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