The diagnosis of leiomyosarcoma (LMS) presents significant challenges due to overlapping features with other mesenchymal tumors, particularly leiomyomas. A study by Alves-Vale proposed an immunohistochemical algorithm aimed at differentiating LMS from leiomyomas with bizarre nuclei (LM-BN) and fumarate hydratase-deficient leiomyomas (FH-LM). This algorithm leverages the genomic landscape of these tumors to enhance diagnostic accuracy, addressing the complexities that arise from the histological similarities between these entities (ref: Alves-Vale doi.org/10.1111/his.15420/). In another investigation, Zhang utilized contrast-enhanced endoscopic ultrasonography (CE-EUS) to identify a 7 cm mass in the inferior vena cava (IVC), demonstrating that CE-EUS can effectively reveal hypoechoic lesions indicative of LMS, thus providing a non-invasive diagnostic tool (ref: Zhang doi.org/10.1055/a-2534-3191/). Xu further corroborated these findings by analyzing imaging features of IVC LMS, reporting that a heterogeneous mass with progressive enhancement on contrast-enhanced CT scans was a strong indicator of the disease, with 61.9% of patients exhibiting these characteristics (ref: Xu doi.org/10.3389/fonc.2025.1442674/). Together, these studies underscore the importance of advanced imaging techniques and immunohistochemical strategies in the accurate diagnosis of LMS.

Treatment strategies for leiomyosarcoma (LMS) have evolved, particularly regarding the use of chemotherapeutic agents. A propensity score-matched analysis by Berclaz compared the efficacy of doxorubicin combined with dacarbazine (AD) versus doxorubicin with ifosfamide (AI), both in conjunction with regional hyperthermia (RHT). The results indicated that the AD + RHT regimen significantly improved progression-free survival (PFS) with a hazard ratio of 0.32, suggesting a more favorable outcome for patients receiving this combination (ref: Berclaz doi.org/10.1002/cam4.70655/). Additionally, Sobczuk's retrospective analysis highlighted the role of trabectedin in treating patients with liposarcoma and LMS, noting that long-term outcomes were comparable to other studies, thus reinforcing the drug's utility in advanced cases (ref: Sobczuk doi.org/10.1038/s41598-025-89977-z/). Furthermore, the updated clinical practice guidelines from the Korean Society of Gynecologic Oncology emphasized the combination of doxorubicin and trabectedin for metastatic or recurrent unresectable LMS, reflecting a consensus on the treatment's effectiveness based on recent randomized controlled trials (ref: Hwang doi.org/10.3802/jgo.2025.36.e71/). These findings collectively advocate for a tailored approach to LMS treatment, integrating both established and emerging therapies.

Molecular and genetic research has provided critical insights into the pathogenesis and classification of leiomyosarcoma (LMS). The Rare Gynecologic Sarcoma Study, which analyzed 379 uterine sarcomas, revealed that low-grade endometrial stromal sarcomas (LG-ESS) frequently harbor recurrent fusions in 75.9% of cases, while high-grade endometrial stromal sarcomas (HG-ESS) showed a 43.7% occurrence of similar genetic alterations. This underscores the diagnostic and prognostic significance of molecular testing in differentiating between various uterine sarcomas, including LMS (ref: Dundr doi.org/10.1016/j.labinv.2025.104092/). In a separate study, Yang explored the expression of extra spindle pole bodies like 1 (ESPL1) in LMS, utilizing bioinformatics to analyze data from The Cancer Genome Atlas. The findings suggested that dysregulation of ESPL1 may play a role in the biology of LMS, highlighting the potential for targeted therapies based on molecular profiles (ref: Yang doi.org/10.25259/Cytojournal_178_2024/). Together, these studies illustrate the importance of molecular characterization in understanding LMS and developing personalized treatment strategies.

Clinical guidelines for the management of leiomyosarcoma (LMS) have been updated to reflect the latest evidence-based practices. The Korean Society of Gynecologic Oncology's recent guidelines emphasize the integration of new treatment modalities, particularly the combination of doxorubicin and trabectedin for patients with metastatic or recurrent unresectable LMS. This recommendation is grounded in significant survival benefits observed in recent randomized controlled trials, reinforcing the need for clinicians to adopt these updated protocols in practice (ref: Hwang doi.org/10.3802/jgo.2025.36.e71/). The guidelines also highlight the importance of multidisciplinary approaches in the management of LMS, advocating for collaboration among oncologists, pathologists, and radiologists to ensure comprehensive care. By incorporating the latest research findings into clinical practice, these guidelines aim to improve patient outcomes and standardize treatment approaches across different healthcare settings.

Immunohistochemical and histopathological studies play a pivotal role in the diagnosis and differentiation of leiomyosarcoma (LMS) from other sarcomas. Alves-Vale's research introduced a tailored immunohistochemistry algorithm designed to address the diagnostic challenges posed by leiomyomas with bizarre nuclei and fumarate hydratase deficiency, which can mimic LMS. This algorithm is based on the genomic landscape of these tumors, aiming to enhance diagnostic accuracy and reduce misclassification (ref: Alves-Vale doi.org/10.1111/his.15420/). Additionally, a study by Tasar Kapakli evaluated the expression of SOX11 in various sarcomas, including LMS, finding that SOX11 was positive in 58% of rhabdomyosarcomas and 67% of malignant peripheral nerve sheath tumors, suggesting its potential as a diagnostic marker (ref: Tasar Kapakli doi.org/10.1016/j.anndiagpath.2025.152447/). These findings highlight the importance of immunohistochemical profiling in refining the diagnostic process for LMS and differentiating it from other sarcomas.