In summary, when encountering a bland spindle cell neoplasm with classic hemangiopericytoma-like blood vessels, it is prudent to consider a diagnosis of LGFMS besides solitary fibrous tumor--particularly in the absence of CD34 immunoreactivity as it may be a rare, mimicking variant of LGFMS.
FUS-CREB3L2 was capable of activating transcription from CD24 regulatory sequences in luciferase assays, suggesting an important role for the upregulation of this gene in LGFMS.
This was further confirmed by the gene expression analysis and FACS analysis on Tet-On 3G cells expressing <i>EWSR1-CREB3L1</i><b>Conclusions:</b> Although gene fusions are the primary tumorigenic events in both SEF and LGFMS, additional genomic changes explain the differences in aggressiveness and clinical outcome between the two types.
While the majority of LGFMS cases are characterized by a FUS-CREB3L1 fusion, both FUS-CREB3L2 and EWSR1-CREB3L1 fusions were recently demonstrated in a small number of LGFMS and SEF/LGFMS hybrid tumors.
Our results indicate that EWSR1 and CREB3L1 rearrangements are predominant over FUS and CREB3L2 rearrangements in pure SEF, highlighting that SEF and LGFMS are different tumor types, with different impacts on patient outcome.
Our findings therefore expand the spectrum of gene fusions that characterize LGFMS and suggest that the EWSR1 gene may substitute for the function of FUS in gene fusions of sarcoma.
To that end, dual-color, break-apart fluorescence in situ hybridization (FISH) probes spanning the genomic regions of EWSR1 (22q12), DDIT3 (12q13), and FUS (16p11) (Vysis, Downer's Grove, IL) were evaluated in formalin-fixed, paraffin-embedded tissues from myxoid neoplasms, including intramuscular myxoma (n=10), myxoid liposarcoma (n=18), low-grade fibromyxoid sarcoma (n=10), extraskeletal myxoid chondrosarcoma (n=13), and myxofibrosarcoma (n=8).
Immunohistochemical analysis showed immunoreactivity for MUC4 and break-apart fluorescence in situ hybridization was positive for FUS rearrangement, confirming the diagnosis of LGFMS.
Low-grade fibromyxoid sarcoma (LGFMS) and sclerosing epithelioid fibrosarcoma (SEF) are rare tumors with distinct sets of morphological features, both characterized by MUC4 immunoreactivity.
Hyalinized spindle cell tumor with giant rosettes (HSCTGR) is a morphological variant of LGFMS that shares the same balanced translocation, and is also immunoreactive for MUC4.
While the majority of LGFMS cases are characterized by a FUS-CREB3L1 fusion, both FUS-CREB3L2 and EWSR1-CREB3L1 fusions were recently demonstrated in a small number of LGFMS and SEF/LGFMS hybrid tumors.
This is the first report of "pure" or true SEF presenting as intraabdominal sarcomatosis with confirmation of the recently described unique Ewing sarcoma breakpoint region 1-cAMP-responsive element-binding protein 3-like 1 gene fusion in SEF without areas of low-grade fibromyxoid sarcoma.
Our results indicate that EWSR1 and CREB3L1 rearrangements are predominant over FUS and CREB3L2 rearrangements in pure SEF, highlighting that SEF and LGFMS are different tumor types, with different impacts on patient outcome.