Thoracic SMARCA4-deficient undifferentiated tumor

Abstract

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.

Imaging performance of thoracic SMARCA4-deficient undifferentiated tumor: a case report and literature review

“…The tumor imaged by 18 F-FDG-PET/CT also demonstrated a strong metabolic activity. In addition, SMARCA4-UT often showed marked necrosis ( 20 ). It should be suspected if the chest mass is large, heterogeneous, and exhibits infiltration and compression of surrounding tissues, accompanied by necrotizing lymphadenopathy ( 21 ).…”

A Rare Case of Thoracic SMARCA4-Deficient Undifferentiated Tumor With Diffuse Brain Metastasis

“…The location of the metastasis will also contribute to other symptoms such as neurological deficits and seizures from brain metastasis, localized pain and pathological fractures from bone metastasis, or jaundice and elevated liver enzymes from liver metastasis. It can be difficult to distinguish from other thoracic tumor diagnoses, and differential diagnoses include non-small cell lung cancer (NSCLC), small cell lung cancer (SCLC), SMARCA4-deficient NSCLC, breast cancer, renal cell carcinoma, melanoma, colorectal cancer, gastroesophageal cancer, thyroid cancer, thymic cancer, lymphoma, neuroendocrine carcinomas, malignant mesothelioma, NUT carcinomas, and other rare thoracic sarcomas [1][2][3]. Many other differential diagnoses can present with similar diffuse multiple intracranial lesions as well, including but not limited to glioblastoma multiforme, gliomatosis cerebri, primary central nervous system lymphoma (PCNSL), medulloblastoma, multiple sclerosis, sarcoidosis, acute disseminated encephalomyelitis, neurocysticercosis, toxoplasmosis, tuberculosis, anti-NMDA receptor encephalitis, and progressive multifocal leukoencephalopathy (PML) [11].…”

“…These tumors are characterized by poorly differentiated cells, often with small cell, epithelioid, or rhabdoid appearance, expressing variable epithelial markers [3]. The somatic mutation of SMARCA4 and the loss of Brahmarelated gene 1 (BRG1) protein are hallmarks of these tumors [1][2][3]. Other findings that support this diagnosis include loss of BRM, negative claudin-4, and positive expression of SOX2, CD34, and SALL4 [2][3]9].…”

“…However, SMARCA4-deficient NSCLC (SMARCA4-dNSCLC) typically has differentiated squamous or glandular histology and is recognized as a separate tumor entity from SMARCA4-UT under the WHO Thoracic Tumor Classification [5]. Clinical signs and symptoms of this tumor are similar to other malignancies that involve the thorax, including dyspnea, chest pain, regurgitation, fatigue, unintentional weight loss, appetite change, and local or systemic symptoms determined by the site of distal metastasis [1][2][3]. Thoracic SMARCA4-UT commonly metastasizes to lymph nodes, bones, adrenal glands, liver, gastrointestinal tract, central nervous system, and kidney [6][7][8][9].…”

A Rare Case of Rhabdoid Pancreatic Carcinoma: Prolonged Disease-Free Survival Following Upfront Resection and Adjuvant Chemotherapy

“…Loss of BRG1 or BRM is seen in 30% of NSCLC cell lines; there is concomitant loss in 10% of NSCLC cases which is associated with poor survival [ 34 ]. An aggressive, undifferentiated thoracic malignancy, SMARCA4-UT, is typified by loss of the ATPase BRG1 and cytopathological resemblance to SMARCB1/INI1-deficient rhabdoid tumors [ 35 ].…”