"Double hit" lymphoma or secondary MYC translocation lymphoma?

Chromosomal translocations that juxtapose different genes required for proliferation and differentiation are frequently associated with hematologic neoplasms. A term "double hit" lymphoma refers to a group of mature B-cell malignancies that harbor MYC rearrangement accompanied with another translocation commonly found in lymphomas (i.e. IGH/BCL2). A complex karyotype with multiple abnormalities and very aggressive course of disease are additional characteristics of this group. The response to currently available treatment regimens is unsatisfying, thus reported overall survival of these patients is usually very short. Today, the precise mechanisms of "double hit" lymphoma development are still unclear, although several possible pathways have been proposed in the literature. Similar oncogenic chain of events was also observed in another common hematological malignant neoplasm – multiple myeloma. MYC translocation as a secondary pathogenic phenomenon has been demonstrated in multiple myeloma, as well as complex cytogenetics and very aggressive course of the disease. Therefore, a secondary translocation involving MYC gene might be a potential marker of aggressive neoplasms emerging from different cells of origin, and united under the umbrella of "MYC-plus" malignancies. That concept might, in the future, result in a novel therapy, targeting this distinct, but not unique cytogenetic aberration. WHO CLASSIFICATION OF LYMPHOMAS A used term 'lymphoma' portrays not a single disease, but more than 40 biologically, morphologically and clinically different entities within the category of malignant neoplasms of lymphoid lineage. Classifications are an essential part of modern medicine, offering a consensus on terminology and disease definitions to be used interdisciplinary both in research and clinical practice. Evolution of lymphoma classifications includes numerous attempts from descriptive schemes, relying on morphology (in the Rappaport classification) to strictly clinically oriented stratifications proposed by hematologists (as in the Working Formulation), usually without significant international acceptance (1). The 3rd edition of The World Health Organization (WHO) Classification of Tumours of the Haematopoietic and Lymphoid Tissues that was published in 2001 was regarded as a milestone, because it was the first classification consistently to be used worldwide (2). The WHO classification divides lymphomas primarily into Hodgkin lymphomas and non-Hodgkin lymphomas. Non-Hodgkin lymphomas are further stratified according to the stage of differentiation, as PETRA KORA] SNJE@ANA DOTLI] MARA DOMINIS 1 Faculty of Science, Department of Molecular Biology, University of Zagreb, Zagreb, Croatia 2 Department of Pathology and Cytology, University Hospital Center Zagreb,