Multifocal myxoid liposarcoma: Metastasis or second primary? A molecular biological analysis

Abstract

10576 Background: The metastatic or second primary nature of multifocal myxoid/round cell liposarcoma (MRLS), defined as tumor presentation in at least two separate sites before manifestation in the lungs, is a matter of debate with essential clinical consequences. Characteristic genetic alteration for MRLS include the t(12;16)(q13;p11) or t(12;22)(q13;q12), of which various exon fusion transcripts are described with highly varying incidences, permitting use as a marker for clonality. Moreover, in solid tumors, analysis of loss of heterozygozity (LOH) has proven its value for clonality analysis. Methods: Fifteen patients with features fitting to the criteria of multifocal MRLS with 2–5 metachronous (n= 12) or synchronous (n=3) localizations were investigated. Using RT-PCR, the detailed molecular characteristics of FUS-CHOP and EWS-CHOP breakpoints were determined. LOH analysis at 12 loci on 11 chromosomes was used to further analyze clonal relationships and a dedicated algorithm for interpretation in MRLS was developed. Results: In all patients, tumor sites showed identical FUS-CHOP exon fusion products. In six patients, identical rare fusion transcripts were found, strongly supporting clonal relation. Nine patients had the common exon5-FUS/exon2-CHOP fusion transcript, of which two were identified as clonally related by LOH analysis. In all other patients, LOH analysis was highly suggestive of clonal relation and no evidence for interpretation of a second primary tumor was found. Conclusions: This study supports the metastatic nature of apparent multifocal MRLS. Therefore, in these cases the optimal treatment should be chosen as for this metastasis is preferred, in which case all treatment modalities can be considered. No significant financial relationships to disclose.