SMARCA4-deficient Thoracic Sarcomas Clinicopathologic Study of 30 Cases With an Emphasis on Their Nosology and Differential Diagnoses
SMARCA4-deficient Thoracic Sarcomas Clinicopathologic Study of 30 Cases With an Emphasis on Their Nosology and Differential Diagnoses
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DOI：
10.1097/pas.0000000000001188
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发表时间：
2019-04-01
影响因子：
5.6
通讯作者：
Le Loarer, Francois
中科院分区：
文献类型：
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作者：
Perret, Raul;Chalabreysse, Lara;Le Loarer, Francois
smarca4缺陷胸椎肉瘤（SMARCA4-DTS）是最近发现的一种具有侵袭性临床病程和BAF染色质重塑复合体特异性遗传改变的实体。在本研究中，我们回顾了30例SMARCA4-DTS的临床和病理特征，讨论了其主要的鉴别诊断和一般病理学家可能面临的具有挑战性的诊断情景。此外，我们测试了“SMARCA4- dts免疫组化特征”（SMARCA4和SMARCA2的共同缺失与SOX2的过表达）在大量胸内恶性肿瘤中的特异性。患者年龄28 ~ 90岁（中位48岁），男性明显占优势（男女比例为9:1），多为吸烟者。肿瘤通常为位于纵隔（n =13）、胸膜（n = 5）、肺（n = 2）或上述两个或两个以上的地形（n =10）的大压缩肿块。治疗策略多种多样，其中1例采用EZH2抑制剂治疗。中位总生存期为6个月。组织学上，肿瘤低分化，常表现为横纹肌样特征。一小部分病例表现为局灶性黏液样间质（7%,n = 2/30），少数病例表现为以前未报道的类似结缔组织增生的小圆细胞瘤（7%,n = 2/30）。当处理大量坏死肿瘤的活检材料时，诊断是具有挑战性的，在这种情况下，SOX2、CD34和SALL4的表达被证明是有用的。所有检测的病例均伴有SMARCA4和SMARCA2的缺失，大多数肿瘤表达上皮标记物（Pan -keratin或EMA） （n = 29/30）、SOX2 （n = 26/27）和CD34 （n = 17/27）。所有病例均保留SMARCB1表达（23/23）。SALL4和Claudin-4在部分病例中表达（n分别为7/21和2/19）。TTF-1和P63各1例局灶性表达。P40和NUT未表达（分别为0/23和0/20）。SMARCA4-DTS免疫组化标记既敏感又特异性，只有一小部分卵巢高钙血症型小细胞癌表现出重叠表型。我们的研究证实并扩展了SMARCA4-DTS的具体特征，强调它们可以被病理学家直接识别。
SMARCA4-deficient thoracic sarcoma (SMARCA4-DTS) is a recently described entity with an aggressive clinical course and specific genetic alterations of the BAF chromatin remodeling complex. In the present study, we reviewed the clinical and pathologic features of 30 cases of SMARCA4-DTS, discussed its main differential diagnoses and the challenging diagnostic scenarios that the average pathologist may face. In addition, we tested the specificity of the "SMARCA4-DTS immunohistochemical signature" (co -loss of SMARCA4 and SMARCA2 with overexpression of SOX2) in a large cohort of intrathoracic malignancies. Patients ranged from 28 to 90 years of age (median: 48 y), with a marked male predominance (male:female = 9:1) and they were usually smokers. Tumors were generally large compressive masses located in the mediastinum (n =13), pleura (n = 5), lung (n = 2) or in 2 or more of these topographies (n =10). Treatment strategies were varied, including 1 case treated with EZH2 inhibitors. Median overall survival was 6 months. Histologically, tumors were poorly differentiated frequently showing rhabdoid features. A subset of cases showed a focal myxoid stroma (7%, n = 2/30) and rare cases displayed a previously unreported pattern simulating desmoplastic small round cell tumors (7%, n = 2/30). Making a diagnosis was challenging when dealing with biopsy material from massively necrotic tumors and in this setting the expression of SOX2, CD34, and SALL4 proved useful. All tested cases displayed concomitant loss of SMARCA4 and SMARCA2 and most tumors expressed epithelial markers (Pan -keratin or EMA) (n = 29/30), SOX2 (n = 26/27), and CD34 (n = 17/27). SMARCB1 expression was retained in all cases (23/23). SALL4 and Claudin-4 were expressed in a subset of cases (n = 7/21 and 2/19, respectively). TTF-1 and P63 were focally expressed in 1 case each. P40 and NUT were not expressed (0/23 and 0/20, respectively) The SMARCA4-DTS immunohistochemical signature was both sensitive and specific, with only a subset of small cell carcinoma of the ovary hypercalcemic type showing overlapping phenotypes. Our study confirms and expands the specific features of SMARCA4-DTS, emphasizing the fact that they can be straightforwardly identified by pathologists.