Recurrent BRAF Gene Fusions in a Subset of Pediatric Spindle Cell Sarcomas: Expanding the Genetic Spectrum of Tumors with Overlapping Features with Infantile Fibrosarcoma

Yu-Chien Kao, Christopher D.M. Fletcher, Rita Alaggio, Leonard Wexler, Lei Zhang, Yun Shao Sung, Dicle Orhan, Wei Chin Chang, David Swanson, Brendan C. Dickson, Cristina R. Antonescu

研究成果: 雜誌貢獻文章

31 引文 斯高帕斯(Scopus)

摘要

Infantile fibrosarcomas (IFS) represent a distinct group of soft tissue tumors occurring in patients under 2 years of age and most commonly involving the extremities. Most IFS show recurrent ETV6-NTRK3 gene fusions, sensitivity to chemotherapy, and an overall favorable clinical outcome. However, outside these well-defined pathologic features, no studies have investigated IFS lacking ETV6-NTRK3 fusions, or tumors with the morphology resembling IFS in older children. This study was triggered by the identification of a novel SEPT7-BRAF fusion in an unclassified retroperitoneal spindle cell sarcoma in a 16-year-old female by targeted RNA sequencing. Fluorescence in situ hybridization screening of 9 additional tumors with similar phenotype and lacking ETV6-NTRK3 identified 4 additional cases with BRAF gene rearrangements in the pelvic cavity (n=2), paraspinal region (n=1), and thigh (n=1) of young children (0 to 3 y old). Histologically, 4 cases including the index case shared a fascicular growth of packed monomorphic spindle cells, with uniform nuclei and fine chromatin, and a dilated branching vasculature; while the remaining case was composed of compact cellular sheets of short spindle to ovoid cells. In addition, a minor small blue round cell component was present in 1 case. Mitotic activity ranged from 1 to 9/10 high power fields. Immunohistochemical stains were nonspecific, with only focal smooth muscle actin staining demonstrated in 3 cases tested. Of the remaining 5 BRAF negative cases, further RNA sequencing identified 1 case with EML4-NTRK3 in an 1-year-old boy with a foot IFS, and a second case with TPM3-NTRK1 fusion in a 7-week-old infant with a retroperitoneal lesion. Our findings of recurrent BRAF gene rearrangements in tumors showing morphologic overlap with IFS expand the genetic spectrum of fusion-positive spindle cell sarcomas, to include unusual presentations, such as older children and adolescents and predilection for axial location, thereby opening new opportunities for kinase-targeted therapeutic intervention.

原文英語
頁(從 - 到)28-38
頁數11
期刊American Journal of Surgical Pathology
42
發行號1
DOIs
出版狀態已發佈 - 一月 1 2018
對外發佈Yes

ASJC Scopus subject areas

  • Anatomy
  • Surgery
  • Pathology and Forensic Medicine

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