospective analysis on the outcome of 18 dogs with malignant ovarian tumours. Vet Comp Oncol. 2021; 19: 442-450.

Norris HJ, Garner FM, Taylor HB. (1970) Comparative pathology of ovarian neoplasms. IV Gonadal stromal tumors of canine species. J Comp Path 1970, 80: 399-405

Sforna M, Brachelente C, Lepri E, Mechelli L (2003) Canine Ovarian Tumours: a retrospective study of 49 cases. Vet Res Commun (2003) 27 Suppl 1: 359-361

Rete adenoma

McEntee (1990) reports seeing one of these. He acknowledged the difficulty in differentiating hyperplasia of the rete ovarii, which is common, with rete adenoma.

The Photomicrograph below illustrates this well.

Photomicrographs of rete hyperplasia

McEntee K (1990). Reproductive Pathology of Domestic Mammals. Academic Press p 71.

Rete adenocarcinoma

McEntee (1990) indicated that rete carcinomas were not reported. I have not seen or heard of a convincing example

McEntee K (1990). Reproductive Pathology of Domestic Mammals. Academic Press p 72..

Sex cord-Stromal Tumour (ScST)

The sex cord stromal tumours of the ovary are an intriquing group. They include those neoplasms that phenotypically resemble the cells of the sex cords from which granulosa cells, theca cells and the follicles arise, but separate from those tumours such as pure fibromas and leiomyomas that occur in any location in the body. They include the most well known neoplasm of them all - the granulosa cell tumour, as well as neoplasms with cells that resemble cells of the theca, and the corpus luteum. Some resemble the testicular sustentacular cell tumour of the testis, and the interstitial cell of the testis.

Many of these neoplasms have regions where there is differentiation to multiple cell types or multiple patterns, so separating the neoplasms into groups is artificial and from the knowledge available, has little prognostic relevance. It would be a perfect world if each neoplasm was a pure representative of its type and this was related to a specific prognosis or hormonal profile, but this is not the case. The most common type is reported to be the granulosa cell tumour, although in truth, most of the granulosa cell tumours also have cells resembling the thecal layers and are called granulosa-theca cell tumours. Comparing studies where different criteria are used in classification then becomes problematic.

If one critically examines many of the publications, it is impossible to ascertain exactly which differentiation pattern is present. Based on photographs alone, I would reclassify many, or would simply humbly disagree. The following day, I am likely to reclassify them again differently. The agreement between pathologists would be phenomenally bad. Norris et al (1970) divided the sex cord stromal neoplasms of dogs into 3 groups: granulosa cell tumours, testicular sustentacular (Sertoli) cell tumours and nonspecific gonadal stromal tumours. This has some merit.

I believe the best way to deal with the various naming schemes is to call them all Sex cord-Stromal Tumours and then indicate the different types using this scheme (which is not complete and somewhat arbitary!).

• ScST - granulosa cell tumour
• ScST - thecoma
• ScST - luteoma
• ScST - testicular sustentacular cell tumour
• ScST - interstitial cell tumour
• ScST with _____(insert patterns)____ differentiation, for example 'ScSN with granulosa cell and thecal differentiation'.

The categories below reflect these differentiation patterns.

ScST (pure) Granulosa cell tumour (GCT)

The granulosa cells form from the follicular cells that surround the oocyte, which are thought to be derived from the sex cords. Around the granulosa cells are the thecal cells, which resemble fibrocytes (see normal ovary). Granulosa cells are, according to the WHO classification, round to oval cells with hyperchromatic nuclei, distinct nucleoli, and a scant eosinophilic cytoplasm. Inreality, granulosa cells can have an abundance of cytoplasm, so using this definition is also problematical.

The reports on granulosa cell tumours vary greatly. It is clear that some people 'lumped' most Sex cord - Stromal Neoplasms as granulosa cell tumours, and others 'split' them into distinct (but also overlaping) categories. Those that called them 'granulosa cell tumours' are included here, and those that provided subgroups are listed under their subgroups below.

Macroscopically, These have a nodular surface and are surrounded by ovarian bursa. There are often regions of haemorrhage. The cut surface is cystic with white solid areas.

Histologically they have a variety of arrangements but most have broad fibrous septae, then finer septae that divided the tumours into multiple solid nodules of cells that resembled granulosa cells. Formation of cysts lined by cells resembling the inner lining of follicles happens to a greater or lesser amount. There are subdivisions published, although I dont subdivide them! The arrangement of the cells into follicle-like structures is a feature of follicular (microfollicular or macrofollicular) types. It is in these cysts that rosettes form, where the cells form circular structures with their nuclei at right angles to the central space. Those where the cells are arranged in columns of solidly packed cells (trabeculae) are known as the trabecular type. Thecal cells are often between the trabeculae. Solid granulosa theca tumours are a solid mass of granulosa cells. Insular granulosa theca tumours are those with nodules of granulosa cells surrounded by fibrous tissue.

Dow (1960) found 13 cases of GCT, 9 of which were macroscopically visible. One was bilateral with the second mass being microscopic. None were metastatic. One had regions that resembled theca cells, and 3 had luteal cells.

Cotchin (1961) found 30 cases in 69 tumours. Nineteen had pyometra. Two were malignant; one had metastasis to the retroperitoneum and kidney and the other had metastasis to the internal iliac lymph nodes, liver, pancreas and lung. Five has granulosa cell tumours that blended with papillary adenomas. Four had many eosinophils throughout the tumours.

Norris et al (1970) reported on 15 dogs with granulosa cell tumours. 4 of these had prolonged oestrus, and 6 had vaginal discharges. Three of these had some testicular sustentacular (Sertoli) cell differentiation. Three of the 15 had metastasised to the pelvis or peritoneum.

McCandlish et al (1979) reported on 2 cases of granulosa cell tumour of the ovary. One had histology supporting a follicular pattern. Both dogs had hyperestrogenism.

Buijtels et al (2010) reported on 7 bitches with ScST - granulosa cell tumours and examined the pituitary - ovarian axis by measuring LH and doing GnRH stimulation tests. 4 of the dogs were previously spayed so they developed neoplasia on ovarian remnants.

Christensen et al (2103) reported on an 11 year old dog spayed before 6 months of age that developed signs of estrus and had an ovarian remnant within which had developed a ScST - granulosa cell tumour.

Matos et al (2019) reported finding microscopic granulosa cell tumour in 55 ovaries of 40 dogs. They reported 62% of ovaries has microscopic granulosa cell tumours. Such a huge number is in total contradiction to the rarity of granulosa cell tumour in dogs. The changes of 'pleomorphism' increased with age! I believe they saw hyperplasia of the rete ovarii, a normal feature of ovaries in dogs - as described above.

Goto et al (2021) reported on 9 granulosa cell tumors. The numbers were very low and the median survival time was long - over 1000 days unless there was metastatic disease

 

 

Canine Sex cord - Stromal Tumour within a distended ovarian bursa

Cut surface of a canine Sex cord - Stromal Tumour- Granulosa cell tumour

Sex cord Stromal Tumour - granulosa cell tumour - macrofollicular type.

 

 

Cotchin E. (1961) Canine ovarian neoplasms. Res Vet Sci 1961, 2: 113-142.

Christensen NI, Brain PH, Langova V, Flory AB. (2013) Vaginal discharge in a spayed dog with multiple distinct malignancies. Aust vet J 2013, 91: 287-291

Goto S, Iwasaki R, Sakai H, Mori T. A retrospective analysis on the outcome of 18 dogs with malignant ovarian tumours. Vet Comp Oncol. 2021; 19: 442-450.

Dow C, (1960) Ovarian abnormalities in the bitch. J Comp Path 1960, 70: 59-69

McCandlish IAP, Munro CD, Breeze RG, Nash AS (1979) Hormone producing ovarian tumours in the dog. Vet Record 1979, 105: 9-11

Nelissen S, Miller AD. Comparison of anti-Müllerian hormone and inhibin immunolabeling in canine and equine granulosa cell tumors. J Vet Diagn Invest. 2022.

Norris HJ, Garner FM, Taylor HB. (1970) Comparative pathology of ovarian neoplasms. IV Gonadal stromal tumors of canine species. J Comp Path 1970, 80: 399-405

Buijtels JJ, de Gier J, Kooistra HS, Kroeze EJ, Okkens AC. (2010) Alterations of the pituitary-ovarian axis in dogs with a functional granulosa cell tumor. Theriogenology 2010 73(1): 11-19

Matos ACHDS, Leite JDS, Consalter A, de Mello MFV, de Lourdes Gonçalves Ferreira M, Fosenca ABM, Ferreira AMR. Histopathological findings in the early diagnosis of granulosa cell tumour in bitches. Reprod Domest Anim. 2019; 54: 828-834.

ScST (pure) Thecoma

This latter group change during follicular development to form a fibrous external thecal layer and an epithelioid inner thecal layer that is responsible for estrogenic steroidogenesis. Neoplasms where most cells resemble the cells of the internal or external thecal cells (or both) become thecomas. The cells that are oval or spindle shaped, pale, vacuolated and contain lipid are most easily recognised. They are rare tumours.

Sex cord stromal tumour - granulosa - theca cell tumour.

ScST (pure) luteoma

Cotchin reported seeing one tumour that resembled a luteoma.

Yamini et al (1997) reported on a dog with an ovarian tumour resembling a luteoma. The dog had concurrent hyperadrenocorticism.

Sex cord stromal tumour - luteoma

Cotchin E. (1961) Canine ovarian neoplasms. Res Vet Sci 1961, 2: 113-142.

Yamini B, VanDenBrink PL, Refsal KR (1997) Ovarian steroid cell tumour resembling luteoma associated with hyperadrenocorticism (Cushing's disease) in a dog. Vet Pathol 1997, 34: 57-60

ScST (pure) testicular sustentacular cell tumour

These tumours are so named because they are exactly like testicular sustentacular (Sertoli) cell tumours of the testis. Cotchin (1961) reported that some of the granulosa cell tumours resembled 'Sertoli' cell tumours.

Norris et al (1970) reported on 6 dogs that had ovarian neoplasia of this type.

McCandlish et al (1979) reported on 2 cases of granulosa cell tumour of the ovary. One had histology supporting a testicular sustentacular (Sertoli) cell pattern. Both dogs had hyperestrogenism.

Patnaik et al (1987) described 12 Sertoli Leydig cell tumours of which 4 cases were pure testicular sustentacular (Sertoli) cell tumours. The testicular sustentacular (Sertoli) cell types had tubules containing spindle cells that were separated by fibrous tissue, in a pattern typical of testicular sustentacular (Sertoli) cell tumours. Many tumours in their series also had a component resembling the interstitial endocrine cells of the testis.

 

Sex cord Stromal Tumour - testicular sustentacular (Sertoli) cell tumour of ovary.

Cotchin E. (1961) Canine ovarian neoplasms. Res Vet Sci 1961, 2: 113-142.

McCandlish IAP, munro CD, Breeze RG, Nash AS (1979) Hormone producing ovarian tumours in the dog. Vet Record 1979, 105: 9-11

Norris HJ, Garner FM, Taylor HB. (1970) Comparative pathology of ovarian neoplasms. IV Gonadal stromal tumors of canine species. J Comp Path 1970, 80: 399-405

Patnaik AK, Saigo PE, Lieberman PH, Greenlee PG. (1987). Morphology of canine ovarian Sertoli-Leydig cell neoplasms. A report of 12 cases. Cancer 62: 577-584.

ScST (pure) interstitial endocrine cell tumour

Sex cord stromal tumour - interstitial cell tumour.

ScST with varying differentiation patterns

In truth, most sex-cord stromal tumours have different differentiation patterns. Convention, history and practicalites mean that the name given is usually based on the dominant pattern. The majority of people have heard of a granulosa cell tumour, but who would know what a' ScST with granulosa and theca differention' is. None the less, there are some different tumours that were reported and I have included some below.

ScST with testicular sustentacular and interstitial endocrine cell differentiation

Patnaik et al (1988) described 12 Sertoli Leydig cell tumours. They recognised 3 subtypes: Sertoli Leydig, Sertoli cell and Sertoli-Leydig with retiform pattern. In accordance with the renaming of Leydig cells as interstitial endocrine cells and Sertoli cells as testicular sustentacular cells, I will use this designation

testicular sustentacular-Interstitial endocrine cell tumours have regions with typical testicular sustentacular cell differentiation (as described above) and regions of endocrine cells in clusters, like interstitial endocrine cells of the testis. Patnaik et al (1988) found 5 of their 12 cases were this pattern. One was metastatic and it was poorly differentiated.

 

Patnaik AK, Saigo PE, Lieberman PH, Greenlee PG. (1988). Morphology of canine ovarian Sertoli-Leydig cell neoplasms. A report of 12 cases. Cancer 62: 577-584.

ScST with testicular sustentacular, interstitial endocrine and retiform differentiation

Patnaik et al (1988) recognised three cases of this type of testicular sustentacular-Interstitial endocrine cell tumour. testicular sustentacular cell differentiation, interstitial cell differentiation, are combined with epithelial elements resembling the rete testis. The retiform component had branching, tubular and papillary structures just like rete testis.

Gomez-Laguna et al (2008) reported one case of a bilateral 'Sertoli-Leydig' cell tumour in a bitch, and the neoplastic cells stained immunohistochemically with alpha inhibin and EMA. Portions of theit 'Sertoli-Leydig' cell tumour had rete testis like differentiation. All neoplastic cells including the testicular sustentacular and rete like regions stained with cytokeratin AE1/AE3. Differentiation from epithelial tumours requires staining for alpha inhibin, which should be negative in epithelial tumours.

Gómez-Laguna J, Millán Y, Reymundo C, Domingo V, Martín de las Mulas J. (2008) Bilateral Retiform Sertoli–Leydig Cell Tumour in a Bitch. Alpha-Inhibin and Epithelial Membrane Antigen as Useful Tools for Differential Diagnosis J Comp Path 139: 137-140

Patnaik AK, Saigo PE, Lieberman PH, Greenlee PG. (1988). Morphology of canine ovarian Sertoli-Leydig cell neoplasms. A report of 12 cases. Cancer 62: 577-584.

ScST with testicular sustentacular and luteal differentiation

Ichimura et al (2010) reports on an unusual neoplasm in a spayed dog - presumably developing from an ovarian remnant. It had testicular sustentacular (Sertoli) and Luteal differentiation. I would classify it differently based on the photographs.

Ichimura R, Shibutani M, Mizukami S, Suzuki T, Shimada Y, Mitsumori K.J (2010) A case report of an uncommon sex-cord stromal tumor consisted of luteal and sertoli cells in a spayed bitch.Vet Med Sci 2010 72: 229-234.

Immunohistochemistry

 

Walter et al (2018) found that bitches with 'granulosa cell' tumors had serum antiMullerian hormone concentration of ≥23.0 ng/ml. These granulosa cell tumors were from 0.3 to 15cm diameter. I am not sure I could recognise a 0.3mm granulosa cell tumor! The [AMH] in dogs with follicular cysts were 0.11 to 2.09 ng/ml and in dogs with luteal cysts were 0.16 to 0.72.

Akihara Y, Shimoyama Y, Kawasako K, Komine M, Hirayama K, Terasawa A, Ohmachi T, Matsuda K, Okamoto M, Taniyama H. (2007) Histological and immunohistochemical evaluation of canine ovary. Reprod Domest Anim. 42(5): 495-501.

Riccardi E, Greco V, Verganti S, Finazzi M. (2007) Immunohistochemical diagnosis of canine ovarian epithelial and granulosa cell tumors. J Vet Diagn Invest 19: 431-435

Walter B, Coelfen A, Jäger K, Reese S, Meyer-Lindenberg A, Aupperle-Lellbach H. Anti-Muellerian hormone concentration in bitches with histopathologically diagnosed ovarian tumours and cysts. Reprod Domest Anim. 2018 Jun;53(3):784-792.

 

Nelissen and Miller (2022) reported on inhibin and antiMullerian hormone staining of granulosa cell tumors in dogs. 15 of 15 stained with inhibin and 12 of 15 stained with AMH.

 

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.

Mesenchymal neoplasia, not related to Sex cords

One would think that all mesenchymal neoplasms would be listed under stromal neoplasia! No that is not the way it is done. This group are those that are phenotypically identical to their counterparts in other parts of the body. Any mesenchymal tissue can be represented here. These are some that are reported, or I have seen.

Fibroma - fibrosarcoma

Dow (1960) reported finding one fibroma of the ovary. Cotchin (1961) reported finding one necrotic and one anaplastic sarcoma.

 

Cotchin E. (1961) Canine ovarian neoplasms. Res Vet Sci 1961, 2: 113-142.

Dow C, (1960) Ovarian abnormalities in the bitch. J Comp Path 1960, 70: 59-69

Smooth muscle tumors (leiomyoma - leiomyosarcoma)

Neoplasms of smooth muscle of the ovary are very rare, certainly compared to the number that arise in the uterus and vagina. Some are reported to occur within the mesoovarium, and most are assumed to occur in the ovary, although this is difficult to prove.

Smooth muscle tumours of the ovary are usually identified as an incidental finding, and unassociated with clinical signs.

Their macroscopic appearance varies with the amount of fibrous tissue stroma. Pure leiomyomas are well circumscribed tumours with a smooth outer lining. They should be surrounded by the tissues of the ovarian bursa, including the fimbrial tissues. They have bands of fibrous tissue that course throughout and most of the stroma has a glistening white to tan colour. They are firm and solid tissues.

 

Leiomyomas of the ovaries of 2 bitches

Histologically, they are composed of streams of stromal cells that are arranged in a haphazard fashion, but within bundles the nuclei of adjoining cells may pallisade. Cells tend to have well defined cell boundaries with an abundance of eosinophilic cytoplasm. Nuclei are regular in size, oval, vesicular and symmetrical. They are traditionally described as having blunt ends and are 'cigar' shaped. The mitotic rate is usually very low - less than 1 p10HPF.

Histology of a leiomyomas of the ovary

Immunohistochemical staining is usually cytokeratin negative, vimentin, smooth muscle actin, desmin, and calponin positive. S100 is variable. In humans gastrointestinal stromal tumours (cKit CD117 positive) are sometimes found in the genital tract so staining for these should be done for completeness. In an immunohistochemical study of the canine ovary, Akihara et al (2007) identified SMA positive cells within the capsule of the ovary. Many cells stained for calponin including surface epithelium, cortical tubules (aka subsurface epithelial structures) capsule of the ovary, stromal cells, endocrine cells near the follicles, and rete ovarii. This should be considered when making a diagnosis also.

Smooth muscle cells are normally found in ovarian blood vessels and beneath the serosa of the mesovarium.

 

Norris et al (1970) reports one case of an ovarian leiomyoma in the ovary of a dog.

In 1987, Patniak and Greenlee (1987) reported on 71 primary ovarian neoplasms in dogs and no leiomyomas were found.

McEntee (1990) reports seeing 8 ovarian leiomyomas in dogs.

Sforna M et al (2003) reports finding 1 cases of leiomyoma in 49 cases of ovarian neoplasia in dogs.

There are three cases in the YagerBest Histovet database. One was contiguous with the smooth muscle of the mesovarium (YB75197), one was in the hilus of the ovary and was about 2.5 cm diameter, and the third was a 726g 20x10x10 cm mass (YB223841).

Akihara Y, Shimoyama Y, Kawasako K, Komine M, Hirayama K, Terasawa A, Ohmachi T, Matsuda K, Okamoto M, Taniyama H. (2007) Histological and immunohistochemical evaluation of canine ovary. Reprod Domest Anim. 42(5): 495-501.
McEntee K (1990) Reproductive Pathology of Domestic Mammals. Academic Press p87 Norris HJ, Garner FM, Taylor HB. (1970) Comparative pathology of ovarian neoplasms. IV Gonadal stromal tumors of canine species. J Comp Path 1970, 80: 399-405 Patniak AK, Greenlee PG (1987) Canine ovarian neoplasms: a clinicopathologic study of 71 cases including histology of 12 granulosa cell tumors. Vet Pathol 24: 509-514. Sforna M, Brachelente C, Lepri E, Mechelli L. (2003) Canine ovarian tumours: retrospective study of 49 cases. Vet Res Commun 27 Suppl 1: 359-361.

Rhabdomyosarcoma

There is one report of a primary rhabdomyosarcoma of the ovary of a dog (Boeloni et al 2012). Metastastes were throughout the abdomen.

Boeloni JN, Reis AMS, Nascimento EF, Silva JF, Serakides R, Primary Ovarian Rhabdomyosarcoma in a Dog. J Comp Pathol 2012, 147: 455-459

Lipoma - liposarcoma

I have not seen or heard of a lipoma or lipomatous tumour of the ovary proper. Lipomatous involvement of the bursa (mesovarium) does occur (see below)

 

A lipoma of the ovarian bursa of a dog

Gelberg HB, McEntee K (1986) Pathology of the canine and feline uterine tube. Vet Pathol 23: 770-775

Haemangiosarcoma

Sforna et al (2003) found 1 haemangiosarcoma in their series.

Sforna M, Brachelente C, Lepri E, Mechelli L (2003) Canine Ovarian Tumours: a retrospective study of 49 cases. Vet Res Commun (2003) 27 Suppl 1: 359-361

Germ cell tumours of the ovary including teratoma

There are a bewildering aray of germ cell tumours of the ovary of women, but in the veterinary world there are 2 main types - the dysgerminoma and the teratoma. The former are rare, and the latter are less so.

Dysgerminoma

Dysgerminoma is a well known but rare ovarian germ cell tumour.

Macroscopically, they usually have a smooth but nodular outer surface and vary from white grey to dark red (with haemorrhage and necrosis). The smaller ones are circular and uniformly white and soft, just like the seminoma of the testis - not surprising because these are the ovarian equivalent of the testicular seminoma.

Cotchin (1961) found 8 ovarian tumours that were dysgerminomas (he called them seminomas). One was metastatic to multiple abdominal lymph nodes and liver and kidney.

Andrews et al (1974) reported 2 canine cases, however one had primitive mesenchyme so I assume it was part of a teratoma. The one that had the features of a dysgerminoma had metastasis to pancreas and abdominal lymph nodes.

Greenlee and Patniak (1985) reported seeing 7 cases. One was metastatic and there were intravascular emboli. All were in dogs older than 10. The tumours were from 2 to 21 cm diameter. Most had lymphocytic foci.

Sforna et al (2003) found 2 dysgerminomas and 1 teratoma

Coggshall et al (2012) report on a dog with metastatic neoplasia of the ovary - both teratoma and sex cord stromal neoplasia were identified. The metastases were in the mesovarium.

Wilcox et al (2019) reported on a dog with metastatic dysgerminoma given chemotherapy and radiation therapy. The neoplasm was infiltrative of the retroperitoneum and the metastasis was to the mediastinum. The patient lived for 501 days after radiation therapy.

Goto et al (2021) reported on 5 dysgerminomas. The numbers were very low and the median survival time was long - over 1000 days unless there was metastatic disease

 

 

Microscopically dysgerminomas are round cell tumours with cells forming diffuse sheets. Most cells are uniform but some have giant single nuclei and others are multinucleate. No foci of lymphocytes were seen in the samples examined by Cotchin (1961) but Greenlee and Patniak (1985) reported seeing them in most.

 

 

Canine ovarian dysgerminoma

Canine ovarian dysgerminoma - cut surface

 

Photomicrograph of ovarian dysgerminoma

Immunohistochemistry.

Rosa et al (2021) reported on 14 cases - 1 in a maned wolf and 13 in domestic dogs. All were unilateral, They used immunohistochemistry for Sal-like protein (SALL4), octamer-binding transcription factor 3/4 (OCT3/4), placental alkaline phosphatase (PLAP), cKit and vimentin. Of the 13 domestic dogs, 13 stained for vimentin, 7 of 13 stained for SALL4, 4 stained with OCT3/4, 3 stained for PLAP, 4 had membranous staining and 1 cytoplasmic staining for c-kit,

 

Andrews EJ, Stookey JL, Helland DR, Slaughter LJ (1974). A histopathological study of canine and feline ovarian dysgerminomas. Can J Comp Med 1974, 38: 85-89

Goto S, Iwasaki R, Sakai H, Mori T. A retrospective analysis on the outcome of 18 dogs with malignant ovarian tumours. Vet Comp Oncol. 2021; 19: 442-450.

Greenlee PG, Patniak AK (1985) Canine ovarian tumors of germ cell origin. Vet Pathol 1985, 22: 117-122.

Coggeshall JD, Joanne N. Franks JN, Diane U. Wilson DU, Wiley JL (2012) Primary Ovarian Teratoma and GCT with Intra-abdominal Metastasis in a Dog. J Amer Anim Hosp Assoc 2012, 48: 424-428

Cotchin E. (1961) Canine ovarian neoplasms. Res Vet Sci 1961, 2: 113-142.

Rosa RB, Bianchi MV, Ribeiro PR, Argenta FF, Vielmo A, de Sousa FAB, Piva MM, Pohl CB, Daoualibi Y, Cony FG, Brunner CB, Von Hohendorff R, Sonne L. Comparison of immunohistochemical profiles of ovarian germ cells in dysgerminomas of a captive maned wolf and domestic dogs. J Vet Diagn Invest. 2021; 33: 772-776.

Sforna M, Brachelente C, Lepri E, Mechelli L (2003) Canine Ovarian Tumours: a retrospective study of 49 cases. Vet Res Commun (2003) 27 Suppl 1: 359-361

Wilcox CL, Hansen KS, Kent MS, Phillips KL, Willcox JL. Outcome of Metastatic and Recurrent Ovarian Dysgerminoma Using Radiation Therapy and Chemotherapy in a Dog. J Am Anim Hosp Assoc. 2019; 55: e554-02

 

Dermoid cyst

Dermoid cysts are reported in many locations - usually in the skin and subcutis. They are composed of epidermis and dermis, and may have adnexa like hair follicles. When there are no other structures it is appropriate to call them dermoid cysts. Careful examination of the tissue is required to be certain the lesion is not a teratoma (see below). These are extremely rare.

Riser et al (1959) reported a case of a dermoid cyst of the canine ovary but this mass also had hair, bone, fat and skin. By definition this is now called a teratoma.

Cotchin (1961) reported finding one cyst that was lined with stratified squamous epithelum and partially by columnar epithelium. It was filled with keratin and sebaceous material, but had no hair follicles. He regarded this as a dermoid cyst, but it could have been part of a teratoma.

Cotchin E. (1961) Canine ovarian neoplasms. Res Vet Sci 1961, 2: 113-142.

Riser WH, Marcus JF, Guibor EC, Oldt CC. Dermoid cyst of the canine ovary. J Am Vet Med Assoc. 1959 134(1): 27-28.

Teratoma

Teratomas have several of the 3 germ cell layers - ectoderm, mesoderm and endoderm - all within the same tumour. It is believed that they arise from totipotent germ cells and differentiate along all pathways. The requirement of having tissue from all 3 germ cell layers is not necessary - a minimum of 2 is recognised as being required in Veterinary Pathology.

Macroscopically most are multinodular with a smooth outer contour, because most are well differentiated and non invasive. They usually have cyst like structures containing hair and greasy gelatinous material, and solid areas with grey white areas, bone, translucent blue (cartilage) and black foci.

 

A large ovarian teratoma in a young bitch.

A small ovarian teratoma

Histologically, they contain epidermis, hair, respiratory epithelium, cartilage, bone, fat, collagen and brain and nerves and any other tissue found in the body.

Examples of the types of tissue seen in ovarian teratomas including, from left to right, cartilage and fat, nervous tissue, epidermis and ciliated 'respiratory' epithelium.

 

Riser et al (1959) reported a single case of what they called a dermoid cyst, but which was actually a teratoma. They also had 3 other masses that contained dermoid cysts - so presumably they also were teratomas. No indication of malignancy was given.

Andrews et al (1974) reported on 2 cases of dysgerminoma. One had primitive mesenchyma so it may have been a primitive teratoma. It was not metastatic.

Crane et al (1975) reported a malignant teratoma in a 3 yr old St Bernard. It had perioneal metastases of epithelial tissue.

Greenlee and Patniak (1985) reported seeing 7 cases of teratoma and 3 had metastasis. One had peritoneal implants and 2 had widespread metastasis. They were from 2 to 10 cm diameter.

Patniak and Greenlee (1987) reported seeing 7 teratomas and these are presumably the ones described in detail in Greenlee and Patniak (1985)

Rotal et al (2013) reported on a single case where the ovarian mass was in a remnant in a speyed dog. The mass was brain tissue so was considered a monophasic teratoma.

Pires et al (2019) reported on a single case of an ovarian mass which was composed of brain tissue only and thus a monophasic teratoma.

Other publications are summarised below.

Author	#	Age(yr)	Benign or malignant	Breed	Side
Riser et al 1959	4
Clayton 1975
Crane et al 1975	1	3	Malignant	St Bernard	L
Gruys, et al 1976	4	9, 9, 19, 11	Benign 2, Malignant 2	Var	3L, 1R
Greenlee, Patnaik 1985	7	2, 3, 3, 4, 5, 9, 9	Benign ?, Malignant 3	Var	2L, 2R
Trasti, Schlafer 1999	1	2	Malignant	Labrador	R
Nagashima et al 2000	1	2	benign	Labrador	L
Sforna et al 2003	1	?	?	?	?
Yamaguchi et al 2004	1	10	Benign	GSD	R
Rotal et al 2013	1	5	Benign monophasic (brain)	Mixed	L
Pires et al (2019)	1	10	Benign monophasic (brain)	Boxer	L

 

 

Clayton HM. (1975) A canine ovarian teratoma. Vet Rec. 1975 96(26): 567-568.

Crane SW, Slocum B, Hoover EA, Wilson GP. (1975) Malignant ovarian teratoma in a bitch. J Am Vet Med Assoc 1975 167(1): 72-74.

Greenlee PG, Patniak AK (1985) Canine ovarian tumors of germ cell origin. Vet Pathol 1985, 22: 117-122.

Gruys E, van Dijk JE, Elsinghorst Th AM, van der Gaag I (1976) Four canine ovarian teratomas and a nonovarian feline teratoma. Vet Pathol. 1976 13(6): 455-459.

Nagashima Y, Hoshi K, Tanaka R, Shibazaki A, Fujiwara K, Konno K, Machida N, Yamane Y. (2000) Ovarian and retroperitoneal teratomas in a dog. J Vet Med Sci. 2000 Jul;62(7):793-795.

Riser WH, Marcus JF, Guibor EC, Oldt CC. Dermoid cyst of the canine ovary. J Am Vet Med Assoc. 1959 134(1): 27-28.

Sforna M, Brachelente C, Lepri E, Mechelli L (2003) Canine Ovarian Tumours: a retrospective study of 49 cases. Vet Res Commun (2003) 27 Suppl 1: 359-361

Patnaik AK, Greenlee PG. (1987) Canine ovarian neoplasms: a clinicopathologic study of 71 cases, including histology of 12 granulosa cell tumors. Vet Pathol. 1987 Nov;24(6):509-14.

Pires MDA, Catarino JC, Vilhena H, Faim S, Neves T, Freire A, Seixas F, Orge L, Payan-Carreira R. Co-existing monophasic teratoma and uterine adenocarcinoma in a female dog. Reprod Domest Anim. 2019l; 54: 1044-1049.

Rota1 A, Tursi1 M, Zabarino S Appino S. (2013) Monophasic Teratoma of the Ovarian Remnant in a Bitch. Reprod Dom Anim 2013; 48: e26–e28.

Trasti SL, Schlafer DH. (1999) Theriogenology question of the month. Malignant teratoma of the ovary. J Am Vet Med Assoc 1999 214(6): 785-786.

Yamaguchi Y, Sato T, Shibuya H, Tsumagari S, Suzuki T. (2004) Ovarian teratoma with a formed lens and nonsuppurative inflammation in an old dog.
J Vet Med Sci. 2004 Jul;66(7):861-4.

Mixed germ cell tumors

Neoplasms of germ cells that display different types of germ cell tumors are exceedingly rare.

Robinson et al (2013) described a neoplasm of the ovary of a dog that had a teratoma (embryonal) and a yolk sac tumor (extra-embryonal) combined. The latter had metastasised. The yolk sac component stained for alpha fetal protein.

Banco et al (2017) reported finding an embryonal carcinoma in a 17 month old dog. It had metastases to the serosa of the mesometrium and adjacent structures.

 

Banco B, Ferrari R, Stefanello D, Groppetti D, Pecile A , Faverzan S*, Longo M, Zani DD, Ravasio G, Caniatti M, Grieco V. Ovarian Embryonal Carcinoma in a Dog. J Comp Path 2017: 157: 291-295.

Robinson NA, Manivel JC, Olson EJ. Ovarian mixed germ cell tumor with yolk sac and teratomatou scomponents in a dog. J Vet Diagn Invest 2013; 25: 447-452.

Mixed ovarian neoplasms - (mixed Müllerian tumours, carcinosarcoma, mixed germ cell sex cord stromal tumor)

To be a mixed Müllerian tumour or fibroadenoma or carcinosarcoma, the neoplasm must be shown to be of paramesonephric (Müllerian) differentiation (or histogenesis). Malignant teratomas can be primitive tumours with epithelial and stromal components. If the tumour has a distinct endometrioid appearance, there is little argument. A pure carcinosarcoma is clearly of this category. Tumours with representations from all 3 germ cell layers is more likely to be a teratoma. The presence of estrogen receptors in the stromal tissues is also helpful - teratomas (benign or malignant) should not have these.

These tumours are extremely rare, and there are only a couple reports. I have seen one.

Norris et al (1970) reports on mixed mesodermal tumour of the ovary.

McEntee (1990) reports seeing a single fibroadenoma in the ovary of a dog.

Antuofermo et al (2009) reported one case of a malignant mixed Mullerian Tumour in a dog. It was bilateral and had metastasised to the peritoneum (where the tissue was carcinomatous) and to the lung where it was sarcomatous. The carcinomatous portions were positive for CK (AE1/AE3) and CK7 plus vimentin and Estrogen Receptors, and the sarcomatous component was vimentin positive only.

Flores et al (2019) reported on a tumor of the ovary which they describe as a dysgerminoma and sex cord stromal tumor combined. There was no indication of other disease 11 months after diagnosis.

 

 

Antuofermo E, Cocco R, Borzacchiello G, Burrai GP, Meloni F, Bonelli P, Pirino S, Cossu-Rocca P, Bosincu L. (2009) Bilateral Ovarian Malignant Mixed Müllerian Tumor in a Dog Vet Pathol 2009 46: 453-456.

Flores AR, Lobo J, Nunes F, Rêma A, Lopes P, Carvalho L, Bartosch C, Amorim I, Gärtner F. Canine ovarian gonadoblastoma with dysgerminoma overgrowth: a case study and literature review. J Ovarian Res. 2019; 12: 89.

McEntee K (1990). Reproductive Pathology of Domestic Mammals. Academic Press p 74.

Norris HJ, Garner FM, Taylor HB. (1970) Comparative pathology of ovarian neoplasms. IV Gonadal stromal tumors of canine species. J Comp Path 1970, 80: 399-405

Neoplasms in ovarian remnants.

There is increasing evidence that gonadal remnants within the abdomen have a higher likehood of developing neoplasia. In males, testicular remnants form testicular sustentacular cell tumours and interstitial cell tumours, although the incidence is not known (see Male dog - extratesticular testicular neoplasms). In females, those with ovarian remnant syndrome are more likely to develop sex cord - stromal tumours. In the mouse world, inhibin is considered a tumour supressor. Neutered animals have higher GnRH and serum LH concentrations and this continuous stimulation of small remnants is thought to be the reason for eventual carcinogenesis.

Sivacolundhu et al (2001) published a clinical paper on 2 cases of ScST - granulosa cell tumour that developed in bitches that were speyed before 1 year of age. One was a 7year old, and the other was 10. These had clinical signs of persistent vulval bleeding. One was on the left and the other the right side.

Buijtels et al (2010) reported on 7 bitches with ScST - granulosa cell tumours and examined the pituitary - ovarian axis by measuring LH and doing GnRH stimulation tests. 4 of the dogs were previously spayed so they developed neoplasia of ovarian remnants. These 4 dogs had increased serum LH concentrations over other dogs - those entire bitches with ScST had lower serum [LH] suggesting a pathogenetic roll of increased LH resulting in continuous stimulation of ovarian remnants.

Ichimura et al (2010) reported on one case where a 10 years old dog spayed at one year of age developed a bloody vulval discharge and had a ScST of an unusual type.

Of the 34 cases of ovarian remnants I have seen at YagerBest, there were 3 ScST and 2 cases of hyperplasia of remnants.

Buijtels JJ, de Gier J, Kooistra HS, Kroeze EJ, Okkens AC. (2010) Alterations of the pituitary-ovarian axis in dogs with a functional granulosa cell tumor. Theriogenology 2010 73(1): 11-19

Ichimura R, Shibutani M, Mizukami S, Suzuki T, Shimada Y, Mitsumori K.J (2010) A case report of an uncommon sex-cord stromal tumor consisted of luteal and sertoli cells in a spayed bitch.Vet Med Sci 2010 72: 229-234.

Pluhar GE, Memon MA, Wheaton LG. (1995) Granulosa cell tumor in an ovariohysterectomized dog. J Am Vet Med Assoc 1995 207: 1063-1065.

Sivacolundhu RK, O'Hara AJ, Read RA.(2001) Granulosa cell tumour in two speyed bitches. Aust Vet J. 2001 79: 173-176.

Neoplasms metastatic to the ovary

It is really difficult to accurately review the types of neoplasms that metastasise to the ovary. It appears to happen so infrequently that surveys of the ovary do not report many. This is no doubt because the ovary is not routinely examined in cases of metastatic neoplasia, because many dogs are neutered and no longer have ovaries, or because mention of the ovarian involvment is not reported or is an afterthought. One would have to read through all papers of all neoplasms looking specifically for ovarian involvement. Search engines do not cover all the text of papers. One may be lucky to remember if the ovary is mentioned in a paper.

It was once thought that the bilateral nature of some neoplasms (epithelial especially) indicated metastasis, but many of the affected ovaries have multifocal lesions so it is likely that bilaterality is because of multiple de novo development. I am not sure of bilateral involvement of sex cord stromal tumours. The fertile soil concept of metastasis may come into play here.

Below are some examples that I was able to find.

Endometrial carcinoma

Norris et al (1970) found one case of endometrial carcinoma that metastasised to the ovary.

Lymphoma

Dow (1960) reported on 3 bitches with tumours in the ovary that were from other locations. Two dogs had lymphoma secondary to intestinal involvement, and one had a microscopic focus from metastatic mammary carcinoma.

Jo et al (2023) reported on one case of lymphoma.

Mammary carcinoma

Norris et al (1970) found one case of metastatic mammary carcinoma that affected the ovary.

Skin tumour (not specified)

Norris et al (1970) reports a case of a metastatic neoplasm from skin. The type was not reported.

Transmissible venereal tumour

Norris et al (1970) found one case of CTVT that involved the ovary of a dog.

Bastan et al (2008) report metstasis of canine transmissible venereal tumour to the uterus and ovaries of a 7 year old dog . This boxer had a vaginal CTVT.

 

Bastan A, Baki Acar D, Cengiz M (2008) Uterine and ovarian metastasis of transmissible venereal tumor in a bitch. Turk J Vet Anim Sci 32: 65-66

Dow C, (1960) Ovarian abnormalities in the bitch. J Comp Path 1960, 70: 59-

Jo J, Son M, Chae Y, et al. T-cell lymphoma infiltrating the uterus and ovaries of a Golden Retriever: a case report. Ir Vet J. 2023; 76: 23.

Norris HJ, Garner FM, Taylor HB. (1970) Comparative pathology of ovarian neoplasms. IV Gonadal stromal tumors of canine species. J Comp Path 1970, 80: 399-405

Ovarian hypoplasia

Small ovaries are recognised at about the time that oestrus should occur. Bitches have a lack of oestrus activity or they never develop oestrus. The clinical syndrome is called "premature gonadal failure". I find the term 'premature' unnecessary here and I dont use this term. These dogs actually have primary anoestrus. There are several mechanisms that result in this however.

Hypoplastic ovaries are part of Disorders of Sexual Development and will be considered in that section.

Ovarian atrophy

There are several situations where the ovaries become smaller than normal, including physiological atrophy of anoestrus, malnutrition or cachexia, treatment with hormone modulating drugs and as an age associated condition.

There is little written in the pathology literature about ovarian atrophy of bitches, and as it is a functional condition, it is mentioned in the Theriogenology literature. Johnston (1989) reviews premature gonadal failure and indicates that hypothyroidism is a cause of ovarian atrophy.

There are several toxicological studies on the effects of various substances on the ovary including zearalenone (Gajecka et al 2008a, b; ), estrogen modulating drugs (Rehm et al 2007), difluoromethylornithine and or tamoxifen (Brown et al 1999), or progestagens (El Etreby 1979)

 

Brown AP, Morrissey RL, Crowell JA, Levine BS. (1999) Thirteen-week oral toxicity study of difluoromethylornithine in combination with tamoxifen citrate in female dogs. Cancer Chemother Pharmacol. 1999 43(6): 479-488

.El Etreby MF. (1979) Effect of cyproterone acetate, levonorgestrel and progesterone on adrenal glands and reproductive organs in the beagle bitch.Cell Tissue Res. 1979 200(2): 229-243.

Gajecka M, Obremski K, Jakimiuk E, Skorska-Wyszyńska E, Zielonka L, Gajecki M. (2008) Histopathological examination of ovaries in bitches after experimental zearalenone mycotoxicosis. Pol J Vet Sci. 2008;11(4):363-366.

Gajecka M, Przybylska-Gornowicz B, Obremski K, Polak M, Jakimiuk E, Skorska-Wyszyńska E, Zielonka L, Gajecki M. (2008) Ultrastructural changes of ovarian follicle and corpus luteum after experimental zearalenone mycotoxicosis in bitch. Pol J Vet Sci. 2008;11(4):327-337.

Johnston SD (1989) Premature gonadal failure in female dogs and cats. J Reprod Fert Suppl 1989 39: 65-72

Rehm S, Solleveld HA, Portelli ST, Wier PJ. (2007) Histologic changes in ovary, uterus, vagina, and mammary gland of mature beagle dogs treated with the SERM idoxifene. Birth Defects Res B Dev Reprod Toxicol. 2007 80(3): 225-232.

Ovarian atrophy with single large follicle

Older bitches who are close to having or have no primordial follicles develop a condition where there is 1 or 2 usually large ovarian follicles which are anywhere from 8 to 12 (or more) millimetres in diameter. These frequently have a layer of granulosa cells that is about 10 to 12 cells thick and some show papillary rejections or undulations into the lumen. Occasionally these will be luteinised or partially luteinised. The dogs have a history of persistent estrus or a hyperestrogenism type syndrome. This is usually why they are ovariectomized. Histologically there is atrophy of the ovary with a thin cortex and no visible primordial or primary follicles, or they may be very sparse. Granulosa cell rests appeared to be more numerous than usual, and there is a single large follicle or perhaps a single large follicle and 1 or 2 smaller follicles.

Oophoritis

Inflammation of the ovary is called oophoritis. Ovaritis is now an accepted term in some circles and is listed in a dictionary I checked.

Oophoritis is an extremely rare disease, and many people will never see a case. I have seen one case. Dogs with pyometra do not get oophoritis (as occurs in the cat). Despite its rarity, oophoritis is blamed for unexplained premature ovarian failure (POF) in bitches. It is called a disease of exclusion - exclude everything else and what you are left with is 'oophoritis'. This approach however will cause many other causes of POF to be missed. It would be better to use the term 'idiopathic ovarian failure' than to give a potentially incorrect diagnosis.

Johnston (1989) reports on two cases of oophoritis, one from a 5 yr old Cocker Spaniel and one from a 2 yr old Airedale, both with primary anoestrus. Nickel et al (1991) documented a case in a 3.5 yrs old Rhodesian Ridgeback dog with persistent oestrus and then infertility. She had adhesions between the ovary and bursa and large numbers of lymphocytes and plasma cells throughout both ovaries and especially around primary and secondary follicles.

Johnston SD (1989) Premature gonadal failure in female dogs and cats. J Reprod Fert Suppl 1989 39: 65-72

Nickel RF, Okkens AC, van der Gaag I, van Haaften B. (1991). Oophoritis in a dog with abnormal corpus luteum function. Vet Rec 1991 128: 333-334

Varicocele

Dilated and thrombosed veins in and around the ovary and mesovarium are very rare. They are not reported (to my knowledge). They are most well known in the mare. I have seen a couple cases and they were submitted because of an unusual appearance of the ovaries in dogs presented for a mature spay. They look just like varices elsewhere - dilated veins some of which have laminated thrombi in various stages of organisation and endothelialisation.

Dilated tortuous and thrombosed ovarian vein (centre). Ovary has been sectioned in this formalin fixed specimen.

Vascular lesions

Atherosclerosis

Atherosclerosis is unusual in dogs, and is seen in hypothyroidism and in diabetes mellitus. While these causes of atherosclerosis are well recongised, the ovarian arteries and veins are seldom examined.

Ushio et al (2021) reported atherosclerosis (they classified it as vacuolar change) in 7 of 105 dogs. The exact location of the vessels were not given - presumably it was the pampiniform plexus of the ovary.

Ushio N, Chambers JK, Watanabe K, Kayano M, Uchida K. Age-Related Arteriolar Changes With Lipid and Amyloid Deposits in the Gonads of Dogs. Vet Pathol. 2021; 58: 558-567.

Fibromuscular hypertrophy

Ushio et al (2021) reported fibromuscular hypertrophy in 50 of 105 dogs. The exact location of the vessels were not given - presumably it was the pampiniform plexus of the ovary.

Ushio N, Chambers JK, Watanabe K, Kayano M, Uchida K. Age-Related Arteriolar Changes With Lipid and Amyloid Deposits in the Gonads of Dogs. Vet Pathol. 2021; 58: 558-567.

Hyalinosis

Ushio et al (2021) reported hyalinosis in 3 of 105 dogs. The exact location of the vessels were not given - presumably it was the pampiniform plexus of the ovary.

Ushio N, Chambers JK, Watanabe K, Kayano M, Uchida K. Age-Related Arteriolar Changes With Lipid and Amyloid Deposits in the Gonads of Dogs. Vet Pathol. 2021; 58: 558-567.

Vasculitis

Vasculitis was only seen in the epididymis, but the exact location of the vessels were not given. it was seen in 2 of 105 dogs.The exact location of the vessels were not given - presumably it was the pampiniform plexus of the ovary.

Ushio N, Chambers JK, Watanabe K, Kayano M, Uchida K. Age-Related Arteriolar Changes With Lipid and Amyloid Deposits in the Gonads of Dogs. Vet Pathol. 2021; 58: 558-567.

Diseases of the mesovarium and bursa

The mesovarium and bursa are not considered important by most people, especially from a disease perspective. They are important from a functional point of view because the bursa, an outpouching of the mesovarium surrounds the ovary and keeps oocytes from floating off into the abdomen. The oocyte, once contained, can be taken by the fimbria and transported further into the uterine tube.

The bursa can be affected by any disease of fat or peritoneum as it is a reflection of peritoneum. Ovarian neoplasms that shed into the periovarian regions will be trapped by the bursa, inflammation ascending the uterine tube will be contained around the ovary, and if there are adhesions on the ovary, they will be between the ovary and the bursa.

Primary neoplasms of the bursa are rare and are indicated next.

Lipoma

This is the most well known of the neoplasms of the ovarian bursa. A lipoma of the bursa or of the mesovarium is just like lipoma elsewhere - it is an expansile and usually well circumscribed mass of well differentiated and mature adipocytes. The bursa of the dog is filled with fat - a fact that makes speying of a bitch difficult, especially if she is overweight and has a deep chest!

Gelberg and McEntee (1986) report on 2 cases.

I have seen one case.

Lipoma of the ovarian bursa (opened)

 

Cystic bursa

The bursa becomes cystic when the opening to the peritonal cavity becomes blocked allowing fluid to accumulate in the cavity. Cysts also form when there are adhesions of the bursa to the ovary in such a way that fluid produced cannot escape. Because dogs do not have accessible ovaries, except by laparotomy or endoscopy, this seldom occurs. This is unlike large animals where rectal palpation and aggressive manipulation cause scar tissue. Dogs rarely get perioophoritis, so adhesions from inflammatory conditions are rare.

I have only seen a couple of these. None had an apparent underlying cause.

Cystically dilated bursa with ovarian elements in its wall. The lower example is one that Dr Maria Spinato showed me.

Return to Table of Contents

Perioophoritis (periovaritis)

Rubio et al (2014) examined the bursa of dogs with pyometra, mucometra and normal dogs and found that a low number had culturable bacteria. Of 118 with pyometra, there were 9 with unilateral and 15 with bilateral recoverable bacteria. These were not always the same as the bacteria within the uterus. 4 of 26 control dogs has recoverable bacteria (2 unilateral and 2 bilateral). 10% of dogs with pyometra had septic peritoneal fluid. Histology was not a part of this project.

Rubio A, Boyen F, Tas O, Kitshoff A, Polis I, Van Goethem B, de Rooster H. Bacterial colonization of the ovarian bursa in dogs with clinically suspected pyometra and in controls. Rubio A, Boyen F, Tas O, Kitshoff A, Polis I, Van Goethem B, de Rooster H. Theriogenology 2014; 82: 966-971.

 

Ovarian remnant syndrome

Ovarian remnant syndrome is discussed under the section on 'Complications of Ovariohysterectomy'