Case Report: Synaptophysin-positive SMARCA4-deficient undifferentiated thoracic tumour: a diagnostic pitfall with therapeutic implications.

SMARCA4-deficient undifferentiated thoracic tumour (SMARCA4-UT) is a rare and highly aggressive malignancy with a poor prognosis and no established standard therapy. Isolated synaptophysin (Syn) expression may further complicate its differential diagnosis, particularly from neuroendocrine tumours. We report a 43-year-old male smoker with metastatic SMARCA4-UT, characterised by complete loss of SMARCA4/BRG1, a high Ki-67 index, and isolated Syn positivity, whereas other neuroendocrine markers were negative. The patient achieved a durable partial response lasting more than 12 months after platinum-based chemoimmunotherapy. This case highlights the potential clinicopathologic relevance of isolated Syn positivity in SMARCA4-UT. In this setting, isolated Syn positivity is more likely to reflect limited lineage de-repression rather than true neuroendocrine differentiation, and it may be associated with meaningful clinical benefit from chemoimmunotherapy. Isolated Syn positivity in SMARCA4-UT may represent a clinicopathologically relevant phenotype with potential therapeutic implications. Further studies are needed to clarify its diagnostic value and its possible association with treatment response.