Advances in understanding the pathogenesis of systemic anaplastic large cell lymphomas

Summary The currently used 2008 World Health Organization classification recognizes two types of systemic anaplastic large T cell lymphoma according to ALK protein expression in tumour cells. First, the ‘anaplastic large cell lymphoma, ALK positive’ (ALK+ ALCL) that is characterized by the presence of ALK gene rearrangements and consequent ALK protein expression, and, second, the ‘anaplastic large cell lymphoma, ALK negative’ (ALK− ALCL) that is a provisional entity lacking ALK protein expression but cannot be distinguished morphologically from ALK+ ALCL. In this review we summarize the current knowledge on the genetic lesions and biological features that underlie the pathogenesis of ALK+ and the ALK− ALCL and that can lead to the use of targeted anti-cancer agents.