Pleura-Based Lipomatous Neoplasm with RUNX1T1::PLAG1 Rearrangement and RB1 Gene Deletion

Abstract

Background

Lipoblastoma is a benign tumor arising from embryonic white fat, commonly observed in infancy and early childhood. It manifests in two pathologically identical forms: circumscribed and diffuse. Typically, it is found in the extremities, trunk, and head and neck regions. The genetic hallmark involves clonal rearrangements of the chromosomal region 8q11 > q13 (8q12). The oncogene PLAG1 (pleomorphic adenoma gene 1) is situated on band 8q12. PLAG1 gene rearrangements have been identified in various lipomatous tumors and, more recently, in a superficial spindle cell lipoma.

Here, we present the case of a 54-year-old gentleman with a sizable right pleural mass, histologically characterized as a spindle cell lipomatous tumor. Immunohistochemistry revealed diffuse expression of CD34 in spindle cells, mosaic staining of RB1, diffuse positivity for p16, and patchy positivity for desmin, while adipocytes were positive for S100. Remarkably, the next-generation sequencing assay unveiled a previously unreported RUNX1T1::PLAG1 fusion, in addition to RB1 gene deletion. The patient underwent excision of the right pleural mass. Based on morphology, location, immunohistochemistry, and molecular analysis, this results confirms pleural-based (deep seated) lipomatous tumor with features of lipoblastoma and spindle cell lipoma. This case introduces a unique pleural-based lipomatous tumor with a novel PLAG1 fusion partner, associated with RB1 gene deletion, further expanding the spectrum of genetic findings within this category of lipogenic neoplasms.