897585

research-article2019
VDIXXX10.1177/1040638719897585Renal interstitial cell tumor in a dogCho et al.

Brief Communication

Journal of Veterinary Diagnostic Investigation

Renal interstitial cell tumor in a dog: 2020, Vol. 32(1) 124­–127

© 2019 The Author(s)
Article reuse guidelines:
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DOI: 10.1177/1040638719897585
https://doi.org/10.1177/1040638719897585
jvdi.sagepub.com
histologic features

Seung-Hee Cho, Byung-Joon Seung, Soo-Hyeon Kim, Ha-Young Lim,

Gyu-Seok Lee, Mi-Suk Chae, Jung-Hyang Sur 1

Abstract. Renal interstitial cell tumors are benign tumors of renomedullary origin; however, malignant features have not
been reported in dogs, to our knowledge. A 17-y-old spayed female Maltese dog was presented to a local animal hospital with
a mass in the right abdomen. Clinicopathologic findings prior to surgery revealed renal insufficiency and anemia. Imaging
revealed that the right kidney was enlarged by an amorphous mass with opaque areas, indicative of mineralization. Upon
histologic examination, the mass was comprised of malignant mesenchymal cells that produced mucinous matrix. The tumor
cells were positive for vimentin and COX-2, but negative for pancytokeratin; the matrix stained positively with alcian blue.
Therefore, the mass was diagnosed as a renal interstitial cell tumor, with malignant features. COX-2 may be useful in the
diagnosis of canine renal interstitial cell tumors, similar to its diagnostic role in humans.

Key words: dogs; image; immunohistochemistry; malignant; renal interstitial cell tumor.

In dogs, primary renal tumors are relatively uncommon,
comprising 0.3–1.5% of all reported canine tumors.1,2,11
Nearly 70% of canine renal tumors are derived from epithe-
lial cells, 25% are derived from mesenchymal cells, and 5%
are nephroblastomas.10 Notably, renal interstitial cell tumors
have been reported only rarely.10
Renal interstitial cell tumors are believed to arise from
renal interstitial cells that contain prostaglandin and arachi-
donic acid.10 Renal interstitial cells exhibit distinctive
ultrastructural features such as lipid-rich cytoplasmic vesi-
cles; this neutral antihypertensive lipid can lower arterial
blood pressure.5,10 Most renomedullary interstitial cells
express high levels of cyclooxygenase-2 (COX-2), which is
the inducible isoform of prostaglandin-endoperoxide syn-
thase 2.5,13 In humans, renal interstitial cell tumors are
known to be COX-2 positive.10
Moreover, in humans, these mesenchymal tumors are
known as renomedullary interstitial cell tumors, which are
benign neoplasms diagnosed only rarely prior to death; they
were previously described as medullary fibromas or hamarto-
mas.12,13 The tumors are commonly identified at autopsy, in up
to 50% of autopsy cases; most are asymptomatic and < 5 mm
diameter, hence the antemortem diagnostic rate is low.12
In previously reported cases of canine renal interstitial
cell tumors, only benign features were observed as in
humans; moreover, there were no data regarding clinicopath-
ologic or imaging findings (e.g., radiography, ultrasonogra-
phy, or computed tomography).4 We describe herein a renal
interstitial cell tumor with malignant features in a dog.
A 17-y-old spayed female Maltese dog weighing 3.9 kg
was presented because of anorexia and an enlarged right
side of her abdomen. Blood was collected for a complete
blood count and chemistry panel. Creatinine and urea con-
centrations were increased as were the activities of amylase
and lipase; moderate anemia and leukocytosis were present
(Table 1).
Radiographic findings included an ovoid mass with soft
tissue opacity in the right side of the abdominal cavity, as
well as deviation of the pylorus and intestines in the opposite
direction. A large amorphous structure with mineralization
opacity was identified in the right cranio–mid-abdominal
cavity (2.5 cm3) and was located in the mass. The right kid-
ney was enlarged on ultrasonographic examination, and
normal architecture was lost. A heterogeneously hyper-
echoic lesion was identified in the right renal mass, caudal
to the anechoic lesion. Computed tomography revealed
an irregularly enlarged caudal pole of the right kidney (71
× 81 × 54 mm; Fig. 1). A 2.5-cm3 stellate-shaped area of
Small Animal Tumor Diagnostic Center, Department of Veterinary
Pathology, College of Veterinary Medicine, Konkuk University, Seoul,
Republic of Korea (Cho, Seung, Kim, Lim, Sur); Wooridle Animal
Medical Center, Seoul, Republic of Korea (Lee); Samsung Animal
Medical Center, Seoul, Republic of Korea. (Chae)
1
Corresponding author: Jung-Hyang Sur, Department of Veterinary
Pathology, Konkuk University, 120, Neungdong-ro, Gwangjin-gu, Seoul,
Republic of Korea. jsur@konkuk.ac.kr
 Renal interstitial cell tumor in a dog 125

Table 1.  Clinicopathologic findings prior to surgery in a dog

with a renal interstitial cell tumor.

Parameter Unit Result Reference interval6

CBC
 Leukocytes ×109/L 27 4.0–15.5
 RBC ×1012/L 3.7 4.8–9.3
 Hemoglobin g/L 95 122–203
 Hematocrit L/L 0.25 0.36–0.6
Chemistry
 Albumin g/L 12 27–44
 Creatinine µmol/L 194 44.2–141.4
 Urea mmol/L 15.5 2.1–8.9
 Amylase U/L 5,480 219–1,125
 Lipase U/L 1,026 77–695
CBC = complete blood count; RBC = red blood cells. Figure 2. Renal interstitial cell tumor in a dog. The mass
replaced ~30% of the right kidney; recognizable kidney tissue
remained. Bar = 1 cm.

The mass was processed routinely, and sections were

Figure 1.  Computed tomography of renal interstitial cell tumor
in a dog. The preoperative image showed an irregularly enlarged
mass. The cranial region of the right kidney maintained a normal
shape, but its position was changed in the cranial direction by the
mass. The mineralized region (arrow) was found between normal
kidney and the mass.
mineralization was identified in the right renal pelvis and
diverticulum; the mass displaced other abdominal organs
to the left. No other abnormalities or metastases of the
tumor were found in other organs by imaging. The mass
was removed surgically under general anesthesia. The
excised mass was fixed in 10% neutral-buffered formalin,
and was sent to the Department of Veterinary Pathology,
College of Veterinary Medicine, Konkuk University,
Republic of Korea. The dog died one week after surgery,
and an autopsy was not performed at the referral hospital.
On gross examination, the right kidney contained one
irregular, large, red-to-ivory mass (70 × 78 × 55 mm) on
the elongated caudal pole; the cranial pole was of normal
shape (Fig. 2). The center of the tumor was mineralized
extensively, as noted in radiographic analysis and com-
puted tomography; thus, the tumor was sectioned after
demineralization. Cross-section of the cranial pole of the
right kidney revealed tissue similar to that of normal kid-
ney macroscopically.
stained with hematoxylin and eosin for histologic examina-
tion. Microscopically, there was multifocal necrosis within
the mass. The right adrenal gland was not clearly identified
on the image and gross findings, but was confirmed near the
mass on histologic examination. The tumor was nonencapsu-
lated and comprised interlacing bundles of uniform spindle
cells with basophilic nuclei and slight-to-moderate amounts
of eosinophilic cytoplasm. The neoplastic cells invaded peri-
nephric fat (Supplementary Fig. 1) and connective tissue
adjacent to the adrenal gland (Supplementary Fig. 2). The
neoplastic cells had intracytoplasmic vacuoles (Fig. 3) and
mild-to-moderate pleomorphic nuclei with single-to-multi-
ple prominent nucleoli; moreover, the mitotic count was high
(53 mitoses in 2.37 mm2; Fig. 4). One bizarre mitosis per
2.37 mm2 was observed. The mineralized portion found
between normal kidney and tumor was identified as exten-
sive osseous metaplasia (Supplementary Fig. 3). Dilated
tubules were observed in the cranial pole of the kidney, as
well as mild lymphoplasmacytic interstitial nephritis (Sup-
plementary Fig. 4).
An autopsy was not performed on the dog, but there was
no suspicion of metastasis, such as alterations in size in the
lung or lymph nodes, on computed tomography. Therefore,
a differential diagnosis was made based on the primary
tumor in the kidney. Immunohistochemical staining using
primary antibodies against vimentin (M0725; Dako, Glos-
trup, Denmark) and cytokeratin AE1/AE3 (M3515; Dako)
was performed to rule out epithelium-derived tumors.11 In
addition, antibodies against CD31 (M0823; Dako) were
used to rule out primary tumors of renal vascular origin. To
distinguish between renal fibrous tissue–derived tumors
and renal interstitial cell tumors, immunohistochemical
staining for COX-2 (PG46; Oxford Biomedical Research,
Rochester Hills, MI), alcian blue staining, and oil red O stain-
ing were performed. Deparaffinized slides were rehydrated
126
Cho et al.

Figure 3.  Histologic features of renal interstitial cell tumor in a dog. Some neoplastic cells contain intracytoplasmic vacuoles (arrows).
H&E. Bar = 20 µm. Figure 4. Histologic features of renal interstitial cell tumor with numerous mitotic figures (80/2.37 cm2) in a dog
(arrows). Some nuclei have multiple nucleoli. H&E. Bar = 20 µm. Figure 5. Immunohistochemical feature of renal interstitial cell tumor in
a dog. The cytoplasm of some tumor cells was positive for COX–2. Immunohistochemistry. Bar = 50 µm. Figure 6. Histologic features of
renal interstitial cell tumor in a dog. The extracellular matrix was strongly alcianophilic. Alcian blue stain. Bar = 50 µm.

in phosphate-buffered saline (PBS) and incubated in 3%
hydrogen peroxide for 20  min. Heat-induced antigen
retrieval using a microwave oven was performed in Tris–
EDTA (pH 9.0) for detection of vimentin and CD31, and in
citric acid (pH 6.0) for detection of cytokeratin AE1/AE3
and COX–2. Blocking was performed with 5% normal
goat serum for 30 min at room temperature, and the slides
were incubated with each of the primary antibodies as fol-
lows: 2 h for the antibody against vimentin, and 3 h for the
antibodies against cytokeratin AE1/AE3, COX-2, and
CD31; all incubations were performed at room tempera-
ture. The slides were washed 3 times in PBS and incubated
with secondary antibody (K5007; Dako) for 40 min. All
slides were counterstained with Gill hematoxylin. Positive
control staining was performed using tissues from other
dogs: canine normal skin tissue was used for cytokeratin
AE1/AE3, vimentin, and CD31; canine colorectal cancer
was used for COX–2. Isotype-matched immunoglobulins
were used as negative controls.
The tumor cells were positive for vimentin and negative
for cytokeratin AE1/AE3; thus, the tumor was confirmed to
be of mesenchymal origin. Mesenchymal tumors originating
from the kidney are derived from vascular tissue or fibrous
tissue.9 Vascular endothelial-derived tumors (e.g., solid hem-
angiosarcoma) were ruled out because of negative CD31
expression. The cytoplasm of several neoplastic cells was
positive for COX-2 (Fig. 5), and the myxoid matrix was pos-
itive with alcian blue stain (Fig. 6). Oil red O staining showed
a positive reaction in the cytoplasmic vacuoles of some cells.
COX-2–positive reaction and cytoplasmic vacuoles are
known to be present in the cytoplasm in human renomedul-
lary interstitial cell tumors,5 and alcian blue stain is regarded
as a negative sign for fibroma10; the mass was therefore diag-
nosed as a renal interstitial cell tumor.
The clinicopathologic findings (i.e., increased creatinine,
urea, amylase, and lipase) indicated that the tumor might
have caused renal insufficiency and anemia. Mild lympho-
plasmacytic interstitial nephritis and tubule dilation were
observed in the portions that appeared to be normal kidney
on imaging and gross examination. Renal tubule dilation can
arise from several conditions (nephropathy, obstruction,
etc.).8 In our case, the kidney tumor was large, and mineral-
ization was present in the right renal pelvis and diverticulum,
perhaps partially blocking the tubule pathway.
Enlargement of the caudal pole of the right kidney with
extensive osseous metaplasia, approximately one-third the
size of the kidney, was confirmed on radiographic, computed
tomographic, and histologic examinations. This differed from
the findings of a prior report, in which only small mineralized
foci were observed.4 In previous reports,4 mineralized foci
 Renal interstitial cell tumor in a dog
were observed only on radiographic analysis; these gradually
increased in size and may have developed osseous metapla-
sia, as in our case.
Regarding histopathology features, renal interstitial cell
tumors have been reported to consist of interstitial cells with
lipid-rich cytoplasmic vesicles, high prostaglandin content,
and positive extracellular alcian blue staining plus a positive
lipid reaction in cytoplasmic droplets.10 Renal interstitial cell
tumors express cytoplasmic COX-2, whereas fibrosarcomas
do not.5,7 Importantly, renal interstitial tumors occur in the
cortex and medulla of older dogs (10–18 y old); the tumors
are often bilateral and multiple.4 In our case, although no
mass was found in the opposite kidney by imaging, various
features including imaging findings (location in kidney with-
out metastatic lesions), age (17 y), and microscopic features
(i.e., alcian blue–positive matrix, vimentin- and COX-2–pos-
itive reactions in the cytoplasm) met the criteria for a diagno-
sis of renal interstitial cell tumor.
In histologic examination, the tumor showed variable
degrees of cell proliferation. There were regions with rela-
tively few mitotic figures (e.g., 38 mitoses/2.37 mm2, mini-
mal nuclear pleomorphism, and few nucleoli). Other regions
had numerous mitotic figures (80 mitoses/2.37 mm2) and
increased nuclear pleomorphism with many nucleoli per
nucleus. In regions with low mitotic activity, relatively high
numbers of cytoplasmic vacuoles were observed, whereas
there were fewer cytoplasmic vacuoles in regions with high
mitotic activity. We concluded that this aspect was consistent
with the reduced degree of differentiation in the presence of
increased anaplasia.3
Although metastases were not found by computed tomog-
raphy, an autopsy was not performed, and there may have
been undetected metastases. The tumor showed malignant
features, such as invasiveness, pleomorphic nuclei with mul-
tiple prominent nucleoli, marked mitotic activity, and bizarre
mitoses. These histopathologic malignant features differ
from those of the typical benign renomedullary interstitial
cell tumors found in humans and dogs.4,10,12,13 In addition, no
mitoses were observed in previous reports of canine intersti-
tial cell tumors. Our case demonstrates that a renal interstitial
cell tumor in a dog can be aggressive and can have malignant
histologic features, and that COX-2 can be useful in the diag-
nosis of this tumor.
Declaration of conflicting interests
The authors declared no potential conflicts of interest with respect
to the research, authorship, and/or publication of this article.
127
Funding
This work was supported by the Bio & Medical Technology Devel-
opment Program of the National Research Foundation (NRF), funded
by the Korean government (MSIT; grant 2016M3A9B6903437).
ORCID iD
Jung-Hyang Sur https://orcid.org/0000-0003-4496-7582
Supplemental material
Supplemental material for this article is available online.
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