Spindle Cell Carcinoma of the Head and Neck: Clinical Characteristics and Molecular Signatures.

Objective/Hypothesis: Spindle cell carcinoma of the head and neck (HNSpCC) is a rare variant of head and neck squamous cell carcinoma (HNSCC). This study evaluated the clinical characteristics and molecular signatures of such tumors. Study Design: Retrospective analysis. Methods: Medical records of patients diagnosed with HNSpCC from 1996 to 2018 were reviewed. The clinicopathologic features, treatment modalities, and survival status were carefully recorded. Whole exome sequencing (WES) was performed to evaluate the genetic signatures of HNSpCC. Results: We found that among all 71 patients included in this study, the majority of them were male, with tumors developing predominantly in the oral cavity. The 1‐, 3‐, and 5‐year disease‐specific survival (DSS) rates were 64.6%, 49.5%, and 43.9%, respectively. A high local recurrence (LR) and distant metastasis (DM) rate (47.9%–25.3%, respectively) were observed. A significant proportion (28.2%) of patients with the worst prognosis had history of previous head and neck cancer (HNC) and had been treated with radiotherapy (RT). WES revealed that those post‐RT SpCC shared common mutations with their previous HNC (pre‐RT SCC), but gained additional genetic traits, such as hypoxia and cell‐ECM interaction that were favorable for survival in an irradiated microenvironment. Distinct genetic landscapes in primary and post‐RT SpCC were also found. Conclusions: This study demonstrates that HNSpCC is a unique entity with more aggressive behavior than conventional HNSCC. HNSpCC arising from a previously irradiated field is a predictor of dismal survival. Both genetic and microenvironmental factors contribute to this highly invasive tumor. Level of Evidence: 4 Laryngoscope, 133:2183–2191, 2023 [ABSTRACT FROM AUTHOR]