Diagnosis and management of gastrointestinal SMARCA4-deficient undifferentiated tumors

Clin J Gastroenterol. 2023 Dec;16(6):807-814. doi: 10.1007/s12328-023-01853-3. Epub 2023 Aug 31.


SMARCA4-deficient undifferentiated tumors are a rare clinical entity with an aggressive clinical course, poor prognosis, and no standard-of-care therapeutic approach. These have most frequently been documented in the lung and thoracic cavity. There is a growing body of evidence for the role of immunotherapy in SMARCA4-deficient lung cancer, a disease process that historically does very poorly with cytotoxic chemotherapy alone. We present three cases where the primary tumors were instead found within the gastrointestinal system: two originating from the small bowel and one from the esophagus. In all three cases, clinical response was seen with pembrolizumab therapy, with two of the three patients receiving long-term benefit. Our series suggests that anti-PD1 immunotherapy may have promising efficacy for undifferentiated carcinomas of the gastrointestinal tract with SMARCA4 deficiency.

Keywords: Immunotherapy; Oncology; PD-L1; SMARCA4; Sarcoma.

MeSH terms

  • Biomarkers, Tumor
  • Carcinoma* / pathology
  • DNA Helicases / genetics
  • Gastrointestinal Tract / pathology
  • Humans
  • Nuclear Proteins / genetics
  • Transcription Factors / genetics


  • Biomarkers, Tumor
  • SMARCA4 protein, human
  • DNA Helicases
  • Nuclear Proteins
  • Transcription Factors