Dedifferentiated Liposarcoma with "Homologous" Lipoblastic (Pleomorphic Liposarcoma-Like) Differentiation: Clinicopathologic and Molecular Analysis
A Marino-Enriquez, CDM Fletcher, P Dal Cin, JL Hornick. Brigham and Women's Hospital, Boston; Hospital Universitario La Paz, Madrid, Spain
Background: Dedifferentiated liposarcoma (DDLPS) is a malignant adipocytic neoplasm defined as transition from well-differentiated liposarcoma (WDLPS) to a non-lipogenic sarcoma. Heterologous differentiation is seen in 5% of DDLPS, usually with myogenic or osteo/chondrosarcomatous elements; adipocytic differentiation in the high grade component is incompatible with the current definition of DDLPS. Pleomorphic liposarcoma (pLPS) is a high grade sarcoma containing lipoblasts. pLPS can be indistinguishable from DDLPS, except for the presence of lipoblasts in pLPS and WDLPS areas in DDLPS.
Design: We evaluated 10 unusual liposarcomas: 9 WDLPS/DDLPS with high grade areas showing lipoblastic differentiation and 1 resembling inflammatory "MFH" with scattered lipoblasts. Clinical and histologic features were reviewed. Immunohistochemistry for MDM2 and CDK4 was performed. Amplification of 12q15 was studied by FISH analysis of the HMGA2 locus.
Results: Tumors arose in the retroperitoneum (7), proximal lower extremity (2) and neck (1) of 7 males and 3 females (median 67 yrs, range 49-76). Size ranged from 9-32 cm. In 3 cases there was abrupt transition between WDLPS/DDLPS and sheets of pleomorphic lipoblasts, indistinguishable from pLPS. Four cases consisted of otherwise typical DDLPS (with adjacent WDLPS), except for the focal presence of lipoblasts in the high grade component. One case contained both non-lipogenic spindle cell areas and an inflammatory "MFH"-like component with numerous admixed lipoblasts. Two cases were composed exclusively of pLPS-like areas developing in one of the recurrences of DDLPS. Two also showed heterologous smooth muscle differentiation. MDM2 and CDK4 were positive in both the DDLPS and pLPS-like components in 8/8 and 7/8 cases, respectively. Karyotyping, available for 1 case, showed giant marker chromosomes. FISH analysis showed high-level amplification of 12q15 in 3 cases tested so far. Follow-up, available on 8 patients, ranged from 21-196 mos (median 42). Four patients developed local recurrences (multiple in 3), and 2 lung metastases. Thus far, 5 patients died of disease, 1 died of unknown cause and 2 are alive with no evidence of disease.
Conclusions: DDLPS can show lipoblastic differentiation in the high grade component, resulting in areas indistinguishable from pLPS. Available clinical and molecular data support the notion of "homologous" lipoblastic differentiation in DDLPS, rather than mixed-type liposarcomas.
Category: Bone & Soft Tissue
Monday, March 22, 2010 8:15 AM
Platform Session: Section F, Monday Morning