Liquid-Based Cytology of SMARCA4-Deficient Undifferentiated Tumor: A Case Report.

BACKGROUND

SMARCA4-deficient undifferentiated tumor (SMARCA4-UT) is a recently recognized and highly aggressive malignancy characterized by loss of SMARCA4 (BRG1) expression. Although initially described in thoracic locations, involvement of the esophagus is rare, and cytopathologic experience remains limited, particularly using liquid-based cytology (LBC).

CASE: A 51-year-old man presented with cervical lymphadenopathy and widespread metastatic disease. Excisional lymph node biopsy established the diagnosis of SMARCA4-UT. After initial chemotherapy and immunotherapy, he developed progressive dysphagia, and imaging demonstrated upper-esophageal stenosis and mural thickening. Cytologic evaluation of both a cervical lymph node and a subcutaneous back lesion using LBC showed moderately to markedly cellular preparations composed of dispersed malignant cells and loosely cohesive clusters in a necrotic background. Tumor cells displayed marked nuclear pleomorphism, eccentrically located nuclei, prominent nucleoli, and focal rhabdoid features. Immunohistochemical studies showed focal synaptophysin positivity but absence of chromogranin, INSM1, epithelial, and lymphoid markers. SMARCB1 (INI1) expression was retained, whereas SMARCA4 (BRG1) showed markedly reduced to complete loss of nuclear expression, confirming SMARCA4-UT. Esophageal biopsy demonstrated identical findings, supporting esophageal involvement. Despite treatment, the disease progressed rapidly, and the patient died 9 months after diagnosis.

CONCLUSION

This case demonstrates that LBC specimens from metastatic sites can preserve diagnostic cytomorphologic features of SMARCA4-UT and highlights this rare presentation with esophageal involvement and reproducible findings across two metastatic sites. Awareness of cytologic features and potential diagnostic pitfalls is essential for timely diagnosis and appropriate ancillary testing.