Veterinary Quarterly

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Hyperoestrogenism and mammary adenosis

associated with a metastatic Sertoli cell tumour in
a male Pekingese dog

James Warland , Fernando Constantino-Casas & Jane Dobson

To cite this article: James Warland , Fernando Constantino-Casas & Jane Dobson (2011)
Hyperoestrogenism and mammary adenosis associated with a metastatic Sertoli cell tumour in a
male Pekingese dog, Veterinary Quarterly, 31:4, 211-214, DOI: 10.1080/01652176.2011.653593

To link to this article: https://doi.org/10.1080/01652176.2011.653593

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Veterinary Quarterly
Vol. 31, No. 4, December 2011, 211–214

CASE REPORT
Hyperoestrogenism and mammary adenosis associated with a metastatic
Sertoli cell tumour in a male Pekingese dog
James Warland*, Fernando Constantino-Casas and Jane Dobson
Department of Veterinary Medicine, Queen’s Veterinary School Hospital, Cambridge, Cambridgeshire, United Kingdom
(Received 28 September 2011; final version received 23 December 2011)

Keywords: canine; dog; Sertoli cell tumour; hyperoestrogenism; adenosis; mastitis

A 5.5-year-old male, cryptorchid Pekingese dog was
referred to a University teaching hospital for manage-
ment of an abdominal ‘‘tennis ball’’-sized mass. He
suffered from exposure keratitis and brachycephalic
obstructive airway syndrome (BOAS). He had a 2-year
history of bilateral symmetrical alopecia. His owners
reported that he was dysuric, with marked pollakuria.
His right (descended) testicle was atrophied.
Haematology and serum biochemistry analyses
were unremarkable. Ultrasound examination carried
out by the referring veterinary surgeon revealed a mass
extending from the kidneys to the pelvis, with marked
cranial displacement of the small intestines, and caudal
displacement of the colon and urinary bladder.
Further imaging was impossible under sedation due
to the dog’s temperament. Radiographs of the thorax
taken under general anaesthesia showed enlargement
of sternal lymph nodes. His owner opted to proceed to
exploratory coeliotomy despite the presence of sus-
pected metastatic disease.
During the surgery, a neoplastic, retained, left testis
(10  8  7 cm) was removed along with four further
abdominal tumours, from around the left kidney and
adrenal gland. His right testicle (2.5  1.0  0.5 cm)
was removed through routine closed castration.
Postoperatively, he developed a urinary tract infection.
He was orally treated with 11.5 mg/kg BW paracetamol
(Calpol; McNeil Healthcare) twice daily for 5 days, and
16 mg/kg BW clavulanate-potentiated amoxicillin,
twice daily for 10 days (Clavaseptin; Vetoquinol).
Histopathology of the left testicular mass demon-
strated an encapsulated neoplasm, with two distinct
patterns; the tumour showed either dense sheets of
neoplastic cells or tubular structures supported by
fibrous connective stroma. The neoplastic cells were
round to polygonal and showed moderate eosinophilic
cytoplasmic staining as well as moderate anisocytosis
and anisokaryosis. Nuclei were round to ovoid with
vesicular chromatin. Mitoses were seen at 8 per 10
high-powered fields. Therefore, the left testicular mass
was consistent with a diffuse form Sertoli cell tumour
(SCT), with areas of tubular form. The other
abdominal masses were all consistent with metastases.
The right testicle showed reduced connective tissue,
seminiferous tubule number and lack of spermatogen-
esis. These findings were consistent with an atrophic
testicle.
The dog received palliative oral treatment
with meloxicam (Metacam; Boehringer Ingelheim),
0.1 mg/kg BW once daily. This continued for
6 months, until he developed haematochezia and
diarrhoea, which resolved on treatment cessation.
The dog was presented 7 months later after the
referring veterinary palpated further abdominal
masses. Examination revealed cachexia, marked alo-
pecia, thin skin, pendulous prepuce and an ill defined,
dorsal abdominal mass (Figure 1). The skin had several
brown, hyperkeratotic, epidermal comedomes. He had
a 1.5 cm diameter mass associated with the right 4th
nipple. The BOAS and keratitis had not changed
significantly.
Haematology revealed a mild, non-regenerative
anaemia, PCV 35% and left-shifted neutrophilia.
Serum biochemistry, T4 & TSH were unremarkable.
Thoracic radiography showed enlarged sternal and
tracheo-bronchial lymph nodes (Figure 2). Abdominal
ultrasound demonstrated a large coalescing mass in the
dorsal abdomen along the lymphatic chain. Fine needle
aspiration (FNA) of the abdominal mass was consis-
tent with SCT; FNA of the mammary mass was
consistent with pyogranulomatous inflammation along
with clusters of epithelial cells, showing mild anisocy-
tosis and anisokaryosis. Serum oestradiol concentra-
tion was >200 pmol/L (normal range for males
<10 pmol/L). Meloxicam was reinstigated as a pallia-
tive measure until he died 6 weeks later.
Post-mortem examination was carried out by the
referring veterinarian. The dog was found to have a

*Corresponding author. Email: jhw36@cam.ac.uk

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212 J. Warland et al.
Figure 1. The dog on second presentation, showing cachexia,
marked feminisation, extensive alopecia, skin thinning and a
pendulous prepuce.
Figure 2. Left lateral thoracic radiograph taken under
general anaesthesia at the time of second presentation,
showing soft tissue opacities in the regions of the sternal
and tracheo-bronchial lymph nodes.
large, firm, white and brown mottled, coalescing mass
in the dorso-caudal abdomen, and three similar masses
in the thorax, the largest in the cranio-ventral thorax.
The right, 4th mammary gland was thickened.
The abdominal and thoracic masses were consistent
with metastatic SCT (Figure 3). The mammary gland
demonstrated a multifocal, expansile, multilobular
mass; the lobules were formed by variable proportions
of well-differentiated ductular epithelium, myoepithe-
lial cells and fibrous connective tissue. Multifocally,
some mammary lobules demonstrated coagulative
necrosis with scattered lymphocytes, plasma cells,
a few neutrophils and cocci bacterial colonies.
The mammary mass was consistent with lobular
hyperplasia-type adenosis, with necrotising, neutrophi-
lic mastitis (Figure 4).
This report describes the management and post-
mortem findings of a Pekingese dog with metastatic
SCT, leading to hyperoestrogenism and concurrent
mammary adenosis and mastitis.
Figure 3. Histological section of sternal lymph node with
metastatic Sertoli cell tumour. Neoplastic cells in parallel
arrangement are within tubular structures surrounded by
fibrous connective stroma. Individual neoplastic cells are
elongated with round to oval nuclei. Occasionally a
vacuolated cytoplasm is present. H&E,  200.
Figure 4. Histological section of mammary adenosis show-
ing a lobular growth with well-differentiated ductular
epithelium, surrounded by variable amounts of myoepithe-
lium and fibrous connective tissue. H&E  40.
Sertoli cell tumours represent malignant transfor-
mation of sustentacular cells of the seminiferous
tubules. These represent the third most common
neoplasm of canine testes, after interstitial cell tumours
and seminomas (Grieco et al. 2008). The usual clinical
course is a solitary, benign mass; metastatic tumours
occur in less than 10% of cases. SCTs are more
common in retained testicles. Feminising syndrome is a
recognised complication, due to hyperoestrogenism,
with signs of alopecia and skin thinning; some dogs
present with anaemia and oestrogen myelotoxicosis
(Fan and de Lorimier 2007).
Sertoli cell tumours are the third most common
canine testicular tumour; the vast majority are benign,
with few malignant variants reported. They typically
occur in older animals (Reif et al. 1979). In contrast,
men typically develop metastatic testicular tumours,
most commonly seminoma, when young (20–35 years
old). In dogs, the risk of developing SCTs increases in
 Veterinary Quarterly
undescended testicles; one study reported that 54%
occurred in undescended testicles (Reif and Brodey
1969). This tumour was present in the left testicle, but
the right is more commonly reported as it is more
frequently retained (Reif et al. 1979). Although
commonly reported to occur in boxers, border collies,
Cairn terriers and Shetland sheepdogs, one report has
suggested that Pekingese are predisposed to SCTs
(Weaver 1983).
Environmental factors may contribute to the risk of
testicular neoplasia (Fan and Lorimier 2007); this may
be the reason for an increasing incidence over the past
40 years, also reported in men (Grieco et al. 2008).
SCTs can cause feminisation syndromes due to
hyperoestrogenism, affecting up to 57% of cases in one
study (Weaver 1983). As in this case, dogs with SCTs
have higher levels of oestradiol than normal male dogs;
these animals also have significantly reduced testoster-
one levels (Mischke et al. 2002). The precise mechan-
ism of oestrogen production is not fully understood,
but it likely relates to direct production and/or
conversion of testosterone to oestrogen by the
tumour. This leads to a wide range of clinical signs,
such as symmetrical alopecia, gynecomastia, galactor-
rhoea, contralateral testicular atrophy and pendulous
prepuce (Lipowitz et al. 1973). The protracted clinical
signs seen in this case, including a 2-year period of
alopecia, probably relate to a prolonged period of
hyperoestrogenism, which began months or years
before initial diagnosis. Hyperoestrogenism can cause
myelotoxicosis and bone marrow hypoplasia; this can
lead to pancytopaenia with anaemia, haemorrhage or
sepsis (Sherding et al. 1981). The mild anaemia found
during this dog’s final visit could be due to bone
marrow suppression or, more likely, chronic disease.
Abdominal metastatic lesions were surgically
accessible in this patient, and thoracic lesions were
not investigated at the time of diagnosis. It has been
reported that the measurement of excessive intrale-
sional oestradiol concentration can assist with the
confirmation of the SCT metastasis (Gopinath et al.
2009). Although SCTs are the most common testicular
neoplasia to cause hyperoestrogenaemia, others have
been reported, including a case of seminoma in a
Yorkshire terrier (Kim and Kim 2005).
The mammary mass in this case report was
consistent with adenosis where proliferation of epithe-
lial and myoepithelial cells formed well-differentiated
lobules. Mammary adenosis is a non-neoplastic pro-
liferation of epithelial cells within intratubular duc-
tules, myoepithelium and fibrous tissue (Misdorp et al.
1999). Mammary adenosis is far less frequent in dogs
than in women (Hampe and Misdorp 1974). Some
cases of mammary adenosis may be a pre-malignant
transformation; such cases have been reported in
humans (Shui and Yang 2009). In dogs and cats, the
exact mechanism of hormonal influence on mammary
dysplasia and tumour development is unknown.
However, the involvement of steroid hormones in the
development of mammary carcinomas is supported by
213
the protective effects of ovariectomy before 2.5 years of
age (Schneider et al. 1969). Oestrogen and progester-
one receptor expression is an important prognostic
factor in mammary tumours of dogs; normal mam-
mary gland, dysplastic tissue and benign tumours
express higher oestrogen and progesterone receptor
levels than malignant tumours, and lack of expression
in malignant tumours indicates a worse prognosis
(Chang et al. 2009). As in human breast cancer, there is
increasing evidence that canine mammary tissue
progresses from normal through dysplastic and
benign stages before producing a malignant tumour
(Sorenmo et al. 2009); this is hormonally driven, but
alterations in hormone receptors in more aggressive
tumours suggest that as they progress the lesions
change to become less reliant on external, hormonal
stimuli (Geraldes et al. 2000). This is further supported
by lower oestrogen receptor levels in metastatic lesions
(Rutteman et al. 1988).
Curative treatment of most canine SCTs is achieved
with surgery alone due to the low metastatic potential
(Fan and de Lorimier 2007). Chemotherapy using
cisplatin and bleomycin has been attempted, but
efficacy cannot be assessed given the small scale of
the study (Dhaliwal et al. 1999). In man, cisplatin- and
bleomycin-based chemotherapy protocols have revo-
lutionised the treatment of testicular tumours with
5-year survival rates to now over 95% (Verdecchia
et al. 2007). However, SCTs are rare in man, consisting
of less than 1.5% of testicular tumours (Littleton et al.
1981), with the successful treatment being described for
seminomas. Given the paucity of data on the treatment
for metastatic canine SCT and patient factors, such as
size and temperament, cytotoxic chemotherapy admin-
istration was deemed inappropriate in this case.
Although the survival time from diagnosis was
7 months, the dog had unexplained alopecia for 2 years,
possibly indicating a more protracted clinical course.
It is likely in this case that the onset and persistence of
alopecia was related to the presence of the oestrogen
secreting SCT, suggesting that it was present for at least
2 years before diagnosis. It is unknown at what stage in
tumourigenesis a SCT would cause hyperoestrogenism
sufficient to lead to systemic paraneoplastic disease.
There are no specific reports of survival times in cohorts
of dogs with metastatic SCT.
In this article we have reported the first case of a
male dog with mammary adenosis and mastitis second-
ary to the SCT. The mammary dysplasia is most likely
to be due to long-term effects of the SCT-related
hyperoestrogenism on the mammary gland.
Acknowledgements
The authors would like to thank the referring veterinarian,
Christopher Booth, for his help and ongoing interest in this
case, and the dog’s owners for their dedication and
permission to carry out post-mortem examination. Ian
Nicholson and Laura Owen are acknowledged for their
roles as the primary clinicians and surgeons at original
presentation. The authors would also like to thank the
214 J. Warland et al.

radiologists, clinical pathologists, anaesthetists and other and testosterone/oestradiol ratio in dogs with neoplastic
staff at the Queen’s Veterinary School Hospital involved in and degenerative testicular diseases. Res Vet Sci.
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Misdorp W, Else RW, Hellmen E, Lipscomb TP. 1999
Histological classification of mammary tumors of the dog
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