Diagnosis of essential thrombocythemia (ET) has been updated in the last

© F e r r a t a S t o r t i F o u n d a t i o nBCL2 translocations are more frequently found in the GCB subtype, whereas 18q21 locus amplification is more common in the ABC subtype of DLBCL. 3,8,10 The prognostic significance of BCL2 amplification or translocations in de novo DLBCL in the era of CHOP therapy alone, without rituximab, was controversial. [11][12][13][14][15][16][17][18][19][20] Some data on the prognostic significance of BCL2 aberrations in patients treated with R-CHOP have recently become available, with two studies reporting no influence of BCL2 gene rearrangements on the survival of DLBCL patients. 21,22 On the other hand, the concomitant presence of t(14;18) or variants and MYC rearrangements, referred to as double hit lymphomas, has consistently been associated with adverse outcome in DLBCL patients treated with R-CHOP. [23][24][25] Bcl-2 protein expression seems only partially related to BCL2 gene abnormalities as analyzed by fluorescence in situ hybridization (FISH), as Bcl-2 is expressed in a greater number of DLBCL cases than in those tumors carrying t(14;18)(q32;q21). [10][11][12] Indeed, in the absence of BCL2 translocations, amplification of 18q21 and/or activation of the nuclear factor κB (NF-κB) pathway can cause Bcl-2 protein overexpression. 26 The prognostic significance of Bcl-2 expression is also controversial, and comparison between different studies is hampered by the choice of different cut-offs of positive cells, and by the variability of treatments. In patients treated with R-CHOP, Bcl-2 protein did not correlate with outcome, 5,27 since the addition of rituximab seemed to improve survival of Bcl-2-positive patients, [28][29][30] apparently eliminating the gap between Bcl-2-positive and Bcl-2-negative patients found in the pre-rituximab era. This result does, however, appear to be contradicted in a very recent study in which Bcl-2 expression in GCB-DLBCL was associated with poorer outcome. 22 The goal of this study was to investigate the prognostic value of BCL2 gene aberrations and Bcl-2 expression in a large number of patients with de novo DLBCL, uniformly treated with R-CHOP, for whom MYC and GEP characterization was available. Design and Methods PatientsWe studied 327 cases of previously untreated de novo DLBCL, diagnosed between January 2002 and October 2009, and collected as part of the International DLBCL Rituxan-CHOP Consortium Program Study. These cases were analyzed for Bcl-2 protein expression, and BCL2 and MYC gene abnormalities, and gene expression profiling (GEP) was performed. All cases were reviewed by a group of hematopathologists (SMM, MAP, MBM, AT, and KHY), and the diagnoses were confirmed based on World Health Organization classification criteria. Patients with transformation from low grade lymphoma, those with composite follicular lymphoma, primary mediastinal large B-cell lymphoma, primary cutaneous and primary central nervous system DLBCL were excluded from the analysis due to the unique biological features of these types of lymphoma. All pat...

Our study, which to our knowledge includes the largest series of childhood systemic ALK-positive ALCL so far, demonstrates the adverse prognostic value of SC and/or LH morphologic features. Combining these histologic characteristics with other biologic or clinical factors might have a high potential for future risk stratification and treatment.