Rokia Sakr, Jingjing Hu, Charmi Patel
Esophageal squamous cell carcinoma (SCC) is a significant global health issue, and spindle cell squamous cell carcinoma (SpCC) is a rare variant accounting for up to 2% of cases. SpCC is characterized by a biphasic histological pattern comprising both carcinomatous and sarcomatous components. Patients typically present with dysphagia, painful swallowing, and weight loss. Diagnosis is challenging due to sampling limitations in biopsy specimens, often leading to misclassification as conventional SCC or sarcoma. In this case, a white American 65-year-old male presented with worsening dysphagia and weight loss. Endoscopic evaluation revealed a large fungating mass in the middle third of the esophagus. Initial biopsy showed a high-grade malignant neoplasm, but immunohistochemistry (IHC) was inconclusive. Further imaging confirmed a primary esophageal tumor with regional lymph node involvement. The patient underwent neoadjuvant therapy followed by surgical resection. Post-treatment pathology confirmed SpCC with nodal metastasis. SpCC pathogenesis remains unclear, but high Programmed death-ligand 1 (PD-L1) expression at the tumor invasive front, along with epithelial-mesenchymal transition (EMT) markers ZEB1 and TWIST, suggests a role in tumor progression. Molecular studies indicate frequent TP53 mutations, receptor tyrosine kinase alterations, and PI3K pathway mutations. While surgical resection remains the primary treatment, emerging evidence supports the role of PD-L1 inhibitors and targeted therapies. Despite its aggressive histology, SpCC has a relatively favorable prognosis when diagnosed early, with a five-year survival rate of approximately 60%. Further research is needed to optimize treatment strategies for this rare malignancy.