Li Qinyuan, Abi-Saab Tarek, Prilutskiy Andrey, Horner Vanessa, Frater-Rubsam Leah, Peng Yajing, Huang Wei, Kimple Randall J, Harari Paul M, Lloyd Ricardo V, Hu Rong
Department of Pathology and Laboratory Medicine, University of Wisconsin-Madison, Madison, WI, 53705, USA.
Wisconsin State Laboratory of Hygiene, Madison, WI, 53706, USA.
Head Neck Pathol. 2025 May 14;19(1):60. doi: 10.1007/s12105-025-01788-w.
SMARCB1-deficient and SMARCA4-deficient sinonasal carcinomas are rare, with only a few systematic studies available in the literature. Secondary EWSR1 gene abnormalities have been reported in SMARCB1-deficient tumors. This study aimed to systematically investigate SWI/SNF complex-deficient sinonasal carcinomas in a single-institution cohort, perform clinicopathologic characterization, and explore the underlying molecular mechanisms.
Immunohistochemistry (IHC) of INI1 and BRG1 was performed on tissue microarrays containing tumor tissue from 149 consecutive sinonasal carcinomas. Single nucleotide polymorphism (SNP) array and EWSR1 gene fluorescence in situ hybridization (FISH) analyses were conducted on SMARCB1-deficient sinonasal carcinomas. Clinicopathologic characterization was studied.
Of the 149 sinonasal carcinomas, 7 (4.7%) showed SMARCB1 loss, while none demonstrated SMARCA4 loss. All patients were male and presented with advanced-stage tumors. Four SMARCB1-deficient sinonasal carcinomas exhibited basaloid morphology, two displayed eosinophilic tumor morphology, and one had mixed morphology. Homozygous and heterozygous SMARCB1 deletions were identified in 4/6 and 2/6 cases respectively. Heterozygous loss involving genes neighboring SMARCB1 gene, including EWSR1, was observed in four cases. One tumor showed a heterozygous loss of the entire chromosome 22q. EWSR1 FISH assay revealed concordant heterozygous EWSR1 loss in these five cases.
SMARCB1-deficient carcinomas account for 4.7% of sinonasal carcinomas in this single-institution cohort, while SMARCA4-deficient tumors are even rarer, with none identified. SMARCB1-deficient sinonasal carcinomas exhibit a broad spectrum of morphologic and immunohistochemical features. These carcinomas show complex genetic alterations, with homozygous SMARCB1 deletions present in the majority of cases.
SMARCB1缺陷型和SMARCA4缺陷型鼻窦癌较为罕见，文献中仅有少数系统性研究。有报道称SMARCB1缺陷型肿瘤存在继发性EWSR1基因异常。本研究旨在对单机构队列中的SWI/SNF复合物缺陷型鼻窦癌进行系统研究，进行临床病理特征分析，并探索潜在的分子机制。
对包含149例连续鼻窦癌肿瘤组织的组织芯片进行INI1和BRG1的免疫组织化学（IHC）检测。对SMARCB1缺陷型鼻窦癌进行单核苷酸多态性（SNP）阵列和EWSR1基因荧光原位杂交（FISH）分析。研究临床病理特征。
在149例鼻窦癌中，7例（4.7%）显示SMARCB1缺失，而无一例显示SMARCA4缺失。所有患者均为男性，且均为晚期肿瘤。4例SMARCB1缺陷型鼻窦癌表现为基底样形态，2例表现为嗜酸性肿瘤形态，1例为混合形态。分别在4/6和2/6的病例中鉴定出纯合和杂合的SMARCB1缺失。在4例病例中观察到涉及SMARCB1基因邻近基因（包括EWSR1）的杂合缺失。1例肿瘤显示整个22q染色体杂合缺失。EWSR1 FISH检测显示这5例病例中EWSR1杂合缺失一致。
在这个单机构队列中，SMARCB1缺陷型癌占鼻窦癌的4.7%，而SMARCA4缺陷型肿瘤更为罕见，未发现此类病例。SMARCB1缺陷型鼻窦癌表现出广泛的形态学和免疫组织化学特征。这些癌显示出复杂的基因改变，大多数病例存在纯合的SMARCB1缺失。
