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International Journal of Surgical Pathology
http://ijs.sagepub.com/content/20/4/386
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DOI: 10.1177/1066896911424897
2012 20: 386 originally published online 17 October 2011 INT J SURG PATHOL
Jaime Villaroel-Salinas, Jess Campos-Martinez and Carlos Ortiz-Hidalgo
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Fusion Gene SYT-SSX2 Synovial Sarcoma of the Tongue Confirmed by Molecular Detection of the
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International Journal of Surgical Pathology
20(4) 386 389
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DOI: 10.1177/1066896911424897
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424897IJSXXX10.1177/1066896911424897Villaro
el-Salinas et alInternational Journal of Surgical Pathology
1
The American British Cowdray Medical Centre, Mexico City, Mexico
2
Instituto Mexicano del Seguro Social, Mrida, Yucatn, Mxico
3
Universidad Panamericana, Mxico City, Mexico
Corresponding Author:
Carlos Ortiz-Hidalgo, Department of Pathology, The American British
Cowdray Medical Center, Sur 136#116. Col Las Amricas, Mexico DF
01120, Mexico
Email: cortiz@abchospital.com
Synovial Sarcoma of the Tongue
Confirmed by Molecular Detection
of the SYT-SSX2 Fusion Gene Transcript
Jaime Villaroel-Salinas, MD
1
, Jess Campos-Martinez, MD
2
,
and Carlos Ortiz-Hidalgo, MD
1,3
Abstract
Involvement of the tongue by a synovial sarcoma (SS) is an extremely rare event; there have only been 13 cases
previously reported. The authors present herein a case of monophasic SS arising in the tongue in a 32-year-old woman.
The neoplasm expressed cytokeratins AE1-3, OSCAR, and EMA as well as Bcl-2 and TLE1. Molecular analysis indicated
that the patient tested positive for the SYT/SS2 fusion transcript.
Keywords
synovial sarcoma, tongue, oral cavity, TLE1, SYT/SSX2
Introduction
Synovial sarcoma (SS) is a malignant soft-tissue tumor of
unknown histogenesis that arises primarily in the para-
articular region of the lower extremities, with a peak inci-
dence between the ages of 10 and 35 years.
1
About 5% to
10% of SSs occur in the head and neck region, and the
presence of a SS in the oral cavity is a rare finding with
fewer than 50 well-documented cases reported in the litera-
ture.
2
We report herein a case of primary SS of the tongue
with molecular detection of the STY-SSX2 fusion gene
transcript using reverse transcription-polymerase chain
reaction (RT-PCR) and immunohistochemical analyses,
the latter of which includes the TLE1 antibody test.
3,4
Case Report
A 31-year-old woman presented with a 1-month history of
a progressively growing tumor in the base of the tongue.
Physical examination revealed a tumor that measured 7.5
5.0 cm
2
and was solid with a smooth surface covered by
mucosa. The tumor showed a broad-based pedicle, based
on the lateral pharyngeal wall and the base of the tongue
(Figure 1). The tumor did not obstruct the epiglottis, and
there was no cervical lymph node enlargement. A CT scan
revealed a rounded, enhancing tumor mass in the posterior
aspect of the tongue that measured 3.4 2.3 cm
2
(Figure 1).
With the patient under general anesthesia, the mass was
completely excised.
The specimen was fixed in 10% buffered formalin and
was embedded in paraffin. Histologic 5-m sections were
stained by hematoxylin and eosin. Immunohistochemistry
was performed using the standard streptavidinbiotin
complex method. The antibodies and methodology used in
this study are summarized in Table 1. The surgical speci-
men measured 3.5 2.0 2.0 cm
3
and had a firm, tan-
yellow irregular surface. Sectioning revealed a
homogeneous cut surface with brown to tan-yellow areas.
Microscopically, the tumor was composed of closely
packed, short, uniform spindle cells with tapering nuclei,
with scant pale cytoplasm. The proliferating cells were
arranged in irregular fascicles. Only 3 mitotic figures per
10 high-power fields (40) were seen. Focally, numerous
branching hemangiopericytoma-like areas were present in
addition to variable amounts of fibrosis and numerous
mast cells scattered throughout the tumor (Figure 2). The
tumor cells were immunoreactive for EMA, Bcl-2, vimentin,
and PGP 9.5, and they and showed a strong nuclear expres-
sion of TLE1 with a proliferation rate of 5%. Cytokeratin
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Villaroel-Salinas et al. 387
Figure 1. Left panel: a solitary nodule located in the base of the tongue and extending to the oropharynx. Middle panel: axial
enhanced CT showing a well-defined, heterogeneous mass located in the base of the tongue and oropharynx. Right panel: sagittal
enhanced CT reconstruction of the oropharynx showing a solid nodular lesion in the base of the tongue and oropharynx
Table 1. Immunohistochemistry: Antibodies, Clones, Source
Antigen Retrieval, and Dilutions
Antibody Clone Source Pretreatment Dilution
TLE1 M-101 Santacruz Biotech Trilogy 100
EMA E-29 DAKO Trilogy 1:150
OSCAR Phenopat ACD Trilogy 1.40
Bcl-2 124 BIOSB Evision-Flex 1.15
Vimentin 9 BIOGENEX Declere 1.2000
CD99 CD99/B5 BIOSB Trilogy 1.25
PGP 9.5 Polyclonal NEOMARKERS Declere 1.600
Ki-67 MIB-1 DAKO Trilogy 1.50
Actin HHF35 DAKO Declere 1:300
Desmin D33 DAKO Declere 1:50
CD34 QBend10 DAKO Declere 1:50
S-100 15E2E2 Bio Genex 1:100
ACD: Seattle, WA; BIOGENEX: San Ramon, CA; BIOSB: Santa Barbara,
CA; DAKO: Carpinteria, CA; NEOMAKERS: Fremont, CA; Santa Cruz
Biotech: Santa Cruz, CA.
OSCAR was focally positive, and CD99, actin, desmin,
CD34, and S-100 protein were all uniformly negative
(Table 1). The patient was diagnosed with monophasic SS
and was lost to follow-up.
RT-PCR analysis was performed at Quest Diagnostics
Nichols Institute (San Juan Capistrano, CA). RNA was
extracted from paraffin-embedded tissue, purified after
DNAse treatment, and run in agarose gel electrophoresis
to determine quality. RNA was reverse transcribed to
cDNA and amplified by PCR using a fluorescence reporter
probe method for multiplex analysis to detect primary
fusion transcripts of the following tumors: SS (SYT/SSX1;
SYT/SSX2), Ewings sarcoma (EWS/FLI1; EWS/ERG),
rhabdomyosarcoma (FKHR/PAX3; FKRH/PAX7), and
desmoplastic small round-cell tumor (EWS/WT1).
Molecular analysis indicated that the patient tested posi-
tive for the SYT/SS2 fusion transcript.
Discussion
More than 80% of SSs arise in the lower limbs, with the
head and neck region being the second most common site
of involvement.
1
In the oral cavity, SS has been reported
in the oral maxillofacial region,
5
including the buccal
mucosa,
2,6
the floor of the mouth and the retromolar area,
7

tonsils,
8
soft and hard palates,
9,10
and the tongue.
3,4,8,11-13
The tongue is the most frequently affected intraoral site of
SS, and it was first described as a site of SS occurrence by
Mir-Abedy in 1962.
13
There have been 13 cases of SS
reported in the tongue in the English language literature.
3,4

de Almeida et al,
3
reported 12 cases of SS originating in the
tongue (8 in the base, 3 in the lateral border, and 1 in the
dorsum). In these 12 reported cases, there is only 1 woman;
therefore, we are presenting the case of the second woman
with SS in the tongue. A recent new case of monophasic SS
in the base of the tongue has been reported in a 22-year-old
man by Agarwal et al.
4
All but 1 of the tumors in the reported
cases of SS in the tongue have exhibited a biphasic configu-
ration; the tumor in our case exhibited a fibrous, monophasic
pattern (the whole tumor was removed and submitted com-
pletely in 2 slides, and various deep sections were studied).
The typical clinical presentation of SS is a slow-growing,
deep-seated, palpable mass associated with pain in about
50% of cases. Microscopically, SSs fall into 3 groups: (1) a
more common type (70%), with monophasic spindle cells
that show little or no evidence of epithelial differentiation;
(2) a biphasic type (25%), with distinct epithelial and spindle
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388 International Journal of Surgical Pathology 20(4)
Figure 2. Monophasic synovial sarcoma of the tongue: the upper panels shows representative areas stained with hematoxylin and
eosin. The middle and lower panels demonstrate immunohistochemical staining showing positivity for PGP 9.5, EMA, OSCAR, TLE1,
Bcl-1, and Ki-67 (see text)
cell components present in various proportions and pat-
terns; and (3) a rare, poorly differentiated type, which
accounts for less than 5% of SS cases.
14,15
Immunohistochemically, the SS tumor cells are strongly
and uniformly positive for vimentin, with at least focal posi-
tivity for various cytokeratins and EMA, which are particu-
larly strong in the biphasic areas. At least 1 of these 2
epithelial markers is expressed in 90% of SSs. Positive
cytoplasmic Bcl-2 staining is present in up to 93% of
tumors, and almost 73% of SSs stain positively for CD99 in
the cytoplasm of the neoplastic cells. In up to 21% of
tumors, the S-100 protein may be focally expressed.
16
In addition, negative immunohistochemical findings
also have an important diagnostic value in excluding
tumors that may be confused with SS. No immunoreactiv-
ity has been described for actin (HHF-35), myoglobin,
CD34, and desmin.
16
It is interesting to note that the tumor in our case showed
diffuse nuclear-positive staining for the TLE1 antibody,
which is a highly sensitive marker of SS.
17
The TLE1
(transducin-like enhancer of split1)/E(sp1) homolog,
Drosophila corepressor groucho is 1 of 4 members of the
TLE gene family that is involved in the control of hemato-
poiesis and has been associated with immature cells that
progress toward a terminally differentiated state, suggest-
ing a role during differentiation.
18,19
TLE1 is a transcrip-
tional corepressor that binds to a number of transcription
factors and plays an important role in the WNT/b-catenin
signaling pathway, which is known to be associated with
SSs.
20
Positive nuclear expression of TLE1 occurs in close
to 90% of SS cases, typically in more than 50% of the
cells.
17,19
Although a highly sensitive and specific marker
of SS, TLE1 may be expressed in some other tumors that
may enter into the differential diagnosis, such as
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Villaroel-Salinas et al. 389
MPNST.
17,19
Therefore, TLE1 should be used in the con-
text of a panel of antibodies, including keratins, EMA,
Bcl-2, and CD34.
17,19
Occasionally, molecular confirmation
of the SS-associated fusion gene, [t(X:18)(p11.2:q11.2)],
may be required.
21
In our case, molecular analysis using a
multiplex florescence RT-PCR assay was used for the
identification of the primary fusion transcript types from
formalin-fixed, paraffin-embedded tissues. The tumor
tested positive for the SYT/SSX2 fusion transcript,
which is usually associated with the t(X;18)(p11;q11)
translocation.
According to de Almeida et al,
3
SSs of the tongue are
less aggressive because of the possibility of early detec-
tion, small size, and young ages of the patients.
3

Unfortunately, the patient presented in this study was
lost to follow-up.
Conclusions
We reported a case of SS of the tongue with strong immu-
nohistochemical expressions of TLE1 and the SYT/SSX
fusion transcript, allowing for confirmation of the diagno-
sis. SS rarely involves the tongue; nevertheless, it should
be considered in the differential diagnosis of tumors that
affect this anatomical structure.
Declaration of Conflicting Interests
The author(s) declared no potential conflicts of interest with respect
to the research, authorship, and/or publication of this article.
Funding
The author(s) received no financial support for the research,
authorship, and/or publication of this article.
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