Primary Signet-Ring Carcinoma (SRC) of the Lung A Population-Based Epidemiologic Study of 262 Cases with Comparison to Adenocarcinoma of the Lung

Background: The presence of signet-ring cell component has been described as a prominent feature of EML4-ALK positive non-small cell lung cancer. We investigated the clinicopathologic features and survival outcome of primary signet-ring carcinoma (SRC) of the lung with comparison to adenocarcinoma of the lung. Methods: Retrospective population-based analysis of histologically diagnosed primary SRC of the lung in the California Cancer Registry between 1989 and 2006 with comparison with adenocarcinoma of the lung. Results: Two hundred sixty-two histologically diagnosed primary SRC of the lung were compared to 50,089 patients with lung adenocarcinoma. Patients with primary SRC of the lung were significantly younger than patients with adenocarcinoma, with a significantly higher proportion of poorly differentiated tumor and stage IV disease. There was no difference in the distribution of gender and ethnicity among patients with SRC when compared to patients with adenocarcinoma. Subset analysis of patients with available smoking status revealed never smokers comprised a significantly higher proportion of patients with SRC (30.8%) when compared to patients with adenocarcinoma (11.0%; p = 0.0013). Never smokers with SRC tended to be younger with a trend to improved survival (median age = 55 years, median overall survival [OS] = 8 months) than ever smokers with SRC (median age = 59 years, median OS = 4.5 months). Patients with SRC had decreased OS (versus adenocarcinoma; unadjusted hazard ratio = 1.507; 95% confidence interval: 1.326-1.714; p < 0.0001) and was an independent unfavorable prognostic factor by multivariate analysis (versus adenocarcinoma, hazard ratio 1.214, 95% confidence interval: 1.068-1.381; p = 0.0030). Conclusions: Primary SRC of the lung is a rare subtype of adenocarcinoma, carries a worse prognosis when compared to adenocarcinoma and shares many of the recently identified clinicopathologic characteristics ascribed to EML4-ALK positive non-small cell lung cancer.