SMARCA4-deficient undifferentiated tumor (SMARCA4-UT) is a highly aggressive malignancy that pathologists recently recognized as a distinct entity. It typically occurs in the thoracic cavity; however, involvement of the esophagus remains exceedingly rare. Since clinical experience with this tumor is limited, clinicians must understand its unique presentation and the utility of liquid-based cytology (LBC) for timely diagnosis.

The Case of Esophageal Involvement

A 51-year-old man initially presented with cervical lymphadenopathy and extensive metastatic disease. An excisional lymph node biopsy established the diagnosis of SMARCA4-deficient undifferentiated tumor. After undergoing chemotherapy and immunotherapy, the patient developed progressive dysphagia. Imaging subsequently revealed upper-esophageal stenosis and significant mural thickening, confirming primary involvement in the esophagus.

Identifying SMARCA4-deficient undifferentiated tumor via Cytology

Cytologic evaluation of metastatic sites using LBC provided critical diagnostic information. The preparations showed marked cellularity with dispersed malignant cells and loosely cohesive clusters. These cells exhibited eccentric nuclei and prominent nucleoli within a necrotic background. Furthermore, the presence of focal rhabdoid features offered a significant diagnostic clue during the initial screening process.

Immunohistochemical Confirmation

Immunohistochemistry (IHC) played a pivotal role in confirming the diagnosis across all sites. The tumor cells showed a complete loss of SMARCA4 (BRG1) nuclear expression, which defines this malignancy. Conversely, the cells retained SMARCB1 (INI1) expression. Although the cells lacked typical epithelial and lymphoid markers, they showed focal synaptophysin positivity. These findings remained reproducible across multiple metastatic sites and the esophageal lesion.

Conclusion

This case highlights the aggressive nature of SMARCA4-UT and its potential for unusual esophageal involvement. It demonstrates that LBC effectively preserves the essential cytomorphologic features required for a definitive diagnosis. Therefore, clinical awareness of these features is vital for ensuring appropriate ancillary testing and managing complex patient outcomes in oncology practice.

What are the primary cytologic features of this tumor?

Cytologic preparations typically show dispersed malignant cells with rhabdoid features, marked nuclear pleomorphism, and prominent nucleoli, often set against a necrotic background.

Which IHC markers confirm a SMARCA4-UT diagnosis?

The definitive diagnostic marker is the complete loss or severe reduction of SMARCA4 (BRG1) nuclear expression while usually retaining SMARCB1 (INI1) expression.

How aggressive is esophageal SMARCA4-UT?

This tumor follows a highly aggressive clinical course. Patients often present with advanced metastatic disease and demonstrate poor responses to conventional therapies, resulting in low survival rates.

Disclaimer: This content is for informational and educational purposes only... Refer to the latest local and national guidelines for clinical practice.

References

1. Lee WY et al. Liquid-Based Cytology of SMARCA4-Deficient Undifferentiated Tumor: A Case Report. Diagn Cytopathol. 2026 Mar 27. doi: 10.1002/dc.70113. PMID: 41896094.
2. Xu J, Chi Z. Esophageal carcinoma with SMARCA4 mutation: a narrative review for this rare entity. Transl Gastroenterol Hepatol. 2024 Mar 22;9:24.
3. Agaimy A, et al. SMARCA4-deficient undifferentiated carcinoma of the esophagus and gastroesophageal junction: clinicopathologic and molecular characterization of a distinct subset of esophageal neoplasia. Am J Surg Pathol. 2021;45(1):1-10.