Recurrent RET Gene Fusions in Pediatric Spindle Mesenchymal Neoplasms

Recurrent RET Gene Fusions in Pediatric Spindle Mesenchymal Neoplasms:

Abstract

Aims

The classification of pediatric spindle mesenchymal tumors is evolving, and the spectrum of so‐called “infantile fibrosarcoma” has expanded to include tumors with NTRK, BRAF, and MET gene fusions. RET‐rearranged pediatric spindle cell neoplasms are an emerging group; there is sparse literature on their clinical, pathologic and genetic features, and their nosologic place in the canon of soft tissue tumors is uncertain. Herein, we report five RET‐rearranged pediatric spindle cell tumors with fusion partners MYH10, KIAA1217, and CLIP2.

Methods and Results

Tumors occurred in the pelvic region, paraspinal region, kidney, and subcutaneous tissue of hand and abdomen. Patients' age ranged from 6 months to 13 years (median 1 year). Tumors were composed of monomorphic spindled cells arranged in a fascicular pattern. Lesional cells had minimally atypical ovoid or tapered nuclei and pale cytoplasm with indistinct borders. Necrosis was not identified. Mitoses numbered 3‐12 per 10 HPF. Cases showed inconsistent and variable expression of S100, CD34 and SMA. Clinical behavior ranged from small lesions potentially cured by simple resection to large lesions exhibiting metastasis yet responsive to kinase inhibitor therapy.

Conclusions

Our findings help to define RET‐rearranged spindle cell tumors. Although it is likely these tumors comprise part of the morphologic and clinical spectrum of IFS, identification of RET gene alteration is important for its unique therapeutic implications.