SMARCA4 alterations can be encountered in a variety of human neoplasms, and metastases to the central nervous system (CNS) are rare, offering a challenge to neuropathologists despite not representing a distinct diagnostic entity. To better understand the clinical and histologic presentation of such neoplasms, we report an observational case series and systematic review of 178 unique articles that yielded 15 published cases and 7 cases from institutional files. In the systematic review, the median age was 58 years, the male-to-female ratio was 2:1, and the most common diagnosis was lung adenocarcinoma; all CNS metastases were discovered within 1 year of presentation. In the case series, the median age was 58 years, the male-to-female ratio was 6:1, and all known metastases originated from the lung. Most patients had a smoking history and died of disease. GATA-3 positivity was seen in most case series examples. Concurrent TP53 mutations (83.3%) and a high tumor mutation rate (60%) were common. To our knowledge, this is the only case series and systematic review in the English literature aimed at assessing SMARCA4-altered metastases in the CNS and vertebral column. We highlight the challenges of neuropathologic evaluation of such tumors and provide observational evidence of early metastases, histologic appearances, and immunohistochemical findings, including previously unreported GATA-3 positivity.

Primary cutaneous SMARCA4-deficient undifferentiated malignant neoplasm (SD-UMN) is a rare and recently described entity characterized by the loss of expression of the SMARCA4 (BRG1) protein, which is involved in chromatin remodeling. SD-UMN presents a diagnostic challenge due to its rarity and unique histopathological and immunohistochemical features. In this report, we present a case of primary cutaneous SD-UMN in a 67-year-old man who presented with a rapidly growing, ulcerated, and bleeding nodule on his right cheek. Histopathological examination revealed a highly cellular dermal tumor consisting of pleomorphic epithelioid cells with prominent mitotic figures and necrosis, lacking any morphological evidence of differentiation. Immunohistochemical analysis showed a complete loss of SMARCA4 and SMARCA2 expression, while INI-1 expression remained intact. p53 was diffusely expressed, and p16 was completely absent. In addition, a range of markers, including high-molecular-weight cytokeratin, p63, SOX10, INSM1, MCPyV, NKX2.2, CD99, CDX2, CD56, ERG, NUT, desmin, androgen receptor, chromogranin, CD34, and CD43 were all negative. To date, only two cases of primary cutaneous SMARCA4-deficient undifferentiated tumors have been reported in the literature. Therefore, this case report adds to the limited body of knowledge on the clinical and histopathological features of this novel entity. The report highlights the importance of considering SD-UMN in the differential diagnosis of undifferentiated cutaneous tumors.