SMARCA4-deficient central nervous system metastases: A case series and systematic review

Area of Science:

• Neuropathology
• Oncology
• Molecular Pathology

Background:

• Metastases with SMARCA4 alterations to the central nervous system (CNS) are rare and pose diagnostic challenges for neuropathologists.
• Understanding the clinical and histological presentation of these neoplasms is crucial for accurate diagnosis and patient management.

Approach:

• Conducted an observational case series and systematic review of 178 articles, analyzing 15 published cases and 7 institutional cases of SMARCA4-altered CNS metastases.
• Systematic review identified median age of 58 years, a 2:1 male-to-female ratio, and lung adenocarcinoma as the most common primary diagnosis, with CNS metastases often detected within 1 year.
• Case series revealed similar median age, a 6:1 male-to-female ratio, lung origin for all metastases, and frequent smoking history.

Key Points:

• Most patients had a smoking history and succumbed to the disease.
• GATA-3 positivity was observed in the majority of case series examples.
• Concurrent TP53 mutations (83.3%) and a high tumor mutation rate (60%) were frequently noted.

Conclusions:

• This is the first case series and systematic review in English literature focusing on SMARCA4-altered metastases in the CNS and vertebral column.
• Highlights challenges in neuropathologic evaluation of these tumors.
• Provides evidence of early metastasis, characteristic histologic appearances, and immunohistochemical findings, including novel GATA-3 positivity.