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Available online http://breast-cancer-research.com/content/6/4/R300
R300
Vol 6 No 4
Research article
First description of feline inflammatory mammary carcinoma:
clinicopathological and immunohistochemical characteristics of
three cases
M Dolores Pérez-Alenza, Ángeles Jiménez, Ana I Nieto and Laura Peña
Department of Animal Medicine and Surgery, Animal Pathology, Veterinary Teaching Hospital, School of Veterinary Medicine, Complutense University,
Madrid, Spain
Corresponding author: Laura Peña, laurape@vet.ucm.es
Received: 12 Jan 2004 Revisions requested: 12 Feb 2004 Revisions received: 12 Mar 2004 Accepted: 16 Mar 2004 Published: 26 Apr 2004
Breast Cancer Res 2004, 6:R300-R307 (DOI 10.1186/bcr790)http://breast-cancer-research.com/content/6/4/R300
© 2004 Pérez-Alenza et al.; licensee BioMed Central Ltd. This is an Open Access article: verbatim copying and redistribution of this article are per-
mitted in all media for any purpose, provided this notice is preserved along with the article's original URL.
Abstract
Introduction Inflammatory breast cancer is a special type of
locally advanced mammary cancer that is associated with
particularly aggressive behaviour and poor prognosis. The dog
was considered the only natural model in which to study the
disease because, until now, it was the only species known to
present with inflammatory mammary carcinoma (IMC)
spontaneously. In the present study we describe
clinicopathological and immunohistochemical findings of three
cats with IMC, in order to evaluate its possible value as an animal
model.
Methods We prospectively studied three female cats with
clinical symptoms of IMC, identified over a period of 3 years.
Clinicopathological and immunohistochemical evaluations of Ki-
67, and oestrogen, progesterone and androgen receptors were
performed.
Results All three animals presented with secondary IMC
(postsurgical) characterized by a rapid onset of erythema,
severe oedema, extreme local pain and firmness, absence of
subjacent mammary nodules, and involvement of extremities.
Rejection of the surgical suture was observed in two of the cats.
Histologically, highly malignant papillary mammary carcinomas,
dermal tumour embolization of superficial lymphatic vessels, and
severe secondary inflammation were observed. The animals
were put to sleep at 10, 15 and 45 days after diagnosis.
Metastases were detected in regional lymph nodes and lungs in
the two animals that were necropsied. All tumours had a high Ki-
67 proliferation index and were positive for oestrogen,
progesterone and androgen receptors.
Conclusion Our findings in feline IMC (very low prevalence, only
secondary IMC, frequent association of inflammatory reaction
with surgical suture rejection, steroid receptor positivity)
indicate that feline IMC could be useful as an animal model of
human inflammatory breast cancer, although the data should be
considered with caution.
Keywords: Animal natural model, feline inflammatory mammary carcinoma
Introduction
Inflammatory mammary carcinoma (IMC) is a special type of
locally advanced mammary cancer that is associated with
particularly aggressive behaviour and poor prognosis in
women (in which case it is termed 'inflammatory breast car-
cinoma' [IBC]) [1-3] and in the dog (in which case it is
termed IMC) [4,5]. Until now these were the only species
in which spontaneous inflammatory carcinoma of the mam-
mary gland had been reported [6].
Clinically, IBC and IMC typically present with a rapid onset
of symptoms resembling an inflammatory process (ery-
thema, firmness and warmth in the skin of the mammary
gland), often without an underlying mass. In fact, this con-
dition can be misdiagnosed as dermatitis or mastitis
[1,4,5]. IBC and IMC are clinical diagnoses that can be
confirmed pathologically by the observation of neoplastic
emboli in dermal lymphatic vessels. This is the only histo-
logical criteria for their pathological diagnosis, because
several histological types of carcinomas have been
described to cause the disease [1,6,7]. In most cases the
clinical and pathological diagnoses coincide, but some
patients may present with clinical or pathological evidence
alone [3,8]. The presence of dermal lymphatic involvement
AR = androgen receptor; ER = oestrogen receptor; HMG = histological malignant grade; IBC = inflammatory breast cancer; IMC = inflammatory
mammary carcinoma; PR = progesterone receptor; TBS = Tris-buffered saline.
Breast Cancer Research Vol 6 No 4 Pérez-Alenza et al.
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(emboli) in the absence of clinical characteristics of inflam-
matory carcinoma is called occult inflammatory carcinoma,
and this frequently precedes clinical presentation of IBC
[9,10] and IMC [5]. Two clinical types of inflammatory car-
cinoma have been described in women [2,8,10] and in the
dog [5,11]: primary (without previous mammary tumour)
and secondary (after surgical excision of a malignant mam-
mary tumour) IBC and IMC.
Fortunately, this very aggressive type of cancer is uncom-
mon in humans [12] and in dogs [5]. However, the preva-
lence of the disease has doubled over the past 15 years in
both species [5,12].
In comparison with other types of breast cancer, several dif-
ferences in the biology of IBC and IMC have been reported,
including gene mutations, angiogenesis, angioinvasiveness
and endocrine mechanisms [3,6,12-15]. Treatment and
research in human IBC remains problematic [3]. In vitro
models include cell lines derived from primary IBC tumours;
a xenograft murine model has also been developed [3,16].
The dog was proposed as a natural model in which to study
the disease, because it was the only species thought to
present with IMC spontaneously [6].
Mammary tumours are commonly observed in the female
cat. The percentage of malignant mammary tumours is
higher in the cat (86%) than in the dog (42%) [17], and the
histology of feline mammary tumours is closer to that in
human breast cancer [18]. For these reasons, feline mam-
mary cancer might be a more useful model in which to
study the disease than the canine model. Nevertheless,
IMC has not been described in the cat.
In the present study we describe clinicopathological and
immunohistochemical findings in three cats with IMC, and
we compare the condition with characteristics previously
described in canine IMC.
Methods
Animals and clinical data
This is a prospective study including three female cats that
were presented at the Veterinary Teaching Hospital of
Madrid with clinical symptoms of IMC over a period of 3
years. The animals ranged in age from 12 to 15 years; one
was Siamese (case 1) and two were of short hair common
European breed (cases 2 and 3). Cases 1 and 3 were
referred from private clinics. In the three cats a complete
history was obtained indicating recent mastectomies
because of the presence of malignant mammary tumours.
In the physical examination mammary glands and regional
lymph nodes (axillary and inguinal) were evaluated. The
three cats had clinical signs of IMC, as described in the
dog [4].
Routine vaccination and antiparasitic drugs had been cor-
rectly administered. Serological tests for feline viral dis-
eases (i.e. feline leukaemia virus and feline
immunodeficiency virus) had recently been conducted and
were negative in the three animals.
Radiological evaluation of the thorax (three projections)
was performed in order to evaluate the presence of distant
metastases. Blood samples were taken to evaluate haema-
tology and biochemistry profiles and clotting times in case
1. Cytological examination with fine-needle aspirates of the
mammary area was performed to differentiate neoplastic
from inflammatory processes in the three cases.
No other concurrent diseases were found at the time of
presentation.
Pathology
Incisional biopsies and histopathological examinations of
skin areas with symptoms compatible with IMC were per-
formed in cases 1 and 3. In case 2, previous biopsy material
obtained after mastectomy of the primary tumour (before
IMC development) was available. Necropsies and corre-
sponding histopathological study were conducted in cases
2 and 3. All the samples were fixed in 10% neutral formalin,
embedded in paraffin, cut into sections 4 µm thick, and
stained with haematoxylin–eosin. The mammary tumours
were diagnosed histopathologically according to the World
Health Organization classification for feline mammary gland
tumours [18]. In each tumour the histological malignant
grade (HMG) was established by scoring tubule formation,
nuclear pleomorphism and mitotic rate from 1 to 3 points,
according to a human grading system [19].
Immunohistochemistry
Ki-67 proliferation marker was determined, and immunos-
taining for oestrogen receptor (ER)-α, progesterone recep-
tor (PR) and androgen receptor (AR) were done on
deparaffined 4-µm sections, using the streptavidin–biotin
complex peroxidase method following a high-temperature
antigen unmasking protocol (boiling slides in pressure
cooker 2 min, in buffer citrate pH 6). The slides were
cooled down in distilled water and washed in Tris-buffered
saline (TBS; 0.1 mol/l Tris base, 0.9% NaCl; pH 7.4).
Endogenous peroxidase activity was blocked in 1.5 ml
H2O2/100 ml methanol for 15 min. Ki-67 immunostaining
sections were incubated for 1 hour with primary mouse
monoclonal antibody anti-MIB1 nuclear proliferation marker
(dilution 1:30; Master Diagnostica, Granada, Spain).
ER-α and PR immunostaining were performed by overnight
incubation at 4°C with mouse monoclonal antihuman ER-α
(clone CC4-5, NCL-ER-LH2, dilution 1:40; Novocastra
Laboratories Ltd, Newcastle upon Tyne, UK) and mouse
monoclonal antihuman PR (clone 1A6, NCL-PR-123,
Available online http://breast-cancer-research.com/content/6/4/R300
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dilution 1:40; Novocastra). AR sections were incubated
overnight at 4°C with a rabbit polyclonal antibody (RB-
1358, dilution 1:15; Neomarkers, Fremont, CA, USA). After
incubation with the mouse monoclonal primary antibodies
(ER and PR), the slides were incubated with antimouse
biotinylated secondary antibody (E04233, dilution 1:200;
Dako, Glostrup, Denmark) for 30 min at room temperature.
AR slides were subsequently incubated with antirabbit
biotinylated secondary antibody (BA1000, 1:400; Vector
Laboratories, Burlingame, CA, USA) for 30 min at room
temperature. Afterward, all of the slides were incubated
with streptavidin conjugated with peroxidase (P50242,
1:400; Zymed, South San Francisco, CA, USA) for 30 min
at room temperature. All washes and dilutions were done in
TBS.
The slides were developed for 10 min using a chromogen
solution containing 3-3' diaminobenzidine tetrachloride
(D5059; Sigma Chemical Co., St Louis, Missouri, USA)
and H2O2 in TBS. After washing in distilled water for 10
min, slides were counterstained in haematoxylin (GH5-2-
16; Sigma Chemical Co.), washed in tap water, dehy-
drated, cleared in xylene, and mounted. Negative control
slides were made by substituting the primary antibody with
TBS.
Normal feline uterus was used as a positive control for ER
and PR detection. Adjacent normal mammary gland or
hyperplasia was used as an internal positive control in many
slides. Normal feline sebaceous glands in the skin were
internal positive controls for AR immunostaining. Ki-67
stained mitotic figures were considered positive internal
controls for Ki-67 immunostaining. Tumours were consid-
ered positive for ER, PR, or positive when more than 10%
positive cells were observed in 10 selected fields. In each
case, the Ki-67 index was calculated as the mean of the
proportion of positive nuclei in 8–10 representative fields.
Counting was done with a computer-assisted image ana-
lyzer (Olympus Microimage™ Image Analysis, software ver-
sion 4.0 for Windows, Media Cybernetics, Silver Spring,
MD, USA).
Results
History and clinical findings
The three cats were not ovariectomized at diagnosis, and
case 1 had been (10 years) receiving progestins routinely
to prevent oestrus (medroxyprogesterone acetate 25 mg
injected every 6 months). Mastectomies due to malignant
mammary tumours had been performed 4 months (case 1)
and 1 month (cases 2 and 3) before clinical signs of IMC
suddenly appeared (secondary IMC). When clinical signs
of IMC were detected, the cats had a slight decrease in
appetite and weight loss, but no other complaints were
noted apart from those described under clinical signs of
IMC (see below). At physical examination the cats had a
normal body condition, despite the weight loss observed by
the owners, and respiratory movements, hydration, rectal
temperature, mucous membranes, pulse and thoracic aus-
cultation were normal. Popliteal lymph nodes of the extrem-
ities affected by the mammary tumor were enlarged in all
three cases. At diagnosis of the IMC, radiological evalua-
tion of the thorax revealed only a slight interstitial pattern in
case 1, but no evidence of thoracic metastasis was found
in any cat. Secondary inflammatory carcinoma was diag-
nosed in the three cats, based on clinical history and signs
and histopathological features (see below).
Clinical signs of inflammatory mammary carcinoma
The mammary region (previous mastectomy wound and
adjacent areas) presented a rapid onset of erythema,
severe oedema, extreme local pain, and small areas of skin
ulceration and firmness, without subjacent mammary nod-
ules. Severe oedema and rejection of the surgical suture,
which were observed in cases 2 and 3 (surgically treated 1
month before), were the most evident clinical signs in these
two cases (Fig. 1). Cutaneous signs were also present in
the surgical wound in case 1, despite the fact that the sur-
gical procedure had taken place 4 months before and the
healing process was completed.
Involvement of the extremities was present in all three
cases, consisting of severe oedema and erythema of the
medial face of rear extremities (cases 1 and 2) and fore
limbs (case 3).
Laboratory results
In cases 2 and 3 examination of fine-needle aspiration
cytology samples revealed a severe inflammatory process
(neutrophilic and lymphocytic), in which some large
isolated or grouped epithelial cells exhibited cytological
Figure 1
Case 3: secondary inflammatory mammary carcinomaCase 3: secondary inflammatory mammary carcinoma. Erythema and
suture rejection after radical mastectomy (surgical excision of primary
mammary tumour).
Breast Cancer Research Vol 6 No 4 Pérez-Alenza et al.
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features of malignancy. In case 1 cytology was
nondiagnostic.
In case 1, routine laboratory blood analysis was performed
at diagnoses of the IMC. In the other two cats previous
analyses obtained 1 month earlier were available and within
normal ranges, with the exception of a slight hyperglycae-
mia (mean 7.8 ± 1.0 mmol/l).
In case 1 haematology revealed an haematocrit of 35%, an
haemoglobin of 12 g/dl and a total red cell count of 8.6 ×
106/µl (mean corpuscular volume 40.6 fl, mean corpuscu-
lar haemoglobin 14.0 pg, mean corpuscular haemoglobin
concentration 34.2 g/dl). Total leucocyte count was 22.2 ×
103/µl, with elevated neutrophil count (90%) and lympho-
paenia (6%). The biochemistry profile revealed the follow-
ing: glucose 10.5 mmol/l, urea 22.13 mmol/l, creatinine
132.6 µmol/l, total protein 78 g/l, alanine aminotransferase
10 IU/l, potassium 4.6 mmol/l, and corrected calcium 2.5
mmol/l. Clotting times were as follows: prothrombin time
14 s (reference range 9–14 s) and activated partial throm-
boplastin time 27.5 s (reference range 14–20 s). Fibrino-
gen concentration was 188 mg/dl (reference range 110–
400 mg/dl).
Histopathology
In case 1 incisional biopsy of the skin covering mammary
area with IMC signs was obtained. Histology revealed the
presence of an infiltrating mammary tumour classified as
papillary carcinoma of high HMG (grade III). The patholog-
ical features confirmed the presence of an IMC. In case 2
previous biopsy of the mammary tumour (before IMC
occurred) was available and showed the presence of a
HMG III papillary carcinoma. These pathological character-
istics in the absence of clinical signs of IMC, suggested a
diagnosis of occult IMC. Three weeks later, signs of clinical
IMC appeared. In case 3, incisional biopsy of the skin in the
mammary region demonstrated the presence of a highly
malignant tubular carcinoma (HMG III) with scattered lipid-
rich cells. The pathological diagnosis confirmed the pres-
ence of an IMC.
Dermal invasion, dermal tumour embolization of superficial
lymphatics (Fig. 2), dermal oedema, and severe secondary
inflammation with elevated amounts of neutrophils (case 1),
or lymphocytes, plasma cells and macrophages (cases 2
and 3) were also observed.
Treatment and follow-up
According to the therapeutic protocols for IBC and IMC,
surgery of the affected area is not a first choice approach.
The owners did not consent to administration of chemo-
therapeutic agents, and only palliative treatment with
broad-spectrum antibiotics and anti-inflammatories (piroxi-
cam) was given. The clinical condition of the animals wors-
ened a few days after IMC diagnosis (weakness, anorexia,
pain) and they were put down at 10 days (case 2), 15 days
(case 3) and 45 days (case 1) after IMC diagnosis, with the
owners' consent.
Necropsy findings
The owners gave consent for necropsy procedures in
cases 2 and 3.
Case 2
Gross examination of the carcass revealed severe lesions
in the skin of the mammary region, consisting of a nonheal-
ing wound with suture rejection and bilateral elevated white
plaques in the inguinal area. Severe oedema in both rear
limbs (Fig. 3) was observed. Medial muscles of the right
rear extremity had multiple small white nodules (less than
0.5 cm). Histopathological examination of the skin and
mammary gland revealed HMG III papillary mammary carci-
noma, as described previously in the biopsy, with metas-
tases in inguinal lymph nodes, muscles and lungs. Severe
signs of inflammatory reaction with an intense vascular con-
gestion of subepidermal neovessels, haemorrhages, exten-
sive neutrophilic infiltration in dermis and epidermal
micropustules were present in the necropsy samples.
Other histopathological findings were hepatic fatty change,
cystic ovaries and mild cystic endometrial hyperplasia.
Case 3
This animal presented with moderate obesity and an open
wound because of surgical suture rejection, with very thick-
ened and elevated margins. Moderate subcutaneous and
muscular emphysema in the wound area were observed.
Small (<0.5 cm diameter), elevated white nodules were
noticed in both sides of the wound. Histologically, apart
Figure 2
Case 3: incisional biopsyCase 3: incisional biopsy. Tumour embolization of dermal lymph ves-
sels. Haematoxylin–eosin; original magnification 10×.
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from the carcinoma, the skin of the mammary area exhibited
a severe neutrophilic dermatitis with fibrosis, abundant
pustules and marked hyperkeratosis. Adipose tissue sur-
rounding the mammary area also had severe fibrosis and
neutrophilic panniculitis. Bilateral metastases in inguinal
lymph nodes, massive pulmonary tumour embolization,
hepatic fatty change, mild multifocal neutrophilic hepatitis,
cystic ovaries, and moderate cystic endometrial hyperpla-
sia were also detected. No other significant findings were
observed in the remaining organs.
Immunohistochemistry
Ki-67 tumor proliferation index was similarly and markedly
elevated in the three animals: in case 1 it was 37.50%, in
case 2 it was 37.9% , and in case 3 it was 32.5%. ER immu-
nostaining was positive in case 1 (90% ER+ nuclei) and in
case 3 (100% ER+ nuclei). Case 2 was ER-negative in the
biopsy (occult IMC; 0% ER+) but ER-positive in the subse-
quent mammary sample with clinical symptoms of IMC
taken at necropsy (75% ER+; Fig. 4). In all three animals the
mammary tumours were PR-positive (95–100% PR+
nuclei; Fig. 5). AR immunostaining was very intense and
positive in the three tumours (AR+ 100% in case 1, AR+
80% in case 2, and AR+ 100% in case 3; Fig. 6).
Discussion
To our knowledge this is the first complete description of
feline IMC. The term 'inflammatory mammary carcinoma' is
widely used to describe locally advanced mammary
carcinoma, which simulates an inflammatory process and is
associated with poor prognosis. This condition has been
identified in humans (in which case it is termed IBC) [1-3,7-
13,15,16] and in the dog (in which case it is termed IMC)
[4-6,14]. Similarities among clinical features and preva-
lence have been found both in women and in the dog [6].
Thus far, spontaneous IMC has only been described in
these two species. Although feline mammary malignant
tumours are frequent in nonspayed female cats, IMC has
not been described in this species. The lack of information
on feline IMC may be due to a very low prevalence of the
disease in this species (even lower than in the dog) and to
difficulties associated with its recognition and accurate
diagnosis. In one study on feline mammary tumours, the
authors used the term 'inflammatory mammary carcinomas'
to include all tumours with any histological lymphatic
invasion (not only dermal invasion), which is not the diag-
nostic criterion for this type of tumour, and data concerning
the clinical features were not provided [20].
Two clinical types of presentation of IMC and IBC have
been described in humans and in dogs: primary (with no
previous mammary tumour) and secondary (postsurgical
and non-postsurgical) [2,5,8,10]. Slightly better clinical
evolution (survival in days, local pain and pulmonary metas-
tases) and better histological features (lower mitotic count,
atypical mitosis and pleomorphism; papillary–tubular ver-
sus solid dermal tumour infiltration) have been reported in
secondary canine IMC in comparison with primary IMC
[5,7]. In humans, neglected locally advanced breast cancer
can develop secondary inflammatory characteristics, which
may also follow a better clinical course [2]. In the three
feline cases presented here, inflammatory carcinoma
occurred after surgical excision of a malignant mammary
tumour, and therefore they can be classified as secondary
postsurgical IMC. In one case, dermal lymphatic emboli
were present in the previous biopsy at time of mastectomy
(before detection of clinical IMC), indicating the possible
presence of an occult inflammatory carcinoma. In our opin-
ion a histopathological diagnosis of occult inflammatory
carcinoma, as in case 2 in the present study, may be useful
Figure 3
Case 2: severe oedema of rear limbs observed at necropsyCase 2: severe oedema of rear limbs observed at necropsy.
Figure 4
Case 2: positive embolus to oestrogen receptorCase 2: positive embolus to oestrogen receptor. Streptavidin–biotin–
peroxidase; original magnification 20×.
Breast Cancer Research Vol 6 No 4 Pérez-Alenza et al.
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to the clinician because it provides information on the pos-
sible evolution of the disease.
The clinical condition of the animals in the present study
was better than that described in canine IMC. This might be
due to a slightly more favourable course of feline IMC than
occurs in canine IMC, but it might also be due to the better
clinical evolution that is typical of the secondary type of IMC
as compared with primary IMC. As the disease progressed
the clinical status of the cats worsened as well. The clinical
signs of IMC are similar to those described in the dog, but
erythema, ulceration and inflammatory reaction, with rejec-
tion of the surgical suture, appear to be the most evident
signs in the cat in comparison with those observed in the
dog. Rejection of the surgical suture is not a common find-
ing among dogs with secondary IMC.
Haematology and biochemistry results at the time of IMC
occurrence were normal in one cat, with the exception of
slight leucocytosis and prolonged coagulation times. In the
other two cats, laboratory results obtained one month
before IMC occurrence were normal. Unfortunately, these
data were not available at the time of IMC presentation.
Prolonged clotting times have been observed in dogs with
advanced mammary carcinoma and with distant metas-
tases, suggesting a disseminated intravascular coagulation
[21]. Probably in the cat with advanced IMC, disseminated
intravascular coagulation takes place, but more clinical
studies are necessary to confirm this.
There are few reports concerning histological aspects of
human IBC. It is well known that IBC is not a specific histo-
logical subtype; infiltrating ductal carcinomas, other carci-
nomas and unspecified malignant tumours have been
found to be involved with IBC [1,3,22,23]. In canine IMC,
histology revealed several types of carcinomas (solid, tubu-
lar, papillary and adenosquamous) and lipid-rich carcino-
mas [6]. The diagnosis of lipid-rich carcinoma was
established in canine IMC, according to human pathology
criteria [1], when more than 80% of the tumour cells were
lipid producing. The three feline IMC cases presented here
were histologically papillary/tubular mammary carcinomas
of high histological malignancy. In case 3, a low proportion
of lipid-rich cells was found (<80%). Lipid-rich carcinoma
is considered a rare type of mammary carcinoma in humans
[1] and dogs [18,24]. Lipid droplets in lipid-rich carcino-
mas have been associated with steroids and special neo-
plastic endocrine mechanisms in canine IMC [14]. In the
cat, this type of carcinoma has not previously been
described and it is not included in the histological
classifications.
The presence of neoplastic emboli in superficial dermal
lymph vessels (the hallmark of histological diagnosis of
IBC) was seen in all feline cases, confirming similarities
among the three species. In contrast, feline IMC had a
severe inflammation in dermis and adipose tissue, which is
is unusual in human and canine cases, and accounts for the
vascular reaction observed in one case (severe vascular
congestion and proliferation of subepithelial sanguineous
capillaries). Two types of neoplastic dermal infiltration have
been described in canine IMC: papillary type
(characteristic of secondary IMC) and sarcomatous type
(more malignant and typical of primary IMC, the most
aggressive type) [6]. In the feline cases studied here the
infiltration was always of the papillary type, and this is coin-
cident with the secondary IMC that the animals had devel-
oped. At necropsy the presence of pulmonary metastases
(not detected previously by radiology) and cystic ovaries
Figure 5
Case 2: positive embolus to progesterone receptor (same embolus as in Fig. 4)Case 2: positive embolus to progesterone receptor (same embolus as
in Fig. 4). Streptavidin–biotin–peroxidase; original magnification 20×.
Figure 6
Case 2: strong positive reaction to androgen receptorCase 2: strong positive reaction to androgen receptor. Streptavidin–
biotin–peroxidase; original magnification 20×.
Available online http://breast-cancer-research.com/content/6/4/R300
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with endometrial cystic hyperplasia are common findings in
dogs (unpublished data) and cats with IMC.
ER-α immunohistochemistry was positive in the tumours of
cats with clinical IMC. This is different than in the dog, in
which all the studied tumours were ER-negative [6].
Although the antibody and the technique used was the
same in feline and canine IMC, there might be stronger sim-
ilarities between human and feline ER-α with respect to the
particular epitope recognized by the monoclonal antibody
used. In addition, comparisons between hormonal analyses
in these two species should be considered with caution.
Presentation of canine IMC has been found to be signifi-
cantly associated with the luteal phase [5]. The luteal phase
is shorter (mean duration 36 days in cats) and is less fre-
quent in female cats than in female dogs, because in the cat
coitus-induced ovulation is required for initiation of the
luteal phase. The three cats in the present study had no coi-
tal exposure, and IMC appeared during the inter-oestrus
period.
Comparison of ER status of IMC tumours between species
cannot be properly done using immunohistochemical pro-
cedures only. A detailed molecular study of ER would be
desirable. The high positive immune reaction to PR and AR
found in feline IMC cases is comparable to that described
in canine IMC [6] and suggests, as in the dog, the possible
involvement of special endocrine mechanisms in IMC
development [14]. In this sense, it is interesting to note the
reversion in the ER immunoexpression status in feline IMC
case 2, which was ER-negative when the animal did not
have inflammatory signs and ER-positive in the samples
corresponding with clinical IMC. There is no explanation for
this ER reversion, but it could be related to a special endo-
crine cellular phenotype related to the 'inflammatory' type.
Several studies on ER and PR expression in human IBC
have yielded variable results [3]. ER-positive cases varied
from 22% to 52% and PR varied from 16% to 34% [25-
28]. In metastatic IBC the proportion of steroid receptors
was low, with the PR being more expressed than the ER
(8.7% ER+ and 17.4% PR+) [29]. Other authors consider
most IBC cases to be ER and PR negative [3]. There are
no studies concerning AR expression in human IBC.
The main differences observed between canine IMC and
feline IMC may be summarized as follows. Secondary post-
surgical presentation is the only clinical presentation of
IMC observed in the cat thus far. The most severe clinical
signs of IMC in the cat are inflammatory signs with oedema,
ulceration of the skin and rejection of surgical suture, with
no healing process completed after surgery (observed in
two out of three cases). This latter feature is not commonly
present in the dog. Histologically, apart from the typical
neoplastic embolization of superficial dermal lymphatics
(which are characteristic of IMC), a severe inflammatory
infiltrate composed of large amounts of neutrophils and
other inflammatory cells was seen in the three feline cases.
This histologically severe inflammation is not common in
canine IMC or human IBC, and cannot be accounted for
only by an inflammatory response in the wound healing
area, because in one cat (case 1) the repair process had
completed. A specific antineoplastic immune reaction
should be considered in feline cases.
In general, spontaneously occurring canine and feline mam-
mary tumours can be used as models of human cancer
[30]. On the basis of histological characteristics and clini-
cal outcome, feline mammary tumours are better models of
human breast cancer than are canine mammary tumours.
However, the information we have obtained thus far in feline
IMC (lower prevalence, only secondary IMC described,
associated with wound infection, ER+) appears to indicate
that, in this particular type of mammary cancer, canine IMC
is a better model. Feline IMC should be viewed with caution
as a natural model of human IBC.
Conclusion
The information provided herein regarding feline IMC (very
low prevalence, only secondary IMC, frequently associated
with wound infection, steroid receptor positivity) indicate
that feline IMC could be useful as a natural model of human
IBC, but the findings should be considered with caution.
Competing interests
None declared.
Acknowledgements
We thank the veterinarians caring for the referred cases (Veterinary Clin-
ics 'Indra' for case 3 and 'Mi Mascota' for case 1) and Pedro Aranda and
Mario Hernando for their technical support.
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