Expanding the Molecular Genetic Spectrum of Bone and Soft Tissue Fibrosarcomas: An Institutional Experience

• Published in: International journal of surgical pathology Vol. 30; no. 2; p. 145
• Main Authors: Leckey, Jr, Bruce D, John, Ivy, Wald, Abigail, Naous, Rana
• Format: Journal Article
• Language: English
• Published: United States 01.04.2022
• Subjects: Biomarkers, Tumor - genetics; Female; Fibrosarcoma - diagnosis; Fibrosarcoma - genetics; Fibrosarcoma - pathology; Humans; Male; Middle Aged; Molecular Biology; Sarcoma - pathology; Soft Tissue Neoplasms - diagnosis; Soft Tissue Neoplasms - genetics; Soft Tissue Neoplasms - pathology; fusion; FNDC3B-PIK3CA; Fibrosarcoma; CDKN2A/B; BRAF; NTRK
• ISSN: 1940-2465
• DOI: 10.1177/10668969211037861

Fibrosarcomas, once comprising the majority of unclassifiable spindle-cell sarcomas, are now regarded as a diagnosis of exclusion. Prompted by an index report of neurotrophic receptor tyrosine kinase fusion in fibrosarcomas by Yamazaki et al bone/soft tissue tumors diagnosed as fibrosarcoma at our institution were evaluated in an attempt to expand the genetic spectrum of fibrosarcomas and identify therapeutically targetable cases. Institutional archives were searched for cases diagnosed as "fibrosarcoma" involving bone/soft tissue from 2000 to present. Twenty-one cases meeting inclusion criteria were identified, 10 of which had formalin-fixed paraffin-embedded tissue available for molecular testing. One case, at the submitting clinician's request, underwent outside deoxyribonucleic acid/ribonucleic acid (DNA/RNA) sequencing while the 9 remaining cases underwent in-house next-generation sequencing RNA fusion analysis. At the time of diagnosis the mean age was 54.5 (range 14-88) with a male to female ratio of 1.5:1. Locations included soft tissue of the lower extremity (3), trunk (2), pelvis (2), head (1), upper extremity (1), and bone (1). Of the 10 cases, 1 demonstrated an gene fusion and 1 demonstrated a p.G469A mutation and loss. In conclusion, our study demonstrated gene fusions in 1 (10%) of 10 fibrosarcomas diagnosed at our institution in the past 20 years, including gene fusion. Additionally, 1 case harbored (p.G469A) mutation and loss with no evidence of gene fusion. rearrangements were not detected. The significance of these molecular aberrations is presently unclear and future studies are needed to establish whether these findings carry any clinicopathologic significance.