Mammary Carcinoma in A Male Cat Following Long-Ter
Mammary Carcinoma in A Male Cat Following Long-Ter
Mammary Carcinoma in A Male Cat Following Long-Ter
https://doi.org/10.1007/s11259-024-10553-3
CASE REPORT
Abstract
In male cats, as in men, mammary carcinomas are rarely reported. However, like in females, hormonal therapy is a sig-
nificant risk factor. This study reports the case of an 11-year-old male cat with multiple mammary tumours and a history
of long-term medroxyprogesterone acetate therapy for the suppression of sexual behaviour, along with a brief review of
the literature. Complete surgical removal of the right mammary chain and the ipsilateral inguinal lymph nodes was per-
formed, and all tissues were submitted for histology. Histological examination revealed the presence of a tumour in the
third and fourth mammary glands, consisting of neoplastic cells arranged in various structures, including tubulopapillary
and tubular structures, sometimes cystically dilated, and solid areas. The inguinal lymph nodes were also involved. The
morphology was consistent with a diagnosis of mammary carcinoma, tubulopapillary type, with nodal metastases. Immu-
nohistochemistry revealed that tumour cells were positive for cytokeratin (clones AE1/AE3), while stromal cells were
positive for vimentin (clone V9). The proliferation marker Ki-67, evaluated on both the primary tumour and the nodal
metastases, was strongly expressed in the nuclei of neoplastic cells, with a Ki-67 proliferation index of 8.9% and 20%
for the primary tumour and the metastases, respectively. This case highlights the importance of considering the possibility
of malignant mammary tumours not only in female but also in male cats with a history of long-term hormonal treatment
for suppression of sexual behaviour.
Background
13
Content courtesy of Springer Nature, terms of use apply. Rights reserved.
Veterinary Research Communications
be protective, several studies indicate that chemical spay- lesions (most likely mammary carcinoma or adenocarci-
ing through exogenous administration of progestogens noma) or fibroadenomatous hyperplasia.
represents a major risk factor in the development of these Tissue samples from all the mammary glands and the
tumours in cats of both sexes (Skorupski et al. 2005; Jacobs lymph nodes were collected, fixed in 10% neutral buffered
et al. 2010; Spugnini et al. 2010; Gregório et al. 2012). formalin for three days, and then trimmed and routinely
In the present report, we describe the histological and processed for histology. Briefly, samples were dehydrated
immunohistochemical features of a mammary carcinoma through graded alcohols, clarified in xylene, and embedded
with lymph node metastases in a male cat with a history of in paraffin. Four-micrometre-thick sections were obtained
long-term treatment with medroxyprogesterone acetate for from the paraffin blocks and stained with haematoxylin and
the suppression of sexual behaviour. eosin (H&E). Histologically, the first mammary gland was
characterised by moderate lobular hyperplasia, multifocal
ductal cysts, and duct ectasia. The second mammary gland
Case presentation was characterised by lobular mammary hyperplasia and
cysts filled with abundant proteinaceous material consistent
An 11-year-old male Domestic Shorthair cat was referred to with mammary secretion; the third and fourth mammary
the Veterinary Teaching Hospital of the University of Milan glands were entirely replaced by a highly cellular, unencap-
for multiple mammary nodules. The owner reported that the sulated, multinodular, infiltrative neoplasm, with multifo-
cat was cryptorchid and that the descended testis had been cal large necrotic areas. Neoplastic cells were cuboidal to
removed at an early age, while the undescended one was not columnar, ranging from 10 to 15 micrometres in diameter,
found until 1.5 years before the clinical examination, when with indistinct cell borders, a moderate amount of eosino-
it was finally removed in a second surgery. philic cytoplasm, and a large vesicular round to oval nucleus
After the first orchiectomy, for suppression of male with a prominent centrally located nucleolus. Neoplastic
behaviour caused by the presence of the undescended testis, cells were arranged in tubular and papillary structures, with
the cat received three subcutaneous injections per year of occasional areas of solid growth, supported and separated
medroxyprogesterone acetate (50 mg/ml) over an eight-year by dense fibrovascular and desmoplastic stroma (Fig. 1a).
period. The treatment was discontinued after the removal Tubular lumina contained necrotic debris, sloughed epithe-
of the undescended testis. The cat was regularly vaccinated lial cells admixed with secretion, and scattered neutrophils
and otherwise healthy. The clinical examination identified and foamy macrophages. Peri- and intraluminal lympho-
multiple subcutaneous nodules (ranging from 0.3 to > 3 cm plasmacytic aggregates were also observed. Lymphatic
in diameter), non-painful and movable in the right third and vessels were often ectatic, and multifocally contained solid
fourth mammary glands. On palpation, no inguinal lymph- aggregates of neoplastic cells (emboli).
adenomegaly was noted, and the physical examination was To better characterise the neoplasia, serial sections were
otherwise unremarkable. The nodules were sampled for obtained and automatically stained for immunohistochem-
cytology, and a diagnosis of carcinoma was achieved. On istry (IHC) with the avidin-biotin-peroxidase complex
clinician recommendation, the owner decided to proceed method using the Thermo Scientific™ Autostainer 480 S.
with the unilateral mastectomy of the right chain. Before The primary antibodies used are listed in Table 1. For all
surgery, thoracic radiographs and abdominal ultrasonog- markers, internal positive controls were used, while sections
raphy were performed to exclude distant metastases, and of the samples without primary antibodies were used as
both exams were negative. Laboratory tests (blood count, negative controls. For double immunofluorescence (IF), the
biochemistry profile, and urine analysis) were within the same mouse anti-vimentin antibody (1:1500) used for IHC
normal range, except for mild thrombocytopenia and lym- was applied, along with a goat polyclonal anti-Iba-1 anti-
phopenia. Therefore, a unilateral mastectomy of the right body (1:1000; Novus Biologicals, Centennial, CO, USA).
chain with the removal of the ipsilateral inguinal lymph For both markers, internal positive controls were used.
nodes was performed. The tissues removed were sent to the Neoplastic cells lining the tubules and papillae displayed
Pathology Unit for histological examination. strong cytoplasmic immunolabelling for cytokeratins
Grossly, the first thoracic mammary gland was apparently (Fig. 1b), while vimentin was positive in the cytoplasm of
normal; the second was characterised by multiple small cys- stromal and desmoplastic fibroblasts (Fig. 1c). Moreover,
tic lesions, and the third and fourth mammary glands were some neoplastic cells sloughed in the lumen of the ducts,
expanded by a white and solid plaque-like lesion of approxi- either isolated or in small groups, were variably positive for
mately 4 cm in diameter. Multifocal whitish lesions were both markers (Fig. 1d, e). Confirmation that sloughed cells
noted within the inguinal lymph nodes as well. Based on were actually neoplastic and not macrophages came also
gross findings, differential diagnoses included neoplastic from the double IF (Fig. 2).
13
Content courtesy of Springer Nature, terms of use apply. Rights reserved.
Veterinary Research Communications
The nodal parenchyma was extensively replaced by and 200 (20%) for the primary tumour and the metastases,
multiple metastases, morphologically consistent with the respectively.
neoplasia previously described (Fig. 3a, c). Follicular hyper- The adjuvant chemotherapy was proposed, but the owner
plasia was also present. Immunolabelling for cytokeratins refused it. One year after the diagnosis, the owner reported
revealed neoplastic cells mainly concentrated within the that the cat was humanely euthanised due to progressive
subcapsular and medullary sinuses and within the medul- respiratory distress and cachexia. Based on the owner’s
lary cords (Fig. 3b, d). Based on histomorphology and IHC, information, metastatic spread to other organs, particularly
a diagnosis of tubulopapillary mammary carcinoma with the lungs, may be hypothesised.
inguinal lymph node metastases was made.
The proliferative index measured by Ki-67 was also eval- Discussion and conclusions
uated on both the primary tumour and the nodal metastases,
as previously described (Castagnaro et al. 1998; Millanta et Male breast cancer (MBC) is relatively rare in human medi-
al. 2002; Soares et al. 2016). Briefly, the Ki-67 proliferation cine. On average, men are diagnosed at a later age com-
index was determined by assessing the percentage of posi- pared to women (the median age being 65 years) and at a
tively stained tumour cell nuclei in 1000 tumour cells. Ki-67 more advanced stage (Yalaza et al. 2016; Giordano 2018;
was strongly expressed in the nuclei of neoplastic cells Zheng and Leone 2022). They also have a lower overall sur-
(Fig. 4a, b). The Ki-67 proliferation index was 89.4 (8.9%) vival rate. Due to low public awareness and the absence of
screening programmes, men are more likely than women
13
Content courtesy of Springer Nature, terms of use apply. Rights reserved.
Veterinary Research Communications
Table 1 Primary antibodies for immunohistochemistry (IHC) Testicular abnormalities (e.g., cryptorchidism, orchitis,
IHC Marker Antigen Primary Code Spe- orchidectomy) may also be associated with MBC (Yalaza et
retrieval antibody cies
al. 2016; Giordano 2018; Zheng and Leone 2022). High oes-
Cytokeratin HIER; Mono- M3515 Mouse
(AE1/AE3) Buffer H clonal, trogen levels play an important role in MBC development,
pH 9* dilution: as do obesity and cirrhosis, which can both lead to increased
1:1000; oestrogen levels (Yalaza et al. 2016; Giordano 2018; Zheng
Agilent
and Leone 2022). Interestingly, men have a poorer progno-
Dako,
Santa sis despite having a high rate of hormone receptor immu-
Clara, CA, nohistochemical expression, which in women is associated
USA with a more favourable outcome (Giordano 2018; Zheng
Ki-67 (MIB-1) HIER; Mono- M7240 Mouse and Leone 2022).
Buffer H clonal,
pH 9 dilution:
Similar to humans, mammary carcinoma is rare in male
1:1000; cats (Hayes 1977; Skorupski et al. 2005; Gregório et al.
Agilent 2012). Mammary tumours in cats are usually diagnosed
Dako, between 10 and 12 years of age, are highly aggressive,
Santa
Clara, CA,
and frequently metastasise to regional lymph nodes (Gold-
USA schmidt et al. 2016). Regarding breed predisposition, they
Vimentin (V9) HIER; Mono- MA5-11883 Mouse seem to be more common in Siamese cats (Goldschmidt
Buffer H clonal, et al. 2016). Only a few studies on mammary tumours in
pH 9 dilution: male cats are available in the literature (Skorupski et al.
1:3000;
Thermo 2005; Baștan et al. 2007; Loukopoulos et al. 2007; Pires
Fisher et al. 2008; Jacobs et al. 2010; Gregório et al. 2012), and
Scientific, they indicate similar behaviour to tumours in female cats.
Waltham, The mean age at diagnosis (11.5 years) is also similar to
MA, USA
females (Skorupski et al. 2005; Loukopoulos et al. 2007;
*Dewax and HIER Buffer H (Epredia, Kalamazoo, MI, USA)
Gregório et al. 2012; Connah 2016; Tay et al. 2024). The
overall median survival time (calculated on a caseload of 27
cats) is 344 days for male cats with mammary carcinoma,
which is greater than the 7–10 months reported for female
cats (Skorupski et al. 2005). Reported breeds of male cats
with mammary carcinoma are Domestic short-hair, Sia-
mese, Domestic long-hair, and Persian (Skorupski et al.
2005; Baștan et al. 2007; Loukopoulos et al. 2007; Gregório
et al. 2012; Tay et al. 2024).
In men, ductal carcinoma is the most prevalent histologi-
cal subtype (Yalaza et al. 2016; Giordano 2018; Zheng and
Leone 2022). In male cats, the few cases described in the lit-
erature are either ductal adenocarcinomas or invasive micro-
papillary carcinomas (Pires et al. 2008; Gregório et al. 2012;
Connah 2016; Tay et al. 2024). In our study, a mixed pattern
was observed, with some areas consistent with a tubulopap-
Fig. 2 Mammary gland. Tumour papilla lined by neoplastic epithelial
cells. Neoplastic cells attached to the stalk of the papilla are negative
illary type and others encompassing more solid areas. How-
for vimentin (red), while the group of sloughed cells (white arrow- ever, the paucity of cases described so far makes it difficult
heads) are strongly positive for the same marker. Neoplastic cells to determine whether there is a characteristic histological
are negative for Iba-1 (green). Nuclei are stained with DAPI (blue). subtype for male cats’ mammary carcinomas, and studies on
Vimentin V9 + Iba-1 + DAPI (merged); IF; 1000x
larger caseloads are needed for confirmation. Nonetheless, it
is known that feline invasive micropapillary carcinoma is a
to present with regional nodal metastases (Giordano 2018). biologically aggressive tumour with decreased survival due
Risk factors include hormone imbalance, occupational and to its tendency to invade lymphatic vessels and metastasise
environmental exposures, and genetic factors such as family (Seixas et al. 2007). Tumour size (> 3 cm) and lymphatic
history, BRCA2 mutations, or Klinefelter syndrome (Yalaza invasion are, to date, the only factors negatively correlated
et al. 2016; Giordano 2018; Zheng and Leone 2022). with the survival of male cats with mammary carcinoma
13
Content courtesy of Springer Nature, terms of use apply. Rights reserved.
Veterinary Research Communications
Fig. 4 Mammary gland (a) and inguinal lymph node (b). Strong nuclear staining for Ki-67 in the neoplastic cells. Note the higher number of neo-
plastic positive cells in the nodal metastasis compared with the primary tumour; IHC; 200x
(Skorupski et al. 2005). The case described herein had both two different grading systems have been proposed for feline
lymphatic invasion and a tumour size > 3 cm. However, the mammary carcinomas, there is no definitive consensus on
cat survived up to one year after diagnosis without adjuvant which system should be used (Zappulli et al. 2019; Aval-
antineoplastic chemotherapy, which is longer than what is lone et al. 2021). The proliferative index measured by Ki-67
reported in the literature for tumours with these features was evaluated in a single case of male feline mammary
(Skorupski et al. 2005). On the other hand, this time span carcinoma (Gregório et al. 2012). To date, no consensus
matches the overall median survival time for male cats with or standardisation has been reached regarding Ki-67 index
mammary carcinoma (Skorupski et al. 2005). Grading has cut-offs for feline mammary carcinomas (Castagnaro et al.
not been performed in previously reported cases of mam- 1998; Millanta et al. 2002; Zappulli et al. 2015; Soares et al.
mary carcinoma in male cats (Skorupski et al. 2005; Pires 2016). As a confirmation of the lack of consistency on this
et al. 2008; Jacobs et al. 2010; Gregório et al. 2012). While matter, the Ki-67 proliferation index in our case was below
13
Content courtesy of Springer Nature, terms of use apply. Rights reserved.
Veterinary Research Communications
both the earliest cut-off proposed (25.2%) (Castagnaro et al. and proliferative keratopathies (Spiess et al. 2009). The use
1998), and the cut-off proposed later on (14%) (Soares et of progestins as therapeutic agents for cats increases the
al. 2016). Interestingly, in agreement with the same study possibility of serious side effects such as adrenal cortical
(Soares et al. 2016), the Ki-67 index in the case described suppression, glucose intolerance, hepatotoxicity, pyome-
herein was higher in the nodal metastases than in the pri- tra, mammary fibroadenomatous hyperplasia (Dorn et al.
mary tumour. 1983; Hayden et al. 1989; MacDougall 2003; Torrigiani et
Moreover, in our case, a few neoplastic cells, especially al. 2022), and/or mammary carcinoma (Oen 1977; Tom-
those detached and free in the ducts, were positive for linson et al. 1984; Goldschmidt et al. 2016; Zappulli et al.
vimentin, which is suggestive of epithelial-to-mesenchymal 2019). The risk of these side effects is significantly higher
transition (EMT). Since foamy macrophages are frequently in animals undergoing long-term (several years) treatment
found in mammary tumours admixed with sloughed neo- (Romagnoli and Concannon 2003). Dysplastic lesions of
plastic cells and secretion within ductal and tubular lumina mammary tissue, such as fibroadenomatous change, may
(Zappulli et al. 2019), the possibility that a small number eventually undergo malignant transformation with contin-
of these vimentin positive cells were macrophages cannot ued progestin treatment (Mol et al. 1996; Loretti et al. 2005;
be completely excluded, especially for rounded and indi- Skorupski et al. 2005; Jacobs et al. 2010; Goldschmidt et al.
vidualised cells. However, double IF revealed the neoplastic 2016). We do not exclude such a situation for the present
origin in the vast majority of these cells, further supporting case, given that the first and second glands were affected
the EMT transition. EMT is a well-described process that by hyperplastic changes. A possible initial development of
allows a polarised epithelial cell to assume a mesenchymal fibroadenomatous hyperplasia was considered, which could
phenotype (Kalluri and Weinberg 2009; Nistico et al. 2012). have represented a preneoplastic lesion.
This has been closely associated with cancer cell aggres- Moreover, as in this case, the development of a mammary
siveness, invasiveness, and elevated resistance to apoptosis tumour may occur years after drug administration (Jacobs et
and has also been reported in feline mammary carcinomas al. 2010). Interestingly, wild felids treated with contracep-
(Sammarco et al. 2023). This feature correlates well with tives for reversible reproductive control develop the same
the presence of nodal metastases in our case. kind of lesions described in domestic cats (Kollias Jr 1988).
The role of hormones in the development of feline mam- One study also reported mammary carcinoma in two male
mary carcinoma remains central. Exogenous progestins cats following contraceptive treatment with the steroid anti-
have been shown to increase the risk of developing mam- androgen cyproterone acetate (Spugnini et al. 2010). The
mary tumours by 3.4 times in both female and male cats mechanism of action of this substance on male cat mam-
(Skorupski et al. 2005; Goldschmidt et al. 2016). Spayed mary tissue is unknown; however, the authors described a
females and intact or castrated males exposed to progestins possible gestagenic effect, which might have contributed
are also at risk of developing mammary neoplasia (Hayden to the initial hyperplastic changes and secondary malignant
et al. 1989; Zappulli et al. 2019). The case reported herein transformation (Spugnini et al. 2010). The same substance
had features consistent with those previously described in has been reported as the cause of gynaecomastia in a male
both female and male cats treated with progestin therapy cat (Jelinek et al. 2007). Cyproterone acetate has occasion-
(Skorupski et al. 2005; Jacobs et al. 2010). In the retrospec- ally been associated with the development of gynaecomas-
tive study by Skorupski and colleagues (Skorupski et al. tia and breast cancer in men treated for prostatic malignancy
2005), one-third of the male cats with mammary carcinoma (d’Ancona and Debruyne 2005; Spugnini et al. 2010).
had a history of progestin therapy. Local and/or regional In this report, we described a case of mammary carci-
relapse was commonly reported (45%), and lymphatic inva- noma with a histopathological diagnosis of metastasis in
sion was identified in 44% of male cats. Similar results were the regional inguinal lymph node in a male cat follow-
also reported by Jacobs and colleagues (Jacobs et al. 2010), ing several years of treatment with medroxyprogesterone
who described local recurrences despite radical mastecto- acetate. While mammary carcinoma is still a rare entity in
mies being performed (Jacobs et al. 2010). male cats, veterinary clinicians and pathologists should be
Medroxyprogesterone acetate, also known as aware of this possibility, especially in animals with a his-
17α-hydroxy-6α-methylprogesterone acetate, is a steroidal tory of long-term hormonal treatment for the suppression of
progestin, a synthetic variant of the human hormone proges- sexual behaviour. For this reason, surveillance for immedi-
terone. It is commonly given to female cats for reproductive ate and long-term adverse effects, as well as knowledge of
control and to male cats as an alternative to gonadectomy for the benefit-cost ratio of currently available contraceptives,
behavioural modification (urine spraying/marking, reducing is recommended.
sexual behaviour including mounting, mating, and aggres-
sion) (Hart 1980; Kutzler and Wood 2006) and eosinophilic Author contributions A.M.P.: Data curation; Investigation; Meth-
odology; Validation; Visualisation; Writing - original draft. A.C.: In-
13
Content courtesy of Springer Nature, terms of use apply. Rights reserved.
Veterinary Research Communications
vestigation; Methodology; Visualisation; Writing - review & editing. Gregório H, Pires I, Seixas F, Queiroga F (2012) Mammary invasive
L.S.: Investigation; Methodology B.B.: Investigation; Methodology; micropapillary carcinoma in a male cat: immunohistochemical
Writing - review & editing. C.G.: Investigation; Methodology. D.S.: description and clinical follow-up. Acta Vet Hung 60:257–261.
Investigation; Methodology. MM: Supervision, Investigation; Writing https://doi.org/10.1556/avet.2012.022
- review & editing. V.G.: Supervision, Investigation; Methodology; Hart BL (1980) Objectionable urine spraying and urine marking in
Writing - original draft; Writing - review & editing. All authors read cats: evaluation of progestin treatment in gonadectomized males
and approved the final manuscript. and females. J Am Vet Med Assoc 177:529–533
Hayden DW, Barnes DM, Johnson KH (1989) Morphologic changes
Funding Open access funding provided by Università degli Studi di in the mammary gland of megestrol acetate-treated and untreated
Milano within the CRUI-CARE Agreement. cats: a retrospective study. Vet Pathol 26:104–113. https://doi.
org/10.1177/030098588902600202
Data availability No datasets were generated or analysed during the Hayes A (1977) Feline mammary gland tumors. Vet Clin North Am
current study. 7:205–212. https://doi.org/10.1016/S0091-0279(77)50017-2
Jacobs TM, Hoppe BR, Poehlmann CE et al (2010) Mammary adeno-
carcinomas in three male cats exposed to medroxyprogesterone
Declarations acetate (1990–2006). J Feline Med Surg 12:169–174. https://doi.
org/10.1016/j.jfms.2009.08.004
Ethics approval The present study, not conducted on experimental Jelinek F, Barton R, Posekana J, Hasonova L (2007) Gynaecomastia in
animals, is a retrospective one, totally based on pathology archive a tom-cat caused by cyproterone acetate: a case report. Vet Med
samples, realised with the permission of the owner and in line with (Praha) 52:521–525. https://doi.org/10.17221/2065-VETMED
the institutional Organisms for the Animal Welfare (OPBA_60_2022). Kalluri R, Weinberg RA (2009) The basics of epithelial-mesenchymal
transition. J Clin Invest 119:1420–1428. https://doi.org/10.1172/
Competing interests The authors declare no competing interests. JCI39104
Kollias GV Jr (1988) Complications of progestogen contraception in
exotic felids. In: Proceedings of the American Association of Zoo
Open Access This article is licensed under a Creative Commons
Veterinarians. pp 149–152
Attribution 4.0 International License, which permits use, sharing,
Kutzler M, Wood A (2006) Non-surgical methods of contracep-
adaptation, distribution and reproduction in any medium or format,
tion and sterilization. Theriogenology 66:514–525. https://doi.
as long as you give appropriate credit to the original author(s) and the
org/10.1016/j.theriogenology.2006.04.014
source, provide a link to the Creative Commons licence, and indicate
Loretti AP, da Silva Ilha MR, Ordás J, de las Mulas JM (2005) Clinical,
if changes were made. The images or other third party material in this
pathological and immunohistochemical study of feline mammary
article are included in the article’s Creative Commons licence, unless
fibroepithelial hyperplasia following a single injection of depot
indicated otherwise in a credit line to the material. If material is not
medroxyprogesterone acetate. J Feline Med Surg 7:43–52
included in the article’s Creative Commons licence and your intended
Loukopoulos P, Sutton RH, Lynch P, Gee DC (2007) Ectopic mam-
use is not permitted by statutory regulation or exceeds the permitted
mary carcinoma in a male cat. Vet Rec 160:203–204. https://doi.
use, you will need to obtain permission directly from the copyright
org/10.1136/vr.160.6.203-a
holder. To view a copy of this licence, visit http://creativecommons.
Łukasiewicz S, Czeczelewski M, Forma A et al (2021) Breast Cancer—
org/licenses/by/4.0/.
epidemiology, risk factors, classification, prognostic markers,
and current treatment Strategies—An updated review. Cancers
(Basel) 13:4287. https://doi.org/10.3390/cancers13174287
References MacDougall LD (2003) Mammary fibroadenomatous hyperplasia in
a young cat attributed to treatment with megestrol acetate. Can
Vet J 44:227
Avallone G, Rasotto R, Chambers JK et al (2021) Review of histologi-
Millanta F, Lazzeri G, Mazzei M et al (2002) MIB-1 labeling index
cal Grading systems in Veterinary Medicine. Vet Pathol 58:809–
in Feline Dysplastic and neoplastic mammary lesions and its
828. https://doi.org/10.1177/0300985821999831
relationship with Postsurgical Prognosis. Vet Pathol 39:120–126.
Baștan A, Anadol E, Özenç E, Yardımcı B (2007) A case of mam-
https://doi.org/10.1354/vp.39-1-120
mary neoplasm in a male cat. ANKARA Univ Vet Fak Derg
Mol JA, Van Garderen E, Rutteman GR, Rijnberk A (1996) New
54:139–140.
insights in the molecular mechanism of progestin-induced prolif-
Castagnaro M, De Maria R, Bozzetta E et al (1998) Ki-67 index as
eration of mammary epithelium: induction of the local biosynthe-
indicator of the post-surgical prognosis in feline mammary
sis of growth hormone (GH) in the mammary gland of dogs, cats
carcinomas. Res Vet Sci 65:223–226. https://doi.org/10.1016/
and humans. J Steroid Biochem Mol Biol 57:67–71
S0034-5288(98)90147-3
Nistico P, Bissell MJ, Radisky DC (2012) Epithelial-mesenchymal
Connah JG (2016) Metastatic mammary adenocarcinoma initially mis-
transition: General principles and pathological relevance with
diagnosed as a mast cell tumour in a male cat. Aust Vet Pract
special emphasis on the role of Matrix metalloproteinases. Cold
46:56–59
Spring Harb Perspect Biol 4:a011908–a011908. https://doi.
d’Ancona FCH, Debruyne FMJ (2005) Endocrine approaches in the
org/10.1101/cshperspect.a011908
therapy of prostate carcinoma. Hum Reprod Update 11:309–317.
Oen EO (1977) The oral administration of megestrol acetate to post-
https://doi.org/10.1093/humupd/dmi004
pone oestrus in cats. Nord Vet Med 29:287–291
Dorn AS, Legendre AM, McGavin MD (1983) Mammary hyperpla-
Pires I, Silva F, Queiroga FL (2008) Invasive Micropapillary Mam-
sia in a male cat receiving progesterone. J Am Vet Med Assoc
mary Carcinoma in a male cat: First Report. Vet Pathol 45:723–
182:621–622
723. https://doi.org/10.1354/vp.45-5-723
Giordano SH (2018) Breast Cancer in men. N Engl J Med 378:2311–
Romagnoli S, Concannon PW (2003) Clinical use of progestins in
2320. https://doi.org/10.1056/NEJMra1707939
bitches and queens: a review. Recent Adv Small Anim Reprod Int
Goldschmidt MH, Peña L, Zappulli V (2016) Tumors of the mammary
Vet Inf Serv (www ivis org), Ithaca, New York, USA A 1206:903
gland. Tumors in domestic animals. Wiley, pp 723–765
13
Content courtesy of Springer Nature, terms of use apply. Rights reserved.
Veterinary Research Communications
Sammarco A, Gomiero C, Beffagna G et al (2023) Epithelial-to-mes- Tomlinson MJ, Barteaux L, Ferns LE, Angelopoulos E (1984) Feline
enchymal transition and phenotypic marker evaluation in Human, mammary carcinoma: a retrospective evaluation of 17 cases. Can
Canine, and Feline Mammary Gland tumors. Animals 13:878. Vet J 25:435
https://doi.org/10.3390/ani13050878 Torrigiani F, Moccia V, Brunetti B et al (2022) Mammary fibroade-
Seixas F, Palmeira C, Pires MA, Lopes C (2007) Mammary invasive noma in cats: a matter of classification. Vet Sci 9:253. https://doi.
Micropapillary Carcinoma in cats: clinicopathologic features org/10.3390/vetsci9060253
and nuclear DNA content. Vet Pathol 44:842–848. https://doi. Yalaza M, Inan A, Bozer M (2016) Male breast Cancer. J Breast Heal
org/10.1354/vp.44-6-842 12:1–8. https://doi.org/10.5152/tjbh.2015.2711
Skorupski KA, Overley B, Shofer FS et al (2005) Clinical characteris- Zappulli V, Rasotto R, Caliari D et al (2015) Prognostic evaluation of
tics of mammary carcinoma in male cats. J Vet Intern Med 19:52. Feline Mammary Carcinomas. Vet Pathol 52:46–60. https://doi.
https://doi.org/10.1892/0891-6640(2005)19%3C;52:CCOMCI% org/10.1177/0300985814528221
3E;2.0.CO;2 Zappulli V, Peña L, Rasotto R, et al (2019) Surgical pathology of
Soares M, Ribeiro R, Carvalho S et al (2016) Ki-67 as a prognos- tumors of domestic animals volume 2: Mammary tumors. Kiupel,
tic factor in Feline Mammary Carcinoma. Vet Pathol 53:37–43. M, Ed
https://doi.org/10.1177/0300985815588606 Zheng G, Leone JP (2022) Male breast Cancer: an Updated Review of
Spiess AK, Sapienza JS, Mayordomo A (2009) Treatment of prolif- Epidemiology, Clinicopathology, and treatment. J Oncol 2022:1–
erative feline eosinophilic keratitis with topical 1.5% cyclo- 11. https://doi.org/10.1155/2022/1734049
sporine: 35 cases. Vet Ophthalmol 12:132–137. https://doi.
org/10.1111/j.1463-5224.2008.00679.x Publisher’s note Springer Nature remains neutral with regard to juris-
Spugnini EP, Mezzanotte F, Freri L et al (2010) Cyproterone acetate- dictional claims in published maps and institutional affiliations.
induced mammary carcinoma in two male cats. J Feline Med Surg
12:515–516. https://doi.org/10.1016/j.jfms.2010.01.009
Tay KL-Y, Cowan G, Chatterji S et al (2024) Exploring the One Health
paradigm in male breast Cancer. J Mammary Gland Biol Neopla-
sia 29:8. https://doi.org/10.1007/s10911-024-09560-6
13
Content courtesy of Springer Nature, terms of use apply. Rights reserved.
Terms and Conditions
Springer Nature journal content, brought to you courtesy of Springer Nature Customer Service Center GmbH (“Springer Nature”).
Springer Nature supports a reasonable amount of sharing of research papers by authors, subscribers and authorised users (“Users”), for small-
scale personal, non-commercial use provided that all copyright, trade and service marks and other proprietary notices are maintained. By
accessing, sharing, receiving or otherwise using the Springer Nature journal content you agree to these terms of use (“Terms”). For these
purposes, Springer Nature considers academic use (by researchers and students) to be non-commercial.
These Terms are supplementary and will apply in addition to any applicable website terms and conditions, a relevant site licence or a personal
subscription. These Terms will prevail over any conflict or ambiguity with regards to the relevant terms, a site licence or a personal subscription
(to the extent of the conflict or ambiguity only). For Creative Commons-licensed articles, the terms of the Creative Commons license used will
apply.
We collect and use personal data to provide access to the Springer Nature journal content. We may also use these personal data internally within
ResearchGate and Springer Nature and as agreed share it, in an anonymised way, for purposes of tracking, analysis and reporting. We will not
otherwise disclose your personal data outside the ResearchGate or the Springer Nature group of companies unless we have your permission as
detailed in the Privacy Policy.
While Users may use the Springer Nature journal content for small scale, personal non-commercial use, it is important to note that Users may
not:
1. use such content for the purpose of providing other users with access on a regular or large scale basis or as a means to circumvent access
control;
2. use such content where to do so would be considered a criminal or statutory offence in any jurisdiction, or gives rise to civil liability, or is
otherwise unlawful;
3. falsely or misleadingly imply or suggest endorsement, approval , sponsorship, or association unless explicitly agreed to by Springer Nature in
writing;
4. use bots or other automated methods to access the content or redirect messages
5. override any security feature or exclusionary protocol; or
6. share the content in order to create substitute for Springer Nature products or services or a systematic database of Springer Nature journal
content.
In line with the restriction against commercial use, Springer Nature does not permit the creation of a product or service that creates revenue,
royalties, rent or income from our content or its inclusion as part of a paid for service or for other commercial gain. Springer Nature journal
content cannot be used for inter-library loans and librarians may not upload Springer Nature journal content on a large scale into their, or any
other, institutional repository.
These terms of use are reviewed regularly and may be amended at any time. Springer Nature is not obligated to publish any information or
content on this website and may remove it or features or functionality at our sole discretion, at any time with or without notice. Springer Nature
may revoke this licence to you at any time and remove access to any copies of the Springer Nature journal content which have been saved.
To the fullest extent permitted by law, Springer Nature makes no warranties, representations or guarantees to Users, either express or implied
with respect to the Springer nature journal content and all parties disclaim and waive any implied warranties or warranties imposed by law,
including merchantability or fitness for any particular purpose.
Please note that these rights do not automatically extend to content, data or other material published by Springer Nature that may be licensed
from third parties.
If you would like to use or distribute our Springer Nature journal content to a wider audience or on a regular basis or in any other manner not
expressly permitted by these Terms, please contact Springer Nature at
onlineservice@springernature.com