Human Pathology (2010) 41, 14951499

www.elsevier.com/locate/humpath

Case study

Anaplastic sarcoma of the kidney with chromosomal

abnormality: first report on cytogenetic findings
Kiyoshi Gomi MD, PhD a,, Satoshi Hamanoue MD, PhD b , Mio Tanaka MD, PhD a ,
Masae Matsumoto MD, PhD b , Norihiko Kitagawa MD, PhD c , Tetsu Niwa MD, PhD d ,
Noriko Aida MD, PhD d , Hisato Kigasawa MD, PhD b , Yukichi Tanaka MD, PhD a
a

Division of Pathology, Kanagawa Children's Medical Center, Yokohama, 232-8555 Japan

Division of Hemato-oncology, Kanagawa Children's Medical Center, Yokohama, 232-8555 Japan
c
Division of Surgery, Kanagawa Children's Medical Center, Yokohama, 232-8555 Japan
d
Division of Radiology, Kanagawa Children's Medical Center, Yokohama, 232-8555 Japan
b

Received 6 January 2010; revised 22 February 2010; accepted 11 March 2010

Keywords:
Anaplastic sarcoma of
kidney;
Renal tumor;
Children;
Chromosomal abnormality

Summary We report a case of anaplastic sarcoma of the kidney (ASK) with cytogenetic findings. A 12year-old Japanese girl presented with buttock pain and urinary incontinence. Radiological investigations
revealed a right renal tumor with multiple distant metastases and multicystic thyroid tumor. She
underwent radical right nephrectomy and subsequently received chemotherapy and radiation therapy.
Histologically, the renal tumor demonstrated admixture of various types of mesenchymal elements:
cellular spindle cells with anaplastic features, cartilage, and rhabdomyoblastic cells consistent with
ASK. Chromosomal analysis revealed the karyotype of the tumor cells to be 46, XX, +8, 10, der (18) t
(10; 18) (q21; p11.2). The thyroid tumor was removed later and diagnosed as adenomatous goiter. To
our knowledge, this is the first case of ASK with chromosomal abnormality and may provide new
insight into the molecular biologic basis of this rare renal tumor.
2010 Elsevier Inc. All rights reserved.

1. Introduction
Anaplastic sarcoma of the kidney (ASK) is a rare and
newly recognized renal neoplasm, first described by Vujanic
et al in 2007 [1]. According to their report, ASK mainly
occurs in children or adolescents younger than 15 years and
is histologically characterized by widespread anaplastic
changes such as pleomorphic cells and highly atypical
mitotic figures, polyphenotypic mesenchymal differentiation, and absence of blastemal element, neoplastic epithelial
structure, and nephrogenic rest. The only subsequent case
Corresponding author. Division of Pathology, Kanagawa Children's
Medical Center, Yokohama City, Kanagawa Prefecture, 232-8555, Japan.
E-mail address: gomikiyoshi@yahoo.co.jp (K. Gomi).
0046-8177/$ see front matter 2010 Elsevier Inc. All rights reserved.
doi:10.1016/j.humpath.2010.03.008

report describing ASK [2] does not discuss cytogenetic

abnormality in ASK. ASK was previously diagnosed as
various types of tumor, most often as anaplastic nephroblastoma, and was treated accordingly, with relatively good
overall outcome [1]. To better understand the nature of ASK,
further molecular studies are desirable. Here, we report the
clinicopathological findings of a new case of ASK with
chromosomal abnormality.

2. Clinical case
A 12-year-old Japanese girl presented at a regional
hospital with buttock pain and urinary incontinence. No past

1496

K. Gomi et al.

history was relevant. Her mother underwent subtotal

thyroidectomy for diffuse hyperplasia of the thyroid at the
age of 17 years. Magnetic resonance imaging revealed tumor
in the sacral bone with extension into the surrounding soft
tissue. After open biopsy, Ewing sarcoma family tumor was
suspected. The patient was transferred to our hospital, where
extensive imaging studies revealed a right renal mass and
metastases to the lungs (multiple, up to 1 cm in diameter),
sacral bone, pubic region, and right femur. The biopsied
sacral bone lesion was considered a metastatic lesion. A
multicystic tumor was also noted in the right lobe of the
thyroid gland. Right radical nephrectomy was performed
immediately. Under the diagnosis of unclassified sarcoma,
the patient received postoperative intensive chemotherapy
for Ewing sarcoma family tumors and radiation therapy. Six
months later, the thyroid tumor was resected and diagnosed
as adenomatous goiter. At follow-up at 28 months, the lung
and bone metastases showed a significant decrease in size,
and there was no sign of local recurrence or newly developed
distant metastasis.

3. Materials and methods

The resected tissue samples were fixed in 10% formalin
and embedded in paraffin. Serial paraffin sections (3-4 m
Table 1

thick) were cut from the blocks and stained with hematoxylin
and eosin. Immunohistochemical study was performed using
antibodies against the antigens, as shown in Table 1, and the
indirect immunoperoxidase method. Frozen section tumor
samples were studied for EWS-FLI1, EWSR1-ERG,
EWSR1-WT1, ETV6-NTRK3, SS18-SSX, PAX3-FOXO1A,
and PAX7-FOXO1A chimeric transcripts, as described
previously [3-7]. Chromosomal preparations of disaggregated tumor cells were made after 3 days culture using
standard methods. The choromosomes were G-banded with
trypsin and Giemsa. Karyotype descriptions were made
according to the International System of Cytogenetic
Nomenclature of 1995.

4. Results
4.1. Pathological findings
The right kidney measured 17 9.5 8.5 cm and weighed
985 g. A well-demarcated tumor (15 8 5.5 cm) was
located in the superior portion. Cut sections revealed a gray
colored, friable tumor tissue with multifocal necrosis, cystic
degeneration, and a large subcapsular hematoma (Fig. 1).
The tumor exhibited focal invasion into the renal pelvis, and
no extension beyond the renal capsule was noted.

Results of immunohistochemistry

Antibodies to

Vimentin
Cytokeratin
Cytokeratin
EMA
Synaptophysin
S-100 protein
GFAP
Muscle specific actin
Desmin
Myoglobin
Myogenin
CD34
CD56 (N-CAM)
CD99 (MIC-2)
Bcl-2
Beta-catenin
BAF47 (INI-1)
WT-1
Ki-67

Antibody
clone

Source

V9
CAM5.2
AE1/AE3
E29
SY38
2A10
6F2
HHF-35
D33
polyclonal
F5D
NU-4A1
123C3
12E7
DAKO124
14
14
6F-H2
MIB-1

DC
BDB
NCR
DC
DC
IBL
DC
ENZ
DC
BMD
DC
NCR
IVG
DC
DC
TDL
BDT
DC
DC

Dilution/Antigen
retrieval cells
tissue cells

Reactivity for tumor cells

Spindle
cells

Cartilaginous
tissue

Rhabdomyoblastic
cells

1:100/MW
1:1/MW
1:1/MW
1:50/MW
1:20/MW
1:800/untreated
1:100/untreated
1:50/untreated
1:100/MW
1:1/untreated
1:25/MW
1:1/untreated
1:1/MW
1:50/untreated
1:50/MW
1:100/MW
1:300/AC
1:25/AC
1:100/MW

+++

+
+

+++

LI: 20-30%

++

+++

N.E

++
++
++
++

+++

N.E

DC, DAKO Cytomation Glostrup Denmark; BDB, BD Bioscience, Sandiego, CA; NCR, Nichirei Biosciences Inc, Tokyo, Japan; IBL, Immuno-Biological
Laboratories, Takasaki, Japan; ENZ, Enzo Life Science International; BMD, Biomeda Corp; IVG, Zymed-Invitrogen Corp, Carlsbad, CA; TDL,
Transduction Laboratories, Lexington, KY; BDT, BD Transduction labs, San Diego, CA; MW, microwave treatment in 0.01 mol/L citrate buffer (pH 6.0)
using a 500-W oven; AC, autoclave in 0.01 mol/L citrate buffer (pH 6.0); , no positive cell; +, less than 10% of positive cells; ++, 10%-50% of positive
cells; +++, 50%-90% of positive cells; N.E, not examined; LI, labeling index.

ASK with chromosomal abnormality

1497

Histologically, the tumor revealed fascicular growth of

oval or short spindle cells having hyperchromatic nuclei with
coarse chromatin and inconspicuous nucleoli. The tumor
cells showed frequent mitotic figures and karyorrhectic
appearances. Anaplastic features, such as large irregularshaped nuclei, atypical or multipolar mitoses, and bizarre
multinucleated giant cells, were commonly found (Fig. 2A).
Throughout the tumor, there existed scattered foci of hyaline
cartilaginous tissue with various atypical features (Fig. 2B)
and clusters of brightly eosinophilic, rounded/elongated
rhabdomyoblastic cells occasionally displaying straplike

Fig. 1 Gross appearance of radical nephrectomy specimen. A

large, encapsulated tumor is noted in the superior portion of the
right kidney. The tumor was gray colored and fleshy with
multifocal necrosis and hemorrhage (red arrowheads). A metastatic
satellite nodule (yellow arrowheads) is observed.

Fig. 2 Microscopic findings of ASK (hematoxylin-eosin). A,

Anaplastic features are present, including pleomorphic cells, bizarre
multinucleated giant cells, and atypical mitotic features (original
magnification 400). B, Chondroid differentiation: note the islands
of hyaline cartilaginous tissue (original magnification 200). C,
Rhabdomyoblastic differentiation: rounded or elongated rhabdomyoblastic cells are present (original magnification 200) (inset:
cross-striations are seen in some cells [red arrowheads]; original
magnification 1000).

1498
appearance with distinct cross-striations (Fig. 2C). No
blastemal element, epithelial structure, or nephrogenic rest
was identified. Immunohistochemically, the tumor cells were
diffusely positive for vimentin and focally positive for
muscle-specific actin, desmin, myoglobin, and myogenin
(mainly in rhabdomyoblastic cells), or S-100 alpha and S100 beta (cartilaginous tissue). They were negative for
cytokeratin, EMA, synaptophysin, GFAP, CD99, CD34,
CD56, nuclear beta catenin, and WT-1. Diffuse and strong
nuclear staining for BAF47 was observed. MIB-1 labeling
index was 20% to 30%.
Differential diagnoses included anaplastic nephroblastoma, synovial sarcoma, and malignant mesenchymoma.
Because the tumor showed 2 types of overt malignant
mesenchymal differentiation in addition to undifferentiated
(rather than blastemal) spindle cell areas, we initially
considered the tumor to be within the spectrum of malignant
mesenchymoma. It has been suggested, however, that the
diagnosis of malignant mesenchymoma should be removed
from the classification of soft tissue tumors because this term
appears to have become a wastebasket for poorly differentiated sarcomas [8]. Thus, our initial diagnosis was
unclassified anaplastic sarcoma with rhabdomyoblastic and
cartilaginous differentiation. The diagnosis of ASK was
reached at a later date, following reference to the article by
Vujanic et al [1]; this diagnosis was subsequently confirmed
by Dr Beckwith, who was a coauthor on the original article.
The resected thyroid tumor was adenomatous goiter rather
than a metastatic lesion.

4.2. Molecular findings

In reverse transcriptase-polymerase chain reaction assay,
fusion transcripts for EWSR1-FLI1, EWSR1-ERG, EWSR1-

Fig. 3 G-banding karyotype of the tumor cells showing 46, XX, +8,
10, der (18) t (10; 18) (q21; p11.2). The red arrow indicates
translocation between chromosome 10 and 18 and monosomy of
chromosome 10. The blue arrowhead shows trisomy of chromosome 8.

K. Gomi et al.
WT1, ETV6-NTRK3, SS18-SSX, PAX3-FOXO1A, and
PAX7-FOXO1A were not detected in the renal tumor tissue.

4.3. Chromosomal analysis

G-banding cytogenetic analysis revealed the karyotype of
the neoplastic cells (20/20) to be 46, XX, +8, 10, der (18) t
(10; 18) (q21; p11.2) (Fig. 3). The patient's karyotype from
lymphocytes from peripheral blood was normal female type,
46, XX.

5. Discussion
ASK is a very rare renal neoplasm first described by
Vujanic et al in 2007 [1], who detected 20 cases of ASK
from among 3 large pathology collections, including the
National Wilms Tumors Study Pathology Center (7400
cases), the International Society of Pediatric Oncology
(4000 cases), and the United Kingdom Children's Cancer
Study Group (1600 cases). Histologically, all 20 cases of
ASK displayed a spindle cell component, which contained
either multiple foci or diffuse, widespread anaplastic
changes with bizarre pleomorphic cells and highly atypical
mitotic features. Chondroid differentiation was seen as
islands of hyaline cartilage or chondroid matrix and was
observed in most cases (16/20, 80%). In a few cases, osteoid
component (2/20, 10%), osteoclast-like giant cells (4/20,
20%), and rhabdomyoblastic cells (2/20, 10%) were noted.
An additional case in a 24-year-old woman has recently been
reported by Labanaris et al [2], without a description of the
histological details.
The present tumor showed diffuse anaplastic changes,
islands of cartilage (with or without atypia), and rhabdomyoblastic cells. Rhabdomyoblastic cells with cross-striation, which were not observed in the 21 published cases of
ASK, were also found. The present tumor lacked blastemal
cells positive for CD56 or WT-1, neoplastic epithelial
components, and a nephrogenic rest; these findings are
inconsistent with nephroblastoma. Based on molecular
studies using reverse transcriptase-polymerase chain reaction
assay, synovial sarcoma, congenital mesoblastic nephroma
(cellular variant), Ewing sarcoma family of tumor, and
desmoplastic small round cell tumor were also excluded. The
diagnosis of malignant mesenchymoma was avoided for the
reason mentioned in the Pathological Findings section,
although there are some case reports of malignant mesenchymoma arising in the kidney, some of which may correspond
to ASK [9-12].
Cytogenetic abnormalities such as specific translocation
in chromosome and aberrant genes have never been
described in ASK. The present renal tumor demonstrated
chromosomal abnormality, that is, 46, XX, +8, 10, der
(18) t (10; 18) (q21; p11.2) in 20 of 20 tumor cells
examined. This type of translocation has not been reported

ASK with chromosomal abnormality

in any other tumor, and the relationship between ASK and
this chromosomal abnormality remains unknown. Although
further molecular genetic studies are required, this novel
chromosomal translocation may play a critical role in the
pathogenesis of ASK.
Vujanic et al reported that the patients with ASK were
treated according to different therapeutic protocols and even
different diagnoses, but with reasonably good overall
outcome, and appeared to have responded well to treatment
given to anaplastic nephroblastoma [1]. The present case was
stage IV, but the patient is alive, with disease, 2 years after
the onset, after chemotherapy against the Ewing sarcoma
family of tumors. More appropriate treatment, however,
should be obtained based on an understanding of the
molecular characters of the tumor.
In conclusion, this study is the first to report ASK with
chromosomal findings, including rearrangement between
10q21 and 18p11.2. Further molecular analysis, with a focus
on 10q21 and 18p11.2, could be helpful in clarifying the
pathogenesis of this unusual renal tumor.

Acknowledgments
The authors thank Dr Beckwith JB, Pathology and
Human anatomy, Loma Linda University and School of
Medicine, for confirming our diagnosis and Ms Yukari
Hasegawa, Ms Takako Yokomori, and Ms Sayuri Oda for
their valuable technical assistance.

1499

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