Publication

The histologic spectrum of soft tissue spindle cell tumors with NTRK3 gene rearrangements

Suurmeijer, A. J., Dickson, B. C., Swanson, D., Zhang, L., Sung, Y-S., Huang, H-Y., Fletcher, C. D. & Antonescu, C. R., Nov-2019, In : GENES CHROMOSOMES & CANCER. 58, 11, p. 739-746 8 p.

Research output: Contribution to journalArticleAcademicpeer-review

APA

Suurmeijer, A. J., Dickson, B. C., Swanson, D., Zhang, L., Sung, Y-S., Huang, H-Y., ... Antonescu, C. R. (2019). The histologic spectrum of soft tissue spindle cell tumors with NTRK3 gene rearrangements. GENES CHROMOSOMES & CANCER, 58(11), 739-746. https://doi.org/10.1002/gcc.22767

Author

Suurmeijer, Albert J. ; Dickson, Brendan C. ; Swanson, David ; Zhang, Lei ; Sung, Yun-Shao ; Huang, Hsuan-Ying ; Fletcher, Christopher D. ; Antonescu, Cristina R. / The histologic spectrum of soft tissue spindle cell tumors with NTRK3 gene rearrangements. In: GENES CHROMOSOMES & CANCER. 2019 ; Vol. 58, No. 11. pp. 739-746.

Harvard

Suurmeijer, AJ, Dickson, BC, Swanson, D, Zhang, L, Sung, Y-S, Huang, H-Y, Fletcher, CD & Antonescu, CR 2019, 'The histologic spectrum of soft tissue spindle cell tumors with NTRK3 gene rearrangements', GENES CHROMOSOMES & CANCER, vol. 58, no. 11, pp. 739-746. https://doi.org/10.1002/gcc.22767

Standard

The histologic spectrum of soft tissue spindle cell tumors with NTRK3 gene rearrangements. / Suurmeijer, Albert J.; Dickson, Brendan C.; Swanson, David; Zhang, Lei; Sung, Yun-Shao; Huang, Hsuan-Ying; Fletcher, Christopher D.; Antonescu, Cristina R.

In: GENES CHROMOSOMES & CANCER, Vol. 58, No. 11, 11.2019, p. 739-746.

Research output: Contribution to journalArticleAcademicpeer-review

Vancouver

Suurmeijer AJ, Dickson BC, Swanson D, Zhang L, Sung Y-S, Huang H-Y et al. The histologic spectrum of soft tissue spindle cell tumors with NTRK3 gene rearrangements. GENES CHROMOSOMES & CANCER. 2019 Nov;58(11):739-746. https://doi.org/10.1002/gcc.22767


BibTeX

@article{fb563833b52f4ba0b333f1b3de9efb3f,
title = "The histologic spectrum of soft tissue spindle cell tumors with NTRK3 gene rearrangements",
abstract = "NTRK3-rearranged tumors other than infantile fibrosarcomas (IFSs) harboring the canonical ETV6-NTRK3 fusions are uncommon, and include mainly inflammatory myofibroblastic tumors and gastrointestinal stromal tumors. Herein, we describe an additional subset of seven tumors sharing NTRK3 gene rearrangements. The cohort included five females and two males (age range 1-67 years). Tumors were located in extremities, trunk, retroperitoneum, or intra-abdominal. In all tumors, fluorescence in situ hybridization (FISH) revealed rearrangements in NTRK3 accompanied by NTRK3 amplification in two cases. In three cases, RNA sequencing identified a fusion transcript composed of NTRK3 exon 14 fused to ETV6, TFG, and TPM4, respectively, retaining the NTRK3 kinase domain. All tumors were positive for pan-TRK by immunohistochemistry (IHC). Two cases showed low- to intermediate-grade histology composed of monomorphic spindle cells arranged in a patternless architecture, stromal bands, and perivascular rings of hyalinized collagen and coexpression of S100 and CD34. The remaining five cases were high-grade fascicular monomorphic spindle cell sarcomas, morphologically somewhat reminiscent of either malignant peripheral nerve sheath tumors (MPNSTs) or fibrosarcomas (FSs). Two high-grade NTRK3 sarcomas showed aggressive clinical behavior with development of lung metastases. Identification of high-grade NTRK3-rearranged sarcomas is clinically important, since the development of selective NTRK inhibitors has opened new avenues for targeted therapy. Although IHC for pan-TRK can be applied as a screening tool, molecular studies are recommended for a conclusive diagnosis of NTRK-rearranged neoplasms.",
keywords = "fibrosarcoma, fusion, malignant peripheral nerve sheath tumor, NTRK3, sarcoma, SOLITARY FIBROUS TUMOR, FUSIONS, LAROTRECTINIB, EXPRESSION, SUBSET",
author = "Suurmeijer, {Albert J.} and Dickson, {Brendan C.} and David Swanson and Lei Zhang and Yun-Shao Sung and Hsuan-Ying Huang and Fletcher, {Christopher D.} and Antonescu, {Cristina R.}",
year = "2019",
month = "11",
doi = "10.1002/gcc.22767",
language = "English",
volume = "58",
pages = "739--746",
journal = "GENES CHROMOSOMES & CANCER",
issn = "1045-2257",
publisher = "WILEY",
number = "11",

}

RIS

TY - JOUR

T1 - The histologic spectrum of soft tissue spindle cell tumors with NTRK3 gene rearrangements

AU - Suurmeijer, Albert J.

AU - Dickson, Brendan C.

AU - Swanson, David

AU - Zhang, Lei

AU - Sung, Yun-Shao

AU - Huang, Hsuan-Ying

AU - Fletcher, Christopher D.

AU - Antonescu, Cristina R.

PY - 2019/11

Y1 - 2019/11

N2 - NTRK3-rearranged tumors other than infantile fibrosarcomas (IFSs) harboring the canonical ETV6-NTRK3 fusions are uncommon, and include mainly inflammatory myofibroblastic tumors and gastrointestinal stromal tumors. Herein, we describe an additional subset of seven tumors sharing NTRK3 gene rearrangements. The cohort included five females and two males (age range 1-67 years). Tumors were located in extremities, trunk, retroperitoneum, or intra-abdominal. In all tumors, fluorescence in situ hybridization (FISH) revealed rearrangements in NTRK3 accompanied by NTRK3 amplification in two cases. In three cases, RNA sequencing identified a fusion transcript composed of NTRK3 exon 14 fused to ETV6, TFG, and TPM4, respectively, retaining the NTRK3 kinase domain. All tumors were positive for pan-TRK by immunohistochemistry (IHC). Two cases showed low- to intermediate-grade histology composed of monomorphic spindle cells arranged in a patternless architecture, stromal bands, and perivascular rings of hyalinized collagen and coexpression of S100 and CD34. The remaining five cases were high-grade fascicular monomorphic spindle cell sarcomas, morphologically somewhat reminiscent of either malignant peripheral nerve sheath tumors (MPNSTs) or fibrosarcomas (FSs). Two high-grade NTRK3 sarcomas showed aggressive clinical behavior with development of lung metastases. Identification of high-grade NTRK3-rearranged sarcomas is clinically important, since the development of selective NTRK inhibitors has opened new avenues for targeted therapy. Although IHC for pan-TRK can be applied as a screening tool, molecular studies are recommended for a conclusive diagnosis of NTRK-rearranged neoplasms.

AB - NTRK3-rearranged tumors other than infantile fibrosarcomas (IFSs) harboring the canonical ETV6-NTRK3 fusions are uncommon, and include mainly inflammatory myofibroblastic tumors and gastrointestinal stromal tumors. Herein, we describe an additional subset of seven tumors sharing NTRK3 gene rearrangements. The cohort included five females and two males (age range 1-67 years). Tumors were located in extremities, trunk, retroperitoneum, or intra-abdominal. In all tumors, fluorescence in situ hybridization (FISH) revealed rearrangements in NTRK3 accompanied by NTRK3 amplification in two cases. In three cases, RNA sequencing identified a fusion transcript composed of NTRK3 exon 14 fused to ETV6, TFG, and TPM4, respectively, retaining the NTRK3 kinase domain. All tumors were positive for pan-TRK by immunohistochemistry (IHC). Two cases showed low- to intermediate-grade histology composed of monomorphic spindle cells arranged in a patternless architecture, stromal bands, and perivascular rings of hyalinized collagen and coexpression of S100 and CD34. The remaining five cases were high-grade fascicular monomorphic spindle cell sarcomas, morphologically somewhat reminiscent of either malignant peripheral nerve sheath tumors (MPNSTs) or fibrosarcomas (FSs). Two high-grade NTRK3 sarcomas showed aggressive clinical behavior with development of lung metastases. Identification of high-grade NTRK3-rearranged sarcomas is clinically important, since the development of selective NTRK inhibitors has opened new avenues for targeted therapy. Although IHC for pan-TRK can be applied as a screening tool, molecular studies are recommended for a conclusive diagnosis of NTRK-rearranged neoplasms.

KW - fibrosarcoma

KW - fusion

KW - malignant peripheral nerve sheath tumor

KW - NTRK3

KW - sarcoma

KW - SOLITARY FIBROUS TUMOR

KW - FUSIONS

KW - LAROTRECTINIB

KW - EXPRESSION

KW - SUBSET

U2 - 10.1002/gcc.22767

DO - 10.1002/gcc.22767

M3 - Article

VL - 58

SP - 739

EP - 746

JO - GENES CHROMOSOMES & CANCER

JF - GENES CHROMOSOMES & CANCER

SN - 1045-2257

IS - 11

ER -

ID: 98545365