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R. Payan-Carreira and M.A. Pires. Ovarian Cysts in Dogs´
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In: Advances in Medicine and Biology. Vol 94 ISBN: 978-1-63484-185-6


Editor: Berhardt, L.V. © 2016 Nova Science Publishers, Inc.

Chapter XX

OVARIAN CYSTS IN DOGS´ PRACTICE

Rita Payan-Carreira* and Maria dos Anjos Pires

CECAV - Animal and Veterinary Research Centre, Universidade de Trás-os-Montes e


Alto Douro (UTAD), Vila Real, Portugal

Abstract
In dogs, ovarian cysts include the fluid-filled structures of any size present within the ovaries,
outside physiological proestrus and estrus; they may be unilateral or bilateral. They are a
common finding, particularly in older females and in females under contraceptive treatments.
In dogs, cysts can originate from various structures in and around the canine ovary; therefore
not all the ovarian cysts are hormonally active. Like in other domestic species, canine ovarian
cysts may be grouped into follicle-derived cysts, which are hormonally active, and the non-
follicular cysts, which are known to be incapable of steroid production, thereby evolving often
silently, in the absence of specific clinical signs, in contrast to follicle-derived cysts that
usually interfere with the female normal cyclicity. Yet, most types of cysts may compromise
fertility. Recent surveys suggests that the prevalence of one type of the other may vary with
the region of the study, possibly representing differences in the reference dog population, in
the strategies used to control female dog reproductive status, in methodological approaches to
diagnosis or in the routine procedures for the practitioner facing the problem.
The morphology of the canine ovary, together with the tendency for a disturbed growth of the
subepithelial structures, makes it prone to the cystic degeneration of the ovarian surface that
may physically compromise ovulation and limits the bitch fertility. On another hand, follicular
cysts that can arise spontaneously or in consequence of the stimulation of a cycle, can either
compromise the ovulation rate of a female and reduce the litter size or predispose to uterine
diseases due increased levels of estrogens. Either way, it is important to establish an early
diagnose of the condition, and try to restore fertility if the female are intent to be breed.
This work intended to provide a comprehensive overview of available information on dog
ovarian cysts. Based on our practice, we discuss the trends on prevalence of ovarian cysts in
the species, the different types of ovarian cysts and the corresponding clinical conditions and
the available diagnostic approaches as well as the existing therapeutic options. The
information provided in constitutes a helpful tool in the clinical approach to canine ovarian
cysts.

*
E-mail address: rtpayan@gmail.com
2

Payan-Carreira and Pires

Introduction
In dogs, cysts arising within or from around the ovaries are relatively common in the clinical
practice. However, it is difficult to quantify the prevalence of ovarian cysts from the
literature, as most reports describe particular clinical situations affecting a very small number
of individuals [1-3] or they focus on particular aspects of the disease [4] or its diagnosis [5].
Clinical studies on the incidence or prevalence of ovarian cysts are rare in dogs, and the
existing report cases referred to histopathology services, which per se present an important
limitation since they are based on the necropsies findings [6, 7] or depend on the practitioner
perception of an existing lesion in an ovariectomy/ovariohysterectomy specimen for which
he/she needs a diagnosis and by the owner which accepts to request the histopathological
evaluation. An old study refer that non-neoplasic ovarian cysts account to 78% of all canine
ovarian diseases [6]. More recently, Pires and Payan-Carreira [8] referred that ovarian cysts
(neoplasic and non-neoplasic) represented around 35% of the lesions found in canine ovaries,
but only in ca. 54% of the situations the cysts were visible under gross inspection of the
ovaries. Therefore, it is possible that prevalence of canine ovarian cysts vary with:
- The geographical location, in particular because of the differences regarding the usual
contraceptive practices (whether or not a female is spayed at youngest ages);
- The breeds represented in the region, as often the breeds change with time, modes and
even with the sort of veterinary establishment participating in the studies;
- The use of drugs to manipulate the canine estrous cycle, particularly for induction of
estrus;
- The procedures used for diagnosing ovarian cysts (such as ultrasonography, endocrine
determinations, visual inspection, or histopathology).

Ovarian cysts are broadly defined as fluid-filled structures of any size within the ovary,
present outside the physiological follicular phase of the estrous cycle [9]. Although this
definition covers both neoplastic and non-neoplastic cavitary lesions, when talking about
ovarian cysts the neoplasic cystic lesions (adenomas or carcinomas of the ovary) are usually
unconsidered.
It is essential for the clinician as well as for the pathologist to be aware of the structures from
which cysts may arise in the canine ovary, either for the implications of its origin on the cyst
ability to produce steroid hormones, and thereby to interfere with the female estrous cycle and
to induce mammary or uterine diseases, or to hinder ovulation and thus interfering with the
female fertility in the absence of other clinical signs. These issues will be detailed in
following sections.

The morphology of the canine ovary

In dogs, the ovary is completely enclosed within the ovarian bursa, a structure resulting from
the fusion of the distal mesovarium and the mesosalpinx, located close to the caudal pole of
the ipsilateral kidney [10, 11]. The ovarian bursa contains a large amount of adipose tissue
that hides the ovary from view, except in a small clear area of the mesosalpinx [12]. In
general, fat content increases with age, in particular after puberty, so that young female dogs
3

Ovarian cysts in dogs

may present a more translucent ovarian bursa whereas older or overweighed females have it
opaque.
The gonads are long and slightly flattened, and their size may be influenced by breed size.
Table 1 summarizes the main available information on the ovary size and weight in dogs. It is
generally accepted that differences in size between the right and the left ovary are
insignificant [13] provided that no lesions are presented. In dogs the opening (ostium) of the
ovarian bursa is very narrow; it is usually made obvious by the predominance of few reddish
tubal fimbriae [11]. Normally, neither the ovary nor any ovarian structure protrudes at the ostium
of the ovarian bursa.
Small, minor variations in the ovary size may be perceived when large antral follicles (during final
proestrus and estrus until ovulation) or mature corpora lutea (in early and mid diestrus) protrude
above the ovarian surface, but it returns to its regular size when these structures sank below the
ovarian surface. The changes in size will depend on the number of structures developing in each
cycle [14]. The contour of the mature canine ovary is irregular from proestrus to mid-diestrus (i.e.,
during the follicular and luteal stages of the estrous cycle) because of the presence of follicles and
corpora lutea [12]; during anestrus, the surface of the ovary is smooth.

Table 1. Reported size and weight of the canine ovary


Average size (in mm) Weight of the
Body size of dogs Reference
(length x width x thickness) ovary (gr.)
Medium sized breeds 15 to 20 X 10 to 15 X 8 to 10 1 to 3 [10]
Small sized dogs (± 11 kg) 15 X 7 X 5 0.3 [15]
Not mentioned 15 X 10 X 6 -- [11]

The ovary is outlined by a surface epithelium [10, 16], originated from the coelomic
epithelium, which is constituted by a simple layer of low cuboidal to columnar epithelial cells
[10, 16]. In older references the surface epithelium of the ovary was named “germinal
epithelium” [17]. It is possible to find some small invaginations arising from the surface
epithelium, simple or branched tubular, with a variable disposition, that some authors
suggested to be at the origin of the sub-surface crypts [12] also named sub-surface epithelial
structures (SES) [7, 17, 18]. SES are ingrowths of the peritoneal covering of the ovary that
continue to develop throughout life; they are only described in dogs among all other domestic
species [12].
The surface epithelium covers a densification of the cortical stroma, inaccurately called
ovarian albuginea, disposed as a thin layer of regularly organized, denser connective tissue,
poorly delimited on profundity, as it progress into the interstitial stroma of the ovary [10].

Ovarian cortex
As in other mammalian species, the canine ovary comprises a cortex and a medulla (Figure
1). In dogs, the ovarian cortex is rather thin compared with the medulla. The ovarian cortex is
sustained by a dense stroma, rich in reticular and collagen fibres and in a particular type of
fusiform cells that resemble smooth muscle cells but are devoid of any striation [10].
Fibroblasts with epithelial-like characteristics are disposed around follicles as follicular theca
[19]. A rich network of thin blood vessels covers the cortical area of the ovary and shows a
spherical, denser disposition around the follicles, in particular in those on latter
developmental stages. In the cortex, a variable number of follicles can also be observed.
4

Payan-Carreira and Pires

Neoangiogenesis is particularly evident in early developing corpora lutea. Many lymphatic


vessels are associated with the external follicular theca layer [19]. It is also possible to
observe in the ovarian cortex of female dogs particular structures once named granulosa cell
cords or islands [20] also called as interstitial gland. These structures, that possibly arise from
atresia of large follicles, form cords of clarifying cytoplasm cells where granulosa cells
continued to proliferate [21]; these structures may further differentiate into pseudotesticular
tubules [12, 20].

Figure 1. Drawing of the morphology of the canine ovary

The morphology and size of the follicles varies according to their developmental stage and
the stage of the cycle. Dogs are a polytocous species, so multiple follicles develop in each
cycle [22]. At birth, most oogonia are surrounded by pre-granulosa cells, and follicle
differentiation is not completed. Oogonia enter the meiotic prophase shortly after birth, the
primordial follicles becoming increasingly abundant by 2 months of age [20, 23]. At 4
months of age, primary follicles are recognized in the canine ovarian cortex, surrounded by a
single layer of cuboidal granulosa cells. Secondary follicles show two or more layers of
granulosa cells disposed around fully-grown oocytes [24]. Synthesis of follicular fluid marks
the transition into tertiary or early antral follicles; these can be found in the canine ovary
between 4 and 5 months of age, whereas large, advanced antral follicles can be found in the
ovary of female dogs reaching to puberty, close to 6 months of age [20, 24]; from this
moment on, the development of large antral follicles coincides the follicular stage of each
ovarian cycle.
In dogs, follicular recruitment occurs in the last third of anestrus [25], but it is only in late
proestrus that follicles are perceived at the ovarian surface as small vesicular structures. The
periovulatory size of canine follicles may vary slightly with the size of dogs. In general,
ovarian follicles at ovulation measure 9 to 12 mm in diameter [22]. Fontbonne [26] reports
that the average size at ovulation, assessed by ultrasound measurement of the inner follicular
diameter, increased with the size of female (4.5±0.5mm 5.3±0.9mm, 5.9±0.4mm and
5.8±1mm, respectively in small, medium, large and giant females), although the differences
among groups were devoid of significant, maybe due to the limited number of females. Table
2 provides a summary of available information on the size of antral follicles and corpora lutea
5

Ovarian cysts in dogs

in dogs. Once the size is an important parameter for the diagnosis of ovarian cysts, it is
important that the practitioner and the pathologist to know the size and appearance of normal
mature follicles in the species.
After ovulation, the post-ovulated follicles transform into corpora lutea that bulge above the
ovarian surface until the 5th week, and gradually decrease in size until they are no longer
perceived below the ovarian surface (Table 2). Nevertheless, corpora lutea can still be traced
on the canine ovary over the next two estrous cycles.

Ovarian medulla
The medulla is usually in a central position in the ovary, taking a more superficial position at
the level of the hilum, where blood vessels and nerves enter and exit from the gonad. The
medulla consists of loose collagenous tissue mingled with elastic and reticular fibres [19].
Besides the large blood and lymphatic vessels and the nerves, the medulla of the canine ovary
also presents embryonic remnants that form the rete ovarii, formed by intraovarian
mesonephric-derived cells. This structure is located adjacent to the hilum [12] and extends
into the medulla; its development and disposition may vary among females [7]. The rete ovarii is
a cluster of cell cords and tubules, lined with a densely stained cuboid epithelium and
containing scant fluid [18]; it frequently forms small papillae, particularly in mature and old
females. Andersen and Simpson [20] refer the existence of changes in the size of rete ovarii
in diestrus and anestrus, thought Mialot and Parodi [7] could not detect changes in this
structure during the stages of the cycle.
In carnivores, the rete system extends, into the periovarian tissue, forming the extra-ovarian
rete that ends blindly, derived from mesonephric tubules and cords or the mesonephros [9].

Cyst in and around the canine ovary

There are different types of cyst that develop within and around the ovary (Figure 2; Table 3).
Cysts occurring in the ovary may be of two main types [5, 9, 12]:
- The follicular cysts (Figure 2), arising from medium-large antral anovulatory
follicles that often originate during a follicular phase and remain in the ovary for
longer periods;
- The non-follicular cysts (Figure 2) that include cysts originated from the
mesonephric tubules (cysts from the rete ovarii and paraovarian cysts), cysts derived
from the surface epithelium (that might evolve to adenoma of the ovary) and cysts
coming from the subsurface epithelial structures (SES).

Although in the literature the existence of luteal cysts in dogs is mentioned [4, 6, 27], their
existence as a clinical entity is uncertain. Cystic corpora lutea are described in dogs, but in
fact antral corpora lutea are always present in the first ~20 days of diestrus; thus, unless a
clinical situation encompassing an elongation of the interestrous interval due to prolonged
luteal stage (evidenced by higher levels of peripheral progesterone for a period over 60-70
days) accompanies the presence of corpora lutea (CL) larger than the usual for the breed size,
the diagnosis of cystic CL should be disregarded. Nonetheless, in dogs, the most frequent
cause for interestrous elongation is a prolonged anestrus [28].
6

Payan-Carreira and Pires

Figure 2. Macroscopic features of canine ovarian cysts. Follicular cysts – non-movable regular cysts
(arrows) delimited by a thick and regular wall, containing a serous fluid, that may escort corpora lutea (CL).
On cut sections, the luteinization of the walls is usually limited to the inner mural surface. Rete ovarii cysts
(red arrows or *) are cysts located in the hilum (arrowhead) of the ovary. Therefore, ovarian parenchyma
(Ov) appears parallel to the cyst origin; the vascular network supplying the ovary is usually found between
the cysts and the ovary. SES cysts are usually small sized surface cysts (Cyan arrows) presenting a regular
and thin wall, that do not support blood vessels, and containing a serous fluid; they are frequently multiple. In
this image, they co-exist with a large follicular cyst (FC). Ovarian adenoma (delimited by the red oval
shape) represents a benign proliferation of the surface and SES epithelium, originating multiple small cysts
that give the ovary surface a foaming appearance. Usually, the gonad (Ov) is contained within the ovarian
bursa and the tubal fimbriae show a normal surface. On the cut surface, the differences in individual cysts
sizes are noticeable. In the ovarian adenocarcinoma the size of the cysts at the ovarian surface is rather
variable, and its appearance quite heterogeneous. On the cut surface the ovarian parenchyma is usually not
visible, and often the entire gonad presents a sponge feature.
7

Ovarian cysts in dogs

Epidemiological aspects

The majority of ovarian cysts present no signs or symptoms [8]. Thereby, they frequently
remain undiagnosed, which makes it difficult to estimate the incidence and prevalence of the
condition. As said before, the incidence of the different types of ovarian cysts is difficult to
establish in dogs. Moreover, some confusion exits on the classification of cysts, particularly
in clinical practice, because the available complementary diagnostic methodologies do not
allow to clearly distinguish among the different epithelial ovarian cysts (cystic rete tubules,
cysts of SES, paraovarian cysts or adenomas), which impairs to establish the true incidence of
the different type of cysts in dogs´ practice. The existence or the absence of pathology in the
uterus of the mammary gland may be of additional value for the clinical diagnosis. Although
the practitioner must be aware that both the uterine and mammary diseases may co-exists with
non-follicular cysts following independent age-related process, and therefore may have
independent courses. Aging increases the prevalence of uterine diseases that in dogs are
associated with characteristic features of the species reproductive cycle, namely the relatively
long recurrent progesterone dominance stages [25].

No clear information exists on the epidemiologic aspects of the canine ovarian cysts. Seldom
information based on clinical surveys is reported in the literature. In previous surveys, follicular
cysts would be less frequent than those originating from SES or the rete [5, 8, 27] (Table 4). Yet,
the number of published case descriptions is higher for the later compared to the former, for which
it would surely contribute the fact that follicular cysts or malignant ovarian adenocarcinoma
usually evidences exuberant clinical signs, while the cysts of the SES and rete, as well as the
surface epithelium adenoma usually progresses in a silent clinical form. Data compiled on Table 4,
resulting from the studies of several veterinary histopathology laboratories [8, 27, 29], clearly
show that epithelial cysts originated from the surface-SES and rete structures are those presenting
a higher prevalence worldwide. In opposition, among the ovarian cystic tumours, adenocarcinoma
is rarer than the adenoma [6].

Most reports agree that incidence of cystic disease in dog ovaries increase with age [6, 8, 9],
particularly on what concerns epithelial cysts originating from the SES or the rete ovarii [28],
which is also true for ovarian adenoma. Age predisposition for follicular cysts is not so
clearly defined, in particular because some evidences now exists that deslorelin treatments
may induce follicular cysts [2, 30] due to anovulation. Nevertheless, spontaneous follicular
cyst have been described more frequently in female dogs above 5 to 6 years of age [2, 31, 32]
than in younger females. In contrast, the ovarian adenocarcinoma develops in older females,
between 8 to 10 years of age [33, 34] albeit the most exuberant situations have been described
in younger females, in general 3-4 years of age [34, 35].
Ovarian cysts in dogs
8

Table 2. Size and appearance of normal antral follicles and corpora lutea (CL) in dogs. [14, 22]
Developmental stage Stage of the cycle Size (mm) Gross appearance
Late anestrus Not visible on the ovarian surface
0.2 – 1.5
Only visible in longitudinal cuts of the ovary
Antral follicle
Early proestrus Randomly distributed in the ovarian surface as clear greyish areas, with indistinct
1.5 - 3
boundaries.

Follicles appear as vesicular structures bulging from the ovarian surface, spherical in
Late proestrus
Pre-ovulatory follicles 5–8 shape
and early estrus
Follicular walls are translucent and support a convoluted vascular network

The follicular wall become rigid and opaque due to pre-ovulatory luteinization of the
One day post
4 -13 mural granulosa layer
LH surge
Prior to ovulation, the stigma is visible as a grey spot in the follicular dome
Peri-ovulatory follicles

The follicle tension decreases, but the follicular walls do not collapse at ovulation, and
At ovulation 9 -12
the haemorrhage within the follicle cavity is negligible

Luteinization of the post-ovulatory follicles is completed in 2-3 weeks. Changes in


colour, size, protrusion above the ovarian surface and consistency occur during CL
lifespan. In brief, in the initial stages of CL maturation, a slightly eccentric antrum is
visible; the follicular walls become opaque and are pinkish to carmine in colour. After
two weeks, the mature CL are compact, carmine and still protrude above the surface of
6.5 – 12
Corpora lutea Diestrus the ovary; after the 5th week, the projection of the CL at the ovarian surface decreases,
(1st week post-ovulation)
as it decreases in size and become more firm and yellowish in colour. By week 12
post-ovulation CL are visible as small pale yellow structures within the ovarian cortex;
although not bulging they can be found by visual inspection until week 16 post-
ovulation. Corpora lutea continue to decrease in size, but they can be traced over the
next 2 estrous cycles.
Payan-Carreira and Pires
9

Table 3. Main classification of ovarian cysts by origin


Origin Type of cysts Brief macroscopic description * Brief histological description**
CYSTS WITHIN THE OVARY
Cysts are lined by granulosa cells, expressing inhibin
alpha, but negative for desmin or cytokeratins (AE1/AE3)
Variable in number and size Variable number of granulosa cell layers, that may
Follicular cysts Non-movable cysts bulging above the ovarian surface present signs of atresia
Follicle
[Graafian or non-ovulatory cysts] In the ovary, normally developed CL may co-exist Luteinization of the mural granulosa may or may not be
May originate syndromes of estrogen imbalance present
The oocyte is degenerated
Theca layer may be replaced by fibrous tissue
Starting often as a dysplastic proliferation of SES Lined by simple-cuboid cells similar to those of the
leading to the formation of vesicles; confluent vesicles surface or SES epithelium
remain separated by thin lamellae of connective tissue May present vegetative ingrowths
Sub-surface
As they growth, SES cysts deform the ovarian surface Strong expression of cytokeratins (AE1/AE3+) and
epithelial SES cysts
Rarely larger than 5 mm desmin.
structures
Often bilateral May weakly express placental alkaline phosphatase
More often in older animals and females under (PLAP), while the surface epithelium shows moderate
progestagen treatment expression
Represents cystic dilatations of the rete tubules in the
peri-hilar area of the ovary
Cysts lined by a single layer of cuboid epithelium; may
Multiple cysts of variable size
Rete ovarii Rete cysts be ciliated
When large, they may compress the ovarian cortex
Positive for S100, desmin and cytokeratins (AE1/AE3)
Frequently unilateral
Mainly in older animals
CYSTS AROUND THE OVARY
Cysts arising from Wolfian remnants locate in the
Wolfian cysts are composed of thin wall of connective
mesovarium, close to the ovary tubular extremity.
tissue and muscle, lined by a single layer of cuboidal or
Müllerian duct cysts locate in the fimbriae.
low columnar cells with clear cytoplasm, covering a
Paraovarian Wolfian or Movable cysts of thin walls on the cranial surface of the
basement membrane. Some cells are ciliated
cysts Müllerian ducts ovaries, that may protrude from the ostium of the
Müllerian cysts present an epithelium similar to that of
ovarian bursa
the uterine tubes, may or not be ciliated, and lacks a
Variable in number, if solitary they tend to achieve big
basement membrane
dimensions
Ovarian cysts in dogs
10

CYSTS EPITHELIAL TUMOURS OF THE OVARY


[Benign lesion]
Covering the ovarian surface Infoldings and papillary projections of the ovarian
Enlarged and irregular shape of the ovary surface and SES structures
Smoothed or nodular Scant connective tissue stroma
Ovarian adenoma Frequently bilateral Cysts are lined by small cuboidal or cylindrical cells that
Multiple cystic differently sized structures may present cilia
The enlarged ovary is confined within the ovarian bursa Less often, cells are arranged in a glandular pattern
Mainly in middle aged or old females or in females Rare mitotic figures
under contraceptive treatment Positive to cytokeratins (AE1/AE3)
SES and
Surface
Covering the ovarian surface [Malignant lesion]
epithelium
Irregular shape of the ovary Malignant form: Similar histological appearance to the ovarian adenoma
Adenocarcinoma Increased mitotic activity
Multiple cysts of different size and aspect Invasion into the ovarian stroma
Rapid growth and proliferation Extension into tissues adjacent to the ovary
Ovarian adenocarcinoma
Destroys the ovarian bursa, freeing the ovary in the Vascular invasion may be observed
abdominal cavity
Highly metastatic à sudden clinical onset Size and surface permeation are important criteria of
accompanied by ascites and depression malignancy
Develops in young females
* Based on the references [7, 9, 12]
** Based on the references [5, 36]
11

Ovarian cysts in dogs

Table 4. Prevalence of canine ovarian cysts (%) according to the type*


Ovarian cysts Paraovarian Cystic epithelial neoplasia
Reference
Follicular Rete ovarii SES cysts Adenoma Carcinoma
19% -multiple
8% 17.4% -- 8.7% 0.9% [6]
36% -solitary
10% 48% 22% -- -- [27]
24% 11% 52% -- -- -- [5]
-- 26% 20% -- -- -- [7]
1% 20% 4% 7% 3% 9% [29]
6% 57%** 39% 12% -- 4% [8]
* The percentages were estimated from the total number of ovaries with lesions or with cysts, according to
references
** this value represents cyst located in the rete ovarii and hilar region, therefore it may include also
paraovarian cysts.

Pregnancy and parturition seems not to have a protective role for cystic diseases in the canine
ovaries. Independently of the cyst type (epithelial vs. follicular, or neoplasic vs. non-neoplasic
cysts), they develop in both the nulliparous and multiparous females. Moreover, in our
practice, development of epithelial cysts from SES tends to be anticipated in females under
contraceptive treatment.
In dogs, ovarian cysts can evolve as solitary or multiple structures and also can develop on
only one ovary or on both ovaries [6]. Nevertheless, epithelial cysts in the ovary are
frequently bilateral while paraovarian cysts tend to occur as unilateral structures. In a recent
publication, Knauf and colleagues [4] found that multiple follicular cysts were more frequent
than the solitary and also that they occurred often in both ovaries, contrasting to our personal
experience, corroborated by Dow findings [6] who also observed more often solitary
follicular cysts than multiple follicular cysts.
Until now no breed predisposition has been described for the occurrence of ovarian cysts,
whether concerning the epithelial or the follicular cysts. Nonetheless, case reports on
follicular cysts represented more frequently purebred bitches than mongrels. This can be
related to the fact that most mongrels are spayed or under medical contraceptive treatments
(depending on the country) to avoid breeding.

Signalement and clinical aspects

The origin of the ovarian cysts clearly influences the development of overt clinical symptoms.
Grossly, follicular cysts are often associated with more or less clear signs of
hyperestrogenism, particularly when they are multiple, whereas the cysts originating from the
ovarian epithelial structures frequently develops for long unnoticed since they do not produce
sex steroids. Additionally, ovarian adenocarcinoma is usually accompanied of a severe
clinical form distinctive from the other epithelial cysts or cystic tumours of ovarian origin.
Therefore, we will distinguish in this section between follicular cysts, silent epithelial ovarian
cysts and ovarian adenocarcinoma.
12

Payan-Carreira and Pires

Follicular cysts
Follicular cysts are hormonally active structures that develop in the female dog ovary. They
often represent large antral follicles that failed to ovulate, but did not respond to atresia
stimulus. Therefore, under gross examination, follicular cysts resemble Graafian follicles,
larger than a normal follicle (see table 2 to evoke the follicular size in dogs).
In the bitch, anovulatory cysts may develop as solitary or multiple structures, and they may
also be unilateral or bilateral. As main difference to other carnivore species, the follicular
cysts do not luteinise past the existing mural granulosa luteinization existing at the moment of
its formation. Therefore, changes from an estrogen to progestagen dominance does not occur
in dogs, compared to cats and cows [37].
Spontaneous follicular cysts tend to occur in middle and old age groups. For the canine
follicular cysts, based on the literature, Johnston and colleagues [28] describe an age range of
1-19 years and an average age at diagnosis of 8 years old. Recently, evidences exist that they
also develop following therapeutic induction of estrus when deslorelin, an GnRH analogue, is
used [2, 30]. Authors agree on the need to implant only female in anestrus, after a thoroughly
gynaecological exam. However it is important to remember that the interestrous interval may
vary between bitches, and this parameter should always be taken into consideration when
defining the most suitable moment for insertion of deslorelin implants.

Under gross inspection, ovarian cysts may appear as thin-wall structure(s) containing clear
serous fluid (Figure 2), similar in appearance but larger in size than the cohort of existing
follicles or corpora lutea bulging above the ovary. In the wall of the cysts, small blood vessels
may appear, but the blood network is often less expressive than in normally developing large
antral follicles. The size of the cystic follicles varies from 1-1.5 to 10 mm in diameter [9, 12],
though sporadic reports on larger [27] or smaller [4] cysts exists.
The pathogenesis of the process remains unclear. It has been proposed that follicular cysts
originate from an inability of a large antral follicle to respond to the ovulatory stimulus [37,
38]. This mechanism may originate from a central failure to produce an adequate amount of
gonadotropins, in particular of LH, to sustain an adequate follicular growth and ovulation [4],
or from at peripheral level due to imbalances in the follicular molecular homeostasis
compromising its response to the pre-ovulatory LH surge. The former hypothesis would
explain the occurrence of multiple follicular cysts in dogs, while the later would rather apply
to the occurrence of solitary follicular cysts.
Follicular cysts are known to be productive, that is they retain the capacity to produce
estrogens and/or progesterone, thereby presenting the potential to cause disease [4]. Their
reflexes on the bitch´ clinical condition depends on the amount of sex steroids, in particular
the estrogens, produced by the cyst(s), which may depend also from the number of the cysts
developing in the ovaries. Marino et al. [27] report changes in the ovarian cycle in 53% of the
surveyed cases, coexisting with uterine dysfunctions, while the remainder 47% were
asymptomatic due to its association with corpora lutea. Moreover, Knauf and colleagues [4]
found only a fair correlation between the sex steroid peripheral levels and the estradiol and
progesterone in matched follicular cysts, whilst the estradiol or progesterone concentrations in
blood were not correlated with the number of ovarian cysts present in a given individual.
Moreover, they also refer to the co-existence of follicular cysts and corpora lutea [4], which
could be explained by the fact that steroids hormones concentration, particularly those of
estrogens, was higher and highly variable in the cyst-fluid than in the peripheral blood.
13

Ovarian cysts in dogs

In dogs, antral non-ovulatory follicles will suffer atresia during diestrus, sequential
degeneration of the oocyte and granulosa cells [6, 9, 27], suggesting that this may be a self-
limiting condition, in the absence of co-existing uterine or mammary dysfunction (which in
dogs are importing clinical entities requesting treatment by themselves). This can also be the
fate for the follicular cysts induced by deslorelin treatment, since as inferred from Borges and
collaborators [30] the females recover the ovulation rates in subsequent induced or
spontaneous cycles. The role of the progesterone levels in diestrus on the follicular cysts
regression has yet to be explored in dogs.
Hyperestrogenism represents a syndrome that may present a variety of clinical signs or
symptoms depending on the relative amount of estrogens/progesterone in tissues. The owner
could report either persistent estrus [27, 28, 31], which may be lengthened up to 3 months, or
shortened interestrous interval [4, 28] compared to the normally exhibited by the female with
recurrent heat behaviour. Seldom, if estrogen production by cysts is insufficient to contradict
the progesterone dominance, the ovarian cycle may not be disturbed and the female retain her
normal cyclicity. In females exhibiting elongated estrus, the visual inspection of the perineum
reveals the existence of vulvar oedema; however, if estrogen stimulation persists for more
than 30-40 days, the vulva losses the typical turgid swollen aspect displayed during heat, and
a flaccid oedema can be noticed; estrogen impregnation may be confirmed in the vaginal
cytology, by the presence of typical keratinised cells. Swelling of the mammary glands [9],
which can be observed in some cases [39], is not always perceived by the owners.
If the ability to produce estradiol encompasses or overcome that of the progesterone
production, changes in the estrogen and progesterone in target tissues for sex steroid would
reflect in the onset of disease, particularly in the uterus. Often, the disturbances in the sex
steroid ratios will favour the development of mucometra and pyometra [6, 9], which can be
favoured by pre-existent cystic endometrial hyperplasia, particularly in older females [37].
Developing mucometra or pyometra may originate main clinical symptoms, particularly the
later, which include: anorexia, depression or lethargy, polyuria and polydipsia, vomiting,
abdominal distension, abdominal distress or pain, mucous or purulent vaginal discharge and
in some cases, sepsis [40]. Less frequently, possibly associated with a chronic exposure to
low levels of estrogen, the uterus develops keratinizing squamous metaplasia and chronic
endometritis [9], perceived by a chronic purulent vaginal discharge, which is frequently
associated with more severe symptoms of uterine endometritis/pyometra.
Skin diseases can be an important symptom that often takes the owner attention [27, 32, 37]
in chronic low estrogen impregnation. These include a nonpruritic symmetrical bilateral
alopecia, lignification, hyperpigmentation and hyperkeratosis. Alopecia most frequently
develops on the caudal aspects of both thighs [32].
Toxic effects associated with chronic exposure to estrogens may also escort
hyperestrogenism. The following problems may combine in hyperestrogenism cases:
pancytopenia, anaemia, thrombocytopenia and consequent bleeding (represented by epistaxis,
haematuria, petechia or haemorrhagic vulvar discharge) or granulocytopenia [9].
Sporadically, the owner complains of disturbed behaviour, in particular pseudopregnancy, but
which is seldom clinically confirmed, and no references to it have been found in the literature.
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Ovarian epithelial cysts and ovarian adenomas


Ovarian epithelial cysts (whether they are SES or rete cysts) are non-productive, i.e. they do
not produce sex steroid hormones, and therefore they progress asymptomatically [41].
Consequently, they are often found as an incidental finding during routine physical or
abdominal ultrasound examinations, during uterine surgery or at necropsy, in the absence of
ovarian disorder. As they do not disturb the normal cyclicity of the female dog, they are
detected in otherwise normal ovaries [6]. Due to these characteristics, information on the
pathology and the clinical course of epithelial cysts of the canine ovary is scarce.
The co-existence of uterine or mammary diseases with ovarian epithelial cysts must not be
understood as indicator of an overproduction of sex steroid hormones. As their incidence
increase with age, in general, the concomitant present of other age-related diseases should be
primarily foresee as a coincidence of independent processes.

SES cysts (Figure 2) develop in the ovarian cortex, contrasting to those of the rete ovarii or
the derived from Wolfian ducts, that are found in the ovarian hilus [7, 9] SES and rete cysts
may co-exist in the same ovary [12].
Frequently, the SES cysts are small, its size ranging from microscopic cysts, barely visible
during visual inspection, until close to 5mm, that give a spumous aspect to the ovarian
surface, but they are seldom larger than this [12]; they tend to spread through the ovarian
surface, as they are commonly multiple. In general, cysts of the surface/SES extending at the
ovarian surface, alike adenomas, usually enlarges the normal ovary size; beyond a given
dimension, enlarged ovaries can be palpated in the caudal pole of the kidney, as small,
relatively firm ovoid masses, in mature to old females, above 7 years old. Occasionally,
during the physical examination, unspecific signs of abdominal distress during
transabdominal palpation can be observed. Distinction between SES cysts grossly visible and
covering the ovarian surface and adenoma is difficult [9, 38], although the later tend to show
thicker, irregular walls; moreover, adenomas increase usually the dimension of the ovary,
which appear as large, floating masses caudal to the kidney. Most SES cysts and adenoma are
recovered by the surface epithelium of the ovary [7]. It is possible that in more advances
situations, the cystic proliferation of the cysts in the ovarian cortex may impose a physical
barrier or in some way disturb the ovulation, thus being associated with infertility. Still this
hypothesis was never proved.

Contrasting to the SES structures, cystic rete ovarii (Figure 2) are often unilateral, and they
develop in the whole or in a segment of the rete tubules. They are easily confounded with
paraovarian cysts under macroscopic examination. MacLachlan [38] refers that rete ovarii
cysts may induce the compression of the ovarian cortex due to their size; however our
practice shows that this is observed when cysts develop as solitary or a small numbered cysts
of larger dimensions. According to Mialot and Parodis [7], age seems not to predispose to the
development of rete ovarii cysts.

Cysts originating from remnants of the Wolfian ducts and other paraovarian cysts (Figure 2)
also develop near the ovarian hilus, and they reach dimensions over the 4 and 5 mm [7, 12].
They are thin-walled, slow growing cysts, which allows them to protrude from the ostium of
the ovarian bursa as they became large. Still, the paraovarian cysts are not report to impair
ovarian function or compromise the fertility potential for the female.
15

Ovarian cysts in dogs

Ovarian adenocarcinoma
Ovarian adenocarcinomas are rare malignant tumour of the superficial structures of the
ovarian cortex. They are usually multicentric and may be bilateral, which suggests the
existence of a genetic background. In the study by Patniak and Greenlee [34], about one third
of the ovarian carcinomas were bilateral.
Ovarian carcinomas may vary in size; ovaries are frequently are detected as irregular,
multicystic masses above 10 cm, with a typical cauliflower aspect [9] (Figure 2).
Nevertheless, small-sized ovarian carcinomas were found in older females [6, 28, 33]; the size
of the tumour does not seem to determine the existence of metastatic disease [6]. In most
severe situations, they invade and completely destroy the ovarian bursa, thereby exposing the
ovary within the abdominal cavity. Our experience suggest that size does not relate with the
tumour invasiveness, therefore a more complete histopathological assessment of the tumour
(invasion of the ovarian capsules, number of mitosis per high power filed, the presence of
necrotic areas, for instance) is needed to provide valuable information concerning the survival
expectancy.
Once free of the bursa confinement, the tumour rapidly spread and abdominal implantation
quickly occurs [9], and in rare cases giving distant metastasis in the lung or liver, originating
exuberant clinical signs. There are evidences that this tumour responds to estrogen
stimulation [9], but they are not productive by themselves; thus ovarian carcinoma does not
disturb the normal ovarian cycle. The tumours are initially insidious, and initially progresses
sub-clinically; clinical symptoms are usually detected when the carcinoma invade and
originates metastatic syndromes. Abdominal effusion is commonly associated with
carcinomatosis of the peritoneal cavity. Metastasis occurs by invasion and implantation in
adjacent tissues but also by lymphatic and vascular permeation [9, 34].
Most reports on ovarian adenocarcinomas describe an acute onset of abdominal distension in
a female close to 3 years of age that had recently become lethargic and losing weight [35, 42,
43]. Previous reproductive history is not helpful to the diagnosis of ovarian carcinoma, as
they may be diagnosed in nulliparous females, but also in females with a pregnancy and
parturition in the previous cycle [9] and the female maintain regular estrous cycles [42].
During physical examination, the palpation of an abdominal mass in the caudal abdomen, as
described by Ajadi et al. [35], it is not always possible, depending on the amount of ascites
and the abdominal tension. Pleural effusion may be present in more severe situation and with
lung metastasis [28], raising difficulties to heart and lung auscultation; in those situations
distressful respiratory movements and altered respiratory rate may be observed in the female.
Abdominal discomfort may be present, and often the owners report a reduction of activity in
particular concerning abdominal stressing exercises. Vulvar discharge is occasionally
reported [42]. Dehydration may be detected, which along with diverse degrees of renal
insufficiency, may influence the levels of some biochemical parameters in blood analysis
[35]. Non-regenerative anaemia and leucocytosis are mentioned in most cases. Additionally,
hypercalcemia has been referred due to altered parathyroid function [43].

Diagnosing ovarian cysts

Cystic structures that do involve follicles and thereby do not originate hyperestrogenism may
persist silent for long period of time, thus remaining undiagnosed until they have enough size
16

Payan-Carreira and Pires

to be detected upon abdominal palpation or during an abdominal ultrasound scan. Diagnosis


should results from the integration of the information collected by different methods.
An attentive collection of the reproductive anamnesis, along with the physical examination
will discard suspicions of hyperestrogenism that accompanies follicular cysts. Although the
measurements of peripheral levels of estradiol are considered effective (but not
pathognomonic) for its diagnosis, the vaginal cytology may be helpful to confirm the
existence of persistently elevated estrogen impregnation if females with history of persistent
heat or recurrent short interestrous interval (provided they are in heat). In the physical exam,
the vulva is frequently swollen, and a more or less abundant dark sero-haemorrhagic or
mucous discharge is present [41, 42]; if estrus symptoms last for more than 28 days, a flaccid
oedema of the vulva may be found, and the vulvar discharge may become whitish or mucous-
purulent. The existence of a chronic vaginal discharge is also a common complaint. Although
the female displayed estrus behaviour, in general she does not allow mounting, and its
personality may become altered when heat is prolonged for more than a month. Follicular
cysts diagnosis is made based on the history of persistent estrus and/or hyperestrogenism. The
main differential diagnosis sought to be made with granulosa cell tumours producing high
levels of estrogens, for which the results from the abdominal palpation and the abdominal X-
ray and ultrasound are important diagnostic criteria.

On the physical examination, bitches are often alert and do not present discomfort, and the
rectal temperature, pulse and respiratory rates were within reference ranges. An exception to
this apparent normality is the ovarian adenocarcinoma, which generally is accompanied by
complaints of anorexia, discomfort, apathy, pronounced weight loss and ascites [35, 43].
Besides the adenocarcinoma situations, only dogs presenting large ovarian cysts may show
abdominal distension. Refusal to climb or descend stairs may, however, be reported by
owners when the ovarian masses reach a significant increase in size, which may be associated
with stimulation of adrenergic pathways due to distension of the ovarian bursa. Non-pruritic
bilateral symmetrical alopecia in the trunk and perineum, as well as lichenification and
hyperkeratosis, suggests hormonal imbalance and are associated to excessive estrogen
impregnation [35, 37], supporting the diagnosis of productive ovarian cysts.
The transabdominal palpation will allow detecting changes in the ovarian dimensions that
often accompanies benign cystic conditions of the ovary, in particular in the case of adenoma.
Adenomas increases the size and consistency of the ovary, that can became palpable as a
movable mass in the mid-caudal abdomen, close to kidney, and are often bilateral, while most
follicular cysts remains undetected in transabdominal palpation. Ovarian tumours, such as
granulosa cell tumours, teratoma or disgerminoma, are the main differential diagnosis for
ovary enlargement; in those cases, the abdominal ultrasonography and/or the X-ray are
crucial to distinguish between the clinical situations.

The use of ultrasonography may be helpful to diagnose ovarian cysts. In general, SES and
rete cysts not attaining large dimensions may remain unperceived at the ultrasound scanning
of the ovaries. Contrasting, follicular cysts are usually visible on ultrasound scans as anechoic
structures with thin walls (Figure 3) and acoustic enhancement [44], while the ovary retains
its normal ovoid shape; seldom, some of them may evidence signs of granulosa cell
luteinisation similar to the detected in normal developing follicles, although thinner. Size is
an important parameter when diagnosing follicular cysts as in the majority of the cases they
17

Ovarian cysts in dogs

will be slightly larger than the coexisting cohort of follicles in the same or the contralateral
ovary (Figure 3). Moreover, follicular cysts may be single or multiple. In the later case, larger
anechoic structures separated by thin hyperechoic walls are perceived. Frequently, follicular
sizes are similar and present normal echoic pattern. If doubts arise, a second scanning could
be arranged for 1 to 2 weeks later, to establish comparison to the structures in the ovary.
Follicular productive cysts remain unchanged for some weeks, while follicles that ovulated
assume the echoic pattern of corpora lutea, with disappearance of the anechoic antrum [45].
Non-follicular cystic structures representing adenomas, rete cysts or paraovarian cysts may
incidentally be found during abdominal ultrasonography. Only rete cysts and paraovarian
cysts larger than 5mm are detected as anechoic regular structures that a rounder contour to the
image of the ovary or are located parallel to the ovary (Figure 3). Distinction from follicular
cysts is difficult in US images, particularly when they are not large structures. Adenomas
appear as multiple anechoic cavities located within the ovary, with diverse size and
echogenicity, and the overall size of the gonad is usually increased. When small cysts
compose adenomas, the ovary presents an irregular [44], foamy contour. Acoustic
enhancement is sporadic. In the case of adenocarcinoma, the ultrasound image of the ovary is
similar in appearance to that evidenced by adenomas. However, the former most frequently
appear with more heterogeneous cysts in both size and sonographic pattern [44]; it often co-
exists with signs of free abdominal fluid (Figure 3). Then the multicystic ovary seems to float
from a pedicle, the representation of the ovarian bursa being inexistent.
Coexistence of uterine disease is possible, but the non-productive cysts seldom cause uterine
disease; however, it should be annotated in the clinical file, as it may dictate the available
options.

Abdominal radiography is less helpful than ultrasound imaging, and therefore less frequently
accounted for the diagnosis of ovarian cysts. Unless it exists an important difference in the
ovarian size or in the adnexal tissues, usually associated with the existence of extremely large
cysts, no changes are perceived on X-rays. Rather large cysts may be identified as a soft
tissue-density mass in the central abdomen, caudal to the kidney. If the cyst is large enough, a
colon filled with faeces, suggesting delayed intestinal transit.

The peripheral measurements of estrogen and progesterone determination are not always
helpful in the diagnosis of follicular cysts, because they not always evidence clear changes in
the serum levels of estrogen [4]; moreover, they do not correlate with the severity of the
process. In other hand, assays for canine estrogen are not always readily available and the
normal range values also greatly vary among laboratories. Estrogen impregnation may also be
suspected from the results of vaginal cytology. However one should remember that if the
follicular cyst does not produce enough amount of estrogen to compromise the progesterone
dominance in the luteal stage, the values for peripheral estrogens might be unchanged or
inconclusive.
Complete blood count is expectably altered when signs of hyperestrogenism and of estrogen-
related toxicity accompany follicular cysts; but the inexistence of changes should not limit the
diagnosis, particularly on respect to epithelial ovarian cysts or epithelial tumours of the ovary.
In ovarian adenocarcinomas, multiple changes in the blood parameters may escort the clinical
condition, derived from the systemic disease (such as azotemia or metabolic acidosis) or
hypercalcemia due to paraneoplasic syndrome.

Image 4 represents a brief map for guiding the diagnosis of ovarian cysts in dogs.
18

Payan-Carreira and Pires

Figure 3. Ultrasonographic features of canine ovarian cysts. Follicular cysts (arrows) appear as
anechoic structures slightly larger than co-existing follicles (Fol), and fail to evidence the regular
echoic pattern of granulosa luteinization (yellow bar) typically found in late antral follicles in
dogs. Paraovarian cysts are observed as larger anechoic thin-wall structures (Cyst) that often are
observed close to the ovary (Ov.). The Adenoma scans show usually multiple anechoic cavities
with heterogeneous size and echogenicity. In this image od adenocarcinoma, the gonad presents
multiple hypoechoic to anechoic structures with different size and ultrasonographic pattern,
surrounded by a collection of free abdominal fluid.
Ovarian cysts in dogs
19

Figure 4. Diagnostic map for ovarian cysts in dogs


20

Ovarian cysts in dogs

Therapeutic strategies
Two main issues regarding the available therapeutic approaches to ovarian cysts in dogs
concern: the value or interest of the animal for breeding, which in turn also depends on the
age, and the type of cystic pathology diagnosed in a particular animal.
As stated by Sontas et al.[3], in veterinary medicine the therapeutic options focus mainly on
follicular cysts since other cysts do not cause a clinical disease. Therefore,
ovariohysterectomy is often offered as curative and to eliminate the risk of recurrence in non-
breeding female dogs or when the cystic condition escorts other genital diseases such as
pyometra.

Treatment proposed for follicular cysts is based on the attempt to luteinize the cystic structure
so it can regress later, by the end of a diestrus stage. Available options include the
administration of GnRH (Gonadotropin-releasing Hormone, 50µg, intramuscular) or hCG
(human Chorionic Gonadotropin; 500UI, intramuscular, twice at 48h interval). However the
success of these treatments is limited. Data compiled by Johnston and colleagues [28]
reveales that the success of GnRH treatment was higher compared with hCG (64% of the
cases were resolved by GnRH administration, compared to 43% of resolved cases with hCG).
Nevertheless, in 43% and 33% of the situations responding to GnRH and hCG administration,
respectively, recurred therefore demanding for a surgical alternative.
Sporadically, follicular cysts have been tentatively treated with tamoxifen citrate or
prostaglandin F2 , but application of these drugs ensued recurrence and failure of resolution
α

respectively (Olson et al. 1989, cited in [28]).

Surgical approaches to ovarian cysts of follicular type also traditionally encompass the
ovariohysterectomy [28] whenever the female presents degenerative cystic uterine diseases or
pyometra and it is not intent to reproduction or the clinical condition does not respond to
medical therapy. Occasionally, the surgical drainage and flushing of the cystic structures has
been attempted, and the few reports available mentioned the cure for the situation [46, 47].

As previously mentioned, non-productive benign cysts are usually found as an incidental


finding during physical or ultrasound examination, and at OVH. No medical treatment is been
available to these cysts, since their etiopathogenesis is unclear. Therefore, surgery is the
option remaining. Although the usefulness of OVH may be questionable, since these cysts do
not induce clinical disease, nonetheless they will growth with time, and in some situations
they may reach such a size that unspecific symptoms of abdominal discomfort may became
apparent.

Conversely, the treatment of choice for ovarian adenocarcinomas is surgery, which should be
performed according to standard oncologic surgical principles to minimize further tumour
seeding into the abdominal cavity. Ideally, the excised genital tract should be sent for
histopathological analysis. The characterization of the tumour aggressively and the
confirmation of the type of tumour are crucial to establish a prognosis or even to attempt
complementary medical treatment. However, rather limited information is available on the
21

Payan-Carreira and Pires

use of chemotherapy or radiation therapy in the treatment of ovarian tumours in veterinary


medicine, which compromises possible recommendations.

Final comments
This work revised the available information on the different types of cysts arising within and
around the canine ovary. Although follicular cysts are often referred in the literature, this sort
of lesions is less frequent in the canine practice, albeit they may present exuberant
hyperestrogenism syndrome that draw the clinician or the owner´s attention. In contrast, cysts
arising from the epithelial structures are commonly found in mature and older female dogs,
but evolve silently and remain undiagnosed for longer periods. Most infrequently, ovarian
adenocarcinoma is diagnosed in females presented at the clinic for a sudden abdominal
dilatation, weight loss and depression . The sudden onset of the clinical symptoms and the
degradation of the animal condition are often negative prognostic signs.
It was intent to gather in one chapter the scattered information on the ovarian cysts in dogs,
including the pathologic aspects of the lesions, while reviewing the symptoms or the clinical
findings that will orientate the diagnosis. Definitive diagnosis should be supported by
histopathology, as not always the macroscopic assessment of ovarian lesions will allow the
practitioner to reach a final diagnosis.
Finally, an attempt was made to summarize the information necessary to establish a tentative
diagnosis in a concept map, particularly helpful to students and young professionals.

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