背景:胸部SMARCA4缺陷型未分化肿瘤(SMARCA4-UT)是一种最近描述的年轻吸烟者的侵袭性肿瘤,由SMARCA4失活突变定义并以横纹肌形态细胞为特征,高有丝分裂活性,和丰富的坏死。
目的:描述并比较老年人SMARCA4-UT的3种异常表现,包括一个表现为模仿原发性骨肉瘤的转移灶。讨论SMARCA4-UT的分子特征及其与非小细胞肺癌SMARCA4的关系。
方法:使用CoPath中的自然语言搜索确定了三名SMARCA4-UT患者。检查了所有患者的苏木精和曙红切片以及第一例患者的Papanicolaou染色的载玻片和Diff-Quik染色的载玻片。广泛的免疫染色,包括BRG1/SMARCA4,进行了评估。通过下一代测序进行分子检测。
结果:3例患者年龄分别为58、70和70岁。他们都有明显的吸烟史。首例患者表现为髂骨量和纵隔淋巴结肿大,第二个是纵隔腺病,第三个有气管旁肿块。3例肿瘤均表现为弥漫性多形性增生,横纹肌样细胞有丝分裂活性高,肿瘤坏死。通过免疫组织化学,SMARCA4在所有3种肿瘤中丢失。分子测试显示SMARCA4在前2个中有改变。
结论:在有吸烟史的老年人多形性横纹肌样瘤的鉴别诊断中,应考虑胸部SMARCA4-UT。尽管大多数表现为肺和/或纵隔肿块,它们可能偶尔表现为转移和模拟未分化肉瘤,代表潜在的诊断缺陷。
BACKGROUND: Thoracic SMARCA4-deficient undifferentiated tumor (SMARCA4-UT) is a recently described aggressive neoplasm of young smokers defined by SMARCA4 inactivating mutations and characterized by cells with rhabdoid morphology, high mitotic activity, and abundant necrosis.
OBJECTIVE: Describe and compare 3 unusual presentations of SMARCA4-UT in older adults, including one presenting as a metastatic lesion mimicking a primary bone sarcoma. Discuss the molecular characteristics of SMARCA4-UT and their relationship to nonsmall-cell lung carcinomas with SMARCA4.
METHODS: Three patients with SMARCA4-UTs were identified utilizing a natural language search in CoPath. hematoxylin and eosin sections from all patients as well as Papanicolaou-stained slides and Diff-Quik-stained slides for the first patient were examined. A broad range of immunostains, including BRG1/SMARCA4, were evaluated. Molecular testing was performed via next-generation sequencing.
RESULTS: The 3 patients were aged 58, 70, and 70 years. All had a significant smoking history. The first patient presented with an iliac bone mass and mediastinal lymphadenopathy, the second with mediastinal adenopathy, and the third with a paratracheal mass. All 3 tumors showed a diffuse proliferation of pleomorphic, rhabdoid cells with high mitotic activity and tumor necrosis. SMARCA4 was lost in all 3 tumors by immunohistochemistry. Molecular testing revealed SMARCA4 alterations in the first 2.
CONCLUSIONS: Thoracic SMARCA4-UT should be considered in the differential diagnosis of pleomorphic rhabdoid tumors in older adults with a smoking history. Although most present as lung and/or mediastinal masses, they may occasionally present as a metastasis and mimic an undifferentiated sarcoma, representing a potential diagnostic pitfall.