Thoracic SMARCA4-deficient undifferentiated tumor prone to misdiagnosis as lung adenocarcinoma: a case report and literature review

Thoracic SMARCA4-deficient undifferentiated tumor (T-SMARCA4-DUT) is a rare neoplastic entity with a high risk of being misdiagnosed. We report the case of a 64-year-old male initially suspected of having mediastinal lymphoma by contrast-enhanced chest computed tomography (CECCT), and pathologically diagnosed with metastatic poorly differentiated lung adenocarcinoma via cervical lymph node biopsy. Initial immunohistochemical (IHC) results showed TTF-1 (clone SPT24) (+), Napsin A (-), p40 (-), and next-generation sequencing (NGS) detected KRAS amplification and TP53 missense mutation. Combined chemotherapy plus immunotherapy initially shrank the tumor, but bilateral axillary lymphadenopathy subsequently developed. Pathological analysis of axillary metastases and supplementary IHC of the original cervical biopsy revealed SMARCA4/Brg1 (-), SOX2 (+) and TTF-1 (clone 8G7G3/1) (-), leading to a revised diagnosis of lymph node-metastatic T-SMARCA4-DUT. This case identifies the non-specific clinical features of T-SMARCA4-DUT and an inadequate initial IHC panel as the core causes for misdiagnosis and confirms that a definitive diagnosis requires testing for SMARCA4/Brg1, SOX2, and the highly specific TTF-1 (clone 8G7G3/1).