1. Synovial sarcoma (SS) accounts for 5-10% of all soft tissue sarcomas and ranks as the second most common
soft tissue sarcoma in children and as the fifth most common soft tissue sarcoma in adults. Although SS occurs at
quite unusual localisations, e.g. in the heart and kidney, and has a wide range of age at presentation, the tumor
most commonly presents as a deep seated tumor in the lower or upper extremity of a young adult patient aged
15-40 years. The histologic spectrum of SS encompasses biphasic SS, monophasic SS, and poorly differentiated
SS. Biphasic SS is differentiated from the two other SS subtypes by microscopic epithelial differentiation, which
was erroneously thought to represent synovial differentiation over a period of more than 70 years, between the
first detailed morphological description of a biphasic SS in 1910 and immunohistochemical demonstration of
keratins in both biphasic and monophasic SS in the early 1980s. However, despite its inherent capacity to acquire
epithelial differentiation, SS is still considered a tumor of uncertain differentiation, because its exact origin and
histogenesis have not been fully elucidated as yet.
Concerning pathobiologic behavior, SS is a high grade sarcoma and patients afflicted by this sarcoma type have
a rather poor prognosis with a long term survival rate of less than 50%. Most tumor recurrences develop within a
few years after initial diagnosis, but late recurrences do occur, even after 10 years. Major prognostic determinants
in long term follow up studies are age, tumor stage at presentation, tumor size, and French tumor grade
(FNCCLC). Because SS shows only limited sensitivity to chemotherapy, adequate surgery with optimal margins is
of utmost importance, as inadequate surgical margins negatively influence tumor prognosis. If surgical margins
are inadequate, radiotherapy is indicated, as this will reduce local recurrence rate.

2. Biphasic SS comprises about 20-30% of all SS and because of (glandular) epithelial differentiation, this subtype is
diagnosed relatively easy upon histologic examination. On the other hand, in order to make a conclusive
histologic diagnosis of monophasic SS (50-60%) or poorly differentiated SS (15-25%), the surgical pathologist
often needs to apply additional diagnostic methods. In order to establish an accurate diagnosis of SS, molecular
methods can be applied, taking advantage of the fact that at least 95% of SS bear a unique t(X;18)(p11;q11)
translocation, which results in the formation of SYT-SSX fusion genes and chimeric proteins, in which the last
eight amino acids of SYT are replaced by 78 amino acids of the C terminal of SSX, either the SSX1 or SSX2 , and
rarely SSX4. The t(X;18) translocation may be detected on the chromosome level by conventional cytogenetics,
but this is rather unattractive, because conventional cytogenetics relies on tissue culture and chromosome
banding of metaphases, by which it is labor intensive and failure prone. Nowadays, most modern pathology
laboratories use molecular genetic methods, in particular RT-PCR and FISH, to test for specific SYT-SSX gene
fusions. Compared to RT-PCR, FISH has the advantage of being a microscopic in situ technique. Commercially
available FISH assays allow highly reliable visual control of SYT gene breaks, which can be used as specific
diagnostic markers for all known SS translocations. Technically, FISH is easy to perform, which makes it very
appealing, in particular for pathology laboratories that do not have expensive molecular pathology facilities.
However, as we found and other have reported,, the sensitivity of FISH (82%) is clearly inferior to RT-PCR (94%).
RT-PCR is only available to laboratories with molecular pathology facilities. Moreover, RT-PCR may give false
positive results due to tissue contamination, by which this technique is seldom employed as a single diagnostic
method, but instead used for confirmation of a tumor suspected to be a synovial sarcoma.
Immunohistochemistry keratins, EMA, TLE-1 SYT-SSX