SMARCA4-Deficient Thoracic Sarcoma

Foot, Oliver; Hällin, Magnus; Jones, Robin L.; Thway, Khin

doi:10.1177/1066896920938134

Cited by 3 publications

(4 citation statements)

References 5 publications

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“…Inactivating mutations of the SMARCA4 gene and loss of the BRG1 protein define a recently recognized entity, SMARCA4‐dTS, which is a very aggressive neoplasm with an often fatal outcome 9‐13 . Similar SMARCA4 mutations/BRG1 loss also are reported in a small subset (range, 3%‐6%) of NSCLCs (SMARCA4‐dNSCLCs) 15‐17 .…”

Section: Discussionmentioning

confidence: 93%

“…The loss of SMARCA4/BRG1 was first identified as a feature of high‐grade thoracic sarcomas, termed SMARCA4‐deficient thoracic sarcomas , which are driven by somatic mutation of SMARCA4 and occur more often in adult male smokers, with rapid progression and a poor prognosis 9‐12 . These sarcomas commonly express CD34, SALL4 (Sal‐like protein), and, with increased genomic instability, frequent TP53 mutations, along with higher tumor mutation burdens 9,11,13,14 …”

Section: Introductionmentioning

confidence: 99%

“…[9][10][11][12] These sarcomas commonly express CD34, SALL4 (Sal-like protein), and, with increased genomic instability, frequent TP53 mutations, along with higher tumor mutation burdens. 9,11,13,14 Mounting evidence also indicates that SMARCA4/ BRG1 loss is associated with subsets of poorly differentiated/undifferentiated carcinomas in adults in various anatomic sites, including the lung. 14,15 As a result of increased recognition of SMARCA4 alterations due to the use of comprehensive next-generation sequencing as a routine workup for non-small cell lung carcinoma (NSCLC), SMARCA4-deficient NSCLC (SMARCA4-dNSCLC) has arisen as a distinct NSCLC subset.…”

Section: Introductionmentioning

confidence: 99%

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Cytomorphologic features of SMARCA4‐deficient non–small cell lung carcinoma and correlation with immunohistochemical and molecular features

Sun

Gilani

Podany

et al. 2022

Cancer Cytopathology

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BACKGROUND: SMARCA4/BRG1-deficient tumors and those that have loss of SMARCA/BRG1 have been described as various aggressive carcinomas and sarcomas, including a subset of non-small cell lung carcinoma (NSCLC). Cytomorphologic features of NSCLCs are yet to be described. The objective of this study was to evaluate the cytomorphologic features, immunohistochemical profile, and molecular profile of SMARCA4/BRG1-deficient NSCLC (SMARCA4-dNSCLC). METHODS:The authors retrospectively searched for cases with SMARCA4/BRG1 functional loss alterations, which were identified in molecular studies and further confirmed by immunocytochemistry, and they reviewed the cytomorphologic features. Tumors with BRG1 loss were also stained with an extensive antibody panel. Molecular profiling and clinical information of the identified cases were scrutinized. RESULTS: In total, 12 cytopathology cases from different anatomic sites were included. All cases showed variable expression of cytokeratin irrespective of type. One-half of cases had glandular features, followed by squamoid features, and poorly differentiated features. The most common cytologic features included sheets or papillary architecture, round or oval cell shapes, nuclear enlargement, moderate-to-marked pleomorphism, and coarse chromatin. Two cases with poorly differentiated cytomorphology had a predominance of single cells, scant cytoplasm, and macronucleoli. Variable expression of epithelial markers was noted in all cases. TP53 was the most frequently co-mutated gene in SMARCA4-dNSLCs. CONCLUSIONS: This study demonstrates that SMARCA4-dNSCLCs can have a wide spectrum of cytomorphologic features, ranging from a relatively well differentiated adenocarcinoma to a poorly differentiated/undifferentiated carcinoma, with the majority of cases exhibiting some high-grade features, such as mitosis, apoptosis, necrosis, and marked pleomorphism.

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Section: Discussionmentioning

confidence: 93%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Cytomorphologic features of SMARCA4‐deficient non–small cell lung carcinoma and correlation with immunohistochemical and molecular features

Sun

Gilani

Podany

et al. 2022

Cancer Cytopathology

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“…SMARCA4-UT cells exhibited well-defined boundaries, sparse to medium cytoplasm, enlarged vesicular nuclei, and prominent nucleoli. Moreover, some SMARCA4-UT cells were observed to exhibit nuclear eccentricity and eosinophilic cytoplasm [ 7 , 20 – 23 ]. SMARCA4-UT is highly malignant and exhibits some necrosis areas [ 24 ].…”

Section: Introductionmentioning

confidence: 99%

Thoracic SMARCA4-deficient undifferentiated tumor

Jiang¹,

Chen²,

Gong³

et al. 2023

Discov Onc

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Thoracic SMARCA4-deficient undifferentiated tumor (SMARCA4-UT) is a recently described smoking-related malignancy. The pathogenesis of SMARCA4-UT is the mutational inactivation and loss of expression of a subunit encoding the mammalian switch/sucrose nonfermenting ATPase-dependent chromatin remodeling complex (which can be mobilized using adenosine triphosphate hydrolysis nucleosomes and regulate other cellular processes including development, differentiation, proliferation, and apoptosis), in particular SMARCA4 and SMARCA2. The dynamic activity of this complex plays an important role in regulating the activation and repression of gene expression programs. SMARCA4-UT exhibits morphological features similar to the malignant rhabdoid tumor (MRT), small cell carcinoma of the ovary of the hypercalcemic type (SCCOHT), and INI1-deficient tumor, but SMARCA4-UT differs from SCCOHT and MRT from a genomic perspective. SMARCA4-UT mainly involves the mediastinum and lung parenchyma, and appears as a large infiltrative mass that easily compresses surrounding tissues. At present, chemotherapy is a common treatment, but its efficacy is not clear. Moreover, the inhibitor of the enhancer of zeste homolog 2 showed promising efficacy in some patients with SMARCA4-UT. This study aimed to review the clinical characteristics, diagnosis, treatment, and prognosis of SMARCA4-UT.

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