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 Chapter 10

Proliferative Endometrial Lesions Hidden behind the

Feline Pyometra

Maria dos Anjos Pires, Hugo Vilhena, Sónia Miranda,

Miguel Tavares Pereira, Fernanda Seixas and Ana Laura Saraiva

Additional information is available at the end of the chapter

http://dx.doi.org/10.5772/62788

Abstract
The literature refers to pyometra as the most important pathology in the feline uterus,
which is often associated with cystic endometrial disease (cystic endometrial hyperplasia/
pyometra complex or CEH-Pyo). The etiology of pyometra is complex and probably mul‐
tifactorial, but hormonal influences are suggested to play an important role in the patho‐
genesis. Progestagen-based contraceptives may be risk factors for the CEH-Pyo
syndrome, for endometrial adenocarcinoma and also to mammary tumors in this species.

The histopathological descriptions of pyometra include an enlarged uterus containing

purulent fluid, variable endometrial infiltration of neutrophils and bacterial colonization.
The degree of hyperplasia of endometrial glands is variable, and frequently the endome‐
trium becomes atrophic. The severity of endometritis is variable. Thereby, the type of in‐
flammatory cells infiltrating the uterine wall or lumen varies accordingly and may
include neutrophils, macrophages, plasma cells and lymphocytes.

The clinical diagnosis of pyometra is often based on the clinical signs and the physical
examination, supported by ultrasound findings. The surgical excision of the uterus is the
recommended treatment when the animal is not intent for breeding, as most pyometra
clinical signs resolve after ovariohysterectomy.

Nevertheless, our clinical practice demonstrated that, in cats, pyometra often masks other
uterine conditions that may present a worst prognosis and may interfere with the expect‐
ed outcome. Thus, although seldom requested, the pathological analysis of the uterus
with pyometra should be performed following surgery, even if significant macroscopic
alterations are not visible, as one frequent finding in pyometra specimens is the co-exis‐
tence of feline endometrial adenocarcinoma (FEA).

FEA is usually described as a rare pathology in cats, but recent descriptions suggest that
it may be more frequent than thought. Some morphological and clinical features of FEA,
as well as molecular markers, have been recently described. Moreover, age is not an ade‐
quate factor for triage, since some FEA cases were described in young animals, prompt‐
ing pathologists, clinicians and researchers into this new reality.

© 2016 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons
Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution,
and reproduction in any medium, provided the original work is properly cited.
228 Insights from Animal Reproduction

Therefore, this chapter proposes to highlight aspects that reinforce the need for careful
observation of all the cases of CEH-Pyo, to exclude the co-existence of FEA that can
worsen the prognosis.

Keywords: Cat, cystic hyperplasia, endometrial adenocarcinoma, pyometra, queen

1. Introduction

The cystic endometrial hyperplasia-pyometra (CEH-Pyo) complex is the most frequent and
important uterine disorder in queens [1–5]. Ovarian hormones are considered the main factors
in CEH-Pyo complex development, and progesterone is considered the principal component
in its pathogenesis. Nevertheless, estrogen’s effects in uterus have also been implicated as
causing hyperplasia of the endometrium and cystic dilation of endometrial glands, with
concomitant increased secretion of fluid that favors the progression of CEH to pyometra [6,
7]. Pyometra is characterized by uterine inflammation and infiltration of the endometrium and
uterine lumen by neutrophils and bacteria, leading to the development of the clinical signs [8].
Ultimately, the condition may originate sepsis [2, 9, 10].

In queens, pyometra has been described co-existing with other uterine conditions, such as a
disorder of sexual development [11], uterine torsion [12], in ovariectomized (but not hyster‐
ectomized) cats [13] and in the uterine stump of neutered queens with ovarian remnant
syndrome [14, 15]. Moreover, several cases of uterine neoplasia associated with pyometra have
been reported in queens [16–18]. The factors involved in the development of feline endometrial
adenocarcinomas (FEA) are still unclear. However, it seems probable that the endogenous or
exogenous ovarian steroid hormones that are associated with CEH and pyometra development
might also influence endometrial carcinogenesis and tumor progression [1, 2, 12, 17, 18].
Moreover, one could also hypothesize that the feline uterus reacts to any irritative stimulus
by enhancing the inflammatory response, like it happens in dogs, which would lead to
pyometra [8].

2. Pathophysiology of the cystic endometrial hyperplasia-pyometra

complex

Female cats are a polyestrous seasonal species (Figure 1). The photoperiod is a major factor
influencing the onset and duration of seasonal ovarian activity [19]. During the breeding
season, queens may show ovulatory or anovulatory estrous cycles. In cats, spontaneous
ovulation seldom occurs. Cats are considered a species with induced ovulation in which a
physical repetitive stimulus, as the one associated with coitus or mechanical stimulation of the
vagina, is required to trigger a consistent pulse of pre-ovulatory luteinizing hormone (LH).
This will stimulate the ovulation of large ovarian follicles, which occurs in approximately 30
 Proliferative Endometrial Lesions Hidden behind the Feline Pyometra 229
http://dx.doi.org/10.5772/62788

to 50 hours after the LH surge [6]. However, less frequently, ovulation can also occur without
mating and is designated as spontaneous ovulation. Frequent grooming, self-grooming and
presence of a tomcat are putative pheromonal, tactile and visual stimuli that may trigger LH
secretion and induce ovulation [20–22].

In anovulatory cycles, recurrent follicular (estrogen-dominated) phases develop and in

absence of a luteal phase, they are separated only by a short period corresponding to follicular
atresia and emergence of a new follicular wave. Consequently, in non-ovulatory cycles, the
uterus is not exposed to progesterone [6, 19, 22].

In ovulatory cycles, follicular and luteal (progesterone-dominated) phases alternate. The

follicular stage is similar to that of non-ovulatory cycles. After ovulation, progesterone
secretion by corpora lutea initiates within 24 to 48 hours. The luteal phase lasts approximately
30 days in non-pregnant cycles (diestrous or luteal phase), but it may also last up to 50 days if
a pseudopregnancy develops, and in pregnant cycles the progesterone dominancy lasts about
60 days [6, 19, 22].

Figure 1. Drawing of the queen’s reproductive cycle—the estrous cycles begin at puberty or after a seasonal anestrous.
The figure compares the alternacy of the stages of the cycle in the anovulatory (top) or ovulatory (bottom) estrous cy‐
cles. The season onset always originates a new cycle whereas, at the end of season, the female can enter anestrous is‐
sued from an anovulatory cycle or at the end of a luteal phase (diestrous, pseudopregnancy or pregnancy) if the cycle
was ovulatory.

The effects of progesterone in the uterus are major players in the pathogenesis of the CEH-Pyo
complex. Progesterone plays diverse physiological roles designed to facilitate embryo survival
230 Insights from Animal Reproduction

and the success of a term pregnancy. These include the following: (1) the increase in coiling
and in the secretory activity of endometrial glands (which expand the surface and the amount
of fluid produced), (2) the decreased myometrial contractility, (3) the closure of the uterine
cervix and (4) a depression in the uterine immune response [6, 21]. Our studies showed that
T lymphocytes are the most common immune cells found in the cyclic feline endometrium,
and we noted a variation of these cells and macrophage localization in the uterus between
follicular and luteal stages, with an apparent migration of these cell populations from the
surface layers to deeper layers of the endometrium during the luteal stages, which favor the
embryo implantation [23].
Repeated exposure to consecutive progesterone cycles or the exogenous administration of
progestagens for contraception may aggravate these effects, and stimulate the proliferation
and cystic dilation of the endometrial glands leading to CEH development, luminal fluid
accumulation, and uterine distention [24]. These changes in the uterine microenvironment, in
particular the accumulation of a mucinous fluid in the uterus and the immune suppression,
predispose to colonization of the uterine content by ascending bacteria from vaginal micro‐
biota, originating pyometra [2, 6, 8, 21].
Pyometra is often diagnosed with functional ovarian corpora lutea. The progesterone is
considered the main hormone implicated, although estrogens are also considered important
in the CEH-Pyo complex pathogenesis. The disease has also been reported in cats with ovaries
containing only follicles and basal serum progesterone concentrations or in cats with inactive
ovaries [5, 25]. Estrogens cause dilation of the cervix during estrous, predisposing the uterus
to ascending bacterial colonization by the normal vaginal biota [2, 19, 26]. In fact, the existence
of a subclinical chronic low-grade bacterial uterine infection that may develop during the
proestrous or estrous has also been implicated as a causative factor responsible for the
endometrial proliferation occurring earlier in the pathogenesis of the CEH-Pyo complex [8].
Moreover, estradiol increases the estrogen and progesterone receptors in the uterus and
enhances uterine response to continued stimulation with estradiol and concurrent or subse‐
quent stimulation by progesterone [21].
It is questionable who comes first in the pyometra pathology: the colonization by bacteria that
promotes inflammation or the instability or anomalous morphology/physiology of the
endometrium (as CEH or FEA), which endorse the proliferation of opportunist bacteria that
arrive from the cervix and vagina [6]. The most common bacteria isolated from feline pyometra
is Escherichia coli, but other agents of the normal vaginal flora and of suspected fecal contam‐
ination have been also detected, including Streptococcus spp., Staphylococcus spp., Pasteurella
spp., Klebsiella spp., Proteus spp., Pseudomonas spp., Moraxella spp., and Tritrichomonas foetus [6,
19, 25, 27, 28]. Sterile pyometra may also be observed [2].

3. Epidemiology

Cystic endometrial hyperplasia/pyometra complex is considered to be frequent in female cats.

However, information on prevalence of feline pyometra is scarce. The few published studies
 Proliferative Endometrial Lesions Hidden behind the Feline Pyometra 231
http://dx.doi.org/10.5772/62788

suggest that it is less frequent than in dogs [3], which is in accordance with our experience
(unpublished data). This difference has been attributed to two main factors. The first is related
to the fact that queens are induced ovulators, and therefore, the feline uterus is less frequently
exposed to progesterone influence [20, 24]. The second is related with the habit to neuter queens
at younger ages to prevent unwanted pregnancies and heat behavior [15].
The prevalence of feline CEH-Pyo complex increases with age and is considered a common
condition in cats older than 5 years of age and in cats receiving exogenous progestogens [1, 3,
5, 29–32]. Age effects in CEH-Pyo complex are associated to a cumulative effect of repeated
hormonal stimulation in subsequent estrous cycles. Spontaneous ovulations and progestogen
treatments predispose the uterus to abnormal endometrial proliferation, which leads to CEH
development [25]. However, pyometra can also develop in younger animals, presumably due
to other etiological process not yet described in the literature.
Feline breeds like the Sphynx, Siberian cat, Ocicat, Korat, Siamese, Ragdoll, Maine Coon, and
Bengal seem to present a higher rate of pyometra, according to a study performed in Sweden
[3]. Age at first mating, age at first parturition, and the number of parturitions do not appear
to influence pyometra development [6].
Although feline pyometra is associated with a high morbidity, the mortality rate is relatively
low, ranging from 5.7 to 8.0% of cases [3, 4].

4. Diagnosis

CEH is usually a silent pathology, with infertility being the main symptom in the early stages
of the disease [6, 21, 33]. At this stage, queens are usually asymptomatic, and the physical
examination, results from hematology, serum biochemistry, and urinalysis are unremarkable
in most cases [5]. In cases of marked hyperplasia, or when mucometra develops, abdominal
distention can be observed and an enlarged uterus can be detected on abdominal palpation [6].
In some cases, the uterus can be visualized on abdominal radiographs, but this diagnostic
procedure presents low sensitivity in CEH. Abdominal ultrasound and histopathology are the
most reliable methods for CEH diagnosis [19].
Pyometra is commonly associated with overt clinical symptoms and the abnormalities
detected on complementary diagnostic exams vary with the severity of the disease, which
typically develop one week to two months after estrous [2, 34]. The most common clinical
symptoms include a mucous-purulent to hemorrhagic vulvar discharge (Figure 2), anorexia,
lethargy, abdominal distention, dehydration, a palpable uterus, fever, and leukocytosis [4,
19]. The vulvar discharge is present in cases of open-cervix pyometra, but it can be unapparent
due to the fastidious grooming habits of queens [6]. Queens with closed-cervix pyometra often
have a significant abdominal distention and signs of severe illness [19].
Diagnosis is based on the history and clinical signs, and it is usually confirmed by abdominal
radiography and/or ultrasound [13]. On abdominal radiology, an enlarged uterus with dorsal
and cranial displacement of the small intestine can be detected, but these are also found in
232 Insights from Animal Reproduction

Figure 2. Purulent vulvar discharge in a queen with open-cervix pyometra.

early pregnancy [6]. In the abdominal ultrasound, it is possible to observe an enlarged uterus
containing hypoechoic to anechoic intraluminal fluid (Figures 3A and B). This is the diagnostic
procedure of choice in most cases [25].

Figure 3. Pyometra in a female cat. (A) Abdominal ultrasound of a queen with pyometra showing a marked uterine
distention with a narrow uterine wall, and the presence of hypoechoic intraluminal fluid; the loss of definition of the
uterine contour and the unfolding of uterine walls are also observed. (B) Macroscopic aspect of the uterus after surgi‐
cal excision.

5. Treatment

Pyometra is considered an emergency; thus, treatment should be rapid and aggressive due to
the risk of septicemia, endotoxemia, azotemia, uterine rupture, peritonitis and shock [9, 10, 24,
 Proliferative Endometrial Lesions Hidden behind the Feline Pyometra 233
http://dx.doi.org/10.5772/62788

34]. Surgical treatment (ovariohysterectomy—Figures 3B and 4) associated with supportive

therapy is considered the treatment of choice [25, 26]. Support treatment includes intravenous
fluid therapy and antibiotics administration [19]. Fluid therapy is directed to correct fluid
deficits and electrolytic and acid-base imbalances, to correct azotemia and to maintain
adequate tissue perfusion [6]. Whenever possible, antibiotics should be chosen based on
bacterial culture and sensitivity. However, these procedures may take longer than the time
available to recover the female from a life-threatening situation. Therefore, if not possible or
during pending culture results, wide broad bactericide antibiotics effective against the most
common bacteria are recommended, including ampicillin, amoxicillin + clavunalate, trime‐
thoprim sulfonamide, cephalosporins and enrofloxacin [6]. Ovariohysterectomy rapidly and
permanently eliminates the site of infection, and most cats recover successfully [19].

Figure 4. Different morphological aspects and sizes of queen’s uterus collected at ovariohysterectomy. Each specimen
represents a different clinical condition: (A) late-pregnant uterus; (B) uterus in a follicular stage; (C) uterus in anes‐
trous; (D) uterus with pyometra.

Medical treatment could be considered in queens with reproductive added value, which are
clinically stable and present an open-cervix pyometra [24, 35]. Medical treatment is directed
to avoid synthesis or effects of progesterone, and to evacuate the uterine content.

Treatment with prostaglandins (natural or synthetic prostaglandin F2α, such as cloprostenol)

or with aglepristone (an anti-progestagen) has proved to be effective in feline pyometra [36–
39]. However, care should be taken before starting a treatment with prostaglandins as they
should not be used in closed-cervix pyometra due to the risk of uterine rupture [24, 35, 38].
Prostaglandins promote luteolysis, consequently decreasing plasma concentrations of
progesterone, and stimulate myometrial contraction leading to uterine evacuation [24, 40].
Mild and transient side effects, such as vocalization, panting, restlessness, grooming, tenes‐
mus, salivation, diarrhea, mydriasis, emesis, urination and lordosis, can develop after
prostaglandin administration [38, 39].
234 Insights from Animal Reproduction

Aglepristone binds to the progesterone receptors and consequently inhibits progesterone

effects. Once progesterone influences are withdrawn, the cervix will open and allow the
elimination of the uterine content [37]. No side effects were observed in cats treated with
aglepristone [37]. This compound may be used to treat a closed pyometra if the animal is
stabilized and the risks of septicemia are residual. Prostaglandins and aglepristone can be used
in association [25]. One good approach is to start the treatment with aglepristone and to
associate the prostaglandins 24 to 48 h after the first aglepristone administration [37].

Queens submitted to medical treatment will be at risk for recurrence of pyometra at every
ovulation after treatment if they do not become pregnant. To prevent it, they should be bred
on the next cycle and then spayed when no longer needed for breeding [34].

6. Morphological aspects of cystic endometrial hyperplasia

It is well acknowledged that CEH pathogenesis involves the hyperplasia of the endometrium
with cyst formation, which causes the accumulation of endometrial secretions [8], first into the
glands lumen and then into the uterine lumen, with variable amount of serous, mucous, or
purulent (neutrophils) content [6, 26].

Cysts develop from the endometrial glands (Figure 5A), and their number, size, distribution,
histological morphology, and clinical relevance are variable [8]. As previously stated, CEH is
usually a silent pathology, mainly if the cysts are small-sized. Cystic endometrial hyperplasia
can progress into pyometra, and may or may not be associated with bacterial infection [41].

The morphology of CEH is variable, ranging from small gland dilatations to cystic structures
occupying the entire endometrium and protruding into the uterine lumen. It is possible that
the increased pressure of the cystic fluid modifies the morphology of glandular epithelium
from cubic to squamous. In our experience (unpublished data), the size and number of cysts
are not related with the grade of endometritis (mainly composed of a plasma cell and macro‐
phages infiltrate) or with pyometra.

Dow [26] classified the severity of the CEH in four grades, being grade 1 the less severe,
characterized by an endometrium with approximately normal dimensions and the presence
of small cysts; and grade 4, the most severe, characterized by a significantly thickened
endometrium or an atrophic endometrium with large ulcers associated to pyometra [26].
Different degrees of inflammation exist, ranging from a discreet mononuclear endometrium
infiltration around the cysts in grade 2 to a severe infiltration of neutrophils, macrophages,
and plasma cells in grade 4 [8].

The stimulus for connective tissue deposition around small aggregates of endometrial cystic
glands can cause expansion and protrusion of a small portion of the endometrium, originating
endometrial polyps, which are considered as morphologic variations of CEH. Queens can
present single or multiple endometrial polyps, with variable dimensions [8], which can be
spread along the uterine horns due to estrogen or progesterone influence [7].
 Proliferative Endometrial Lesions Hidden behind the Feline Pyometra 235
http://dx.doi.org/10.5772/62788

Figure 5. (A) Histological aspect of grade 2 CEH showing a hyperplastic endometrium with differently sized cysts. (B)
Histological aspect of pyometra in a queen. Note the endometrium with cystic structures filled with neutrophils (*)
opening into the lumen (arrow). An intense mononuclear infiltrate in endometrium characterizes endometritis (arrow‐
head) in a hyperplastic endometrium when concomitant CEH exists. Hematoxylin and Eosin. Bar = 500 μm.

7. Morphological aspects of pyometra

Morphological aspects of pyometra in queens are similar to those observed in the bitch and
other species. The enlargement of the uterus is variable, ranging from a subtle increase to a
severe enlargement in the endometrium dimension when associated to harsh glands and
epithelium hyperplasia. The major feature of pyometra is the presence of neutrophils in the
lumen of the uterus [7]. The glands are filled with mucous and neutrophils (Figure 5B) in a
hyperplastic endometrium, evolving to the rupture of cysts into the lumen. Contrasting to that
observed in the healthy endometrium, a raise of macrophages and B lymphocytes in the lumen
and in the endometrium is observed following an initial rise in neutrophils, but only minor
changes on the values for T lymphocytes are reported [23]. An asymptomatic pyometra often
evolves to an atrophic and ulcerated endometrium, the final phase of this disease. The
myometrium becomes thinner and uterine rupture can be eminent in more severe cases.
Endometritis is a concomitant feature with pyometra (Figure 5B). In the beginning of the
process, neutrophils are the predominant cell type in the endometrium stroma, but macro‐
phages and mainly plasma cells become more intense in chronic cases, presenting ulcerated
and atrophic endometrium [7].

8. Feline endometrial adenocarcinoma: frequency, morphological and

clinical aspects

Adenocarcinoma of the uterus is a malignant neoplasm, which arises from the endometrial
epithelia [42]. Although reported in the rabbit, cow, rat, mouse, guinea pig, horse, dog, and
236 Insights from Animal Reproduction

cat [43], it is considered to be rare in domestic animals [44, 45]. In the literature, feline endo‐
metrial adenocarcinoma (FEA) is referred as an infrequent tumor [44]. However, recent reports
of FEA suggest that the disease might be more common than assumed, and its incidence may
be underestimated [18, 47, 46]. Feline endometrial adenocarcinoma is usually reported in
geriatric queens, older than nine years of age [42, 48–50], but recently Cho et al. [51] and Payan
at al. [18] reported FEA in young queens, less than two and one years old, respectively [18, 51].

The common practice of elective ovariohysterectomy in cats is being referred as protective

from uterine neoplasia [11, 52]. Notwithstanding, the rarity of these tumors might be related
to inadequate post-surgical or post-mortem evaluation of the genital tract [7, 53]. In fact, most
clinicians do not require a histopathological evaluation of genital apparatus based on the
assumption that “it is normal” or “only a pyometra”.

Data related to the factors involved in the development of feline endometrial adenocarcinomas
(FEA) are still insufficient. However, it seems probable that the endogenous or exogenous
ovarian steroid hormones, associated to pyometra development, might also influence endo‐
metrial carcinogenesis and tumor progression [1, 18]. As recently reported, according to the
database of our laboratory in a 13-year period, feline endometrial adenocarcinoma was
diagnosed in 20.30% of cases (n = 37/197) while 33.5% (66/197) presented uterine inflammatory
disease [12]. However, in 41.16% (81/197), the queen failed to manifest signs of uterine
dysfunction or history of infertility. FEA either evolves as a silent disease [3, 47] or is associated
to nonspecific and vague clinical signs that can be associated to other uterine disorders,
including CEH, pyometra, or abortion. Therefore, there is a strong possibility that these tumors
may be underdiagnosed [16, 18, 47].

Uterine tumors are more commonly found in sexually intact queens [54], but there are three
reported cases of FEA in the uterine stump of ovariohysterectomized cats [44, 43, 54]. As such,
these cases represent unusual complications following an incomplete ovariohysterectomy of
the uterine body in a previously undiagnosed diseased uterus [44, 54].

Saraiva et al. [47] described three different histotypes of FEA based on cell features, growth
pattern, and invasiveness, which included papillary serous carcinoma, clear cell carcinoma
and “in situ” (non-invasive) carcinoma [16]. Microscopically, this classification resembles the
human endometrial carcinoma classification [55]. Macroscopically, these patterns are indis‐
tinguishable, presenting as a multiple whitish papillary masses or a diffuse thickening of the
endometrium along both uterine horns and corpus, which are better appreciable in a longitu‐
dinal section of this organ. Occasionally, the uterine wall may be thinner (atrophic) and when
a concomitant pyometra is present, a purulent exudate may be observed in the lumen. Tumor
invasion of the myometrium may be detected, and serosa rupture can occur promoting
peritonitis and peritoneal carcinomatosis. Distant metastases in lungs or liver were seldom
reported [54].

Regarding the cyclic uterus, in the presence of tumors we found higher numbers of macro‐
phages and T lymphocytes. An increased number of B cells was only observed in pyometra
cases and in FEA cases associated with pyometra. These findings suggest that B lymphocytes
may be more relevant in uterine inflammation and that T cells may be more important in
 Proliferative Endometrial Lesions Hidden behind the Feline Pyometra 237
http://dx.doi.org/10.5772/62788

endometrial tumor oncobiology. These findings deserve more investigation to ascertain the
real function of the various cell types on the etiopathogeny of uterine inflammation and
neoplasia [23].

9. Hidden behind feline pyometra

In our experience, pyometra may not be the only uterine pathology observed in a queen that
presents a mucous, hemorrhagic, or purulent vulvar discharge accompanied with other clinical
signs compatible with pyometra.

Chronic inflammation associated with pyometra has been suggested to have a tumorigenic
effect, and the inflammatory process may itself mask an underlying neoplasm in an under-
evaluated uterus [56]. Association of pyometra with FEA was also suggested by some authors
reporting cases of endometrial carcinoma in queens with pyometra [1, 16–18, 44]. Data related
to the etiological factors involved in the development of feline endometrial adenocarcinomas
are still scarce; however, it seems possible that the endogenous or exogenous ovarian steroids
hormones associated with pyometra development might also influence endometrial carcino‐
genesis and tumor progression [1, 18].

Our laboratory records show that approximately 44% (29/66) of diagnosed pyometra co-
existed with FEA, and that 24.2%(16/66) had concurrent CEH.

The clinical anamnesis is an important tool that must be explored to exclude the possibility of
gestation or abortion. Whenever ovariohysterectomy is the adopted solution, the uterus must
be totally excised, including the body and the cervix in the excised specimen. The histopa‐
thology is the unique complementary analysis that can distinguish and discard pyometra from
other uterine lesions. Thus, it is of utmost importance to submit these organs to histopatho‐
logical examination. At surgery, if any part of the uterine horns or the uterus is left in place
(partial hysterectomy), it can bring problems in a near future, as some description of FEA [25]
and pyometra were reported in uterine stumps of spayed queens [5, 14, 47, 54]. So, the complete
and careful surgery associated with histopathological observation, alongside to a correct
clinical monitoring, are the most important points to discard possible lesions that could be
hidden behind a pyometra.

Acknowledgements

This work was sponsored/financed/founded by the Portuguese Science and Technology

Foundation (FCT) under the Project PEst-OE/AGR/UI0772/2011, PEst-OE/AGR/UI0772/2014
and UID/CVT/00772/2013.

The authors would like to thank Mrs. Lígia Lourenço (UTAD) for her excellent contribution
processing the histology samples. We also thank to all colleagues who sent feline OVH
238 Insights from Animal Reproduction

specimens for diagnosis to the Laboratory of Histology and Anatomical Pathology of the
University of Trás-os-Montes and Alto Douro (UTAD).

Author details

Maria dos Anjos Pires1,2*, Hugo Vilhena1,3,4, Sónia Miranda1,3,4, Miguel Tavares Pereira5,
Fernanda Seixas1,2 and Ana Laura Saraiva2,3

*Address all correspondence to: apires@utad.pt

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

Douro, Vila Real, Portugal

2 Veterinary Sciences Department, Universidade de Trás-os-Montes e Alto Douro, Portugal

3 Department of Veterinary Medicine, Escola Universitária Vasco da Gama, Coimbra,

Portugal

4 Baixo Vouga Veterinary Hospital, Águeda, Portugal

5 Vet4, Estarreja, Portugal

References

[1] Keskin A, Yilmazbas G, Yilmaz R, Ozyigit MO, Gumen A. Pathological abnormalities

after long-term administration of medroxyprogesterone acetate in a queen. J Feline
Med Surg. 2009; 11:518-21.

[2] Johnson CA. Medical management of feline pyometra. In: Kirk´s Current Veterinary
Therapy XI, ed. Kirk RW and Bonagura JD, 1992, pp. 969-71. Elsevier Saunders,
Pennsylvania.

[3] Hagman R, Ström Holst B, Möller L, Egenvall A. Incidence of pyometra in Swedish

insured cats. Theriogenology. 2014; 82:114-20.

[4] Kenney KJ, Matthiesen DT, Brown NO, Bradley RL. Pyometra in cats: 183 cases
(1979-1984). J Am Vet Med Assoc. 1987; 191:1130-2.

[5] Potter K, Hancock DH, Gallina AM. Clinical and pathologic features of endometrial
hyperplasia, pyometra, and endometritis in cats: 79 cases (1980-1985). J Am Vet Med
Assoc. 1991; 198:1427-31.

[6] Agudelo CF. Cystic endometrial hyperplasia-pyometra complex in cats. A review.

Vet Quart. 2005; 27(4):173-82.
 Proliferative Endometrial Lesions Hidden behind the Feline Pyometra 239
http://dx.doi.org/10.5772/62788

[7] Schlafer DH, Miller RB. Female genital system. In: Jubb, Kennedy & Palmer's Pathol‐
ogy of Domestic Animals. Edited by M. Grant Maxie. Vol 3. Chap 4. 2007; pp.
460-473.

[8] Schlafer DH, Gifford AT. Cystic endometrial hyperplasia, pseudo-placentational en‐
dometrial hyperplasia, and other cystic conditions of the canine and feline uterus.
Theriogenology. 2008; 70:349-58.

[9] Costello MF, Drobatz KJ, Aronson LR, King LG. Underlying cause, pathophysiologic
abnormalities, and response to treatment in cats with septic peritonitis: 51 cases
(1990-2001). J Am Vet Med Assoc. 2004; 225(6):897-902.

[10] Brady CA, Otto CM, Van Winkle TJ, King LG. Severe sepsis in cats: 29 cases
(1986-1998). J Am Vet Med Assoc. 2000;217:531-5.

[11] Schulman J, Levine SH. Pyometra involving uterus masculinus in a cat. J Am Vet
Med Assoc. 1989; 194:690-1

[12] Stanley SW, Pacchiana PD. Uterine torsion and metabolic abnormalities in a cat with
a pyometra. Can Vet J. 2008; 49:398-400.

[13] de Faria VP, Norsworthy GD. Pyometra in a 13-year-old neutered queen. J Feline
Med Surg. 2008; 10:185-7.

[14] Rota A, Pregel P, Cannizzo FT, Sereno A, Appino S. Unusual case of uterine stump
pyometra in a cat. J Feline Med Surg. 2011; 13:448-50.

[15] Demirel MA, Acar DB. Ovarian remnant syndrome and uterine stump pyometra in
three queens. J Feline Med Surg. 2012; 14:913-8.

[16] Saraiva AL, Payan-Carreira R, Gärtner F, Pires MA. Feline Endometrial Adenocarci‐
nomas. In: MA Longoria and JI Alcalá (Eds.) Adenocarcinoma: Pathogenesis, Treat‐
ment and Prognosis. Series Cancer Etiology, Diagnosis and Treatments. Nova
Science Publishers, Hauppauge, NY, 2012; pp. 175–189.

[17] Sontas BH, Erdogan Ö, Apaydin Enginler SÖ, Turna Yilmaz Ö, Şennazli G, Ekici H
(2013) Endometrial adenocarcinoma in two young queens. J Small Anim Pract 2013;
54:156-9.

[18] Payan-Carreira R, Saraiva A, Santos T, Vilhena H, Sousa A, Santos C, Pires MA. Fe‐
line endometrial adenocarcinoma in females < 1 year old: a description of four cases.
Reprod Domest Anim. 2013; 48:70-7.

[19] Feldman EC, Nelson RW. Feline reproduction. In: Canine and Feline Endocrinology
and Reproduction, 3rd Ed, ed Feldman EC and Nelson RW, 2004, pp. 1016-1045.
Elsevier Saunders, Missouri.

[20] Lawler DF, Johnston SD, Hegstad RL, Keltner DG, Owens SF. Ovulation without cer‐
vical stimulation in domestic cats. J Reprod Fertil Suppl. 1993; 47:57-61.
240 Insights from Animal Reproduction

[21] von Reitzenstein M, Archbald LF, Newell SM. Theriogenology question of the
month. Pyometra, hydrometra, or mucometra. J Am Vet Med Assoc. 2000; 216:1221-3.

[22] England GC. Physiology and endocrinology of the female. In: BSAVA Manual of Ca‐
nine and Feline Reproduction and Neonatology, 2nd Ed, ed. England G and von Hei‐
mendahl A, 2010; pp. 1-12. British Small Animal Veterinary Association, Gloucester.

[23] Tavares Pereira M. Comparison of Macrophages and Lymphocytes in Non-diseased

Endometrium and Feline Endometrial Adenorcarcinomas, 2013; Master Thesis,
UTAD, Vila Real, Portugal.

[24] Wiebe VJ, Howard JP. Pharmacologic advances in canine and feline reproduction.
Top Companion Anim Med. 2009; 24:71-99

[25] Axnér E. Clinical approach to conditions of the non-pregnant and neutered queen.
In: BSAVA Manual of Canine and Feline Reproduction and Neonatology, 2nd Ed, ed.
England G and von Heimendahl A, 2010; pp. 185-190. British Small Animal Veterina‐
ry Association, Gloucester.

[26] Dow C. The cystic hyperplasia-pyometra complex in the cat. Veterinary Record,
1962; 74:141.

[27] Dahlgren SS, Gjerde B, Pettersen HY. First record of natural Tritrichomonas foetus
infection of the feline uterus. J Small Anim Pract. 2007; 48:654-7.

[28] Majoy SB, Sharp CR, Dickinson AE, Cunningham SM. Septic pericarditis in a cat
with pyometra. J Vet Emerg Crit Care (San Antonio). 2013; 23:68-76.

[29] Lawler DF, Evans RH, Reimers TJ, Colby ED, Monti KL. Histopathologic features,
environmental factors, and serum estrogen, progesterone, and prolactin values asso‐
ciated with ovarian phase and inflammatory uterine disease in cats. Am J Vet Res.
1991; 52:1747-53.

[30] Chatdarong K, Rungsipipat A, Axnér E, Linde Forsberg C. Hysterographic appear‐

ance and uterine histology at different stages of the reproductive cycle and after pro‐
gestagen treatment in the domestic cat. Theriogenology. 2005; 64:12-29.

[31] Bellenger CR, Chen JC. Effect of megesterol acetate on the endometrium of the pre‐
pubertally ovariectomised kitten. Res Vet Sci. 1990; 48:112-8.

[32] Romagnoli S. Progestins to control feline reproduction: historical abuse of high doses
and potentially safe use of low doses. J Feline Med Surg. 2015; 17:743-52.

[33] Baldwin, CJ. Pregnancy Loss in the Queen. In: Kirk´s Current Veterinary Therapy
XIV, ed. Bonagura JD and Twedt DC, 2009; pp. 1041-1045. Elsevier Saunders, Mis‐
souri.

[34] Traas AM. Feline reproduction. In: Textbook of Veterinary Internal Medicine, 7th Ed,
ed. Ettinger SJ and Feldman EC, 2010, pp. 1729-1746. WB Saunders, Philadelphia.
 Proliferative Endometrial Lesions Hidden behind the Feline Pyometra 241
http://dx.doi.org/10.5772/62788

[35] Biddle D, Macintire DK. Obstetrical emergencies. Clin Tech Small Anim Pract. 2000;
15:88-93.

[36] Arnbjerg J, Flagstad A. Prostaglandin F2 alpha treatment of feline open pyometra.

Nord Vet Med. 1985; 37:286-90.

[37] Nak D, Nak Y, Tuna B. Follow-up examinations after medical treatment of pyometra
in cats with the progesterone-antagonist aglepristone. J Feline Med Surg. 2009;
11:499-502.
[38] García Mitacek MC, Stornelli MC, Tittarelli CM, Nuñez Favre R, de la Sota RL, Stor‐
nelli MA. Cloprostenol treatment of feline open-cervix pyometra. J Feline Med Surg.
2014; 16:177-9.

[39] Davidson AP, Feldman EC, Nelson RW. Treatment of pyometra in cats, using prosta‐
glandin F2 alpha: 21 cases (1982-1990). J Am Vet Med Assoc. 1992; 200:825-8.

[40] Verstegen JP, Onclin K, Silva LD, Donnay I. Abortion induction in the cat using pros‐
taglandin F2 alpha and a new anti-prolactinic agent, cabergoline. J Reprod Fertil
Suppl. 1993; 47:411-7.
[41] De Bosschere H, Ducatelle R, Vermeirsch R, Van Den BroeckW, Coryn M. Cystic en‐
dometrial hyperplasia-pyometra complex in the bitch: should the two entities be dis‐
connected? Theriogenology 2001; 55:1509-19.

[42] Preiser H, 1964. Endometrial Adenocarcinoma in a Cat Pathol Vet, 1964; 1: 485
[43] Meier H (1956). Carcinoma of the uterus in the cat: two cases. Cornell vet 46: 188-200.
as quoted by McEntee (1990).
[44] Miller MA, Ramos-Vara JA, Dickerson MF, Johnson GC, Pace LW, Kreeger JM, Turn‐
quist SE, Turk JR. Uterine neoplasia in 13 cats. J Vet Diagn Invest. 2003; 15:515-22.
[45] Cotchin E, Spontaneous uterine cancer in animals. Br J Cancer, 1964; 18:209-27.
[46] Saraiva AL, Payan-Carreira R, Gartner F, Santana I, Rema A, Lourenço LM, Pires
MA. Immunohistochemical expression of cyclooxygenase-2 (COX-2) in feline endo‐
metrial adenocarcinoma and in normal and hyperplastic endometria. Reprod Domest
Anim. 2015; 50(2):333-40.

[47] Saraiva AL, Payan-Carreira R, Gärtner F, Fortuna da Cunha M, Rêma A, Faria F,

Lourenço LM, Pires MA. An immunohistochemical study on the expression of sex
steroid receptors, Ki-67 and cytokeratins 7 and 20 in feline endometrial adenocarci‐
nomas. BMC Vet Res, 2015; 11:204.
[48] Belter LF, Crawford EM, Bates HR. Endometrial adenocarcinoma in a cat. Pathol Vet.
1968; 5:429-31.
242 Insights from Animal Reproduction

[49] McEntee K. The uterus: atrophic, metaplastic and proliferative lesions – neoplasia. In:
Reproductive Pathology of Domestic Animals, Academic Press, San Diego, CA, 1990;
pp. 179–190.
[50] Klein MK, Tumours of the female reproductive system: uterine tumours. In: Withrow
S, Vail D (eds), Withrow and MacEwen’s Small Animal Clinical Oncology, 4th Ed,
Saunders/Elsevier Health Sciences, St Louis, Missouri, USA, 2007; pp. 613-614.

[51] Cho S-J, Lee H-A, Hong S, Kim O. Uterine adenocarcinoma with feline leukaemia vi‐
rus infection. Lab Anim Res. 2011; 27:347–51.

[52] Taylor KH. Female reproductive tumours. In: Henry CJ, Higginbotham ML (Eds.),
Cancer Management in Small Animal Practice [Part V: Specific Tumours. Saunders,
Elsevier, St. Louis, Missouri, 2010; pp. 268–274.
[53] Sontas BH, Erdogan Ö, Apaydin Enginler SÖ, Turna Yilmaz Ö, Şennazli G, Ekici H
(2013) Endometrial adenocarcinoma in two young queens. J Small Anim Pract. 2013;
54:156-9.

[54] Anderson C, Pratschke K. Uterine adenocarcinoma with abdominal metastases in an

ovariohysterectomised female cat. J Fel Med Surg. 2011; 13(1): 4-47.

[55] Horn L-C, Meinel A, Handzel R, Einenkel J. Histopathology of endometrial hyper‐

plasia and endometrial carcinoma – an update. Annal Diag Pathol. 2007; 11(4):
297-311.

[56] McEntee K. The uterus: atrophic, metaplastic and proliferative lesions – neoplasia. In:
Reproductive Pathology of Domestic Animals, Academic Press, San Diego, CA, 1990;
pp. 179-190.