Search

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]

Background: Radiation‐induced sarcoma of the head and neck (RISHN) is a rare yet devastating potential complication of radiotherapy treatment. We aimed to evaluate the clinicopathological characteristics and molecular signatures of RISHN in patients who underwent radiotherapy for head and neck cancer (HNC) to identify high‐risk patients and enable earlier cancer detection. Methods: This study retrospectively evaluated 24 sarcoma patients who received radiotherapy for HNC between 1994 and 2019. Patients were divided into two groups based on RISHN latency period. Patient demographics, initial tumor staging, risk factors, and survival between groups were analyzed, and whole‐exome sequencing (WES) of selected samples was performed. Results: The median age at diagnosis of RISHN was 54 years, and the male‐to‐female ratio was 2:1. The latency period ranged from 0.8 to 64.4 years (median 6.5 years), with a median survival of 21.5 months. Primary cancer in the oral cavity, treatment with alkylating agents, alcohol consumption, betel nut chewing, and smoking were identified as risk factors for short (<5 years) latency periods. The majority of RISHN cases occurred in the oral cavity (58.3%). WES analysis showed that tumor necrosis factor and cell cycle checkpoint pathways were differentially involved in both patient groups. Conclusions: Although case numbers were small, our cohort represents the largest case series of RISHN from a single institution to date. Clinicians must be aware of factors affecting RISHN development and latency, and risk factor identification may lead to earlier detection and prevention in the future. [ABSTRACT FROM AUTHOR]

The cell dynamics and cell origin for anagen hair follicle (HF) repair following chemotherapeutic injury are unclear. We first mapped the HF response to cyclophosphamide (CYP) at natural anagen VI in mice. We found that 30‐60 mg/kg of CYP leads to dose‐dependent HF dystrophy that was spontaneously repaired with anagen resumption, while 120 mg/kg of CYP prematurely induced catagen/telogen entry. To explore how anagen HF repair is achieved in the dystrophic anagen pathway, we analysed the cell dynamics at 30 mg/kg of CYP. Hair bulbs first shrunk due to matrix cell apoptosis associated with DNA double‐strand breaks. DNA damage was repaired, and ordered hair bulb structures were restored within 96 hours. Bulge stem cells did not undergo apoptosis nor proliferation. K5+ basal lower proximal cup cells and outer root sheath cells quickly replenished the cells in the germinative zone and regenerated the concentric layered structures of the lower HF segment. Therefore, anagen HFs are able to summon extra‐bulge progenitor cells in close proximity to the damaged matrix for quick repair after CYP injury. [ABSTRACT FROM AUTHOR]