Added Value of Molecular Biological Analysis in Diagnosis and Clinical Management of Liposarcoma: A 30-Year Single-Institution Experience

Abstract

BackgroundTreatment decisions and prognosis assessment for liposarcoma is based on a classification that depends on morphological and genetic features. Revisions by experienced referral pathologists are often advocated.MethodsThe process of histopathological classification in referring hospitals and subsequently in a referral center in relation to molecular biological information is evaluated. A total of 331 consecutive liposarcoma patients were evaluated for the added value of histological review at time of referral. Subsequently, cases were reclassified with implementation of present-day molecular information. For all patients, complete data on staging, treatment, and follow-up were available.ResultsUpon histological revision, 15/54 (28%) diagnoses were reclassified in the first decade, 14/65 (22%) in the second, and 14/53 (26%) in the last decade. Molecular biological analysis enabled well-differentiated liposarcoma with or without dedifferentiated component to be better recognized as such and distinguished from myxoid liposarcoma and pleomorphic liposarcoma. Inclusion of cytogenetic information resulted in reclassification after revision in 4/18 (22%) cases in the first decade, 10/38 (26%) cases in the second decade, and 19/75 (25%) cases in the last decade.ConclusionsThis study indicates that liposarcomas are heterogeneous tumors. Expert assessment and implementation of molecular biological analysis are valuable for adequate classification as a basis for treatment decisions.

Comparison of Chromogenic In Situ Hybridization and Fluorescence In Situ Hybridization for the Evaluation of MDM2 Amplification in Adipocytic Tumors

“…MDM2 is amplified in close to 100% of ALT-WDLPS and DDLPS and is not amplified in benign lipomas (10). Myxoid liposarcomas also do not show MDM2 amplification; instead they are associated with a classical t(12;16)(q13;p11) or t(12;22)(q13;q12) translocation (11). The results of the present study are consistent with these observations.…”

Amplification of FRS2 and Activation of FGFR/FRS2 Signaling Pathway in High-Grade Liposarcoma

“…Recent reports indicate that "UHGPS" has been misused for several better classifiable, poorly differentiated soft-tissue sarcomas (14). For example, a study reported that 23% of 163 high-grade liposarcomas in the Netherlands Cancer Institute were reclassified on the basis of molecular characteristics of liposarcoma (15). Similarly, another study re-evaluated 159 cases of previously diagnosed UHGPS and found that a total of 97 of these cases could be reclassified as other sarcomas and 20 were proven to be nonmesenchymal neoplasms (16).…”

Potential for immunotherapy in soft tissue sarcoma

“…Without genetic and cytogenetic characterization, there can be significant overlap in the histologic appearance between the liposarcoma subtypes which can frequently lead to misdiagnosis. 16 Rationale for immunotherapy in STS From an immunotherapy standpoint, the fusion proteins which result from chromosomal translocations (not found on normal cells) represent attractive potential targets in STS. Although there may be tolerance toward epitopes within the separate proteins, the area of fusion represents a foreign antigen that can be targeted either by the natural immune response or actively induced through immunotherapy.…”