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Open Access 09-02-2024 | Sarcoma | ORIGINAL ARTICLE

Small cell osteosarcoma versus fusion-driven round cell sarcomas of bone: retrospective clinical, radiological, pathological, and (epi)genetic comparison with clinical implications

Authors: Laura S. Hiemcke-Jiwa, Vaiyapuri P. Sumathi, Daniel Baumhoer, Stephanie E. Smetsers, Lianne M. Haveman, Max M. van Noesel, Kirsten van Langevelde, Arjen H. G. Cleven, Michiel A. J. van de Sande, Simone A. J. ter Horst, Lennart A. Kester, Uta Flucke

Published in: Virchows Archiv | Issue 3/2024

Abstract

Small cell osteosarcoma (SCOS), a variant of conventional high-grade osteosarcoma (COS), may mimic fusion-driven round cell sarcomas (FDRCS) by overlapping clinico-radiological and histomorphological/immunohistochemical characteristics, hampering accurate diagnosis and consequently proper therapy. We retrospectively analyzed decalcified formalin-fixed paraffin-embedded (FFPE) samples of 18 bone tumors primarily diagnosed as SCOS by methylation profiling, fusion gene analysis, and immunohistochemistry.

In eight cases, the diagnosis of SCOS was maintained, and in 10 cases it was changed into FDRCS, including three Ewing sarcomas (EWSR1::FLI1 in two cases and no identified fusion gene in the third case), two sarcomas with BCOR alterations (KMT2D::BCOR, CCNB3::BCOR, respectively), three mesenchymal chondrosarcomas (HEY1::NCOA2 in two cases and one case with insufficient RNA quality), and two sclerosing epithelioid fibrosarcomas (FUS::CREBL3 and EWSR1 rearrangement, respectively).

Histologically, SCOS usually possessed more pleomorphic cells in contrast to the FDRCS showing mainly monomorphic cellular features. However, osteoid was seen in the latter tumors as well, often associated with slight pleomorphism. Also, the immunohistochemical profile (CD99, SATB2, and BCOR) overlapped.

Clinically and radiologically, similarities between SCOS and FDRCS were observed, with by imaging only minimal presence or lack of (mineralized) osteoid in most of the SCOSs.

In conclusion, discrimination of SCOS, epigenetically related to COS, versus FDRCS of bone can be challenging but is important due to different biology and therefore therapeutic strategies. Methylation profiling is a reliable and robust diagnostic test especially on decalcified FFPE material. Subsequent fusion gene analysis and/or use of specific immunohistochemical surrogate markers can be used to substantiate the diagnosis.

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Title: Small cell osteosarcoma versus fusion-driven round cell sarcomas of bone: retrospective clinical, radiological, pathological, and (epi)genetic comparison with clinical implications
Authors: Laura S. Hiemcke-Jiwa
Vaiyapuri P. Sumathi
Daniel Baumhoer
Stephanie E. Smetsers
Lianne M. Haveman
Max M. van Noesel
Kirsten van Langevelde
Arjen H. G. Cleven
Michiel A. J. van de Sande
Simone A. J. ter Horst
Lennart A. Kester
Uta Flucke
Publication date: 09-02-2024
Publisher: Springer Berlin Heidelberg
Keywords: Sarcoma
Osteosarcoma
osteosarcoma
Chondrosarcoma
Published in: Virchows Archiv / Issue 3/2024
Print ISSN: 0945-6317
Electronic ISSN: 1432-2307
DOI: https://doi.org/10.1007/s00428-024-03747-2

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Small cell osteosarcoma versus fusion-driven round cell sarcomas of bone: retrospective clinical, radiological, pathological, and (epi)genetic comparison with clinical implications

Abstract

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Springer Medicine

Abstract

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