title: Primary retroperitoneal myxoid/round cell liposarcoma is a nonexisting disease: an immunohistochemical and molecular biological analysis.
abstract: Almost all primary retroperitoneal liposarcomas can be classified as well-/dedifferentiated liposarcoma. Rarely, however, primary retroperitoneal liposarcoma is classified as myxoid/round cell liposarcoma, based on the presence of myxoid areas and vascular crow's feet pattern, which has resulted in a debate on the classification of liposarcoma in the retroperitoneum. Genetically, myxoid/round cell liposarcoma and well-/dedifferentiated liposarcoma are different diseases. Myxoid/round cell liposarcoma is characterized by a translocation causing FUS-CHOP or EWSR1-CHOP fusion, whereas well-/dedifferentiated liposarcoma is characterized by an amplification of the 12q13-15 region, including MDM2 and CDK4 genes. As myxoid/round cell liposarcoma is highly radio- and chemosensitive, differentiation between subtypes is important to optimize treatment. We studied whether primary retroperitoneal liposarcomas diagnosed as myxoid/round cell liposarcoma represent molecularly true myxoid/round cell liposarcoma or are histopathological mimics and represent well-/dedifferentiated liposarcoma. Primary retroperitoneal myxoid/round cell liposarcoma (n=16) were compared to primary extremity myxoid/round cell liposarcoma (n=20). Histopathological and immunohistochemical features were studied. Amplification status of the 12q13-15 region was studied using a multiplex ligation-dependent probe amplification analysis, and FUS-CHOP or EWS-CHOP translocations were studied using RT-PCR. In primary retroperitoneal myxoid/round cell liposarcoma, MDM2 and CDK4 staining was both positive in 12 of 15 cases. In primary extremity myxoid/round cell liposarcoma, MDM2 was negative in 18/20 and CDK4 was negative in all cases. Multiplex ligation-dependent probe amplification showed the amplification of 12q13-15 region in 16/16 primary retroperitoneal myxoid/round cell liposarcomas and in 1/20 primary extremity myxoid/round cell liposarcomas. Translocation was present in all (18/18) primary extremity myxoid/round cell liposarcomas, but absent in all primary retroperitoneal myxoid/round cell liposarcomas. On the basis of immunohistochemical and molecular characteristics, apparent primary retroperitoneal myxoid/round cell liposarcoma can be recognized as well-/dedifferentiated liposarcoma with morphological features mimicking myxoid/round cell liposarcoma. In these cases, treatment should probably be specifically designed as for well-/dedifferentiated liposarcoma. Moreover, finding of myxoid/round cell liposarcoma translocations in a retroperitoneal localization is highly suggestive of metastasis and should prompt search for a primary localization outside the retroperitoneum.
authors.affiliation: Department of Surgical Oncology, Antoni van Leeuwenhoek Hospital, The Netherlands Cancer Institute, Amsterdam, The Netherlands. r.d.vreeze@nki.nl
authors.forename: Ronald S A
authors.initials: RS
authors.lastname: de Vreeze
authors.forename: Daphne
authors.initials: D
authors.lastname: de Jong
authors.forename: Ivon H G
authors.initials: IH
authors.lastname: Tielen
authors.forename: Henrique J
authors.initials: HJ
authors.lastname: Ruijter
authors.forename: Petra M
authors.initials: PM
authors.lastname: Nederlof
authors.forename: Rick L
authors.initials: RL
authors.lastname: Haas
authors.forename: Frits
authors.initials: F
authors.lastname: van Coevorden
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002148:Calmodulin-Binding Proteins / Q000235:genetics; D002454:Cell Differentiation; D002881:Chromosomes, Human, Pair 12; D051358:Cyclin-Dependent Kinase 4 / Q000032:analysis / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D018208:Liposarcoma, Myxoid / Q000737:chemistry / Q000145:classification / Q000235:genetics / Q000473:pathology* / Q000628:therapy; D008297:Male; D008875:Middle Aged; D015514:Oncogene Proteins, Fusion / Q000235:genetics; D016133:Polymerase Chain Reaction; D051736:Proto-Oncogene Proteins c-mdm2 / Q000032:analysis / Q000235:genetics; D034802:RNA-Binding Protein EWS; D034702:RNA-Binding Protein FUS / Q000235:genetics; D016601:RNA-Binding Proteins / Q000235:genetics; D012186:Retroperitoneal Neoplasms / Q000737:chemistry / Q000145:classification / Q000235:genetics / Q000473:pathology* / Q000628:therapy; D009626:Terminology as Topic; D051742:Transcription Factor CHOP / Q000235:genetics; D014178:Translocation, Genetic
chemical_list: D002148:Calmodulin-Binding Proteins; C500986:EWSR1 protein, human; D015514:Oncogene Proteins, Fusion; D034802:RNA-Binding Protein EWS; D034702:RNA-Binding Protein FUS; D016601:RNA-Binding Proteins; C106030:TLS-CHOP fusion protein, human; D051742:Transcription Factor CHOP; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2; C495900:CDK4 protein, human; D051358:Cyclin-Dependent Kinase 4