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

Abstract

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.

Keywords: Chemoradiation; Esophageal cancer; Histopathology; SMARCA genes; Undifferentiated carcinoma.

Fig. 1

Endoscopy from Case 1 showed a necrotic friable, hard mass extending from 30 to 38 cm. Salmon colored mucosa noted in the background in combination with the mass suggested malignancy in the background of Barrett’s esophagus

Fig. 2

H&E-stained sections of tumor from Case 2 showed an invasive high-grade epithelioid malignancy with sheet-like pattern of growth infiltrating below benign glandular epithelium (×40 total magnification). Separate biopsy fragments demonstrated Barrett’s esophagus with glandular dysplasia (inset, ×100)

Fig. 3

High magnification (×400) H&E-stained section from Case 2 showed discohesive cells with moderate amounts of eosinophilic cytoplasm and focal features suggestive of rhabdoid morphology (center of image). The tumor nuclei were enlarged and somewhat monomorphic with prominent nucleoli and mitotic activity was brisk. SMARCA4 immunohistochemistry (inset, ×100) showed loss of nuclear expression in the tumor cells while retained within the benign glandular epithelium and inflammatory cells which served as a positive internal control