Gastric SMARCA4-deficient undifferentiated tumor (SMARCA4-UT) - a clinicopathological analysis of four rare cases

Sep 21, 2026

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Gastric SMARCA4-deficient undifferentiated tumor (SMARCA4-UT) is an uncommon, difficult-to-diagnose gastric cancer entity. This report summarizes four retrospectively collected rare cases to clarify clinicopathological features and genetic alterations. The tumors were observed in males aged 61–82 years and typically presented as ulcerated, transmural infiltrative masses. Histology showed undifferentiated solid architecture with frequent necrosis and rhabdoid morphology, coupled with epithelial marker negativity and SMARCA4 loss. Additional findings included Syn/SALL4 positivity, frequent mutant p53 accumulation, high Ki-67, occasional dMMR, and variable SMARCA4 gene alterations, with poor treatment response in one case.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages10

Reading Time25 min

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Abstract

Background

Results

Conclusions

Keywords

Immunohistochemistry and diagnostic implications

Zhou et al. Orphanet Journal of Rare Diseases (2024) 19:237 [https://doi.org/10.1186/s13023-024-03244-4](https://doi.org/10.1186/s13023-024-03244-4) Orphanet Journal of Rare Diseases RESEARCH Open Access Gastric SMARCA4-deficient undifferentiated tumor (SMARCA4-UT): a clinicopathological analysis of four rare cases Ping Zhou 1, Yiyun Fu 1, Weiya Wang 1, Yuan Tang 1 and Lili Jiang 1* Abstract Background SMARCA4, as one of the subunits of the SWI/SNF chromatin remodeling complex, drives SMARCA4-deficient tumors. Gastric SMARCA4-deficient tumors may include gastric SMARCA4-deficient carcinoma and gastric SMARCA4-deficient undifferentiated tumor (SMARCA4-UT) . Gastric SMARCA4-UT is rare and challenging to diagnose in clinical practice. The present report aims to provide insight into the clinicopathological characteristics and genetic alterations of gastric SMARCA4-UTs. Results We retrospectively reported four rare cases of gastric SMARCA4-UTs. All four cases were male, aged between 61 and 82 years. These tumors presented as ulcerated and transmural masses with infiltration, staged asTNM IV in cases 1, 2 and 4, and TNM IIIA in case 3. Pathologically, four cases presented solid architecture with undifferentiated morphology. Cases 2 and 3 showed focal necrosis and focal rhabdoid morphology. Immunohistochemical staining showed negative expression of epithelial markers and deficient expression of SMARCA4 . Furthermore, positivity for Syn (cases 1, 2 and 3) and SALL4 (cases 1 and 2) were observed. Mutant p53 expression occurred in four cases, resulting in strong and diffuse staining of p53 expression in cases 1, 2 and 4, and complete loss in case 3. The Ki67 proliferative index exceeded 80% . 25%(1/4, case 4) of cases had mismatch repair deficiency (dMMR) . Two available cases (cases 1 and 3) were detected with SMRACA4 gene alterations. The response to neoadjuvant therapy was ineffective in case 1. Conclusions Gastric SMARCA4-UT is a rare entity of gastric cancer with a poor prognosis, predominantly occurs in male patients. The tumors are typically diagnosed at advanced stages and shows a solid architecture with undifferentiated morphology. Negative expression of epithelial markers and complete loss of SMARCA4 immunoexpression are emerging as a useful diagnostic tool for rare gastric SMARCA4-UTs. Keywords SWI/SNF, SMARCA4, BRG1, Gastric cancer, Undifferentiated tumor *Correspondence: Lili Jiang [879876047@qq.com](879876047@qq.com) 1Department of Pathology, West China Hospital, Sichuan University, No. 37 Guo Xue Xiang, Chengdu 610041, Sichuan, P. R. China © The Author(s) 2024. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit [http://creativecommons.org/l](http://creativecommons.org/l)icenses/by/4.0/. The Creative Commons Public Domain Dedication waiver ([http://creativecommons.org/publicdomain/zero/1.0/](http://creativecommons.org/publicdomain/zero/1.0/)) applies to the data made available in this article, unless otherwise stated in a credit line to the data. Zhou et al. Orphanet Journal of Rare Diseases (2024) 19:237 Background Gastric cancer (GC) is one of the most common malignancies globally and has poor outcome, especially in Asia [1, 2]. According to the

FAQs

What is the main focus of the clinicopathological analysis in this report?

The report investigates the clinicopathological characteristics and genetic alterations of gastric SMARCA4-deficient undifferentiated tumors (SMARCA4-UT).

What clinical and pathological patterns were observed across the four cases?

All four cases were male (61–82 years) with ulcerated, transmural infiltrative masses. Pathology showed undifferentiated solid architecture, and some cases also had focal necrosis and rhabdoid morphology.

How do immunohistochemical findings support diagnosis of SMARCA4-UT?

SMARCA4 expression was deficient/absent, while epithelial markers were negative. Syn and SALL4 positivity occurred in selected cases, and mutant p53 staining patterns varied by case.

Sep 21, 2026

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