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Malignant fibrous histiocytoma and fibrosarcoma of bone: a re-assessment in the light of currently employed morphological, immunohistochemical and molecular approaches

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Abstract

Malignant fibrous histiocytoma (MFH) and fibrosarcoma (FS) of bone are rare malignant tumours and contentious entities. Sixty seven cases labelled as bone MFH (57) and bone FS (10) were retrieved from five bone tumour referral centres and reviewed to determine whether recent advances allowed for reclassification and identification of histological subgroups with distinct clinical behaviour. A panel of immunostains was applied: smooth muscle actin, desmin, h-caldesmon, cytokeratin AE1–AE3, CD31, CD34, CD68, CD163, CD45, S100 and epithelial membrane antigen. Additional fluorescence in situ hybridisation and immunohistochemistry were performed whenever appropriate. All cases were reviewed by six bone and soft tissue pathologists and a consensus was reached. Follow-up for 43 patients (median 42 months, range 6–223 months) was available. Initial histological diagnosis was reformulated in 18 cases (26.8 %). Seven cases were reclassified as leiomyosarcoma, six as osteosarcoma, three as myxofibrosarcoma and one each as embryonal rhabdomyosarcoma and interdigitating dendritic cell sarcoma. One case showed a peculiar biphasic phenotype with epithelioid nests and myofibroblastic spindle cells. Among the remaining 48 cases, which met the WHO criteria for bone FS and bone MFH, we identified five subgroups. Seven cases were reclassified as undifferentiated pleomorphic sarcoma (UPS) and 11 as UPS with incomplete myogenic differentiation due to positivity for at least one myogenic marker. Six were reclassified as spindle cell sarcoma not otherwise specified. Among the remaining 24 cases, we identified a further two recurrent morphologic patterns: eight cases demonstrated a myoepithelioma-like phenotype and 16 cases a myofibroblastic phenotype. One of the myoepithelioma-like cases harboured a EWSR1–NFATC2 fusion. It appears that bone MFH and bone FS represent at best exclusion diagnoses.

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Acknowledgments

We would like to thank M. Niero for her expert technical assistance and I. Carraretto for fruitful discussion. This study was funded by EuroBoNeT, a European Commission-granted European Network of excellence for studying the pathology and genetics of bone tumours.

Conflict of interest statement

We declare that we have no conflict of interest.

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Authors and Affiliations

  1. Department of Pathology, Treviso Regional Hospital, Piazza Ospedale 1, 31100, Treviso, Italy

    Salvatore Romeo, Lucia Zanatta & Angelo Paolo Dei Tos

  2. Department of Pathology, Leiden University Medical Center, Leiden, The Netherlands

    Judith V. M. G. Bovée & Pancras C. W. Hogendoorn

  3. Department of Radiology, Leiden University Medical Center, Leiden, The Netherlands

    Herman M. Kroon

  4. Department of Pathology, Royal National Orthopaedic Hospital, London, UK

    Roberto Tirabosco

  5. Department of Pathology, Rovigo Regional Hospital, Rovigo, Italy

    Cristina Natali

  6. Department of Pathology, Leuven University, Leuven, Belgium

    Raf Sciot

  7. Department of Clinical Genetics, Lund University Hospital, Lund, Sweden

    Fredrik Mertens

  8. Department of Pathology, Nuffield Orthopaedic Center, Oxford, UK

    Nick Athanasou

  9. Department of Pathology, Rizzoli Orthopaedic Institute, Bologna, Italy

    Marco Alberghini

  10. Department of Molecular Cell Biology, Leiden University Medical Center, Leiden, The Netherlands

    Karoly Szuhai

Authors
  1. Salvatore Romeo
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  2. Judith V. M. G. Bovée
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  6. Lucia Zanatta
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  7. Raf Sciot
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  8. Fredrik Mertens
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  10. Marco Alberghini
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  11. Karoly Szuhai
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  12. Pancras C. W. Hogendoorn
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  13. Angelo Paolo Dei Tos
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Corresponding author

Correspondence to Angelo Paolo Dei Tos.

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Among the patients without metastases at diagnosis, leiomyosarcomas and myxofibrosarcomas showed a trend to better overall survival in comparison to the remaining cases. A similar trend was observed for UPS with myogenic differentiation which had a slightly better prognosis as compared to UPS. (JPEG 12 kb)

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Romeo, S., Bovée, J.V.M.G., Kroon, H.M. et al. Malignant fibrous histiocytoma and fibrosarcoma of bone: a re-assessment in the light of currently employed morphological, immunohistochemical and molecular approaches. Virchows Arch 461, 561–570 (2012). https://doi.org/10.1007/s00428-012-1306-z

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  • DOI: https://doi.org/10.1007/s00428-012-1306-z

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