Morphologic features of carcinomas with recurrent gene fusions.

Recurrent gene fusions have been thought to play a central role in leukemias, lymphomas, and sarcomas, but they have been neglected in carcinomas, largely because of technical limitations of cytogenetics. In the past few years, an increasing number of recurrent gene fusions have been recognized in epithelial cancers. The majority of prostate cancers, for example, have an androgen-regulated fusion of one of the ETS transcription factor gene family. Notably, the fusion genes can often serve as specific diagnostic markers, criteria of molecular classification and therefore potential therapeutic targets. Recent studies have focused on investigations of morphologic features (phenotype) of recurrent gene fusions (genotype) in malignancies. In this review, we will summarize the histologic features of known recurrent genomic rearrangements in carcinomas, especially focusing on TMPRSS2-ERG fusion in prostate cancer, EML4-ALK in lung cancer, ETV6-NTRK3 in secretory breast cancer, RET/PTC and PAX8/PPARγ1 rearrangements in thyroid cancer. In addition, we will describe how these features could potentially be used to alert the pathologists of the diagnosis of fusion-positive tumor. A combination of histologic validation with other screening strategies (eg, immunohistochemistry) for recognition of recurrent gene fusions is also highlighted.