Case Report: SMARCA4-deficient uterine sarcoma with exceptional response to immune checkpoint inhibitor therapy
- 1Department of Gynecological Oncology, Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing Maternal and Child Health Care Hospital
- 2Laboratory for Clinical Medicine, Capital Medical University
- 3Department of Pathology, Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing Maternal and Child Health Care Hospital
Abstract
Background: SMARCA4-deficient uterine sarcoma (SDUS) is a rare and aggressive undifferentiated uterine mesenchymal malignancy characterized by inactivation of SMARCA4 gene leading to loss of nuclear SMARCA4/BRG1 immunohistochemical staining. Fewer than 40 cases have been reported worldwide since its first description in 2018, and the disease carries a median overall survival of only 7–9 months. SMARCA4 loss is observed across a spectrum of aggressive neoplasms, including smallcell carcinoma of the ovary, hypercalcemic type (SCCOHT), SMARCA4-deficient thoracic sarcoma, and SMARCA4-deficient nonsmallcell lung cancer, suggesting shared therapeutic vulnerabilities.
Case: A 48-year-old woman presented with irregular vaginal bleeding for two years. Physical examination and magnetic resonance imaging (MRI) revealed a large pelvic mass centered in the uterus. The patient underwent total abdominal hysterectomy with bilateral salpingectomy, and pathological examination confirmed SDUS (stage IB, FIGO 2018). Genetic testing identified a somatic SMARCA4 splice-site variant (c.3951 + 2T>G). The tumor was TMB-low (0.06 Mut/Mb), PD-L1-negative (<1% by 22C3 pharmDx), microsatellite stable (MSS), and HLA-class-I heterozygous. Despite these conventional immunotherapy-unfavorable markers, adjuvant Gemcitabine-Docetaxel chemotherapy combined with pembrolizumab yielded a progression-free survival (PFS) of 23 months as of the last follow-up, far exceeding the previously reported median survival of SDUS.
Conclusion: This case demonstrates that immune checkpoint inhibitors (ICI) may provide meaningful therapeutic benefit in selected patients with SDUS, including those lacking conventional predictive biomarkers (TMB-high, PD-L1 positivity, or MSI-H). While the observed 23-month PFS supports the hypothesis that SMARCA4 deficiency merits further investigation as a candidate molecular correlate of ICI responsiveness, definitive validation requires larger cohorts and ideally prospective, biomarker-driven studies. Definitive diagnosis relies on morphologic evaluation, loss of BRG1 protein expression by immunohistochemistry with retained INI-1, and detection of SMARCA4 gene alterations through genetic testing.
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BibTeX
@article{liu2026case,
title = {{Case Report: SMARCA4-deficient uterine sarcoma with exceptional response to immune checkpoint inhibitor therapy}},
author = {Qun Liu and Haili Kang and Jiao Wang and Haiyun Yu and Shuli Yang},
journal = {Frontiers in Oncology},
year = {2026},
month = oct,
doi = {10.3389/fonc.2026.1966486},
url = {https://www.frontiersin.org/articles/10.3389/fonc.2026.1966486/full},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Case Report: SMARCA4-deficient uterine sarcoma with exceptional response to immune checkpoint inhibitor therapy
AU - Qun Liu
AU - Haili Kang
AU - Jiao Wang
AU - Haiyun Yu
AU - Shuli Yang
PY - 2026
DA - 2026/10/20
JO - Frontiers in Oncology
DO - 10.3389/fonc.2026.1966486
UR - https://www.frontiersin.org/articles/10.3389/fonc.2026.1966486/full
AB - Background: SMARCA4-deficient uterine sarcoma (SDUS) is a rare and aggressive undifferentiated uterine mesenchymal malignancy characterized by inactivation of SMARCA4 gene leading to loss of nuclear SMARCA4/BRG1 immunohistochemical staining. Fewer than 40 cases have been reported worldwide since its first description in 2018, and the disease carries a median overall survival of only 7–9 months. SMARCA4 loss is observed across a spectrum of aggressive neoplasms, including smallcell carcinoma of the ovary, hypercalcemic type (SCCOHT), SMARCA4-deficient thoracic sarcoma, and SMARCA4-deficient nonsmallcell lung cancer, suggesting shared therapeutic vulnerabilities. Case: A 48-year-old woman presented with irregular vaginal bleeding for two years. Physical examination and magnetic resonance imaging (MRI) revealed a large pelvic mass centered in the uterus. The patient underwent total abdominal hysterectomy with bilateral salpingectomy, and pathological examination confirmed SDUS (stage IB, FIGO 2018). Genetic testing identified a somatic SMARCA4 splice-site variant (c.3951 + 2T>G). The tumor was TMB-low (0.06 Mut/Mb), PD-L1-negative (<1% by 22C3 pharmDx), microsatellite stable (MSS), and HLA-class-I heterozygous. Despite these conventional immunotherapy-unfavorable markers, adjuvant Gemcitabine-Docetaxel chemotherapy combined with pembrolizumab yielded a progression-free survival (PFS) of 23 months as of the last follow-up, far exceeding the previously reported median survival of SDUS. Conclusion: This case demonstrates that immune checkpoint inhibitors (ICI) may provide meaningful therapeutic benefit in selected patients with SDUS, including those lacking conventional predictive biomarkers (TMB-high, PD-L1 positivity, or MSI-H). While the observed 23-month PFS supports the hypothesis that SMARCA4 deficiency merits further investigation as a candidate molecular correlate of ICI responsiveness, definitive validation requires larger cohorts and ideally prospective, biomarker-driven studies. Definitive diagnosis relies on morphologic evaluation, loss of BRG1 protein expression by immunohistochemistry with retained INI-1, and detection of SMARCA4 gene alterations through genetic testing.
SN - 2234-943X
ER -