SMARCA4-deficient lung adenocarcinoma with oral cavity metastasis: a case report

SMARCA4-deficient non-small cell lung cancer (NSCLC) is a distinct molecular subtype associated with aggressive clinical behavior and poor prognosis. Oral cavity metastasis from lung adenocarcinoma is rare, and presentation with gingival masses as the initial manifestation is exceptionally uncommon. A 79-year-old man, a never smoker presented with bilateral gingival masses. PET-CT revealed a primary tumor in the right lung with extensive systemic metastases (cT3N3M1c, Stage IVB). Biopsies of both the lung and gingival lesions demonstrated moderately to poorly differentiated adenocarcinoma with complete loss of SMARCA4 (BRG1) expression by immunohistochemistry. A notable diagnostic challenge was the absence of TTF-1 expression in both primary and metastatic sites, which is atypical for conventional lung adenocarcinoma. Molecular testing excluded common driver mutations and MAML2 rearrangement. Following multidisciplinary discussion, the patient was diagnosed with SMARCA4-deficient adenocarcinoma. First-line systemic therapy with chemotherapy plus bevacizumab and a PD-1 inhibitor was planned; however, the patient was subsequently lost to follow-up. This case highlights the aggressive nature and atypical metastatic pattern of SMARCA4-deficient lung adenocarcinoma, which can present with isolated oral manifestations despite advanced stage IVB disease. The lack of TTF-1 expression may pose a diagnostic pitfall, underscoring the importance of including SMARCA4 immunohistochemistry in the workup of poorly differentiated carcinomas of unknown primary. Clinicians should consider lung primary in patients presenting with unexplained oral lesions.