Comprehensive histopathologic and genomic analysis of a novel case of lipoblastoma-like tumour of the vulva demonstrating malignant behaviour

Abstract

Lipoblastoma-like tumour of the vulva (LLTV) is a rare soft tissue neoplasm with only nineteen reported cases to date. The clinical behaviour in all cases has been benign, with a small number of local recurrences and no incidences of metastasis described. We present an unusual case of LLTV that arose in a 16-year-old female who subsequently developed histologically identical lesions in the breast, chest wall and retroperitoneum, over the course of three and a half years. Our comprehensive histopathological analysis and molecular genetic studies supported the diagnosis of LLTV, with absence of DDIT3 rearrangement and absence of other specific diagnostic genetic events for any other soft tissue neoplasm. Whole exome sequencing was performed on the vulva, vulva recurrence, breast, and lung lesions and revealed a complex genome with striking similarity between the tumours. Multiple somatic mutations of interest were identified, including in MTOR and the TERT promoter, which enabled patient treatment with a specific inhibitor. To our knowledge, this is the first reported case of metastasising LLTV, and the first comprehensive genetic analysis of such a tumour.