Diagnosis & Discussion
Diagnosis
Dedifferentiated liposarcoma
Discussion
Dedifferentiated liposarcoma (DDL) is defined as a well-differentiated liposarcoma/atypical lipomatous tumor (WDL/ALT) with dedifferentiation, either de novo or in a recurrent tumor, to a typically non-lipogenic sarcoma. It presents most frequently in middle-aged and older adults with a roughly equal gender distribution (peak incidence in the 6th to 8th decades), although rare occurrences have been reported in children and adolescents. The retroperitoneum is the most frequent site by far followed by the extremities. DDL may also occur in the spermatic cord, head/neck, and mediastinum.
Grossly, DDLs are usually large (>10 cm), bulky, multinodular tumors that vary from yellow and fatty (WDL/ALT components) to tan-gray or tan-white firm, solid areas (DDL components). Areas of necrosis or hemorrhage are common.
Histologically, there is an abrupt or gradual transition between the WDL/ALT and DDL components and these tumors typically show moderate to marked pleomorphism with high cellularity and necrosis. The grade of the DDL component may be variable but is most commonly high-grade. DDL can have a mixture of different morphologies including: fascicular spindle cell (the low-grade variant may resemble fibromatosis), pleomorphic and cellular “malignant fibrous histiocytoma-like”, inflammatory with abundant neutrophils, storiform resembling a neural tumor or dermatofibrosarcoma protuberans, or epithelioid with diffuse, sheet like growth, which may contain rhabdoid-like cells. The stroma can be collagenous, myxocollagenous, or myxoid which can mimic a high-grade myxofibrosarcoma. Approximately 5% of DDL show heterologous differentiation towards other mesenchymal lines including muscle (rhabdomyosarcoma, leiomyosarcoma), osteosarcoma, chondrosarcoma, or rarely angiosarcoma. The diagnosis of DDL can be difficult in neoplasms that lack a component of WDL, and in patients who lack a previous history of WDL/ALT. Accurately diagnosing DDL is of prognostic significance because of its better prognosis with lower tendency towards local recurrence and metastasis, compared with morphologically similar pleomorphic sarcomas such as undifferentiated pleomorphic sarcoma or leiomyosarcoma.
DDL behaves as a high-grade sarcoma, with aggressive local growth and a high rate of local recurrence. Metastasis can occur in any cases, independent of the grade and dedifferentiation. Of interest, DDL can recur as WDL/ALT without evidence of dedifferentiated tumor. The most important adverse prognostic factor for DDL has been described to be retroperitoneal location, with tumors at this anatomic site showing significantly worse survival than those at other locations.
Immunohistochemically, DDL express MDM2 and CDK4, with strong correlation of marker expression with gene amplification status. Use of the combination of CDK4, MDM2 and p16 is helpful in distinguishing WDL/ALT and DDL from other adipocytic tumors and other non-lipogenic sarcomas in the histologic differential diagnosis. DDL must be excluded in any retroperitoneal sarcoma or neoplasm, which can be aided by adequate sampling particularly peripheral/solid areas, immunohistochemistry, and/or molecular studies.
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