Soft Tissue Tumors in Children and Adolescents:
A Morphologic Pattern Oriented Approach with Molecular and Genetic Correlations
Section 5 -
Cheryl M. Coffin, M.D.
David M. Parham, M.D.
A 16-year old female developed a soft tissue mass on the right anterior tibia. A biopsy was performed
and consisted of a 4 cm aggregate of soft, myxoid, tan and pink tissue.
Discussion and Differential Diagnosis:
This case represents an example of biphasic synovial sarcoma. The points for discussion about this
case include the pathologic findings, the cytogenetic and molecular genetic abnormalities in synovial
sarcoma, and the differential diagnosis.
Histologically the biopsy from the right anterior tibial soft tissue mass showed a tumor with a
variety of patterns including a proliferation of spindle and polygonal cells with variable amounts of
cytoplasm, more myxoid hypocellular areas, and foci of gland-like structures containing dense
eosinophilic intraluminal material. The gland-like structures comprised less than 50% of the area of the
tumor. Focal round cell undifferentiated and rhabdoid foci were present. Necrosis involving less than
15% of the area of the biopsy was observed. The mitotic rate varied with up to 50 or more mitoses per 10
high power fields. Immunohistochemical stains revealed positive stainings in the epithelial and
glandular areas for AE1/AE3 cytokeratin, cytokeratin 7, epithelial membrane antigen, and cytokeratin
903. The spindle cell areas showed reactivity for vimentin. Cytogenetic analysis revealed
Synovial sarcoma, as defined by the World Health Organization in 2002, is a mesenchymal spindle cell
tumor, which displays variable epithelial differentiation, including glandular formation, and has a
specific chromosomal translocation t(X;18)(p11;q11). It accounts for 5 to 10% of soft tissue sarcomas
and 42% of non-rhabdomyosarcomas in children. More than 95% arise in juxta-articular locations such as
the knee and ankle. Unusual sites include the head and neck, chest, abdomen, retroperitoneum, and solid
organs. The peak incidence is in the second decade of life.
Synovial sarcoma is a circumscribed or infiltrative mass with a tan or grey soft cut surface. It is
frequently multinodular and can be multicystic, hemorrhagic, and necrotic. The two main histologic
subtypes are biphasic and monophasic. Biphasic synovial sarcoma has both epithelial and spindle cell
components in varying proportions, while most monophasic synovial sarcomas display a spindle cell
pattern. Both types can exhibit a prominent hemangiopericytomatous vascular pattern. Histologic
variants include small cell, rhabdoid, myxoid, calcifying, and poorly differentiated types.
Ancillary tests useful in the diagnosis of synovial sarcoma include immunohistochemistry, electron
microscopy, cytogenetics, and molecular genetics. Nearly all synovial sarcomas express cytokeratin,
especially in the epithelial component and occasionally in the spindle cell component. Cytokeratin
subtypes expressed include AE1/AE3, CAM 5.2, cytokeratin 7, and cytokeratin 19. Epithelial membrane
antigen is expressed more frequently and more widely than cytokeratin. Mesenchymal markers include S100
protein, CD99, CD56, CD57, neurofilament, muscle-specific or smooth muscle actin, vimentin, and type 4
collagen. Bcl-2 overexpression is found in more than 90% of synovial sarcomas. Epidermal growth factor
receptor, e-cadherin, p53, and Her2-Neu expression have been observed. Ultrastructurally, synovial
sarcoma displays external lamina, intermediate filaments, cell junctions, and surface microvilli in the
epithelial component. The spindle cell component does not have specific features, but may display
processes protruding into intercellular gaps or short segments of external lamina.
The t(X;18)(p11;q11) is thought to be present in more than 90% of synovial sarcomas and variant
translocations have been described. The genes affected by this translocation include SS18 (SYT or SSXT) from
chromosome 18 and SSX1, SSX2, and SSX4 from the X chromosome. The molecular genetic abnormalities can be detected
by fluorescent in situ hybridization and RT-PCR.
Prognostic factors in synovial sarcoma include size (favorable < 5.0 cm in diameter), age, stage,
grade, mitotic rate (favorable if less than 10 mitoses per 10 high power fields), ploidy, rhabdoid cells
(adverse), and > 50% necrosis (adverse). The calcifying variant is considered a favorable
histologic-prognostic subtype. Data suggests that p53 overexpression is an unfavorable prognostic
indicator. Up to half of synovial sarcomas recur usually within 2 years of diagnosis, and sometimes up
to 3 decades later. Approximately 40% metastasize with a predilection for regional lymph nodes, lungs,
and bone. There is some debate about whether specific molecular genetic fusion subtypes have prognostic
The differential diagnosis of synovial sarcoma include malignant peripheral nerve sheath tumor,
fibrosarcoma, leiomyosarcoma, spindle cell rhabdomyosarcoma, extraosseous osteosarcoma, other spindle
cell neoplasms, and in the case of the round cell variant, Ewing sarcoma/PNET, and malignant rhabdoid
tumor. Usually these distinctions can be made on the basis of light microscopy and immunohistochemistry,
but occasionally cytogenetic or molecular genetic analysis is very useful, particularly in differential
diagnosis between synovial sarcoma and malignant peripheral nerve sheath tumor.
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