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

Area of Science:

• Oncology
• Pathology
• Genetics

Background:

• Thoracic SMARCA4-deficient undifferentiated tumor (SMARCA4-UT) is an aggressive neoplasm associated with SMARCA4 inactivating mutations.
• This tumor type is characterized by rhabdoid morphology, high mitotic activity, and necrosis, typically affecting young smokers.

Purpose of the Study:

• To describe and compare three unusual presentations of SMARCA4-UT in older adults.
• To discuss the molecular characteristics of SMARCA4-UT and their relation to SMARCA4-altered non-small-cell lung carcinomas.
• To highlight a case presenting as a metastatic lesion mimicking primary bone sarcoma.

Main Methods:

• Case identification via natural language search in CoPath.
• Histopathological examination of hematoxylin and eosin, Papanicolaou, and Diff-Quik stained slides.
• Immunohistochemical evaluation including BRG1/SMARCA4 staining.
• Next-generation sequencing for molecular testing of SMARCA4 alterations.

Main Results:

• Three patients aged 58-70 years with significant smoking history were identified.
• Presentations included an iliac bone mass with mediastinal lymphadenopathy, mediastinal adenopathy, and a paratracheal mass.
• All tumors exhibited diffuse proliferation of pleomorphic rhabdoid cells, high mitotic activity, necrosis, and loss of SMARCA4 expression; molecular testing confirmed SMARCA4 alterations in two cases.

Conclusions:

• Thoracic SMARCA4-UT should be included in the differential diagnosis of pleomorphic rhabdoid tumors in older adults with a smoking history.
• While typically presenting as lung/mediastinal masses, SMARCA4-UT can present as metastasis, mimicking undifferentiated sarcoma and posing a diagnostic challenge.