Infantile fibrosarcoma (IFS) is a soft tissue tumour of intermediate malignant potential that commonly affects the extremities of young children and is characterised by an ETV6::NTRK3 fusion.1 2

Recurrent copy number changes, including the gain of chromosomes 8, 17 and 20, have been reported in IFS,3–5 but pathogenic mutations in other pathways are rare in this tumour type.6

We previously reported on a 5-year-old male patient with IFS of the right gluteal region/pelvis treated with chemotherapy, radiotherapy and TRK inhibition who developed metastatic, progressive disease with multiple acquired mutations, including TP53, SUFU and an NTRK F617L gatekeeper mutation.7 Due to acquired larotrectinib resistance, he was started on repotrectinib (according to phase I/II study NCT04094610 protocol).8 In this follow-up report, we describe the transformation (dedifferentiation) of the patient’s IFS to a high-grade osteosarcoma.

The patient initially presented at 5 months of age with a mass on the right buttocks. Histological assessment of the ultrasound-guided biopsy tissue showed a cellular spindle cell neoplasm, which was positive for ETV6 rearrangement by fluorescence in situ hybridisation (FISH) and had an ETV6::NTRK3 fusion identified by reverse transcriptase PCR (RT-PCR), supporting a diagnosis of IFS (figure 1A).

Morphological and phenotypic progression of a case of recurrent and metastatic infantile fibrosarcoma with multiple acquired mutations and dedifferentiation to high-grade osteosarcoma. Initial biopsy showed a well-vascularised malignant fibroblastic neoplasm composed of a monomorphic population of spindled cells with eosinophilic cytoplasm and round-to-elongated nuclei (A); p53 stain was positive in less than 10% of tumour cell nuclei (G). Post-therapy sample (17 months from initial diagnosis) showed dense collagenisation and rare atypical cells (B); p53 stain was positive in rare tumour cell nuclei (H). Increased cytological atypia over time and p53 overexpression in nearly all tumour nuclei were seen on specimens taken at 36 …