Epithelioid and spindle cell rhabdomyosarcoma with FUS-TFCP2 or EWSR1-TFCP2 fusion: report of two cases

Chrisinger, John S.A.; Wehrli, Bret; Dickson, Brendan C.; Fasih, Samir; Hirbe, Angela C.; Shultz, David; Zadeh, Gelareh; Gupta, Abha; Demicco, Elizabeth G.

doi:10.1007/s00428-020-02870-0

Cited by 49 publications

(79 citation statements)

References 37 publications

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“…It was initially recognised as a distinct pathological entity on the basis of its recurrent gene fusions, including TFCP2 fusions with either EWSR1 or FUS , and less commonly MEIS – NCOA2 fusions 5,6 . To date, <40 cases of intraosseous RMS with confirmed FUS / EWSR1 – TFCP2 or MEIS – NCOA2 fusions have been reported 5–14 . Whereas intraosseous RMSs with MEIS – NCOA2 fusions have been reported exclusively in the pelvic bones, RMSs with TFCP2 fusions show a striking predilection for a craniofacial intraosseous location, although large series are not yet available.…”

Section: Introductionmentioning

confidence: 99%

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

Suurmeijer²,

Agaram

et al. 2021

Histopathology

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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.

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Section: Introductionmentioning

confidence: 99%

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

Suurmeijer²,

Agaram

et al. 2021

Histopathology

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“…6 Included in this group are infantile/congenital SpRMS with VGLL2-associated gene fusions that has a very good prognosis, an aggressive MYOD-1 mutant Sp/Scl RMS with a poor outcome that affects children and adults, and aggressive SpRMS with FET(EWSR1)-TFCP2 rearrangements; the latter tumor may contain a round cell component, and often originates in bone. [7][8][9] More recently, two cases of primary intraosseous aggressive RMSs consisting of spindle cells arising in the iliac bone harboring a novel MEIS1-NCOA2 gene fusion have been published. 10 Herein, we describe the clinicopathological characteristics of three SpRMS that have unusual gene fusions and discuss the spectrum of SpRMS.…”

Section: Introductionmentioning

confidence: 99%

Novel fusion genes in spindle cell rhabdomyosarcoma: The spectrum broadens

Montoya-Cerrillo

Díaz-Pérez

Torres

et al. 2021

Genes Chromosomes & Cancer

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Rhabdomyosarcoma (RMS) encompasses a heterogeneous group of tumors with striated muscle differentiation. RMSs are classified as alveolar, embryonal, spindle cell/sclerosing, and pleomorphic types and molecular analysis of these tumors has identified aberrations that are useful in their further subclassification. Spindle cell rhabdomyosarcoma (SpRMS) is uncommon and has been described with VGLL2 fusions, EWSR1/FUS-TFCP2 rearrangements, and myoD1 mutations-the mutations are associated with significantly different prognoses. In addition, the NCOA2-MEIS1 fusion gene was recently described in two primary intraosseous RMS that contained spindle cell components. Herein, we report three cases of SpRMS harboring different novel fusion genes, one possessing EP300-VGLL3, a second with NCOA2-MEIS1 and CAV1-MET, and the third case had HMGA2-NEGR1 and multiple amplified genes.

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“…A RNA based approach was used as described in detail in the material -methods section and the study revealed the FUS-TFCP2 fusion. The case was diagnosed as "epithelioid and spindle cell rhabdomyosarcoma with FUS-TFCP2 fusion" in accordance with the morphological, immunohistochemical and molecular findings (15,16).…”

Section: Rare Fusions In Rare Tumors Either For Diagnosis or For Treatmentmentioning

confidence: 67%

What would next generation sequencing bring to the diagnosis and treatment of sarcomas? a series of 20 cases, a single institutionÂ’s experience

Kulaç¹,

Bulutay²,

Mericoz³

2021

TJPATH

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Objective: Soft tissue tumors comprise a small proportion of a pathologist's routine practice. Although morphology and immunohistochemistry are quite helpful for diagnosing these tumors, many require molecular tests. Fluorescence in-situ hybridization has been the most commonly used method for the detection of specific genomic alteration, but next generation sequencing (NGS) could be more informative in many ways.Here we present our targeted NGS experience on soft tissue tumors with a series of 20 cases. Material and Method:The Laboratory Information System (LIS) was screened for soft tissue tumors that had been sequenced by NGS (between January 2018 -February 2021). 20 consecutive cases were included in the study. All cases were sequenced using a commercial targeted sequencing panel designed for soft tissue tumors. Results:We were able to run a reliable sequencing study for 16 (80%) of the cases but 4 (20%) of them failed in quality tests. We have found pathogenic alterations in 12 (60%) of the cases. The most common alterations were EWSR1 fusions, FLI1 being the most common partner. NGS results drastically changed the initial diagnosis, and thus the treatment modalities, in 3 cases (15%): the case with ETV6-NTRK3 fusion, the case with FUS-TFCP2 fusion, and the case of rhabdomyosarcoma (RMS) that was favored to be of the alveolar subtype and turned out to lack FOXO1 fusions. Conclusion:A targeted NGS panel is robust and very informative. It not only allows pathologists to further specify and/or confirm their diagnosis but it could also play an important role in predicting the outcome.

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Epithelioid and spindle cell rhabdomyosarcoma with FUS-TFCP2 or EWSR1-TFCP2 fusion: report of two cases

Cited by 49 publications

References 37 publications

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

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

Novel fusion genes in spindle cell rhabdomyosarcoma: The spectrum broadens

What would next generation sequencing bring to the diagnosis and treatment of sarcomas? a series of 20 cases, a single institutionÂ’s experience

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