Case Series of SMARCA4-Deficient Undifferentiated Esophageal Carcinoma

Abstract

Undifferentiated esophageal carcinomas (UEC) are rare, with aggressive behavior and a dismal prognosis. An extremely rare subset is the SMARCA4-deficient UEC, which has only been reported in 14 cases to date. We present two cases of male patients (39- and 64-year-old) with SMARCA4-deficient UEC. Both patients had evidence of metastatic disease on presentation, progressed rapidly, and passed away within three months from the presentation. We aim to raise awareness of this underreported disease and contribute to the exploration of the possible underlying pathology and risk factors.

Keywords: brg1; carcinoma; deficient; esophageal; malignancy; smarca4; tumor; undifferentiated.

Figure 1. Case 1 images

A: CT showing an esophageal heterogeneous mass that is 26.9 mm thick in the distal third of the esophagus. B: CT showing innumerable solid hypodense hepatic masses (largest measuring 39.1 mm) with associated upper abdominal lymphadenopathy. C: EGD showing a large, non-obstructing, circumferential, ulcerating mass in the lower third of the esophagus. EGD: esophagogastroduodenoscopy

Figure 2. Case 2 images

A: CT abdomen showing irregular thickening of the distal esophagus and neoplastic infiltration and necrosis along the lateral walls of the esophagus (red arrow). B: CT showing multiple hepatic metastases (red arrows); the largest was 18.4 mm (not shown). C: EGD showing a fungating circumferential, necrotic, distal esophageal ulcer with stigmata of recent bleeding. EGD: esophagogastroduodenoscopy

Figure 3. Pathology findings in both cases

A: Both tumor biopsies showed undifferentiated tumor cells consisting of epithelioid cells arranged in small clusters with overlying intestinal metaplasia (seen as columnar cells with goblet cells on top of the tumor cells). B: Tumor cells strongly positive for SALL4, only in Case 1. C: Loss of SMARCA4/BRG1 within the tumor cells while retained within inflammatory cells (internal control). D: Diffuse infiltration of liver parenchyma with tumor cells, predominantly within the hepatic sinusoids and portal triads (red circle) in Case 2.

Figure 4. Postpartum pathology of Case 2

A: 16 mm liver metastasis (lower right) in a background of diffuse yellow-mottled appearance, consistent with an extensive tumor infiltration within the hepatic sinusoids. B: Near circumferential, 10 cm, necrotic, distal esophageal mass extending through the lateral esophageal walls.