Case Report: Thoracic SMARCA4-deficient undifferentiated tumor with extraocular muscle metastasis: a rare case hidden...

Thoracic SMARCA4-deficient undifferentiated tumor (SMARCA4-UT) is a recently recognized, highly aggressive malignancy characterized by loss of SMARCA4 (BRG1) expression and a strong propensity for early metastasis. Orbital metastases are rare, and involvement of extraocular muscles (EOMs) has not been previously reported.

A 60-year-old man presented with a 5-day history of binocular diplopia and significant ocular pain. Ophthalmic examination revealed mild left eye proptosis, exotropia, and restricted ocular motility. Orbital imaging demonstrated a nodular lesion involving the left inferior rectus muscle, initially suspected to be an orbital inflammatory pseudotumor. Despite systemic steroid therapy, symptoms progressed. Surgical excision of the lesion revealed an undifferentiated tumor with cystic-solid features. Immunohistochemistry showed positivity for cytokeratin and INI-1, complete loss of BRG1 expression, a high Ki-67 index, and wild-type p53, consistent with SMARCA4-deficient undifferentiated tumor. Subsequent systemic evaluation identified a primary lesion in the left upper lung lobe with mediastinal lymphadenopathy and adrenal gland involvement. Mediastinal lymph node biopsy confirmed metastatic SMARCA4-UT. The patient died soon after one cycle of chemotherapy and immunotherapy, with brain metastases as the likely cause of death.

This case represents the first reported instance of thoracic SMARCA4-UT presenting initially as an isolated metastasis to the inferior rectus muscle. It underscores the diagnostic challenges posed by atypical orbital lesions and highlights the importance of early tissue diagnosis when a suspected inflammatory condition fails to respond to therapy. SMARCA4-UT should be considered in the differential diagnosis of extraocular muscle masses, as early recognition is critical for appropriate oncologic management.