Soft Tissues: Synovial sarcoma with t(X;18)(p11;q11) SS18/

2000-02-01   Christine Pérot 

Summary

Atlas Image
t(X;18)(p11.2;q11.2) in synovial sarcoma G-banding - Courtesy Charles Bangs

Clinics and Pathology

Epidemiology

rare soft tissue tumor, it accounts for up to 5 to 8% of soft tissue sarcomas , the fourth most common type of sarcoma after malignant fibrous histyocytoma, liposarcoma and rhabdomyosarcoma ; the most common pediatric non rhabdomyosarcomatous soft tissue cancer; average incidence : 2,75 per 100000 population based on a canandian study

Clinics

most prevalent in adolescents and young adults, it occurs primarily in the para-articular regions of the extremities, especially the lower ones; rarely, it is encountered in various areas such as parapharyngeal region, abdominal wall, lung or cardiac tissue, ä

Pathology

well-defined, apparently unrelated to synovium (cf various rare localisations), it displays characteristics of concurrent epithelial and spindle cell proliferation; several types are recognized : two major ones:
  • biphasic, with epithelial and spindle cell components in various proportions and
  • monophasic fibrous type;
  • monophasic epithelial type is much less common ;
  • may also present as a poorly differentiated small cell neoplasm; diagnosis may be difficult especially for the two later.
    in general, very few problems in diagnosis in the biphasic type, may be not ascertained in some instances even after immunohistochemical examination
  • Treatment

    complete surgical excision of the primary tumor is actually the basis of the treatment; the optimal treatment approach is to be determined as post operative radiotherapy and adjuvant chemotherapy may permit limb preserving surgery and limit local recurrence and (micro) metastasis disease (lung+++)

    Prognosis

  • traditionnally has had a bad prognosis whateither the biphasic or monophasic type, poorer in the poorly differentiated small cell neoplasm.
  • EFS at 5 years : 45-60%; improved in a recent german study to 74% for children and adolescents; improvements in adults too
  • recents prognostic studies to identify risk groups and adequate treatment strategies indicate that synovialosarcomas might not be uniformely high grade tumors
  • Cytogenetics

    Cytogenetics morphological

    a t(X;18)(p11.2;q11.2) is found in almost all synovial sarcomas (8O%) whatsoever the histologic type may be; t(X ;18)(p11.2 ;q11.2) seems to be specific : it is not found in other spindle cell sarcomas, and very rarely detected in other tumors as malignant fibrous histyocytoma or fibrosarcomas

    Cytogenetics molecular

    detectable by metaphasic and/or interphasic dual colour fluorescent in situ cytogenetics; hybridization combining centomere X or 18 probes with respectively 18 or X whole chromosome painting or YAC probes

    Additional anomalies

    both numerical and structural anomalies are found in 50% of cases, numerical anomalies only in 20% (+7,+8,+12,+21,-3, -11, -14, -22) and structural.anomalies only in 20% (involving chromosomes 1, 3, 11, 12, 15, 17 and 21: tumors may be hypodiploid, pseudodiploid, hyperdiploid or near tetraploid without a common pattern; DNA flow cytometry study revealed poorer prognosis for aneuploid tumors

    Variants

    a few variants have been described, involving chromosomes 1, 3, 15 or 21, ...; masked translocations were identified as t(5 ;18), t(X ;7) without chromosome X or 18 apparent involvement respectively

    Genes Involved and Proteins

    Gene name

    SS18 (synovial sarcoma translocation, chromosome 18)

    Location

    18q11.2

    Dna rna description

    3,7 kb mRNA

    Protein description

    387 amino acids; glutamin, prolin and glycin rich; three potential SH2 binding domains and one SH3; widely expressed, limited to cartlagenous and nervous tissues in early embryonal development; biological properties still unknown

    Gene name

    SSX1 (SSX family member 1)

    Location

    Xp11.23

    Dna rna description

    1,6 kb mRNA

    Protein description

    188 amino acids; 81% homologie for SSX1 and SSX2; Kruppel associated box (KRAB) homology; restricted expression to testis and thyroid; biological properties still unknown

    Result of the chromosomal anomaly

    Description

    5 prime SYT- 3 prime SSX1/2

    Oncogenesis

  • SYT/SSX1 variant might be less favorable, associated with higher tumor proliferating rate and reduced overall survival (metastasis free survival 42% vs 80%)
  • Bibliography

    Pubmed IDLast YearTitleAuthors
    103751081999Synovial sarcoma: identification of low and high risk groups.Bergh P et al
    79513201994Identification of novel genes, SYT and SSX, involved in the t(X;18)(p11.2;q11.2) translocation found in human synovial sarcoma.Clark J et al
    13797141992Chromosomes in the diagnosis of soft tissue tumors. I. Synovial sarcoma.Dal Cin P et al
    99177501999Synovial sarcoma: report of a series of 25 consecutive children from a single institution.Ferrari A et al
    99305761998Synovial sarcoma.Fisher C et al
    97390251998Masked t(X;18)(p11;q11) in a biphasic synovial sarcoma revealed by FISH and RT-PCR.Geurts van Kessel A et al
    30305371987Translocation (X;18) in a synovial sarcoma.Griffin CA et al
    94288161998SYT-SSX gene fusion as a determinant of morphology and prognosis in synovial sarcoma.Kawai A et al
    13386921992Localization of the synovial sarcoma t(X;18)(p11.2;q11.2) breakpoint by fluorescence in situ hybridization.Knight JC et al
    16573671991Mediastinal synovial sarcoma with t(X;18)Le Marc'hadour F et al
    34618811986Translocations involving the X chromosome in solid tumors: presentation of two sarcomas with t(X;18)(q13;p11).Limon J et al
    16657041991Cytogenetics of synovial sarcoma: presentation of ten new cases and review of the literature.Limon J et al
    103972631999The SYT-SSX1 variant of synovial sarcoma is associated with a high rate of tumor cell proliferation and poor clinical outcome.Nilsson G et al
    85791181996Interphase fluorescence in situ hybridization and reverse transcription polymerase chain reaction as a diagnostic aid for synovial sarcoma.Shipley J et al
    81528061994The t(X;18)(p11.2;q11.2) translocation found in human synovial sarcomas involves two distinct loci on the X chromosome.Shipley JM et al
    103595531999A novel fusion gene, SYT-SSX4, in synovial sarcoma.Skytting B et al
    30305361987A consistent chromosome translocation in synovial sarcoma.Smith S et al
    30316591987Involvement of chromosome X in primary cytogenetic change in human neoplasia: nonrandom translocation in synovial sarcoma.Turc-Carel C et al
    81740961994Distinct Xp11.2 breakpoint regions in synovial sarcoma revealed by metaphase and interphase FISH: relationship to histologic subtypes.de Leeuw B et al
    103962841999Absence of SYT-SSX fusion products in soft tissue tumors other than synovial sarcoma.van de Rijn M et al

    External Links

    Citation

    Christine Pérot

    Soft Tissues: Synovial sarcoma with t(X;18)(p11;q11) SS18/

    Atlas Genet Cytogenet Oncol Haematol. 2000-02-01

    Online version: http://atlasgeneticsoncology.org/solid-tumor/5044/soft-tissues-synovial-sarcoma-with-t(x;18)(p11;q11)-ss18