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: Ronald S A de Vreeze, Daphne de Jong, Ivon H G Tielen, Henrique J Ruijter, Petra M Nederlof, Rick L Haas, Frits van Coevorden
• Journal: Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc (Mod Pathol) Vol. 22 Issue 2 Pg. 223-31 (Feb 2009) ISSN: 1530-0285 [Electronic] United States
• PMID: 18820664 (Publication Type: Journal Article)

Chemical References

• Calmodulin-Binding Proteins
• EWSR1 protein, human
• Oncogene Proteins, Fusion
• RNA-Binding Protein EWS
• RNA-Binding Protein FUS
• RNA-Binding Proteins
• TLS-CHOP fusion protein, human
• Transcription Factor CHOP
• MDM2 protein, human
• Proto-Oncogene Proteins c-mdm2
• CDK4 protein, human
• Cyclin-Dependent Kinase 4

Topics

• Adult
• Aged
• Aged, 80 and over
• Calmodulin-Binding Proteins (genetics)
• Cell Differentiation
• Chromosomes, Human, Pair 12
• Cyclin-Dependent Kinase 4 (analysis, genetics)
• Female
• Gene Expression Regulation, Neoplastic
• Humans
• Immunohistochemistry
• Liposarcoma, Myxoid (chemistry, classification, genetics, pathology, therapy)
• Male
• Middle Aged
• Oncogene Proteins, Fusion (genetics)
• Polymerase Chain Reaction
• Proto-Oncogene Proteins c-mdm2 (analysis, genetics)
• RNA-Binding Protein EWS
• RNA-Binding Protein FUS (genetics)
• RNA-Binding Proteins (genetics)
• Retroperitoneal Neoplasms (chemistry, classification, genetics, pathology, therapy)
• Terminology as Topic
• Transcription Factor CHOP (genetics)
• Translocation, Genetic