Volume 79, Issue 3 pp. 347-357

Original Article

Head and neck rhabdomyosarcoma with TFCP2 fusions and ALK overexpression: a clinicopathological and molecular analysis of 11 cases

Bin Xu,

Bin Xu

orcid.org/0000-0003-4638-9835

Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA

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Albert J H Suurmeijer,

Albert J H Suurmeijer

Department of Pathology and Laboratory Medicine, University Hospital Groningen, Groningen, The Netherlands

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Narasimhan P Agaram,

Narasimhan P Agaram

Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA

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Lei Zhang,

Lei Zhang

Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA

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Cristina R Antonescu,

Corresponding Author

Cristina R Antonescu

[email protected]

orcid.org/0000-0002-9717-8205

Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA

Address for correspondence: C R Antonescu, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY 10065, USA. e-mail: [email protected]

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Bin Xu,

Bin Xu

orcid.org/0000-0003-4638-9835

Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA

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Albert J H Suurmeijer,

Albert J H Suurmeijer

Department of Pathology and Laboratory Medicine, University Hospital Groningen, Groningen, The Netherlands

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Narasimhan P Agaram,

Narasimhan P Agaram

Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA

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Lei Zhang,

Lei Zhang

Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA

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Cristina R Antonescu,

Corresponding Author

Cristina R Antonescu

[email protected]

orcid.org/0000-0002-9717-8205

Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA

Address for correspondence: C R Antonescu, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY 10065, USA. e-mail: [email protected]

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First published: 31 December 2020

https://doi.org/10.1111/his.14323

Citations: 36

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Abstract

Aims

Primary intraosseous rhabdomyosarcoma (RMS) is a rare entity defined by EWSR1/FUS–TFCP2 or, less commonly, MEIS1–NCOA2 fusions. The lesions often show a hybrid spindle and epithelioid phenotype, frequently coexpress myogenic markers, ALK, and cytokeratin, and show a striking propensity for the pelvic and craniofacial bones. The aim of this study was to investigate the clinicopathological and molecular features of 11 head and neck RMSs (HNRMSs) characterised by the genetic alterations described in intraosseous RMS.

Methods and results

The molecular abnormalities were analysed with fluorescence in-situ hybridisation and/or targeted RNA/DNA sequencing. Seven cases had FUS–TFCP2 fusions, four had EWSR1–TFCP2 fusions, and none had MEIS1–NCOA2 fusions. All except one case were intraosseous, affecting the mandible (n = 4), maxilla (n = 3), and skull (n = 3). One case occurred in the superficial soft tissue of the neck. The median age was 29 years (range, 16–74 years), with an equal sex distribution. All tumours showed mixed epithelioid and spindle morphology. Immunohistochemical coexpression of desmin, myogenin, MyoD1, ALK, and cytokeratin was seen in most cases. An intragenic ALK deletion was seen in 43% of cases. Regional and distant spread were seen in three and four patients, respectively. Two patients died of their disease.

Conclusions

We herein present the largest series of HNRMSs with TFCP2 fusions to date. The findings show a strong predilection for the skeleton in young adults, although we also report an extraosseous case. The tumours are characterised by a distinctive spindle and epithelioid phenotype and a peculiar immunoprofile, with coexpression of myogenic markers, epithelial markers, and ALK. They are associated with a poor prognosis, including regional or distant spread and disease-related death.

Graphical Abstract

In this study, we present the largest series of head and neck rhabdomyosarcoma harboring TFCP2 fusions. These tumors have a strong predilection for skeleton, a spindle and epithelioid phenotype, and a poor outcome. They often express ALK, myogenic and epithelial markers.

Conflict of interest

The authors state that they have no competing financial interests.

Supporting Information

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Citing Literature

Volume79, Issue3

September 2021

Pages 347-357