Identification and Treatment of SMARCA4 Deficient Poorly Differentiated Gastric Carcinoma

Abstract

Loss of expression of the SMARCA4 gene, a subunit of the SWI/SNF complex, has been historically associated with thoracic sarcomas. This loss of expression is extremely rare in gastric cancers, and its role in gastrointestinal tract carcinomas has not been fully elucidated. We report a case of a 73-year-old male with poorly differentiated, SMARCA4-deficient gastric cancer, showing that this immunophenotype is not limited to thoracic sarcomas or advanced-stage tumors. These tumors are often resistant to conventional FLOT chemotherapy and have poor prognoses, necessitating the need for early identification and alternative therapeutic approaches. New therapies such as EZH2 inhibitors and etoposide should be considered in cases where standard treatments are ineffective.

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

“…SMARCA4 deficient carcinoma of stomach has been reported to be chemotherapy resistant in individual case report. 12 The treatment response to immune checkpoint inhibitors in patients with thoracic SMARCA4 deficient tumor is controversial in the literature, with some paper reporting a partial treatment response 13 and the other reported limited efficacy. 14 In summary, awareness of the morphology and immunophenotype of this entity, including undifferentiated appearance, variable amount of rhabdoid cells and expression of no more than one neuroendocrine marker is important for making the correct diagnosis.…”

“…SMARCA4 deficient carcinoma of stomach has been reported to be chemotherapy resistant in individual case report. 12 The treatment response to immune checkpoint inhibitors in patients with thoracic SMARCA4 deficient tumor is controversial in the literature, with some paper reporting a partial treatment response 13 and the other reported limited efficacy. 14…”