A fifteen-year-old mongrel bitch was admittedat the Veterinary Hospital of the Universidade Federal
de Minas Gerais (Belo Horizonte, Brazil) with a right
cranio-ventral cervical enlargement of approximately
20 centimeters in diameter (Figure. 1A). The bitch
underwent surgery and the invasive mass in
submandibular region involving salivary gland was
removed. Before surgery, 200 ml of serous-bloody
fluid were drained from cystic area of tumor. The mass
was firm, poorly mobile, highly vascularized with
approximately 20 cm in diameter, and extended into
adjacent tissues including muscular tissues and the
jugular vein (Fig. 1B).
The tumor was submitted for histopathology,
and representative samples of the neoplastic tissue
Salivary gland carcinosarcoma in a dog
were fixed by immersion in 10% buffered formalin,
processed for paraffin embedding,and stained with
hematoxylin and eosin (HE). Three-μm sections were
stained by standard streptavidin-biotin
immunoperoxidase method (LSAB+ Kit, Dako Corp.,
Carpinteira, CA) with the following primary
antibodies: monoclonal mouse anti-human cytokeratin
AE1/AE3 (Dako, dilution 1:50), monoclonal mouse
anti-vimentin (Dako, dilution 1:100). Negative control
sections of the tumor lacked primary antibody, and in
addition to internal controls (i.e. epithelial and
mesenchymal tissues in the remaining normal tissues in
the section), positive control tissue sections were
include for each antibody.
firm with an irregular and nodular surface, and on the
cut surface, there were mixed areas of brownish and/or
whitish color and firm or friable consistency.
Histopathology revealed simultaneous proliferation of
both epithelial and mesenchymal malignant
components. The tumor displayed two clearly distinct
areas partially separated by connective tissue. One
portion presented neoplastic cells aligned along small,
thin or globular, poorly calcified trabeculae of osteoid
(Fig. 2A). The cells were oval to spindle shaped, and
not had discernable cell boundaries and moderate,
eosinophilic, fibrillar, and often vacuolated cytoplasm.
The nuclei were round, oval, and had stippled
chromatin and prominent nucleoli. In addition, there
were multiple areas of necrosis, and presence of
metaplastic cartilage and bone among myoepithelial
cells. In other areas, carcinomatous cells with dense
sheets of basophilic pleomorphic cells appearing to
form acini, solid cords, and nests were supported by
collagenous stroma (Fig. 2B). The neoplastic cells were
polyhedral or rounded, with a high nucleus/cytoplasm
ratio, they had a scant basophilic cytoplasm, and the
nuclei were irregularly shaped with prominent nucleoli.
High anisocariosis and high mitotic index were
observed, and bizarre mitotic figures were common.
Immunohistochemistry results for vimentin and
cytokeratin confirmed the presence of carcinomatous
and sarcomatous components. The mesenchymal cells
were strongly positive for vimentin (Fig. 3A), where
most cells adjacent to osteoid was immunoreactive.
Conversely, the majority of neoplastic glandular
structures marked strongly for cytokeratin AE1/AE3
(Fig. 3B).
Following surgical resection of neoplasic mass
without proper surgical margins, and the
histopathological diagnosis of carcinosarcoma,
chemotherapy was elected due a high risk of
recurrence. Treatment started 15 days after surgery
with Carboplatin (300 mg/m2) administered
intravenously at 21 days/cycle, 3 cycles. The bitch
presented no significant clinical changes during
chemotherapy, without side effects caused by the
cytostatic drug. However, the chemotherapy was
interrupted due to the owner´s decision. There was
recurrence of neoplasic growth in the cervical region at
the site of the previous surgical exeresis. The owners
then elected euthanasia. The time of survival of this
animal was 180 days. The owner did not authorize a
necropsy.
shape aligned along poorly calcified matrix osteoid. B) Section with area the malignant proliferation of cell epithelial
forming acini and solid nest supported by collagenous stroma. HE, 400x
population showing immunoreactivity for vimentin (brown). B) Carcinosarcomatous zone with a squamous patter
expressing immunoreactivity for cytokeratin (brown), adjacent mesenchymal cells without marking . Streptavidin-biotin
peroxidase. 400x.
Discussion
Benign mixed tumor is most common
neoplasm of gland salivary human (13), but it is
uncommon dogs (9). Conversely, malignant mixed
salivary gland tumor refers to carcinoma in
pleomorphic adenoma (9, 11), which is a tumor
characterized by a malignant epithelial component in a
previously pleomorphic adenoma, and it has been
described in dogs (3, 9, 20, 21). However, true
carcinosarcoma is very rare in dog and cats (3, 9), and
this case is only the second case report of salivary
gland carcinosarcoma in a dog that was confirmed by
immunohistochemistry (16). Carcinosarcoma is also
considered a rare salivary gland neoplasia in man (11).
The diagnosis of carcinosarcoma in this case
was based on the presence the two malignant
components, one epithelial or myoepithelial and
another mesenchymal. These morphological findings
were further characterized by immunohistochemistry,
with sarcomatous and carcinomatous components
being immunoreactive for vimentin and cytokeratin,
respectively, as previously described (11, 16).
Immunohistochemistry is extremely important for
accuracy of the diagnosis of carcinosarcoma,
supporting the differential diagnosis with other
neoplasms (6, 17, 19). Other neoplasms that should be
considered in the differential diagnosis includes
malignant mixed tumor (20), spindle cell carcinoma,
teratoma (19), and osteosarcoma, which has been
reported as a primary neoplasm in salivary gland (23).
Our study reports a case of salivary gland
carcinosarcoma in a dog with 15-year-old, without
clinical manifestations other than local swelling, which
is similar to other reported cases of salivary gland
tumors (3, 8). Metastases were not clinically identified
but the necropsy was not performed in this case.
Malignant salivary gland neoplasms are usually
metastasize mostly to regional lymph nodes (3).
Therefore, malignant salivary gland has a poor
prognostic since the diagnosis is of often delayed
because of asymptomatic development of the tumor.
The indicated treatment of malignant salivary
gland tumor is surgery resection. However, invasive
tumors that involve adjacent vital structures complete
resection is impractical. In these cases, radiotherapy is
indicated as auxiliary treatment to promote local
control of neoplasm and long-term survival (8). The
use of chemotherapy as treatments of malignant
salivary gland tumor has been not explored in dog. The
media of survival of dogs treated with surgery and
radiotherapy is about 550 days (8), however, the
endurance of animals that suffer only tumor resection
is 74 days (7) and association of surgery and
chemotherapy has not been described in literature.
Malignant salivary gland tumor may have
variable histology, biological behavior and
responsiveness to systemic therapy. There is not any
standard protocol of chemotherapy for these tumors,
but platin-based treatment is often used in man (12).
Since that the association of surgery and radiotherapy
treatments was not possible, we opted for
chemotherapy using carboplastin. The survival of this
animal was 180 days, which is longer than the survival
time of dogs treated with surgery only (7), but shorter
than surgery associated with radiotherapy
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