Work

Cervical SMARCA4-Deficient Undifferentiated Tumor: A Rare Case Report and Literature Review

Year: 2025

Type: article

Abstract: Background: The cervical switch (SWI)/sucrose non-fermentable (SNF) related, matrix associated, actin dependent regulator of chromatin, subfamily a, member 4 (SMARCA4)-deficient undifferentiated tumor (SMARCA4-UT) constitutes a rare, highly aggressive malignancy that is currently unclassified by the World Health Organization (WHO). The published literature comprises predominantly sporadic case reports. Clinically characterized by an unfavorable prognosis, distinctive histopathological morphology, and specific immunophenotypic profiles, a cervical SMARCA4-UT exhibits relatively nonspecific molecular alterations that closely mirror those of a thoracic SMARCA4-UT. Notably, optimal therapeutic algorithms and management paradigms remain incompletely delineated. Case: We report a case of cervical SMARCA4-UT in a 58-year-old female presenting with persistent abnormal uterine bleeding. The initial clinical evaluation, including ultrasonography, identified a cervical mass. The patient was subsequently referred to a hospital. Comprehensive staging, using whole-body positron emission tomography-computed tomography (PET-CT) and pelvic magnetic resonance imaging (MRI), confirmed a large cervical neoplasm consistent with clinical stage IV disease, precluding radical surgical resection. Analysis of biopsy specimens demonstrated partial pan-cytokeratin [anti-epithelial cytokeratin 1 (AE1)/anti-epithelial cytokeratin 3 (AE3)] immunoreactivity, focal claudin-4 expression, and complete loss of SMARCA4 protein expression. Next-generation sequencing (NGS) identified a microsatellite instability-high (MSI-H) status, with mutations in genes such as phosphatase and tensin homolog deleted on chromosome ten (PTEN) and AT-rich interaction domain 1A (ARID1A), among others; notably, pathogenic SMARCA4 mutations were absent. A definitive diagnosis of SMARCA4-UT was established. Therapeutic intervention comprised percutaneous radioactive seed implantation followed by combination chemotherapy with etoposide-cisplatin (EP regimen) plus bevacizumab, complicated by bone marrow suppression. Therapy was transitioned to pembrolizumab combined with paclitaxel-carboplatin (TP regimen). Disease progression prompted the reversion to a reduced EP regimen with bevacizumab dosage. The patient demonstrated sustained disease control from her third discharge until the conclusion of the follow-up. Conclusions: Single-agent immunotherapy has shown limited efficacy in the inoperable setting, whereas combination chemotherapy regimens incorporating anti-vascular endothelial growth factor (VEGF) agents may have conferred a clinical benefit for tumor control.

Source: Clinical and Experimental Obstetrics & Gynecology

DOI: 10.31083/ceog45103

Authors: Jin Wang, Yanli Li, Wanhui Dong, Chuanying Li

Institutions: West Anhui Health Vocational College, Anhui Medical University, Shanghai Jiao Tong University, Ruijin Hospital

Language: English

Topic: Chromatin Remodeling and Cancer

Subfield: Molecular Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $1,500