Leiomyosarcoma

These findings highlight the clinical relevance of immune infiltration in retroperitoneal DDLPS and LMS. Moreover, they support the rationale for further exploration of the immune architecture for prognostic biomarkers and development of targeted immunotherapeutic strategies to improve the clinical outcomes of the patients.

P2/3, N=140, Completed, National Cancer Institute (NCI) | Active, not recruiting --> Completed | Trial completion date: Dec 2026 --> Mar 2026

Primary breast leiomyosarcoma is a rare entity that remains diagnostically challenging. Immunohistochemistry is essential for accurate diagnosis, and optimal management requires a dedicated multidisciplinary approach.

Histological subtype, stage, and coagulative necrosis were critical prognostic factors in uterine sarcoma. The findings suggest that vigilant pulmonary surveillance and further investigation into tailored therapeutic strategies may be warranted-including endocrine therapy for hormone-receptor-positive tumors, immunotherapy for high-grade ESS, and PARP inhibitors for uLMS. However, these hypotheses require thorough preclinical and clinical validation. Additionally, caution should be exercised to avoid overtreatment of chemotherapy in early-stage uLMS.

Histologic subtyping of unclassified sarcomas predicted prognosis and therapeutic response. We propose universal MMR IHC screening of (1) PRMS, (2) uterine LMS, (3) unclassified/UPS, and (4) any sarcoma in a patient with a personal or family history of Lynch syndrome.

Our data show that GPNMB is highly expressed by LAM in the lung, with immunohistochemistry performance similar to cathepsin K but superior to traditional melanocytic markers. GPNMB may be useful to confirm diagnostically challenging cases of LAM and to exclude most non-PEComatous mimics presenting with cystic lung metastases, but metastatic dermatofibromas can be a diagnostic pitfall.

In short, attention is on translating PI3K/AKT inhibitors into clinical practice to provide patients with new targeted therapy. This review summarizes the molecular mechanisms underlying LMS pathogenesis and discusses emerging therapeutic strategies to improve clinical outcomes.

This report, representing the first documented case of LLMS from Central Asia, contributes to the limited global experience with this rare tumor. Our review identified four additional LLMS cases published between 2021 and 2024, totaling five recent reports including the present case. Collectively, these demonstrate persistent male predominance, glottic and supraglottic predilection, and survival outcomes consistent with previous observations. Complete surgical excision remains the cornerstone of therapy, while multidisciplinary-guided adjuvant treatment may benefit selected high-grade or high-risk patients. Continued accumulation and molecular characterization of cases are needed to refine prognostic assessment and optimize management strategies.

P1, N=85, Terminated, Boundless Bio, Inc. | Trial completion date: Mar 2027 --> Mar 2026 | Active, not recruiting --> Terminated | Trial primary completion date: Sep 2026 --> Mar 2026; Decision was made to halt the study based on overall clinical experience and market considerations. This decision was not driven by any safety signal.

P1, N=15, Not yet recruiting, M.D. Anderson Cancer Center

P2/3, N=345, Active, not recruiting, Pharma Mar S.A. | Recruiting --> Active, not recruiting

In xenografts, atorvastatin suppressed ULMS tumor growth by ~50% with minimal toxicity, as evidenced by normal serum ALT and creatinine levels and preserved organ histology. These findings identify protein geranylgeranylation as a novel therapeutic vulnerability in ULMS and support statin repurposing as a promising treatment strategy.