Atypical spindle cell/pleomorphic lipomatous tumour: a clinicopathologic, immunohistochemical and molecular study of 55 cases, highlighting TP53 gene alterations as a genetic hallmark of atypical pleomorphic lipomatous tumour.

Aims: Atypical spindle cell lipomatous tumour (ASLT) and atypical pleomorphic lipomatous tumour (APLT) have been grouped together under the umbrella designation atypical spindle cell/pleomorphic lipomatous tumour (ASPLT) in the 2020 edition of the World Health Organization (WHO) Classification of Soft Tissue and Bone Tumours. They are thought to exist on a morphologic spectrum and share similar clinicopathologic and biological characteristics. The aim of this study was to further explore the genetic background of ASLTs and APLTs by employing DNA-based next-generation sequencing and immunohistochemistry, with a specific focus on the TP53 gene.

Methods and results: Using DNA-based NGS and immunohistochemistry, TP53 alterations were identified in 20 out of 21 APLT cases (95%). This is in contrast to the ASLT cases, in which no TP53 alterations could be observed. Among APLT cases with an abnormal p53 immunohistochemical profile and successful DNA NGS testing, 92% (12 of 13 cases) harboured a TP53 alteration.

Conclusions: APLTs predominantly harbour a TP53 alteration in contrast to ASLT cases. Our findings support the classification of APLT as a distinct (sub)entity within a spectrum that overlaps with ASLT, and it remains to be determined whether the broader term 'ASPLT' will hold up. Furthermore, p53 immunostaining proved to be a potentially valuable diagnostic tool, aiding pathologists in differentiating between ASLT and APLT.