Undifferentiated Carcinoma of Esophagus with SMARCA4 Deletion Expressing Synaptophysin: A Potential Diagnostic Pitfall

Abstract

Undifferentiated carcinoma of the esophagus is an entity that is included in WHO classification of digestive systems fifth edition (2018). The definition of this entity is a malignant esophageal epithelial tumor that lacks definite microscopic features of squamous, glandular, or neuroendocrine differentiation. It is a challenging diagnosis to make due to lack of diagnostic criteria. We report a case from a 45 years old man with a mass in the lower third of esophagus. Biopsy showed an epitheloid neoplasm with sheet like growth pattern and no glandular formation. The tumor cells had prominent nucleoli and indistinct cell borders. There were occasional rhabdoid cells. By immunostains, tumor cells were focally positive for pankeratin, keratin 7, synaptophysin, negative for CDX2 and p40, INSM1, chromogranin, and CD56. Background intestinal metaplasia (Barrett esophagus) was present. Next generation sequencing of the tumor revealed SMARCA4 deep deletion. The tumor showed loss of SMARCA4 by immunostain. This case demonstrates that undifferentiated carcinoma of the esophagus with SMARCA4 deletion can express synaptophysin. Awareness of this entity is important for the correct classification of this tumor.