From Gene Mark and colleagues: Tumor Islands in Resected Early-stage Lung Adenocarcinomas are Associated With Unique Clinicopathologic and Molecular Characteristics and Worse Prognosis

http://www.ncbi.nlm.nih.gov/pubmed/23095504

Am J Surg Pathol. 2012 Oct 19. [Epub ahead of print]

Tumor Islands in Resected Early-stage Lung Adenocarcinomas are Associated With Unique Clinicopathologic and Molecular Characteristics and Worse Prognosis.

Onozato ML, Kovach AE, Yeap BY, Morales-Oyarvide V, Klepeis VE, Tammireddy S, Heist RS, Mark EJ, Dias-Santagata D, Iafrate AJ, Yagi Y, Mino-Kenudson M.

Source

*Department of Pathology †Cancer Center, Massachusetts General Hospital Departments of ‡Medicine §Pathology, Harvard Medical School, Boston, MA.

Abstract

Tumor islands-large collections of tumor cells isolated within alveolar spaces-can be seen in lung adenocarcinomas. Recently we observed by 3-dimensional reconstruction that these structures were connected with each other and with the main tumor in different tissue planes, raising the possibility of tumor islands being a means of extension. However, the clinical and prognostic significance of tumor islands remains unknown. In this study, we compared clinicopathologic and molecular characteristics and prognosis of stages I to II lung adenocarcinomas with tumor islands (n=58) and those without (n=203). Lung adenocarcinomas with tumor islands were more likely to occur in smokers, exhibit higher nuclear grade and a solid or micropapillary pattern of growth, and harbor KRAS mutations. In contrast, lung adenocarcinomas without tumor islands were more likely to present as minimally invasive adenocarcinoma, show a lepidic pattern of growth, and harbor EGFR mutations. Although there was no difference in stage, the prognosis of lung adenocarcinomas with tumor islands was significantly worse than those without. The 5-year recurrence-free survival for patients with tumor islands and those without was 44.6% and 74.4%, respectively (log rank P=0.010). The survival difference remained significant (P <0.020) by multivariate analysis, and the presence of tumor islands was associated with almost 2-fold increase in the risk of recurrence. Even in the stage IA cohort, more than half of the patients with tumor islands experienced recurrence within 5 years. Thus, aggressive surveillance and/or further intervention may be indicated for patients whose tumors exhibit tumor islands.