Challenging dedifferentiated liposarcoma identified by MDM2-amplification, a report of two cases

Suvi Lokka, Andreas H Scheel, Sebastian Dango, Katja Schmitz, Rudolf Hesterberg, Josef Rüschoff, Hans-Ulrich Schildhaus, Suvi Lokka, Andreas H Scheel, Sebastian Dango, Katja Schmitz, Rudolf Hesterberg, Josef Rüschoff, Hans-Ulrich Schildhaus

Abstract

Background: Liposarcoma is the most frequent soft tissue sarcoma. Well differentiated liposarcoma may progress into dedifferentiated liposarcoma with pleomorphic histology. A minority additionally features myogenic, osteo- or chondrosarcomatous heterologous differentiation. Genomic amplification of the Mouse double minute 2 homolog (MDM2) locus is characteristic for well differentiated and dedifferentiated liposarcomas. Detection of MDM2 amplification may supplement histopathology and aid to distinguish liposarcoma from other soft tissue neoplasia.

Case presentation: Here we present two cases of dedifferentiated liposarcoma with challenging presentation. Case 1 features a myogenic component. As the tumour infiltrated the abdominal muscles and showed immunohistochemical expression of myogenic proteins, rhabdomyosarcoma had to be ruled out. Case 2 has an osteosarcomatous component resembling extraosseous osteosarcoma. The MDM2 status was determined in both cases and helped making the correct diagnosis. Overexpression of MDM2 and co-overexpression of Cyclin-dependent kinase 4 is demonstrated by immunohistochemistry. The underlying MDM2 amplification is shown by fluorescence in situ hybridisation. Since low grade osteosarcoma may also harbour MDM2 amplification it is emphasised that the amplification has to be present in the lipomatous parts of the tumour to distinguish liposarcoma from extraosseous osteosarcoma.

Conclusions: The two cases exemplify challenges in the diagnoses of dedifferentiated liposarcoma. Liposarcoma often has pleomorphic histology and additionally may feature heterologous components that mimic other soft tissue neoplasms. Amplification of MDM2 is characteristic for well differentiated and dedifferentiated liposarcomas. Determination of the MDM2 status by in situ hybridisation may assist histopathology and help to rule out differential diagnoses.

Keywords: Dedifferentiated Liposarcoma; Fluorescence in situ hybridisation; Liposarcoma with osteoblastic component; MDM2.

Figures

Figure 1
Figure 1
Clinical presentation of Case #1: Preoperative CT-scan (A) of the tumour in the lower left abdominal wall. Macroscopic presentation of the surgical specimen (B); central parts of the tumour are well delimited ('core'); the path of the primary laparoscopy is visible. The tumour infiltrated the abdominal skeletal muscles but did not extra into the abdominal cavity.
Figure 2
Figure 2
Histopathology of Case #1: The tumour shows patches of higher differentiated atypical lipomatous tissue (A) but mostly displays only poorly differentiated spindle-shaped cells (B). Prominent areas with myofibroblastic morphology were noticed (C) and immunohistochemistry was positive for Desmin (D) and Actin.
Figure 3
Figure 3
Molecular hallmarks of Case #1: Immunohistochemistry demonstrates co-overexpression of CDK4 (B) and MDM2 (C) in both the poorly and higher differentiated areas (A: HE-staining of corresponding region). Fluorescence in situ hybridisation shows strong amplification of the MDM2 locus as underlying genetic alteration (D; Green: MDM2 probe, Red: Chromosome 12 reference probe). The features are characteristic of dedifferentiated liposarcoma.
Figure 4
Figure 4
Histopathology and molecular hallmarks of Case #2: The tumour showed heterogeneous morphology. Most cells were spindle-shaped but giant cells with segmented nuclei were also present. Focally, transitions into higher differentiated lipomatous tissue were noticed (A). Other areas were of osteoblastic/osteosarcomatous (B) and fibrosarcomatous appearance (C). Fluorescence in situ hybridisation of the MDM2 gene revealed highly amplified clusters in the lipomatous (D, left), fibrosarcomatous and the osteosarcomatous regions (D, right).

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