Monoclonality of multifocal myxoid liposarcoma: Confirmation by analysis of TLS-CHOP or EWS-CHOP rearrangements

Multifocal presentation, defined as the presence of tumor at two or more an atomically separate sites, before the manifestation of disease in sites whe re sarcomas usually metastasize (e.g., lungs) occurs in about 1% of extremi ty soft tissue sarcomas (STSs), Debate still persists whether multifocal ST Ss represent an unusual pattern of metastasis or multiple separate primary tumors. Among STSs with multifocal presentation, myxoid liposarcoma is the predominant histological type. This subtype of liposarcoma contains the spe cific t(12;16) chromosomal translocation, which results in rearrangement of the TLS and CHOP genes that is clone specific at the DNA level. We, theref ore, sought to address the question of clonality by molecular analysis in s ix patients who presented with either synchronous or metachronous multifoca l myxoid liposarcoma, In all six cases, adequate frozen tumor was available for DNA extraction from at least two distinct anatomical sites. Southern b lot analysis using CHOP, TLS, and EWS cDNA probes was performed on genomic DNA, Five cases contained a TLS-CHOP rearrangement, and one case had the va riant EWS-CHOP fusion (seen in <5% of cases). The size of the rearranged CH OP fragment differed among the six patients, as expected, but was identical in all anatomically separate tumor samples from each patient. Likewise, th e sizes of the rearranged bands observed with either the TLS or EWS probes supported the monoclonality of all cases, Our results confirm the monoclona l origin of multifocal myxoid liposarcoma, establishing the metastatic natu re of distant soft tissue lesions in these cases, It remains unclear whethe r this unusual pattern of metastasis represents an intrinsic property of th is subset of myxoid liposarcoma or merely a rare chance occurrence. The cli nical outcomes observed in this small series suggest that the prognosis of multifocal myxoid liposarcoma is poor, regardless of its often bland or "lo w-grade" histological appearance.