RT-PCR and FISH for the FUS-CREB3L2 fusion transcript are useful tools for confirming LGFMS diagnosis, but have no role in predicting medium-term clinical outcome.
Low-grade fibromyxoid sarcoma (LGFMS) is a distinctive fibroblastic neoplasm that is characterized by alternating collagenous and myxoid areas, deceptively bland spindle cell morphology, a whorling architecture, and a t(7;16) translocation involving FUS and CREB3L2.
Recently, a link has been suggested between SEF and low-grade fibromyxoid sarcoma (LGFMS) on the basis of the finding of the characteristic translocation t(7;16) (FUS-CREB3L2) of LGFMS in a small number of studied cases of SEF.
We present a case of an ossifying tumor of the perineum that required an open biopsy and fluorescent in situ hybridization testing for FUS and CREB3L2 for diagnosis as a variant of low-grade fibromyxoid sarcoma.
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.
Results showed 50% of cases tested positive for the FUS-CREB3L2 translocation by RT-PCR and 81.8% by FISH, suggesting FISH is more sensitive than RT-PCR for confirming LGFMS diagnosis.
However, supernumerary ring chromosomes have been identified in a subset of FUS/CREB3L2-positive LGFMS, but it has not yet been formally demonstrated that such ring chromosomes harbor the FUS/CREB3L2 fusion gene.
Postoperative pathology of the resected specimen revealed the tumor to be LGFMS based on its histological appearance, immunohistological staining, and evidence of fused in sarcoma (FUS) translocation by fluorescence in situ hybridization.
Distinct chromosomal translocations have been identified in several myxoid sarcomas, including t(12;16)(q13;p11) FUS-DDIT3 in myxoid liposarcoma, t(7;16)(q34;p11) FUS-CREB3L2 in low-grade fibromyxoid sarcoma, and t(9;22)(q31;q12) EWSR1-NR4A3 in extraskeletal myxoid chondrosarcoma.
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).
Reported herein is a case of primary pulmonary HSCT that had FUS-CREB3L2 fusion transcripts, a product of characteristic chromosomal abnormality t(7;16)(q33;p11) of HSCT and LGFMS.
Reported herein is a case of primary pulmonary HSCT that had FUS-CREB3L2 fusion transcripts, a product of characteristic chromosomal abnormality t(7;16)(q33;p11) of HSCT and LGFMS.
We also tested a primer set to detect the FUS-CREB3L1 fusion transcript, which is a rare variant of the gene fusion in LGFMS, although no PCR products were identified in any case.
Reverse transcriptase-polymerase chain reaction analysis disclosed a FUS/CREB3L2 fusion transcript in 22 of the 23 (96%) cases that remained classified as LGFMS after the histologic re-evaluation and from which RNA of sufficient quality could be extracted, whereas none of the cases that were classified as other tumor types was fusion-positive.
Reverse transcriptase-polymerase chain reaction analysis disclosed a FUS/CREB3L2 fusion transcript in 22 of the 23 (96%) cases that remained classified as LGFMS after the histologic re-evaluation and from which RNA of sufficient quality could be extracted, whereas none of the cases that were classified as other tumor types was fusion-positive.
The results indicated that FUS/CREB3L2 is specifically associated with LGFMS and that RT-PCR or FISH analysis may be useful for the differential diagnosis.
The results indicated that FUS/CREB3L2 is specifically associated with LGFMS and that RT-PCR or FISH analysis may be useful for the differential diagnosis.