The patient is a 19-year-old man with a soft tissue mass
involving the right buttock and lung masses. (Images 4A-4C)
The smears are highly cellular and composed of mostly
individually dispersed and scattered, small cohesive clusters of tumor cells (Image A). The latter
appear mostly uniform, round to ovoid with high nuclear to cytoplasmic ratios, round, hyperchromatic
nuclei with inconspicuous nucleoli, and scant rims of dense cytoplasm (Images B and C). No bi- or
multi-nucleated tumor cells are present. Cell block material reveals similar features but appears more
spindled than was perhaps appreciated in the cytologic smears.
Figure 4A - Highly cellular smear composed of individually dispersed and scattered, small cohesive clusters of tumor cells. (Diff-Quik stain, low power)
Figure 4B - Tumor cells appear round to ovoid with high nuclear to cytoplasmic ratios. (Diff-Quik stain, high power)
Figure 4C - Tumors cells have round hyperchromatic nuclei with inconspicuous nucleoli and scant rims of cytoplasm. (Papanicolaou stain, high power)
The cells in the cell block material show diffuse and
strong membranous positivity for CD99 and focal reactivity for cytokeratin (AE1/AE3). The tumor cells
appeared uniformly negative for myogenin, desmin, and S-100 protein.
Conventional cytogenetic analysis revealed the
The patient underwent a resection of the right neck
mass that confirmed the cytologic diagnosis of alveolar rhabdomyosarcoma. Additionally, at least 8 of 10
lymph nodes were positive for alveolar rhabdomyosarcoma. Bone scans and CT scans of the chest and
abdomen revealed no other evidence of disease. The patient was staged as T1bN1M0, Group III, Stage I,
and enrolled on CCG protocol. He is currently doing well, without local recurrence or metastasis at 6
months following the initial diagnosis.
Synovial sarcoma (SS). SS is a soft
tissue malignancy of uncertain histogenesis. Based on its morphologic and immunohistochemical
properties, it may be more accurately characterized as a "carcinosarcoma" of soft tissues. The original
designation of "synovial sarcoma" was based partly on the fact that these tumors frequently arose in soft
tissues near, but rarely within, large joints and, histologically, had an epithelial component that was
likened to synovium. However, it should be remembered that normal synovium lacks immunoreactivity to
keratins. SS typically arises in adolescence and young adults, with a peak incidence between 20 and 40
years of age. The lower extremity is more commonly afflicted than the upper extremity and proximal more
often than distal. Radiologically, SS are almost always deeply-seated, presenting as deceptively
well-circumscribed but nonspecific soft tissue masses, often containing stippled calcifications.
On the basis of morphologic features, SS may be subtyped into four distinct categories: monophasic
fibrous, monophasic epithelial, biphasic, and poorly differentiated.1 The latter
categorization likely represents a poorly differentiated form of monophasic fibrous. The monophasic
fibrous subtype, according to most recent series, represents the most common variant, followed in
decreasing order of frequency by biphasic, poorly differentiated, and monophasic epithelial subtypes.
Cytologic preparations from SS are generally highly cellular and composed of a mostly dyscohesive
tumor cell population accompanied by occasional tumor cell aggregates.2 In most cases,
individual tumor cells are remarkably uniform with high nuclear to cytoplasmic ratios, round to ovoid
hyperchromatic nuclei, inconspicuous nucleoli, and absent to scant, slightly tapering cytoplasm. As
expected, the epithelial tumor cells typically exhibit a mostly round, vesicular nucleus and occasional
prominent nucleoli. Unfortunately, in my experience, the vast majority of SS, including the biphasic
variant, lack such cells on cytologic smears.2 This is usually not problematic, as the
diagnosis is easily rendered when material is available for ancillary studies.
Both the monophasic and epithelial components usually express keratins and epithelial membrane
antigen. Epithelial membrane antigen appears to represent a more sensitive marker than cytokeratin,
especially for the poorly differentiated subtype of SS.3 Cytoplasmic CD99 reactivity has been
reported in greater than 50% of tumors, causing a potential source of confusion with Ewing's
sarcoma.4 Additionally, up to 20% of Ewing's sarcoma may show focal positivity for
In a majority of cases, conventional cytogenetic analysis reveals a balanced relatively specific
translocation t(X;18)(p11.2;11.2) with the fusion product SYT-SSX. This finding is observed in both
biphasic and monophasic subtypes. Furthermore, we now know that two related but distinct X-chromosomal
genes may be rearranged in this translocation, producing distinct fusion products, SYT-SSX1 and SYT-SSX2.
Kawai et al.6 documented an association between SS subtype and the SYT-SSX subtype. In their
series, biphasic tumors exclusively harbored the SYT-SSX1 rearrangement while monophasic fibrous types
were predominantly (but not exclusively) found to have the SYT-SSX2 rearrangement. However, other
investigators have not shown such a relationship.7 We should also point out that fine needle
aspirates have proven successful in detecting the t(X;18) and its fusion product, SYT-SSX.8
Estimated 5-, 10-, and 15-year survival rates for SS range from 50 to 75%, 20 to 50%, and 10-45%,
respectively. Risk factors for disease progression have included older age of patient (>25 years),
large tumor size (>5 cm), poorly differentiated subtype (high nuclear grade), extensive tumor
necrosis (>50%), presence of rhabdoid morphology, presence of bone and/or neurovascular invasion, and
high tumor stage. SS containing the SYT-SSX1-type fusion appear to be associated with worse prognosis
than those harboring the SYT-SSX2 subtype.6-7 At most institutions, SS is considered an
intermediate to high grade sarcoma requiring not only surgical resection, but adjuvant therapy, including
chemotherapy and/or radiation therapy. Adequate primary surgery appears to represent the most
significant factor for local control and the prevention of recurrence.1
- Bergh P, Meis-Kindblom JM, Gherlinzoni F, et al. Synovial sarcoma: identification of low and high
risk groups. Cancer 1999;85:2596-2607.
- Kilpatrick SE, Teot LA, Stanley MW, et al. Fine-needle aspiration biopsy of synovial sarcoma: a
cytomorphologic analysis of primary, recurrent, and metastatic tumors. Am J Clin Pathol
- Folpe AL, Schmidt RA, Chapman D, et al. Poorly differentiated synovial sarcoma: immunohistochemical
distinction from primitive neuroectodermal tumors and high-grade malignant peripheral nerve sheath
tumors. Am J Surg Pathol 1998;22:673-682.
- Dei Tos AP, Wadden C, Calonje E, et al. Immunohistochemical demonstration of glycoprotein p30/32
MIC2 (CD99) in synovial sarcoma: a potential cause of diagnostic confusion. Appl Immunohistochem
- Gu M, Antonescu CR, Guiter G, et al. Cytokeratin immunoreactivity in Ewing's sarcoma: prevalence in
50 cases confirmed by molecular diagnostic studies. Am J Surg Pathol 2000;24:410-416.
- Kawai A, Woodruff J, Healey JH, et al. SYT-SSX gene fusion as a determinant of morphology and
prognosis in synovial sarcoma. N Engl J Med 1998;338:153-160.
- Inagaki H, Nagasaka T, Otsuka T, et al. Association of SYT-SSX fusion types with proliferative
activity and prognosis in synovial sarcoma. Mod Pathol 2000;13:482-488.
- Nilsson G, Wang M, Wejde J, et al. Reverse transcriptase polymerase chain reaction on fine needle
aspirates for rapid detection of translocations in synovial sarcoma. Acta Cytol1998;42:1317-1324.