Clinicopathological characteristics and genetic variations of uterine tumours resembling ovarian sex cord tumours

Abstract

Aims To investigate the clinicopathological and molecular characteristics of uterine tumours resembling ovarian sex cord tumours (UTROSCTs) and the value of molecular diversity in the clinical diagnosis and treatment. Methods Five patients with UTROSCT were enrolled, and their clinical data, pathological morphologies, immunophenotypes and molecular features were analysed. Fluorescence in situ hybridisation for NCOA1, NCOA2, NCOA3, JAZF1 and PHF1 and next-generation sequencing for 27 homologous recombination/repair (HRR) pathway genes were performed on five and three UTROSCT specimens, respectively. Results All five patients were treated for abnormal uterine bleeding and grossly presented with intrauterine polyps. Under a microscope, tumour cells grew diffusely and presented a cordlike arrangement and glandular duct-like structures, with nuclei ranging from round to oval, vesicular chromatin and visible nucleoli in some cases. The mitotic count was less than 3/10 high-power fields. Immunohistochemistry showed sex cord, epithelial cell and smooth muscle cell biomarkers and diffuse, strong staining for B cell lymphoma-2 (BCL-2). NCOA1 and NCOA3 rearrangements were identified in 80% (4/5) of the cases. JAZF1 and PHF1 rearrangements were not detected in any of five patients. HRR pathway gene mutations were detected in all three patients, including FANCE, ATR and ARID1A mutations in one case each. Conclusion UTROSCT is a rare mesenchymal tumour, and biopsy specimens are easily misdiagnosed. UTROSCT diagnosis requires the combined use of biomarkers and molecular detection. BCL-2 has potential diagnostic value as a marker. UTROSCT can have mutations related to the HRR pathway, suggesting that this tumour type may be sensitive to platinum/poly (ADP-ribose) polymerase inhibitors.