Histomorphology and Molecular Profiling of Well-Differentiated Squamous Cell Carcinoma of the Esophagus Including its Unusual Variants

Esophageal verrucous squamous cell carcinoma and esophageal carcinoma cuniculatum are rare variants of extremely well-differentiated squamous cell carcinoma. These rare tumors share similar risk factors and clinical presentations with conventional esophageal squamous cell carcinoma. However, these tumors have distinct morphological features, molecular mutation profiles, and clinical outcomes. Diagnosis of esophageal verrucous squamous cell carcinoma and esophageal carcinoma cuniculatum can be challenging, requires high clinical suspicion, and often can only be diagnosed on a deep mucosal biopsy or resection specimen. Surgical treatment or endoscopic resection can be curative in early disease. This review presents the histomorphology and molecular profiling of the conventional type and the rare variants of the esophageal well-differentiated squamous cell carcinoma.