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Inflammatory leiomyosarcoma shows frequent co-expression of smooth and skeletal muscle markers supporting a primitive myogenic phenotype: a report of 9 cases with a proposal for reclassification as low-grade inflammatory myogenic tumor

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Abstract

Inflammatory leiomyosarcoma (ILMS) is a very rare soft tissue tumor that usually follows an indolent clinical course, but long-term follow-up studies are lacking. Recent publications primarily focused on its genetic profile characterized by a near haploid genome. One study also showed these tumors to have upregulation of genes known to be crucial for skeletal muscle differentiation. Nevertheless, immunohistochemical expression of skeletal muscle markers, as well as markers that would help to distinguish ILMS from a long list of relevant differential diagnostic entities, has not been extensively studied. Nine cases of ILMS were collected and stained by a broad IHC panel which, besides others, contained MyoD1, myogenin, and PAX-7. A subset of cases was also analyzed by 2 different NGS assays and by MDM2 fluorescence in situ hybridization. Five male and 4 female patients ranged in age from 25 to 54 years (mean, 36 years). The tumors showed a predilection for intramuscular sites of the lower limbs (n = 4) and back (n = 2), whereas the remaining 3 cases affected an unspecified skeletal muscle, lung, and omentum. Follow-up with an average length of 10.6 years (range 0.5–22) was available for 8 patients. The omental tumor spread locally within the abdominal cavity, but the patient has been free of disease 7 years after treatment. None of the 5 patients with somatic soft tissue tumors (and follow-up longer than 1.5 years) had either recurrence or metastasis. Immunohistochemical studies revealed a substantial expression of skeletal muscle markers in almost all cases. This phenotype coupled with a highly characteristic genotype and significantly more indolent clinical behavior as compared with conventional leiomyosarcoma of deep soft tissue offers a strong rationale to change the current nomenclature. Based on the clinicopathological features and gene expression profile, we propose the name low-grade inflammatory myogenic tumor.

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Funding

Supported in parts by the National Sustainability Program I (NPU I) Nr. LO1503 and by the grant SVV–2019 No. 260 391 provided by the Ministry of Education Youth and Sports of the Czech Republic.

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Authors and Affiliations

  1. Department of Pathology, Charles University, Faculty of Medicine in Plzen, Plzen, Czech Republic

    Michael Michal, Dmitry V. Kazakov, Květoslava Michalová, Marian Švajdler & Michal Michal

  2. Biomedical Center, Charles University, Faculty of Medicine in Plzen, Plzen, Czech Republic

    Michael Michal

  3. Bioptical Laboratory, Ltd., Plzen, Czech Republic

    Michael Michal, Dmitry V. Kazakov, Květoslava Michalová, Petr Šteiner, Petr Grossmann, Veronika Hájková, Petr Martínek, Marian Švajdler & Michal Michal

  4. Department of Pathology, Cleveland Clinic, Cleveland, OH, USA

    Brian P. Rubin

  5. Institute of Pathology, University Hospital, Friedrich-Alexander University Erlangen-Nürnberg, Erlangen, Germany

    Abbas Agaimy

  6. Department of Pathology, First Faculty of Medicine, Charles University in Prague, Prague, Czech Republic

    Ladislav Hadravský

  7. CSD Health Care, Ltd., Kyiv, Ukraine

    Antonina V. Kalmykova

  8. Department of Pathology, Kyoto Prefectural University of Medicine, Kyoto, Japan

    Eiichi Konishi

  9. Department of Radiology, Charles University, Faculty of Medicine in Plzen, Plzen, Czech Republic

    Filip Heidenreich

Authors
  1. Michael Michal
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  2. Brian P. Rubin
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  3. Dmitry V. Kazakov
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  4. Květoslava Michalová
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  5. Petr Šteiner
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  6. Petr Grossmann
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  7. Veronika Hájková
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  8. Petr Martínek
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  9. Marian Švajdler
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  10. Abbas Agaimy
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  11. Ladislav Hadravský
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  12. Antonina V. Kalmykova
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  13. Eiichi Konishi
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  14. Filip Heidenreich
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  15. Michal Michal
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Contributions

Michael Michal-designed the study, selected cases, performed histological analyses, and wrote the manuscript

Brian P. Rubin-designed the study, selected cases, performed histological analyses, and edited the manuscript

Dmitry V. Kazakov-provided cases and edited the manuscript

Květoslava Michalová-composed figures and tables and edited the manuscript

Petr Šteiner-FISH analysis, NGS sequencing, editing of the molecular genetic section

Petr Grossmann-FISH analysis and NGS sequencing

Veronika Hájková-NGS sequencing

Petr Martínek-NGS sequencing, editing of the molecular genetic section

Marian Švajdler-provided cases and clinical information and edited the manuscript

Abbas Agaimy-edited the manuscript, reviewed the cases, and provided deeper insight into some aspects of the tumor

Ladislav Hadravský-collected follow-up

Antonina V. Kalmykova-provided cases and clinical information

Eiichi Konishi-provided cases and clinical information

Filip Heidenreich-radiological findings

Michal Michal-designed the study, selected cases, performed histological analyses, and edited the manuscript

All authors approved the manuscript.

Corresponding author

Correspondence to Michael Michal.

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Michal, M., Rubin, B.P., Kazakov, D.V. et al. Inflammatory leiomyosarcoma shows frequent co-expression of smooth and skeletal muscle markers supporting a primitive myogenic phenotype: a report of 9 cases with a proposal for reclassification as low-grade inflammatory myogenic tumor. Virchows Arch 477, 219–230 (2020). https://doi.org/10.1007/s00428-020-02774-z

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  • DOI: https://doi.org/10.1007/s00428-020-02774-z

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