Human · observationalMechanismReported positiveLimited evidenceTier 3 · early humann = 31
Histopathology · Apr 2026 · molecular DNA methylation and copy-number profiling of a series of uterine tumours
GREB1-rearranged uterine tumourUTROSCT (uterine tumour resembling ovarian sex cord tumour)uterine smooth muscle tumours (leiomyoma, leiomyosarcoma)endometrial stromal sarcomaembryonal rhabdomyosarcomaSMARCA4-deficient uterine sarcoma
The authors performed global DNA methylation and copy-number analyses on 10 GREB1-rearranged uterine tumours and 21 classic UTROSCTs (including 7 with ESR1::NCOA2/3 fusions). GREB1-rearranged tumours shared a DNA methylation cluster with UTROSCTs and were distinct from other uterine sarcoma types, but showed greater genomic complexity (more copy-number alterations) and more often lacked overt sex cord morphology.
Reported effects: Number of GREB1-rearranged uterine tumours 10 · Number of classic UTROSCTs 21 · +2 more
Key findings
- GREB1-rearranged uterine tumours show overlap in global methylation profiles with UTROSCT, including ESR1::NCOA2/3 positive cases, forming a DNA methylation cluster separate from several other uterine sarcoma types.
- GREB1-rearranged tumours displayed a greater degree of genomic complexity with more extensive copy number alterations than conventional UTROSCTs, including those with ESR1::NCOA2/3.
- GREB1-rearranged tumours frequently lacked overt sex cord morphology: only 1 GREB1-rearranged tumour displayed a prominent trabecular pattern while the remaining cases had diffuse/solid growth.
- All 7 ESR1::NCOA2/3-positive UTROSCTs demonstrated corded, nested, trabecular and/or tubular/sertoliform patterns.
Limitations: Small case series (31 tumours total) limits generalisability.; Observational molecular profiling without clinical outcome or functional validation data.; Comparisons are limited to the tumour types included; methylation/copy-number differences may not generalise to all uterine tumours..
AI summary of the abstract, human-reviewed · Sep 2026. Describes what this study reported, not medical advice. View on PubMed · Full text
ReviewMechanismMixed resultsLimited evidenceTier 4 · clinical
International journal of gynecological cancer : official journal of the International Gynecological Cancer Society · Jan 2026
uterine leiomyosarcoma
This is a narrative review of the immune environment of uterine leiomyosarcoma and the potential role of immune checkpoint inhibitors. The authors report variable PD-L1 expression, heterogeneous lymphocytic infiltration, and interactions with tumor-associated macrophages, note modest response rates to checkpoint inhibitors in clinical trials, and discuss that dual PD-1/CTLA-4 blockade and chemotherapy-induced immunogenic cell death may enhance immune activation in select patients. They conclude that combinatorial and personalized strategies, improved immune profiling, and macrophage-targeted approaches merit further study.
Studied with: anti-CTLA-4 + anti-PD-1 dual checkpoint blockade, chemotherapy (to induce immunogenic cell death), targeted immunomodulation, macrophage-targeted therapies.
Key findings
- Uterine leiomyosarcoma has a variable tumor immune microenvironment including variable PD-L1 expression and differential lymphocytic infiltration.
- Interactions with tumor-associated macrophages shape immune responses in leiomyosarcoma.
- Clinical trials of immune checkpoint inhibitors in leiomyosarcoma have produced modest response rates.
- Molecular analyses suggest that specific sub-groups of leiomyosarcoma patients may derive greater benefit from checkpoint inhibition.
- Dual-checkpoint blockade combining anti-PD-1 and anti-CTLA-4 has demonstrated enhanced immune activation in select patients.
- Chemotherapy-induced immunogenic cell death has been explored as a complementary approach to immunotherapy.
- Authors recommend innovative combinatorial strategies, improved patient selection, enhanced macrophage-targeted therapies, and optimized immune profiling for future research.
Limitations: Narrative review only—no new primary experimental or patient-level data are presented.; Conclusions are based on heterogeneous published studies and molecular analyses rather than definitive randomized trial evidence.; Abstract reports only 'modest response rates' in trials without quantitative pooled estimates or meta-analysis.; Leiomyosarcoma heterogeneity and rarity limit generalizability of existing trial results (as noted by authors)..
AI summary of the abstract, human-reviewed · Jun 2026. Describes what this study reported, not medical advice. View on PubMed
Human · observationalMechanismReported positiveLimited evidenceTier 3 · early humann = 71
Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc · Nov 2025 · Array-based global methylation profiling analysis of tumor samples (71 uterine leiomyosarcoma) compared with several other uterine mesenchymal tumors and soft tissue leiomyosarcoma
uterine leiomyosarcomauterine mesenchymal tumorssoft tissue leiomyosarcoma
Researchers performed array-based global methylation profiling on 71 uterine leiomyosarcoma samples and compared them to other uterine mesenchymal tumors and soft tissue leiomyosarcoma. They found that uLMS have distinct methylation patterns versus other tumor types and that methylation profiling identifies two distinct uLMS subgroups with differing copy number alterations and distinct histologic and clinical behaviors. The authors report this is the first study to describe methylation profiling as a diagnostic tool to differentiate uLMS from its mimics.
Key findings
- uLMS demonstrated distinct methylation patterns differing from all other tumor types.
- Methylation profiling defines 2 distinct subgroups of uLMS with differing copy number alterations.
- The two methylation-defined subgroups exhibit unique histologic and clinical behaviors, supported by differences in methylation pathway analysis.
- This study is the first to report methylation profiling as a useful diagnostic tool in differentiating uLMS from mimics.
Limitations: Observational molecular profiling study without interventional or longitudinal clinical trial data; Sample size limited to 71 uLMS; sizes of comparator tumor groups not reported in abstract; No external validation cohort reported in the abstract; No functional validation experiments described to confirm biological significance of methylation differences; Details on clinical outcome measures, follow-up duration, and statistical metrics are not provided in the abstract.
AI summary of the abstract, human-reviewed · Sep 2026. Describes what this study reported, not medical advice. View on PubMed
Human · observationalMixed resultsModerate evidenceTier 3 · early humann = 661
Journal of surgical oncology · Nov 2025 · nationwide population-based cohort study (patients diagnosed 1980–2022)
cutaneous leiomyosarcomasubcutaneous leiomyosarcomadermal leiomyosarcomaleiomyosarcomaskin neoplasms
This nationwide Danish cohort study (1980–2022) compared outcomes in 196 patients with subcutaneous and 465 patients with dermal cutaneous leiomyosarcoma (total n=661). At 10 years the local recurrence rates were similar (15% vs 11%, p=0.13), but subcutaneous tumors had a much higher 10-year metastasis risk (25% vs 2.7%, p<0.001) and lower 10-year overall survival (56% vs 64%, p=0.02). The authors conclude that grade 2–3 subcutaneous leiomyosarcoma should be considered high-risk and recommend 5 years of follow-up including clinical exam plus PET/CT or chest CT, while dermal leiomyosarcoma can have clinical follow-up for 4 years.
Reported effects: 10-year local recurrence 15%, p 0.13, n=196 · 10-year risk of metastasis 25%, p <0.001, n=196 · +1 more
Key findings
- Cohort included 196 patients with subcutaneous leiomyosarcoma and 465 with dermal leiomyosarcoma (total n=661).
- The 10-year local recurrence rate was similar: subcutaneous 15% and dermal 11% (p = 0.13).
- The 10-year risk of metastasis was substantially higher for subcutaneous leiomyosarcoma (25%) versus dermal (2.7%), p < 0.001; metastases were primarily observed in grade 2 and 3 tumors.
- Ten-year overall survival was lower for subcutaneous compared with dermal leiomyosarcoma (56% vs. 64%), p = 0.02.
- Authors recommend classifying grade 2–3 subcutaneous leiomyosarcoma as high-risk and performing clinical examinations plus PET/CT or CT thorax for 5 years; dermal leiomyosarcoma follow-up can focus on clinical exams for 4 years given very low metastasis risk.
Limitations: Observational, registry-based cohort (potential for residual confounding and unmeasured variables).; Long study period (1980–2022) during which diagnostic methods, staging, and treatments likely changed, which may affect outcomes.; Abstract does not report details on treatments, adjuvant therapy, or timing of interventions that could influence recurrence, metastasis, or survival.; Potentially incomplete or variable clinical data quality across decades and centers (not detailed in abstract).; Findings are from Denmark and may not generalize to other healthcare settings or populations..
Provides 10-year estimates of local recurrence, metastasis, and overall survival for dermal versus subcutaneous cutaneous leiomyosarcoma and gives follow-up recommendations.
AI summary of the abstract, human-reviewed · Jun 2026. Describes what this study reported, not medical advice. View on PubMed · Full text
Human · observationalMechanismReported positiveLimited evidenceTier 3 · early humann = 6
Frontiers in immunology · Aug 2025 · Single-cell RNA sequencing (scRNA-seq) of metastatic lesions from a treatment-naïve uterine leiomyosarcoma patient compared to normal uterine myometrium samples (MMM, n=5); integrated analyses including CNV, pseudotime, cell-cell communication, functional enrichment, and mpIF validation; survival correlations with TCGA-SARC cohort.
uterine leiomyosarcoma
The authors performed single-cell RNA sequencing on metastatic lesions from one treatment-naïve uterine leiomyosarcoma patient and compared the data to five normal myometrium samples. They found an immunosuppressed tumor microenvironment characterized by exhausted CD8+ T cells, M2-like tumor-associated macrophages, and immature N2 neutrophils enriched in metastatic foci; these features correlated with poorer prognosis in TCGA-SARC analyses. The study also identified cell-cell communication axes (MIF-(CD74+CD44), CXCL8) and candidate biomarkers (EDARADD, CLDN10, TMIGD2) and dysregulated pathways (TGF-beta, angiogenesis, MIF signaling).
Key findings
- The tumor microenvironment showed prominent immunosuppression with exhausted CD8+ T cells, with initial markers (CCR7, MAL) diminishing over time and exhaustion markers (LAG3, HAVCR2, TIGIT) enriched.
- M2-polarized macrophages were mainly composed of M2-like TAMs with tumor-promoting characteristics (CD163, FTH1, FTL, TIMP1) and there was a polarization trajectory from M1 to M2.
- Immature, tumor-promoting N2 neutrophils (CD15+EDARADD+) were enriched in metastatic foci and associated with poor prognosis.
- Cell-cell communication analyses highlighted MIF-(CD74+CD44) interactions between T/B cells and a role for the CXCL8 signaling axis in promoting angiogenesis, TAM polarization, and immunosuppression.
- Constructed a comprehensive single-cell map of ULSA, defined a metastasis-susceptible cell subset (U11-EDARADD), and nominated biomarkers (EDARADD, CLDN10, TMIGD2) and dysregulated pathways (TGF-β, angiogenesis, MIF signaling) as possible targets for future combined-immunotherapy development.
Limitations: Tumor single-cell data derive from a single ULSA patient (metastatic lesions from one individual), limiting generalizability.; Normal comparator samples are limited (MMM, n=5) and cohort sizes are small.; Observational single-cell profiling cannot establish causal relationships between identified cell states/pathways and clinical outcomes or therapy resistance.; Survival associations were assessed using TCGA-SARC correlations (indirect validation) rather than validation in an independent ULSA cohort.; No interventional or functional experiments reported to validate that identified biomarkers/pathways drive immunosuppression or therapy resistance..
AI summary of the abstract, human-reviewed · Sep 2026. Describes what this study reported, not medical advice. View on PubMed · Full text
ReviewMechanismInconclusiveLimited evidenceTier 4 · clinical
American Society of Clinical Oncology educational book. American Society of Clinical Oncology. Annual Meeting · Jun 2025
uterine neoplasmsleiomyosarcomauterine stromal tumorsmesonephric-like carcinomaserous carcinoma
This is a review of rare uterine malignancies (including leiomyosarcomas, uterine stromal tumors, mesonephric-like and serous carcinomas). The authors summarize recent advances in diagnostic precision, risk stratification, and identification of biomarker-guided therapeutic options, and note that improved molecular understanding has led to development of targeted approaches. They conclude that further progress requires coordinated global efforts and enrollment of patients on biomarker-driven clinical trials.
Key findings
- Rare uterine malignancies are clinically and biologically heterogeneous, creating treatment challenges.
- The rarest uterine cancers discussed include leiomyosarcomas, uterine stromal tumors, and mesonephric-like and serous carcinomas.
- Recent advancements have improved diagnostic precision and risk stratification for these rare subtypes.
- Identification of biomarker-guided therapeutic options and improved molecular profiling have led to development of targeted treatment approaches.
- Further progress depends on coordinated, global characterization efforts and enrollment of patients on biomarker-driven clinical trials.
Limitations: Review article — does not present new primary experimental or clinical trial data.; Focuses on rare, heterogeneous tumor subtypes for which evidence is often limited.; Conclusions are broad and dependent on availability of biomarker-driven trials rather than on definitive trial results..
AI summary of the abstract, human-reviewed · Aug 2026. Describes what this study reported, not medical advice. View on PubMed