Department of Pathology and Laboratory Medicine, Emory University Hospital Midtown, Emory University School of Medicine, Atlanta, Georgia; Department of Pathology and Genomic Medicine, Houston Methodist Hospital, Houston, Texas.
Department of Pathology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois.
J Am Soc Cytopathol. 2022 Jul-Aug;11(4):183-193. doi: 10.1016/j.jasc.2022.04.001. Epub 2022 Apr 6.
Inactivation of SMARCA4/BRG1 (Brahma-related gene 1), a member of the switch/sucrose nonfermentable subfamily of adenosine triphosphate-dependent chromatin remodeling complexes, has been demonstrated in a subset of non-small cell lung carcinomas (NSCLCs). However, the cytomorphologic features of SMARCA4-deficient NSCLCs (SMARCA4-dNSCLC) have only rarely been reported.
Eight cytology cases of SMARCA4-dNSCLC and eight SMARCA4-retained NSCLC (SMARCA4-rNSCLC) cases were retrieved from our institution's database. These were compared cytologically and immunophenotypically.
All 8 patients with SMARCA4-dNSCLC had a smoking history, and 4 of 8 cases had a prior cancer history. Cytologically, the tumors demonstrated predominantly loosely cohesive and high-grade epithelioid cells with markedly pleomorphic nuclei and prominent nucleoli. Binucleated/multinucleated cells were seen in 5 cases. Six cases showed focal plasmacytoid morphology, and 2 cases showed necrosis. In contrast, in all 8 cases of SMARCA4-rNSCLC, the aspirates were predominantly cohesive with focal, loosely cohesive epithelioid cells showing mild to moderate pleomorphism and lacked necrosis. Only 1 case showed multinucleated cells. All 8 cases of SMARCA4-dNSCLC showed an immunoprofile similar to that of the SMARCA4-rNSCLC cases, including immunoreactivity for AE1/AE3, a lack of immunoreactivity for thyroid transcription factor-1/Napsin A, and p40/p63 but with a loss of BRG1 expression.
SMARCA4-dNSCLCs exhibited high-grade cytologic features with marked pleomorphism and might show multinucleation and plasmacytoid morphology. In contrast, SMARCA4-rNSCLCs often show mild to moderate pleomorphism with round to polygonal shapes. Both characteristically lack expression of lung adenocarcinoma/squamous markers. Increased awareness of their cytomorphologic features on fine needle aspiration can ensure consideration of the diagnosis.
SMARCA4/BRG1（Brahma 相关基因 1）的失活已在一部分非小细胞肺癌（NSCLC）中得到证实，SMARCA4/BRG1 是腺苷三磷酸依赖性染色质重塑复合物的开关/蔗糖非发酵亚家族的成员。然而，SMARCA4 缺陷型 NSCLC（SMARCA4-dNSCLC）的细胞形态特征很少有报道。
从我们机构的数据库中检索了 8 例 SMARCA4-dNSCLC 细胞学病例和 8 例 SMARCA4 保留型 NSCLC（SMARCA4-rNSCLC）病例，并对其进行了细胞学和免疫表型比较。
8 例 SMARCA4-dNSCLC 患者均有吸烟史，4 例有既往癌症史。细胞学上，肿瘤主要表现为松散聚集的高级别上皮样细胞，核异型性明显，核仁显著。5 例可见双核/多核细胞。6 例有局灶性浆细胞样形态，2 例有坏死。相比之下，8 例 SMARCA4-rNSCLC 病例的抽吸物主要为黏附性，局灶性、松散聚集的上皮样细胞表现为轻度至中度异型性，无坏死。仅 1 例有多核细胞。8 例 SMARCA4-dNSCLC 病例均表现出与 SMARCA4-rNSCLC 病例相似的免疫表型，包括 AE1/AE3 阳性，甲状腺转录因子-1/Napsin A 阴性，p40/p63 阳性，但 BRG1 表达缺失。
SMARCA4-dNSCLC 具有高级别的细胞学特征，异型性明显，可能表现出多核化和浆细胞样形态。相比之下，SMARCA4-rNSCLC 通常表现为轻度至中度异型性，形状为圆形至多边形。两者均特征性地缺乏肺腺癌/鳞状标记物的表达。在细针抽吸细胞学中提高对其细胞形态特征的认识，可以确保考虑到这一诊断。
