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SMARCA4-deficient uterine tumors in young women: response to immune checkpoint inhibitors
Riku Suzui1, Mana Taki1, Sachiko Kitamura1
1Department of Gynecology and Obstetrics, Kyoto University Graduate School of Medicine, 54 Shogoin Kawahara-Cho, Sakyo-Ku, Kyoto, 606-8507 Japan.
Abstract:
SMARCA4-deficient tumors have been reported in various organs and are associated with a poor prognosis. SMARCA4-deficient undifferentiated uterine sarcoma (SDUS) was first described in 2018. Conversely, loss of SMARCA4 (BRG1) expression, as observed by immunostaining, has been observed in several cases of undifferentiated endometrial carcinoma. SDUS has considerable morphologic overlap with undifferentiated endometrial carcinoma, while there are differences in their clinicopathological features. Here, we present two cases of SMARCA4-deficient uterine tumors in patients in their 20 s: SDUS (Case 1) and undifferentiated endometrial carcinoma without SMARCA4 nuclear expression (Case 2). Using comprehensive genome profiling, we found that both cases had SMARCA4 mutations, with tumor mutation burdens of 0 and 68 Muts/Mb, respectively. Case 1 had multiple lung metastases 9 months after surgery. We treated the patients with combination of an immune checkpoint inhibitor (pembrolizumab) and a multikinase inhibitor (lenvatinib), and the response to the treatment was stable. This study presents the first report on the response to immune checkpoint inhibitor and multikinase inhibitor in SDUS.
Supplementary Information:
The online version contains supplementary material available at 10.1007/s13691-024-00721-2.
Insights
SMARCA4-deficient uterine tumors, including undifferentiated uterine sarcoma, present diagnostic challenges. This study details two young patients and their response to immune checkpoint inhibitors and multikinase inhibitors.
Area of Science:
- Gynecologic Oncology
- Cancer Genomics
- Pathology
Background:
- SMARCA4-deficient tumors are aggressive with poor prognoses.
- SMARCA4-deficient undifferentiated uterine sarcoma (SDUS) is a rare entity.
- Morphologic overlap exists between SDUS and undifferentiated endometrial carcinoma.
Purpose of the Study:
- To present two cases of SMARCA4-deficient uterine tumors in young patients.
- To compare clinicopathological features of SDUS and undifferentiated endometrial carcinoma.
- To report the treatment response of SDUS to immune checkpoint and multikinase inhibitors.
Main Methods:
- Comprehensive genome profiling for SMARCA4 mutations.
- Immunohistochemical analysis for SMARCA4 (BRG1) expression.
- Clinical follow-up and treatment response assessment.
Main Results:
- Two cases presented: SDUS (Case 1) and undifferentiated endometrial carcinoma (Case 2).
- Both cases harbored SMARCA4 mutations.
- Case 1 showed metastasis and stable response to pembrolizumab and lenvatinib.
Conclusions:
- SMARCA4-deficient uterine tumors require careful diagnosis due to overlapping features.
- This is the first report on combination therapy with immune checkpoint and multikinase inhibitors in SDUS.
- Further research is needed to optimize treatment strategies for these rare tumors.
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