PLAG1-Driven Lipoblastomatosis: Diagnostic Insights from a Case Report and Literature Review

Lipoblastomatosis is a rare benign adipocytic tumour of infancy and early childhood, characterized by rapid growth. Diagnosis is challenging, owing to tumour heterogeneity and overlap with other pediatric soft-tissue neoplasms. PLAG1 rearrangement is the defining molecular hallmark, with an expanding list of fusion partners. We report a case of a 1-year-old child with a firm, nonmobile mass in the right thigh, which on CECT was deep-seated and heterogeneously enhanced. Gross evaluation of the excision specimen demonstrated an ill-circumscribed soft tissue mass. Histopathologically, the tumour showed myxoid nodules with primitive mesenchymal spindle-cell areas, and peripheral adipose tissue containing scattered lipoblasts, features suggestive of lipoblastomatosis. The IHC study showed S100 and CD34 positivity in adipocytes, and desmin and myogenin positivity in spindle-cell components. Molecular testing by NGS revealed a COL1A2::PLAG1 gene fusion, thus further establishing the diagnosis. Differentials such as myxoid liposarcoma, fibrous hamartoma of infancy, and infantile fibrosarcoma also harbour distinct genetic drivers, including EWSR1::DDIT3, EGFR exon 20 alterations, and ETV6::NTRK3, respectively. This case highlights the diagnostic workup of soft-tissue tumours and underscores the importance of integrating histopathology, IHC, and molecular testing. Identification of PLAG1 rearrangement is crucial for confirming the diagnosis. With the growing number of molecularly defined soft-tissue tumours of diagnostic and prognostic significance, incorporating molecular analysis is essential in the evaluation of soft-tissue lesions.