Thoracic SMARCA4-Deficient Undifferentiated Tumors With Unusual Presentations: A Case Series

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.

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.

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.

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.

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.