SMARCA4-deficient undifferentiated malignant tumor of the urinary bladder without a detectable coding SMARCA4 alteration: a case report and literature review
Year: 2026
Type: article
Study design: Case Report
Abstract: Background SMARCA4 encodes BRG1, the ATPase catalytic subunit of the SWI/SNF chromatin remodeling complex. SMARCA4-deficient tumors are typically undifferentiated or rhabdoid in morphology, are aggressive, prone to early recurrence and are frequently resistant to conventional chemotherapy. In the bladder, such tumors are exceedingly rare, with only four cases reported to date, and no standard treatment has been defined. Case presentation A 69-year-old man presented with painless gross hematuria and was found to have a pT3N0 tumor arising within a right bladder-wall diverticulum. Robot-assisted partial cystectomy yielded an undifferentiated malignant tumor with epithelioid/rhabdoid morphology, complete loss of BRG1 (SMARCA4) expression, HER2 expression (IHC 2+), low PD-L1 expression (tumor cell score(TC) <25%, immune cell population score(ICP) <1%) and a Ki-67 index of approximately 60%. Paired tumor and adjacent non-tumor whole-exome sequencing detected no detectable pathogenic coding SMARCA4 point mutation or indel; copy-number and B-allele-frequency analyses further excluded deletion or loss of heterozygosity at 19p13.2, indicating that BRG1 loss in this tumor was not genomically encoded and was most plausibly epigenetically mediated. The patient received two cycles of adjuvant tislelizumab monotherapy. Intravesical recurrence occurred at 23 months and was treated with disitamab vedotin, a HER2-directed antibody-drug conjugate, combined with tislelizumab, followed by maximal transurethral resection and, at the time of bone progression, selective arterial embolization. Despite incomplete adherence to therapy, he remains alive 48 months after diagnosis, the longest survival reported for this entity to date. Conclusion Immunohistochemistry, rather than sequencing, should be regarded as the diagnostic reference standard for SMARCA4 deficiency, since BRG1 loss may occur without any detectable genomic alteration. Immune-checkpoint blockade combined with a HER2-directed antibody-drug conjugate produced meaningful and durable disease control despite low PD-L1 expression, and warrants prospective evaluation in this rare subtype.
Source: Frontiers in Oncology
Institution: First Affiliated Hospital of Zhengzhou University
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $3,801
OpenAlex ID: W7223000993