Sequential Esophageal Squamous Cell Carcinoma and Small Cell Carcinoma Following Prior Nissen Fundoplication

Primary small cell carcinoma of the esophagus (PSCCE) is a rare and aggressive malignancy with clinical features that often resemble more common esophageal cancers, leading to delayed diagnosis and uncertainty in management. We present a unique case of sequential squamous cell carcinoma followed by PSCCE in the distal esophagus after a previous Nissen fundoplication, emphasizing diagnostic and surveillance challenges. A 63-year-old man with a history of gastroesophageal reflux disease (GERD) and prior fundoplication presented with chest pain and progressive dysphagia. Initial esophagogastroduodenoscopy (EGD) revealed a distal esophageal lesion, and biopsy confirmed invasive squamous cell carcinoma arising from Barrett's mucosa, which was treated with endoscopic mucosal resection. One month later, the patient underwent endoscopic ultrasound (EUS) and endoscopic mucosal resection (EMR); the resection specimen showed squamous cell carcinoma in situ without residual invasive carcinoma and had negative margins. Four months after resection, surveillance endoscopy identified a new friable nodular mass in the distal esophagus. Histopathologic evaluation revealed poorly differentiated small cell carcinoma with a high proliferative index, positive staining for synaptophysin and CAM 5.2, and negative staining for chromogranin and CD45. Staging evaluation revealed no evidence of distant metastases. This report illustrates the rare occurrence of metachronous esophageal cancers with distinct histologic subtypes arising within a short time interval. The rapid development of a second malignancy suggests multifactorial carcinogenesis, including chronic mucosal injury and previous surgical alterations. Given the aggressive nature of PSCCE and the limited evidence available to guide treatment, close surveillance following endoscopic resection of esophageal malignancies is essential, particularly in patients with underlying esophageal pathology. Further studies are needed to better define risk factors and optimal management strategies.