SMARCA4-Deficient Undifferentiated Tumor: A Rare Malignancy With Distinct Clinicopathological Characteristics

Area of Science:

• Oncology
• Genetics
• Pathology

Background:

• SMARCA4-deficient undifferentiated tumors (SMARCA4-dUT) are rare malignancies characterized by inactivating mutations in the SMARCA4 gene within the SWI/SNF chromatin remodeling complex.
• These aggressive tumors predominantly affect middle-aged male smokers, often presenting with nonspecific respiratory symptoms and advanced metastatic disease.

Observation:

• Metastatic patterns resemble carcinomas, with common sites including lymph nodes, bones, and adrenal glands.
• Histological features include sarcomatoid or mixed carcinoma-sarcoma morphology, extensive necrosis, and high mitotic activity.
• Immunohistochemistry is notable for negative keratin and claudin-4 expression, and a characteristic lack of BRG1 expression in tumor cell nuclei.

Findings:

• Two cases of SMARCA4-dUT are presented, detailing their clinical course and management.
• The study provides a perspective on the tumor's behavior within a Western population cohort.

Implications:

• The rarity of SMARCA4-dUT has precluded the establishment of standard treatment guidelines.
• Systemic chemoimmunotherapy has shown potential benefit in some cases, warranting further investigation.
• Understanding the clinical and pathological characteristics is crucial for improving patient outcomes and developing targeted therapies.