Clear cell–type squamous cell carcinoma: An NCDB analysis.

Abstract

e21549 Background: Clear cell–type squamous cell carcinoma (ccSCC) is a rare, aggressive histologic variant of squamous cell carcinoma characterized by clear cytoplasmic features resulting from glycogen accumulation. Immunohistochemical evaluation is essential to distinguish ccSCC from other clear cell neoplasms. Given its rarity, ccSCC is mainly documented in small case series, though available reports highlight recurrence, metastatic potential, and limited therapeutic guidance, underscoring the challenges in management. Population-level data are needed to better define its presentation. To address this, the National Cancer Database (NCDB) was analyzed to determine the demographic profile of patients diagnosed with ccSCC. Methods: A retrospective cohort analysis of the 2004–2020 NCDB identified 476 patients with histologically confirmed ccSCC (ICD-O-3 code 8084). Demographic and clinical variables (age, sex, race, ethnicity, primary site, stage, urban/rural residence, income, insurance status, facility type, treatment, and survival) were analyzed using descriptive statistics, and incidence trends were assessed via regression analysis. Results: This study identified 476 patients with ccSCC diagnosed between 2004 and 2020. The mean age at diagnosis was 67.0 years (SD = 12.3, range = 27–90 years), and the cohort was predominantly female (55.3%), White (82.6%), and non-Hispanic (91.0%). The upper lobe of the lung was the most common primary site (45.2%), and 44.5% presented with Stage I disease. Socioeconomic patterns demonstrated that 80.3% of individuals resided in metropolitan areas and 33.3% lived in the highest income quartile (≥$74,063). Medicare coverage was most common (61.6%), and treatment was largely concentrated in academic/research (40.4%) and comprehensive community cancer programs (34.9%). Tumors measured an average of 46 mm. Surgical intervention was performed in 72.3% of patients, yielding negative margins in 66.0%; radiation and chemotherapy were administered in 32.4% and 34.2% of cases, respectively. Long-term outcomes were poor, with overall survival of 62.7% at two years, 43.4% at five years, and 26.0% at ten years, and a mean survival of 73.3 months. Conclusions: This NCDB analysis provides one of the first large, population-level assessments of ccSCC and reveals several clinically meaningful patterns. Although nearly half of patients presented with Stage I disease, long-term survival remained poor, indicating that early clinical stage may not mitigate the aggressive behavior of this variant. Tumors most often originated in the upper lobe of the lung and occurred predominantly in older, Medicare-insured individuals living in metropolitan areas. Surgical management was common, yet margin-negative resection did not translate into durable survival outcomes. These findings highlight the need for better prognostic tools and more effective treatment strategies for this rare malignancy.