Background and purpose: Gene fusions have been identified as recurrent oncogenic events in lung adenocarcinoma. Our purpose are to study the histologic features of anaplastic lymphoma kinase (ALK)

c-ros oncogene 1 receptor tyrosine kinase (ROS1) and RET proto-oncogene fusion-positive lung adenocarcinomas and to evaluate the correlation between psammoma bodies and fusion-positive lung adenocarcinomas. Methods: In this study

we performed a comprehensive histologic analysis of 44 fusion-positive (including 15 RET

20 ALK and 9 ROS1) lung adenocarcinomas and 111 fusion-negative [including 20 epidermal growth factor receptor (EGFR)

20 Kirsten rat sarcoma viral oncogene (K-ras)

71 pan-negative] lung adenocarcinomas. Results: ALK

RET and ROS1 fusionpositive lung adenocarcinomas were more prevalent in solid or acinar predominant adenocarcinoma. Multivariate analysis showed that tumors harboring a fusion gene had significantly higher prevalence of the presence of signet ring cells (P=0.000)

micropapillary component (P=0.044)

mucinous cribriform pattern (P=0.000) and extracellular mucin (P=0.010). The incidence of psammoma bodies was higher in the lung adenocarcinomas with a gene fusion than in tumors without gene fusions (P=0.000). Psammoma bodies were more likely to be found in tumors with any micropapillary component and/or mucinous cribriform pattern than in tumors lacking a micropapillary component and/or mucinous cribriform pattern (P=0.000). Conclusion: Our data showed that the presence of psammoma bodies

micropapillary component

mucinous cribriform pattern

extracellular mucin or signet ring cells may be either sensitive or specific to predict tumors harboring a fusion gene. These distinct morphologic features may be helpful in selecting cases for further accurate molecular testing.