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Myxoid liposarcoma with nuclear pleomorphism: a clinicopathological and molecular study

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Abstract

Myxoid liposarcoma (MLS) is a common type of liposarcoma. It is characterized by variably lipogenic uniform cells in myxoid stroma with arborizing capillaries and DDIT3 fusion. Nuclear uniformity is the rule, which is maintained even in high-grade round cell examples. In this study, we conducted an in-depth investigation of four MLS tumors that demonstrated nuclear pleomorphism in three patients. These cases accounted for 2.1% of 142 patients with MLS. All patients were male aged 26, 33, and 49 years. Nuclear pleomorphism was observed in both primary and metastatic tumors in one patient, a primary tumor in one patient, and a metastatic tumor in another patient. Pleomorphism was severe in three tumors and moderate in one. Histology resembled that of dedifferentiated liposarcoma with myxoid features, pleomorphic liposarcoma with myxoid features, or myxoid pleomorphic liposarcoma in two tumors, pleomorphic sarcoma with focal cartilaginous and rhabdomyoblastic differentiation in one tumor, and epithelioid pleomorphic liposarcoma in one tumor. All tumors harbored FUS::DDIT3 fusions and immunohistochemically expressed DDIT3. All tumors had TP53 mutations, whereas previous specimens with uniform cytology from the same patients lacked TP53 mutations. One tumor showed RB1 deletion and complete loss of Rb expression, which was unclassifiable using DNA methylation-based methods. The rare occurrence of nuclear pleomorphism is underrecognized in MLS and increases the complexity to the diagnosis of liposarcoma. DDIT3 evaluation can be liberally considered in liposarcoma assessment even in the presence of nuclear pleomorphism.

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Acknowledgements

The authors thank Sachiko Miura, Toshiko Sakaguchi, Chizu Kina, Eijitsu Ryo, Kaori Yamaguchi, Kazuhiro Yoshida, Hiroshi Chigira, and Hiroki Kakishima for their excellent technical assistance.

Funding

This work was partly supported by JSPS KAKENHI (grant number JP21K06919, AY) and the Rare Cancer Grant of National Cancer Center Hospital (G007, AY).

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Authors and Affiliations

  1. Department of Diagnostic Pathology, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan

    Naoki Kojima, Taisuke Mori, Kaishi Satomi, Yasushi Yatabe & Akihiko Yoshida

  2. Department of Clinical Genomics, National Cancer Center Research Institute, Tokyo, Japan

    Takashi Kubo & Hitoshi Ichikawa

  3. Department of Pathology, Kyorin University Faculty of Medicine, Tokyo, Japan

    Kaishi Satomi

  4. Department of Brain Disease Translational Research, Juntendo University Graduate School of Medicine, Tokyo, Japan

    Yuko Matsushita & Koichi Ichimura

  5. Department of Musculoskeletal Oncology, National Cancer Center Hospital, Tokyo, Japan

    Shintaro Iwata & Akira Kawai

  6. Rare Cancer Center, National Cancer Center, Tokyo, Japan

    Shintaro Iwata, Akira Kawai & Akihiko Yoshida

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  1. Naoki Kojima
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Contributions

AY designed the study. NK and AY collected samples/data and conducted histological and immunohistochemical analyses. AY, TK, TM, KS, YM, KI, and HI performed and interpreted molecular data. AK, SI, and YY provided samples and clinical data. NK and AY drafted the manuscript. All authors reviewed and approved the final manuscript.

Corresponding author

Correspondence to Akihiko Yoshida.

Ethics declarations

This study was approved by the institutional review boards of the National Cancer Center Hospital (No. 2014-089). The study was performed in accordance with the Declaration of Helsinki. Informed consent was obtained from all patients included in the study, except in cases where its requirement was waived by the IRB.

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The authors declare no competing interests.

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Kojima, N., Kubo, T., Mori, T. et al. Myxoid liposarcoma with nuclear pleomorphism: a clinicopathological and molecular study. Virchows Arch 484, 71–81 (2024). https://doi.org/10.1007/s00428-023-03631-5

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