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270
Pakistan Veterinary Journal
ISSN: 0253-8318 (PRINT), 2074-7764 (ONLINE)
Accessible at: www.pvj.com.pk
Tubulopapillary Adenocarcinoma of the Mammary Gland in an Amazon Jaguar (Panthera
onca)
Sung-ho Yun§, Chun-ho Park 1§, Hwan-soo Jang2, Sae-kwang Ku 3, Kwang-ho Jang and Young-sam Kwon*
Department of Veterinary Surgery, College of Veterinary Medicine, Kyungpook National University, Daegu 702-701,
Korea; 1Department of Veterinary Pathology, School of Veterinary Medicine, Kitasato University, 23-35-1 Higashi,
Towada, Aomori 034-8628, Japan; 2Department of Pet Management, Suseong College, Daegu 708-711, Korea;
3Department of Anatomy and Histology, College of Oriental Medicine, Daegu Haany University, Daegu, 712-715, Korea
*Corresponding author: kwon@knu.ac.kr
ARTICLE HISTORY (13-339)
ABSTRACT
Received:
Revised:
Accepted:
July 26, 2013
August 08, 2013
August 10, 2013
A 17-years-old, female Amazon jaguar (Panthera onca) was presented for a
subcutaneous mass of the mammary gland. Surgical excision and microscopic
examination of the mass was performed. Histopathologically, the mass was
uncapsulated and composed of tubulopapillary lobules of atypical round to
polygonal epithelial cells. Tumor cells showed invasive growth into the connective
tissue of the dermis and mitotic figures were frequently observed. Tumor cells also
showed diffusely strong positive for cytokeratin (CK) AE1/AE3, proliferation cell
nuclear antigen (PCNA) and Ki-67 antibodies. But, CK14, vimentin and P63
immunoreactivity was mainly expressed in the myoepithelial cell layer. Based on
these pathological findings, present case was diagnosed as tubulopapillary
adenocarcinoma of the mammary gland of Amazon Jaguar (Panthera onca).
©2013 PVJ. All rights reserved
Key words:
Adenocarcinoma
Jaguar
Mammary gland
To Cite This Article: Yun SH, CH Park, HS Jang, SK Ku, KH Jang and YS Kwon, 2014. Tubulopapillary
adenocarcinoma of the mammary gland in an Amazon jaguar (Panthera onca). Pak Vet J, 34(4): 270-272.
INTRODUCTION
The neoplasia of genus Panthera of the family
Felidae has rarely been reported. Previous reports of
tumor of jaguar included glucagonoma (Ramos-Vara et
al., 2000), visceral mast cell tumor (de Castro et al.,
2003), and multiple neoplasia (Frazier et al., 1994). It has
been reported that mammary mucinous carcinoma in an
African lion metastasized to various organs (Cagnini et
al., 2012).
Immunohistochemistry is useful method for
identification of neoplasms and their origins. Proliferating
cell nuclear antigen (PCNA) is a nuclear protein which
has maximal concentration in the G1 and S phases of the
cell cycle. Also, Ki-67 is nuclear protein present in active
parts of all cell cycle. PCNA and Ki-67 are mainly used to
evaluating cell proliferation (Ozmen et al., 2008). The
nature of tumor cell could be differentiated with AE1/AE3
(epithelial cell marker), CAM5.2 (epithelial cell marker),
CK14 (myoepithelial cell marker), and vimentin
(myoepithelial cells and mesenchymal cells marker)
(Toniti et al., 2010). In this case report, we describe
histologic and immunohistochemical features in a case of
§These authors contributed equally to this manuscript.
tubulopapillary adenocarcinoma of mammary gland of
Amazon Jaguar (Panthera onca).
Case history, examination and findings: A 17-years-old
intact female Amazon jaguar (Panthera onca) that
weighed about 80 kg, was referred to the Veterinary
Medical Teaching Hospital of Kyungpook National
University with a history of slightly anorexia and ataxia
for the last few weeks. Physical examination revealed
single subcutaneous mass (13 cm in diameters) with ulcer
at the left fifth mammary gland (Fig. 1-A). Metastatis was
not confirmed by radiography and sonography. The mass
showed well demarcated, moveable, no adhered with deep
tissue and large multiple ulceration with serosanguineous
exudate were also seen. The jaguar had been treated with
antibiotics for several weeks. Mastectomy was performed
to remove the mass. The tumor mass was then submitted
for histopathological examination. In cut section, the mass
were well demarcated, multilobulated, grayish white with
partial hemorrhage and necrosis (Fig. 1-B).
Excised tissues were fixed in 10% neutral-buffered
formalin solution, embedded in paraffin according to a
conventional method, sectioned about 3 µm thick were cut
and mounted on glass slides. Sections were stained with
hematoxylin and eosin (HE) and serial sections were
CASE REPORT
Pak Vet J, 2014, 34(2): 270-272.
271
Fig. 1: Macroscopic and histopathological findings. As gross, single subcutaneous mass with hemorrhage was observed in the mammary gland (A). The
cut surface of the subcutaneous mass was grayish white and hemorrhagic areas with necrosis were observed (B). The subcutaneous mass divided into
lobules by thin fibrous stroma and the center of the tubules filled with the cell debris and eosinophilic secretes (∗) (C). The nuclei of tumor cells were
round to ovoid and mitotic figures (arrows) were frequently observed (D). Tumor cells showed infiltrative growth into the surrounding connective
tissue and invasion within lymphatic vessels (arrow) were seen (E). Small nests of tumor cells infiltrated into the collagenous dermis (arrows). Dilated
lymphatic vessels (∗) were also seen (F).
Fig. 2: Immunohistochemical findings. Most of tumor cells stain positively for CK AE1/AE3 (A). Most of tumor cells were stained positively for PCNA
(B). Many of the nuclei and mitotic figures (arrows) of the tumor cells were positively stained for Ki-67 (C). Occasionally, tumor cells were positive
for CK14 (D). Basal layer of the tubules were only stained for vimentin (E). Tumor cells reacted with antibody to CAM5.2 (F).
prepared for immunohistochemistry. The following
primary antibodies were used: cytokeratin (CK) AE1/AE3
(Zymed, Carlsbad, CA, USA), CK14 (Thermo Fisher
Scientific, Fremont, CA, USA), CAM5.2 (Becton
Dickinson, CA, USA), α-smooth muscle actin (SMA)
(DAKO, Glostrup, Denmark), vimentin (Nichirei, Tokyo,
Japan), proliferaion cell nuclear antigen (PCNA) (DAKO,
Carpinteria, CA, USA), P63 (Thermo Fisher Scientific,
Fremont, CA, USA) and Ki-67 (DAKO, Carpinteria, CA,
USA). Each antibody was visualized using 3-3’-
diaminobenzidine (DAB, Dako, Japan). Slides were
counterstained with hematoxylin.
Histopathologically, the subcutaneous mass located in
the mammary gland was divided into lobules by thin
fibrous stroma. Tumor cells formed acinus and tubular
structures and partial papillary projections. The center of
the tubules was filled with the cell debris and eosinophilic
secretes (Fig. 1-C). Some acinus produced lactating
materials, and sometimes formed large cysts. The tumor
cells had round to ovoid and constricted hyperchromatic
nuclei. Eosinophilic cytoplasm was relatively narrow and
cuboidal shape. Mitotic figures were observed at the rate
of over 5 per one field at ×400 magnification (Fig. 1-D).
Tumor cells showed infiltrative growth into the
Pak Vet J, 2014, 34(2): 270-272.
272
surrounding connective tissue (Fig. 1-E) and collagenous
dermis (Fig. 1-F). Occasionally, tumor cells were found
within adjacent lymphatic vessels. There were no
neoplastic changes of myoepithelial cells and no
differentiation to the chondroid or bone tissues.
Immunohistochemically, most of the tumor cells were
stained positively for AE1/AE3 (Fig. 2-A), PCNA (Fig. 2-
B), and 50-70% of the cells were positive for Ki-67 (Fig.
2-C) antibodies. Approximately 10% of tumor cells
aligning innermost in the tubules expressed CK14 (Fig. 2-
D). Myoepithelial cells located at the periphery of some
neoplastic lobules and a part of cuboidal cells in the
tubules were stained for SMA (data not shown), vimentin
(Fig. 2-E) and P63 (data not shown) antibodies. Tumor
cells and myoepithelial cells slightly react with CAM5.2
antibody (Fig. 2-F). Based on these histopathological and
immunohistochemical observations, this tumor diagnosed
as tubulopapillary adenocarcinoma of the mammary
gland.
DISCUSSION
Lifelong sex hormonal exposure may influence
tumorigenesis and tumor progression. Longevity also
regarded as one risk factor of the mammary gland tumor.
Geriatric jaguars (>16 years), especially in female, were
highly prevalent in reproductive disease (Hope and Deem,
2006). In this case, the jaguar was sexual intact and 17
years old and she could be considered to geriatrics.
There were some reports that melengestrol acetate
(MGA) treatment as contraception has close link with
increase in the risk of mammary cancer. According to the
other reports, regardless of MGA exposure, jaguars have
higher prevalence of mammary gland cancer than other
felids (Hope and Deem, 2006; McAloose et al., 2007).
She was adapted in the owner’s zoo 12 years ago and
there have been no administration history of MGA.
Another risk was proposed as carnivores are at the top of
the food chain, they could have high chance of exposure
to the diet contained environmental carcinogens or high
level harmful hormones. In the literature, regardless of
MGA administration, tubulopapillary pattern was most
common and majority of mammary carcinomas were
multiple histologic pattern (Munson and Moresco, 2007).
In this case, tubulopapillary pattern which has varying
sized tubes was prevalent and, although necrosis was
observed in some areas, combinations with other pattern,
such as solid or comedone form, were not shown.
Immunohistochemically, the expression of Ki-67 was
strong (50~70%), especially in the tumor cells showing
mitotic figure, and PCNA positivity was also observed in
most cells. These findings support that the tumor is highly
malignant and aggressive. Similarly, it was reported that
most zoo felids had a high grade cancer with comparable
aggressive metastasis regardless of treatment of MGA or
not (McAloose et al., 2007).
Mammary gland epithelium is mainly consisted with
two layer; basal/myoepithelial layer and inner luminal
layer. To identify the nature of tumor cells, the expression
pattern of AE1/AE3, vimentin, and CK14 needs to be
examined. As a result, strong expression of AE1/AE3 was
seen in epithelial cell. Tumor cells were diffusely positive
for CAM5.2. Myoepithelial cells stained positively for
SMA and vimentin were mainly located at the periphery
of neoplastic lobules. Although infiltrative growth to
surrounding tissue could be seen, most proliferative tumor
cells were surrounded by a layer of myoepithelial cells
that did not present neoplastic proliferations. CK14 was
detected with slight and diffused positivity in some
neoplastic cell. Attenuated vimentin and CK14 reaction
could imply that the tumor was invasive (Sopel, 2010) and
luminal to myoepithelial ratio was increased. According to
these findings, most tumor cells thought to be originated in
luminal cells, not in basal or myoepithelial cells.
During 6 months follow-up after surgical excision, no
sign of tumor recurrence was observed and the jaguar
remained clinically well. After 9 months from the
operation, the jaguar was suddenly dead. Postmortem
necropsy could not be performed and additive data or
samples could not be collected. Therefore, we cannot
identify the cause of mortality or the fact of recurrence or
metastasis to the other organs.
Conclusion: Based on the histopathologic and
immunohistochemical findings, it was concluded that the
tumor of jaguar was simple adenocarcinoma which is
classified as tubulopapillary, and it may be useful to
understand the characteristics of mammary gland tumor in
jaguar.
Acknowledgement: This research was supported by
Kyungpook National University Research Fund, 2012.
This research was supported by Basic Science Research
Program through the National Research Foundation of
Korea (NRF) funded by the Ministry of Education,
Science and Technology (2010-0007523).
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