Thoracic SMARCA4-deficient undifferentiated tumour: Diagnostic challenges and potential for misdiagnosis in small...

We report a diagnostically challenging case of a SMARCA4-deficient undifferentiated tumour to emphasize its potential to mimic other malignant tumours on histology, especially in small biopsies and where rhabdoid morphology is lacking. A 48-year-old man, who was known for chronic obstructive pulmonary disease and polysubstance use, presented with dyspnoea and an anterior mediastinal mass that had grown rapidly over a seven-month period. The rapid growth and location in the anterior mediastinum raised clinical suspicion for lymphoma or a germ cell tumour. Microscopic examination of a transthoracic, ultrasound-guided, core needle biopsy revealed relatively uniform, malignant epithelioid cells with clear cytoplasm, but lacking any rhabdoid features. Tumour necrosis was prominent. The immunohistochemistry panel was negative for lymphoma markers, but positive for SALL4 (a marker typically associated with germ cell tumours), CD34, EMA, and HepPar1, while expression of SMARCA4 and claudin-4 was entirely lost. Only focal cytokeratin expression was demonstrated. SMARCB1 (INI1) expression was retained. The diagnosis of SMARCA4-DUT was made based on these findings. Unfortunately, the tumour was already at an advanced stage at diagnosis (stage IVA) and the patient had a poor performance status. He was treated with palliative radiotherapy with no significant improvement in performance status and passed away 3 months after diagnosis. The case highlights the importance of considering SMARCA4-DUT in the differential diagnosis of an undifferentiated, rapidly growing thoracic tumour and the potential for misdiagnosis on a small tissue sample, particularly as rhabdoid morphology may be absent.