PLAG1 ‐rearranged paediatric fibromyxoid tumour: clinicopathological, molecular and epigenetic analysis of 10 cases supporting a morphological spectrum with lipoblastoma

AIM: Paediatric PLAG1-rearranged fibromyxoid tumour (P-FMT) is an emerging soft-tissue neoplasm characterized by predominantly fibromyxoid morphology, minimal to absent adipocytic differentiation and consistent CD34 and desmin positivity. It is debated whether P-FMT represents a distinct entity or a morphological variant of lipoblastoma. We aim to better characterize P-FMT and assess its relationship with lipoblastoma. METHODS AND RESULTS: We assembled the largest cohort of P-FMT (n = 10) and performed comprehensive clinicopathological, molecular and epigenetic characterization. The cohort comprised five males and five females, aged 3 months to 10 years (median 4 years), with tumours arising in the extremities, trunk and neck. Histologically, all were well-demarcated lesions with bland fibroblastic spindle cells in collagenous to myxoid stroma; two cases focally contained mature adipocytes. All tumours expressed CD34 and desmin. PLAG1 rearrangements were confirmed by fluorescence in situ hybridization or molecular sequencing, with fusion partners identified as COL1A2 (n = 3), MEG3 (n = 2), BOC (n = 1), YWHAZ (n = 1), EEF1A1 (n = 1) and CHCHD7 (n = 1). DNA methylation profiling demonstrated that all P-FMTs grouped with lipoblastoma on hierarchical clustering and dimensionality reduction analysis and segregated from other mesenchymal tumours. Copy number profiles showed statistically significant chromosome 8 gain in both P-FMT and lipoblastoma. All cases with follow-up (median 22 months) demonstrated benign behaviour without recurrence. CONCLUSIONS: Our findings of morphological resemblance to fibroblastic lipoblastoma and multiple similarities to classic lipoblastoma, including identical immunophenotype, PLAG1 rearrangements with overlapping partners, common epigenetic signature and uniformly benign behaviour, support classification of P-FMT as a fibroblastic or minimally adipocytic subtype within the lipoblastoma spectrum, rather than a distinct entity.