Uterine Leiomyosarcoma

Secondary morphological changes in uterine leiomyosarcomas associated with hormone therapy pose significant diagnostic challenges. Next generation sequencing can provide valuable evidence for the diagnosis of morphologically challenging cases of leiomyosarcoma in clinical practice.

P2, N=72, Active, not recruiting, City of Hope Medical Center | Trial completion date: Oct 2025 --> Sep 2026 | Trial primary completion date: Oct 2025 --> Sep 2026

Metastasis to the thyroid gland is an exceedingly rare phenomenon and can be difficult to differentiate from primary thyroid malignancy based on clinical presentation especially when the primary site is unknown. The cytomorphological features may also be diagnostically challenging. Detailed clinical and radiological information combined with astute analysis of morphological features as well as the judicious application of immunomarker panels may be valuable. Patient prognosis and management are greatly influenced by early diagnosis and differentiating metastasis from primary malignancies.

While these findings validate the sensitivity of an IHC-based diagnostic panel in confirming the vast majority of LMS diagnoses, a subset, which more likely shows ambiguous diagnostic features, probably requires genomic testing. The previously proposed morphologic criteria seem to provide a robust prognostic stratification.

These cases expand the landscape of FOXO1-rearranged neoplasms and describe a potential new uterine mesenchymal entity. Further study of additional cases is needed to establish whether these rearrangements truly represent an initiating event for a distinct subset of uterine sarcomas, or whether FOXO1 rearrangements simply represent an additional noninitiating/nondriver event within other established tumor types.

The integration of checkpoint inhibitors with targeted immunomodulation and personalized therapeutic approaches may improve treatment efficacy. Future research should focus on refining patient selection criteria, enhancing macrophage-targeted therapies, and optimizing immune profiling techniques to maximize therapeutic outcomes for uterine leiomyosarcoma.

Although trabectedin-olaparib combination reached the prespecified threshold for statistical significance for PFS (p<0.10), the benefit was marginal in the all-comers STS population. Nonetheless, patients affected by PARP1-expressing STS and uterine leiomyosarcoma derived substantial benefit from the combination, supporting further histology- and biomarker-driven investigation in these settings.

P2, N=23, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Mar 2026 --> Nov 2026

ATRX status may serve as a potential biomarker for prognosis and therapeutic stratification. Future clinical trials investigating epigenetic therapies could offer novel treatment strategies for ATRX-deficient sarcomas.

In cancer treatment, contrast-enhanced MRI is useful for identifying the size and location of tumor masses. However, contrast-enhanced MRI does not lead to the diagnosis of tumor masses. Therefore, early blood tests and tumor biopsy results are important for differential diagnosis and early treatment decisions.

Emerging therapeutic approaches aim to restore the tumor-suppressive miRNAs or inhibit oncogenic ones using mimics or antagomiRs. Overall miRNAs represent critical regulators of uLMS pathogenesis and hold significant potential for precision diagnosis, prognostication, and targeted therapy, though larger validation studies and improved delivery systems are required before clinical translation.

P2, N=17, Active, not recruiting, Stanford University | Recruiting --> Active, not recruiting | N=25 --> 17 | Trial completion date: Dec 2025 --> May 2026 | Trial primary completion date: Dec 2025 --> May 2026