SMARCA4-Deficient Undifferentiated Esophageal Carcinoma: A Clinical Case Series and Literature Review

• Published in: Journal of gastrointestinal cancer Vol. 55; no. 3; pp. 1433 - 1440
• Main Authors: Shweikeh, Faris, Hong, Gordon, Walter, Jacob, Hoscheit, Matthew, Lembo, Anthony, Mouchli, Mohamad, Lane, Jason
• Format: Journal Article
• Language: English
• Published: New York Springer US 01.09.2024
• Subjects: Aged, 80 and over; Cancer Research; Case Report; DNA Helicases - deficiency; DNA Helicases - genetics; Esophageal Neoplasms - genetics; Esophageal Neoplasms - pathology; Female; Gastroenterology; Humans; Internal Medicine; Male; Medicine; Medicine & Public Health; Middle Aged; Nuclear Proteins - deficiency; Nuclear Proteins - genetics; Oncology; Radiotherapy; Transcription Factors - deficiency; Transcription Factors - genetics; Undifferentiated carcinoma; SMARCA genes; Histopathology; Chemoradiation; Esophageal cancer
• ISSN: 1941-6628; 1941-6636; 1941-6636
• DOI: 10.1007/s12029-024-01060-4

Purpose Undifferentiated carcinoma of the esophagus (UEC) is a rare malignancy. Deficiency in SMARCA genes, critical for chromatin regulation, has been observed in cases of UEC. Research in UEC is sparse, however, and we present a case series along with a comprehensive review of the literature. Case Series Case 1 is a 49-year-old female with abdominal pain and dysphagia and esophagogastroduodenoscopy (EGD) showing a friable mass at the gastroesophageal (GE) junction. Biopsies showed a poorly differentiated neoplasm and immunohistochemistry showed loss for SMARCA4. With metastatic disease, she agreed to undergo palliative chemotherapy and radiation, passing away at 4 months. Case 2 is an 88-year-old male with dysphagia, nausea, vomiting, and distal esophageal mass with biopsy showing a malignancy with loss of SMARCA4 expression. Due to extensive metastases, he was counseled on hospice care. Case 3 is a 53-year-old male with extensive alcohol and smoking history presenting with hematemesis, passing away shortly. Posthumous histopathology consistent with undifferentiated SMARCA4-deficient carcinoma of the esophagus. Results of the literature review indicate a predilection towards males (75.0%) and a variable age range (39–88 years). Majority (76.2%) reported with a distal esophagus location. Metastatic disease was common at initial presentation. Median survival was 2.60 months. Some were managed with chemotherapy and radiation. Conclusions Research in SMARCA-deficient UEC is very limited. It is more common in men, age is variable, and associated with Barret’s esophagus. Further research is necessary to better understand it and to establish treatment guidelines; however, it is clear that SMARCA4-deficient UEC carries a significantly poor prognosis.