Malignant struma ovarii: Advances in molecular pathogenesis, classification, diagnosis and treatment

Malignant struma ovarii (MSO) is an extremely rare ovarian teratoma containing malignant thyroid tissue, typically presenting in middle-aged women. Molecularly and histologically, MSO mirrors thyroid carcinoma and includes analogous subtypes as defined in the 2022 WHO classification: 'BRAF-like' tumours (commonly driven by BRAF^V600E mutations or kinase fusions) and 'RAS-like' tumours (driven by mutations in the RAS pathway), along with rare high-grade variants with aggressive behaviour. Next-generation sequencing shows that MSO harbours a mutational spectrum closely matching primary thyroid cancers. Genotype-guided targeted therapies (e.g. BRAF/MEK inhibitors, selective RET or NTRK inhibitors and multikinase inhibitors) are emerging as promising options for advanced or radioiodine-refractory cases. Surgical excision of the ovarian tumour is typically curative for localized disease. Thyroidectomy followed by radioactive iodine (RAI) is reserved for high-risk tumours. Long-term surveillance is essential, as late recurrences can occur. In this first comprehensive review of MSO, we integrate our own case series findings with published data to provide an up-to-date synthesis of its clinicopathologic spectrum and management.