Uterine Leiomyosarcoma

P2, N=30, Not yet recruiting, Dana-Farber Cancer Institute

This case emphasizes including GIST in the differential diagnosis of large pelvic masses, even when imaging suggests a gynecologic origin. Definitive diagnosis relies on a multidisciplinary approach to ensure accurate classification and appropriate oncologic therapy.

P2, N=48, Recruiting, M.D. Anderson Cancer Center | Not yet recruiting --> Recruiting

Mgenes modulate ULMS's TIME, offering immunotherapeutic targets. This study advances ULMS molecular/immune understanding for translational research.

P2/3, N=73, Active, not recruiting, National Cancer Institute (NCI) | N=190 --> 73 | Trial completion date: Mar 2030 --> Jan 2027

The strong and diffuse staining pattern of desmin and SMA can be very helpful in distinguishing leiomyosarcoma from its spindle cell mimics. A novel finding is that SMA positivity was identified in malignant endothelium. Immunolabelling for CD34 and KIT provides reliable markers for vascular neoplasms and GISTs. Vimentin does not allow to distinguish between different mesenchymal malignancies in guinea pigs. Occasional positivity for keratins and S100 points to potential pitfalls and emphasised the need for a panel of immunohistochemical stains in the investigation of mesenchymal tumours.

Although PARP inhibitors have been utilized in BRCA-mutated ULMS, this case underscores the potential efficacy of platinum-based chemotherapy as an alternative treatment strategy. Furthermore, a therapeutic approach integrating platinum-based chemotherapy followed by PARP inhibitor maintenance, similar to that employed in platinum-sensitive ovarian cancer, warrants further investigation.

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.