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Apocrine Sweat Gland Ductal Adenoma with Sebaceous Differentiation in a Dog

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Case Reports in Veterinary Medicine
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A 7-year-old male, Border Collie, developed a firm mass, measuring approximately 1 cm in diameter, in the left buccal skin. Histologically, the mass was composed of ductal structures lined by bilayered luminal epithelial and basaloid tumor cells along with a few nests of sebaceous cells. Immunohistochemical staining revealed that the luminal epithelial tumor cells were positive for cytokeratin (CK, CAM5.2) and CK19 but not for CK14 or p63. In contrast, the basaloid tumor cells were positive for CK14, p63, and αSMA but not for CK19 or CAM5.2. CK8 expression was observed in both luminal epithelial and basaloid tumor cells. The tumor cells with sebaceous differentiation were positive for CK14 but not for the other markers. This is the first case of an apocrine sweat gland ductal adenoma with sebaceous differentiation occurring in the buccal skin of a dog.
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Case Reports in Veterinary Medicine
Volume , Article ID , pages
http://dx.doi.org/.//
Case Report
Apocrine Sweat Gland Ductal Adenoma with
Sebaceous Differentiation in a Dog
Masaki Michishita, Junki Yasui, Rei Nakahira,
Hisashi Yoshimura, and Kimimasa Takahashi
Department of Veterinary Pathology, Nippon Veterinary and Life Science University,
1-7-1 Musashino, Kyounan-cho, Tokyo 180-8602, Japan
Correspondence should be addressed to Masaki Michishita; michishita@nvlu.ac.jp
Received  November ; Accepted  November 
Academic Editors: N.-Y. Park and R. L. Santos
Copyright ©  Masaki Michishita et al. is is an open access article distributed under the Creative Commons Attribution
License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly
cited.
A -year-old male, Border Collie, developed a rm mass, measuring approximately  cm in diameter, in the le buccal skin.
Histologically, the mass was composed of ductal structures lined by bilayered luminal epithelial and basaloid tumor cells along
with a few nests of sebaceous cells. Immunohistochemical staining revealed that the luminal epithelial tumor cells were positive for
cytokeratin (CK, CAM.) and CK but not for CK or p. In contrast, the basaloid tumor cells were positive for CK, p, and
𝛼SMA but not for CK or CAM.. CK expression was observed in both luminal epithelial and basaloid tumor cells. e tumor
cells with sebaceous dierentiation were positive for CK but not for the other markers. is is the rst case of an apocrine sweat
gland ductal adenoma with sebaceous dierentiation occurring in the buccal skin of a dog.
1. Introduction
Apocrine sweat gland tumors are rather common in dogs and
tend to occur on the head, neck, and limb. Approximately
% of canine apocrine sweat gland tumors are benign in
nature [].Benigntumorsoftheapocrinesweatglandare
classied as apocrine adenomas, complex and mixed apoc-
rine adenomas, or apocrine ductal adenomas []. Apocrine
ductal adenomas in dogs are uncommon benign neoplasms
and accounted for only .% of canine skin tumors in a
large survey []. In dogs, sebaceous dierentiation has been
described in ve cases of mammary gland tumors [].
However, to the authors’ knowledge, a nonmammary-asso-
ciated apocrine tumor with sebaceous dierentiation in dog
has not been previously reported.
2. Case Report
A-year-oldmale,BorderCollie,developedarmmassin
thelebuccalskin,whichwassurgicallyremovedandsub-
mitted to the Department of Veterinary Pathology, Nippon
Veterinary and Life Science University (Tokyo, Japan), for
histopathological examination. Grossly, the mass was approx-
imately  cm in diameter, and a cut surface of the mass
appeared homogeneously greyish-white in color. A physical
examination including complete blood count and a routine
serum biochemical prole revealed no further abnormalities.
Detailed radiographic and X-ray examinations did not reveal
any mass suggestive of a tumor in the thoracic and abdominal
cavities. No tumor recurrence or metastasis was noted aer
 months of surgical excision. Additional therapy was not
performed.
e excised mass was xed in % neutral buered for-
malin, embedded in paran wax, cut into  𝜇msections,
and stained with hematoxylin and eosin (HE), periodic acid-
Schi(PAS),alcianblue,andoilredOstains.Serialsec-
tions were subjected to immunohistochemical (IHC) staining
using a labeled streptavidin-biotin peroxidase technique with
mouse monoclonal antibodies against low molecular weight
cytokeratin (CK; clone CAM., prediluted, BD Biosciences,
Franklin Lakes, NJ, USA), CK (clone Ks .,  : , Pro-
gen Biotechnik GmbH, Heidelberg, Germany), CK (clone
LC,  : , BioGenex Laboratories Inc., San Ramon, CA,
USA), 𝛼-smooth muscle actin (𝛼SMA; clone A,  : ,
Case Reports in Veterinary Medicine
DAKO, Glostrup, Denmark), CK (clone ..,  : ,
Boehringer Mannheim, Germany), and p (clone A,
:, NeoMarkers Inc., Fremont, CA, USA). All tissue sec-
tions were pretreated with citrate buer (pH .) and incu-
bated at C for  min. e reaction to each antigen was
visualized by the addition of ,󸀠-diaminobenzidine tetrahy-
drochloride chromogen and counterstained with hema-
toxylin.
Histologically, the mass was well demarcated and encap-
sulated. It consisted of various nodules and proliferating nests
mainly composed of bilayered ductal structures with an inner
layer of cuboidal to columnar luminal epithelial tumor cells
and an outer layer of basaloid tumor cells separated by a thin
brous stroma (Figure ). e inner layer of luminal epithelial
cells had clear cytoplasm and small hyperchromatic nuclei.
e outer layer of basaloid tumor cells had scant eosinophilic
cytoplasm and slightly larger euchromatic nuclei. Mitotic
activity was moderate. Within the tumor, there were a few
nests of large foamy cells similar to the sebaceous cells sur-
roundedbybasaloidcells(Figure ). e nuclei of these cells
were centrally located with nely vacuolated cytoplasm and
werenegativeforPASandalcianbluestainingbutpositive
for lipids by oil red O staining (Figure  inset). No squamous
dierentiation or keratinization was observed within the
tumor. Furthermore, no necrosis, invasion, or emboli of the
tumor cells was observed.
As shown in Ta b l e  ,immunohistochemicalstaining
revealed that the luminal epithelial tumor cells were positive
for CK (Figure ) and CAM. but not for CK, 𝛼SMA,
and p. In contrast, basaloid tumor cells were positive for
CK (Figure ), p (Figure ), and 𝛼SMA but not for CK
and CAM.. CK expression was observed in both luminal
epithelial and basaloid tumor cells (Figure ). e tumor cells
showing sebaceous dierentiation were positive for CK but
not for the other markers.
3. Discussion
On the basis of the histological and immunohistochemical
ndings, the tumor was diagnosed as an apocrine sweat gland
ductal adenoma with sebaceous dierentiation. According to
the World Health Organization classication of epithelial and
melanocytic tumors of the skin of domestic animals, benign
tumors of the apocrine sweat gland are classied as apocrine
adenomas, complex and mixed apocrine adenomas, or apoc-
rine ductal adenomas []. In dogs, sebaceous dierentiation
has been described in four cases of mammary gland tumors:
two complex adenomas [,] and two carcinomas [,]and
a case of salivary gland tumor [],whereasonehasnotbeen
previously described in apocrine sweat glands. e present
report describes a case of apocrine sweat gland ductal ade-
noma with sebaceous dierentiation occurring in the buccal
skin of Border Collie.
CK and CAM. are useful markers of luminal cell
markers, while CK, p, and 𝛼SMA are markers of basal/
myoepithelial cells in dogs [,]. CK expression has
been observed in both luminal and basaloid cells in canine
apocrine gland tumors []. In contrast, CK was expressed
F : Histopathological appearance of the buccal mass. e
mass is composed of the ductal structures lined by the bilayered
luminal epithelial and basaloid tumor cells. Hematoxylin and eosin
(HE). Bar =  𝜇m.
F : Sebaceous dierentiation observed within the apocrine
ductal adenoma. Sebaceous cells are characterized by abundant,
clear, and vacuolated cytoplasm and a centrally located nucleus
surrounded by basaloid cells in the apocrine ductal adenoma. HE.
Bar =  𝜇m. Inset: a frozen section stained with oil red O revealing
the lipid droplets within the cytoplasm of sebaceous cells.
T : Summary of immunohistochemical ndings.
Tumor cell type CAM. CK CK CK p 𝛼SMA
Luminal cells + + +−−
Basaloid cells ++ ++
Sebaceous-like cells −−+−− −
inthenormalsebaceousglandandmyoepithelialcellsof
apocrine and mammary glands [,,]. 𝛼SMA expression
was observed in the myoepithelial cells but not in the basaloid
cells in apocrine gland tumors []. In canine apocrine
carcinoma, p+SMA+,p
+SMA,andCK
+pcells
were identied in myoepithelial, basaloid, and luminal cells,
respectively []. Additionally, in concordance with previous
studies, this tumor primarily consisted of two tumor cell
types, luminal cells and basaloid cells, with sebaceous dier-
entiation.
is tumor appeared to b e dierentiated from a sebaceous
adenoma and trichoblastoma of the skin. e tumor char-
acteristics in the present case included cellular proliferation
with bilayered ductal structures with sebaceous dierentia-
tion, which is not a feature of a sebaceous tumor or trichoblas-
toma. Canine mammary gland tumors are oen observed in
squamous dierentiation [,]. Some canine apocrine sweat
gland ductal adenomas have foci of squamous dierentiation
Case Reports in Veterinary Medicine
F : Luminal tumor cells are positive for CK. Immunohisto-
chemistry for CK with hematoxylin counterstain. Bar =  𝜇m.
F : Basaloid tumor cells and cells showing sebaceous dieren-
tiation are positive for CK. Immunohistochemistry for CK with
hematoxylin counterstain. B ar =  𝜇m.
F : Basaloid tumor cells are positive for p. Immunohisto-
chemistry for p with hematoxylin counterstain. Bar =  𝜇m.
F : Both luminal and basaloid tumor cells are positive for
CK. Immunohistochemistry for CK with hematoxylin counter-
stain. Bar =  𝜇m.
with small keratin deposits in the infundibular portion of the
apocr ine duct []. However, squamous dierentiation was not
observed in this case.
e origin of the sebaceous component in this tumor
was unclear. However, previous studies suggested that tumor
basaloid cells can dierentiate into sebaceous epithelial cells
and that cutaneous stem cells might give rise to sebocytes in
canine mammary tumors [,,]. erefore, we propose
that the sebaceous dierentiation in this tumor may have
been derived from basaloid cells or local pluripotent stem
cells, similar to canine mammary gland tumors.
Conflict of Interests
e authors declare that there is no conict of interests.
Acknowledgments
e authors would like to thank Dr. Hidemi Kitagawa for
providing the follow-up information and the tumor specimen
for this study and Drs. Yoko Matsuda, Toshiyuki Ishiwata, and
Zenya Naito from Departments of Pathology and Integrative
Oncological Pathology, Nippon Medical School, for their
helpful discussions.
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