Biopsies and cell lines of natural killer/ T-cell lymphoma, nasal type (NKTCL)were subject to combined gene expression profiling and array-based comparative genomic hybridization analyses. Compared with peripheral T-cell lymphoma, not otherwise specified, NKTCL had greater transcript levels for NK-cell and cytotoxic molecules, especially granzyme H. Compared with normal NKcells, tumors were closer to activated than resting cells and overexpressed several genes related to vascular biology, Epstein-Barr Virus-induced genes, and PDGFRA. Notably, platelet-derived growth factor receptor ␣ and its phosphorylated form were confirmed at the protein level, and in vitro the MEC04 NKTCL cell line was sensitive to imatinib. Deregulation of the AKT, Janus kinase-signal transducers and activators of transcription, and nuclear factor-B pathways was corroborated by nuclear expression of phosphorylated AKT, signal transducers and activators of transcription 3, and RelA in NKTCL, and several deregulated genes in these pathways mapped to regions of recurrent copy number aberrations (AKT3 [1q44]

Rare cases of peripheral T-cell lymphomas with follicular growth pattern (PTCL-F) have been recently reported, and their association with t(5;9)(q33;q22) involving ITK and SYK has been suggested. However, the clinicopathologic aspects of PTCL-F are poorly described and the normal cell counterpart of this subgroup of lymphoma is still unknown. Therefore, we analyzed the pathologic, phenotypic, and cytogenetic features of a series of 30 patients (range: 33 to 88 y) that showed histopathologic features of PTCL-F in at least 1 biopsy (n=30), either at initial presentation (n=26) or at relapse (n=4). Neoplastic cells were medium-sized clear cells that were CD4+ (24/27, 89%), CD10+ (21/29, 72%), BCL-6+ (14/19, 74%), and expressed programed death-1 (27/27, 100%), CXCL13 (23/27, 85%), and ICOS (11/11, 100%), markers of follicular helper T cells (TFH). Four of 22 patients (18%) had t(5;9)(q33;q22) detected by fluorescence in situ hybridization. Patients with clinical data available had multiple lymphadenopathies (25/28, 89%), stage III to IV diseases (17/26, 65%), B symptoms (7/27, 26%), and skin lesions (6/23, 26%). Three patients with sequential biopsies disclosed clinical and histopathologic features of angioimmunoblastic T-cell lymphoma at initial presentation. Our results show that this rare form of PTCL-F (1) has an immunophenotype indicative of derivation from TFH cells, (2) is associated with t(5;9) in a proportion of cases, and (3) shows some overlapping features with angioimmunoblastic T-cell lymphoma, raising the question of a possible relationship.

Reliable information regarding the current prevalence of peripheral T-cell lymphoma (PTCL) entities is missing. Herein we report on the frequency of PTCL entities in France between 2010 and 2013. Using Lymphopath, a national lymphoma network established by the French National Cancer Agency, which covers about 70 % of all lymphomas currently diagnosed in France, we found that PTCL comprised 6.5 % of non-cutaneous lymphomas with angioimmunoblastic T-cell lymphoma (AITL) being the most frequent (739 cases; 36 %), followed by peripheral Tcell lymphoma not otherwise specified (PTCL-NOS) (550 cases, 27%). These data were verified in an independent data set from a transnational research consortium active in three European countries. In comparison to epidemiologic data reported previously, we show that AITL is by far the most common PTCL subtype. In light of the results of recent molecular findings highlighting the heterogeneity of T-cell lymphomas and the advent of targeted therapies, these data have important implications for both basic and clinical research.Peripheral T-cell lymphomas (PTCLs) represent diverse and complex diseases, estimated to represent an overall 10-15% of all lymphomas worldwide, with the highest incidence rates occurring in Asia.1,2 The relative prevalence of PTCL entities delineated according to the criteria of the REAL (1994) /WHO (2001) classification systems, was evaluated in multiple institutions in the late 1990s and early 2000s, based on retrospective cohorts of patients. In those series, PTCL-NOS (a "by default" diagnosis for cases not fulfilling the criteria for other more specific entities) was the most frequent entity, followed by anaplastic large cell lymphoma (ALCL) and AITL, while extranodal entities, in general, accounted for a small proportion of the cases. 1,3,4 This worldwide epidemiology was most recently addressed by the International PTCL study, which reviewed more than 1,300 patients diagnosed with PTCL between 1990 and 2002 in North America, Europe and Asia.5 In this cohort, PTCL-NOS was the most common diagnosis (25,9%), followed by AITL (18,5%), representing 30.4% and 21.7% of non-cutaneous PTCL, respectively (Figure 1). 5This study also confirmed geographic variations in the distribution of PTCL entities, notably demonstrating that the highest frequencies of AITL and enteropathy-associated Tcell lymphoma (EATL) are in Europe.Here, we provide recent data obtained from a large prospective survey in France. The prevalent analysis of PTCL was derived from data collected through Lymphopath, a national network of 33 expert reference centers for hematopathology which was established by the French National Cancer Agency in 2010. Non-expert pathologists are encouraged to refer every newly diagnosed lymphoma for review to a Lymphopath center. Diagnoses provided by experts, following slide review and additional ancillary techniques performed in the reference center, are entered into a central database. Of the 31,401 non-cutaneous lymphomas reviewed in Lymphopath over four years (20...

p53 alterations constitute a pejorative biological indicator able to discriminate among clinically defined lower risk patients with DLBCL.

A real-time quantitative PCR assay has been developed to measure human herpesvirus 6 (HHV-6) DNA in biological specimens. The assay sensitivity was 10 copies of DNA per well, with a linear dynamic range of 10 to 10 7 copies of HHV-6 DNA. Intra-and interassay variations were, respectively, 0.88 and 0.8% for samples containing 10 2 DNA copies, 0.99 and 0.96% for samples containing 10 4 copies, and 0.76 and 0.9% for samples containing 10 6 copies. Among 34 saliva samples from healthy subjects, 26 were found to contain HHV-6 DNA (76.5%; median, 23,870 copies/ml), and following a single freeze-thaw cycle, 25 of the same samples were found to be positive for HHV-6 DNA, although at a statistically significantly lower concentration (median, 3,497 copies/ml). The assay enabled detection of HHV-6 DNA in lymph node biopsies from patients with Hodgkin's disease (